Nathalie Wambang

Nadege Schifano

Alain Martoriati

Natacha Henry

Brigitte Baldeyrou

Christine Bal

Till Bousquet

Sylvain Pellegrini

Samuel Meignan

Katia Cailliau

Nadège Schifano-Faux

Christine Bal-Mahieu

Jean- François Goossens

Jean-François Bodart

Peter T Ndifon

Lydie Pélinski

Synthesis, Structure, and Antiproliferative Activity of Ruthenium(II) Arene Complexes of Indenoisoquinoline Derivatives

published or not. The documents may come

INTRODUCTION

Metal-based compounds have become the most widely used chemotherapeutic agents. In particular, platinum complexes such as cisplatin, carboplatin and oxaliplatin are widely used in the clinical treatment of a broad range spectrum of cancer. 1 Ruthenium complexes are also considered to be one of the most promising types of metal-based drugs. 2 Particularly, two Ru(III) species, KP1019 1 and NAMI-A 2, are presently undergoing clinical trials (Figure 1). 3 In addition, some Ru(II) complexes, such as RAPTA-C 3 and Ru(II)(arene) complexes of bidentate ethylenediamine 4, exhibit interesting in vitro and in vivo anticancer activity and are already under preclinical evaluation (Figure 1). 4 Recently, indenoisoquinolines have been identified as novel topoisomerase I inhibitors exhibiting better pharmacokinetic features and greater chemical stability than camptothecin. 5 In particular, two anticancer agents, indotecan 5 (LMP400) and indimitecan 6 (LMP776), were promoted to a Phase I clinical trial at the National Institute of Health. Interestingly, structural modifications of the indenoisoquinolines induced good topoisomerase II inhibition properties. 6 As part of our ongoing effort to develop metal-based indenoisoquinoline derivatives as anticancer agents, 7 we report our preliminary results on the preparation and the characterization of Ru(II)-arene complexes 8 and 9 containing diamines as ligand. Their cytotoxicities on cancer cell lines and their DNA interaction were evaluated. (Figure 2).

RESULTS AND DISCUSSION

Synthesis and characterization. The synthesis of ruthenium complexes 8 and 9 are described in Scheme 1. Indenoisoquinolines 11 and 12 were first obtained in a four step reaction. Condensation of the benzo [d]indeno [1,2-b]pyran-5,11-dione 10 with a primary aminoalcohol was followed by tosylation of the alcohol function. The substitution of the tosyl group by the protected ethylenediamine and the consecutive deprotection of the Boc group led to the indenoisoquinolines 11 and 12 in 65-68% global yield. Their complexation in the presence of [(p-cymene)RuCl2]2 in ethanol followed by an exchange of chloride by hexafluorophosphate afforded the ruthenium indenoisoquinolines 8 and 9 in 95% and 88% yields respectively. 8 The structure of 9 was established by single crystal X-ray analysis. The drawing is displayed in Figure 3. The Ru-complex 9 crystallizes in the triclinic space group P1̅ with two formula units per unitcell. As can be seen in Figure 3, the complex shows a mononuclear structure in which the Ru(II) atom is four coordinated by one chlorine atom, an arene ligand and two nitrogen atoms from the indenoisoquinoline-diamine ligand. The compound 9 demonstrated good stability in water and in BPE buffer as no significant change of their UV-Vis absorption spectra over a period of 24 h was observed (Figure S3, ESI). 13); N2-Ru-Cl, 86.88 (11).

Additionally, the ESI-MS of complex 9 has been acquired to understand its relative composition and stability. ESI-MS spectra were recorded directly after dissolution in water and after 2 and 6 h. Besides the anticipated parent mass peaks, a peak at m/z (9-HCl) was also observed and was attributed to the cleavage of the Ru-Cl bond. This result suggests that the chlorine atom of the Ru-complex is highly labile. An identical ESI-MS profile was obtained when the complex 9 was dissolved in acid solution at pH = 2.7. It can be noted that the cleavage of the Ru-Cl bond is more important in an acidified aqueous solution than in water (Figures S4 and S5, ESI) Biological studies. The ability of drugs to protect calf thymus DNA (CT DNA, 42% GC bp) against thermal denaturation was used as an indicator of the relative capacity of indenoisoquinoline derivatives to bind and to stabilize the DNA double helix. ΔTm values are reported in Table 1. 9 The ruthenium complexes 8 and 9 displayed similar ΔTm values (21°C for 8 and for 9, drug/DNA ratio = 1). Binding affinities were determined using a fluorescence method. Since a weak intrinsic fluorescence was observed for our compounds, an indirect method was preferred. 10 Scheme 1. Synthesis of Ruthenium Complexes. 2.30 ± 0.40 a Drug concentration that inhibits cell growth by 50% after incubation for 72h. Data are the mean of at least three independent experiments. b Variations in melting temperature (ΔTm = Tm drug-DNA complex -Tm DNA alone ) at ratio of 1. c Apparent binding constant measured by fluorescence using [EB]/[DNA] = 1.26. d Not determined. We used the conventional fluorescence quenching assay based on DNA binding competition between the intercalating drug ethidium bromide (EB) and the tested molecules. Indeed, EB displacement studies were preformed to have deep insight into both binding affinities with DNA and the binding mode. Intrinsic fluorescence of compounds was firstly verified. 9 The apparent DNA binding constant Kapp values were calculated using the equation: Kapp = 1.26Kapp(EB)/IC50 with Kapp(EB) = 10 7 M -1 and IC50 in M. In agreement with ΔTm, Ru-complexes have good binding affinities with DNA. However, it should be noted that complex 9, possessing four methylene units, exhibited a higher Kapp value (Kapp = 3.19 10 7 M -1 ) than the complex 8 (Kapp = 0.76 10 7 M -1 ) (Table 1). The antiproliferative activity of ruthenium complexes was tested on breast cancer (MDA-MB-231 and MCF-7) and human embryonic kidney (HEK-293), colon carcinoma (HT-29) and prostate cancer (DU-145) cell lines using a colorimetric cell proliferation assay. Cisplatin was used as reference compound. The ability of ruthenium complexes to inhibit the growth of cancer cells is summarized in Table 1. The Ru-complex 9 exhibited excellent antiproliferative activities with IC50 values ranging from 0.79 to 1.10 M. This compound was found to be more effective than the platinum compound cisplatin with the five cancer cell lines. The complex 8, possessing three methylene units, is less active than its analogue 9 with four methylene units.

CONCLUSION

In summary, new ruthenium complexes containing an indenoisoquinoline scaffold were synthesized. The molecular structure of complex 9 has been confirmed by single-crystal X-Ray diffraction analysis. These compounds displayed strong DNA interaction and excellent cytotoxic activities against five cancer cell lines. These preliminary results will be continued by biological studies. Particularly, the influence of the complexation of the indenoisoquinoline amines by other metals will be investigated.

EXPERIMENTAL SECTION

Chemistry. All commercial reagents and solvents were used without further purification. Melting points were determined with a Barnstead Electrothermal (BI 9300) capillary melting point apparatus and are uncorrected. The 1 H and 13 C NMR spectra were recorded on a Bruker AC300 spectrometer at 300 and 75.5 MHz respectively using tetramethylsilane (TMS) as internal standard and DMSO-d6 as solvent. HRMS experiments were performed on Q Exactive Benchtop LC-MS/MS (Thermo Scientific). ESI-MS studies were realized on a Obitrap LTQ XL (ThermoFisher) in positive ionization (NanoESI, 1µL/mn, complex concentration 80 pmol/µL in water/DMSO: 95/5). Thin layer chromatography (TLC) was carried out on aluminium-baked Macherey-Nagel silica gel 60. Column chromatography was performed on silica gel (230-400 mesh). The electronic absorption spectra were acquired on a UV-Vis double beam spectrophotometer SPECORD ® PLUS (Analytikjena). The molar conductance measurement was carried out using a CDRV 62 Tacussel electronic bridge, employing a calibrated 10 -2 M KCl solution and 10 -3 M solutions of compounds in DMSO. Purities of all tested compounds were ≥95%, as estimated by HPLC analysis. HPLC analyses were performed on a Thermo Finnigam using a 5 μM C18 Gravity Nucleodur column. Elemental analyses were performed with a varioMICRO analyser. Ligands 11 and 12 were synthesized according the literature procedure. 6b Ruthenium complex 8: To a solution of [( 6 -p-cymene)RuCl2]2 (56 mg, 0.09 mmol) in dry ethanol (20 mL) was added diamine 11 (63 mg, 0.18 mmol). After stirring at 50°C for 45 min, the reaction mixture was filtered and NH4PF6 (100 mg, 0.6 mmol) was added to the filtrate. After standing at room temperature for 16h, the solvent was removed and the powder was recrystallized in a mixture methanol/ether to give 1H, NH), 5.63-5.54 (m, 4H, PhH), 4.58 (m, 2H, CONCH2), 3.75 (br s, 1H, NH), 3.25 (m, 2H, CH2), 3.00 (m, 1H, CHMe2), 2.77 (m, 2H, CH2), 2.26 (m, 3H, CH2), 2.16 (s, 3H, CH3), 1.85 (b, 1H, CHH), 1.20 (d, 3 JHH = 6.9 Hz, 3H, CH3), 1.12 (d, 3 JHH = 6.9 Hz, 3H, CH3). 13 C NMR (DMSO-d6)  189.9, 162.9, 156.2, 136.4, 134.4, 134.0, 133.9, 131.8, 131.4, 128.1, 127.2, 123.9, 122.8, 122.7, 122.6, 107.2, 105.6, 94.6, 82.2, 82.0, 81.2, 79.2, 51.2, 49.8, 40.3, 40.1, 30.0, 28.2, 22.3, 21.4, 16.8. Λm (Ω -1 .cm 2 .mol -1 ) 26. HRMS m/z (ESI) calcd for C31H35ClN3O2Ru (M) + 618.1461 found 618.14551. Ruthenium complex 9: To a solution of [( 6 -p-cymene)RuCl2]2 (51 mg, 0.08 mmol) in dry ethanol ( 30 mL) was added diamine 12 (60 mg, 0.16 mmol). After stirring at 50°C for 45 min, the reaction mixture was filtered and NH4PF6 (100 mg, 0.6 mmol) was added to the filtrate. After standing at room temperature for 16h, the solvent was removed and the powder was recrystallized in a mixture methanol/ether to give orange crystals (104 mg, 88% yield). Anal.

Calc. for C32H37ClF6N3O2PRu. H2O: C, 48.34; H, 4.94; N, 5.28. Found: C, 48.38; H, 4.90; N, 5.33. Orange crystals, m.p. 178°C. 1 H NMR (DMSO-d6)  8.60 (d, 3 JHH = 8.1 Hz, 1H), 8.26 (d, 3 JHH = 7.5 Hz, 1H), 7.86 (t, 3 JHH = 7.2 Hz, 1H, ArH), 7.80 (m, 1H, ArH), 7.63 (m, 2H, ArH), 7.56 (m, 2H, ArH), 6.57 (b, 1H), 6.44 (b, 1H), 5.66 (d, 3 JHH = 6.0 Hz, 1H, PhH), 5.63 (d, 3 JHH = 6.0 Hz, 1H, PhH), 5.57 (d, J = 6.0 Hz, 1H, PhH), 5.51 (d, 3 JHH = 6.0 Hz, 1H, PhH), 4.6 (m, 2H), 3.77 (m, 1H, CONCH2), 3.71 (br s, 1H, NH), 3.13 (m, 2H, CH2), 2.68 (m, 1H, CHMe2), 2.46 (m, 2H, CH2), 2.15 (s, 3H, CH3), 1.83 (m, 4H, CH2), 1.21 (d, 3 JHH = 6.0 Hz, 3H, CH3), 1.19 (d, 3 JHH = 6.0 Hz, 3H, CH3). 13 C NMR (DMSO-d6)  189.9, 162.6, 156.1, 136.4, 134.4, 134.1, 133.9, 131.8, 131.4, 128.1, 127.2, 123.7, 122.8, 122.7, 122.6, 107.0, 105.7, 94.3, 82.2, 82.1, 81.1, 79.5, 54.4, 49.5, 45.0, 40.3, 30.1, 26.7, 25.3, 22.6, 21.1, 16.8. Λm (Ω - 1 .cm 2 .mol -1 ) 30. HRMS m/z (ESI) calcd for C32H37ClN3O2Ru (M) + 632.1618 found 632.1612. X-ray Crystallography. Suitable crystal of Ru complex 9 [C32H37ClN3O2Ru, F6P, 0.5(H2O)] with approximate dimension 0.30 × 0.05 × 0.02 mm 3 was selected under polarizing optical microscope and glued on a glass fiber for a single-crystal X-ray diffraction experiment.

X-ray intensity data were collected on a Bruker X8-APEX2 CCD areadetector diffractometer using Mo-K radiation ( = 0.71073 Å) with an optical fiber as collimator. Several sets of narrow data frames were collected at different values of  (2.302 to 26.54°) and 2 initial values of  and , respectively, using 0.3° increments of  or . Data reduction was accomplished using SAINT V7.53a. The substantial redundancy in data allowed a semi-empirical absorption correction (SADABS) [START_REF] Sheldrick | version 2[END_REF] to be applied, on the basis of multiple measurements of equivalent reflections. The structures were solved by direct methods (SHELXS) [START_REF] Sheldrick | [END_REF] and refined by full-matrix least-squares procedures (SHELXL) using Olex program. 13 All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were included in the refinement at calculated positions using a riding model. The PF6 -anions in the crystal structure were disordered over several orientations and were taking account by two different orientations. Aqueous stability assays. Aqueous stability of the Ru-complex 9 was monitored using UV-Vis spectroscopy. Complex 9 was dissolved in DMSO and diluted with water or with BPE buffer to give 50 M solution. The UV-vis peak profile of the sample was monitored for 24 h at 1h intervals. The temperature was kept constant at 25°C throughout. Biological testing assay. DNA and Drugs Solutions. Calf thymus DNA (CT DNA, Pharmacia) was deproteinized with sodium dodecyl sulfate (SDS, protein content less than 0.2%) and extensively dialyzed against the required experimental buffer. An extinction coefficient of 6600 M -1 cm -1 was used to measure the nucleotide concentration of DNA solutions. 9a All synthesized compounds were dissolved as 10 mM solutions in DMSO. Further dilutions were made in the appropriate aqueous buffer. Melting Temperature Studies. Melting curves were obtained using an Uvikon 943 spectrophotometer coupled to a Neslab RTE111 cryostat. To perform the melting temperature (Tm) measurements, CT DNA (20 µM) was incubated alone (control Tm) then, each compound was incubated with CT DNA at a drug/CT DNA ratio of 0.25, 0.5 and 1. Typically, 20, 10, 5µM of the various drugs were prepared in 1 mL of BPE buffer (6 mM Na2PO4, 2 mM NaH2PO4, 1 mM EDTA, pH 7.1) in the presence or absence of 20 µM of CT DNA and transferred into a quartz cuvette of 10 mm path length. The absorbance at 260 nm was measured every minute over the range 20-100°C with an increment of 1°C per minute and the spectra were recorded from 230 to 500 nm and referenced against a cuvette containing the same DNA concentration in the same buffer. The Tm values were obtained from first-derived plots. Fluorescence measurements. Fluorescence titration data were recorded at room temperature using a SPEX Fluorolog fluorometer. Since compounds show weak fluorescence intensity variation with DNA titration, the binding studies were carried out through a competitive displacement fluorimetry assay using DNA-bound ethidium bromide. 10b Excitation was set at 546 nm and the fluorescence emission was monitored over the range 490-630 nm. Experiments were performed with an ethidium bromide/DNA molar ratio of 12.6/10 and drug concentration ranges of 0.02-4 µM in a BPE buffer, pH 7.2. IC50 values for ethidium bromide displacement were calculated using a fitting function incorporated into GraphPad Prism 3.0 software, and the apparent binding constant was calculated as follows: Kapp = (1.26/IC50)Kethidium, with Kethidium = 10 7 M -1 . Cell cultures and antiproliferative assay. Cells were grown at 37°C in a humidified atmosphere containing 5% CO2 in DMEM medium, supplemented with 10% fetal bovine serum, 2 mM L-glutamine, 1.5 g/L sodium bicarbonate, 4.5 g/L glucose, 10 mM HEPES, 1 mM sodium pyruvate, penicillin (100 IU/mL), and streptomycin (100 µg/mL). The cytotoxicity of the tested compounds was assessed using a cell proliferation assay developed by Promega (CellTiter 96 Aqueous one solution cell proliferation assay). Briefly, 2 x 10 4 exponentially growing cells were seeded in 96-well microcultures plates with various drug concentrations in a volume of 100 µL. After 72h incubation at 37°C, 20 µL of the tetrazolium dye was added to each well and the samples were incubated for a further 1h at 37°C. Plates were analysed on a Labsystems Multiskan MS (type 352) reader at 492 nm.

Figure 1

 1 Figure 1 Ruthenium anticancer agents.

Figure 2

 2 Figure 2 Indenoisoquinoline derivatives.

Figure 3

 3 Figure 3 Molecular structure of Ru-complex 9 showing the local geometry around the Ruthenium and ligand. Selected bond lengths (Ǻ) and angles (°): Ru-N1, 2.128 (4); Ru-N2, 2.167 (4); Ru-Cl, 2.3893 (15); Ru-C1, 2.167 (4); Ru-C2, 2.167 (5); Ru-C3, 2.191(5); Ru-C4, 2.178 (5); Ru-C5, 2.168 (5); Ru-C6, 2.209 (5); N1-Ru-N2, 79.60 (15); N1-Ru-Cl, 85.04 (13); N2-Ru-Cl, 86.88(11).

Table 1 . Interaction of Ruthenium complexes with DNA and IC50 values (M) against human cancer cells after 72h. a

 1

	Compd	Tm (°C) b	Kapp (10 7 M -1 ) c	MDA-MB-231	MCF-7	IC50 (M) HEK-293	HT-29	DU-145
	8	21	0.76±0.07	19.16 ± 1.85	>50	18.07 ± 0.64	16.30 ± 0.10	>50
	9	21	3.19±0.01	1.04 ± 0.10	1.10 ± 0.40	0.79 ± 0.09	2.02 ± 0.20	0.93 ± 0.11
	Cisplatin Nd d	Nd	33.80 ± 1.27	40.39 ± 11.96	16.47 ± 1.61	178 ± 14

ASSOCIATED CONTENT Supporting Information

The Supporting Information is available free of charge on the ACS Publications website. NMR of all new compounds, UV-Vis and ESI-MS spectra and crystallographic data for 9 (PDF and CIF)

AUTHOR INFORMATION

The contribution of authors was detailed as follows: Performed the experiments: NW, NH, AM Conceived and designed the experiments: LP, JFG. Analyzed the data: NSF, JFG, SP, PTN. Contributed reagents/materials/analysis tools: BB, CBM, SM, JFB Wrote the paper: LP, TB, NSF, NW, JFG.

Corresponding Author

*Email for L.P.: lydie.pelinski@univ-lille1.fr

ACKNOWLEDGMENT

Chevreul institute (FR 2638), Ministère de l'Enseignement Supérieur et de la Recherche, Région Nord -Pas de Calais and FEDER are acknowledged for supporting and funding this work. This research was supported by the "Ligue contre le Cancer" and the MUNDUS ACP II Project (grant for NW). Thanks are due to Dr Jerôme Vicogne (IBL, Lille) for providing cancer cells and to Arlette Lescuyer for cell culture. We are indebted to the Research Federation FRABio (Univ. Lille, CNRS, FR 3688, FRABio) for providing the scientific and technical environment conducive to achieving this work. We thank Christian Rolando and Christophe Penverne for ESI-MS experiments.


Christian Henriot

Who owns China's Past? American Universities and the Writing of Chinese History

Keywords: modern, history, western, century, knowledge, intellectual, cultural, twentieth, early This topic lack coherence and precision, although it cultural, social, socialist, Hong Kong, culture, history, state, historical, film women, social, medical, education, womens, female, Christian, gender, family, missionaries This topic seems buddhist, religious, ritual, buddhism, practices, religion, zhou, early, period, culture This topic centers around aspect of religion in pre-modern shanghai, social, cultural, urban, city, literary, culture, literature, public, popular relations, asia, foreign, states, east, american, international, policy, world, asian This topic emphasizes China Topic 7. Japan, Taiwan japanese, taiwan, economic, development, state, colonial, rural, taiwanese, economy, manchuria qing, local, state, imperial, century, empire, system, officials, power, legal political, movement, government, communist, party, nationalist, national, revolution, people, military This topic focuses on political movements, particularly communist and socialist movements, and and revolutionary changes in China song, ming, literati, painting, political, tang, historical, history, dynasty, paintings

This topic explores the political dynamics during the Qing, Ming, and Song dynasties. The topic delves into power struggles, court politics, and state governance.

Compared to the 7-topic models, the results from the ten-topic model delineates more precisely the dominant themes in all dissertations, except topic 1. Selecting an appropriate model always involves an element of subjectivity to determine which in the end provides an optimal coverage of the content of the dataset. Although topic modeling relies on accurate statistics, it is an exercise that also engages one's individual judgment as to what produces a better interpretive model.

Introduction

The past is a realm of contestation, and China's history exemplifies this. China boasts a longstanding tradition of meticulous historical recording, with rulers recognizing that future generations would judge them by the annals left behind. 1 Yet the rise of historians as a recognized profession within academia in China, mirroring Europe, was a relatively late development. Nonetheless, by the time the Chinese Communist Party (CCP) ascended to power, a robust historical discipline had been established in Chinese academic circles, complete with departments, journals, associations, and a plethora of historians. 2 Until 1949, the chronicling of Chinese history was predominantly the domain of Chinese historians. Western contributions were few and peripheral. However, in subsequent decades, ideological shifts, increasing isolation from international academia, and a retreat from archival resources diminished the intellectual merit of much of China's historical scholarship. Modern history bore the brunt of this decline. The post-maoist period saw the progressive reprofessionalization of historical research, although it was not until the mid-1980s that Chinese historical research began aligning with global academic standards, and another ten years before it regained its original vigor and became again the driving force in shaping the writing of Chinese history.

While domestic historical research in China faced challenges, studies of China thrived abroad, most notably in the United States, and secondarily in Europe, Japan, and Taiwan. Although initially limited in volume, the influence of these foreign works was profound. Historians outside China not only set the research agenda but also introduced innovative conceptual frameworks. From the 1960s to the mid-1990s, the major historiographical shifts regarding China were primarily driven by Western scholars, influenced by broader currents in global historical research.

The last three decades have seen a resurgence in Chinese historical research, resulting in an overwhelming volume of academic output that no historian today is able to cope with. This intellectual boom unfolded hand in hand with the prodigious digital transformation in China, making all publications and even historical sources accessible through online platforms. Today, however, the current climate of heightened censorship and restricted international collaboration threatens again China's integration with the global historical community. The challenge is not the volume of research -China has a thriving army of historians and historians to be-but rather the potential isolation from international scholarship. Understanding China's past is not merely an academic exercise; it is a crucial endeavor that holds profound contemporary relevance. The Chinese Communist Party is acutely aware of the power of historical narrative. As China's global influence grows, so too does the imperative to understand its history through independent and professional inquiry, as well as a deep intellectual engagement among the various communities of historians.

In this essay, I will narrow my focus to one vital aspect of scholarship on China: doctoral dissertations from American universities. They represent at any time the most advanced and refreshing state of research. All historians have gone through this stage that they often prolonged with a book monograph and subsequent publications. Many dissertations remain unpublished, but they constitute a trove a historical knowledge widely available through ProQuest. 3 My aim is to examine this body of knowledge to shed light on how American academia has approached, analyzed, and interpreted Chinese history, providing insights into the evolving U.S.-China relationship from a scholarly lens.

American Academia's Impact on Chinese History Studies

The contributions of American universities to the academic exploration of Chinese history cannot be understated. These institutions, with their long history of scholarship, rigorous academic curricula, unparallel library collections, and global reach, have been at the forefront of Chinese studies for over a century.

3 From the time I started my own journey in historical research, I have been an avid reader of dissertations. As I was reading the authorative works of Lloyd Eastman on Nationalist China for my study of Shanghai in 1927Shanghai in -1937, I also encountered unpublished dissertations as they became available years after their completion through UMI: Parls M. Coble, "The Shanghai Capitalist Class andthe Nationalist Government, 1927-1937" (Doctoral dissertation, University of Illinois at Urbana-Champaign, 1975); Bradley K. Geisert, "Power and Society: The Kuomintang and Local Elites in Kiangsu Province, China, 1924-1927" (Doctoral dissertation, University of Virginia, 1979); Edward R. Hammond, "Organized Labor in Shanghai, 1927-1937". Doctoral Thesis, Berkeley, University of California, 1978" (Doctoral dissertation, University of California, Berkeley, 1978); Jeh-hang Lai, "A Study of a Faltering Democrat: The Life of Sunfo, 1891-1949" (Doctoral dissertation, University of Illinois at Urbana-Champaign, 1976); Noel R. Miner, "Chekiang: The Nationalists' Effort in Agrarian Reform and Construction, 1927-1937" (Doctoral dissertation, Stanford University, 1973); John K. Olenik, "Left-Wing Radicalism in the Kuomintang: Teng Yen-Ta and the Genesis of the Third Party Movement in China". Doctoral Thesis, 1973" (Doctoral dissertation, Cornell University, 1973); Helen R. Chauncey, "Education and Social Mobilization: Tradition and Radical Transformation in Central China" (Doctoral dissertation, Stanford University, 1982). American academia's foray into Chinese history dates to the late 19th and early 20th centuries. 4 As global geopolitical dynamics shifted and China's position on the world stage became increasingly significant, there was a burgeoning interest among American scholars to understand this complex nation. Universities became hubs for this exploration, fostering a generation of Sinologists whose research would lay the foundations for modern Chinese historical studies. By the 1960s, after a prolonged debate on the relation of area studies and the disciplines of the humanities and social science, the heretofore dominant sinological paradigm faded away and the study of China found its place in the various disciplinary departments of universities. 5 This generated a prodigious proliferation of works in all fields of knowledge, while European universities remained stuck in the sinology paradigm. 6 Prominent institutions such as Harvard, Yale, and Columbia, among others, established dedicated libraries and centers for East Asian and Chinese studies. These became crucibles for academic innovation, where interdisciplinary approaches melded history, literature, anthropology, and political science to provide a holistic view of China's past. Through the decades, these institutions have produced seminal works that have not only enriched the academic discourse on China but have also played a pivotal role in informing American foreign policy and business strategies. 7

The global reputation of American universities further amplified the influence of their research. The collaborative ethos of American academia facilitated exchanges with institutions in Europe, Asia, and other parts of the world. In the case of China, this needs to be framed in the context of a massive brain migration to the United States before 1949, establishing the foundations for scholarly exchange that persist to this day. 8 This cross-pollination of ideas has been instrumental in shaping a nuanced and multifaceted understanding of Chinese history. Furthermore, American universities have been instrumental in training a cadre of scholars who have gone on to teach and research in institutions across the globe. The role of American universities in the study of Chinese history is no less than monumental.

The central aim of this essay is to delve into the academic contributions of American universities, specifically examining doctoral dissertations on Chinese history. These dissertations offer a unique window into the evolving understanding of China's past. They reflect not only the depth of individual research but also the broader academic trends, interests, and shifts that have transpired over the years. (1882-1936)," in Modern China in Flux: Networks, Mobility, and Transformation, ed. Christian Henriot (Berlin: De Gruyter, 2024); Stacey Bieler, "Patriots" or "Traitors"?: A History of American-Educated Chinese Students (Oxfordshire, England: Routledge, 2015).

My objective is multifaceted. First, I seek to identify the overarching trends -how has the focus of research shifted over the decades? Which historical periods have garnered more attention, and why? Second, I aim to unearth the dominant themes that have resonated across multiple dissertations. These themes, be they related to politics, culture, society, or economy, provide insights into the areas of Chinese history that have been of particular significance to scholars. Lastly, by examining the contributions from different universities, I aspire to understand the institutional dynamics -which universities have been the flag bearers in this academic endeavor, and how have their contributions shaped the field?

To guide readers through this exploration, the essay is structured into distinct sections. After this introductory segment, I will start with a temporal analysis of dissertations, understanding the distribution over time. Subsequent sections will shed light on the institutional contributions, highlighting the pivotal role of top American universities. A deep dive into the themes and topics of dissertations will follow, using advanced methodologies like topic modeling. I shall also present case studies, such as an exploration of research on the Republican period, to provide more granular insights. By its end, I hope to have painted a comprehensive picture of American doctoral research on Chinese history, capturing its nuances, its evolution, and its profound impact on the field.

The corpus

My quest started from the ProQuest Dissertations database.9 There is no straightforward way to define what constitutes a dissertation "on China" by relying simply on a keyword search. Even by restricting the search to the title and the abstract, one gets a lot of noise. The second challenge was to identify more specifically the dissertations in history. There was no way to select exactly the dissertations produced in history departments. The ProQuest metadata for the departments where the dissertation was filed is very incomplete. I used a combination of two keywords -"China" and "History"-to explore the ProQuest Dissertations database and retrieve all the dissertations that potentially addressed historical subjects. This produced a large dataset of dissertations with basic metadata (author, university, title, year). Thanks to help from the ProQuest team, I received the complete set of metadata, including the abstract, for the selected sample. I curated the dataset manually by removing all the titles that were unambiguously not of a historical nature. I processed the ambiguous titles by reading the abstract. At the end of the process, I had a dataset of 1,132 dissertations, that I processed through computational methods based on the R programming language (4.3.1).10

Even with the metadata provided by the ProQuest team, I had to accept the fact that the name of the department where the dissertation was filed was often missing. There were altogether 836 dissertations without department information (74 percent). My analysis of the distribution by department of origin among the identified 296 dissertations shows that there was a vast majority of dissertation labelled under "History department" (163 dissertations), while on the other hand, a number of dissertations with a clear historical approach were also produced in other departments, especially "East Asian Studies" (64 dissertations). Other significant contributors were "Religious Studies" (11), "Art History" (8), and "History of Science" (6). It is not fully satisfying, but until ProQuest supplements the missing metadata, we may assume that this distribution reflects the general pattern of production of dissertations with a historical content. Rather than being strict on the departmental origin of dissertations, I used the actual content, based on the title and abstract, to decide what to incorporate in the dataset.

Graph 1. Distribu/on of disserta/ons by department of gradua/on.

The distribution of dissertations, from the early 20th century to our present day, provides a mirror to both the academic priorities and the broader socio-political context of each era. From the early 20th century, there was a nascent interest in Chinese history. Yet the dataset does not reflect the actual production of doctoral dissertations before 1985. This is something that I cannot explain and that may require a second round of data retrieval. It is obvious from the years and of course from the names of authors, that major works are missing (e.g., Joseph Escherick, Frederic Wakeman, etc.). The 1950s-1970s are glaringly absent from the dataset. In this study, I will focus on the period 1985-2022 which also parallels my previous study of French doctoral dissertations on China for the same period.11

Graph 2. Distribu/on of disserta/ons over /me .

The timeline of dissertations on Chinese history from American universities reveals a remarkable surge starting in the mid-1980s. This period stands out not merely for the sheer volume of academic output but also for the depth and diversity of research topics tackled by scholars. The temporal distribution of dissertations is not just a reflection of academic outputs; it tells a story. A story of changing global dynamics and of evolving academic interests. What may have precipitated this pronounced increase from 1985 onwards? First and foremost, the geopolitical landscape of the era played a significant role. The year 1978 marked the beginning of China's economic reforms and opening-up policy under the leadership of Deng Xiaoping. By the mid-80s, the implications of these reforms were becoming evident. China was rapidly integrating with the global economy, shifting from a closed, centrally planned system to a more market-oriented one. This transformation had profound implications not just for China's economy but also for its society, culture, and politics. The world watched with keen interest as China grappled with these monumental changes, and scholars were eager to document, analyze, and understand this transformation.

Second, the production of doctoral dissertations in Chinese history reflects to a certain extent not just intellectual curiosity, but the constraints -real or perceived -of doing research in China. For historians, access to archives is paramount. Heretofore closed libraries and archives progressively opened their collections to readers, both Chinese and foreigners. Scholars found it easier to access primary sources, archives, and local records. The late 1990s-early 2000s saw a small decline, followed by a substantial rebound until 2010. The following decade was almost one of constant recess, back to the level of the early 1990s in 2016. The last few years have been more productive, yet at a level far below the average trend throughout the 1998-2010 period. Overall, however, this increased accessibility allowed for more in-depth research, leading to dissertations that were not only richer in content but also more varied in their thematic focus and more innovative in their approach.

Third, the globalization of academia meant increased collaboration. Scholars from American universities frequently interacted with their counterparts in China and other parts of the world. These exchanges, facilitated by conferences, seminars, and academic programs, provided fresh perspectives and new methodologies, enriching the research on Chinese history. The monumental changes in China, combined with the evolution of the academic landscape, created a fertile ground for research. This period, therefore, marks not just a spike in a graph; it reflects the dynamism and adaptability of academic scholarship in the face of global change.

Finally, the digital age has also revolutionized research. Databases, digital archives, and collaborative platforms have made it easier for scholars to access resources, share findings, and collaborate on research projects. This technological boon has undoubtedly contributed to the uptick in dissertations. The trends that we observe in the production of dissertations on Chinese history from American universities reflect this complex interplay of global events, academic evolution, and technological advancements. They provide a fascinating lens through which we can understand not just the history of China but also the history of historical research itself.

The Top Universities Shaping Chinese Historical Studies

The vast academic terrain of Chinese historical studies in American universities is dominated by a few institutions that cast long shadows of influence and contribution. These universities, with their robust academic traditions and resources, have emerged not just as centers of learning but as trendsetters, defining the contours of discourse and direction in pioneering research on China's past. 12 The significance of institutions like Harvard, Princeton, Columbia, and their peers cannot be understated. Their contributions transcend mere numbers; they shape narratives, mold thought processes, and lay the foundation for future research.

The top institutions have a unique position in shaping the academic discourse. Their research output often becomes the benchmark for quality. When a dissertation on Chinese history emerges from Harvard or UC Berkeley, it carries with it a certain weight of credibility. These works, by virtue of their depth and rigor, often set the tone for discussions, debates, and further research. Moreover, these universities have the resources to undertake extensive research projects and build infrastructures, allowing for deeper dives into specific topics. 13 Such comprehensive studies often open new avenues of exploration, challenging existing notions and setting new research agendas. The ripple effects of their work are felt far and wide, influencing scholars not just in the US but globally.

These institutions play a pivotal role in nurturing the next generation of scholars. Their doctoral programs attract the best minds, offering them mentorship, resources, and an environment conducive to groundbreaking research. The scholars they produce often go on to become eminent scholars. This is especially relevant in the field of Chinese history. Although there is no way to know for certain the national origin of the authors of dissertations, a rough count based on authors with transliterated names (pinyin, Wade-Giles, etc.) shows that 45 percent of all works were authored by persons originating from China, Taiwan, or Hong Kong. My count also includes names that I labeled as "Overseas", for lack of a better definition, to refer to persons of Chinese descent most likely born or raised in the United States. They represent 7 percent of all dissertations. A smaller contingent of dissertations was produced by Japanese and Koreans, altogether 3 percent of the total. Whether they remained in the United States in a professional capacity or returned to their home country, these scholars constitute as much essential contributors to shaping historical knowledge about China as they represent seeds of American scholarship in the global China field.

The top ten universities that produced the highest number of doctoral dissertations include the "usual suspects", namely universities with a long history of China studies, especially in Chinese history.

Graph 3. The ten universi/es that produced the highest number of disserta/ons.

With more than 100 dissertations, Harvard University emerges as a giant in this landscape. With its history of academic excellence and its dedicated centers for East Asian and Chinese studies, Harvard has consistently been at the forefront of Chinese studies. The university's alumni, mentors, and scholars have produced a significant number of dissertations that span the breadth and depth of Chinese history. From ancient dynastic studies to modern political analyses, Harvard's contributions are both voluminous and impactful.

Graph 4. Distribu/on of disserta/ons over /me at Harvard University.

Princeton University also stands as a key contributor in the study of China's history (73 dissertations), particularly visible since the mid-1990s. With its strong commitment to interdisciplinary studies and international scholarship, Princeton has generated a steady stream of dissertations that delve into various facets of China's complex past. Whether exploring ancient history or dissecting modern geopolitical shifts, Princeton's scholars bring a nuanced and comprehensive approach to the field. The frequency of dissertations produced at Princeton not only signifies the institution's focus on Chinese studies but also its role in shaping academic discourse on China at large.

Graph 5. Distribu/on of disserta/ons over /me at Princeton University.

Columbia University in New York, with its global reputation and strategic location, has also played a pivotal role. Its proximity to global policy-making institutions, think tanks, and international organizations has provided a unique context for its research on Chinese history. Columbia's contributions -68 dissertations -reflect a blend of deep historical scholarship and contemporary geopolitical analysis, making its dissertations particularly relevant for both academics and policymakers.

Graph 6. Distribu/on of disserta/ons over /me at Columbia University.

This brief review overlooks the larger distribution of knowledge production in Chinese history across the United States, which reflects how much and how deep Chinese studies have found their place in American academia.

Another way to assess the production of dissertations on Chinese history, to include all the universities, is to situate the place of production on a map. We present below a map that represents universities by the number of dissertations that they have produced. The purpose of the map is to highlight the relative level of concentration of Chinese historical studies in a given location or region. We can see very clearly three main clusters of different sizes. The densest cluster is located on the east coast along a Washington D.C.-Cambridge axis. The second most important cluster can be found in California, with two sub-clusters around Berkeley-Stanford and Los Angeles. A less compact cluster can also be seen in the Great Lakes area, with Chicago at its center.

Map. 1 Distribu/on of the place of produc/on of disserta/ons.

Harvard University and Chinese Historical Studies

As we explore the institutional contributions to Chinese historical studies, Harvard University emerges as a particularly intriguing case study. Its legacy, trajectory, and influence in the realm of Chinese historical research make it not just a leading institution but also a trendsetter in many respects.

From its inception, Harvard has been at the vanguard of academic pursuits with China. But what sets it apart in the study of Chinese history is its amalgamation of deep-rooted academic traditions with a forward-looking approach. The university's close link to Yenching University in China before 1949 has laid the ground for a long-lasting intellectual engagement. 14 The Harvard-Yenching Library, with its rich archives and collections, the East Asian Studies department, and the Fairbank Center for Chinese Studies, provide an unparalleled ecosystem for budding China scholars.

Harvard's journey in Chinese historical studies mirrors the broader trends in the field but with its distinctive flavor. In the early days, the focus might have been more on classical studies and ancient dynasties. However, as the 20th century progressed, there was a noticeable shift. The dissertations started reflecting a broader spectrum, encompassing not just political history but also social, cultural, and economic facets. The Republican era, the socio-cultural upheavals of the 20th century, and China's rise in global politics have all been extensively covered. Harvard has produced a staggering 111 dissertations on Chinese history, indicating its sustained commitment over the years. These dissertations span all eras, from ancient to contemporary, providing a panoramic view of China's past. A deeper dive into Harvard's dissertations reveals certain thematic concentrations. While the university has covered a broad spectrum, certain themes resonate more prominently. For instance, the interplay of tradition and modernity, the role of intellectuals in shaping societal narratives, and the impact of global events on China's internal dynamics are recurrent themes. Topic modeling will provide a more refined insight in the nature of Harvard's contribution to the study of China's past.

Dominant Periods in the Study of China's Past

The distribution of dissertations by main historical period is very uneven. I made a choice of periodization that broadly follows historical conventions for Chinese history. Contemporary covers the late Qing-Republican-early PRC period, from the 1800s to the 1960s. Modern refers basically to the Ming-Qing period, before 1800. Pre-modern was carved out to identify dissertation on the dynasties from Han to Sui. Medieval includes the Tang-Song-Yuan period. Ancient means the pre-Han period.

With 700 dissertations, the Contemporary period garners by far the largest number of dissertations with 62 per cent of the total. The Modern period ranks second, far behind, with 198 dissertations (18 per cent). The medieval period comes next with a total of 129 dissertations (11 per cent). The Pre-modern and Ancient periods amount respectively to 28 (3 percent) and 76 dissertations (7 percent).

Graph 7. Distribu/on of disserta/ons by historical period.

The distribution reflects both academic and practical considerations. The Modern and Contemporary periods are more immediately relevant to current global contexts, making them more popular for research. Understanding modern China is crucial for comprehending today's global geopolitics. The Modern and Contemporary periods have a wealth of resources available for research, from archives and newspapers to firsthand accounts and interviews. These periods, given their multifaceted nature, appeal to scholars from various disciplines. Historians, but also political scientists, economists, and sociologists find a confluence of interests in studying modern China. As we move backward in time, historical research requires more specialized skills and faces challenges like source limitations, leading to fewer dissertations on those periods. The perspective of employment for scholars specializing in ancient and pre-modern history is much more limited, mostly in academia and with a lesser number of positions than in modern and contemporary history.

Our first inroad into the content of the dissertations will start with the keywords and subjects that each author attached to the dissertation. The metadata for dissertations include both subjects and keywords that sum up in a few words the content of each dissertation. The actual separation was artificial, with a lot of overlaps. I chose to combine both categories and to keep the unique terms that described each dissertation. Keywords offer a preliminary entry into the dominant themes of the dissertations from the perspective of their authors. I excluded "China" and "History" from the analysis as they were akin to stop words in this context. I also removed the cases where keywords or subjects were missing.

Graph 8. The ten most frequent keywords associated to disserta/ons.

Asian Literature is the most frequently occurring keyword, which suggests a strong interest in the literary aspects of Chinese culture and history. Religious history comes in second, indicating a significant focus on the religious aspects of China's history. This could range from the study of traditional Chinese religions to the role religion plays in modern China. We also find terms that point to disciplinary approaches, such as art history, political science, or cultural anthropology. The Qing dynasty infers a focus on this period of Chinese history, that covers both the modern and contemporary periods. The prevalence of Social structure emphasizes an inclination toward social history. We can also see that Taiwan is very present, indicating a historical gaze that is not centered only on the mainland. Finally, Women's studies denotes a focus on gender studies within the context of Chinese history, exploring topics like women's roles, feminism, and gender relations. This is of course a very basic reading of broad research directions that we shall explore further in the next sections of this paper.

Before addressing issues of content in the dataset, I propose a focus on the Republican period. It is a personal choice inspired by my own decades-long engagement with this period. This brief yet tumultuous era in Chinese history has been a focal point of academic inquiry for its profound transformations, geopolitical significance, and cultural metamorphoses. The Republican era was marked by a quest for a modern identity. As China grappled with the remnants of its imperial past and the aspirations of a republic, the country saw the rise of new ideologies, the clash of traditions with modernity, and a reimagining of China's place in the world. The Sino-Japanese War, the complexities of World War II, and the Cold War's early days intertwined China's fate with global geopolitics. The era was marked by stark contrastswhile there were aspirations for democracy and modern governance, there were also struggles with warlordism, foreign aggression, and internal strife. This juxtaposition makes it a rich field of study, offering insights into the complexities of nation-building. The Republican era stands as a testament to a nation's resilience, adaptability, and quest for identity.

Altogether, the Republican period is represented by 217 dissertations, with a wide distribution among many universities. Although there is a certain parallel with the general distribution of dissertations, we can observe asymmetries. The metadata does not include the composition of the dissertation committee or the name of the advisor(s), but we can make some hypothesis. Perhaps the main surprise here is the number of dissertations produced at the University of California, Irvine, which places it in the second rank almost at par with Harvard University. The University of California, San Diego -probably under the stewardship of both Joseph Esherick and Paul Pickowicz-has also been a major source of dissertations on the Republican period.

Graph 9. Distribu/on of disserta/ons on Republican China by university.

Textual Analysis of Dissertation Abstracts

The statistical analysis above only offers a limited view of the contribution of doctoral dissertations to Chinese history. Another way to examine the nature of the contributions of American dissertations is to study their content. Ideally, I would have liked to use the full content of the dissertations, but this was a goal beyond my ability in terms of retrieving the text of all the dissertations. They are stored behind a paywall that limit download to only one dissertation at a time. It would take about 100 hours to download the whole dataset. Yet, I must also admit that using all the dissertations would also make the task of analysis extremely complex. For these reasons, I have opted for the more practical approach of analyzing the abstracts. These short texts generally offer a concise and well-focused description of the dissertation.. In the section below, one should keep in mind that the text of the abstracts is an extreme reduction of the content of the original dissertations.

Methodologically, I explored the abstracts through topic modeling. Topic modeling is a statistical method that identifies topics or clusters of co-occurring words in large textual datasets, helping us make sense of the textual sea. The strength of topic modeling lies in its ability to process large volumes of text, identify dominant themes, and offer a bird's-eye view of the dataset. However, it is not without limitations. The model's interpretations require human judgment, and there is always the risk of over-simplification or overlooking nuanced themes.

One of the challenges in topic modeling is determining the optimal number of topics. Too few might oversimplify, while too many might muddle the insights. This is where metrics like perplexity and coherence come into play. Both perplexity and coherence are metrics used to evaluate topic models, but they measure different aspects of the model's performance. Perplexity gauges how well the model predicts a sample, with a lower score indicating better generalization performance on unseen data. However, a good perplexity score does not always translate to interpretable topics. This is where coherence steps in. Coherence measures the degree of semantic similarity between high scoring words within each topic, serving as a proxy for topic interpretability. If a topic mostly consists of words that are often mentioned together in the same context (like "hospital", "doctor", and "patient"), it is likely to be more coherent and meaningful. On the other hand, a topic that brings together words that rarely appear together (like "hospital", "moon", and "tree") might be considered less coherent.

The choice of evaluation metric often depends on the specific topic modeling algorithm and the inference technique used. In this study, I used the Latent Dirichlet Allocation (LDA)15 model implemented in the stm and stm_insights R libraries (Gensim library in Python). I implemented topic modeling on the whole dataset and on each group of dissertations by period. Since I cannot examine each period in this paper, I shall discuss here only three subsets: Ancient, Republican, and Harvard to highlight the differences in the dominant themes.

A global analysis through topic modeling offers a bird's-eye view of the dominant themes across all periods of Chinese history. By examining the topics generated from the entire dataset, we can gauge which themes are universally significant across multiple periods and which are period-specific. Some dissertations might bridge multiple periods or introduce interdisciplinary themes, and a global analysis can capture these nuances better. By comparing the global topics with period-specific ones, we can pinpoint shifts in academic interest over time. There is a possibility that the global analysis will produce topics that are very similar to the ones identified in period-specific analyses, especially due to the sheer weight of dissertations for the Contemporary period. Nevertheless, such an approach can be particularly valuable to identify broad trends, shifts, and overarching themes in the academic study of Chinese history.

For the sake of brevity, I shall spare the reader the intricacies of the topic modeling methodology. Suffice it to say here that there is no predetermined number of topics. One needs to compute various models to decide which one is optimal. The table below provides the list of models that I computed and their metrics for coherence and perplexity. I shall provide these metrics only for the whole dataset as an indicator of the methodology that I implemented for each sub-period. For the entire dataset, the main metrics are as follows:

Table 1. Basic metrics of the topic models trained on the corpus of disserta/on abstracts.

For Coherence, the model with 7 topics has the highest coherence score, suggesting that it might provide the most interpretable and meaningful set of topics. For Perplexity, the model with 5 topics performed the best. This means it is most likely to accurately predict new, unseen data. Overall, considering both coherence and perplexity, the 7-topic model offered a balanced choice, with the highest coherence and a relatively low perplexity (See Graph 1). Yet, at the same time, the 7-topic model constrained my objective to provide a more granular view of the overarching themes in the dataset. For this reason, after examining the results from the 7-topic model, I will eventually revert for a 10-topic model for a discussion of the identified topics.

Graph 10. Diagnos/c values by number of topics for 5-, 6-, 7-and 10-topic models.

The results of topic modeling come in the forms of list of the most frequently found terms in the abstracts for each topic. The topics are not labelled. The labels indicated after each topic reflect my own understanding and interpretation of these topics. The reader shall keep in mind that this is based on the abstracts, not the full text of the dissertations.

The distribution of topics is very uneven. A topic can be highly represented in a document, or a document can relate to several topics. To illustrate this, we can look at the first 15 documents in our 7-topic model. Topic 7 is highly represented in document 3, while Topic 4 is equally highly represented in documents 8, 13 and to a lesser degree documents 4 and 6. Conversely, document 1 contain several topics at almost the same level of importance. These values provide a measure of how the algorithm has calculated the distribution of topics across all documents and for the corpus as a whole.

Graph 11. Distribu/on of topics within documents (first 15 documents).

The topics are "bags of words" that are grouped by their frequency and co-occurrence in the text of the abstracts. To define the nature of the topics, we can start by examining the distribution of the most frequent terms in each topic. The graph below lists the ten most frequent terms for each topic.

Graph 12. Highest word probabili/es in the 7-topic model.

Even with this limited list of terms, one can see differences and emerging topics. Of course, such visualizations are only meant for illustrative purposes. Basically, one needs to rely on data to figure out the characteristics of the topics. Yet rather than displaying a spreadsheet, one can still use different visualizations that extend the range of terms associated to a given topic. In the example below, I chose topic 3 to show the distribution of the top terms of a topic obviously related to women and gender. I produced similar visualizations for each topic. I shall not analyze in detail the results of the 7-topic model. In the section below, I made the choice to select the results of the ten-topic model to obtain a more fine-grained distribution of topics. The model presents a range of very similar topics to those identified in the 7-topic model, but they also delineate new topics.

Beyond a static photograph of topics, we can also chart the prevalence of each topic year to see how scholarly interest in certain topics has evolved. We can identify when certain themes began to gain prominence and when they started to fade.

Graph 14. Evolu/on of topics over /me in the ten-topic model. We conclude from these preliminary observations that the classification of dissertations in Chinese history in ten broad topics reveals fluctuations in the research interests. Yet, the overall pattern is one of diversification, even if topic modeling by nature inevitable tends to flatten the very rich production of historical knowledge about China. Yet, even with the inherent limitations of relying on abstracts, topic modeling only shows what it found in the texts. The ten topics reflect the major trends in historical research. The very fact of processing all the dissertations also cast a shadow on the more nuanced evolutions within each historical period. We can see that the dominant topics relate mostly to issues in the modern and contemporary periods. There is little that relate to topics we may expect, for instance, in ancient history. In the section below, I will examine further the content of dissertation abstracts by period.

Topics in the Ancient history subset

For the Ancient history subset, I trained models for a range of topics between 5 and 10. In the end, based on the usual metrics and the interpretability of the topics, I settled for the 6-topic model: Topic 1. Political and Social Structures -Keywords: political, Shang, early, Han, ritual, Zhou, states, social, period, western This topic seems to focus on the political and social structures of early Chinese history, particularly during the Shang and Han periods. Rituals and states are emphasized, suggesting discussions around governance, ceremonies, and societal norms. -Keywords: early, texts, religious, tombs, tomb, shi, coastal, zi, cultural, text With an emphasis on religious texts, this topic likely delves into the religious beliefs and practices of early China. The mention of "tombs" suggests burial practices, while "coastal" might indicate maritime religious practices or interactions along the coast.

Topic 2. Religious Texts and Funerary Practices

Topic 3. Historical Dynasties and Traditions

-Keywords: Han, history, dynasty, yang, century, religious, tradition, Wei, Chin, western This topic centers on the historical narratives, particularly of the Han dynasty. There is an emphasis on religious and moral traditions, with mentions of other dynasties like Wei and Chin. -Keywords: early, Buddhist, cultural, Han, social, emperor, students, analysis, relationship, text This topic sheds light on early Buddhist practices and their influence on Han China. The keywords suggest discussions around the cultural significance of Buddhism, its relationship with the emperor and governance, and possibly educational aspects given the mention of "students". Culture -Keywords: Han, Sima, interpretations, shiji, ritual, pottery, text, century, second, traditional With a focus on historiographical aspects, this topic likely discusses interpretations of historical records, particularly Sima Qian's "Shiji". The mention of "ritual" and "pottery" indicates a focus on material culture and its interpretations in historical narratives. Topic 6. Imperial Governance and Economy -Keywords: Han, Qin, imperial, economic, new, state, emperor, early, history, political This topic discusses the imperial governance models, particularly of the Han and Qin dynasties. The emphasis on "economic" suggests discussions around economic policies, trade, and fiscal systems. "New" might indicate transformative policies, innovations, or shifts in governance during these periods.

Topic 4. Buddhism and Cultural Interactions

Topic 5. Historiography and Material

We can see that the topics that emerge from the dissertation abstracts in Ancient history are markedly different from the topics identified in the whole dataset. Certain dynasties are mentioned specifically, delineating more precise sub-periods. With nuances, we can also see the prevalence of issues of religion, state governance, and historiography in this body of dissertations.

Topics in the Republican period subset

The preprocessed abstracts for the dataset of Republican period dissertations contained 217 documents. The model with 10 topics had the highest coherence score and the lowest perplexity score, which indicated it might be the most interpretable model.

Topic 1. Traditional Institutions & Development

-Keywords: new, state, century, early, legal, people, Qing, republican, history, development This topic appears to focus on the early Republican period, discussing the Qing dynasty, legal developments, and the overarching theme of new institutions and statehood. -Keywords: political, Taiwan, state, war, rural, local, social, government, new, national This topic covers political dynamics, particularly in Taiwan, and emphasizes the interplay between state and local politics, war, and rural life.

Topic 2. Politics & Rural Life

Topic 3. Foreign Relations & Travel

-Keywords: state, Japanese, American, political, travel, early, government, Japan, nation, Chiang This topic delves into China's foreign relations, especially with Japan and America, and touches upon travel literature and national politics under leaders like Chiang Kai-shek. -Keywords: political, modern, social, new, public, war, century, period, seal, national This topic encapsulates modern political and social transformations, with a focus on public life and the challenges of the war period. -Keywords: social, movement, German, culture, century, new, native, military, war, place This topic delves into various social movements and their cultural impacts, with some focus on military and war events, possibly including foreign influences like Germany.

Topic 10. Religion & Urban Life

-Keywords: church, movement, new, urban, religion, women, Confucianism, political, Shanghai, cultural Focusing on religious institutions like the church and Confucianism, this topic also touches upon urban centers like Shanghai and the associated political and cultural movements.

The dissertations on the Republican period feature a few topics that intersect with those of the whole dataset (State governance, statehood, foreign relations, women), but it exhibits either very different topics, such as urban life, science, rural life, or stronger topics on issues like women associated to nationalism or culture.

Topics in the Harvard subset

Finally, I examined separately the dataset of Harvard dissertation abstracts. Judging from the coherence and perplexity values, I settled for the 6-topic model that offered a balance between coherence and model simplicity.

Topic 1. Social and Cultural Dynamics -Keywords: history, historical, early, knowledge, political, century, life, examination, past, space This topic seems to emphasize the political and cultural dynamics across various historical periods, with a particular focus on the role of the literati.

Topic 2. Intellectual modernity & Foreign Relations

-Keywords: modern, movement, world, intellectual, international, religious, traditional, examines, history, foreign This topic centers around intellectual change with an international dimension. -Keywords: movement, women, literati, history, context, historical, western, Confucianism, ritual, political This topic presents a mix with a variety of terms that highlight both the role of women, Confucian rituals and the influence of Western thought.

The topics derived from Harvard's dissertations on Chinese history reveal a multifaceted engagement with pivotal eras of China's imperial legacy-Song, Ming, and Qing-delving into governance, intellectual discourse, and socio-cultural dynamics. Together, they underscore Harvard's profound influence on the comprehensive study of China's formative historical periods.

Conclusion

This study explored the role of American universities in writing Chinese history. It opened with a provocative quote that history belongs to those who write it, setting the stage for a discussion about the contested nature of historical narratives. Prior to 1949, Chinese history was largely chronicled by Chinese historians. However, the post-1949 era marked a shift with increased Western, particularly American, contributions to Chinese historical studies. Prominent American institutions such as Harvard, Yale, and Columbia established dedicated centers for East Asian and Chinese studies, which became genuine intellectual engines that drove innovative thinking and interdisciplinary research in Chinese history. In short, American academia played a crucial role in shaping the discourse on Chinese history.

Outside of China, no other country has wielded such influence-not for lack of historical production, but due to barriers such as language, institutional weakness, or a greater dispersion of knowledge production on China. Japan, for example, has for decades been a major contributor of historical knowledge on China. Japanese sinologists, historians, and social scientists have published extensively, including many groundbreaking works. Yet, the barrier of the Japanese language has limited the impact of this strand of rich historiography, despite the efforts of a few American scholars like Joshua Fogel to bridge the gap. The case of Europe is more saddening, in part because of the failure in most countries to integrate research on China into universities, outside of area studies departments and specialized institutions.

Moreover, the diversity of languages constitutes another stumbling block for creating a genuine European China field. Last, except in the United and Germany, historical research on China, especially modern China, has suffered from the lack of documentary resources.

The American academic narrative of China's history is both a reflection and a construct of broader global dynamics. The dissertations analyzed have served as a quantitative measure of this academic achievement. They constitute a testament to the complex interplay of global events, academic developments, and technological progress, offering a unique perspective not just on Chinese history but also on the evolution of historical research and its methodologies. Our study suggests a diversification of the disciplines contributing to the understanding of China's past, in line with the deep integration of China studies in all the departments of humanities and social science in American universities. However, the departments of history have remained the bedrock that supplies the highest number of dissertations, even if incomplete metadata inevitably distorts our perspective.

A group of elite American universities, with Harvard University serving as a paradigmatic example, has set the direction of scholarly inquiry into China's past. The transformation in research focus from classical studies to the encompassing of broader socio-cultural and political narratives over the decades signifies a responsive academic milieu that mirrors the dynamism of China's own historical trajectory. The recurrence of themes like modernization, reform, and politics underscores the interconnectedness of China's historical evolution with global historiographical trends, but the identified topics also revealed very specific strands of research for a given period or university. They denote an autonomous and creative intellectual agenda increasingly rooted in a full embrace of the singularity of China's past.

The doctoral dissertations on Chinese history have not merely contributed to a repository of knowledge; they are dynamic dialogues that engage with the past to understand the present and anticipate the future. In the end, the study's insights offer a lens through which we can observe the delicate dance of power, culture, and scholarship. It raises compelling questions about ownership and interpretation: while American universities have indeed become significant custodians and interpreters of China's historical narrative, this study prompts us to consider the implications of such stewardship in the current context of Sino-American rivalry and threats of de-linking.

Since the mid-1990s, Chinese historians have been again at the forefront of historical knowledge about China, so much so that it is no longer feasible for any scholar to cope with the massive historiography produced by researchers, Ph.D., and M.A. students, not even for a sub-field like the history of Shanghai. The thriving historical field in China has come under pressure, however, with restrictions on publishing, teaching, and attending international events. Yet, the solid foundations in scholarly exchange laid in the last two decades will hopefully prevail over these adverse currents.

Graph 13 .

 13 Word probabili/es in Topic 3 of the 7-topic model. After examining the terms associated with each topic, I determined a label that summarized the general profile of the topic. In the 7-topic model, the topics were labeled: Knowledge & Science, Politics and Revolution, Women & Gender, Buddhism & Tang-Song, Culture & Literature, Qing & Imperial state, Taiwan & Japan. These labels inevitably flatten the diversity of the individual dissertations, but they help defining in broad strokes the main research topics in the represented field.

  The graph illustrates the distribution of topics from 1985 to 2022. Topics 7 (Japan, Taiwan & Colonial Rule), 9 (Political Movements & Revolution), and 10 (Tang-Song-Ming, Culture and Arts) appear very strong at the beginning of our period but seem to appear on the wane after 2000. Topics 6 (International Relations) and 8 (Qing empire & State) hover around the same level, with ups and downs throughout the period. Topic 2 (Hong Kong culture & Cinema) made its debut after 1995 and experienced a relative development after 2010. Some topics are quite consistent over time, such as Topic 5 (Shanghai& Urban culture) and Topic 6 (International relations). Topic 3 (Women & Education) seems to exhibit one of the highest fluctuations over time, with peaks and troughs.

Topic 4 .

 4 Culture, Art, & Women's History -Keywords: historical, social, cultural, women, political, art, family, new, history, Hainan A theme revolving around cultural and social history, especially focusing on women, family and art. Topic 5. Public Life & Modernization

4

  David N. Keightley, "Main Trends in American Studies of Chinese History: Neolithic to Imperial Times," The History Teacher 19, no. 4 (1986 527-43; Man Shun Yeung, "The Rise of American Chinese Studies: Changes in Foreign Policy, Academic Foci, and American Perceptions of China," in An American Pioneer of Chinese Studies in Cross-Cultural Perspective (Brill, 2021), 291-339. 5 "Symposium on Chinese Studies and the Disciplines," Journal of Asian Studies 23, no. 4 (August 1, 1964). In its latest issue, The Journal of Chinese History / 中國歷史學刊 has published a full issue devoted to "National traditions of sinology." All major European countries are represented, even Vietnam is included, but the United States is absent from this survey. Joshua A. Fogel, "National Traditions of Sinology," Journal of Chinese History 中國歷史學刊 7, no. 2 (July 2023). 7 Paul A. Cohen, Discovering History in China American Historical Writing on the Recent Chinese Past (New York: Columbia Univ. Pr, 1997); Paul A. Cohen, A Path Twice Traveled: My Journey as a Historian of China (Cambridge (Massachusetts Published by the Fairbank Center for Chinese Studies at Harvard University, 2019). 8 Cécile Armand, "Bonding Minds, Bridging Nations: Sino-American Alumni Networks in the Era of Exclusion

6

  14 Rasmus Gjedssø Bertelsen and Steffen Møller, The Soft Power of American Missionary Universities in China and of Their Legacies Yenching University, St. John's University and Yale in China, Copenhagen Discussion Papers (Copenhagen: Asia Research Centre, Copenhagen Business School, 2010); Arthur Lewis Rosenbaum, New Perspectives on YenchingUniversity, 1916University, -1952. . A Liberal Education for a New China (Leiden: Koninklijke Brill NV, 2015); PhilipWest, Yenching University and Sino-Western Relations: 1916-1952, Harvard East Asian Series (Cambridge, London: Mass. ; Harvard University Press, 1976).

Topic 6. Buddhism & Statehood

  -Keywords: Qing, state, legal, new, history, political, Buddhist, century, nation, modern Discussions around the dynasty's legal and political framework, intertwined with mentions of Buddhist influences, suggest a mix of religious and statehood themes. Keywords: state, new, relativity, modern, post, office, market, credit, Einstein, political An interesting mix of themes around the state, modernity, and market dynamics, with mentions of scientific concepts like relativity and figures like Einstein.

	Topic 7. Women & Nationalism
	-Keywords: women, state, modern, new, social, political, local, cultural, history, nationalist
	This topic highlights the role of women in modern political and social contexts, especially in
	relation to nationalism.
	Topic 8. Science & Market Dynamics
	-Topic 9. Social Movements & War

Topic 3. Qing Dynasty & State Governance

  -Keywords: qing, political, state, century, imperial, empire, power, social, officials This topic emphasizes political power and officialdom during the Qing dynasty.

	Topic 4.

Song-Ming & local power

  -Keywords: local, song, cultural, literati, period, state, ming, elite, government, dynasty This topic highlights issues of culture and power during the Song and Ming dynasties.

	Topic 5. Japan, state & economy
	-Keywords: japanese, development, state, modern, social, economic, asia, government, east,
	military
	This topic delves into the interactions with Japan with an emphasis on political, economic and
	military aspects
	Topic 6. Movements & Confucian Traditions

The author wishes to thank ProQuest for its support in providing the full set of metadata associated to the dataset that I built for this study.

The interested reader will find all the scripts used for this study in the form of markdown scripts on GitHub.

Christian Henriot, "China Dissertations in France. A Preliminary Survey (1)," Billet, Elites, Networks and Power in Modern China (blog), April 30, 2020, https://enepchina.hypotheses.org/3193.

Christine Gross-Loh, "Why Are Hundreds of Harvard Students Studying Ancient Chinese Philosophy?," The Atlantic (blog), October 8, 2013, https://www.theatlantic.com/education/archive/2013/10/why-are-hundreds-ofharvard-students-studying-ancient-chinese-philosophy/280356/.

For example, the China Historical GIS project (https://chgis.fairbank.fas.harvard.edu/) and China-X at Harvard University (https://www.edx.org/chinax-chinas-past-present-future).

David M. Blei, Andrew Y. Ng, and Micheal I. Jordan, "Latent Dirichlet Allocation," Journal of Machine LearningResearch, no. 3 (2003Research, no. 3 ( 993-1022. .

Acknowledgement: This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovaEon programme (grant agreement No 788476).