By targeting the key gene csgD involved in the biofilm formation of Escherichia coli, we employed molecular docking and molecular dynamics simulation to screen the active components of Chinese medicine with inhibitory effects on the biofilm formation from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). After the anti-biofilm properties of the active components were validated in vitro, data-independent acquisition (DIA) proteomics was employed to further identify the differential proteins involved in interfering with the biofilm formation of Escherichia coli. The mechanisms of inhibition were explored with consideration to the phenotype. Through virtual screening, we identified four candidate active components, including tannic acid, narirutin, salvianolic acid B, and rosmarinic acid. Among them, tannic acid demonstrated significant inhibitory effect on the biofilm formation of E. coli. The analysis of differential proteins, combined with relevant phenotype validation, suggested that tannic acid primarily affected E. coli by intervening in pilus assembly, succinic acid metabolism, and the quorum sensing system. This study provided a lead compound for the development of new drugs against biofilm-associated infections in the future.
Biofilms/drug effects* ; Escherichia coli/metabolism* ; Molecular Docking Simulation ; Drugs, Chinese Herbal/chemistry* ; Tannins/chemistry* ; Cinnamates/metabolism* ; Benzofurans/chemistry* ; Depsides/metabolism* ; Rosmarinic Acid ; Anti-Bacterial Agents/chemistry* ; Escherichia coli Proteins/genetics* ; Medicine, Chinese Traditional

OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.

Objective:To investigate the impact of nutrition supplementation (whey protein, fish oil and vitamin D) and physical exercise (resistance and aerobic exercise) on muscle mass and body fat metrics among community elderly with sarcopenia.Method:102 eligible sarcopenic participants per inclusion and exclusion criteria were randomized into the control group (routine consultation, n=34) or the groups receiving nutrition supplementation (Nutr, n=34) or nutrition supplementation combined with exercise (Nutr+Ex, n=34) for 12 weeks. Muscle and body fat related indicators were compared across groups pre- and post-intervention. Results:Analysis of covariance showed that all indicators were significantly different between groups (all P<0.05). Further pairwise comparisons showed that compared with controls, patients in Nutr group showed increased appendicular muscle mass (ASM) by 0.837 kg ( P=0.003, 95% CI: 0.301 to 1.372) and decreased fat mass by 2.876 kg ( P<0.01, 95% CI: -3.941 to -1.812), while patients in Nutr+Ex group showed increased ASM by 0.745 kg ( P=0.010, 95% CI: 0.180 to 1.311) and decreased fat mass by 2.928kg ( P<0.01, 95% CI: -4.408 to -1.808). Other muscle-related indicators also increased while fat-related indicators decreased in both Nutr and Nutr+Ex groups. However, there is no significant difference between Nutr and Nutr+Ex groups. Conclusions:Nutrition supplementation and physical exercise contribute to muscle mass and body fat improvement among sarcopenic elderly. Lifestyle intervention based on nutrition intervention is important for the community elderly with sarcopenia.

Objective:To explore the mechanisms of regulation of miR-575 on the proliferation and invasion properties of non-small cell lung cancer cell (NSCLC).Methods:Real-time PCR was selected to detect the expression of miR-575 and BLID in differ ent NSCLC cell lines.CCK-8 assay was processed to measure the alternations of A549 cell proliferation at different time points after transfection of miR-575 mimic and miR-575 inhibitor.The invasion ability of A549 cells was evaluated by transwell.The targeting of BLID by miR-575 was predicted by Targetcan software and verified by dual-Luciferase assay.BLID protein expression level was detected by western blot.Results:miR-575 highly expressed in NSCLC cell lines,including A549,SPC-A1,H1299,H1650 (P＜0.001),miR-575 mimic could efficiently elevated the expression ofmiR-575 in A549 cells (P＜0.001),and strengthened the proliferation and invasion ability of NSCLC cells (P＜0.05),while,transfection of miR-575 inhibitor could down-regulate the expression ofmiR-575,and also inhibit the proliferation and invasion ability of NSCLC cells (P＜0.01).Targetscan software predicted that BLID might be the target gene of miR-575,and dual-luciferase assay revealed that miR-575 could obviously decrease the luciferase reaction of wild type BLID 3'UTR (P＜0.01),besides,miR-575 could down-regulate the protein expression ofBLID (P＜0.01).Real-time PCR results showed that NSCLC cell lines had lower level of BLID mRNA expression compared with 16HBE control cells (P＜0.001),and restore of BLID could markedly inhibited cell proliferation and invasion ability (P＜0.05),which could be reversed by miR-575 co-tranfection (P＜0.01).Conclusion:In NSCLC cells,the expression ofmiR-575 could promote cell proliferation and invasion ability by directly regulating downstream target tumor-suppressor gene BLID expression.

Objective To determine the feasibility of human routine blood tests as a surrogate for CD4+ T cell count through studying the correlation of CD4+ T cell count with total lymphocyte count(TLC),hemoglobin(Hb),blood platelet(PLT),and white cell count(WBC)in HIV/AIDS patients.Methods 1 038 person-time blood tests among 778 HIV/AIDS patients were performed and Spearman correlation analysis was used.Predictive power and the cut-off for potential predictors of CD4+ T cell count were assessed through receiver operating characteristic(ROC)curves.Combination test was used to assess the capability of multipie indexes to serve as surrogate markers for CD4+ T cell counL Results Significant correlations with CD4+ T cell count were observed for TLC,Hb,PLT and WBC.The Spearman correlation coefficients were r=0.64,P=0.000;r=0.36,P=0.000;r=0.24,P=0,000;r=0.09,P=0.000,respectively.No correlation between TLC and CD4+ T cell count was found when,TLC was more than 2 000 × 106/L(r=0.12,P=0.15).The areas under ROC curve of TLC and Hb for predicting CD4+ T cell count were between 0.82 to 0.84,and 0.66 to 0.70,respectively.When CD4+ T cell count were less than 50,200,350 cells/μl respectively,the optional cut-off value was TLC＜1 100 × 106/L,1 200 × 106/L and 1 400 × 106/L.When the study combined TLC＜1 200 × 106/L and Hb＜120 g/L for prediction of CD4+ T cell count＜200/μl,the sensitivity was 45.3% and specificity was 82.8%.Conclusion There is no significant application value for combination of TLC＜1 200×106/L and Hb＜120 g/L as a surrogate for prediction of CD4+ T cell count＜200/μl.