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 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

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

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 analyze the correlation of monocyte/high density lipoprotein ratio(MHR),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and bone density,bone metabolism markers in elderly essential hypertension with osteoporosis(OP)patients.Methods:This study was a retrospective study,198 elderly essential hypertension patients who were admitted in our hospital from January 2022 to June 2024 were selected.According to the patient's bone mass test results,patients were divided into normal bone mass group(n=79),osteopenia group(n=68)and OP group(n=51).MHR,NLR,PLR,bone density(left hip,left femoral neck and lumbar spine L1-L4)and bone metabolism markers were compared among three groups,the correlation of MHR,NLR,PLR and bone density,bone metabolism markers were analyzed by Pearson correlation.Results:MHR,NLR,PLR in normal bone mass group,osteopenia group and OP group increased in turn(P＜0.05).The left hip,left femoral neck and lumbar spine L1-L4 bone density in normal bone mass group,osteopenia group,OP group decreased in turn(P＜0.05).25-hydroxyvitamin D[25(OH)D]in normal bone mass group,osteopenia group and OP group decreased in turn,alkaline phosphatase(ALP)and parathyroid hormone(PTH)increased in turn(P＜0.05).MHR,NLR and PLR were negatively correlated with left hip bone density,left femoral neck bone density,lumbar spine L1-L4 bone density,25(OH)D and positively correlated with PTH and ALP(P＜0.05).Conclusion:The increase of MHR,NLR and PLR in elderly essential hypertension with OP patients can affect bone mineral density and bone metabolism.

Objective:To analyze the correlation of monocyte/high density lipoprotein ratio(MHR),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and bone density,bone metabolism markers in elderly essential hypertension with osteoporosis(OP)patients.Methods:This study was a retrospective study,198 elderly essential hypertension patients who were admitted in our hospital from January 2022 to June 2024 were selected.According to the patient's bone mass test results,patients were divided into normal bone mass group(n=79),osteopenia group(n=68)and OP group(n=51).MHR,NLR,PLR,bone density(left hip,left femoral neck and lumbar spine L1-L4)and bone metabolism markers were compared among three groups,the correlation of MHR,NLR,PLR and bone density,bone metabolism markers were analyzed by Pearson correlation.Results:MHR,NLR,PLR in normal bone mass group,osteopenia group and OP group increased in turn(P＜0.05).The left hip,left femoral neck and lumbar spine L1-L4 bone density in normal bone mass group,osteopenia group,OP group decreased in turn(P＜0.05).25-hydroxyvitamin D[25(OH)D]in normal bone mass group,osteopenia group and OP group decreased in turn,alkaline phosphatase(ALP)and parathyroid hormone(PTH)increased in turn(P＜0.05).MHR,NLR and PLR were negatively correlated with left hip bone density,left femoral neck bone density,lumbar spine L1-L4 bone density,25(OH)D and positively correlated with PTH and ALP(P＜0.05).Conclusion:The increase of MHR,NLR and PLR in elderly essential hypertension with OP patients can affect bone mineral density and bone metabolism.

Objective To explore the reliability and safety of continuous monitoring of vital signs in patients using wireless wearable monitoring devices after video-assisted thoracoscopic surgery (VATS) for lung cancer. Methods The patients undergoing VATS for lung cancer in West China Hospital, Sichuan University from May to August 2023 were prospectively enrolled. Both wireless wearable and traditional wired devices were used to monitor the vital signs of patients after surgery. Spearman correlation analysis, paired sample t test and ratio Bland-Altman method were used to test the correlation, difference and consistency of monitoring data measured by the two devices. The effective monitoring rate of the wireless wearable device within 12 hours was calculated to test the reliability of its continuous monitoring. Results A total of 20 patients were enrolled, including 15 females and 5 males with an average age of 46.20±11.52 years. Data collected by the two monitoring devices were significantly correlated (P<0.001). Respiratory rate and blood oxygen saturation data collected by the two devices showed no statistical difference (P>0.05), while heart rate measured by wireless wearable device was slightly lower (=−0.307±1.073, P<0.001), and the blood pressure (=1.259±5.354, P<0.001) and body temperature(=0.115±0.231, P<0.001) were slightly higher. The mean ratios of heart rate, respiratory rate, blood oxygen saturation, blood pressure and body temperature collected by the two devices were 0.996, 1.004, 1.000, 1.014, and 1.003, respectively. The 95% limits of agreement (LoA) and 95% confidence interval of 95%LoA of each indicator were within the clinically acceptable limit. The effective monitoring rate of each vital signs within 12 hours was above 98%. Conclusion The wireless wearable device has a high accuracy and reliability for continuous monitoring vital signs of patients after VATS for lung cancer, which provides a security guarantee for subsequent large-scale clinical application and further research.

Objective To analyze the effect of different retained dosage of lauromacrogol within the thyroid cyst in the sclerotherapy of thyroid cysts.Methods A total of 200 patients with thyroid cysts,who were admitted to the Longyan Municipal First Hospital of China between August 2020 and August 2021,were enrolled in this study.The patients were randomly and equally divided into group zero(suctioning out all the amount of the injected lauromacrogol),and,according to the percentage of the retained lauromacrogol dosage to the total cystic fluid,group 10%,group 20%,group 30%and group 50%,with 40 patients in each group.Thyroid color ultrasound was reviewed at 1,3,6,and 12 months after treatment.The changes of capsule volume,curative efficacy,influencing factors,and adverse reactions after the cyst became sclerosis were analyzed.Logistic regression analysis was used to analyze the factors affecting the postoperative efficacy.Results In all the 5 groups,the suctioned fluid was dark red in colour,and the patients had cystic nodules.The preoperative mean cyst volume was(20.43±5.86)cm3.In all the 5 groups,the postoperative changes in cyst volume indicated that the postoperative one-month cyst volume significantly shrank when compared with the preoperative volume,the postoperative 3-month cyst volume remarkably shrank when compared with the postoperative one-month volume,and the postoperative 6-month cyst volume strikingly shrank when compared with the postoperative 3-month volume(all P＜0.05),while no statistically significant difference in the cyst volume existed between the postoperative 12-month value and the postoperative 6-month value(P＞0.05).The postoperative 6-month total effective rate of all the five groups was 87%(174/200),and no statistically significant differences in the postoperative 6-month curative effect existed between each other among the 5 groups(P＞0.05).Taking the postoperative 6-month curative effect as the dependent variable,and the age,sex,thick cystic wall,cystic septum,and preoperative cyst volume as independent variables,the binary logistic regression analysis was conducted,which revealed that the thick cystic wall(OR=0.24,95%CI=0.08-0.72,P=0.01)and the cystic septum(OR=0.21,95%CI=0.07-0.67,P=0.01)were the factors affecting the postoperative 6-month curative effect.The main side reaction was pain,which was tolerable by patients.There was no significant difference in the incidence of adverse reactions between each other among the five groups(all P＞0.05).Conclusion In treating thyroid cysts by using ultrasound-guided lauromacrogol sclerotherapy,there is no relationship between the curative effect and the percentage of the retained lauromacrogol dosage to the total cystic fluid.The best curative effect can be achieved at 6 months after injection of lauromacrogol,which can be used as the optimal time for follow-up check.The thick cystic wall and the cystic septum are the main factors that affect the curative effect of lauromacrogol sclerotherapy.For the treatment of thyroid cyst,lauromacrogol sclerotherapy carries reliable curative effect with few adverse reactions,therefore,this therapy is worthy of clinical application.(J Intervent Radiol,2024,32:69-73)

Objective To investigate the biological function and main molecular mechanism of long noncoding RNA RMRP(lncRNA RMRP)in endometrial carcinoma.Methods The specimens of carcinoma tissues and adjacent tissues of 30 patients with endometrial carcinoma who received surgical treatment in our hospital were collected.RT-qPCR was used to detect the expression of lncRNA RMRP in endometrial carcinoma tissues and adjacent tissues,and HESC cells and HEC-1-A cells.The endometrial carcinoma cell line HEC-1-A was cultured in vitro,and the Vector,pcDNA-RMRP,NC-siRNA,RMRP-siRNA,NC mimic,miR-580-3p mimic,pcDNA-RMRP+NC mimic,pcDNA-RMRP+ miR-580-3p mimic,RMRP-siRNA+Vector,RMRP-siRNA+pcDNA-JAK2,NC inhibitor,and miR-580-3p inhibitor were transfected into HEC-1-A cells as the Vector group,the pcDNA-RMRP group,the NC-siRNA group,the RMRP-siRNA group,the NC mimic group,the miR-580-3p mimic group,the pcDNA-RMRP+NC mimic group,the pcDNA-RMRP+miR-580-3p mimic group,the RMRP siRNA+Vector group,the RMRP-siRNA+pcDNA-JAK2 group,the NC inhibitor group,and the miR-580-3p inhibitor group respectively.RT-qPCR was used to detect the expression of lncRNA RMRP and miR-580-3p in cells.CCK-8 was used to detect cell proliferation rate.The apoptosis rate was detected by flow cytometry analysis.Bioinformatics software and dual luciferase reporter gene experiment were used to predict and verify the targeted relationships between miR-580-3p and lncRNA RMRP,as well as miR-580-3p and JAK2.Western blot was used to detect the protein expression of JAK/STAT signaling pathway.Results Compared with adjacent tissues,lncRNA RMRP was highly expressed in endometrial carcinoma tissues(P<0.05).Compared with HESC cells,the expression of lncRNA RMRP in HEC-1-A cells was significantly increased(P<0.05).pcDNA-RMRP significantly promoted cell proliferation and inhibited cell apoptosis,while RMRP-siRNA significantly inhibited cell proliferation and promoted cell apoptosis,with statistically significant diferences(P<0.05).miR-580-3p was the downstream target miRNA of lncRNA RMRP,and lncRNA RMRP could negatively regulate the expression of miR-580-3p.JAK2 was the downstream target gene of miR-580-3p,and miR-580-3p could negatively regulate the expression of JAK2 protein.pcDNA-RMRP significantly increased the protein levels of JAK2,p-JAK2 and p-STAT3 in the cells,while co-transfection of pcDNA-RMRP and miR-580-3p mimic significantly decreased the protein levels of JAK2,p-JAK2 and p-STAT3,with statistically significant diferences(P<0.05).RMRP-siRNA could signifi-cantly reduce the protein levels of JAK2,p-JAK2 and p-STAT3 in cells.After co-transfection of RMRP-siRNA and pcDNA-JAK2,the protein levels of JAK2,p-JAK2 and p-STAT3 were significantly increased,with statistically significant diferences(P<0.05).In addition,co-transfection of RMRP-siRNA and pcDNA-JAK2 increased cell proliferation and decreased cell apoptosis,with statistically significant diferences(P<0.05).Conclusion Knockdown of lncRNA RMRP could inhibit endometrial carcinoma cell proliferation and promote cell apoptosis by regulating JAK2/STAT3 signaling pathway,which might be a potential therapeutic target for endometrial carcinoma.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.