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Abstract Polyethers play a crucial role in the development of anticancer drugs. To enhance the anticancer efficacy and reduce the toxicity of these compounds, thereby advancing their application in cancer treatment, herein, guided by the structure‐activity relationships of aglycone polyethers, novel aglycone polyethers are rationally redesigned with potentially improved efficacy and reduced toxicity against tumors. To realize the biosynthesis of the novel aglycone polyethers, the gene clusters and the post‐polyketide synthase tailoring pathways for aglycone polyethers endusamycin and lenoremycin are identified and subjected to combinatorial biosynthesis studies, resulting in the creation of a novel aglycone polyether termed End‐16, which demonstrates significant potential for treating bladder cancer (BLCA). End‐16 demonstrates the ability to suppress the proliferation, migration, invasion, and cellular protrusions formation of BLCA cells, as well as induce cell cycle arrest in the G1 phase in vitro. Notably, End‐16 exhibits superior inhibitory activity and fewer side effects against BLCA compared to the frontline anti‐BLCA drug cisplatin in vivo, thereby warranting further preclinical studies. This study highlights the significant potential of integrating combinatorial biosynthesis strategies with rational design to create unnatural products with enhanced pharmacological properties.

Abstract Targeted delivery of glutamine metabolism inhibitors holds promise for cholangiocarcinoma therapy, yet effective delivery vehicles remain a challenge. This study reports the development of a biomimetic nanosystem, termed R‐CM@MSN@BC, integrating mesoporous organosilicon nanoparticles with reactive oxygen species‐responsive diselenide bonds for controlled release of the glutamine metabolism inhibitor bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl) ethyl sulfide (BPTES) and the photosensitizer Ce6. Erythrocyte membrane coating, engineered with Arg‐Gly‐Asp (RGD) peptides, not only enhanced biocompatibility but also improved tumor targeting and tissue penetration. Upon laser irradiation, R‐CM@MSN@BC executed both photodynamic and glutamine‐metabolic therapies, inducing necroptosis in tumor cells and triggering significant immunogenic cell death. Time‐of‐flight mass cytometry analysis revealed that R‐CM@MSN@BC can remodel the immunosuppressive tumor microenvironment by polarizing M1‐type macrophages, reducing infiltration of M2‐type and CX3CR1+ macrophages, and decreasing T cell exhaustion, thereby increasing the effectiveness of anti‐programmed cell death ligand 1 immunotherapy. This strategy proposed in this study presents a viable and promising approach for the treatment of cholangiocarcinoma.

Abstract The Southern Ocean's eddy response to changing climate remains unclear, with observations suggesting non‐monotonic changes in eddy kinetic energy (EKE) across scales. Here simulations reappear that smaller‐mesoscale EKE is suppressed while larger‐mesoscale EKE increases with strengthened winds. This change was linked to scale‐wise changes in the kinetic energy cycle, where a sensitive balance between the dominant mesoscale energy sinks—inverse KE cascade, and source—baroclinic energization. Such balance induced a strong (weak) mesoscale suppression in the flat (ridge) channel. Mechanistically, this mesoscale suppression is attributed to stronger zonal jets weakening smaller mesoscale eddies and promoting larger‐scale waves. These EKE multiscale changes lead to multiscale changes in meridional and vertical eddy transport, which can be parameterized using a scale‐dependent diffusivity linked to the EKE spectrum. This multiscale eddy response may have significant implications for understanding and modeling the Southern Ocean eddy activity and transport under a changing climate.

Abstract Background Cell‐cell communication by carcinoma‐derived exosomes can influence the tumor microenvironment (TME) and regulate cancer progression. Based on the overexpression of microRNA‐21‐5p (miR‐21) in plasma from patients diagnosed with esophageal squamous cell carcinoma (ESCC) and exosomes from ESCC cell lines identified earlier, this study aimed to explore the influence of exosomal miR‐21 within the TME. Method ScRNA‐Seq and Bulk RNA‐Seq were integrated to elucidate the communication between cancer and endothelial cells. The functionality and mechanisms by which exo‐miR‐21 derived from carcinoma regulate endothelial cell‐mediated angiogenesis were assessed using a cocultivation model of EC9706 cells and recipient human umbilical vein endothelial cells (HUVECs), through blood vessel formation experiments, luciferase reporter assays, RT‐qPCR, and western blot analysis. Result A total of 3842 endothelial cells were extracted from the scRNA‐seq data of ESCC samples and reclustered into five cell subtype. Cell‐cell communication analysis revealed cancer cells presented a strong interaction with angiogenesis‐like endothelial cells in secreted signaling. MiR‐21 was unregulated in ESCC and the carcinoma‐derived exo‐miR‐21 was significantly raised in HUVECs. The exo‐miR‐21 promoted the proliferation and migration of HUVECs while also enhancing, closed mesh count, and junction number in HUVECs. Mechanistically, dual‐luciferase reporter assay revealed that PTEN was the target of miR‐21. Meanwhile, p‐Akt was significantly increased and suppressed by inhibition of miR‐21 and PI3K inhibitor LY294002. Conclusion Exo‐miR‐21‐mediated communication between endothelial and cancer cells plays a pivotal role in promoting the angiogenesis of ESCC. Therefore, controlling exo‐miR‐21 could serve as a novel therapeutic strategy for ESCC by targeting angiogenesis.

Objective. To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods. We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results. In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07–1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08–1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04–1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02–1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07–1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61–0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions. Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

Abstract Glioblastoma (GBM) is notorious for malignant neovascularization that contributes to undesirable outcome. However, its mechanisms remain unclear. This study aimed to identify prognostic angiogenesis‐related genes and the potential regulatory mechanisms in GBM. RNA‐sequencing data of 173 GBM patients were obtained from the Cancer Genome Atlas (TCGA) database for screening differentially expressed genes (DEGs), differentially transcription factors (DETFs), and reverse phase protein array (RPPA) chips. Differentially expressed genes from angiogenesis‐related gene set were extracted for univariate Cox regression analysis to identify prognostic differentially expressed angiogenesis‐related genes (PDEARGs). A risk predicting model was constructed based on 9 PDEARGs, namely MARK1, ITGA5, NMD3, HEY1, COL6A1, DKK3, SERPINA5, NRP1, PLK2, ANXA1, SLIT2, and PDPN. Glioblastoma patients were stratified into high‐risk and low‐risk groups according to their risk scores. GSEA and GSVA were applied to explore the possible underlying GBM angiogenesis‐related pathways. CIBERSORT was employed to identify immune infiltrates in GBM. The Pearson's correlation analysis was performed to evaluate the correlations among DETFs, PDEARGs, immune cells/functions, RPPA chips, and pathways. A regulatory network centered by three PDEARGs (ANXA1, COL6A1, and PDPN) was constructed to show the potential regulatory mechanisms. External cohort of 95 GBM patients by immunohistochemistry (IHC) assay demonstrated that ANXA1, COL6A1, and PDPN were significantly upregulated in tumor tissues of high‐risk GBM patients. Single‐cell RNA sequencing also validated malignant cells expressed high levels of the ANXA1, COL6A1, PDPN, and key DETF (WWTR1). Our PDEARG‐based risk prediction model and regulatory network identified prognostic biomarkers and provided valuable insight into future studies on angiogenesis in GBM.

Abstract Background and Aims Leukocytospermia (LCS) is a known cause of male infertility. However, the relationship between seminal leukocytes and semen quality among infertile couples remains controversial. This study aims to investigate the association between semen quality and LCS in male partners of infertile couples. Methods Semen samples were collected from 512 men who asked for a fertility evaluation in a reproductive center in China. Seminal leukocytes were counted following peroxidase staining with benzidine. Other semen parameters were compared in subfertile men with and without LCS. Results Poor semen quality (e.g., low semen volume, sperm concentration, and sperm progressive/total motility) was observed among men with LCS compared to those without LCS. Men with LCS had a higher risk of low sperm progressive motility (OR = 0.99, 95% CI = 0.98−0.99, p = 0.02) and total motility (OR = 0.99, 95% CI = 0.98−0.99, p = 0.02), even after adjustment for potential confounders (both OR = 0.99, 95% CI = 0.98−0.99, p = 0.03). Lower sperm viability was observed in LCS from male partners of secondary couples, while no significant difference in semen parameters was found between men with and without LCS in male partners of primary infertile couples. Low sperm motility and viability were associated with LCS in men from secondary infertile couples after adjusting for confounders (OR = 0.97, 95% CI = 0.95−0.99, p = 0.04; OR = 0.94, 95% CI = 0.89−0.99, p = 0.04, respectively). Conclusions Our findings indicate that a higher risk of abnormal semen parameters was correlated with an increased number of leukocytes in men from secondary infertile couples.

Abstract Background and Objective In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). Material and Methods Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA‐NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S‐1. Multivariate Cox regression was used to confirm optimal predictors of progression‐free survival (PFS), and a nomogram was established to identify patients into low‐risk and high‐risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. Results After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high‐risk cohort had greatly worse 5‐year DMFS, LRFS, PFS and OS compared to low‐risk cohort (all p

Objective C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen and D‐Dimer are used as diagnostic biomarkers of prosthetic joint infection (PJI) after total joint arthroplasty (TJA). The purpose of the study was to investigate the normal trajectory of CRP, ESR, plasma fibrinogen and D‐Dimer at different time points after two‐stage exchange arthroplasty for PJI. Methods We studied 53 patients undergoing two‐stage exchange for PJI at five time points: preoperatively (T0), duration of hospital stays (T1), 30 days (T2), 30–90 days (T3), and 90–180 days (T4) after surgery. The medical records of all patients were well documented and carefully reviewed. The Shapiro–Wilk test was utilized to compare the normal distribution for continuous variables, and the nonnormally distributed data were used for Friedmann's one‐way repeat measures analysis of variances. Post hoc Dunnett's test was used to compare each pair of data to find differences from baseline. Results Compare with T0 point, the levels of CRP and ESR increased significantly and reached peak values at T1 point (all P 0.05). Conclusions The study demonstrated the normal trajectory of CRP, ESR, plasma fibrinogen and D‐Dimer at five time points in patients who underwent two‐stage exchange for PJI. Thus, the results have the possibility of providing signs of infection after the patient receives two‐stage exchange arthroplasty for PJI, which can benefit from early treatment.

Abstract Effective modification of the structure and properties of halide perovskites via the pressure engineering strategy has attracted enormous interest in the past decade. However, sufficient effort and insights regarding the potential properties and applications of the high‐pressure amorphous phase are still lacking. Here, the superior and tunable photoelectric properties that occur in the pressure‐induced amorphization process of the halide perovskite Cs3Bi2I9 are demonstrated. With increasing pressure, the photocurrent with xenon lamp illumination exhibits a rapid increase and achieves an almost five orders of magnitude increment compared to its initial value. Impressively, a broadband photoresponse from 520 to 1650 nm with an optimal responsivity of 6.81 mA W−1 and fast response times of 95/96 ms at 1650 nm is achieved upon successive compression. The high‐gain, fast, broadband, and dramatically enhanced photoresponse properties of Cs3Bi2I9 are the result of comprehensive photoconductive and photothermoelectric mechanisms, which are associated with enhanced orbital coupling caused by an increase in BiI interactions in the [BiI6]3− cluster, even in the amorphous state. These findings provide new insights for further exploring the potential properties and applications of amorphous perovskites.

Objective. We aim to conduct a comparison of the safety and effectiveness performance between left bundle branch area pacing (LBBAP) and right ventricular pacing (RVP) regimens for patients with atrioventricular block (AVB). Methods. This observational cohort study included patients who underwent pacemaker implantations with LBBAP or RVP for AVB indications from the 1st of January 2018 to the 18th of November 2021 at West China Hospital. The primary composite outcome included all-cause mortality, lead failure, or heart failure hospitalization (HFH). The secondary outcome included periprocedure complication, cardiac death, or recurrent unexplained syncope. A 1 : 1 propensity score–matched cohort was conducted for left ventricular (LV) function analysis. Results. A total of 903 patients met the inclusion criteria and completed clinical follow-up. After adjusting for the possible confounders, LBBAP was independently associated with a lower risk of the primary outcome (OR 0.48, 95% CI 0.28 to 0.83, p=0.009), including a lower risk of all-cause mortality and HFH. No significant difference in the secondary outcome was detected between the groups except that LBBAP was independently associated with a lower risk of recurrent unexplained syncope. In the propensity-score matching cohort of echocardiographic analysis, the LV systolic dyssynchrony index was lower in LBBAP compared with that in RVP (5.68±1.92 vs. 6.50±2.28%, p=0.012). Conclusions. Compared to conventional RVP, LBBAP is a feasible novel pacing model associated with a significant reduction in the primary composite outcome. Moreover, LBBAP significantly reduces the risk of recurrent unexplained syncope and improves LV systolic synchrony. This study is registered with ClinicalTrials.gov NCT05722379.

Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient‐ and process‐specific factors affected AVR use in patients with severe AS. Methods and Results We identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area ≤1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08–0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1‐point increase in Combined Comorbidity Index [95% CI, 0.79–0.97]; P=0.01), low‐flow, low‐gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06–0.21]), and low‐gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08–0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38–4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9–130.6) at 730 days. Conclusions The proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low‐gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.

Abstract Background Hypoxia is a hallmark of cancer and is associated with poor prognosis. However, the molecular mechanism by which hypoxia promotes tumor progression remains unclear. MicroRNAs dysregulation has been shown to play a critical role in the tumor and tumor microenvironment. Here, we investigated the roles of miR‐495 and miR‐5688 in human non‐small cell lung cancer (NSCLC) and their underlying mechanism. Methods The expression levels of miR‐495 and miR‐5688 in human NSCLC tissue specimens were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). Deferoxamine (DFO) was used to determine whether the regulation of miR‐495 and miR‐5688 under hypoxia was dependent on hypoxia‐inducible factor 1‐alpha (HIF‐1α). Furthermore, the functions of miR‐495 and miR‐5688 in tumor progression were evaluated using colony formation, 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS), wound healing, transwell assays, and xenograft model. Two algorithms, PicTAR and Targetscan, were used to predict the target gene of these two miRNAs, and dual‐luciferase reporter assay was conducted to confirm the target. The unpaired two‐tailed t test, Pearson correlation analysis, and Fisher's exact probability test were performed for statistical analyses. Results Two miRNAs, miR‐495 and miR‐5688, were found to participate in NSCLC progression under hypoxia. They were down‐regulated in NSCLC tissues compared with normal tissues. We determined that hypoxia led to the down‐regulation of miR‐495 and miR‐5688 in NSCLC cells, which was independent of HIF‐1α and cellular metabolic energy. In addition, miR‐495 and miR‐5688 suppressed cell proliferation, migration, and invasion in vitro. The NSCLC xenograft model showed that miR‐495 and miR‐5688 inhibited tumor formation in vivo. Interestingly, we found that miR‐495 and miR‐5688 had the same target, interleukin‐11 (IL‐11). Recombinant human IL‐11 counteracted the effects of miR‐495 and miR‐5688 on NSCLC cells, suggesting that miR‐495 and miR‐5688 executed their tumor suppressive role by repressing IL‐11 expression. Conclusion We found that hypoxia down‐regulated the expression levels of miR‐495 and miR‐5688 in NSCLC to enhance IL‐11 expression and tumor progression, indicating that the miR‐495/miR‐5688/IL‐11 axis may serve as a therapeutic target and potential biomarker for NSCLC.

Abstract Aims/Introduction The aim of the present study was to identify candidate differentially expressed genes (DEGs) and pathways using bioinformatics analysis, and to improve our understanding of the cause and potential molecular events of diabetic nephropathy. Materials and Methods Two cohort profile datasets (GSE30528 and GSE33744) were integrated and used for deep analysis. We sorted DEGs and analyzed differential pathway enrichment. DEG‐associated ingenuity pathway analysis was carried out. The screened gene expression feature was verified in the db/db mouse kidney cortex. Then, rat mesangial cells cultured with high‐concentration glucose were used for verification. The target genes of transcriptional factor E26 transformation‐specific‐1 (ETS1) were predicted with online tools and validated using chromatin immunoprecipitation assay quantitative polymerase chain reaction. Results The two GSE datasets identified 89 shared DEGs; 51 were upregulated; and 38 were downregulated. Most of the DEGs were significantly enriched in cell adhesion, the plasma membrane, the extracellular matrix and the extracellular region. Quantitative reverse transcription polymerase chain reaction analysis validated the upregulated expression of Itgb2, Cd44, Sell, Fn1, Tgfbi and Il7r, and the downregulated expression of Igfbp2 and Cd55 in the db/db mouse kidney cortex. Chromatin immunoprecipitation assay quantitative polymerase chain reaction showed that Itgb2 was the target gene of transcription factor Ets1. ETS1 knockdown in rat mesangial cells decreased integrin subunit beta 2 expression. Conclusion We found that EST1 functioned as an important transcription factor in diabetic nephropathy development through the promotion of integrin subunit beta 2 expression. EST1 might be a drug target for diabetic nephropathy treatment.

Abstract Aims/Introduction Hyperuricemia (HUA) occurs because of decreased excretion of uric acid, increased synthesis of uric acid or a combination of both mechanisms. The proportions of these three types of HUA in type 2 diabetes patients are not known. In the mean time, we assume that different types of HUA might manifest with different renal damage, even in patients with normal renal filtration function. Materials and Methods We included 435 inpatients with type 2 diabetes at the Metabolic Disease Hospital of Tianjin Medical University from 2015 to 2016. Based on the clearance of uric acid, 90 patients with HUA were divided into three types: synthesis‐increased HUA, excretion‐decreased HUA and mixed type of HUA. Results Patients with the mixed type of HUA had the severest kidney injury manifested by a high level of 24 h urinary microalbumin, urinary immunoglobulin G, transferrin, α‐galactosidase and β2‐microglobulin compared with the normal uric acid group. Urinary immunoglobulin G, transferrin and α‐galactosidase were also increased in patients with synthesis‐increased HUA compared with the normal uric acid group. Patients with excretion‐decreased HUA did not have an increased level of renal impairment markers; however, these patients had an increased body mass index, which might cause dysfunction of kidney excretion. Conclusions Excretion‐decreased HUA is a more common type of HUA in type 2 diabetes patients that might be caused by dysfunction of tubular excretion instead of structural damage. The mixed type of HUA patients had the severest kidney glomerular and tubular damage compared with the normal uric acid group. Clinically, different types of hyperuricemia should be given individualized treatment according to their own characteristics.

Background. Thrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The aim of this study was to evaluate the influence of baseline thrombocytopenia on the prognosis of patients undergoing PCI. Methods. Using the West China Hospital Inpatient Sample database, patients who underwent PCI were identified from August 2012 to January 2019. Baseline thrombocytopenia was defined as a preprocedural platelet count of 100×109/L or less obtained from a routine blood sample taken within 48 hours before coronary PCI. The clinical effect of the advanced thrombocytopenia group (≤85×109/L), according to the median value of platelet count in the thrombocytopenia cohort, was further assessed. The primary outcome was a composite of in-hospital death, bleeding events, and post-PCI transfusion. Results. Of 9531 patients enrolled in our study, 936 had baseline thrombocytopenia and 8595 patients did not have. There were no significant differences in the primary outcome between the two groups. However, advanced thrombocytopenia was independently associated with higher risk of primary outcome (OR 1.67, 95% CI 1.06 to 2.65, p=0.029). Acute coronary syndrome (ACS) patients with thrombocytopenia were associated with higher odds of major bleeding (BARC≥2) (OR 2.56, 95% CI 1.24 to 5.44, p=0.011). Compared with the nonthrombocytopenia group, the thrombocytopenia group with ticagrelor use had higher odds of major bleeding (OR 9.7, 95% CI 1.57 to 60.4 versus OR 0.22, 95% CI 0.03 to 1.69, interaction p=0.025). Conclusions. It seems feasible for patients with thrombocytopenia to receive PCI, but close attention should be paid to advanced thrombocytopenia, the risk of postprocedure bleeding in ACS patients, and the use of more potent P2Y12 inhibitor.

The research of rapid decompression with its effect assessment and protection technology is the problem that must be faced by the future exploration projects such as near space exploration, deep space exploration, and long-term lunar or Mars base. A new reusable quick opening mechanism which can be opened in millisecond is designed to meet the testing requirement of ground simulator for extremely rapid decompression, and the testing results show that the quick opening mechanism can be opened within 0.1 s. The mathematical formulation is also developed, and the comparisons with the results from the literature demonstrate its validity. The CFD simulation and the verification system are established for the airflow in the rapid decompression process under different opening degrees. The simulation results show that the effect of the opening on the decompression process is very obvious and the decompression time corresponding to 50%, 75%, and 100% opening is 479.1 ms, 320.7 ms, and 290.1 ms, respectively. The testing results also show a consistent trend which is 583 ms, 450 ms, and 384 ms, respectively, to reach the equilibrium state.

Abstract Lanthipeptides have extensive therapeutic and industrial applications. However, because many are bactericidal, traditional in vivo platforms are limited in their capacity to discover and mass produce novel lanthipeptides as bacterial organisms are often critical components in these systems. Herein, the development of a cell‐free protein synthesis (CFPS) platform that enables rapid genome mining, screening, and guided overproduction of lanthipeptides in vivo is described. For proof‐of‐concept studies, a type I lanthipeptide, nisin, is selected. Four novel lanthipeptides with antibacterial activity are identified among all nisin analogs in the National Center for Biotechnology Information (NCBI) database in a single day. Further, the CFPS platform is coupled with a screening assay for anti‐gram‐negative bacteria growth, resulting in the identification of a potent nisin mutant, M5. The titers of nisin and the nisin analog are found to be improved with CFPS platform guidance. Owing to the similarities in biosynthesis, the CFPS platform is broadly applicable to other lanthipeptides, thereby providing a universal method for lanthipeptide discovery and overproduction.

Due to the unique and contactless way of identification, radio-frequency identification is becoming an emerging technology for objects tracking. As radio-frequency identification does not provide any distance or bearing information, positioning using radio-frequency identification sensor itself is challenging. Two-dimensional laser range finders can provide the distance to the objects but require complicated recognition algorithms to acquire the identity of object. This article proposes an innovative method to track the locations of dynamic objects by combining radio-frequency identification and laser ranging information. We first segment the laser ranging data into clusters using density-based spatial clustering of applications with noise (DBSCAN). Velocity matching–based approach is used to track the location of object when the object is in the radio-frequency identification reading range. Since the radio-frequency identification reading range is smaller than a two-dimensional laser range finder, velocity matching–based approach fails to track location of the object when the radio-frequency identification reading is not available. In this case, our approach uses the clustering results from density-based spatial clustering of applications with noise to continuously track the moving object. Finally, we verified our approach on a Scitos robot in an indoor environment, and our results show that the proposed approach reaches a positioning accuracy of 0.43 m, which is an improvement of 67.6% and 84.1% as compared to laser-based and velocity matching–based approaches, respectively.

SAP2000 software was used to build the finite element model of a six-storey-three-span reinforced concrete (RC) frame structure. The numerical simulation of the seismic performance of the RC frame structure incorporating different levels of rebar corrosion was conducted using pushover analysis method. The degradation characteristics of the seismic performance of the corroded structure under severe earthquake were also analyzed. The results show that the seismic performance of the RC frame decreased significantly due to corrosion of the longitudinal rebars. And the interstory drift ratios increase dramatically with the increasing of the corrosion rate. At the same time, the formation and development of plastic hinges (beam hinges or column hinges) will accelerate, which leads to a more aggravated deformation of the structure under rare earthquake action, resulting in a negative effect to the seismic bearing capacity of the structure.

Background. Peroxisome proliferator-activated receptor- (PPAR-) γ plays critical roles in human metabolic disorders and has recently been implicated as a regulator of cellular proliferation and inflammatory responses. Regulatory T cells (Tregs), which express high levels of PPAR-γ protein, have the ability to maintain immune tolerance to self-antigens and regulate immune response to Schistosoma infection. However, mechanisms involved in the resolution of these responses are elusive. Methods. Liver and spleen tissue samples in Schistosoma japonicum-infected mice after administration of pioglitazone (a PPAR-γ agonist) were collected. The hepatic and splenic pathologies were detected by H&E and Masson staining. The percentages of Th1/2 and Treg cells in the liver and spleen of each mouse were determined using flow cytometry. Levels of gene expression of PPAR-γ and Foxp3 in tissues or cells were determined using real-time PCR (RT-PCR). Macrophages were treated with pioglitazone in vitro or cocultured with normal purified CD4+ T cells for detecting Treg cells by flow cytometry. The interactions of PPAR-γ with Foxp3 in CD4+ T cells were detected by coimmunoprecipitation. Results. Administration of pioglitazone resulted in the prevention of the development of hepatic and splenic pathologies. Activation of PPAR-γ by pioglitazone resulted in increased percentages of CD4+CD25+Foxp3+ Treg cells and decreased percentages of CD3+CD4+IFN-γ+ and CD3+CD4+IL-4+ cells in the liver and spleen of Schistosoma japonicum-infected mice. In addition, the PPAR-γ agonist can induce Treg cells in vitro directly or by modulating the macrophage’s function indirectly. Furthermore, through interaction with Foxp3 in CD4+ T cells, the PPAR-γ agonist can promote the expression of Foxp3; however, the inhibitor of PPAR-γ weakened the expression of Foxp3 by modifying the coexpression of Foxp3 and PPAR-γ. Conclusions. Our study reveals a previously unrecognized role for PPAR-γ/Foxp3 signaling in regulating the immunopathology that occurs during Schistosoma infection through induction of Treg cells.

Background The optimal range of blood pressure variability remains unclear. We aimed to stratify the degree of risk of stroke based on visit‐to‐visit systolic blood pressure (SBP) variability in a large Chinese hypertensive population in 32 communities. Methods and Results We retrospectively analyzed the data of 20 702 hypertensive patients from the China Stroke Primary Prevention Trial. The participants were randomized into 2 treatment groups to receive either enalapril or enalapril plus folic acid. Their blood pressures were measured every 3 months. The outcome was the first stroke. Three parameters of SBP variability were calculated: standard deviation, coefficient of variation, and average real variability. The records of first 4, 6, 8, 10 and 12 visits at which SBP was measured were used to calculate SBP variability and to predict subsequent stroke risk in adjusted Cox regression models. After median follow‐up of 4.5 years, 597 patients had experienced stroke. Visit‐to‐visit SBP variability was an independent predictor of subsequent stroke (eg, the hazard ratio for the highest quintile of average real variability [22.67–61.07 mm Hg] over 6 visits was 1.55, 95% CI 1.07–2.25, P=0.021), independent of mean SBP over the follow‐up period. Its value was more predictive when more blood pressure records were used. Conclusions Visit‐to‐visit SBP variability is an independent predictor of primary stroke in Chinese hypertensive patients. This predictive value depends on the number of blood pressure measurements used to calculate variability but is independent of mean SBP. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Fraction reduction is a basic computation for rational numbers. P system is a new computing model, while the current methods for fraction reductions are not available in these systems. In this paper, we propose a method of fraction reduction and discuss how to carry it out in cell-like P systems with the membrane structure and the rules with priority designed. During the application of fraction reduction rules, synchronization is guaranteed by arranging some special objects in these rules. Our work contributes to performing the rational computation in P systems since the rational operands can be given in the form of fraction.