Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.

Objective To explore the effect of maternal exercise on blood pressure,cardiac pheno-type and susceptibility to myocardial is chemia/reperfusion(MI/R)injury in adult male offsprings of mice.Methods Pregnant mice were randomly divided into a sedentary group(p-Ctr)and an exercise group(p-EX),each of 12.The exercise group underwent daily 60-minutenon-weight bearing swim-ming from gestational day(GD)1 to 18,6 days a week.Then,their male offsprings at 3 months of age(3M)were selected as the research subjects,namely the Ctr-3M group and the EX-3M group,with 12 mice in each group.The MI/R model was established by ligation of the anterior descending branch of the left coronary artery(LAD)surgery(30 min of ischemia,24 h of reperfusion).Then,the systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP)were monitored non-invasively via tail artery blood pressure measurement,while the cardiac function was detected by using the small animal ultrasound.Moreover,the cardiac morphology and col-lagen volume fraction(CVF)of myocardium was observed by HE staining and Masson staining,respec-tively.Meanwhile,the cross-sectional area(CSA)of myocardial cells and myocardial infarction area(INF/AAR)was measured using WGA staining and Evans Blue-TTC double staining,accordingly.What's more,the apoptosis index(AI)of myocardial cells and serum cardiac troponin I(cTnI)were de-tected by using TUNEL staining and ELISA,respectively,while the expression levels of Bax and Bcl-2 proteins were determined by using Western blotting.Results 1)From GD11 to GD19,the body weight of females in the p-EX group was always significantly lower than that in the p-Ctr group(GD11,GD13;P<0.05;GD12,GD14～GD19;P<0.01),but there was no significant difference in the litter size and abortion rate(P>0.05).2)There were no significant differences between the EX-3M and Ctr-3M groups in the heart weight(HW),body weight(BW)and heart weight to body weight ratio(HW/BW),SBP,DBP,MAP,myocardial CVF,and CSA of male offsprings(P>0.05).After MI/R surgery,in both p-Ctr and p-EX groups,myocardial transverse striations disappeared and cardiomyocytes were disarranged with degeneration and necrosis.Moreover,CVF of the EX-3M group was significantly lower than the Ctr-3M group after MI/R surgery(P<0.05).3)No significant differenc-es were found between the Ctr-3M and EX-3M groups in the average cardiac ejection fraction(EF),fractional shortening(FS),left ventricle internal diameter in diastole(LVIDd),and left ventricle inter-nal diameter in systole(LVIDs)(P>0.05).However,after the MI/R surgery,the postoperative EF and FS(P<0.01),and LVIDs(P<0.05)in the EX-3M group were significantly higher than the Ctr-3M group,without significant difference in LVIDd(P>0.05).4)After MI/R surgery,the average AI,INF/AAR and serum cTnI level of the EX-3M group were significantly lower than the Ctr-3M group(P<0.01 for all).5)The relative expression level of myocardial Bcl-2 protein after MI/R surgery in the EX-3M group was significantly higher than the Ctr-3M group(P<0.05),while that of myocardial Bax protein(P<0.05)and the Bax/Bcl-2 ratio(P<0.01)were significantly lower than the latter.Conclu-sions Prenatal exercise significantly reduces the susceptibility to myocardial ischemia injury in 3-month-old male mice offspring,improves the contractile function of their heart,and attenuates the degree of cardiomyocyte apoptosis and necrosis,exerting a cardioprotective effect in MI/R injury.

Objective To explore the effect of maternal exercise on blood pressure,cardiac pheno-type and susceptibility to myocardial is chemia/reperfusion(MI/R)injury in adult male offsprings of mice.Methods Pregnant mice were randomly divided into a sedentary group(p-Ctr)and an exercise group(p-EX),each of 12.The exercise group underwent daily 60-minutenon-weight bearing swim-ming from gestational day(GD)1 to 18,6 days a week.Then,their male offsprings at 3 months of age(3M)were selected as the research subjects,namely the Ctr-3M group and the EX-3M group,with 12 mice in each group.The MI/R model was established by ligation of the anterior descending branch of the left coronary artery(LAD)surgery(30 min of ischemia,24 h of reperfusion).Then,the systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP)were monitored non-invasively via tail artery blood pressure measurement,while the cardiac function was detected by using the small animal ultrasound.Moreover,the cardiac morphology and col-lagen volume fraction(CVF)of myocardium was observed by HE staining and Masson staining,respec-tively.Meanwhile,the cross-sectional area(CSA)of myocardial cells and myocardial infarction area(INF/AAR)was measured using WGA staining and Evans Blue-TTC double staining,accordingly.What's more,the apoptosis index(AI)of myocardial cells and serum cardiac troponin I(cTnI)were de-tected by using TUNEL staining and ELISA,respectively,while the expression levels of Bax and Bcl-2 proteins were determined by using Western blotting.Results 1)From GD11 to GD19,the body weight of females in the p-EX group was always significantly lower than that in the p-Ctr group(GD11,GD13;P<0.05;GD12,GD14～GD19;P<0.01),but there was no significant difference in the litter size and abortion rate(P>0.05).2)There were no significant differences between the EX-3M and Ctr-3M groups in the heart weight(HW),body weight(BW)and heart weight to body weight ratio(HW/BW),SBP,DBP,MAP,myocardial CVF,and CSA of male offsprings(P>0.05).After MI/R surgery,in both p-Ctr and p-EX groups,myocardial transverse striations disappeared and cardiomyocytes were disarranged with degeneration and necrosis.Moreover,CVF of the EX-3M group was significantly lower than the Ctr-3M group after MI/R surgery(P<0.05).3)No significant differenc-es were found between the Ctr-3M and EX-3M groups in the average cardiac ejection fraction(EF),fractional shortening(FS),left ventricle internal diameter in diastole(LVIDd),and left ventricle inter-nal diameter in systole(LVIDs)(P>0.05).However,after the MI/R surgery,the postoperative EF and FS(P<0.01),and LVIDs(P<0.05)in the EX-3M group were significantly higher than the Ctr-3M group,without significant difference in LVIDd(P>0.05).4)After MI/R surgery,the average AI,INF/AAR and serum cTnI level of the EX-3M group were significantly lower than the Ctr-3M group(P<0.01 for all).5)The relative expression level of myocardial Bcl-2 protein after MI/R surgery in the EX-3M group was significantly higher than the Ctr-3M group(P<0.05),while that of myocardial Bax protein(P<0.05)and the Bax/Bcl-2 ratio(P<0.01)were significantly lower than the latter.Conclu-sions Prenatal exercise significantly reduces the susceptibility to myocardial ischemia injury in 3-month-old male mice offspring,improves the contractile function of their heart,and attenuates the degree of cardiomyocyte apoptosis and necrosis,exerting a cardioprotective effect in MI/R injury.

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

Objective:To explore the correlation between color Doppler ultrasound, Cyfra21-1, Fer and malignant ovarian lesions and the value of combined model identification.Methods:A total of 108 patients with suspected ovarian cancer admitted to our hospital from Jan. 2021 to Dec. 2023 were selected as subjects. All patients were tested by color Doppler ultrasound, Cyfra21-1 and Fer, and were divided into malignant group (61 cases) and benign group (47 cases) according to the pathological test results. The baseline data, ultrasound parameters, Cyfra21-1 and Fer levels of the two groups were compared, and multivariate regression analysis was performed to establish a multi-factor combined model, and ROC curve was used to evaluate the differential efficacy of the combined model.Results:There was no significant difference in baseline data such as age and course of disease between the two groups ( P>0.05). In the malignant group, the lesion diameter was (7.66±1.24) cm, with solid echo detection in 37 cases and inner wall with nipple detection in 38 cases. In the benign group, the lesion diameter was (5.14±1.03) cm, with solid echo detection in 18 cases and inner wall with nipple detection in 17 cases. In the malignant group, PS was (22.94±4.61) cm/s, EDV was (15.67±3.42) cm/s, VM was (12.43±3.15) cm/s. PS, EDV and VM in benign group were (15.63±4.24) cm/s, (8.95±3.04) cm/s and (17.08±4.21) cm/s respectively, and those in malignant group were higher than those in benign group ( P<0.05). RI in the malignant group was 0.35±0.06, RI in the benign group was 0.58±0.13, and RI in the malignant group was lower than that in the benign group ( P<0.05). Multivariate regression analysis showed that lesion diameter, solid echo, inner wall with papilla, PS, EDV, VM, Cyfra21-1, Fer and RI were all independent risk factors for ovarian malignant lesions, and lesion diameter, solid echo, inner wall with papilla, PS, EDV, VM, Cyfra21-1 and Fer were positively correlated with ovarian malignant lesions. RI was negatively correlated with ovarian malignant lesions ( P<0.05). ROC curve results showed that the diagnostic efficiency of the combined model was higher than that of the single use of Doppler ultrasound, Cyfra21-1 and Fer. Conclusion:The combined diagnosis model of color Doppler ultrasound, Cyfra21-1 and Fer is helpful to improve the diagnostic efficiency of ovarian malignant lesions.

Objective:To evaluate the effectiveness of oral-nasal oxygen supply mouth guard in painless gastroscopy for snoring patients.Methods:The snoring patients who underwent painless gastroscopy at two Endoscopy Centers of Shanghai East Hospital, Tongji University in July 2022 were randomly divided into the observation group (using oral-nasal oxygen supply mouth guard) and the control group (using ordinary nasal oxygen tube and mouth guard). Parameters such as the wearing time and the removal time of the mouth guard, lowest pulse oxygen saturation (SpO 2), incidence of hypoxemia, and the satisfaction of medical staff were compared between the two groups. Results:The wearing time of mouth guard was 11.63±0.84 seconds and the removal time was 5.33±0.76 seconds in the observation group ( n=40), which were lower than those in the control group ( n=47) (14.91±1.21 seconds, t=-14.463, P<0.001; 10.38±0.80 seconds, t=-30.095, P<0.001). The wearing satisfaction score was 9.80±0.61, the lowest SpO 2 was (96.70±3.42)%, the removal satisfaction score was 9.75±0.67, and the anesthesiologists' satisfaction score was 9.20±1.42 in the observation group, which were higher than those in the control group [7.70±0.93, t=12.209, P<0.001; (94.06±3.72)%, t=3.417, P=0.001; 7.96±0.98, t=9.803, P<0.001; 8.13±1.35, t=3.615, P=0.001] with significant difference. There was no significant difference in the incidence of hypoxemia [10.00% (4/40) VS 14.89% (7/47), χ2=0.130, P=0.718] and endoscopic physician satisfaction score (9.30±0.97 VS 9.02±1.31, t=1.112, P=0.269) between the two groups. Conclusion:The oral-nasal oxygen supply mouth guard is easy to wear and remove, effectively reducing SpO 2 fluctuations during painless gastroscopy for snoring patients. It can enhance medical staff satisfaction with high clinical value.

Aim Investigating the effects of exercise during pregnancy on blood pressure and brain ischemia-reperfusion injury in 1-month-old(1M)and 3-month-old(3M)offspring of spontaneously hypertensive rat(SHR).Methods SHR and Wistar Kyoto rats(WKY)were selected,they were paired in a 1∶1 male-to-female ratio within the same strain,and the first day of pregnancy was confirmed by the presence of copulatory plugs and sperm on a vaginal smear.Pregnant rats were randomly divided into pregnancy sedentary group(p-WKY-SED,p-SHR-SED)and pregnancy exercise group(p-WKY-EX,p-SHR-EX).The rats in the exercise group were performed non-weight-bearing swimming for 60 minutes per day,6 days per week,in water 40 cm deep at a temperature of 34～35 ℃,until the 20th day of preg-nancy.The body weight of the pregnant rats,as well as physiological indicators such as fetal weight,body length,and placental efficiency were monitored to reflect the growth and development of the fetus.1M and 3M offspring were selected as research subjects,non-invasive blood pressure was measured in the tail artery,a rat middle cerebral artery occlusion(MCAO)model was prepared by using the thread embolism method,and the area of cerebral infarction was observed 24 hours after reperfusion.Results(1)Compared with p-WKY-SED group,the body weight of p-SHR-SED pregnant rats was significantly decreased(P＜0.01);there was no significant difference in the litter size among all groups of preg-nant rats(P＞0.05).(2)Compared with p-SHR-SED group,exercise during pregnancy can significantly increase the body weight and placental efficiency of both female and male fetal rats in the p-SHR-EX group(P＜0.05),and decrease the weight of the placenta(P＜0.05).(3)Compared with p-WKY-SED group,the body weight of both female and male offspring rats at 1M and 3M was significantly decreased in the p-SHR-SED group,and their blood pressure was significantly increased(P＜0.01);Compared with p-SHR-SED group,exercise during pregnancy had no significant effect on the body weight and blood pressure of 1M offspring in the p-SHR-EX group(P＞0.05),but it could significantly reduce the blood pressure of 3M male offspring in the p-SHR-EX group(P＜0.01);The body weight and blood pressure of 3M male off-spring were significantly higher in p-WKY-SED group and p-SHR-SED group than those of female in the same group(P＜0.01).(4)Compared with p-WKY-SED group,the infarct area of MCAO injury in both female and male offspring rats at 1M and 3M was significantly increased in the p-SHR-SED group(P＜0.01);Compared with p-SHR-SED group,exercise during pregnancy can significantly reduce the infarct area of MCAO injury in both female and male offspring at 1M and 3M in the p-SHR-EX group(P＜0.05).Conclusion Aerobic exercise during pregnancy can significantly improve blood pressure in the offspring of hypertensive rats,and reduce their susceptibility to ischemic reperfusion injury in the brain as adults.

Aim Investigating the effects of exercise during pregnancy on blood pressure and brain ischemia-reperfusion injury in 1-month-old(1M)and 3-month-old(3M)offspring of spontaneously hypertensive rat(SHR).Methods SHR and Wistar Kyoto rats(WKY)were selected,they were paired in a 1∶1 male-to-female ratio within the same strain,and the first day of pregnancy was confirmed by the presence of copulatory plugs and sperm on a vaginal smear.Pregnant rats were randomly divided into pregnancy sedentary group(p-WKY-SED,p-SHR-SED)and pregnancy exercise group(p-WKY-EX,p-SHR-EX).The rats in the exercise group were performed non-weight-bearing swimming for 60 minutes per day,6 days per week,in water 40 cm deep at a temperature of 34～35 ℃,until the 20th day of preg-nancy.The body weight of the pregnant rats,as well as physiological indicators such as fetal weight,body length,and placental efficiency were monitored to reflect the growth and development of the fetus.1M and 3M offspring were selected as research subjects,non-invasive blood pressure was measured in the tail artery,a rat middle cerebral artery occlusion(MCAO)model was prepared by using the thread embolism method,and the area of cerebral infarction was observed 24 hours after reperfusion.Results(1)Compared with p-WKY-SED group,the body weight of p-SHR-SED pregnant rats was significantly decreased(P＜0.01);there was no significant difference in the litter size among all groups of preg-nant rats(P＞0.05).(2)Compared with p-SHR-SED group,exercise during pregnancy can significantly increase the body weight and placental efficiency of both female and male fetal rats in the p-SHR-EX group(P＜0.05),and decrease the weight of the placenta(P＜0.05).(3)Compared with p-WKY-SED group,the body weight of both female and male offspring rats at 1M and 3M was significantly decreased in the p-SHR-SED group,and their blood pressure was significantly increased(P＜0.01);Compared with p-SHR-SED group,exercise during pregnancy had no significant effect on the body weight and blood pressure of 1M offspring in the p-SHR-EX group(P＞0.05),but it could significantly reduce the blood pressure of 3M male offspring in the p-SHR-EX group(P＜0.01);The body weight and blood pressure of 3M male off-spring were significantly higher in p-WKY-SED group and p-SHR-SED group than those of female in the same group(P＜0.01).(4)Compared with p-WKY-SED group,the infarct area of MCAO injury in both female and male offspring rats at 1M and 3M was significantly increased in the p-SHR-SED group(P＜0.01);Compared with p-SHR-SED group,exercise during pregnancy can significantly reduce the infarct area of MCAO injury in both female and male offspring at 1M and 3M in the p-SHR-EX group(P＜0.05).Conclusion Aerobic exercise during pregnancy can significantly improve blood pressure in the offspring of hypertensive rats,and reduce their susceptibility to ischemic reperfusion injury in the brain as adults.

The hydrolysis of xylo-oligosaccharides catalyzed by β-xylosidase plays an important role in the degradation of lignocellulose. However, the enzyme is easily inhibited by its catalytic product xylose, which severely limits its application. Based on molecular docking, this paper studied the xylose affinity of Aspergillus niger β-xylosidase An-xyl, which was significantly differentially expressed in the fermentation medium of tea stalks, through cloning, expression and characterization. The synergistic degradation effect of this enzyme and cellulase on lignocellulose in tea stems was investigated. Molecular docking showed that the affinity of An-xyl to xylose was lower than that of Aspergillus oryzae β-xylosidase with poor xylose tolerance. The K_i value of xylose inhibition constant of recombinant-expressed An-xyl was 433.2 mmol/L, higher than that of most β-xylosidases of the GH3 family. The K_m and V_max towards pNPX were 3.6 mmol/L and 10 000 μmol/(min·mL), respectively. The optimum temperature of An-xyl was 65 ℃, the optimum pH was 4.0, 61% of the An-xyl activity could be retained upon treatment at 65 ℃ for 300 min, and 80% of the An-xyl activity could be retained upon treatment at pH 2.0-8.0 for 24 h. The hydrolysis of tea stem by An-xyl and cellulase produced 19.3% and 38.6% higher reducing sugar content at 2 h and 4 h, respectively, than that of using cellulase alone. This study showed that the An-xyl mined from differential expression exhibited high xylose tolerance and higher catalytic activity and stability, and could hydrolyze tea stem lignocellulose synergistically, which enriched the resource of β-xylosidase with high xylose tolerance, thus may facilitate the advanced experimental research and its application.
Aspergillus niger/genetics* ; Xylose/metabolism* ; Molecular Docking Simulation ; Xylosidases/genetics* ; Cellulases ; Tea ; Hydrogen-Ion Concentration ; Substrate Specificity

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation