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Sirtuin 3 has been shown to regulate endothelial function and coronary flow reserve in mice. Knockout of SIRT3 reduced endothelial nitric oxide synthase expression in the mouse hearts. In this study, we investigate whether endothelial SIRT3 regulates vascular function and myogenic responses in distal intramural branches of the left anterior descending coronary artery (CA) and middle cerebral artery (MCA) of mice. Both male and female endothelial SIRT3 knockout (SIRT3ECKO) mice and control SIRT3LoxP mice were used and CA and MCA were dissected and mounted in a myograph system. The myogenic response was evaluated by measuring changes in inner diameter in response to 20 mmHg stepwise increases in intraluminal pressure in PSS (active diameter) and Ca2+‐free PSS (passive diameter). Acetylcholine (Ach)‐induced endothelial‐dependent relaxation (EDR) and sodium nitroprusside (SNP)‐induced endothelial‐independent relaxation (EIR) were examined. Our results showed that the myogenic responses were significantly impaired in both the CA and MCA of SIRT3ECKO mice. Furthermore, female mice had worsened myogenic response in MCA. In CA, EDR was abolished in both male and female SIRT3ECKO mice. Intriguingly, EIR was only reduced in the female mice. In MCA, EDR was reduced in male SIRT3ECKO mice, whereas EIR was decreased in both male and female mice. Female SIRT3ECKO mice had profound dysfunction in CA, whereas male mice exhibited more dysfunction in MCA. These data revealed a sex and organ‐specific role of endothelial SIRT3 in vascular function and myogenic responses. Our study suggests that endothelial SIRT3 is necessary for maintaining vascular function and blood flow autoregulation. [ABSTRACT FROM AUTHOR]

Introduction: Testicular cancer (TC) is the most frequent cancer among men aged 14-44 years. The risk of erectile dysfunction (ED) in TC patients varied within a wide range across different studies. This study aims to estimate the risk of ED in TC patients by conducting a meta-analysis of case-control studies. Material and methods: Relevant studies were searched using PubMed, EMBASE, Scopus, and the Cochrane Library up to June 2019. Case-control studies that reported the incidence of ED in TC patients were included. Results: A total of 8 studies involving 2060 TC patients and 2651 healthy men were included. All the TC patients underwent unilateral orchiectomy; other treatment modalities were also conducted if necessary. ED occurred in 16.9% (348/2060) of TC patients and 9.4% (251/2651) of healthy men. Compared with healthy men, TC patients experienced a significantly increased risk of ED (OR = 2.39, 95% CI: 1.56-3.67). Substantial heterogeneity was observed. In addition, subgroup analysis revealed that the risk (OR = 3.76, 95% CI: 2.45-5.78) for ED in TC patients with follow-up < 5 years was significantly higher than that (OR = 1.61, 95% CI: 1.10-3.67) with follow-up = 5 years. Heterogeneity was improved after subgroup analysis. Conclusions: TC patients experienced an increased risk for ED compared with healthy men. The long-term risk for ED in TC patients was lower than the short-term risk. [ABSTRACT FROM AUTHOR]

Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = − 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility. [ABSTRACT FROM AUTHOR]

Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = − 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility. [ABSTRACT FROM AUTHOR]

Background: Rodents are the predominant natural hosts of orthohantavirus and the source of human infection, hemorrhagic fever with renal syndrome (HFRS) caused by orthohantavirus is a severe public health problem in the Yichun region, Jiangxi Province, China. However, little information is known about the infection of orthohantavirus in humans and rodents, and the genetic characteristics of the epidemic orthohantavirus in the region. Methods: The clinical data of HFRS cases in 2016–2021 was analyzed. Virus infection in rodents was analyzed by orthohantavirus antigen detection using immunofluorescent assay, and the species of orthohantaviruses in rodents and patients were identified by real-time RT-PCR and gene sequencing. The S and M segments of orthohantaviruses from rodents and patients were recovered and analyzed. Results: A total of 1,573 HFRS cases were reported in the Yichun region from 2016 to 2021, including 11 death cases. HFRS cases peaked twice each year: in winter from November to January and early summer from May to June. Farmers constituted the predominant population suffering from HFRS. The orthohantavirus antigen was identified in five species of rodents: Apodemus agrarius (A. agrarius), Rattus norvegicus (R. norvegicus), Sorex araneus, Rattus losea (R. losea), and Niviventer confucianus (N. confucianus). The real-time RT-PCR test and genetic analysis results showed that Hantaan orthohantavirus (HTNV), Seoul orthohantavirus (SEOV), and Dabieshan orthohantavirus (DBSV) were circulated in the rodents. HTNV, SEOV, and DBSV from the rodents were distantly related to other known orthohantaviruses and belonged to novel genetic lineages. SEOV and HTNV were found in HFRS patients, but 97.8% (90/92) of the infections were caused by HTNV. Winter and early summer peaks were both caused by HTNV. The HTNV sequences recovered from HFRS cases were closely related to those from A. agrarius. Conclusions: In the Yichun region, the orthohantaviruses transmitted in rodents include HTNV, SEOV, and DBSV, which have obvious genetic characteristics and high genetic diversity. At the same time, this region is an HFRS mixed epidemic area dominated by HTNV, with two peaks every year, which deserves our high attention. Author summary: HFRS caused by orthohantavirus is a serious public health problem in the Yichun region in Jiangxi Province, China. However, little information is known about the infection of orthohantavirus in humans and rodents, and the genetic characteristics of the epidemic orthohantavirus in the region. To reveal the above problems, we analyzed the epidemiology of HFRS and performed a molecular investigation of orthohantavirus in the Yichun region. During 2016–2021, a total of 1,573 HFRS cases were recorded with an average fatality rate of 0.70%. HFRS consistently occurred and peaked in winter and early summer in the Yichun region, it was a mixed epidemic area of HFRS dominated by HTNV. We identified new genetic variants of SEOV, HTNV, and DBSV from rodent lung samples in the Yichun region, which shows the high genetic diversity of the orthohantaviruses. Special attention should be paid to the high genetic diversity of orthohantavirus when developing vaccines and antiviral drugs. We also found the new genetic variant of HTNV from rodents caused human infection and was the main prevalent virus of human infection in the Yichun region. These results will provide very important information for HFRS control in the Yichun region and other areas in the world. [ABSTRACT FROM AUTHOR]

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels. [ABSTRACT FROM AUTHOR]

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels. [ABSTRACT FROM AUTHOR]

The induction of hypoxia tolerance has emerged as a novel therapeutic strategy for the treatment of ischemic diseases. The disruption of hypoxic signaling by hyperglycemia has been shown to contribute to diabetic cardiomyopathy. In this study, we explored the potential molecular mechanisms by which high glucose (HG) impairs hypoxia-inducible factor-α (HIF-α) signaling in cardiomyocytes. The exposure of H9c2 cell lines to HG resulted in time- and concentration-dependent decreases in HIF-1α and HIF-2α expression together with an increase in prolyl hydroxylase-1,2 (PHD1 and PHD2) expression, the main regulators of HIF-α destabilization in the heart. The exposure of H9c2 cells to normal glucose (5.5 mM) and high glucose (15, 30, and 45 mM) led to dose-dependent increases in p53 and TIGAR and a decrease in SIRT3 expression. The pretreatment of H9c2 with p53 siRNA to knockdown p53 attenuated PHD1 and PHD2 expression, thus significantly enhancing HIF-1α and HIF-2α expression in H9c2 cells under HG conditions. Interestingly, pretreatment with p53 siRNA altered H9c2 cell metabolism by reducing oxygen consumption rate and increasing glycolysis. Similarly, pretreatment with TIGAR siRNA blunted HG-induced PHD1 and PHD2 expression. This was accompanied by an increase in HIF-1α and HIF-2α expression with a reduction in oxygen consumption rate in H9c2 cells. Furthermore, pretreatment with adenovirus-SIRT3 (Ad-SIRT3) significantly reduced the HG-induced expression of p53 and PHDs and increased HIF-1α levels in H9c2 cells. Ad-SIRT3 treatment also regulated PHDs-HIF-1α levels in the hearts of diabetic db/db mice. Our study revealed a novel role of the HG-induced disruption of PHDs-HIF-α signaling via upregulating p53 and TIGAR expression. Therefore, the p53/TIGAR signaling pathway may be a novel target for diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

The vertebrate brain and spinal cord arise from a common precursor, the neural tube, which forms very early during embryonic development. To shape the forming neural tube, changes in cellular architecture must be tightly co-ordinated in space and time. Live imaging of different animal models has provided valuable insights into the cellular dynamics driving neural tube formation. The most well-characterised morphogenetic processes underlying this transformation are convergent extension and apical constriction, which elongate and bend the neural plate. Recent work has focused on understanding how these two processes are spatiotemporally integrated from the tissue- to the subcellular scale. Various mechanisms of neural tube closure have also been visualised, yielding a growing understanding of how cellular movements, junctional remodelling and interactions with the extracellular matrix promote fusion and zippering of the neural tube. Additionally, live imaging has also now revealed a mechanical role for apoptosis in neural plate bending, and how cell intercalation forms the lumen of the secondary neural tube. Here, we highlight the latest research on the cellular dynamics underlying neural tube formation and provide some perspectives for the future. [ABSTRACT FROM AUTHOR]

Based on the type-2 Takagi-Sugeno (IT2 T-S) fuzzy theory, a non-autonomous fuzzy complex-valued dynamical system with discontinuous interconnection function is formulated. Under the framework of Filippov, the finite-time stabilization (FTS) problem is investigated by using an indefinite-derivative Lyapunov function method, where the derivative of the constructed Lyapunov function is allowed to be positive. By designing a fuzzy switching state feedback controller involving time-varying control gain parameters, several sufficient criteria are established to determine the considered system's stability in finite time. Correspondingly, due to the time-varying system parameters and the designed time-dependent control gain coefficients, a more flexible settling time (ST) is estimated. Finally, an example is presented to confirm the proposed methodology. [ABSTRACT FROM AUTHOR]

Background. Lung squamous cell carcinoma (LUSC) has poor survival prognosis and few clinical treatment options. We urgently need to explore new therapeutic drugs in clinical practice. Cepharanthine (CEP) has been shown to have anticancer effects in several tumors, but the mechanism of CEP in treating LUSC has not been reported. Methods. SwissTargetPrediction, PharmMapper, and GeneCards were used to identify targets of CEP and LUSC. Further topological analysis was used to obtain hub genes via Cytoscape. Molecular docking was carried out to verify the combination of CEP with hub targets. Based on bioinformatics, we first analyzed the expression and survival of hub targets in LUSC and further analyzed the correlation between hub targets and cancer stemness, immune cell infiltration, and tumor mutation burden (TMB). Results. A total of 41 targets were identified. Further topological analysis identified 6 hub genes: AURKA, CCNA2, CCNE1, CDK1, CHEK1, and PLK1. Molecular docking analysis showed that CEP had stable binding to all these 6 target proteins. In-depth bioinformatics analysis of these 6 targets showed that high expression of these targets were positively correlated with cancer stemness index and negatively correlated with tumor infiltrating immune cells. In immune subtype analysis, the expressions of these targets were significantly decreased in inflammatory tumors. In addition, we also found that the expressions of these targets were positively correlated with TMB. Conclusion. Based on multidisciplinary analysis, we preliminarily identified potential targets of CEP for LUSC treatment and suggested that CEP may play a role in regulating LUSC stemness. [ABSTRACT FROM AUTHOR]

Stroke is one of the most important acute diseases that endanger human health and result in death, including acute cerebral hemorrhage and acute cerebral ischemia. Acute onset is its most prominent feature. Carbon monoxide (CO) is a colorless and odorless gas existing at room temperature. It is not only a common air pollutant, but also has been found to be closely related to stroke. A large amount of exogenous CO has an important impact on the incidence and prognosis of stroke, while endogenous CO as a gas signal also has an important impact on neuroprotection after stroke. Both low-dose CO inhalation and CO-releasing molecule-3 (a molecule that emits CO) treatment have shown the benefits of stroke, and perhaps the role of CO in stroke is one of the key areas for future research. [ABSTRACT FROM AUTHOR]

In this paper, the mechanical behaviors of different lithological rocks of coal measure strata from Shanxi Formation in the eastern margin of the Ordos Basin, China, were investigated through uniaxial compression tests, and the deformation characteristics and failure modes of different lithological rocks were investigated. On this basis, the energy evolution of different lithology rocks was also discussed. The results show that there are obvious differences in the mechanical properties of different lithology rocks in coal measure strata, resulting in different wellbore instability prevention measures and fracturing measures in different lithology strata. Under the uniaxial compression condition, the peak strain of different lithological rocks is obviously different, and the denaturation characteristics are also obviously different, and the failure modes of rocks are mainly the tensile fracture mode, suggesting that the rock samples have strong brittle characteristics. With the increase of the strain, the total energy of different lithological rocks of the coal measure strata increases, and the elastic energy first increases and then decreases rapidly, whereas the dissipated energy first increases slowly and then increases rapidly. Each energy at the peak point is different, and the average total energy of shale, silty shale, siltstone, fine sandstone, and coal is 0.022 J/cm3, 0.045 J/cm3, 0.052 J/cm3, 0.042 J/cm3, and 0.003 J/cm3, respectively, indicating that there are obvious differences in the energy evolution laws of the different lithological rocks. [ABSTRACT FROM AUTHOR]

Chronic primary pain, characterized by overlapping symptoms of chronic pain, anxiety, and depression, is strongly associated with stress and is particularly prevalent among females. Recent research has convincingly linked epigenetic modifications in the medial prefrontal cortex (mPFC) to chronic pain and chronic stress. However, our understanding of the role of histone demethylation in the mPFC in chronic stress-induced pain remains limited. In this study, we investigated the function of lysine-specific histone demethylase 1A (KDM1A/LSD1) in the context of chronic overlapping pain comorbid with anxiety and depression in female mice. We employed a chronic variable stress model to induce pain hypersensitivity in the face and hindpaws, as well as anxiety-like and depression-like behaviors, in female mice. Our findings revealed that chronic stress led to a downregulation of KDM1A mRNA and protein expression in the mPFC. Notably, overexpressing KDM1A in the mPFC alleviated the pain hypersensitivity, anxiety-like behaviors, and depression-like behaviors in female mice, without affecting basal pain responses or inducing emotional distress. Conversely, conditional knockout of KDM1A in the mPFC exacerbated pain sensitivity and emotional distress specifically in females. In summary, this study highlights the crucial role of KDM1A in the mPFC in modulating chronic stress-induced overlapping pain, anxiety, and depression in females. Our findings suggest that KDM1A may serve as a potential therapeutic target for treating chronic stress-related overlap pain and associated negative emotional disorders. [Display omitted] • Chronic stress is a trigger for pain and emotional distress in female mice. • Chronic stress results in a decrease in the levels of KDM1A within the mPFC. • Elevated KDM1A alleviates the pain and emotional distress caused by stress. • Downregulated KDM1A causes pain and emotional distress in female mice. [ABSTRACT FROM AUTHOR]

Liquid crystal monomers (LCMs) are of emerging concern due to their ubiquitous presence in indoor and outdoor environments and their potential negative impacts on human health and ecosystems. Suspect screening approaches have been developed to monitor thousands of LCMs that could enter the environment, but an updated suspect list of LCMs is difficult to maintain given the rapid development of material innovations. To facilitate suspect screening for LCMs, in-silico mass fragmentation model and quantitative structure-activity relationship (QSPR) models were applied to predict electron ionization (EI) mass spectra of LCMs. The in-silico model showed limited predictive power for EI mass spectra, while the QSPR models trained with 437 published mass spectra of LCMs achieved an acceptable absolute error of 12 percentage points in predicting the relative intensity of the molecular ion, but failed to predict the mass-to-charge ratio of the base peak. A total of 41 characteristic structures were identified from an updated suspect list of 1606 LCMs. Multi-phenyl groups form the rigid cores of 85% of LCMs and produce 154 characteristic peaks in EI mass spectra. Monitoring the characteristic structures and fragments of LCMs may help identify new LCMs with the same rigid cores as those in the suspect list. [Display omitted] • A suspect list of 1606 LCMs is updated. • Multi-phenyl groups form the rigid cores of 85% of LCMs. • 41 characteristic structures representing rigid cores of LCMs were identified. • 154 characteristic ion peaks were identified in EI mass spectra of LCMs. [ABSTRACT FROM AUTHOR]

Background: Computer-assisted preoperative planning, combined with PSI has become an effective technique for treating complex limb deformities. The purpose of this study was to evaluate the efficacy and safety of the novel technique in corrective osteotomy for intra-articular varus ankle deformities associated with osteoarthritis and ankle instability.Methods: Nineteen patients with intra-articular varus ankle arthritis were reviewed between April 2017 and June 2019, including ten men and nine women with a mean age of 58.3 ± 9.9 years (range, 38 to 76 years). All patients underwent intra-articular opening wedge osteotomy assisted by 3D virtual planning and PSI. Weight-bearing radiographs were used to assess the radiographic results, including TAS angle, TT angle, TMM angle, TC angle, TLS angle, opening-wedge angle, and wedge height. Functional outcomes were assessed by the AOFAS score, VAS score, and ROM of the ankle.Results: The average follow-up time was 32.2 ± 9.0 months (range, 22 to 47 months). The average union time was 4.4 ± 0.9 months (range, 3.0 to 6.5 months). The TAS angle significantly changed from 84.1 ± 4.6° preoperatively to 87.7 ± 3.1° at the 1-year follow-up and 86.2 ± 2.6° at the latest follow-up. Similarly, the TT angle, TMM angle and TC angle changed significantly at the 1-year follow-up compared with the preoperative assessment and remained stable until the last follow-up. However, the TLS was not corrected significantly. The postoperative obtained opening-wedge angle, and wedge height showed no significant change with preoperative planning. The overall complication rate was 15.8%. The mean VAS score improved from 5.3 ± 0.6 to 2.7 ± 0.7. The mean AOFAS score improved from 56.2 ± 7.6 to 80.6 ± 4.6. However, the ROM showed no significant change.Conclusions: Accurate correction and satisfactory functional recovery were attained with computer-assisted planning and PSI in the corrective osteotomy of intra-articular varus ankle deformities. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproduction. The Cuscuta-Salvia formula has been widely used to treat for PCOS in clinic. However, its chemical and pharmacological properties remain unclear. We identified the active components and related targets of Cuscuta-Salvia using UHPLC-ESI-Q-TOF-MS and TCMSP database. Disease targets were obtained from the DisGeNET and GeneCards databases. Subsequently, common targets between Cuscuta-Salvia and PCOS were identified using a Venn diagram. PPI network was established. Core genes were selected using a Cytoscape software plugin. GO and KEGG enrichment analyses were performed for common targets using the "pathview" package in R. Several core targets were verified using molecular and Immunological methods. By combining UHPLC-ESI-Q-TOF-MS with a network pharmacology study, 14 active components and a total of 80 common targets were obtained. Ten core genes were regulated by Cuscuta-Salvia in PCOS, including IL6, AKT1, VEGFA, TP53, TNF, MAPK1, JUN, EGF, CASP3, and EGFR. GO results showed that cellular response to drugs, response to oxygen levels, response lipopolysaccharides, and response to molecule of bacterial origin in BP category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in CC category; DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in MF terms. The KEGG enrichment pathway was mainly involved in the PI3K − Akt, MAPK, TNF, IL-17 signalling pathways, and in cellular senescence. Furthermore, the results of the experimental study showed that Cuscuta-Salvia ameliorated the pathological changes in the ovaries, liver and adipose tissue. And it improved the expressions of the genes or proteins. Our results demonstrate that Cuscuta-Salvia may provide a novel pharmacological basis in an experimental model of PCOS by regulating gene expression. This study provides a basis for future research and clinical applications. [ABSTRACT FROM AUTHOR]

A one‐pot approach for the asymmetric synthesis of C2‐tetrasubstituted indolin‐3‐ones from 2‐substituted indoles was developed via merging transition metal catalysis with organocatalysis. This strategy involves two processes, including CuI catalyzed oxidative dearomatization of 2‐substituted indoles using O2 as green oxidant, and followed by an proline‐promoted asymmetric Mannich reaction with ketones or aldehydes. A series of C2‐tetrasubstituted indolin‐3‐ones were obtained in 35–86% yields, 2:1‐>20:1 dr and 48–99% ee. Moreover, the synthetic 2‐tetrasubstituted indolin‐3‐ones could be easily transformed into 1H‐[1,3] oxazino [3,4‐a]indol‐5(3H)‐ones via a [4+1] cyclization process. In addition, the synthetic compound 3 s show certain antibacterial activity against S. aureus ATCC25923 and multi‐drug resistance bacterial strain of S. aureus (20151027077) and its MIC values up to 8 μg/mL and 16 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

Aim: More than 90% of ectopic pregnancies occur in the Fallopian tubes. As the pathogenesis of tubal pregnancy remains largely unclear, the development of strategies to prevent and treat tubal pregnancy still represents a major clinical challenge. This review thoroughly summarizes the current data, aiming to determine the genes and signaling pathways that are involved in the pathophysiology of human tubal pregnancy. Methods: An electronic search from databases of PubMed, Google Scholar, and Chinese databases was carried out using key words pertaining to the pathogenesis of tubal pregnancy from the perspectives of both the Fallopian tubes and the embryo. A review of the literatures including review articles, experimental, and observational studies and case reports published between 1999 and 2021 was conducted. Results: Tubal pregnancy results from the interaction networks between the Fallopian tube and the embryo rather than from simple tubal abnormality. Furthermore, the embryo‐maternal communication is supposed to start from the preimplantation period to the implantation period. Conclusion: A greater understanding of the interaction networks between the Fallopian tubes and the embryo is of great significance for the prevention and medical treatment of tubal pregnancy. [ABSTRACT FROM AUTHOR]

Research using avian embryos has led to major conceptual advances in developmental biology, virology, immunology, genetics and cell biology. The avian embryo has several significant advantages, including ready availability and ease of accessibility, rapid development with marked similarities to mammals and a high amenability to manipulation. As mechanical forces are increasingly recognised as key drivers of morphogenesis, this powerful model system is shedding new light on the mechanobiology of embryonic development. Here, we highlight progress in understanding how mechanical forces direct key morphogenetic processes in the early avian embryo. Recent advances in quantitative live imaging and modelling are elaborating upon traditional work using physical models and embryo manipulations to reveal cell dynamics and tissue forces in ever greater detail. The recent application of transgenic technologies further increases the strength of the avian model and is providing important insights about previously intractable developmental processes. [ABSTRACT FROM AUTHOR]

Background. Polycystic ovary syndrome (PCOS) causes low fertility in females. Coptis chinensis (C. chinensis) is used to clear heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although C. chinensis has demonstrated efficacy against PCOS in clinical practice, there are no available data regarding the bioactive components of C. chinensis, their targets, and molecular mechanisms underlying their effects. Methods and Results. Network pharmacology was used to analyze the bioactive components of C. chinensis, their targets, and signaling pathways underlying their effects. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of C. chinensis. The GeneCards, OMIM, and PharmGkb databases were used to screen 3517 disease targets for PCOS, and 102 common targets of drugs and diseases were screened using R Cytoscape that was utilized to build a drug-active ingredient-disease target interaction network, and the STRING platform was utilized to construct a common target protein-protein interaction network, including 102 nodes and 221 edges. Key targets of C. chinensis for the treatment of PCOS included JUN, MAPK, IL6, CXCL8, FOS, and IL1B. A total of 123 gene ontology (GO) terms and 129 pathways were acquired by GO and KEGG enrichment analyses. The AGEs/RAGE, TNF, IL-17, MAPK, and HIF-1 signaling pathways were closely related to PCOS and may be the core pathways involved in PCOS. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes. Furthermore, based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of C. chinensis. The results showed that C. chinensis treatment reversed histopathological damage of the ovary and also ameliorated the mRNA and protein expression levels of the predicted hub targets (MAPK1, CXCL8, IL-6, and IL-1β). These results indicated that WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy. Conclusions. This preliminary study verified the basic pharmacological effects and mechanisms of C. chinensis, a TCM, in the treatment of PCOS. These results indicate that the therapeutic effects of C. chinensis on PCOS may be achieved by regulating the expression of inflammatory factors. This study provides new insights for the systematic exploration of the mechanism of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Here, we report the generation of a transgenic Lifeact-EGFP quail line for the investigation of actin organization and dynamics during morphogenesis in vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis. Using high-resolution live imaging approaches, we present the dynamic behaviors and morphologies of cellular protrusions in different tissue contexts. Furthermore, through the integration of live imaging with computational segmentation, we visualize cells undergoing apical constriction and large-scale actin structures such as multicellular rosettes within the neuroepithelium. These findings not only enhance our understanding of tissue morphogenesis but also demonstrate the utility of the Lifeact-EGFP transgenic quail as a new model system for live in vivo investigations of the actin cytoskeleton. [ABSTRACT FROM AUTHOR]

Background. Polycystic ovary syndrome (PCOS) causes low fertility in females. Coptis chinensis (C. chinensis) is used to clear heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although C. chinensis has demonstrated efficacy against PCOS in clinical practice, there are no available data regarding the bioactive components of C. chinensis, their targets, and molecular mechanisms underlying their effects. Methods and Results. Network pharmacology was used to analyze the bioactive components of C. chinensis, their targets, and signaling pathways underlying their effects. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of C. chinensis. The GeneCards, OMIM, and PharmGkb databases were used to screen 3517 disease targets for PCOS, and 102 common targets of drugs and diseases were screened using R Cytoscape that was utilized to build a drug-active ingredient-disease target interaction network, and the STRING platform was utilized to construct a common target protein-protein interaction network, including 102 nodes and 221 edges. Key targets of C. chinensis for the treatment of PCOS included JUN, MAPK, IL6, CXCL8, FOS, and IL1B. A total of 123 gene ontology (GO) terms and 129 pathways were acquired by GO and KEGG enrichment analyses. The AGEs/RAGE, TNF, IL-17, MAPK, and HIF-1 signaling pathways were closely related to PCOS and may be the core pathways involved in PCOS. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes. Furthermore, based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of C. chinensis. The results showed that C. chinensis treatment reversed histopathological damage of the ovary and also ameliorated the mRNA and protein expression levels of the predicted hub targets (MAPK1, CXCL8, IL-6, and IL-1β). These results indicated that WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy. Conclusions. This preliminary study verified the basic pharmacological effects and mechanisms of C. chinensis, a TCM, in the treatment of PCOS. These results indicate that the therapeutic effects of C. chinensis on PCOS may be achieved by regulating the expression of inflammatory factors. This study provides new insights for the systematic exploration of the mechanism of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) is a popular hole transport material in inverted perovskite solar cells (PSCs). However, it is required to modify the PEDOT:PSS to achieve high-performance PSCs. Herein, a facile method to modify PEDOT:PSS using water to improve the performance of inverted PSCs is developed. The modification impact on the physical properties of the PEDOT:PSS films is systemically studied. The results show that the transmittance and resistance of the PEDOT:PSS layer are greatly improved by modification using water without changing its work function. The growth of perovskite films on PEDOT:PSS is also influenced by the modification of PEDOT:PSS using water. Better crystallinity and larger grain sizes of the perovskite film are also achieved, leading to recombination loss being greatly reduced and the performance of the devices significantly improved. The PSCs based on modified PEDOT:PSS exhibit a higher power conversion efficiency (PCE) of 17.28 % and higher open-circuit voltage (Voc) of 1.06 V compared to control devices prepared with unmodified PEDOT:PSS (PCE = 12.49%, Voc = 0.99 V). This work provides a facile method to modify PEDOT:PSS to prepare high-performance inverted PSCs. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the efficacy and safety of tanezumab administered as a fixed dosing regimen in patients with knee or hip osteoarthritis. Randomized controlled phase III trials (RCTs) that evaluated the efficacy and safety associated with tanezumab for knee or hip OA were systematically identified by searching electronic databases, including Cochrane Library, PubMed, and Embase, for 30 years from December 1990 up to July 2020. Ten relevant studies were included in our meta-analysis. The research was reported based on the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure the reliability and verity of results. Our study showed that the tanezumab groups were more effective than the placebo groups in terms of mean change from the baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (P <.00001), WOMAC physical functional (P <.00001), and patient's global assessment (PGA) (P <.00001). Discontinued due to adverse events (AEs) (P <.00001), serious AEs (P =.02), abnormal peripheral sensations (both P <.00001), and peripheral neuropathy (P <.002) in tanezumab groups were significantly higher than that in control groups. Compared with placebo, tanezumab can effectively relieve pain and improve WOMAC physical function and patient's global assessment (PGA) in knee and hip osteoarthritis. Meanwhile, adverse events are transient in nature and generally well-tolerated. However, we still need large-sample, high-quality studies to investigate the long-term safety of tanezumab to give the conclusion. [ABSTRACT FROM AUTHOR]

Background: Acromioclavicular joint arthritis is a common, painful, and often missed diagnosis, and it often accompanies other shoulder conditions such as rotator cuff disease. Whether distal clavicle resection is important to perform in patients undergoing surgery for rotator cuff tears and concomitant acromioclavicular joint arthritis is controversial.Questions/purposes: The purpose of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of distal clavicle resection on (1) outcome scores; (2) shoulder ROM, joint pain or tenderness, and joint instability; and (3) risk of reoperation among patients treated surgically for rotator cuff tears who had concomitant acromioclavicular joint arthritis.Methods: We systematically searched the PubMed, EMBASE, and Cochrane databases to find RCTs that met our eligibility criteria, which, in summary, (1) compared rotator cuff repair plus distal clavicle resection with isolated rotator cuff repair for patients who sustained a full- or partial-thickness rotator cuff tear and concomitant acromioclavicular joint arthritis; and (2) the followup period was at least 2 years. Two reviewers screened the studies, extracted the data and evaluated the methodological quality, and performed data analysis. Statistical heterogeneity among studies was quantitatively evaluated with the I index. No heterogeneity was detected (I = 0%; p = 0.75) in terms of acromioclavicular joint pain or tenderness, Constant score, forward flexion, external rotation, and risk of reoperation, so fixed-effect models were used in these endpoints. Heterogeneity was moderate for the American Shoulder and Elbow Surgeons (ASES) score (I = 53%; p = 0.12) and low for the visual analog scale (VAS) score (I = 35%; p = 0.22), so random-effect models were used in these endpoints. Subgroup analysis was stratified by the symptom of acromioclavicular joint arthritis. Three RCTs with 208 patients were included. We evaluated the risk of bias using the Cochrane risk-of-bias tool; in aggregate, the three RCTs included showed low to intermediate risk, although not all parameters of the Cochrane tool could be assessed for all studies.Results: There was no difference between the distal clavicle resection plus rotator cuff repair group and the isolated rotator cuff repair group in ASES score (mean difference =1.41; 95% confidence interval [CI], -3.37 to 6.18; p = 0.56) nor in terms of the VAS score and Constant score. Likewise, we found no difference in ROM of the shoulder (forward flexion, internal rotation, and external rotation) or acromioclavicular joint pain or tenderness between the groups (pooled results of acromioclavicular joint pain or tenderness: risk ratio [RR], 1.59; 95% CI, 0.67-3.78; p = 0.30). Acromioclavicular joint instability was only detected in the rotator cuff repair plus distal clavicle resection group. Finally, we found no difference in the proportion of patients undergoing repeat surgery between the study groups (pooled results of risk of reoperation for the rotator cuff repair plus distal clavicle resection and isolated rotator cuff repair: one of 52 versus two of 78; RR, 0.86; 95% CI, 0.11-6.48; p = 0.88).Conclusions: Distal clavicle resection in patients with rotator cuff tears did not result in better clinical outcome scores or shoulder ROM and was not associated with a lower risk of reoperation. Distal clavicle resection might cause acromioclavicular joint instability in patients with rotator cuff tears and concomitant asymptomatic acromioclavicular joint arthritis. Arthroscopic distal clavicle resection is not recommended in patients with rotator cuff tears and concomitant acromioclavicular joint arthritis. Additional well-designed RCTs with more participants, long-term followup, and data on patient-reported outcomes are needed.Level Of Evidence: Level I, therapeutic study. [ABSTRACT FROM AUTHOR]

Objective: To clarify the regulatory effect of Calcyclin (S100A6) on chondrocytes apoptosis and its relationship with progression of osteoarthritis in an effort to explore potential therapeutic targets for osteoarthritis. Method: Immunofluorescence assay was produced to identify the rat chondrocyte sample and western blots assay was detected the expression changes of S100A6 between control group and osteoarthritis model which induced by interleukin‐1β. Adenovirus were transfected into the chondrocytes in vitro, in order to regulate the S100A6 expression. The influence of S100A6 on inflammatory reaction of osteoarthritis was detected by RT‐PCR. Also, Caspase‐3 activity assay and TUNEL assay were performed to evaluate the apoptosis changes. In addition, RT‐PCR and western blots were performed to verify that S100A6 mediated the PI3K/AKT signaling pathway. Through the usage of pathway regulator, we detected S100A6 produced the effect by mediating the PI3K/AKT pathway. Results: We determined the expression of S100A6 decreased in osteoarthritis model, the relative expression level in osteoarthritis model was about 0.5 fold compared with control group. Through adenovirus transfection we revealed that the inflammatory factors of osteoarthritis (interleukin‐6 and matrix metalloproteinase‐13) showed a negative correlation with the S100A6 expression. The relative expression level of interleukin‐6 and matrix metalloproteinase‐13 were 1.534 and 1.259 when S100A6 was up‐regulated and the values were up to 2.445 and 2.074, respectively, when S100A6 was down‐regulated. Also, the data verified the apoptosis could be reduced when the S100A6 was up‐regulated and be activated when the S100A6 was down‐regulated, the Caspase‐3 activity was 16.512 U/μg and 24.45 U/μg respectively. Similar results were shown in TUNEL assay, the apoptosis index was 4.46% and 31.44%, respectively. Additionally, the results of polymerase chain reaction and western blots both demonstrated that the expression level of PI3K and AKT were increased when S100A6 was up‐regulated, conversely the expression level of those two signal modules were reduced if the S100A6 was down‐regulated. More importantly, the apoptosis triggered by S100A6 can be offset by the PI3K/AKT pathway inhibitor and activator (LY294002 and IGF‐1), the values of Caspase‐3 activity and apoptosis index became close to the untreated osteoarthritis group. The experimental results in this study were statistically significant. Conclusion: We investigated that Calcyclin (S100A6) relieved the inflammation and mediated the chondrocyte apoptosis through PI3K/AKT pathway and we confirmed that S100A6 might be an attractive therapeutic target. [ABSTRACT FROM AUTHOR]

Aflatoxins are extremely harmful carcinogens to humans and animals. In recent years, attention has been directed toward the application of molecular imprinting polymers for the separation and detection of aflatoxin. In this review, polymerization methods for the preparation of molecular imprinting polymers for aflatoxin detection, such as lump-bulk polymerization, spherical molecular imprinting polymer synthesis, surface-imprinted polymerization, and electropolymerization, are described. The applications of molecular imprinting polymers in solid-phase extraction, biosensors, and the surface-enhanced Raman detection of aflatoxin are also reviewed in this paper. [ABSTRACT FROM AUTHOR]

This paper suggests a direct algebraic method for finding exact solutions of the space-time fractional (2+1)-dimensional breaking soliton equation. The solution procedure is reduced to solve a large system of algebraic equations, which is then solved by Wu's method. [ABSTRACT FROM AUTHOR]

To determine the expression profile and clinical significance of long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) of patients with primary gout and healthy control subjects. Human lncRNA microarrays were used to identify the differentially expressed lncRNAs and mRNAs in primary gout patients (n = 6) and healthy control subjects (n = 6). Bioinformatics analyses were performed to predict the roles of differently expressed lncRNAs and mRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of 8 lnRNAs in 64 primary gout patients and 32 healthy control subjects. Spearman's correlation was used to analyze the correlation between these eight lncRNAs and the laboratory values of gout patients. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the lncRNAs identified in gout. The microarray analysis identified 1479 differentially expressed lncRNAs (879 more highly expressed and 600 more lowly expressed), 862 differentially expressed mRNAs (390 more highly expressed and 472 more lowly expressed) in primary gout (fold change > 2, P < 0.05), respectively. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of gout through several different pathways. The expression levels of TCONS_00004393 and ENST00000566457 were significantly increased in the acute gout flare group than those in the intercritical gout group or healthy subjects (P<0.01). Moreover, inflammation indicators were positive correlated with TCONS_00004393 and ENST00000566457 expression levels. The areas under the ROC curve of ENST00000566457 and NR-026756 were 0.868 and 0.948, respectively. Our results provide novel insight into the mechanisms of primary gout, and reveal that TCONS_00004393 and ENST00000566457 might be as candidate targets for the treatment of gout flare; ENST00000566457 and NR-026756 could effectively discriminate between the gout and the healthy control groups. [ABSTRACT FROM AUTHOR]

Background: Guillain-Barré syndrome (GBS) is the most common and serious acute paralytic neuropathy and is usually caused by infection. It is thought to be the result of an aberrant response of the immune system. To our knowledge, GBS, especially severe GBS, after orthopaedic surgery has rarely been reported.Case Presentation: We herein report the case of a 58-year-old man who developed quadriplegia and respiratory failure on the 6th day after surgery for multiple fractures. The patient had no symptoms of respiratory or gastrointestinal tract infection within 4 weeks before the onset. The white blood cell count was normal, and there was no redness, swelling, heat or pain in the surgical incision. Brain, cervical and thoracic magnetic resonance imaging were normal, albuminocytological dissociation was found on cerebrospinal fluid examination, and electrophysiological examination showed that sensory and motor nerve evoked potentials could not be elicited. A diagnosis of post-traumatic GBS was made, and the patient was treated with intravenous immunoglobulin and plasma exchange, as well as supportive care and rehabilitation exercise. The length of stay was 18 months, and the in-hospital-related costs amounted to $127,171. At the last follow-up, the patient had recovered only grade 3 power in the upper limbs and grade 2 power in the lower limbs.Conclusions: Severe GBS is a rare complication after orthopaedic surgery. When progressive weakness occurs in trauma patients, the possibility of GBS should be considered, and cerebrospinal fluid and electrophysiological examinations should be performed in a timely manner. For patients with severe GBS after trauma, the treatment costs may be high, and the prognosis may be poor. [ABSTRACT FROM AUTHOR]

In this article, a method of single-event burnout (SEB) hardening at high linear energy transfer (LET) value range is proposed and investigated by the 2-D numerical simulations. The improved MOSFET using this method and the conventional MOSFET are analyzed and compared to evaluate the effectiveness of this method. Simulation results show that, compared with the conventional MOSFET, the improved MOSFET using this method can effectively and quickly reduce the internal high electric field, thereby reducing the temperature. Under the condition of a LET value of 0.5 pC/μm and a drain voltage of 1200 V, the maximum drain current is 0.168 A, and the maximum global device temperature is 1724 K, which is much lower than the melting down temperature of silicon carbide (SiC) (3100 K). The hardening method in this article can be applied to different breakdown voltages by adjusting structure parameters. [ABSTRACT FROM AUTHOR]

The prompt J / ψ photoproduction within the non-relativistic QCD (NRQCD) framework at the future Circular Electron Positron Collider (CEPC) is studied, including the contributions from both direct and resolved photons. Employing different sets of long distance matrix elements, the total cross section is dominated by the color-octet channel. We present different kinematic distributions of J / ψ production and the results show there will be about 50 J / ψ events when the transverse momentum of J / ψ is up to 20 GeV. It renders that the J / ψ photoprodution at the CEPC is a well laboratory to test the NRQCD and further clarify the universality problem in NRQCD between electron positron collider and hadron collider. [ABSTRACT FROM AUTHOR]

Background: The calcicole or calcifuge behavior of wild plants has been related to element deficiency or toxicity. For fern species, however, knowledge about their adaptive differences and responses to soil environmental changes is virtually absent. In the karst regions of southern China, most Adiantum species favor calcareous soils, but A. flabellulatum prefers acidic soils. Such contrasting preferences for soil types in the same genus are interesting and risky because their preferred soils may "pollute" each other due to extreme precipitation events. We mixed calcareous and acidic soils at 1:1 (v/v) to simulate the "polluted" soils and grew three Adiantum species (the calcicole A. capillus-veneris f. dissectum and A. malesianum and the calcifuge A. flabellulatum) on the calcareous, acidic and mixed soils for 120 d and assessed their growth performance and element concentrations. Results: The calcareous soil showed the highest pH, Ca, Mg and P concentrations but the lowest K concentration, followed by the mixed soil, and the acidic soil. After 120 d of growth, the calcifuge A. flabellulatum on the calcareous and mixed soils exhibited lower SPAD and relative growth rate (RGR) than those on the acidic soil, and its leaf and root Ca, Mg and Fe concentrations were higher and K was lower on the calcareous soil than on the acidic soil. The calcicole A. capillus-veneris f. dissectum on the calcareous soil had similar leaf element concentrations and RGR with those on the mixed soil, but their leaf Ca, Fe and Al were lower and leaf P and K concentrations, SPAD and RGR were higher than those on the acidic soil. For the calcicole A. malesianum, leaf Ca, Fe and Al were lowest and leaf P and RGR were highest when grown on the mixed soil, intermediated on the calcareous soil, and on the acidic soil. Compared with A. malesianum, A. capillus-veneris f. dissectum had lower leaf Ca, Fe and Al but higher leaf Mg concentration when grown on the same calcareous or mixed soils. Conclusions: A. capillus-veneris f. dissectum is a low leaf Ca calcicole species while A. malesianum is an Al accumulating calcicole species. They can effectively take up P and K to leaves and hence can thrive on calcareous soils. In contrast, the calcifuge A. flabellulatum grown on calcareous soils is stunted. Such growth performance may be attributed to the increased leaf Ca and decreased leaf K concentration. If their preferred soils are "polluted", A. flabellulatum can grow worse, A. capillus-veneris f. dissectum can remain almost unaffected while A. malesianum will perform better. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is one of the significant complications of diabetes mellitus (DM), and CASR plays an important role in cellular antiapoptosis and NO production in the vascular endothelium by activating PKC. The present study was aimed to investigate the efficacy of Leech and Centipede Granules (LCG) through the CaSR/PLC/PKC signaling. Fifty male Sprague-Dawley rats were treated with streptozotocin to induce the DM model. After 10 weeks, an apomorphine test was used to confirm DMED. Rats with DMED were administrated with LCG and U73122 for 4 weeks. Fasting blood glucose, body weight, insulin and glucagon levels were measured. Erectile function in rats was assessed by apomorphine. Serums were measured using enzyme-linked immunosorbent assay and flow cytometry, and penile tissues were harvested for histologic and the expression of related targets analyses. After treatment, fasting blood glucose, body weight, insulin, glucagon levels, and erectile function were significantly ameliorated in the LCG groups. The LOX-1, NOX, and EMPs concentrations were significantly decreased with LCG treatment. LCG also continuously increased NO and decreased ET-1 content in penile tissues. LCG and U73122 administration also improved penile fibrosis by significantly decreasing VCAM-1, ICAM-1, and CD62P. The data also showed that LCG reduced the apoptosis level in the penis. Furthermore, the inhibited activation of the CaSR/PLC/PKC pathway was observed in DMED rats with LCG treatment. Collectively, LCG significantly ameliorated erectile function of DMED rats via increased NO generation, inhibiting endothelial cells apoptosis and penile fibrosis, which might benefit from the suppression of CaSR/PLC/PKC pathway in DMED rats. [ABSTRACT FROM AUTHOR]

The present study aimed to analyze the data of embedded intrauterine device (IUD) in the bladder wall with the additional presence of calculus. This case series study included 11 female patients with partially or completely embedded IUD in the bladder wall. Their median age was 34 (range, 32–39) years. The median duration of IUD placement was 36 (range, 24–60) months. The median duration of symptoms was 9 (range, 3–12) months. Six patients underwent laparoscopy: the operation duration was 129 (range, 114–162) min, blood loss was 15 (range, 10–25) mL, the hospital stay was 4 (range, 4–4.5) days, the visual analog scale (VAS) for pain at 6 h after surgery was 3 (range, 2–6), and the time to removal of the urethral catheter was 7 (range, 7–8) days. Five patients underwent open surgery: the operation duration was 126 (range, 96–192) min, blood loss was 30 (range, 20–50) mL, the hospital stay was 7 (range, 7–15) days, the VAS was 6 (range, 4–9) at 6 h after surgery, and the time to removal of the urethral catheter was 9 (range, 8–17) days. The IUD and bladder stones were successfully removed in all 11 (100%) patients. [ABSTRACT FROM AUTHOR]

Cells are internally organized into compartmentalized organelles that execute specialized functions. To understand the functions of individual organelles and their regulations, it is critical to resolve the compositions of individual organelles, which relies on a rapid and efficient isolation method for specific organellar populations. Here, we introduce a robust affinity purification method for rapid isolation of intracellular organelles (e.g. lysosomes, mitochondria and peroxisomes) by taking advantage of the extraordinarily high affinity between the twin strep tag and streptavidin variants. With this method, we can isolate desired organelles with high purity and yield in 3 min from the post-nuclear supernatant of mammalian cells or less than 8 min for the whole purification process. Using lysosomes as an example, we show that the rapid procedure is especially useful for studying transient and fast cellular activities, such as organelleinitiated signaling and organellar contents of small-molecular metabolites. Therefore, our method offers a powerful tool to dissect spatiotemporal regulation and functions of intracellular organelles. [ABSTRACT FROM AUTHOR]

Background: More elderly patients are suffering from intertrochanteric fractures. However, the choice of internal fixation is still controversial, especially in the treatment of unstable intertrochanteric fracture; thus, previous implants continue to be improved, and new ones are being developed. The purpose of our study was to compare the biomechanical advantages between the zimmer natural nail (ZNN) and proximal femoral nail antirotation-II (PFNA-II) in the treatment of elderly reverse obliquity intertrochanteric fractures. Methods: A three-dimensional finite element was applied for reverse obliquity intertrochanteric fracture models (AO31-A3.1) fixed with the ZNN or PFNA-II. The distribution, peak value and position of the von Mises stress and the displacement were the criteria for comparison between the two groups. Results: The stresses of the internal fixation and femur in the ZNN model were smaller than those in the PFNA-II model, and the peak values of the two groups were 364.8 MPa and 171.8 MPa (ZNN) and 832.3 MPa and 1795.0 MPa (PFNA-II). The maximum amount of displacement of the two groups was similar, and their locations were the same, i.e., in the femoral head vertex (3.768 mm in the ZNN model and 3.713 mm in the PFNA-II model). Conclusions: The displacement in the two models was similar, but the stresses in the implant and bone were reduced with the ZNN. Therefore, the ZNN implant may provide biomechanical advantages over PFNA-II in reverse obliquity intertrochanteric fractures, as shown through the finite element analysis. These findings from our study may provide a reference for the perioperative selection of internal fixations. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to introduce and study a class of new two-step viscosity iteration methods for approximating fixed points of set-valued nonexpansive mappings in CAT(0) spaces. Here, the fixed point is unique solution of a variational inequality with a contraction mapping. Further, we prove strong convergence theorem of the two-step viscosity iterations with some general conditions in a complete CAT(0) space. The presented results improve and unify the corresponding results in the literature. [ABSTRACT FROM AUTHOR]

Objective: To investigate the biomechanical effects of reduction quality on patients after femoral neck fracture internal fixation. Methods: The data of individual patients with femoral neck fractures were reviewed. Data for patients with simple unilateral femoral neck fractures whose reduction quality was evaluated as good by hip X‐ray films after internal fixation were collected from January 2013 to January 2017. The CT data of the patients was used to reconstruct 3D models of the femur and the screw. The spatial displacement after the operation of femoral neck fracture was measured, which included the displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head, and the rotational angle. The cases were followed up by telephone consultation and clinical review to determine whether the osteonecrosis of the femoral head occurred. Follow‐up time should be more than 18 months after surgery. The cases were grouped according to the results into an osteonecrosis of the femoral head group and a non‐osteonecrosis of the femoral head group. Finally, the differences in postoperative spatial displacement between the two groups were compared and analyzed. In addition, a mechanical analysis of femoral force during gait was performed via finite element analysis. Results: Data for 241 patients with femoral neck fractures who were treated with closed reduction and internal fixation were collected. 3D measurement showed the average displacement value, including the center of the femoral head (5.90 ± 3.4 mm), the deepest portion of the femoral head fovea (9.32 ± 4.8 mm), and the rotational angle (16.1° ± 9.4°). After telephone consultation and clinical review, osteonecrosis of the femoral head was diagnosed in 28 (11.62%) of the patients. In the osteonecrosis of the femoral head (ONFH) group, the displacement of the deepest portion of the femoral head fovea was 10.92 ± 9.18 mm; the displacement was 8.86 ± 6.29 mm in the non‐ONFH group. The displacement of the center of the femoral head in the ONFH group was 7.575 ± 5.69 mm and 5.31 ± 4.05 mm in non‐ONFH group. The rotational angle was 20.11° ± 10.27° in the ONFH group and 14.19° ± 11.09° in the non‐ONFH group. The statistical analysis showed that the postoperative spatial displacements, including the displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head, and the rotational angle between the two groups, had statistical differences. Finite element analysis showed that as the spatial displacement increased, the stress, the displacement, and the equivalent strain of the proximal femur also increased. Conclusion: Poor reduction quality after femoral neck fracture is a risk factor for re‐fracture and femoral head necrosis, and the measurement method of this study can be used to predict the occurrence of femoral head necrosis early after femoral neck fracture. [ABSTRACT FROM AUTHOR]

Objective: To compare the biomechanical stabilities of less invasive stabilization system (LISS) plate and retrograde intramedullary nail (IMN) for the comminuted femoral supracondylar fracture fractures in the elderly. Methods: Sixteen pairs of embalmed cadaver femurs were obtained to simulate a comminuted supracondylar femur fracture (AO/OTA33‐A3) gap model. All left‐side specimens were fixed with LISS plate, and retrograde IMN were applied to the right‐side specimens. All specimens were tested in torsional, axial and cyclic load mode on an Instron testing machine. Results: The mean torsional stiffness for LISS plate group was 34.1% greater than retrograde IMN group (2.90 vs. 1.91 Nm/degree, P = 0.002), but the mean axial stiffness was greater for the retrograde IMN (199.16 vs. 303.93 N/mm, P < 0.001). The total deformation of LISS plate caused by cyclic axial loading was greater than retrograde IMN (4.17 vs. 3.57 mm, P = 0.014). Significantly less mean irreversible deformation was detected in LISS plate than in retrograde IMN (1.64 vs. 1.69 mm, P = 0.699). Failure loads of the constructs were significantly different between the two groups (LISS plate: 2941±128 N; retrograde IMN: 4022±176 N, P < 0.001). Conclusion: For comminuted femoral supracondylar fractures in the elderly, the tested instruments can both maintain sufficient biomechanical stabilities, but retrograde IMN is superior to LISS plate in deformation of fracture site. [ABSTRACT FROM AUTHOR]

Abstract Developing of high efficient electrode materials for CO 2 reduction is very important in CO 2 conversion and recycling utilization. In this work, we have fabricated ZnS/Zn electrode using sulphur infiltration method. This method is a well-developed technology in surface treatment. ZnS/Zn electrode fabricated via sulphur infiltration method has a crucial advantage: because sulfur atomic is infiltrated into Zn substrate, a translation layer is formed and sandwiches between ZnS layer and Zn substrate. As a result, ZnS connects with Zn substrate firmly, and the exfoliation of ZnS layer from Zn substrate is avoided. The ZnS/Zn has been investigated as the cathode for CO 2 electro-reduction in propylene carbonate/tetrabutylammonium perchlorate (PC/TBAP) in membrane electrolysis cell. The current density of potentiostatic electrolysis remains stable at 6.72 mA/cm2 at voltage −2.4 V and the faradaic efficiency of CO formation reaches to 92%. Comparing with Zn electrode, ZnS/Zn exhibits higher catalytic activity. Highlights • Demonstrating that S-Infiltration is a feasible method for electrode preparation. • Avoiding that the exfoliation of electrode modification layer from the substrate. • ZnS/Zn electrode has large surface roughness that result high current density. • ZnS/Zn electrode shows high CO selectivity and catalytic activity. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to introduce and study a class of new two-step viscosity iteration methods for approximating fixed points of set-valued nonexpansive mappings in CAT(0) spaces. Here, the fixed point is unique solution of a variational inequality with a contraction mapping. Further, we prove strong convergence theorem of the two-step viscosity iterations with some general conditions in a complete CAT(0) space. The presented results improve and unify the corresponding results in the literature. [ABSTRACT FROM AUTHOR]

Abstract A metal-free and solvent free click-chemistry procedure has been revealed for the synthesis of 4-trifluoroacetyl-1,2,3-triazoles from corresponding azides and alkyne with high yield and selectivity. The pure products could be easily obtained via crystallization of the reaction mixture (standing for 1 day). Among the 4-trifluoroacetyl-1,2,3-triazoles, 3ba showed the best anticancer activity against HepG2 cell with IC 50 of 0.0267 μmol/ml. This method has the advantages of less pollution, low cost, simple treatment and more efficiency. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

We conduct Observing System Simulation Experiments (OSSEs) to compare the ability of future satellite measurements of atmospheric methane columns (TROPOMI, GeoCARB, GEO-CAPE) for constraining methane emissions down to the 25 km scale through inverse analyses. The OSSE uses the GEOS-Chem chemical transport model (0.25∘×0.3125∘ grid resolution) in a 1-week simulation for the Southeast US with 216 emission elements to be optimized through inversion of synthetic satellite observations. Clouds contaminate 73 %–91 % of the viewing scenes depending on pixel size. Comparison of GEOS-Chem to Total Carbon Column Observing Network (TCCON) surface-based methane column observations indicates a model transport error standard deviation of 12 ppb, larger than the instrument errors when aggregated on the 25 km model grid scale, and with a temporal error correlation of 6 h. We find that TROPOMI (7×7 km 2 pixels, daily return time) can provide a coarse regional optimization of methane emissions, comparable to results from an aircraft campaign (SEAC 4 RS), and is highly sensitive to cloud cover. The geostationary instruments can do much better and are less sensitive to cloud cover, reflecting both their finer pixel resolution and more frequent observations. The information content from GeoCARB toward constraining methane emissions increases by 20 %–25 % for each doubling of the GeoCARB measurement frequency. Temporal error correlation in the transport model moderates but does not cancel the benefit of more frequent measurements for geostationary instruments. We find that GeoCARB observing twice a day would provide 70 % of the information from the nominal GEO-CAPE mission preformulated by NASA in response to the Decadal Survey of the US National Research Council. [ABSTRACT FROM AUTHOR]

C18H13F2NO4, triclinic, P1̄ (no. 2), a = 7.9002(13) Å, b = 9.9371(16) Å, c = 10.6852(17) Å, α = 101.390(2)°, β = 93.169(2)°, γ = 104.901(2)°, V = 789.7(2) Å3, Z = 2, Rgt(F) = 0.0567, wRref(F2) = 0.1223, T = 296(2) K. [ABSTRACT FROM AUTHOR]

In the original publication of this article [1], Chinese text of the Figs. 3, 4, 5 has not been converted to English. [ABSTRACT FROM AUTHOR]

Background/Aims: Liver disease is a leading cause of high mortality and morbidity worldwide. The aim of the present study is to investigate the regulatory role of prolyl hydroxylase-2 (PHD2)-hypoxia-inducible factor-2a (HIF-2α) axis on nonalcoholic fatty liver disease (NAFLD) and to explore the potential mechanisms by which endothelial (EC)-specific PHD2 deficiency regulates hepatic steatosis and fibrosis. Methods: In the endothelial-specific PHD2 knockout (PHD2ECKO) mouse fed with normal diet or high fat diet (HFD), liver lipid accumulation and fibrosis were measured by Oil Red O and Masson trichrome staining. The fat and body weight (FW/BW) ratio and glucose tolerance were measured. The expression of HIF-2α, atrial natriuretic peptide (ANP), angiopoietin-2 (Ang-2), and transforming growth factor-b (TGF-β) were analyzed by western blot analysis. Results: The steatosis and fibrosis were significantly increased in the PHD2ECKO mice. FW/BW ratio was significantly increased in the PHD2ECKO mice. Moreover, knockout of endothelial PHD2 resulted in an impairment of glucose tolerance in mice. Western blot analysis showed that the expression of HIF-2α in liver tissues was not significantly increased. Interestingly, the expression of ANP was decreased, and Ang-2 and TGF-β levels were significantly increased in the liver of PHD2ECKO mice. The FW/BW ratio was also significantly increased in the PHD2ECKO mice fed with HFD for 16 weeks. Feeding HFD resulted in a significant increase in hepatic steatosis in the control PHD2f/f mice, but did not further enhance hepatic steatosis in the PHD2ECKO mice. Conclusions: We concluded that the endothelial PHD2 plays a critical role in hepatic steatosis and fibrosis, which may be involved in the regulation of ANP and Ang-2/TGF-β signaling pathway, but not the HIF-2α expression. [ABSTRACT FROM AUTHOR]

We evaluate how the coupled aerosol-chemistry-climate model SOCOL-AERv1.0 represents the influence of the 1991 eruption of Mt. Pinatubo on stratospheric aerosol properties and atmospheric state. The aerosol module is coupled to the radiative and chemical modules and includes comprehensive sulfur chemistry and microphysics, in which the particle size distribution is represented by 40 size bins with radii spanning from 0.39 nm to 3.2 µm. SOCOL-AER simulations are compared with satellite and in situ measurements of aerosol parameters, temperature reanalyses, and ozone observations. In addition to the reference model configuration, we performed series of sensitivity experiments looking at different processes affecting the aerosol layer. An accurate sedimentation scheme is found to be essential to prevent particles from diffusing too rapidly to high and low altitudes. The aerosol radiative feedback and the use of a nudged quasibiennial oscillation help to keep aerosol in the tropics and significantly affect the evolution of the stratospheric aerosol burden, which improves the agreement with observed aerosol mass distributions. The inclusion of van der Waals forces in the particle coagulation scheme suggests improvements in particle effective radius, although other parameters (such as aerosol longevity) deteriorate. Modification of the Pinatubo sulfur emission rate also improves some aerosol parameters, while it worsens others compared to observations. Observations themselves are highly uncertain and render it difficult to conclusively judge the necessity of further model reconfiguration. The model revealed problems in reproducing aerosol sizes above 25 km and also in capturing certain features of the ozone response. Besides this, our results show that SOCOL-AER is capable of predicting the most important global-scale atmospheric effects following volcanic eruptions, which is also a prerequisite for an improved understanding of solar geoengineering effects from sulfur injections to the stratosphere. [ABSTRACT FROM AUTHOR]