OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Transformer models have emerged as pivotal tools within the realm of drug discovery, distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes. Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data, these models showcase remarkable efficacy across various tasks, including new drug design and drug target identification. The adaptability of pre-trained transformer-based models renders them indispensable assets for driving data-centric advancements in drug discovery, chemistry, and biology, furnishing a robust framework that expedites innovation and discovery within these domains. Beyond their technical prowess, the success of transformer-based models in drug discovery, chemistry, and biology extends to their interdisciplinary potential, seamlessly combining biological, physical, chemical, and pharmacological insights to bridge gaps across diverse disciplines. This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields. In our review, we elucidate the myriad applications of transformers in drug discovery, as well as chemistry and biology, spanning from protein design and protein engineering, to molecular dynamics (MD), drug target identification, transformer-enabled drug virtual screening (VS), drug lead optimization, drug addiction, small data set challenges, chemical and biological image analysis, chemical language understanding, and single cell data. Finally, we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

AIM To explore the effect of Compound Fo'ercao Mixture on TLR4/MyD88/NF-κB signaling pathway in a rat model of chronic obstructive pulmonary disease(COPD).METHODS Rats were randomly divided into the blank group(n=10),and the model group(n=50)for the establishment of a rat model of COPD by 12-week cigarette smoke exposure combined with intratracheal injection of LPS.The successful rat models were randomly divided into the model group,the dexamethasone group(0.5 mg/kg)and the low,medium and high dose Compound Fo'ercao Mixture groups(6.8,13.6 and 27.2 g/kg),with 10 rats in each group.After 24 weeks of drug intervention,the rats had their lung function detected by animal lung function meter;their pathological changes of lung tissue observed by HE staining;their serum TNF-α,IL-1β,IL-6,and MDA levels and SOD activity detected by ELISA;their pulmonary mRNA expressions of TLR4,MyD88,NF-κB and caspase-3 detected by RT-qPCR;and their pulmonary protein expressions of TLR4,MyD88,NF-κB and TNF-α detected by Western blot.RESULTS Compared with the blank group,the model group displayed obviously pulmonary ventilation dysfunction,damaged lung tissue and bronchus,decreased SOD activity(P＜0.01);increased serum TNF-α,IL-1β,IL-6 and MDA levels(P＜0.01);and increased pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α proteins(P＜0.01).Compared with the model group,all Compound Fo'ercao Mixture groups shared improvement in lung function indices levels and lung tissue damage;decrease in the levels of serum TNF-α,IL-1β,IL-6 and MDA(P＜0.05,P＜0.01);and decrease in the pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α protein(P＜0.05,P＜0.01)in a dose-dependent manner.CONCLUSION Compound Fo'ercao Mixture can improve the lung dysfunction and pathological injury in a rat model of COPD,and its mechanism may be associated with the regulated TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

AP2 transcription factors belong to the AP2/ERF superfamily and are involved in the regula-tion of various biological processes in plant growth and development,as well as in response to biotic and abiotic stresses.However,studies on the AP2 transcription factor family of Perilla frutescens have not been reported.In this study,totally 18 AP2 family members were identified from the Perilla frutescens ge-nome and analyzed for gene structure,conserved motifs,and cis-acting elements using bioinformatics.WRINKLED1(WRI1)is a key regulator of lipid biosynthesis in many plant species and plays an impor-tant role in the regulation of lipid synthesis.Sequence comparison revealed that one member of WRI1 is highly homologous to AtWRI1 and contains two conserved AP2 domains,named PfWRI1.The expression levels of PfAP2 family genes were analyzed in different tissues of Perilla frutescens and at different stages of seed development in conjunction with the transcriptome data,and the results showed that PfWRI1 is highly expressed only in the seeds of Perilla frutescens,suggesting that PfWRI1 may be related to the de-velopmental process of the seeds.The overexpression vector of plant pCAMBIA1303-PfWRI1 was con-structed,and wild-type(Col)and mutant(wri1-1)Arabidopsis thaliana were transformed by Agrobacte-rium tumefaciens to obtain overexpression and complementation lines,respectively.The results showed that the expression of P fWRI1 led to an increase in oil content of Arabidopsis seeds by 8.90％-13.57％compared with Col,and promoted the accumulation of oleic acid(C18:1)and linoleic acid(18:2)and reduced the accumulation of palmitic acid(C16:0),arachidonic acid(C20:0),and cis-11-Eicosenoic acid(C20:1)in transgenic Arabidopsis seeds.In addition,PfWRI1 gene expression increased the ex-pression of glycolysis and fatty acid biosynthesis-related genes AtPKP-α,AtPKP-β1,AtBCCP2,AtSUS2,and AtLIP1.Taken together,PfWRI1 may promote lipid accumulation by increasing unsaturated fatty acid content through interaction with the above genes.