Isocucurbitacin B inhibits glioma growth through PI3K/AKT pathways and increases glioma sensitivity to TMZ by inhibiting hsa-mir-1286a.

Aim: Glioma accounts for 81% of all cancers of the nervous system cancers and presents one of the most drug-resistant malignancies, resulting in a relatively high mortality rate. Despite extensive efforts, the complete treatment options for glioma remain elusive. The effect of isocucurbitacin B (isocuB), a natural compound extracted from melon pedicels, on glioma has not been investigated. This study aims to investigate the inhibitory effect of isocuB on glioma and elucidate its underlying mechanisms, with the objective of developing it as a potential therapeutic agent for glioma. Methods: We used network pharmacology and bioinformatics analysis to predict potential targets and associated pathways of isocuB in glioma. Subsequently, the inhibitory effect of isocuB on glioma and its related mechanisms were assessed through Counting Kit-8 (CCK-8), wound healing, transwell, Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and other in vitro experiments, alongside tumor formation experiments in nude mice. Results: Based on this investigation, it suggested that isocuB might inhibit the growth of gliomas through the PI3K-AKT and MAPK pathways. Additionally, we proposed that isocuB may enhance glioma drug sensitivity to temozolomide (TMZ) via modulation of hsa-mir-1286a. The CCK-8 assay revealed that isocuB exhibited inhibitory effects on U251 and U87 proliferation and outperformed TMZ. Wound healing and transwell experiments showed that isocuB inhibited the invasion and migration of U251 cells by suppressing the activity of MMP-2/9, N-cadherin, and Vimentin. The TdT-mediated dUTP-biotin nick end labeling (TUNEL) and flow cytometry (FCM) assays revealed that isocuB induced cell apoptosis through inhibition of BCL-2. Subsequently, we conducted RT-qPCR and WB experiments, which revealed that PI3K/AKT and MAPK pathways might be involved in the mechanism of the inhibition isocuB on glioma. Additionally, isocuB promoted the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a. Furthermore, we constructed TMZ-resistant U251 strains and demonstrated effective inhibition by isocuB against these resistant strains. Finally, we confirmed that isocuB can inhibit tumor growth in vivo through experiments on tumors in nude mice. Conclusion: IsocuB may protect against glioma by acting on the PI3K/AKT and MAPK pathways and promote the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.

Intracardiac echocardiography-guided catheter ablation of highly symptomatic accelerated idioventricular rhythm originating from the right ventricular apical diverticulum.

Ventricular diverticula are saccule-like structures formed by the protrusion of the ventricular myocardium from the endocardial surface towards the free wall. Most diverticula are muscular structures, and patients usually have no obvious clinical symptoms. However, diverticula may contribute to arrhythmogenesis due to localized myocardial structural disturbances. Right ventricular apical diverticulum (RVAD) is very rare, and we report a case of highly symptomatic accelerated idioventricular rhythm (AIVR) originating from the RVAD that underwent intracardiac echocardiography (ICE)-guided catheter ablation with no recurrence during follow-up.

Regulated cell death in glioma: promising targets for natural small-molecule compounds.

Gliomas are prevalent malignant tumors in adults, which can be categorized as either localized or diffuse gliomas. Glioblastoma is the most aggressive and deadliest form of glioma. Currently, there is no complete cure, and the median survival time is less than one year. The main mechanism of regulated cell death involves organisms coordinating the elimination of damaged cells at risk of tumor transformation or cells hijacked by microorganisms for pathogen replication. This process includes apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, necrosis, parthanayosis, entosis, lysosome-dependent death, NETosis, oxiptosis, alkaliptosis, and disulfidaptosis. The main goal of clinical oncology is to develop therapies that promote the effective elimination of cancer cells by regulating cell death are the main goal of clinical oncology. Recently, scientists have utilized pertinent regulatory factors and natural small-molecule compounds to induce regulated cell death for the treatment of gliomas. By analyzing the PubMed and Web of Science databases, this paper reviews the research progress on the regulation of cell death and the role of natural small-molecule compounds in glioma. The aim is to provide help for the treatment of glioblastoma.

[Trueness of different digital design methods for incisal guidance of maxillary anterior implant-supported single crowns].

OBJECTIVE: To compare the trueness of incisal guidance of implant-supported single crowns designed by patient-specific motion (PSM) with that designed by average-value virtual articulator (AVA). METHODS: The study had recruited 12 participants with complete dentition and stable incisal guidance. An intraoral scanner was used to scan digital casts and record two types of patient-specific motion (data only including protrusive movement, and data including protrusive movement and lateral protrusive movement). The lingual surfaces of the maxillary incisors which guided the protrusive movement was selected and elevated to create a reference cast. A maxillary central incisor of original casts was vir-tually extracted and implanted to generate a working cast. The Dental system software program was used to design implant-supported single crowns with the anatomical coping design method. The incisal guidance was designed by different methods. The incisal guidance in control group was designed by the average-value virtual articulator. The incisal guidance in experiment groups was designed by the patient-specific motion only including protrusive movement (PSM1) and with the patient-specific motion including protrusive movement and lateral protrusive movement (PSM2). The incisal guidance of prosthesis designed by these 3 methods were compared with the original incisal guidance in Geomagic Control 2015 (3DSystem, America). The measurements included: Average of positive values, ratio of positive area and maximum value reflecting supra-occlusion; average of negative values, ratio of negative area and minimum value reflecting over-correction; and root mean square reflecting overall deviation. RESULTS: Statistical data were collected using the median (interquartile range) method. The average of positive values, ratio of positive area and average of negative values of the PSM2 group were smaller than those of the control group [8.0 (18.8) µm vs. 37.5 (47.5) µm; 0 vs. 7.2% (38.1%); -109.0 (63.8) µm vs.-66.5 (64.5) µm], and the ratio of negative area of PSM2 group was larger than those of the control group [52.9% (47.8%) vs. 17.3% (45.3%)], with significant differences (P all < 0.05). The ratio of positive area [0.1% (7.0%)] and average of negative values [-97.0 (61.5) µm] of PSM1 group, were smaller than those of the control group, and the ratio of negative area [40.7% (39.2%)] of the PSM1 group was larger than that of the control group, with significant differences (P < 0.05). The average of positive values [20.0 (42.0) µm] and ratio of positive area of PSM1 group was larger than that of the PSM2 group with significant differences (P < 0.05). CONCLUSION: To establish the incisor guidance of implant-supported single crowns, compared with the average-value virtual articulator and the patient-specific motion only including protrusive movement, the patient-specific motion including protrusive movement and lateral protrusive movement is more conducive to reducing the protrusive interference of prosthesis and improving the occlusal fit.

Temporal-spatial risk assessment of COVID-19 under the influence of urban spatial environmental parameters: The case of Shenyang city.

Respiratory infection is the main route for the transmission of coronavirus pneumonia, and the results have shown that the urban spatial environment significantly influences the risk of infection. Based on the Wells-Riley model of respiratory infection probability, the study determined the human respiratory-related parameters and the effective influence range; extracted urban morphological parameters, assessed the ventilation effects of different spatial environments, and, combined with population flow monitoring data, constructed a method for assessing the risk of Covid-19 respiratory infection in urban-scale grid cells. In the empirical study in Shenyang city, a severe cold region, urban morphological parameters, population size, background wind speed, and individual behavior patterns were used to calculate the distribution characteristics of temporal and spatial concomitant risks in urban areas grids under different scenarios. The results showed that the correlation between the risk of respiratory infection in urban public spaces and the above variables was significant. The exposure time had the greatest degree of influence on the probability of respiratory infection risk among the variables. At the same time, the change in human body spacing beyond 1 m had a minor influence on the risk of infection. Among the urban morphological parameters, building height had the highest correlation with the risk of infection, while building density had the lowest correlation. The actual point distribution of the epidemic in Shenyang from March to April 2022 was used to verify the evaluation results. The overlap rate between medium or higher risk areas and actual cases was 78.55%. The planning strategies for epidemic prevention and control were proposed for the spatial differentiation characteristics of different risk elements. The research results can accurately classify the risk level of urban space and provide a scientific basis for the planning response of epidemic prevention and control and the safety of public activities.

Differential role of STIM1 in calcium handling in coronary and intrarenal arterial smooth muscles.

Calcium (Ca2+) dysregulation contributes to various vascular diseases, but the role and underlying mechanism of stromal interaction molecule-1 (STIM1) in Ca2+ signaling and vasocontraction remain elusive. By using smooth muscle-specific STIM1 knockout (sm-STIM1 KO) mice and a multi myograph system, we investigated the differential role of STIM1 in Ca2+ handling between coronary and intrarenal arterial smooth muscles. After STIM1 deletion, contractile responses to 5-HT were obviously reduced in coronary and intrarenal arteries in the sm-STIM1 KO mice, but not altered in U46619. Phenylephrine barely induced the contraction of coronary arteries, we only detected an effect on the contraction of intrarenal arteries, which was also reduced in the sm-STIM1 KO mice. Then, L-type Ca2+ channel (Cav1.2)- mediated vasocontractions were significantly enhanced in coronary and intrarenal arteries in sm-STIM1 KO mice, similar to treatment with the Cav1.2 agonist Bay K8644 in coronary arteries. However, non-Cav1.2-mediated vasocontractions were remarkably reduced. IP3 receptor- and ryanodine receptor-mediated vasocontractions were both obviously decreased in coronary and intrarenal arteries in sm-STIM1 KO mice. Moreover, STIM1-mediated store operated Ca2+ entry (SOCE) only participated in the contraction of intrarenal arteries. In conclusion, we demonstrate that STIM1 participates in Cav1.2, sarcoplasmic reticulum (SR) Ca2+ release and store-operated Ca2+ (SOC) channels-mediated vasocontraction, which exhibits obvious organ-specificity between coronary and intrarenal arteries.

Advanced glycation end products induce senescence of atrial myocytes and increase susceptibility of atrial fibrillation in diabetic mice.

Diabetes mellitus (DM) is a common chronic metabolic disease caused by significant accumulation of advanced glycation end products (AGEs). Atrial fibrillation (AF) is a common cardiovascular complication of DM. Here, we aim to clarify the role and mechanism of atrial myocyte senescence in the susceptibility of AF in diabetes. Rapid transesophageal atrial pacing was used to monitor the susceptibility of mice to AF. Whole-cell patch-clamp was employed to record the action potential (AP) and ion channels in single HL-1 cell and mouse atrial myocytes. More importantly, anti-RAGE antibody and RAGE-siRNA AAV9 were used to investigate the relationship among diabetes, aging, and AF. The results showed that elevated levels of p16 and retinoblastoma (Rb) protein in the atrium were associated with increased susceptibility to AF in diabetic mice. Mechanistically, AGEs increased p16/Rb protein expression and the number of SA-ß-gal-positive cells, prolonged the action potential duration (APD), reduced protein levels of Cav1.2, Kv1.5, and current density of ICa,L , IKur in HL-1 cells. Anti-RAGE antibody or RAGE-siRNA AAV9 reversed these effects in vitro and in vivo, respectively. Furthermore, downregulating p16 or Rb by siRNA prevented AGEs-mediated reduction of Cav1.2 and Kv1.5 proteins expression. In conclusion, AGEs accelerated atrial electrical remodeling and cellular senescence, contributing to increased AF susceptibility by activating the p16/Rb pathway. Inhibition of RAGE or the p16/Rb pathway may be a potential therapeutic target for AF in diabetes.

Bifidobacterium lactis combined with Lactobacillus plantarum inhibit glioma growth in mice through modulating PI3K/AKT pathway and gut microbiota.

Glioma is a common primary aggressive tumor with limited clinical treatment. Recently, growing research suggests that gut microbiota is involved in tumor progression, and several probiotics can inhibit tumor growth. However, evidence for the effect of probiotics on glioma is lacking. Here, we found that Bifidobacterium (B.) lactis combined with Lactobacillus (L.) plantarum reduced tumor volume, prolonged survival time and repaired the intestinal barrier damage in an orthotopic mouse model of glioma. Experiments demonstrated that B. lactis combined with L. plantarum suppressed the PI3K/AKT pathway and down-regulated the expression of Ki-67 and N-cadherin. The glioma-inhibitory effect of probiotic combination is also related to the modulation of gut microbiota composition, which is characterized by an increase in relative abundance of Lactobacillus and a decrease in some potential pathogenic bacteria. Additionally, probiotic combination altered fecal metabolites represented by fatty acyls and organic oxygen compounds. Together, our results prove that B. lactis combined with L. plantarum can inhibit glioma growth by suppressing PI3K/AKT pathway and regulating gut microbiota composition and metabolites in mice, thus suggesting the potential benefits of B. lactis and L. plantarum against glioma.

Determining the Efficiency of the Sponge City Construction Pilots in China Based on the DEA-Malmquist Model.

Sponge city construction (SCC) has improved the quality of the urban water ecological environment, and the policy implementation effect of SCC pilots is particularly remarkable. Based on the data envelopment analysis (DEA) model, this study employed the related index factors such as economy, ecology, infrastructure, and the population of the pilot city as the input, and the macro factors of SCC as the output, to scientifically evaluate the relative efficiency between the SCC pilots in China. Eleven representative SCC pilots were selected for analysis from the perspectives of static and dynamic approaches, and comparisons based on the horizontal analysis of the efficiency of SCC pilots were conducted and some targeted policy suggestions are put forward, which provide a reliable theoretical model and data support for the efficiency evaluation of SCC. This paper can be used as a reference for construction by providing a DEA model for efficiency evaluation methods and thus helps public sector decision makers choose the appropriate construction scale for SCC pilots.

New antibacterial depsidones from an ant-derived fungus Spiromastix sp. MY-1.

Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data. The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp. MY-1. All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria. Particularly, new bromide compound 4, named spiromastixone S, exhibited the strongest activity against Xanthomonas oryzae pv. oryzae with a MIC value of 5.2 µmol·-1.

Basis and current state of computed tomography perfusion imaging: a review.

Computed tomography perfusion (CTP) is a functional imaging that allows for providing capillary-level hemodynamics information of the desired tissue in clinics. In this paper, we aim to offer insight into CTP imaging which covers the basics and current state of CTP imaging, then summarize the technical applications in the CTP imaging as well as the future technological potential. At first, we focus on the fundamentals of CTP imaging including systematically summarized CTP image acquisition and hemodynamic parameter map estimation techniques. A short assessment is presented to outline the clinical applications with CTP imaging, and then a review of radiation dose effect of the CTP imaging on the different applications is presented. We present a categorized methodology review on known and potential solvable challenges of radiation dose reduction in CTP imaging. To evaluate the quality of CTP images, we list various standardized performance metrics. Moreover, we present a review on the determination of infarct and penumbra. Finally, we reveal the popularity and future trend of CTP imaging.

Noise Characteristics Modeled Unsupervised Network for Robust CT Image Reconstruction.

Deep learning (DL)-based methods show great potential in computed tomography (CT) imaging field. The DL-based reconstruction methods are usually evaluated on the training and testing datasets which are obtained from the same distribution, i.e., the same CT scan protocol (i.e., the region setting, kVp, mAs, etc.). In this work, we focus on analyzing the robustness of the DL-based methods against protocol-specific distribution shifts (i.e., the training and testing datasets are from different region settings, different kVp settings, or different mAs settings, respectively). The results show that the DL-based reconstruction methods are sensitive to the protocol-specific perturbations which can be attributed to the noise distribution shift between the training and testing datasets. Based on these findings, we presented a low-dose CT reconstruction method using an unsupervised strategy with the consideration of noise distribution to address the issue of protocol-specific perturbations. Specifically, unpaired sinogram data is enrolled into the network training, which represents unique information for specific imaging protocol, and a Gaussian mixture model (GMM) is introduced to characterize the noise distribution in CT images. It can be termed as GMM based unsupervised CT reconstruction network (GMM-unNet) method. Moreover, an expectation-maximization algorithm is designed to optimize the presented GMM-unNet method. Extensive experiments are performed on three datasets from different scan protocols, which demonstrate that the presented GMM-unNet method outperforms the competing methods both qualitatively and quantitatively.

Regulation of temozolomide resistance via lncRNAs: Clinical and biological properties of lncRNAs in gliomas (Review).

Gliomas are a primary types of intracranial malignancies and are characterized by a poor prognosis due to aggressive recurrence profiles. Temozolomide (TMZ) is an auxiliary alkylating agent that is extensively used in conjunction with surgical resection and forms the mainstay of clinical treatment strategies for gliomas. However, the frequent occurrence of TMZ resistance in clinical practice limits its therapeutic efficacy. Accumulating evidence has demonstrated that long non­coding RNAs (lncRNAs) can play key and varied roles in glioma progression. lncRNAs have been reported to inhibit glioma progression by targeting various signaling pathways. In addition, the differential expression of lncRNAs has also been found to mediate the resistance of glioma to several chemotherapeutic agents, particularly to TMZ. The present review article therefore summarizes the findings of previous studies in an aim to report the significance and function of lncRNAs in regulating the chemoresistance of gliomas. The present review may provide further insight into the clinical treatment of gliomas.

Exploring the Mechanism of Hawthorn Leaves Against Coronary Heart Disease Using Network Pharmacology and Molecular Docking.

Hawthorn leaves, which is a traditional Chinese medicine (TCM), has been used for treating coronary heart disease (CHD) for a long time in China. But the limited understanding of the main active components and molecular mechanisms of this traditional medicine has restricted its application and further research. The active compounds of hawthorn leaves were obtained from TCMSP database and SymMap database. The targets of it were predicted based on TCMSP, PubChem, Swiss Target Prediction, and SymMap database. The putative targets of CHD were gathered from multi-sources databases including the Online Mendelian Inheritance in Man (OMIM) database, the DrugBank database, the GeneCards database and the DisGeNet database. Network topology analysis, GO and KEGG pathway enrichment analyses were performed to select the key targets and pathways. Molecular docking was performed to demonstrate the binding capacity of the key compounds to the predicted targets. Furthermore, RAW264.7 cells stimulated by lipopolysaccharides (LPS) were treated with three effective compounds of hawthorn leaves to assess reliability of prediction. Quercetin, isorhamnetin and kaempferol were main active compounds in hawthorn leaves. Forty four candidate therapeutic targets were identified to be involved in protection of hawthorn leaves against CHD. Additionally, the effective compounds of it had good binding affinities to PTGS2, EGFR, and MMP2. Enrichment analyses suggested that immune inflammation related biological processes and pathways were possibly the potential mechanism. Besides, we found that three predicted effective compounds of hawthorn leaves decreased protein expression of PTGS2, MMP2, MMP9, IL6, IL1B, TNFα and inhibited activation of macrophage. In summary, the present study demonstrates that quercetin, kaempferol and isorhamnetin are proved to be the main effective compounds of hawthorn leaves in treatment of CHD, possibly by suppressing expression of PTGS2, MMP2, MMP9, inflammatory cytokines and macrophages viability. This study provides a new understanding of the active components and mechanisms of hawthorn leaves treating CHD from the perspective of network pharmacology.

The combination of ciprofloxacin and indomethacin suppresses the level of inflammatory cytokines secreted by macrophages in vitro.

PURPOSE: The combined use of antibiotics and anti-inflammatory medicine to manage bacterial endotoxin-induced inflammation following injuries or diseases is increasing. The cytokine level produced by macrophages plays an important role in this treatment course. Ciprofloxacin and indomethacin, two typical representatives of antibiotics and anti-inflammatory medicine, are cost-effective and has been reported to show satisfactory effect. The current study aims to investigate the effect of ciprofloxacin along with indomethacin on the secretion of inflammatory cytokines by macrophages in vitro. METHODS: Primary murine peritoneal macrophages and RAW 264.7 cells were administrated with lipopolysaccharide (LPS) for 24 h. The related optimal dose and time point of ciprofloxacin or indomethacin in response to macrophage inflammatory response inflammation were determined via macrophage secretion induced by LPS. Then, the effects of ciprofloxacin and indomethacin on the secretory functions and viability of various macrophages were determined by enzyme-linked immunosorbent assay and flow cytometry analysis, especially for the levels of interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF)-α. The optimal dose and time course of ciprofloxacin affecting macrophage inflammatory response were determined by testing the maximum inhibitory effect of the drugs on pro-inflammatory factors at each concentration or time point. RESULTS: According to the levels of cytokines secreted by various macrophages (1.2 × 106 cells/well) after administration of 1 µg/mL LPS, the optimal dose and usage timing for ciprofloxacin alone were 80 µg/mL and 24 h, respectively, and the optimal dose for indomethacin alone was 10 µg/mL. Compared with the LPS-stimulated group, the combination of ciprofloxacin and indomethacin reduced the levels of IL-1ß (p < 0.05), IL-6 (p < 0.05), IL-10 (p < 0.01)), and TNF-α (p < 0.01). Furthermore, there was greater stability in the reduction of inflammatory factor levels in the combination group compared with those in which only ciprofloxacin or indomethacin was used. CONCLUSION: The combination of ciprofloxacin and indomethacin suppressed the levels of inflammatory cytokines secreted by macrophages in vitro. This study illustrates the regulatory mechanism of drug combinations on innate immune cells that cause inflammatory reactions. In addition, it provides a new potential antibacterial and anti-inflammatory treatment pattern to prevent and cure various complications in the future.

Noise modelling of perfusion CT images for robust hemodynamic parameter estimations.

Objective.The radiation dose of cerebral perfusion computed tomography (CPCT) imaging can be reduced by lowering the milliampere-second or kilovoltage peak. However, dose reduction can decrease image quality due to excessive x-ray quanta fluctuation and reduced detector signal relative to system electronic noise, thereby influencing the accuracy of hemodynamic parameters for patients with acute stroke. Existing low-dose CPCT denoising methods, which mainly focus on specific temporal and spatial prior knowledge in low-dose CPCT images, not take the noise distribution characteristics of low-dose CPCT images into consideration. In practice, the noise of low-dose CPCT images can be much more complicated. This study first investigates the noise properties in low-dose CPCT images and proposes a perfusion deconvolution model based on the noise properties.Approach.To characterize the noise distribution in CPCT images properly, we analyze noise properties in low-dose CPCT images and find that the intra-frame noise distribution may vary in the different areas and the inter-frame noise also may vary in low-dose CPCT images. Thus, we attempt the first-ever effort to model CPCT noise with a non-independent and identical distribution (i.i.d.) mixture-of-Gaussians (MoG) model for noise assumption. Furthermore, we integrate the noise modeling strategy into a perfusion deconvolution model and present a novel perfusion deconvolution method by using self-relative structural similarity information and MoG model (named as SR-MoG) to estimate the hemodynamic parameters accurately. In the presented SR-MoG method, the self-relative structural similarity information is obtained from preprocessed low-dose CPCT images.Main results.The results show that the presented SR-MoG method can achieve promising gains over the existing deconvolution approaches. In particular, the average root-mean-square error (RMSE) of cerebral blood flow (CBF), cerebral blood volume, and mean transit time was improved by 40.3%, 69.1%, and 40.8% in the digital phantom study, and the average RMSE of CBF can be improved by 81.0% in the clinical data study, compared with tensor total variation regularization deconvolution method.Significance.The presented SR-MoG method can estimate high-accuracy hemodynamic parameters andachieve promising gains over the existing deconvolution approaches.

Mdivi-1 alleviates cardiac fibrosis post myocardial infarction at infarcted border zone, possibly via inhibition of Drp1-Activated mitochondrial fission and oxidative stress.

Mitochondrial division inhibitor 1(Mdivi-1) has been shown to play a beneficial role in a variety of diseases, mainly by inhibiting Drp1-mediated mitochondrial fission. The effects of Mdivi-1 on cardiac fibrosis at infarcted border zone area and its possible mechanism remain unclear. This study aimed to investigate the effects of Mdivi-1 on reactive cardiac fibrosis and cardiac function post myocardial infarction and its potential mechanisms. Mice were randomly divided into six groups (n = 9 for each group): Sham; Mdivi-1; MI 7d; MI 14d; MI 28d; MI 28d + Mdivi-1. The MI model was induced by ligation of LAD coronary artery. Mdivi-1 (1 mg/kg) was administered to mice every other day at a time from the second day until the sacrifice of the mice (total 14 injection of Mdivi-1). In vitro experiments, the effect of Mdivi-1 on TGF-ß1-induced fibrosis-related pathophysiological changes of fibroblasts was examined in NIH3T3 cells. We found that Mdivi-1 significantly attenuated fibroblast activation, collagen production and fibrosis at infarcted border zone after MI, improved impaired heart function. Mechanistically, we observed that Mdivi-1 reduced the protein expression of P-Drp1-S616 and abnormal mitochondrial fission of cardiac fibroblasts in the infarcted border zone area. In addition, we found that the effects of Mdivi-1 partially relied on increasing the expression of Hmox1 and inhibiting oxidative stress. In conclusion, Mdivi-1 could attenuate cardiac fibrosis at infarcted border zone and improve impaired heart function partially through attenuation of Drp1-mediated mitochondrial fission. Moreover, inhibition of oxidative stress, which is possible due to the up-regulation of Hmox1, may be another potential mechanism of action of Mdivi-1.

Optimal design of building openings to reduce the risk of indoor respiratory epidemic infections.

The design of indoor airflow environments can significantly reduce the risk of respiratory epidemic infections indoors. Some studies have successfully developed theoretical models for calculating the effect of airflow fields on infection rates. However, up until now, studies have primarily focused on simulating and calculating the distribution of viral infection rates in current building scenarios. Due to the lack of a direct influence model for the design parameters and infection rate calculation, the present studies lack a quantitative analysis of the design parameters. This paper investigates the building openings design approach in a medium-sized kindergarten in Germany, intending to explore passive-based design solutions to improve the building's ability to prevent the virus' spread. We calculate the infection rate distribution in space by CFD combined with the Wells-Riley model. And then, use the Grasshopper platform to build an optimization model with the design parameters of building openings and infection rate values to discuss the relationship between geometric parameters and infection rate variation. The results show that the building openings' design parameters in transition spaces significantly affect the indoor infection rate under the condition that the input wind speed at the building openings is stable. We can see that optimizing building openings significantly reduces the average infection rate in space. The infection rate in the area with the largest decrease can be reduced by 18.41%. The distribution of infection rate in space is much more uniform, and the excess area is significantly reduced. This study has implications for future research and practice in designing public buildings under the influence of long-standing and cyclical outbreaks of epidemics.

[Clinical Study of the Impact of ACE I/D Gene Variation on the Clinical Parameters of Patients with Polycystic Ovary Syndrome].

OBJECTIVE: To investigate the relationship between angiotensin Ⅰ-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the genetic risks for polycystic ovary syndrome (PCOS) and to evaluate the impact of ACE I/D genotypes on clinical, hormonal, metabolic and oxidative stress parameters in patients with PCOS. METHODS: This was a retrospective case-control study involving a total of 1 020 PCOS patients and 825 female controls who visited the outpatient clinic of the Department of Reproductive Endocrinology, West China Second Hospital of Sichuan University between 2006 and 2019. The ages of the subjects ranged between 17 and 44. The ACE I/D genotypes were determined by polymerase chain reaction (PCR) and gel electrophoresis. 667 PCOS patients and 527 controls were selected for an analysis of their genotypes and the hormonal, metabolic and oxidative stress parameters. RESULTS: The genotype distributions of the ACE I/D single nucleotide polymorphism was in Hardy-Weinberg equilibrium in both the PCOS group and the control group (all P>0.05), which was representative of the population. There were no statistically significant differences in genotype and allele frequencies between the PCOS and the control groups ( P>0.05). After adjusting for both age and body mass index (BMI), there was no statistically significant difference in clinical characteristics among all genotypes in either the PCOS group or the control group. In the PCOS group, compared with the II genotype subgroup, the ID genotype subgroup had lower luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, while the DD genotype subgroup had higher homeostatic model assessment of insulin resistance (HOMA-IR) and malondialdehyde (MDA) levels. Compared with the ID genotype subgroup, the DD genotype subgroup had lower serum sex hormone binding globulin (SHBG) level, but higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels ( P<0.05). In the control group, II genotype subgroup had a higher level of total oxidant status (TOS) than that of the DD genotype subgroup. CONCLUSION: ACE I/D genetic polymorphism is not associated with risks for PCOS. The I/D variation of ACE gene may be related to insulin resistance, dyslipidaemia, hyperandrogenemia and oxidative stress in PCOS patients.