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Atherosclerosis (AS) and its related cardiovascular diseases (CVDs) remain the most frequent cause of morbidity and mortality worldwide. Researches showed that bisphenol A (BPA) exposure might exacerbate AS progression. However, as an analogue of BPA, little is known about the cardiovascular toxicity of bisphenol S (BPS), especially whether BPS exposure has the pro-atherogenic effects in mammals is still unknown. Here, we firstly constructed an apolipoprotein E knockout (ApoE -/- ) mouse model and cultured cells to investigate the risk of BPS on AS and explore the underlying mechanisms. Results showed that prolonged exposure to 50 μg/kg body weight (bw)/day BPS indeed aggravated AS lesions both in the en face aortas and aortic sinuses of ApoE -/- mice. Moreover, BPS were found to be implicated in the AS pathological process: 1) stimulates adhesion molecule expression to promote monocyte-endothelial cells (ECs) adhesion with 3.6 times more than the control group in vivo; 2) increases the distribution of vascular smooth muscle cells (VSMCs) with 9.3 times more than the control group in vivo, possibly through the migration of VSMCs; and 3) induces an inflammatory response by increasing the number of macrophages (MACs), with 3.7 times more than the control group in vivo, and the release of inflammatory mediators. Furthermore, we have identified eight significant AS-related genes induced by BPS, including angiopoietin-like protein 7 (Angptl17) and lipocalin-2 (Lcn2) in ECs; matrix metalloproteinase 9 (Mmp13), secreted phosphoprotein 1 (Spp1), and collagen type II alpha 1 (Col2a1) in VSMCs; and kininogen 1 (Kng1), integrin alpha X (Itgax), and MAC-expressed gene 1 (Mpeg1) in MACs. Overall, this study firstly found BPS exposure could exacerbate mammalian AS and might also provide a theoretical basis for elucidating BPS and its analogues induced AS and related CVDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical efficacy of roxithromycin combined with azithromycin sequential therapy in the treatment of mycoplasma pneumoniae pneumonia in children., Methods: A retrospective study was conducted on 100 patients with mycoplasma pneumoniae pneumonia admitted to The First Affiliated Hospital of Yangtze University from January 2020 to December 2022. All patients were divided into the observation group (roxithromycin combined with azithromycin sequential therapy) and the control group (azithromycin sequential therapy), with 50 cases in each group. The clinical efficacy, improvement time of clinical symptoms/signs, inflammation indexes, oxidative stress indexes and immune function levels of the two groups were compared. Moreover, the improvement of lung function indexes and the adverse reactions were observed., Results: The overall response rate of the observation group was 96.00%, which was higher than the control group (84.00%) ( p< 0.05). The time of clinical symptoms/signs in the observation group were significantly lower than those in the control group( p< 0.05). After treatment, significant improvements were seen in the levels of CRP, TNF-ɑ, IL-6, GSH-Px, SOD, MDA, CD3 + , CD4 + , CD4 + /CD8 + , IgM, IgG , IgA, FEV 1 , FEV 1 %, FVC and FEV 1 /FVC of the two groups compared with those before treatment ( p< 0.05), and the improvement in the observation group was more obvious than that in the control group( p< 0.05). The overall incidence of adverse reactions in the observation group was 6.00%, which was slightly lower than that in the control group (8.00%) (c²=0.154, P =0.695)., Conclusion: Roxithromycin combined with azithromycin sequential therapy is a safe regimen for the treatment of mycoplasma pneumoniae pneumonia in children., Competing Interests: Declaration of conflicting interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury)., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA., Method: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedure‑related parameters, and follow‑up data and analyzed the impact of previous abdominal surgery and traction technique., Results: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3-15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor., Conclusion: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Different from the traditional frequency-mixing technique which employs a contacting transducer, the laser-induced acoustic nonlinear frequency-mixing detection technique utilizes a laser source to instigate crack motion and generate acoustic waves. Thus, apart from the temperature oscillation induced by the pump laser, the "basic temperature" originating from the probe laser can also influence the crack. This additional variable complicates the contact state of the crack, yielding a more diverse range of nonlinear acoustic signal attributes. In light of this, our study enhances the conventional opto-acoustic nonlinear frequency mixing experimental setup by integrating an independent heating laser beam. This modification isolates the impact of the "basic temperature" on crack width while also dialing down the probe laser power to mitigate its thermal effects. To amplify the sensitivity of crack detection, we deliberated on the optimal laser source parameters for this setup. Consequently, our revamped system, paired with fine-tuned parameters, captures nonlinear acoustic signals with an enriched feature set. This investigation can provide support for the non-contact opto-acoustic nonlinear frequency mixing technique in the detection and evaluation of micro-cracks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chen-Yin NI reports financial support was provided by the Fundamental Research Funds for the Central Universities of China. Zhong-Hua SHEN reports financial support was provided by the National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To analyze the factors affecting the long-term clinical efficacy and quality of life in the treatment of pediatric acute lymphoblastic leukemia (ALL)., Methods: This is a retrospective study. One hundred children with ALL were collected before June, 2018 at The First Affiliated Hospital of Yangtze University and followed up for five years. Not only were their five-years survival rates analyzed, but univariate and multivariate analyses were also performed for factors that might affect their five-year survival rates. The MOS 36-Item Short Form of Health Survey (SF-36) was utilized to investigate the surviving children after five years in order to analyze the factors that may affect the quality of life of the children., Results: The five-years survival rate of one hundred children with ALL after treatment was 91.00% (91/100). Univariate and multivariate Logistic regression analyses were performed on the factors that may affect the long-term efficacy of pediatric ALL. The results showed that white blood cell count at first diagnosis, prednisone response test, treatment compliance and recurrence were independent risk factors for the long-term efficacy of pediatric ALL(p<0.05). The SF-36 survey of 91 surviving children after five years showed that prednisone response test and treatment compliance were independent risk factors affecting the quality of life of pediatric ALL(p<0.05)., Conclusion: In the initial diagnosis of pediatric ALL, sufficient attention and control should be given to the factors that may affect the long-term clinical efficacy and quality of life, and appropriate treatment plans should be adopted. Meanwhile, the treatment compliance of children should be improved during treatment to improve the survival rate and quality of life of pediatric ALL., Competing Interests: Declaration of conflicting interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically., Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated., Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1β, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway., Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research., Competing Interests: The authors declared that they have no conflicts of interest in this work., (© 2024 Zhang et al.)

Photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique is an effective method for detecting micro-cracks. When using this technique for micro-crack detection, the selection of laser source parameters is particularly crucial. Compared to traditional piezo-transducer-based mixing techniques, the characteristic of using a laser as the detection source is the presence of thermal effects. The thermal effect caused by laser irradiation on the sample surface can not only generate acoustic waves but also affect the crack state, thus influencing nonlinear signals. In this paper, an experimental setup using photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique has been set up to investigate the thermal effects of the probe laser source. In addition, a corresponding physical model has been established to discuss the physical mechanisms revealed by the experimental results. This study provides a basis for selecting appropriate probe source parameters and scanning positions of laser sources when detecting micro-cracks using the photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fungal diseases form perforated disease spots in tobacco plants, resulting in a decline in tobacco yield and quality. The present study investigated the antagonistic effect of Bacillus subtilis CTXW 7-6-2 against Rhizoctonia solani , its ability to promote the growth of tobacco seedlings, and the expression of disease resistance-related genes for efficient and eco-friendly plant disease control. Our results showed that CTXW 7-6-2 had the most vigorous growth after being cultured for 96 h, and its rate of inhibition of R. solani growth in vitro was 94.02%. The volatile compounds produced by CTXW 7-6-2 inhibited the growth of R. solani significantly (by 96.62%). The fungal growthinhibition rate of the B. subtilis CTXW 7-6-2 broth obtained after high-temperature and no-high-temperature sterile fermentation was low, at 50.88% and 54.63%, respectively. The lipopeptides extracted from the B. subtilis CTXW 7-6-2 fermentation broth showed a 74.88% fungal growth inhibition rate at a concentration of 100 mg/l. Scanning and transmission electron microscopy showed some organelle structural abnormalities, collapse, shrinkage, blurring, and dissolution in the R. solani mycelia. In addition, CTXW 7-6-2 increased tobacco seedling growth and improved leaf and root weight compared to the control. After CTXW 7-6-2 inoculation, tobacco leaves showed the upregulation of the PDF1.2 , PPO , and PAL genes, which are closely related to target spot disease resistance. In conclusion, B. subtilis CTXW 7-6-2 may be an efficient biological control agent in tobacco agriculture and enhance plant growth potential., (© 2024 Ning Huang et al., published by Sciendo.)

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA)., Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development., Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down., Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ding, Xu, Ding, Wu, Liu, Zhang, Chen, Zhang and Zhou.)

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO 2 (RR = 0.993, lag19 day) and O 3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O 3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO 2 , O 3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reactive oxygen species (ROS) are an important part of adaptation to biotic and abiotic stresses and regulate seed germination through positive or negative signaling. Seed adaptation to abiotic stress may be mediated by hydrogen peroxide (H 2 O 2 ). The effects of the ROS scavenger N,N'-dimethylthiourea (DMTU) on maize seed germination through endogenous H 2 O 2 regulation is unclear. In this study, we investigated the effects of different doses of DMTU on seed endogenous H 2 O 2 and radicle development parameters using two maize varieties (ZD958 and DMY1). The inhibitory effect of DMTU on the germination rate and radicle growth was dose-dependent. The inhibitory effect of DMTU on radicle growth ceased after transferring maize seeds from DMTU to a water medium. Histochemical analyses showed that DMTU eliminated stable H 2 O 2 accumulation in the radicle sheaths and radicles. The activity of antioxidant enzyme and the expression of antioxidant enzyme-related genes ( ZmAPX2 and ZmCAT2 ) were reduced in maize seeds cultured with DMTU compared with normal culture conditions (0 mmol·dm -3 DMTU). We suggest the use of 200 mmol·dm -3 DMTU as an H 2 O 2 scavenger to study the ROS equilibrium mechanisms during the germination of maize seeds, assisting in the future with the efficient development of plant growth regulators to enhance the seed germination performance of test maize varieties under abiotic stress.

Peroxisome proliferator-activated receptor alpha (PPARα) activation-induced hepatomegaly is accompanied by hepatocyte hypertrophy around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area. However, the molecular mechanisms underlying this spatial change of hepatocytes remains unclear. In this study, we examined the characteristics and possible reasons for the zonation distinction of hypertrophy and proliferation during PPARα activation-induced mouse liver enlargement. Mice were injected with corn oil or a typical mouse PPARα agonist WY-14643 (100 mg·kg -1 ·d -1 , i.p.) for 1, 2, 3, 5 or 10 days. At each time point, the mice were sacrificed after the final dose, and liver tissues and serum were harvested for analysis. We showed that PPARα activation induced zonal changes in hepatocyte hypertrophy and proliferation in the mice. In order to determine the zonal expression of proteins related to hepatocyte hypertrophy and proliferation in PPARα-induced liver enlargement, we performed digitonin liver perfusion to separately destroy the hepatocytes around the CV or PV areas, and found that PPARα activation-induced increase magnitude of its downstream targets such as cytochrome P450 (CYP) 4 A and acyl-coenzyme A oxidase 1 (ACOX1) levels around the CV area were higher compared with those around the PV area. Upregulation of proliferation-related proteins such as cell nuclear antigen (PCNA) and cyclin A1 (CCNA1) after WY-14643-induced PPARα activation mainly occurred around the PV area. This study reveals that the zonal expression of PPARα targets and proliferation-related proteins is responsible for the spatial change of hepatocyte hypertrophy and proliferation after PPARα activation. These findings provide a new insight into the understanding of PPARα activation-induced liver enlargement and regeneration., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Cardiac hypertrophy, a kind of cardiomyopathic abnormality, might trigger heart contractile and diastolic dysfunction, and even heart failure. Currently, bisphenols (BPs) including bisphenol A (BPA), and its alternatives bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) are ubiquitously applied in various products and potentially possess high cardiovascular risks for humans. However, the substantial experimental evidences of BPs on heart function, and their structure-related effects on cardiomyocyte hypertrophy are still urgently needed. DNA methylation, a typical epigenetics, play key roles in BPs-induced transcription dysregulation, thereby affecting human health including cardiovascular system. Thus, in this study, we performed RNA-seq and reduced representation bisulfite sequencing (RRBS) to profile the landscapes of BPs-induced cardiotoxicity and to determine the key roles of DNA methylation in the transcription. Further, the capabilities of three BPA analogues, together with BPA, in impacting heart function and changing DNA methylation and transcription were compared. We concluded that similar to BPA, BPAF, BPF and BPS exposure deteriorated heart function in a mouse model, and induced cardiomyocyte hypertrophy in a H9c2 cell line. BPAF, BPF and BPS all played BPA-like roles in both transcriptive and methylated hierarchies. Moreover, we validated the expression levels of four cardiomyocyte hypertrophy related candidate genes, Psmc1, Piptnm2, Maz and Dusp18, which were all upregulated and with DNA hypomethylation. The findings on the induction of BPA analogues on cardiomyocyte hypertrophy and DNA methylation revealed their potential detrimental risks in heart function of humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) poses the leading threats to human health and life, and their occurrence and severity are associated with exposure to environmental pollutants. Per- and polyfluoroalkyl substances (PFAS), a group of widely used industrial chemicals, are characterized by persistence, long-distance migration, bioaccumulation, and toxicity. Some PFAS, particularly perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS), have been banned, leaving only legacy exposure to the environment and human body, while a number of novel PFAS alternatives have emerged and raised concerns, such as polyfluoroalkyl ether sulfonic and carboxylic acid (PFESA and PFECA) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS). Overall, this review systematically elucidated the adverse cardiovascular (CV) effects of legacy and emerging PFAS, emphasized the dose/concentration-dependent, time-dependent, carbon chain length-dependent, sex-specific, and coexposure effects, and discussed the underlying mechanisms and possible prevention and treatment. Extensive epidemiological and laboratory evidence suggests that accumulated serum levels of legacy PFAS possibly contribute to an increased risk of CVD and its subclinical course, such as cardiac toxicity, vascular disorder, hypertension, and dyslipidemia. The underlying biological mechanisms may include oxidative stress, signaling pathway disturbance, lipid metabolism disturbance, and so on. Various emerging alternatives to PFAS also play increasingly prominent toxic roles in CV outcomes that are milder, similar to, or more severe than legacy PFAS. Future research is recommended to conduct more in-depth CV toxicity assessments of legacy and emerging PFAS and explore more effective surveillance, prevention, and treatment strategies, accordingly., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To determine the reproducibility of measuring the gross total volume (GTV) of primary rectal tumor with manual and semi-automatic delineation on the diffusion-weighted image (DWI), examine the consistency of using the same delineation method on DWI images with different high b-values, and find the optimal delineation method to measure the GTV of rectal cancer., Methods: 41 patients who completed rectal MR examinations in our hospital from January 2020 to June 2020 were prospectively enrolled in this study. The post-operative pathology confirmed the lesions were rectal adenocarcinoma. The patients included 28 males and 13 females, with an average age of (63.3 ± 10.6) years old. Two radiologists used LIFEx software to manually delineate the lesion layer by layer on the DWI images (b=1000 s/mm 2 and 1500 s/mm 2 ) and used 10% to 90% of the highest signal intensity as thresholds to semi-automatically delineate the lesion and measure the GTV. After one month, Radiologist 1 performed the same delineation work again to obtain the corresponding GTV., Results: The inter- and intra-observer interclass correlation coefficients (ICC) of measuring GTV using semi-automatic delineation with 30% to 90% as thresholds were all >0.900. There was a positive correlation between manual delineation and semi-automatic delineation with 10% to 50% thresholds (P < 0.05). However, the manual delineation was not correlated with the semi-automatic delineation with 60%, 70%, 80%, and 90% thresholds. On the DWI images with b=1000 s/mm 2 and 1500 s/mm 2 , the 95% limit of agreement (LOA%) of measuring GTV using semi-automatic delineation with 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% thresholds were -41.2~67.4, -17.8~51.5, -16.1~49.3, -26.2~50.1, -42.3~57.6, -57.1~65.4, -67.3~66.5, -101.6~91.1, -129.4~136.0, and -15.3~33.0, respectively. The time required for GTV measurement by semi-automatic delineation was significantly shorter than that of manual delineation (12.9 ± 3.6s vs 40.2 ± 13.1s)., Conclusions: The semi-automatic delineation of rectal cancer GTV with 30% threshold had high repeatability and consistency, and it was positively correlated with the GTV measured by manual delineation. Therefore, the semi-automatic delineation with 30% threshold could be a simple and feasible method for measuring rectal cancer GTV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qiu, Zhou, Li, Zhang, Wang and Yang.)

Background and Aims: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC., Methods: Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells., Results: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8 + T EX s, Tregs and PD1 + CD4 + T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion., Conclusion: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Electromagnetically induced transparency (EIT) and absorption (EIA) are two phenomena that can be observed in whispering-gallery-mode (WGM) optical microresonators. Transition from EIT to EIA has potential applications in optical switching, filtering and sensing. In this paper an observation of the transition from EIT to EIA in a single WGM microresonator is presented. A fiber taper is used to couple light into and out of a sausage-like microresonator (SLM) that contains two coupled optical modes with significantly different quality factors. By stretching the SLM axially the resonance frequencies of the two coupled modes are tuned to the same, a transition from EIT to EIA is then observed in the transmission spectra when the fiber taper is moved closer to the SLM. It is the special spatial distribution of the optical modes of the SLM that provide a theoretical basis for the observation.

The design simulation and fabrication results of a bandpass filter based on micro-electro-mechanical system (MEMS) switches are presented in this paper. The MEMS filter element consists of a MEMS capacitance switch and two resonant rings that are fixed onto coplanar waveguide lines through anchor points. The micromachine characteristics of the filter could be optimized to change the center frequency from 8.5 to 12 GHz by improving the geometrical parameters; other electrical parameters of the filter, such as stopband rejection, insertion loss, and return loss at each center frequency, were simulated and calculated. In order to evaluate the MEMS filter design methodology, a filter working at 10.5 GHz fabricated with an aluminum top electrode was used, and it displayed a low insertion loss of 1.12 dB and a high stopband rejection of 28.3 dB. Compared with the simulation results, these proposed filter showed better electrical performance. Our results demonstrated that the filter with the integrated RF MEMS switch not only provides the benefit of reduced size compared with a traditional filter, but also improves stopband rejection, insertion loss, and return loss.

Objectives: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection., Methods: A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome., Results: Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P <0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination ( P <0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group ( P <0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer ( P <0.05)., Conclusions: Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.

The geographic range of Zika virus (ZIKV) has expanded from Asia to the Americas, leading to the 2015-2016 pandemic with enhanced neurovirulence. At present, ZIKV is continuously circulating in many Southeast Asian countries. Unfortunately, the persistent evolution of ZIKV in Southeast Asia and its influence on the biological characteristics of the virus remain incompletely understood. In this study, the in vitro and in vivo properties of a new ZIKV isolate obtained from Cambodia in 2019 (CAM/2019) were characterized and compared with those of the Cambodian strain (CAM/2010). Compared with CAM/2010, the CAM/2019 virus showed similar plaque morphology and growth curves in cell cultures and induced comparable viremia and organ viral loads profiles in both BALB/c and A129 (IFNAR1 -/- ) mice upon intraperitoneal (i.p.) inoculation. Remarkably, the CAM/2019 virus exhibited enhanced neurovirulence in neonatal mice compared with CAM/2010, with a 74-fold reduction in the 50% lethal dose (LD 50 ). Consistently, CAM/2019 produced higher viral loads in the brains of BALB/c neonatal mice than CAM/2010 did. Sequence alignment showed that the CAM/2019 virus has acquired 12 amino acid substitutions, several of which were found to be associated with neurovirulence. In particular, the CAM/2019 virus shared an A1204T substitution in NS2A with the Thai isolate SI-BKK02 that was isolated from a microcephaly case. Taken together, our results indicate that a ZIKV strain isolated with specific mutations has emerged in Cambodia, highlighting the need for extensive molecular and disease surveillance in Cambodia and other Asian countries., (© 2022 Wiley Periodicals LLC.)

Background: Neer type II/bilateral distal clavicular fracture is an extremely rare injury combination, with few cases having been reported., Case Presentation: This paper reports a case of polytrauma in a 16-year-old female following a road traffic accident. The radiographs revealed distal fractures of the bilateral clavicles (Neer type II), and an open reduction and internal fixation procedure was performed. Initially, the distal fracture of the right clavicle was fixed with a six-hole hook plate before the fracture of the left clavicle was fixed using a pre-contoured lateral locking plate following reduction. At the two-year follow-up, the patient had an excellent constant score in terms of the bilateral shoulder joints., Conclusion: It is important to achieve stability and to aim for excellence in terms of full shoulder function in this rare combination injury.

Introduction: Disorders of sex development (DSDs) are congenital abnormalities in which chromosomal, gonadal, and anatomical sex development are atypical. One of these disorders, 46,XY DSD, is particularly difficult to diagnose and manage because its etiology and clinical phenotypes are highly heterogeneous., Methods: We used a gene panel containing 141 genes implicated in DSDs to perform targeted next-generation sequencing (NGS) in 50 patients with 46,XY DSD., Results: Gene variants were detected in 23 patients (46%). Among them, 13 patients had previously reported pathogenic or likely pathogenic variants, 9 patients had novel variants, and 1 patient had a previously reported variant of uncertain significance. Three of the novel variants were pathogenic, and the remaining were variants of uncertain significance; therefore, 16 patients had pathogenic or likely pathogenic variants according to ACMG guidelines, and the overall diagnostic rate of 46,XY DSD was 32%. The most common gene variants were SRD5A2 variants, followed by the AR variant. In addition, we analyzed the association between gene variants and clinical phenotypes. Most patients presented with multiple DSD phenotypes (i.e., two or more DSD phenotypes were observed, such as micropenis, hypospadias, and cryptorchidism), but the phenotype with the highest diagnostic rate was micropenis., Conclusion: Our results indicate that targeted NGS can effectively detect pathogenic gene variants in patients with 46,XY DSD., (© 2023 S. Karger AG, Basel.)

Pregnane X receptor (PXR) is highly expressed in the liver and plays a pivotal role in xenobiotic and endobiotic metabolism. We previously reported that PXR activation by its specific mouse agonist pregnenolone 16α-carbonitrile (PCN) significantly induces liver enlargement and lipid accumulation. However, the effect of long-term PCN treatment on PXR and mouse liver is still unknown. This study aimed to explore the influence of long-term administration of PCN on mouse liver and hepatic lipid homeostasis. Male C57BL/6 mice were injected intraperitoneally with PCN (100 mg/kg once a week) for 42 weeks. Serum and liver samples were collected for biochemical and histological analysis. PXR activation was investigated by Western blot. Ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)-based lipidomics analysis was performed to explore the change in different lipid categories. The results showed that long-term treatment with PCN significantly promoted hepatomegaly without hepatocyte proliferation and enlargement. Long-term treatment with PCN did not upregulate PXR target proteins in mice, and there was no significant upregulation of CYP3A11, CYP2B10, UGT1A1, MRP2, or MRP4. Lipidomics analysis showed obvious hepatic lipid accumulation in the PCN-treated mice, and the most significant change was found in triglycerides (TGs). Additionally, long-term treatment with PCN had no risk for carcinogenesis. These findings demonstrated that long-term PCN treatment induces hepatomegaly and lipid accumulation without hepatocyte proliferation or enlargement., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

ARCoV is a candidate mRNA vaccine encoding receptor-binding domain of SARS-CoV-2. Its safety, tolerability, and immunogenicity profile have been confirmed in the phase 1 clinical trial in China. A multi-regional phase 3 clinical trial is currently underway to test the efficacy of ARCoV (NCT04847102). Here, we tested the cross-neutralization against SARS-CoV-2 variants of concern (VOCs) of a panel of serum samples from participants in the phase 1 clinical trial of ARCoV by pesudo- and authentic SARS-CoV-2. Our data suggest the immunity induced by the ARCoV vaccine reduced but still has significant neutralization against the Alpha and Delta variants. Moreover, ARCoV maintained activity against the Beta variant, despite of its obvious reduction in neutralizing titers. Our findings further support the solid protective neutralization activity against VOCs induced by ARCoV vaccine.

Piwi-interacting RNAs (piRNAs) are a class of short chain noncoding RNAs that are constituted by 26-30 nucleotides (nt) and can couple with PIWI protein family. piRNAs were initially described in germline cells and are believed to be critical regulators of the maintenance of reproductive line. Increasing evidence has extended our perspectives on the biological significance of piRNAs and indicated that they could still affect somatic gene expression through DNA methylation, chromatin modification and transposon silencing, etc. Many studies have revealed that the dysregulation of piRNAs might contribute to diverse diseases through epigenetic changes represented by DNA methylation and chromatin modification. In this review, we summarized piRNA/PIWI protein-mediated DNA methylation regulation mechanisms and methylation changes caused by piRNA/PIWI proteins in different diseases, especially cancers. Since DNA methylation and inhibitory chromatin marks represented by histone H3 lysine 9 (H3K9) methylation frequently cooperate to silence genomic regions, we also included methylation in chromatin modification within this discussion. Furthermore, we discussed the potential clinical applications of piRNAs as a new type promising biomarkers for cancer diagnosis, as well as the significance of piRNA/PIWI protein-associated methylation changes in treatment, providing disparate insights into the potential applications of them., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases., (© 2022. The Author(s).)

Background: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD)., Methods: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212)., Findings: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19., Interpretation: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale., Funding: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences., Competing Interests: C-FQ and BY are co-inventors on pending patent applications related to the ARCoV mRNA vaccine. LW is an employee of Suzhou Abogen Biosciences. S-YY and ZH are employees of Walvax. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Alleviating odontoblast inflammation is crucial to control the progression of pulpitis. Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from mitochondria of inflamed odontoblasts into the cytosol. Bacteria-induced inflammation leads to a novel type of cell death named pyroptosis. The canonical pyroptosis is a gasdermin (GSDM)-dependent cytolytic programmed cell death characterized by cell swelling and pore formation in the plasma membrane. To date, whether odontoblast cytosolic mtDNA regulates dental pulp inflammation through the canonical pyroptosis pathway remains to be elucidated. In this study, high gasdermin D (GSDMD) expression was detected in human pulpitis. We found that LPS stimulation of mDPC6T cells promoted BAX translocation from the cytosol to the mitochondrial membrane, leading to mtDNA release. Moreover, overexpression of isolated mtDNA induced death in a large number of mDPC6T cells, which had the typical appearance of pyroptotic cells. Secretion of the inflammatory cytokines CXCL10 and IFN-β was also induced by mtDNA. These results suggest that cytosolic mtDNA participates in the regulation of odontoblast inflammation through GSDMD-mediated pyroptosis in vitro. Interestingly, after overexpression of mtDNA, the expression of inflammatory cytokines CXCL10 and IFN-β was increased and not decreased in GSDMD knockdown mDPC6T cells. We further proposed a novel model in which STING-dependent inflammation in odontoblast-like cell is a compensatory mechanism to control GSDMD-mediated pyroptosis, jointly promoting the immune inflammatory response of odontoblasts. Collectively, these findings provide the first demonstration of the role of the mtDNA-GSDMD-STING in controlling odontoblast inflammation and a detailed description of the underlying interconnected relationship., (© 2021. The Author(s).)

Ovarian cancer (OC) is one of the deadliest gynecological malignancies worldwide and has a high mortality rate. Its dismal prognosis is closely related to late diagnosis and drug resistance. Exosomes are a novel means of intercellular communication that are involved in the genesis and development of tumors by delivering a variety of biologically active molecules, including proteins, lipids, and nucleic acids. As an important component, noncoding RNAs (ncRNAs) are selectively enriched in exosomes and participate in the regulation of specific aspects of OC development, such as proliferation, invasion, metastasis, angiogenesis, immune escape, and treatment resistance. Therefore, strategies that specifically target exosomal ncRNAs may be attractive therapeutic options. Exosomes are readily available in almost all types of human biological fluids and are biocompatible, making them promising biomarkers of OC as well as targets for therapeutic applications. In this review, we briefly summarize the biology of exosomes, the function of exosomal ncRNAs in OC development, and their potential clinical applications as biomarkers and therapeutic tools. Ideally, exosomal ncRNAs will become increasingly valuable in the diagnosis and treatment of OC in the near future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wei, Zhang, Liu and Zhang.)

There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution., (© 2021. The Author(s).)

Background: To establish and validate a high-resolution magnetic resonance imaging (HRMRI)-based radiomic nomogram for prediction of preoperative perineural invasion (PNI) of rectal cancer (RC)., Methods: Our retrospective study included 140 subjects with RC (99 in the training cohort and 41 in the validation cohort) who underwent a preoperative HRMRI scan between December 2016 and December 2019. All subjects underwent radical surgery, and then PNI status was evaluated by a qualified pathologist. A total of 396 radiomic features were extracted from oblique axial T2 weighted images, and optimal features were selected to construct a radiomic signature. A combined nomogram was established by incorporating the radiomic signature, HRMRI findings, and clinical risk factors selected by using multivariable logistic regression., Results: The predictive nomogram of PNI included a radiomic signature, and MRI-reported tumor stage (mT-stage). Clinical risk factors failed to increase the predictive value. Favorable discrimination was achieved between PNI-positive and PNI-negative groups using the radiomic nomogram. The area under the curve (AUC) was 0.81 (95% confidence interval [CI], 0.71-0.91) in the training cohort and 0.75 (95% CI, 0.58-0.92) in the validation cohort. Moreover, our result highlighted that the radiomic nomogram was clinically beneficial, as evidenced by a decision curve analysis., Conclusions: HRMRI-based radiomic nomogram could be helpful in the prediction of preoperative PNI in RC patients.

Background: Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts., Methods: The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured., Results: The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown., Conclusion: Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract.

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase-activating protein (GAP) and modulate integrin-mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Thyroid cancer (TC) is one of the most common malignant tumors, with high morbidity and mortality rates worldwide. The incidence of TC, especially that of papillary thyroid carcinoma (PTC); has increased rapidly in recent decades. Autoimmune thyroid disease (AITD) is closely related to TC and has an estimated prevalence of 5%. Thus, it is becoming increasingly important to identify potential diagnostic biomarkers and therapeutic targets for TC and AITD. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently bonded circular structures that lack 5'-3' polarity and polyadenylated tails. Several circRNAs play crucial roles in the development of various diseases, including TC and AITD, and could be important new biomarkers and/or targets for the diagnosis and therapy of such disorders. Although there are four subtypes of TC, research on circRNA has largely focused on its connection to PTC. Therefore, this review mainly summarizes the relationships between circRNAs and PTC and AITD, including the molecular mechanisms underlying these relationships. In particular, the functions of "miRNA sponges" and their interactions with proteins and RNA are discussed. The possible targeting of circRNAs for the prevention, diagnosis, and treatment of TC and AITD is also described. CircRNAs could be potential biomarkers of TC and AITD, although validation will be required before they can be implemented in clinical practice., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Graphene oxide (GO) has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to investigate the effects of cell penetrating peptide (CPP) modified and polyethylene-glycol- (PEG-) grafted GO (pGO) loaded with photosensitive agent 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH) and Epirubicin (EPI) (HPPH/EPI/CPP-pGO) on tumor growth in osteosarcoma. Methods: The HPPH/EPI/CPP-pGO were prepared, and then in vitro drug release assay was conducted. The detection of singlet oxygen ( 1 O 2 ) and cellular uptake of HPPH was performed as well. Next, the effects of control (saline solution), CPP-pGO, EPI, HPPH, HPPH/CPP-pGO, EPI/CPP-pGO, HPPH/EPI/pGO, and HPPH/EPI/CPP-pGO were evaluated by MTT assay, colony-forming assay, and cell apoptosis assay in MG-63 cells. Furthermore, the antitumor effects of HPPH/EPI/CPP-pGO on osteosarcoma xenograft mice were unraveled. Results: The 1 O 2 generation and cellular uptake of HPPH were significantly increased after CPP and pGO modification compared with free HPPH. In addition, compared with control cells, CPP-pGO treatment had low cytotoxicity in MG-63 cells. Compared with free HPPH or EPI, HPPH/CPP-pGO or EPI/CPP-pGO treatment significantly inhibited cell viability and colony forming number, as well as inducing cell apoptosis. HPPH/EPI-pGO treatment showed stronger inhibition effects on MG-63 cells than HPPH/CPP-pGO or EPI/CPP-pGO, and HPPH/EPI/CPP-pGO was the most effective one. Similarly, in vivo experiments revealed that, compared with control group, the tumor size and weight of osteosarcoma xenograft mice were obviously decreased after free HPPH or EPI treatment, which were further reduced in other groups, especially in HPPH/EPI/CPP-pGO group. Conclusion: HPPH/EPI/CPP-pGO had superior tumor-inhibiting effects in vitro and in vivo on osteosarcoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wu, Lan, Chen and Su.)

Two new compounds Talaromycin A ( 1 ) and Talaromycin B ( 2 ) were isolated from a liquid culture of Talaromyces aurantiacus. The structures of 1 and 2 were elucidated by IR, MS, 1D and 2D NMR spectra and comparison of the experimental and calculated electronic circular dichroism spectra. Additional known compounds ( 3-6 ) were also isolated. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but showed only weak activity.

Objective: To explore a method for evaluating the bioequivalence of acarbose based on pharmacodynamic parameters using a single-dose, randomized-sequence, three-way crossover study of acarbose test (T) and reference (R) formulations., Methods: Baseline-adjusted, pre-dose value deduction, and direct comparison methods were used to evaluate the geometric T/R ratios and 90% confidence intervals (CIs) of the ln-transformed pharmacodynamic parameters to identify the most suitable evaluation system. Twelve participants were randomly divided into three groups to receive treatment in the following sequences: TRR, RTR, and RRT, each including a 7-day washout period between treatment periods. The serum glucose concentration (baseline) was determined. Pharmacodynamic parameters, including the maximum reduction in serum glucose concentrations (ΔC SG,max ) and difference of the AUC of glucose between before and after acarbose exposure (ΔAUEC), were tested., Results: Using the direct comparison method, the geometric mean ratios of C SG,max , AUEC (0-2h) , and AUEC (0-4h) were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for C SG,max , AUEC (0-2h), and AUEC (0-4h) all fell between 80% and 125%. Conversely, ΔC SG,max and ΔAUEC (0-4h) were less reliable measures of acarbose bioequivalence., Conclusions: Pre-dose value deduction and direct comparison methods can be initially considered suitable for assessing acarbose bioequivalence.

Epidemiological and animal studies indicate that increased exposure to bisphenol A (BPA) induces various human cardiovascular diseases (CVDs), including myocardial infarction, arrhythmias, dilated cardiomyopathy, atherosclerosis, and hypertension. Bisphenol S (BPS), an alternative to BPA, is increasingly present in various consumer products and human bodies worldwide. Recently, emerging evidence has shown that BPS might be related to cardiovascular disorders. In this review, we present striking evidence of the correlation between BPA exposure and various CVDs, and show that a nonmonotonic dose-response curve (NMDRC) was common in studies of the CV effects of BPA in vivo. The CV impairment induced by low doses of BPA should be highlighted, especially during developmental exposure or during coexposure with other risk factors. Furthermore, we explored the possible underlying mechanisms of these effects-particularly nuclear receptor signaling, ion channels, and epigenetic mechanisms-and the possible participation of lipid metabolism, oxidative stress and cell signaling. As the potential risks of BPA exposure in humans are still noteworthy, studies of BPA in CVDs should be strengthened, especially with respect to the mechanisms, prevention and treatment. Moreover, the potential CV risk of BPS reported by in vivo studies calls for immediate epidemiological investigations and animal studies to reveal the relationships of BPS and other BPA alternatives with human CVDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We examined the effects of a combination of slow-release urea (PCU) and common urea (PU) applied at different soil depths (0-30 cm soil layer) on inorganic nitrogen content, enzyme activity, and crop yield during two years (2017-2018) in a field experiment. There were eight treatments: CK (without N fertilizer); PU 1 (common urea applied at 5-10 cm deep soil layer); PU 2 (common urea applied at 5-10 cm deep soil layer, 60% seed fertilizer + 40% topdressing); PU 3 (20% common urea at 5-10 cm soil depth, 30% common urea at 15-20 cm soil depth, 50% common urea at 25-30 cm soil depth); PCU 1 (20% total nitrogen application rate at 5-10 cm soil depth, 30% total nitrogen application rate at 15-20 cm soil depth, 50% total nitrogen application rate at 25-30 cm soil depth), the N fertilizer at 5-10 cm was common urea, but, at 15-20 and 25-30 cm, it was a combination of PCU and PU at ratios of 3:7 and 3:7; PCU 2 was as PCU 1 but the ratio of PCU and PU was 5:5 at 15-20 cm and 5:5 at 25-30 cm; in PCU 3 , the ratio of PCU and PU was 3:7 at 15-20 cm and 5:5 at 25-30 cm; in PCU 4 , the ratio of PCU and PU was 5:5 at 15-20 cm and 3:7 at 25-30 cm. The results showed that PU 1 could meet nitrogen demand at the 0-10 cm layer in the early growth stage compared with CK. PU 2 and PU 3 could meet nitrogen demand for 10-30 cm soil layer in the early stage of maize development. The combined application of slow release urea and common urea could meet nitrogen demand for the whole growth period of maize. In the filling and maturing period, combined application of slow release and common urea significantly increased not only NO 3 - -N, NH 4 + -N, and alkali-hydrolyzed nitrogen contents but also urease and protease activities in the 10-20 cm and 20-30 cm soil layers compared with PU 1 -PU 3 . Compared with PU 3 , maize yield increased by 2.3%-24.6% and 1.3%-16.5% in the PCU 1 -PCU 4 treatments in 2017 and 2018, respectively. PCU 4 had the highest yield, with 13899 and 12439 kg·hm -2 , respectively. Therefore, the combined application of slow-release and common urea at different soil layers could meet nitrogen demand in the early growth stage of maize and increase the content of inorganic nitrogen and enzyme activities in the 10-30 cm soil layers in the later growth period, which promoted the growth and increased the yield of maize. Among all the treatments PCU 4 treatment was the most effective.

Freshwater aquatic ecosystems are important sources of greenhouse gases, such as CO 2 . However, few studies have presented data on the greenhouse gas flux from coastal aquaculture ponds. Diffusion models are important tools for estimating the CO 2 exchange flux across the water-air interface of aquatic ecosystems. Several different parameterized means were selected to estimate the CO 2 gas exchange rate ( k x ) and CO 2 diffusive flux across the water-air interface of shrimp ponds in the Minjiang River Estuary. The results indicated that:① the CO 2 gas exchange rate and diffusive flux over the culture period all presented significant temporal variation. This variation showed a dynamic trend:October > September > November > July > August and November > July > August > September > October. ② Wind speed, k x , CO 2 concentration, pH, DOC concentration, and Chl-a concentration were important factors affecting the temporal variation of CO 2 diffusive flux. ③ There were differences in the estimated value of CO 2 diffusive flux across the water-air interface of the culture ponds in the Minjiang River Estuary among different parameterized approaches ( P <0.01). This indicates that the model method has some uncertainties in estimating the CO 2 diffusive flux in culture ponds. Our results suggest that the models RC01 and CW03 are more suitable methods for estimating the CO 2 diffusive flux at the water-air interface of estuarine reclaimed aquaculture ponds in the Minjiang River Estuary, after comprehensive analysis of the water environment and the different estimation results.

It is important to identify efficient adsorbents for the removal of dyestuffs from aqueous solutions as this kind of pollution becomes more extensive. In this study, Dioscorea opposita Thunb. (DOT) was modified with polyethylene imine (DOT@PEI) as a novel biosorbent to remove the typical anionic dye indigo carmine (IC) from wastewater. The modified DOT@PEI biosorbent was characterized using BET (Brunauer-Emmett-Teller), SEM (scanning electron microscopy), EDS (energy dispersive spectroscopy), and FTIR (Fourier transform infrared spectroscopy) methods, and the results demonstrated that DOT@PEI is an excellent biosorbent. Batch adsorption studies showed that optimum adsorption parameters were pH 2.0, 1.0 g L -1 dosage, and temperature of 20 °C. The isothermal adsorption data showed good fitting to the Langmuir model, with a maximum adsorption capability of 344.83 mg g -1 for IC. Kinetic experiments showed that the experimental data fitted well to a pseudo-second-order kinetic model and the thermodynamic parameters indicated that adsorption is a spontaneous exothermic process. Adsorption-desorption experiments illustrated the good regeneration capability of DOT@PEI. These results demonstrate that DOT@PEI can be used as an effective biosorbent in water for the removal of anionic dyes such as required for environmental applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Rising atmospheric carbon dioxide (CO 2 ) levels can markedly affect the growth, development, reproduction and behavior of herbivorous insects, mainly by changing the primary and secondary metabolites of their host plants. However, little is known about the host-selection behavior and the respective intrinsic mechanism of sap-sucking insects in response to elevated CO 2 . In this experiment, the host-selection behavior, as well as the physiological mechanism based on the analysis of growth, development and energy substances, and the expression of the olfactory-related genes of the cotton aphid, Aphis gossypii, were studied under ambient (407.0 ± 4.3 μl/L) and elevated (810.5 ± 7.2 μl/L) CO 2 . The results indicated that the aphids reared under ambient and elevated CO 2 did not differ in their level of preference for cotton seedlings, whatever the CO 2 conditions in which the plants developed. However, aphids reared under elevated CO 2 showed a greater ability to respond to the plant volatiles compared to aphids that developed under ambient CO 2 (+23.3%). This suggests that rising atmospheric CO 2 enhances the activity of host selection in this aphid. Compared with ambient CO 2 , elevated CO 2 significantly increased aphid body weight (+36.7%) and the contents of glycogen (+18.9%), body fat (+14.6%), and amino acids (+16.8%) and increased the expression of odor-binding protein genes, OBP2 (+299.6%) and OBP7 (+47.4%), and chemosensory protein genes, CSP4 (+265.3%) and CSP6 (+50.9%), potentially enhancing the overall life activities and upregulating the olfactory ability of A. gossypii. We speculated that the rising atmospheric CO 2 level would likely aggravate the damage caused by A. gossypii due to the higher potential host selection and increased general activity under future climate change., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca 2+ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca 2+ ]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca 2+ ]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.

The mechanisms underlying drug resistance in colorectal cancer (CRC) treatment remain to be fully elucidated. Therefore, the present study aimed to investigate the underlying mechanism resistance to a widely used anticancer drug, 5-Fluorouracil (5-FU). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in cellular protection. In the present study, it was hypothesized that the epigenetic modification of Nrf2 may be a potential target for 5-FU resistance in CRC treatment. Protein and messenger RNA levels of Nrf2, heme oxygenase-1 (HO-1), DNA methylases and DNA methyltransferases were determined and DNA methylation analysis for the Nrf2 promoter was performed in a human CRC control (SNU-C5) and resistant (SNU-C5R) cell line. The results demonstrated that Nrf2 expression levels, nuclear translocation and promoter binding were significantly increased in SNU-C5R cells compared with SNU-C5 cells. Elevated levels of activated Nrf2 in SNU-C5R cells resulted in the increased protein expression and activity of HO-1. In addition, increased production of reactive oxygen species (ROS) and upregulation of ten-eleven translocation (TET)1 were observed in SNU-C5R cells compared with SNU-C5 cells. Furthermore, methylation analysis revealed Nrf2 promoter cytosine-phosphate-guanine island hypomethylation in 5-FU-treated cells. In conclusion, the results indicated that 5-FU-induced ROS production resulted in the upregulation of TET1 expression and function. In addition, these results indicated that TET-dependent demethylation of the Nrf2 promoter upregulated Nrf2 and HO-1 expression, which induced cellular protection mechanisms, ultimately leading to drug resistance.

Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors (Gd3+ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.

Objective: To identify Streptococcus mutans (S. mutans) in carious patients' saliva using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and to establish a faster and more accurate method to identify S. mutans., Methods: In this study, a total of 90 carious patients from Department of Endodontics of Peking University School of Stomatology were recruited. All these patients' saliva was collected. After extracting the protein of the samples, they were identified by MALDI-TOF MS. The composite profile was analyzed using BioExplorer 1.0 software. The scores ≥ 25 were considered as S. mutans, whereas the scores <25 were as considered as non S. mutans. Finally, these results were compared with 16S rDNA sequencing to figure out the sensitivity and concordance rate, respectively., Results: The sensitivity of MALDI-TOF MS was 96.0%, and the concordance rate compared with 16S rDNA sequencing was as high as 98.7%., Conclusion: MALDI-TOF MS is high throughput, rapid and easy to perform in comparison to other conventional methods. It has a high sensivity and concordance rate. Thus, MALDI-TOF MS can serve as an effective tool for identification of S. mutans.

Whether the assessment results of Contingent Valuation Method (CVM) have temporal stability is an important issue in examining the reliability of CVM findings, and also, is critical to decide whether CVM can be applied to evaluate the ecosystem services value in China. Taking the ecological restoration along the Caohejing River in Shanghai as a case, three CVM survey schemes with one month apart and two years apart were designed. Then, 426, 498, and 200 questionnaires in these surveys were comparatively analyzed, respectively. The mean values of the willingness to pay (WTP) from the three surveys were 14. 2, 14. 1, and 18. 0 RMB, and the median values were 5, 5, and 10 RMB, respectively. With the comparison of the WTP distribution and the main statistics, the analysis of the factors affecting the WTP, and the test of the significances of temporal variables, it was found that the CVM results from the surveys with one-month apart had temporal stability, while those from the surveys with two years apart presented definite difference.

Objective: To access the prevalence of menopause-like symptoms, and their related factors in old and middle-aged males in the area of Hefei., Methods: This study included 1 026 males aged over 45 years that came to the clinic for health examination. We collected their personal data, and evaluated their general health status and the results of the questionnaire investigation using the Aging Males' Symptoms (AMS) scale., Results: The total incidence of menopause-like symptoms was 64.7% among the old and middle-aged males in Hefei area, of which 58.1% were mild, 30.9% moderate and 11.0% severe. The average AMS score was 31.2 +/- 6.8, in which the scores on psychological, physical and sexual function symptoms were 8.3 +/- 2.1, 12.4 +/- 4.8 and 9.3 +/- 4.5, respectively. Sexual function symptoms were increased significantly with the increase of age (P < 0.05), but psychological and physical symptoms showed no obvious correlation with age (P > 0.05). The main risk factors of menopause-like symptoms included age, smoking, diabetes, cardiovascular diseases, and obesity, but physical exercise was an important protective factor against them., Conclusion: With the increase of age, the prevalence of male menopause-like symptoms rises and sexual function declines gradually, but psychological and physical scores are not affected significantly. Age, general health status and lifestyle are closely associated with the prevalence of menopause-like symptoms among old and middle-aged males.