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 This study aims to systematically evaluate the evidence-based medicine of traditional Chinese medicine(TCM)in the treatment of dry eye,analyze its efficacy and differences compared with modern Western medicine treatments,and provide a scientific basis for clinical application.Methods By searching Chinese and English databases(including CNKI,Wanfang Data,PubMed,Cochrane Library,etc.),we included meta-analyses and systematic reviews of TCM treatments for dry eye.Literature was screened according to strict inclusion and exclusion criteria,and relevant data were extracted and integrated for analysis.The Mantel-Haenszel fixed-effects model was used to calculate the relative risk(RR)and mean difference(WMD),with the effect size expressed as a 95％confidence interval,to analyze the efficacy in-dicators of TCM treatment for dry eye.Results A total of 21 articles were finally included,involving various TCM inter-ventions for dry eye(such as Chinese herbal medicine,acupuncture,and TCM external therapies).The results showed that TCM treatment was superior to Western medicine alone in improving the overall clinical efficacy[RR=1.63,95％CI(1.46,1.81),P＜0.05],prolonging tear film break-up time[MD=2.23,95％CI(1.85,2.60),P＜0.05],and increasing tear secretion[MD=1.49,95％CI(1.04,1.94),P＜0.05].In addition,acupuncture,the combination of Chinese herbal medicine and Western medicine,and TCM external therapies all demonstrated unique advantages in improving dry eye symptoms and tear function.Conclusion TCM treatment for dry eye shows significant efficacy in key indicators such as overall clinical efficacy,tear film break-up time,and tear secretion,with a high level of safety.

Objective This study aims to systematically evaluate the evidence-based medicine of traditional Chinese medicine(TCM)in the treatment of dry eye,analyze its efficacy and differences compared with modern Western medicine treatments,and provide a scientific basis for clinical application.Methods By searching Chinese and English databases(including CNKI,Wanfang Data,PubMed,Cochrane Library,etc.),we included meta-analyses and systematic reviews of TCM treatments for dry eye.Literature was screened according to strict inclusion and exclusion criteria,and relevant data were extracted and integrated for analysis.The Mantel-Haenszel fixed-effects model was used to calculate the relative risk(RR)and mean difference(WMD),with the effect size expressed as a 95％confidence interval,to analyze the efficacy in-dicators of TCM treatment for dry eye.Results A total of 21 articles were finally included,involving various TCM inter-ventions for dry eye(such as Chinese herbal medicine,acupuncture,and TCM external therapies).The results showed that TCM treatment was superior to Western medicine alone in improving the overall clinical efficacy[RR=1.63,95％CI(1.46,1.81),P＜0.05],prolonging tear film break-up time[MD=2.23,95％CI(1.85,2.60),P＜0.05],and increasing tear secretion[MD=1.49,95％CI(1.04,1.94),P＜0.05].In addition,acupuncture,the combination of Chinese herbal medicine and Western medicine,and TCM external therapies all demonstrated unique advantages in improving dry eye symptoms and tear function.Conclusion TCM treatment for dry eye shows significant efficacy in key indicators such as overall clinical efficacy,tear film break-up time,and tear secretion,with a high level of safety.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Perimenopause is a vulnerable stage for emotional disorders such as anxiety and depression,which is the result of a combination of bio-psycho-social factors,and it seriously affect the quality of life of perimenopausal women.Therefore,finding safe and effective treatments is one of the urgent problems in modern medicine.This paper summarises the etiology and treatment of emotional disorder in perimenopause in Chinese and western medicine,and on this basis,this paper discusses the clinical diagnostic and treatment strategies and research ideas of acupuncture in treating emotional disorder in perimenopause,thus providing a new idea for the prevention and treatment of emotional disorder in perimenopause.

The study aimed to explore the effects of inoculation of Rhizophagus intraradices on the biomass, effective component content, and endogenous hormone content of Salvia miltiorrhiza through pot experiments. The number of leaves, plant height, dry weight of aboveground and underground parts, branch number, root number, root length, root diameter, and other biomass were mea-sured by weighing and counting methods. The content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, tanshinone Ⅱ_A, cryptotanshinone, and other effective components was determined by ultra-high performance liquid chromatography. The content of ABA and GA_3 was determined by triple quadrupole mass spectrometry. The correlations between biomass and effective components and between effective components and plant hormones ABA and GA_3 were analyzed. The results showed that R. intraradices significan-tly increased the aboveground dry weight, leaf number, and root number of S. miltiorrhiza by 0.24-0.65 times, respectively. The content of salvianolic acid B and rosmarinic acid in the aboveground part and the content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, and tanshinone Ⅱ_A in the underground part were significantly increased by 0.44-1.78 times, respectively. R. intraradices infection significantly increased the GA_3/ABA values of aboveground and underground parts by 3.82 and 76.47 times, respectively. The correlation analysis showed that caffeic acid, the effective component of the aboveground part, was significantly positively correlated with plant height, tanshinone Ⅱ_A, the effective component of the underground part, was significantly positively correlated with biomass root number, cryptotanshinone, and dry weight, while rosmarinic acid was significantly negatively correlated with dry weight. There were significant positive correlations between cryptotanshinone and ABA, tanshinone Ⅱ_A and ABA and GA_3, and caffeic acid and GA_3. In conclusion, R. intraradices can promote the accumulation of biomass and secondary metabolites of S. miltiorrhiza and regulate the balance between plant hormones ABA and GA_3, thereby promoting the growth of S. miltiorrhiza.
Salvia miltiorrhiza/chemistry* ; Plant Growth Regulators/analysis* ; Plant Roots/chemistry*

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

Abstract: Objective　To understand the distribution and drug resistance of common pathogens of fungal bloodstream infection in Sichuan, and to provide reference for clinicians to empirically treat fungal bloodstream infection. Methods　From November 1, 2019 to December 31, 2020, fungal strains isolated from blood culture of patients diagnosed with bloodstream infection in 19 tertiary first-class general hospitals in Sichuan Province were collected for mass spectrometry identification and drug susceptibility, and the results were statistically analyzed, along with a retrospective analysis of clinical data. Results　A total of 255 fungal strains were received and identified by mass spectrometry, 215 strains of Candida spp (84.3%), 28 strains of Cryptococcus neoformans (11.0%), 4 strains of Talaromyces marneffei (1.6%) and 8 strains of others (3.1%). Among the Candida spp 90 strains of Candida albicans, 39 strains of Candida parapsilosis complex, 36 strains of Candida glabrata, 33 strains of Candida tropicalis, 8 strains of Candida guilliermondii, and 9 strains of other Candida. In the department, the ICU was predominant, accounting for 35.7%. The top four Candida (Candida albicans, Candida parapsilosis complex, Candida glabrata, Candida tropicalis) were analyzed for drug sensitivity, Candida albicans and Candida parapsilosis complex group were more sensitive to antifungal drugs, the sensitivity rates of Candida albicans to fluconazole, voriconazole, anidulafungin, caspofungin, micarafungin were 89.2%, 92.8%, 97.6%, 97.6%, 96.4%, respectively. The sensitivity rates of Candida parapsilosis to fluconazole and voriconazole were 89.7% and 94.9%, and to anidulafungin, caspofungin and micafungin were all 100%. Echinocandins had stronger antibacterial activity against Candida spp., Candida parapsilosis complex and Candida tropicalis had 100% sensitivity to echinocandins, Candida albicans had more than 95% sensitivity to echinocandins, and Candida glabrata had about 90% sensitivity to echinocandins. Candida tropicalis was less sensitive to fluconazole and voriconazole with 66.7% and 54.5%, and the sensitivity of Candida glabrata to fluconazole was mainly concentrated in susceptible dose dependent (SDD), accounting for 91.4%. The four Candida species did not show resistance to amphotericin B, all of them showed wild-type strains, Candida tropicalis showed the highest non-wild-type rate to posaconazole and itraconazole with 21.2% and 36.4%, and the drug sensitivity results of Cryptococcus neoformans showed that 4 out of 23 strains showed resistance to amphotericin B (non-wild-type) and 3 strains showed resistance to fluconazole (non-wild-type). Conclusions　The fungus of bloodstream infection is mainly Candida spp.. Among of them, Candida albicans accounts for the highest percentage, echinocandins have good antibacterial effect on Candida, Candida is sensitive to amphotericin B as wild type, but Candida tropicalis has slightly higher resistance rate to fluconazole and voriconazole, and the non-wild type rate of Cryptococcus neoformans to amphotericin B is increasing, and clinicians should pay high attention to the rational use of antifungal drugs.

Objective: To understand the characteristics and depressive status of men who have sex with men (MSM) who self-reported HIV infection through heterosexual transmission and to provide evidence for personalized management of HIV infected people. Methods: A cross-sectional survey was carried out in Shandong province from September to December in 2019. Male HIV patients aged ≥15 years who self-reported HIV infection through heterosexual transmission were selected to verify the route of infection by one-to-one interview in Ji'nan, Qingdao, Weifang and Linyi cities of Shangdong province. According to the 1∶1 ratio, local HIV patients with age difference ≤3 years who self-reported MSM were selected as controls. A questionnaire survey was conducted, including data on demographic characteristics, behavior status, CES-D and PSSS. The related factors of the depressive symptoms and characteristics were analyzed. Results: A total of 373 male HIV patients were interviewed, and 39.7%(148/373) were confirmed as MSM after reexamination. The interviewers were: aged (40.3±12.0) years old, 41.9% (62/148) married/cohabiting. 27.0% (40/148) had been tested before HIV diagnosis, 71.6% (106/148) had homosexual partners ≥2 and 55.4% (82/148) had depressive symptom. Multivariate analysis showed that the MSM without HIV testings before diagnosis, had homosexual partners ≥2 before diagnosis, had first homosexual behavior at the age >30 years old and with depressive symptoms were more likely to conceal the true infection route. The incidence of depression among MSM who self-reported HIV infection through heterosexual transmission was related to physical health status social support and occupational stability. Conclusions: Some male HIV persons self-reported as being heterosexually transmitted were really transmitted through homosexual behavior. There were high-risk behaviors such as multiple partners and intersex among this group, and with high incidence of depression. It is necessary to encourage the reexamination program during follow-up and target on psychological and behavioral interventions, continuously.
Male ; Humans ; Adult ; Middle Aged ; Heterosexuality ; Depression/epidemiology* ; HIV Infections/epidemiology* ; Self Report ; Homosexuality, Male ; Cross-Sectional Studies ; Sexual and Gender Minorities