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In the 1960s, to prepare for war, China initiated a massive economic campaign known as “Third Front construction” (sanxian jianshe 三线建设). Third Front construction was largely founded on manufacturi...

Gehang Ju,1 Keyu Yan,1 Youwei Xu,2 Shilin Chen,3 Zhonghui Zheng,2 Wen Qiu4 1School of Pharmacy Lanzhou University, Lanzhou University, Lanzhou, People’s Republic of China; 2Research Institute, Shandong Xinhua Pharmaceutical Company Limited, Shandong, People’s Republic of China; 3The Department of Analysis, Chengdu Fanweixi Pharmaceutical Technology Company, Limited, Chengdu, People’s Republic of China; 4Phase I Clinical Unit, Lanzhou University Second Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Wen Qiu Tel/ Fax +86-931-8487117Email qiuwenmm@sina.comPurpose: Glimepiride, an FDA-approved oral hypoglycemic drug, is a long-acting sulfonylurea (SU), used for treating type 2 diabetes. The study aimed to evaluate the bioequivalence and safety profiles of two different formulations of glimepiride 1 mg from two different manufactures in healthy Chinese subjects in the fasting and fed state in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation.Patients and Methods: This study is an open-label, two-period, two-sequence, randomized, two-way crossover pharmacokinetic study in healthy Chinese subjects in the fasting and fed state. Seventy-two subjects were randomly assigned to the fasting group and the fed group (n=36 each). We collected blood samples, 24-h post drug administration. The plasma concentration of glimepiride was assessed using HPLC coupled with mass spectrometry. The following parameters were evaluated: AUC0-inf, AUC0-last, Cmax, t1⁄ 2, Tmax, and λz. Safety was determined based on the occurrence of adverse events (AEs) and laboratory examinations (biochemistry, hematology, and urinalysis) throughout the entire study period.Results: The geometric mean ratios (GMR) amongst the two glimepiride formulations for the primary pharmacokinetic parameters, ie, AUC0-inf, AUC0-last, and Cmax as well as the corresponding 90% CIs, were all within the range of 80.00– 125.00% in the fasting and fed state. The safety profile for both treatments was comparable.Conclusion: PK analysis revealed that the test and reference formulations of glimepiride were bioequivalent and well tolerated in healthy Chinese subjects. Chinese Clinical Trials Registry identifier: CTR20171121.Clinical Trial Registration Number: CTR20171121.Keywords: glimepiride, bioequivalence, pharmacokinetics, HPLC-MS/MS, adverse event

Daya Bay is an ecologically and economically crucial semi-closed bay along the southern coast of China. It is proven to be a stressed ecosystem and therefore obviously vulnerable to further extrinsic disturbance. This study used fish data from bottom-trawl surveys, conducted from 1985 to 2018, to analyze variations in the fish community structure over the past 30 years. The results showed that warm-water fish species were overwhelmingly dominant during all years, suggesting the bay's tropical to subtropical characteristic. By 2015, the number of fish species had decreased by 29.44% of that caught in 1987, moreover, values of the Shannon–Wiener diversity index and the Margalef richness index were lower in 2015 compared to 2004. There were evident shifts in the fish community composition from pelagic to demersal species, as suggested by the dominant species found in springtime, the dominant families, and percentages denoting the numbers of species in the main orders. Average fish body weight in landings declined from 13.4 g to 7.58 g, the body sizes of four typical commercial fish species decreased by varying degrees over the last 30 years. Abundance–biomass comparison curves suggested that the Daya Bay fish community was more stressed in 2015 than in 2004 during all seasons, except winter. In general, the fish community structure in Daya Bay is consequently in an unsteady state. Multiple anthropogenic disturbances, such as fishing (including overfishing and changes in the main fishing gears), the destruction of natural habitats, pollutants, and anthropogenically induced temperature changes, are likely to have caused obvious shifts in the bay's fish community structure. Therefore, we emphasize the need for integrating management of multiple anthropogenic stressors to achieve ecosystem-based management.

Although the name of Liu Zhidan is a celebrated one in the history of Chinese Communist organizing, Liu provided little hard information about his strategy for creating a revolutionary base in his native “Shaanbei.” Lacking trained recruits for his movement, he sought to win over as many as possible of the bandits created by the area’s widespread political and environmental disruption that had been ongoing since the late nineteenth and early twentieth centuries. However, the opprobrium in which bandits were generally held by Chinese people led most of his fellow revolutionaries to reject this approach, with the result that it has been ignored until now. To better understand Liu’s principles for popular mobilization, and also to show the options available to men of violence in the insurrectionary environment of Shaanbei, this article examines his relationship with three local bandit chiefs. Using hitherto overlooked sources together with personal interviews, it concludes that Liu’s success in winning over men like these owed more to his charisma than to their conversion to abstract revolutionary ideals, but that, for him, it was enough if this brought them around to an overall appreciation of the movement’s aims.

Most fisheries in China do not have maximum sustainable yield (MSY) estimates due to limited and poor data. Therefore, finding a common method to estimate MSY or total allowable catch (TAC) for fishery management is necessary. MSYs of three important fisheries in the East China Sea were evaluated through a catch-based model. Estimates for intrinsic rate of increase (r) and five levels of process error were considered. Results showed hairtail Trichiurus japonicas (Temminck and Schlegel) and small yellow croaker Larimichthys polyactis (Bleeker) fisheries experienced overfishing from the mid-1990s to the early 2000s, and the suggested TACs were 55.8×104 t and 9.06×104 t, respectively. Decades of overfishing in wintering and spawning grounds of large yellow croaker Larimichthys crocea (Richardson) caused the fishery’s collapse in the 1980s, and it has not recovered until today. The Catch–MSY model generated similar estimated MSYs with other methods and may be a useful choice for the assessment of regional stocks in China.

Human lung tissue, directly exposed to the environmental oxidants and toxicants, is apt to be harmed to bring about acute or chronic oxidative insults. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents a central cellular defense mechanism, and is a target for developing agents against oxidative insult-induced human lung diseases. Our previous study found that the EtOH extract of Cinnamomum chartophyllum protected human bronchial epithelial cells against oxidative insults via Nrf2 activation. In this study, a systemic phytochemical investigation of the aerial parts of C. chartophyllum led to the isolation of thirty chemical constituents, which were further evaluated for their Nrf2 inducing potential using NAD(P)H: quinone reductase (QR) assay. Among these purified constituents, a sesquiterpenoid bearing α, β-unsaturated ketone group, 3S-(+)-9-oxonerolidol (NLD), and a diphenyl sharing phenolic groups, 3, 3′, 4, 4′-tetrahydroxydiphenyl (THD) significantly activated Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO-1), and γ-glutamyl cysteine synthetase (γ-GCS), and enhanced the nuclear translocation and stabilization of Nrf2 in human lung epithelial cells. Importantly, NLD and THD had no toxicities under the Nrf2 inducing doses. THD also demonstrated a potential of interrupting Nrf2-Keap1 protein–protein interaction (PPI). Furthermore, NLD and THD protected human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. Taken together, we conclude that NLD and THD are two novel Nrf2 activators with potential application of preventing acute and chronic oxidative insults in human lung tissue., Graphical abstract fx1, Highlights • The chemical compositions of Cinnamomum chartophyllum are firstly identified. • The active ingredients supporting the biological functions of C. chartophyllum are verified. • NLD and THD are identified to be Nrf2 activators for the first time. • NLD and THD protect human lung epithelial cells against As(III)-induced cytotoxicity.

Recent researches have shown that estrogen receptor-β (ERβ) activator may be a potent anticancer agent for prostate cancer (PCa), and our previous study also indicated that dioscin can upregulate the expression of ERβ in MC3T3-E1 cell. In the present work, the activity and mechanism of dioscin, a natural product, against PCa were investigated. The results showed that dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in PC3 cells. Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and reduced aldehyde dehydrogenase (ALDH) level and the CD133+/CD44+ cells, indicating that dioscin had a potent inhibitory activity on prostate cancer stem cells (PCSCs). In vivo results also showed that dioscin significantly suppressed the tumor growth of PC3 cell xenografts in nude mice. Furthermore, mechanism investigation showed that dioscin markedly upregulated ERβ expression level, subsequently increased prolyl hydroxylase 2 level, decreased the levels of hypoxia-inducible factor-1α, vascular endothelial growth factor A and BMI-1, and thus induced cell apoptosis by regulating the expression levels of caspase-3 and Bcl-2 family proteins. In addition, transfection experiment of ERβ-siRNA further indicated that diosicn showed excellent activity against PCa in vitro and in vivo by increasing ERβ expression level. The co-immunoprecipitation (Co-IP) results further suggested that dioscin promoted the interaction of c-ABL and ERβ, but did not change c-ABL expression. Moreover, the molecular docking assay showed that dioscin processed powerful affinity toward to ERβ mainly through the strong hydrogen bonding and hydrophobic effects, and the actions of dioscin on ERβ activation and tumor cells inhibition were significantly weakened in the mutational (Phe-336, Phe-468) PC3 cells. Collectively, these findings proved that dioscin exerted efficient anti-PCa activity via activation of ERβ, which should be developed as an efficient candidate in clinical for treating this cancer in the future.

Dioscin exhibits a range of pharmacological actions but little is known of its effects on cisplatin (CDDP)-induced nephrotoxicity. Here, we have assessed the effects and the possible mechanisms of dioscin against CDDP-induced nephrotoxicity.We used an in vivo model of CDDP-induced nephrotoxicity in rats and mice and, in vitro, cultures of NRK-52E and HK-2 cells. The dual luciferase reporter assay was used to demonstrate modulation, by dioscin, of the targeting of sirtuin 1 (Sirt1) by microRNA (miR)-34a. Molecular docking assays were used to analyse the effects of dioscin with Sirt1, Keap1 and NF-κB.Dioscin attenuated cell damage in vitro and decreased renal injury in rats and mice, treated with CDDP. In terms of mechanisms, dioscin reversed CDDP-induced up-regulation of miR-34a and thus up-regulated Sirt1 levels. In addition, dioscin altered levels of haem oxygenase 1, glutathione-cysteine ligase subunits (GCLC, GCLM) and Keap1, along with increased nuclear translocation of Nrf2, thus decreasing oxidative stress. Also, dioscin affected levels of AP-1, COX-2, HMGB1, IκB-α, IL-1β, IL-6 and TNF-α and decreased the ratio of acetylated NF-κB and normal NF-κB, to suppress inflammation. From molecular docking assays, dioscin directly bound to Sirt1, Keap1 and NF-κBp65 by hydrogen bonding and/or hydrophobic interactions.Our results have linked CDDP-induced nephrotoxicity and the miR-34a/Sirt1 signalling pathway, which was modulated by dioscin. This natural product could be developed as a new candidate to alleviate CDDP-induced renal injury.

Since the appearance of Edgar Snow's Red Star Over China, the achievements of Liu Zhidan (劉志丹) in blending revolutionary ideals with the destructive energy of north Shaanxi's bandit tradition have become well known. Through repeated failures and recoveries, Liu Zhidan perceived that 20th-century China's ubiquitous violence left no alternative for the communists but to seek a military solution. The key to revolutionary success in China was an empowered peasantry fighting in the name of a shared ideal, and Liu Zhidan recognized that, in the remote areas in which the communists sought to "rest their buttocks", armed forces such as those of local bandits and brotherhoods could not be ignored. How to win those forces over to the revolutionary cause, or, failing that, how to nullify and eventually eliminate them became a major strategic problem for Liu and for other early communist militants. Regularly condemned for his attention to such irregular fighters, Liu Zhidan saw that, under the circumstances, they were all "Bro's in the 'Hood", and that the key to creating a successful revolutionary movement in China was to bring people together, not to isolate them. This paper will examine Liu Zhidan's activities in "Shaanbei" from 1928 to 1932, particularly his contacts with bandits and other local power-holders. It will suggest, among other things, that Liu Zhidan's policy of recruiting bandits to the revolutionary movement was anything but plain sailing. While some bandit chiefs were instinctively amenable to the revolutionary call, others became Liu Zhidan's worst enemies. At the same time, the resistance Liu encountered from his fellow-revolutionaries was often fierce, leading to purges and, ultimately, to what deserves to be termed judicial murder.

(2006). Clearing Away the Debris: Chinese Scholarship and the Bai Lang Rebellion. The Chinese Historical Review: Vol. 13, No. 2, pp. 330-356.

The year 1936 was a fateful one in the annals of modern China. Japan's steady encroachment, dating back to the 1931 Mukden Incident, had begun to spill over beyond the Great Wall. A sense of national crisis pervaded the country and calls for unity against Japanese aggression were heard even within the ruling Nationalist Party (Kuomintang) of Chiang Kai-shek, whose policy insisted on first eliminating its arch-rival the Communist Party. As for the Communist Party, the successful arrival of its Central Red Army in northern Shaanxi province in late 1935 following the epochal Long March had enabled it to claim readiness to take on the Japanese threat directly, and its persistent demands for a National United Front in which the Communist Party would be included were meeting with approval from a wide segment of the population.

Confucius (551 av. J.-C. - 479 av. J.-C.) fut un grand enseignant. Il mettait en avant sa philosophie de la generosite dans la vie quotidienne et dans son ideologie esthetique. Sa perception esthetique etait fondee sur les notions de beaute de la forme et du contenu, sur la perfection rendue grâce a la beaute et a la bonte. Il s'interessait autant a la poesie qu'a la musique, pratiquant des instruments, chantant et enseignant cet art. Selon Confucius, a travers l'art chacun devait pouvoir trouver la relaxation.