The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

[Objective]To develop a classification model based on complete blood count(CBC)parameters combined with clinical factors to predict severe respiratory infections caused by Human adenovirus(HAdV)in pediatric patients.[Methods]From September 2023 to September 2024,the CBC parameters and related clinical data from pediatric patients diagnosed with HAdV infection were collected.Principal component analysis and random forest models were used to identify potential predictors of severe cases.[Results]A total of 668 pediatric patients were included,with 564 cases assigned to the training cohort and 104 cases to the validation cohort.Severe cases were defined as pneumonia and/or fever lasting≥5 days(pneumonia or prolonged fever,PorPF).Principal component analysis and feature importance analysis(Mean Decrease Gini value)identified the monocytosis ratio(PMono),red blood cell count(RBC),and platelet count(PLT)as the most critical CBC parameters.Logistic regression analysis revealed that oxygen therapy(OR=4.367,95%CI:1.568-12.161)and increased work of breathing(OR=3.904,95%CI:2.146-7.101)were relative risk factors for PorPF.Meanwhile,higher PMono(OR=0.696,95%CI:0.640-0.757),RBC(OR=0.201,95%CI:0.124-0.325),and PLT(OR=0.990,95%CI:0.987-0.994)were protective factors.When PMono was used as a predictive marker for PorPF,the area under the receiver operating characteristic curve(AUC)was 0.648 and 0.705,respectively.A random forest model incorporating four risk factors[PMono,RBC,PLT,and hematocrit(HCT)]was constructed to classify PorPF and general cases,achieving AUCs of 0.688 and 0.768,respectively.[Conclusions]PMono,RBC,and PLT may serve as characteristic CBC indicators for predicting pneumonia or prolonged fever in children with HAdV infection.A risk factor model built using PMono,RBC,PLT,and HCT offers a relatively simple and accurate approach to predicting severe cases in pediatric HAdV infections.

Objective To evaluate the management and indicators of pathogen detection before antimicrobial treat-ment for inpatients in second level and above medical institutions(MIs)in Guangdong Province,and provide direc-tion and decision-making basis for the improvement of pathogen detection quality in the region.Methods The ma-nagement status,information system functions,and pathogen detection rate indicators of secondary and above MIs in 21 cities in Guangdong Province was surveyed through online questionnaire surveys and system submission.A baseline survey on sentinel monitoring MIs was conducted from July 15th to August 8th,2023.From November 7th to 30th,a baseline survey on non-sentinel monitoring MIs was launched.Surveys on indicator information of all MIs were completed from January 15th to 30th,2024.Results A total of 265 MIs were surveyed,and the proportions of establishing special working groups(83.98％),developing special action improvement plans(79.01％),estab-lishing pathogen detection rate management systems(91.71％),and developing management assessment plans(76.80％)of tertiary MIs were all higher than that of secondary MIs,differences were all statistically significant(all P＜0.05).The proportion of tertiary MIs with various information system functions was higher than that of secondary MIs(all P＜0.05).The pathogen detection rate(61.07％)before antimicrobial treatment and health-care-associated infection(HAI)diagnosis-related pathogen detection rate(88.00％)of inpatients in tertiary MIs were both higher than those in secondary MIs(both P＜0.05).Among different types of MIs,pathogen detection rate before antimicrobial treatment of inpatients in maternal and child health MIs was higher than that in other types of MIs.HAI diagnosis-related pathogen detection rate in other specialized hospitals was the highest,and pathogen detection rate before combined use of key antimicrobial treatment in traditional Chinese medicine hospitals was the lowest,differences were all statistically significant(all P＜0.05).Conclusion Tertiary MIs have more advantages in management strategies and information technology construction than secondary MIs,secondary MIs need more guidance and support.Monitoring and analysis of pathogen detection rate indicators in MIs of different levels and types should be strengthened through special actions.

Objective To evaluate the management and indicators of pathogen detection before antimicrobial treat-ment for inpatients in second level and above medical institutions(MIs)in Guangdong Province,and provide direc-tion and decision-making basis for the improvement of pathogen detection quality in the region.Methods The ma-nagement status,information system functions,and pathogen detection rate indicators of secondary and above MIs in 21 cities in Guangdong Province was surveyed through online questionnaire surveys and system submission.A baseline survey on sentinel monitoring MIs was conducted from July 15th to August 8th,2023.From November 7th to 30th,a baseline survey on non-sentinel monitoring MIs was launched.Surveys on indicator information of all MIs were completed from January 15th to 30th,2024.Results A total of 265 MIs were surveyed,and the proportions of establishing special working groups(83.98％),developing special action improvement plans(79.01％),estab-lishing pathogen detection rate management systems(91.71％),and developing management assessment plans(76.80％)of tertiary MIs were all higher than that of secondary MIs,differences were all statistically significant(all P＜0.05).The proportion of tertiary MIs with various information system functions was higher than that of secondary MIs(all P＜0.05).The pathogen detection rate(61.07％)before antimicrobial treatment and health-care-associated infection(HAI)diagnosis-related pathogen detection rate(88.00％)of inpatients in tertiary MIs were both higher than those in secondary MIs(both P＜0.05).Among different types of MIs,pathogen detection rate before antimicrobial treatment of inpatients in maternal and child health MIs was higher than that in other types of MIs.HAI diagnosis-related pathogen detection rate in other specialized hospitals was the highest,and pathogen detection rate before combined use of key antimicrobial treatment in traditional Chinese medicine hospitals was the lowest,differences were all statistically significant(all P＜0.05).Conclusion Tertiary MIs have more advantages in management strategies and information technology construction than secondary MIs,secondary MIs need more guidance and support.Monitoring and analysis of pathogen detection rate indicators in MIs of different levels and types should be strengthened through special actions.

Objective To investigate the distribution and antimicrobial resistance of bacterial isolates from blood samples in the hospitals participating in China Antimicrobial Surveillance Network (CHINET) from 2015 to 2021.Methods Bacterial strains isolated from blood samples were collected from 52 medical centers participating in CHINET from 2015 to 2021 for analysis of bacetrial distribution and antimicrobial resistance.Results A total of 153591 isolates were collected,48.8％ of which were gram-positive bacteria and 51.2％ were gram-negative bacteria.The top five bacterial strains were coagulase negative Staphylococcus (28.2％),Escherichia coli (20.7％),Klebsiella (13.7％),Enterococcus (7.2％),and Staphylococcus aureus (6.6％).Compard to female patients,male patients showed lower proportion of E.coli and higher proportions of other bacterial species in all the bacterial isolaets from blood samples.The proportions of Streptococcus pneumoniae and Salmonella in all the bacterial isolaets from blood samples were higher in children compared to adults.Enterobacterales species showed various resistance rates to antimicrobial agents.Overall,≥58.0％,≥36.8％ and ≥56.8％ of E.coli strains were resistant to cefotaxime,gentamicin and levofloxacin respectively over the 7-year period.However,less than 2.5％ of the E.coli strains were resistant to carbapenems.K.pneumoniae showed higher resistance rates to imipenem and meropenem than other Enterobacterales species.During the 7-year period,the prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae increased from 21.4％ and 19.9％ in 2015 to 25.7％ and 26.6％ in 2021,respectively.However,carbapenems still maintained good antibacterial activity against other Enterobacterales,associaetd with lower resistance rates.In the 7-year period,Acinetobacter baumannii showed a dwonward trend in the resistance rates to imipenem and meropenem,but remained 72.9％ and 73.2％ respectively in 2021.The prevalence of imipenem-resistant and meropenem-resistant P.aeruginosa decreased from 26.7％ and 22.9％ in 2015 to 18.5％ and 14.7％ in 2021,respectively.The prevalence of PRSP was 1.5％ in the isolaets from adults and and 0.8％ in the isolates from children.Less than 3.0％ of the Enterococcus faecium and Enterococcus faecalis strains were resistant to vancomycin,teicolanin,or linezolid.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase negative Staphylococcus (MRCNS) was 32.1％ and 81.0％,respectively.The prevalence of MRSA was relatively stable,28.5％ in 2015 and 28.0％ in 2021.Conclusions Coagulase negative Staphylococcus,E.coli and K.pneumoniae were the main bacterial species isolated from blood samples in the hospitals participaing in the CHINET from 2015 to 2021.Significant sex and age differences were found in the distribution of bcterial isolates from blood samples.The overall resistance rates of the top bacetrial strains from blood samples to antimicrobial agents showed a downward trend.Ongoing surveillance of antimicrobial resistance for the isolates from blood samples is still essential for prescribing rational antimicrobial therapies and curbing bacterial resistance.

Pharmacy practice in e-hospital is an innovative form that greatly enhances the accessibility,efficiency,and convenience of medical services,providing continuous health management and chronic disease drug treatment management for patients.To ensure the quality of pharmacy practice in e-hospitals,the standard formulation team for pharmacy practice in e-hospitals adhered to the principles of scientific,universal,instructive,and operability.They comb through key management content from national policy documents,domestic and international standards and regulations,and literature analysis.Combined with the actual work situation of pharmacy practice in e-hospitals,the standard is formulated through multiple rounds of opinion collection and expert verification.This paper interprets the key content of the standard,including basic requirements,service content and processes,and quality management and evaluation improvement,to provide guidance and reference for managers and pharmacists to deeply understand the standard and further enhance the quality of pharmacy practice in e-hospitals.