In this article, the projects in drug metabolism and pharmacokinetics funded by NSFC during "10th Five Year Plan" (2001~2005) in China were reviewed. The major research fields of these projects in drug metabolism and pharmacokinetics funded by NSFC during the financial years were overviewed and analyzed. Finally, current problems in these research fields in China were also briefly analyzed.

We analyzed the best light intensity for callus induction and maintenance in Vitis vinifera and explored the mechanism of grape callus browning. Tender stem segments of grape cultivar "gold finger" were used to study the effects of different light intensities (0, 500, 1 000, 1 500, 2 000, 2 500, 3 000 and 4 000 Lx) on the induction rate, browning rate and associated enzyme activity and gene expression during Vitis vinifera callus formation. The callus induction rate under 0, 500, 1 000 and 1 500 Lx was more than 92%, significantly higher than in other treatments (P < 0.05). A lower browning rate and better callus growth were also observed during subculture under 1 000 and 1 500 Lx treatments. We found that chlorogenic acid, caffeic acid, p-hydroxybenzoic acid and coumaric acid contents were correlated with the browning rate of callus, among which chlorogenic acid content was positively correlated with the browning rate (P < 0.05). Peroxidase (POD) and polyphenol oxidase (PPO) activities were negatively correlated with the browning rate of callus (P < 0.01). The POD, PPO and phenylalanine ammonialyase (PAL) expression levels were positively correlated with the browning rate at P < 0.05 or P < 0.01. An appropriate light intensity for the tissue culture of Vitis vinifera was 1 000-1 500 Lx, higher or lower light intensities significantly impaired normal callus growth.
Caffeic Acids ; chemistry ; Catechol Oxidase ; chemistry ; Culture Media ; chemistry ; Gene Expression Regulation, Plant ; Light ; Peroxidase ; metabolism ; Phenylalanine Ammonia-Lyase ; metabolism ; Plant Stems ; enzymology ; radiation effects ; Tissue Culture Techniques ; Vitis ; enzymology ; radiation effects

Objective To explore clinical features,prognosis and study related cancer types in patients with familial gastric carcinoma. Methods Nine families of ICG-HGC and 3 families of suspected-ICG-HGC according with International Collaborative Group on Hereditary Gastric Cancer standard were collected and their pedigree trees were drawn.Clincial features and prognosis of ICG-HGC and suspected-ICG-HGC families were analyzed.and the related cancer types of ICG-HGC and suspected-ICG-HGC kindreds were investigated. Resuits The morbidity of ICG-HGC and suspected-ICG-HGC was 0.99%;The age of patients among the propositi of 12 kindreds were 29～65 years old with the mean age of 56 years old.Among 11 kindreds,there were 45 cases of cancers including 2 cases of multiple cancers.There were 30 foci of gastric cancer,most of which were located in lower and middle third of the stomach,with pathologic type of adenocarcinoma in poor to moderate differentiation.There were totally 15 extrastomach tumors including 7 colorectal cancers.Four cases of 11 kindreds had survived for 3 years including 1 case surviving for more than 10 years. Conclusion The familial gastric cancers in southern China have special characteristics such as poorly pathologic differentiation,advanced cancer stage,early age of onset,distal end of the stomach in location and high incidence of related tumors in colorectum.

Objective: To analyze the HIV detection results through different detection routes in Jiading District, Shanghai Municipality from 2009 to 2023, so as to provide the reference for improving HIV detection measures. Methods: Data pertaining to HIV detection in Jiading District from 2009 to 2023 was collected through the HIV/AIDS Comprehensive Control System of Chinese Disease Prevention and Control Information System. The number of HIV detection and HIV positive rates through detection routes including voluntary counseling and testing (VCT) clinics, sexually transmitted disease (STD) clinics, pre-operation and blood transfusion (products), premarital and antenatal periods, other clinical outpatients and other populations were described. Results: A total of 1 729 347 HIV tests were conducted in Jiading District from 2009 to 2023, with an average annual growth rate of 7.55%. A total of 1 125 HIV positive cases were confirmed, with an HIV positive rate of 6.51/104. The number of HIV detection conducted in VCT clinics, STD clinics, pre-operation and blood transfusion (products), premarital and antenatal periods, other clinical outpatients and other populations were 11 516, 112 880, 692 609, 635 770, 196 315 and 80 257, respectively. The main detection routes were pre-operation and blood transfusion (products) as well as premarital and antenatal periods, accounting for 40.05% and 36.76%, respectively. The HIV positive rates in VCT clinics, STD clinics, pre-operation and blood transfusion (products), premarital and antenatal periods, other clinical outpatients and other populations were 336.05/104, 21.79/104, 2.93/104, 0.35/104, 10.95/104 and 6.48/104, respectively. The HIV positive rate in VCT clinics was higher than that in other detection routes (all P<0.001). Conclusions From 2009 to 2023, the number of HIV tests increased in Jiading District, mainly through pre-operation and blood transfusion (products) as well as premarital and antenatal periods. The HIV positive rate was the highest in VCT clinics.

Chuangxinmycin (CM) from Actinoplanes tsinanensis was an antibiotic discovered by Chinese scientists about 40 years ago. It contains a new heterocyclic system of indole fused with dihydrothiopyran, whose biosynthetic mechanism remains unclear. CM is used as an oral medicine in the treatment of bacterial infections in China. The simple structure makes CM as an attractive candidate of structure modification for improvement of antibacterial activity. Recently, we analyzed the secondary metabolites of Actinoplanes tsinanensis CPCC 200056, a CM producing strain, as a natural CM analogue. We discovered the first natural CM analogue 3-demethylchuangxinmycin (DCM) as a new natural product. Compared to CM, DCM exhibited a much weaker activity in the inhibition of the bacterial strains tested. The finding provides valuable information for the structure-activity relationship in the biosynthesis of CM.

The oral and maxillofacial region contains oral organs and facial soft tissues. Due to the complexity of the structures and functions of this region, the repair of related defects is complicated. Different degrees of defects require different repair methods, which involve a great combination of medicine and art, and the material requirements are extremely high. Hence, clinicians are plagued by contemporary oral repair materials due to the limitations of bone harvesting, immune rejection, low osteogenic activity and other problems. Decellularized extracellular matrix has attracted much attention as a bioactive scaffold material because of its nonimmunogenic properties, good osteogenic properties, slow release of growth factors, promotion of seed cell adhesion and maintenance of stem cell characteristics. This article reviews the sources, preparation methods, application and research progress of extracellular matrix materials in the repair of oral and maxillofacial defects to provide an overview for fundamental research and clinical development.

Three hundred and twenty endophytic actinobacterial strains were isolated from psammophytes collected from Taklamakan Desert and identified.Among them,three strains already had been identified as new species of two genera and sixteen isolates showed relatively low 16S rRNA similarities＜98.6％to validly described species.Seventy-five of the isolates were selected as representative strains to screen antibacterial activity and mechanism.Forty-seven strains showed antagonistic activity against at least one of the indicator bacteria.Two Streptomyces strains produced bioactive compounds inducing DNA damage,and two Streptomyces strains produced bioactive compounds with inhibitory activity on protein biosynthesis.Notably,the strain Streptomyces sp.8P21H-1 that demonstrated both strong antibacterial activity and inhibitory activity on protein biosynthesis was prioritized for exploring new antibiotics.Under the strategy of integrating genetics-based discovery program and MS/MS-based molecular networking,two new streptogramin-type antibiotics,i.e.,acetyl-griseoviridin and desulphurizing gri-seoviridin,along with known griseoviridin,were isolated from the culture broth of strain 8P21H-1.Their chemical structures were determined by HR-MS,and 1D and 2D NMR.Desulphurizing griseoviridin and griseoviridin exhibited antibacterial activities by inhibiting translation.

Objective Using healthy female reproductive-age rhesus macaques as the research subjects,we explored the correlation between menstrual cycle abnormalities and gut microbiota composition by using 16S rRNA metagenomic sequencing.Methods Twenty-seven healthy female rhesus macaques were divided into regular menstrual and irregular menstrual groups.Fecal samples were collected at follicular phase(FP),ovulation phase(OP)and luteal phase(LP)of the two groups.The structure and diversity of bacterial flora in different physiological periods were analyzed and compared between the two groups.Results At the phylum level,Firmicutes,Bacteroidetes,and Proteobacteria dominated the sample flora in the follicular,luteal,and ovulatory phases of the rhesus macaques in both the regular and irregular groups,with a combined percentage of more than 98% .At the genus level,the genus Prevotella_9,Ruminococcaceae_UCG-002,Lactobacillus,Prevotella_2,Phascolarctobacterium,Ruminococcaceae_UCG-005,Streptococcus,Blautia,Prevotellaceae_NK3B31_group,Rikenellaceae_RC9_gut_group were dominant.In the luteal phase the percentage of Firmicutes was higher in the regular group than in the irregular group,while the opposite was true for Bacteroidetes.Spirochaetes were higher in the regular group than in the irregular group at all 3 stages(P＜0.05).Conclusion There were some differences in intestinal microbial composition between the two groups of macaques with regular and irregular menstrual cycles,which provided some reference for the study of intestinal bacteria and ovulation disorders.

Grape (Vitis vinifera L.) in production is frequently exposed to inadequate light, which significantly affects its agronomic traits via inhibiting their physiological, metabolic and developmental processes. To explore the mechanism how the grape plants respond to the weak light stress, we used 'Yinhong' grape and examined their physiology-biochemistry characteristics and transcriptional profile under different levels of weak light stress. The results showed that grape seedlings upon low intensity shading treatments were not significantly affected. As the shading stress intensity was strengthened, the epidermis cells, palisade tissue, and spongy tissue in the leaves were thinner, the intercellular space between the palisade tissue and spongy tissue was larger compared with that of the control, and the activities of superoxide dismutase, catalase and peroxidase were decreased gradually. Additionally, the soluble protein content increased and the free proline content decreased gradually. Compared with the control, significant changes in plant photosynthetic characteristics and physiology-biochemistry characteristics were observed under high intensity of shading (80%). RNA-seq data showed that the differentially expressed genes between CK and T2, CK and T4, T2 and T4 were 13 913, 13 293 and 14 943, respectively. Most of the enrichment pathways were closely related with the plant's response to stress. Several signaling pathways in response to stress-resistance, e.g. JA/MYC2 pathway and MAPK signal pathway, were activated under weak light stress. The expression level of a variety of genes related to antioxidation (such as polyphenol oxidase and thioredoxin), photosynthesis (such as phytochrome) was altered under weak light stress, indicating that 'Yinhong' grape may activate the antioxidation related pathways to cope with reactive oxygen species (ROS). In addition, it may activate the expression of photosynthetic pigment and light reaction structural protein to maintain the photosynthesis activity. This research may help better understand the relevant physiological response mechanism and facilitate cultivation of grape seedlings under weak light.
Vitis/metabolism* ; Gene Expression Regulation, Plant ; Photosynthesis/genetics* ; Plant Leaves ; Light ; Seedlings/metabolism*

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.