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Pei-An Liao,1 Sheng-Wei Pan,2,3 Chun-Yu Chen,4,5 Chung-Yeh Deng,1,4 Yaa-Hui Dong1,4,5 1Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 2Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 3Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Yaa-Hui Dong, Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, 155, Sec 2, Linong Street, Taipei, 112, Taiwan, Tel +886-2-28267986, Fax +886-2-28237929, Email yaahuidong@gmail.comBackground: The clinical guideline recommends use of long-acting β 2 agonists/long-acting muscarinic antagonists (LABA/LAMA) or long-acting β 2 agonists/inhaled corticosteroids (LABA/ICS) combination therapies for patients with severe chronic obstructive pulmonary disease (COPD). The fixed-dose combination (FDC) inhalers of LABA/LAMA and LABA/ICS were reimbursed in Taiwan in 2015 and in 2002, respectively. This study aimed to examine prescription patterns of new use of either FDC therapy in real-world practice.Methods: We identified COPD patients who initiated LABA/LAMA FDC or LABA/ICS FDC between 2015 and 2018 from a population-based Taiwanese database with 2 million, randomly sampled beneficiaries enrolled in a single-payer health insurance system. We compared number of LABA/LAMA FDC and LABA/ICS FDC initiators in each calendar year, from different hospital accreditation levels, and cared for by different physician specialties. We also compared baseline patient characteristics between LABA/LAMA FDC and LABA/ICS FDC initiators.Results: A total of 12,455 COPD patients who initiated LABA/LAMA FDC (n=4019) or LABA/ICS FDC (n=8436) were included. Number of LABA/LAMA FDC initiators increased apparently (n=336 in 2015 versus n=1436 in 2018), but number of LABA/ICS FDC initiators decreased obviously (n=2416 in 2015 versus n=1793 in 2018) over time. The preference of use of LABA/LAMA FDC varied across clinical environments. The proportions of LABA/LAMA FDC initiators were more than 30% in the setting of non-primary care clinics (eg, medical centers) and in the services of chest physicians; but were only less than 10% in primary care clinics and non-chest physicians’ services (eg, family medicine physicians). LABA/LAMA FDC initiators appeared to be older, male, to have more comorbidities, and to utilize resources more frequently compared to LABA/ICS FDC initiators.Conclusion: This real-world study found evident temporal trends, variations in healthcare provider, and differences in patient characteristics among COPD patients who initiated LABA/LAMA FDC or LABA/ICS FDC.Keywords: chronic obstructive pulmonary disease, new users, long-acting β 2 agonists/long-acting muscarinic antagonists fixed-dose combination, LABA/LAMA FDC, long-acting β 2 agonists/inhaled corticosteroids fixed-dose combination, LABA/ICS FDC, temporal trends, healthcare provider characteristics, patient characteristics

Hui Qi1, Zhen Zhong1, Han-Xin Zhou1, Chun-Yan Deng1, Hai Zhu2, Jin-Feng Li2, Xi-Li Wang2, Fu-Rong Li1,31Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, 2Shenzhen Bioeasy Biotechnologies Co, Ltd, 3Shenzhen Institute of Gerontology, Shenzhen, People's Republic of ChinaBackground: Escherichia coli O157:H7 (E. coli O157:H7) is an important pathogenic bacterium that threatens human health. A rapid, simple, highly sensitive, and specific method for the detection of E. coli O157:H7 is necessary.Methods: In the present study, immunomagnetic nanoparticles (IMPs) were prepared with nanopure iron as the core, coated with E. coli O157:H7 polyclonal antibodies. These IMPs were used in combination with immunochromatographic assay (ICA) and used to establish highly sensitive and rapid kits (IMPs+ICA) to detect E. coli O157:H7. The kits were then used to detect E. coli O157:H7 in 150 food samples and were compared with conventional ICA to evaluate their efficacy.Results: The average diameter of IMPs was 56 nm and the amount of adsorbed antibodies was 106.0 µg/mg. The sensitivity of ICA and IMPs+ICA was 105 colony-forming units/mL and 103 CFUs/mL, respectively, for purified E. coli O157:H7 solution. The sensitivity of IMPs+ICA was increased by two orders, and its specificity was similar to ICA.Conclusion: The kits have the potential to offer important social and economic benefits in the screening, monitoring, and control of food safety.Keywords: colloidal gold, immunomagnetic nanoparticles, Escherichia coli O157:H7, immunochromatographic assay

Qing Li1, Hui Qi1, Han-Xin Zhou1, Chun-Yan Deng1, Hai Zhu3, Jin-Feng Li3, Xi-Li Wang3, Fu-Rong Li1,21Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, People's Republic of China; 2Shenzhen Institute of Gerontology, Shenzhen, People's Republic of China; 3Shenzhen Bioeasy Biotechnologies Co Ltd, Shenzhen, People's Republic of ChinaAbstract: Fe3O4 particles are currently used as the core of immunomagnetic microspheres in the immunomagnetic enrichment assay of circulating tumor cells (CTCs). It is difficult to further improve the sensitivity of CTC detection or to improve tumor cell-type identification and characterization. In the present study, we prepared immunomagnetic nanoparticles with nanopure iron as the core, coated with anti-cytokeratin 7/8 (CK7/8) monoclonal antibody. These immunomagnetic nanoparticles (IMPs) were used in conjunction with immunocytochemistry (ICC) to establish a refined immunomagnetic nanoparticle enrichment assay for CTC detection in non-small cell lung cancer (NSCLC). The assay was compared with nested reverse transcription polymerase chain reaction (RT-PCR) to detect CK19 mRNA and lung specific X protein (LUNX) mRNA. Human lung adenocarcinoma cell line A549 was used for sensitivity and specificity evaluation. Peripheral blood samples were collected from each group for CTC detection. The average diameter of the immunomagnetic nanoparticles was 51 nm, and the amount of adsorbed antibodies was 111.2 µg/mg. We could detect down to one tumor cell in 5 × 107 peripheral blood mononuclear cells. The sensitivity was consistent with that of nested RT-PCR; however, the false positive rate was significantly reduced. The modified assay combined with ICC did not differ from nested RT-PCR in sensitivity, but it had significantly increased specificity. This approach could, therefore, contribute to identification of micrometastases, re-defining clinical staging, and guiding individual postoperative treatments. The technique shows considerable potential clinical value and further clinical trials are warranted.Keywords: NSCLC, circulating tumor cells, nested RT-PCR, immunomagnetic nanoparticles, immunocytochemistry

The contractile function of vascular smooth muscle cells (VSMCs) typically undergoes significant changes with advancing age, leading to severe vascular aging-related diseases. The precise role and mechanism of stromal interaction molecule-1 (STIM1) in age-mediated Ca 2+ signaling and vasocontraction remain unclear. The connection between STIM1 and age-related vascular dysfunction was investigated using a multi-myograph system, immunohistochemical analysis, protein blotting, and SA-β-gal staining. Results showed that vasoconstrictor responses in the thoracic aorta, intrarenal artery, and coronary artery decreased with age. STIM1 knockdown in the intrarenal and coronary arteries reduced vascular tone in young mice, while no change was observed in the thoracic aorta. A significant reduction in vascular tone occurred in the STIM1 knockout group with nifedipine. In the thoracic aorta, vasoconstriction significantly decreased with age following the use of nifedipine and thapsigargin and almost disappeared after STIM1 knockdown. The proportion of senescent VSMCs increased significantly in aged mice and further increased in sm-STIM1 KO aged mice. Moreover, the expression of senescence markers p21, p16, and IL-6 significantly increased with age, with p21 expression further increased in the STIM1 knockdown aged group, but not p16 or IL-6. These findings indicate that different arteries exhibit distinct organ-specific features and that STIM1 downregulation may contribute to age-related vasoconstrictive dysfunction through activation of the p21 pathway., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value-added epoxides. However, due to the competitive reaction of water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br - /HOBr-mediated method is developed to achieve a near-quantitative selectivity and ≈100% FE of styrene oxide on α-Fe 2 O 3 , in which low concentration of Br - as mediator and locally generated acidic micro-environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH-dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction., Methods: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction., Results: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively., Conclusion: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction., (© 2024. The Author(s).)

It aimed to explore the correlation of Glu504Lys locus mutation of aldehyde dehydrogenase-2 (ALDH2) with coronary heart disease (CHD) based on gold magnetic nanoparticles (GMNPs) chromatography and amplification refractory mutation system-PCR (ARMS-PCR). 120 CHD patients admitted to the cardiovascular Department of Wenling First People's Hospital affiliated to Wenzhou Medical University from December 2020 to December 2021 were selected as Case group and 80 non-CHD patients admitted during the same period were selected as Ctrl group. The venous blood and indexes of Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Fasting Blood Glucose (FBS) were collected. The ARMS-PCR GMNPs chromatography based on ARMS-PCR and immunochromatography assay was adopted to detect gene polymorphism of ALDH2. Correlation between ALDH2 gene polymorphism and risk factors of CHD was analyzed via logistic regression. In contrast to Ctrl group, the genotypes of GG, GA, and AA in Case group were evidently different (P < 0.05), and the frequency of A allelic gene was obviously increased (P < 0.05). Under the dominant model, frequency of GA + AA genotype in Case group was remarkably higher in contrast to Ctrl group (P < 0.05). Under the recessive model, there was no obvious difference in genotype frequency between two groups. In contrast to Ctrl group, TC, LDL-C, and FBS in Case group were notably increased (P < 0.05), while HDL-C was notably decreased (P < 0.05). The distribution frequency of abnormal LDL-C, HDL-C, and FBS in Case group was notably higher in contrast to Ctrl group (P < 0.05). LDL-C and FBS had no obvious effect on the genotypes and frequency distribution of alleles in CHD patients. However, the frequency distribution of genotypes of GA and AA and A allelic gene in patients with abnormal HDL-C was notably lower in contrast to those with normal HDL-C (P < 0.05). Logistic regression analysis showed that abnormal HDC-C with A allelic gene were independent risk factors for CHD (P = 0.001, OR = 1.934). The gene polymorphism of Glu504Lys locus of ALDH2 was closely related to the pathogenesis of CHD, A allelic gene may be a susceptibility gene for CHD, and patients with abnormal HDC-C and carried A allelic gene had relatively higher incidence of CHD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the process of synaptic formation, neurons must not only adhere to specific principles when selecting synaptic partners but also possess mechanisms to avoid undesirable connections. Yet, the strategies employed to prevent unwarranted associations have remained largely unknown. In our study, we have identified the pivotal role of combinatorial clustered protocadherin gamma (γ-PCDH) expression in orchestrating synaptic connectivity in the mouse neocortex. Through 5' end single-cell sequencing, we unveiled the intricate combinatorial expression patterns of γ-PCDH variable isoforms within neocortical neurons. Furthermore, our whole-cell patch-clamp recordings demonstrated that as the similarity in this combinatorial pattern among neurons increased, their synaptic connectivity decreased. Our findings elucidate a sophisticated molecular mechanism governing the construction of neural networks in the mouse neocortex., Competing Interests: YZ, CD, LF, YW, HZ, HX No competing interests declared, (© 2023, Zhu et al.)

Aims and Objectives: To assess the prognostic accuracy of the surprise question (SQ) when used by nurses working in hospital wards to determine 1-year mortality in acutely hospitalised older patients., Background: The predictive accuracy of the SQ, when used by general nurses caring for older hospitalised patients, has not been comprehensively studied., Design: A prospective cohort study., Methods: This cohort study recruited consecutive 10,139 older patients (aged ≥65 years) who were admitted to Taipei City Hospital and were evaluated for the needs of palliative care in 2015. All patients were followed up for 12 months or until their death. The c-statistic value was calculated to indicate the predictive accuracy of the SQ and Palliative Care Screening Tool (PCST)., Results: Of all participants, 18.8% and 18.6% had a SQ response of 'no' and a PCST score ≥4, respectively. After controlling for other covariates, an SQ response of 'no' (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.83-2.31) and a PCST score ≥4 (AHR = 1.50; 95% CI: 1.29-1.75) were found to be the independent predictors for patients' 12-month mortality. The C-statistic values of the SQ and the PCST at recognising patients in their last year of life were .663 and .670, respectively. Moreover, there was moderate concordance (k = .44) between the SQ and the PCST in predicting 12-month mortality., Conclusions: SQ response of 'no' and a PCST score ≥4 were independent predictors of 12-month mortality in older patients., Relevance to Clinical Practice: The SQ, when used by nurses working in hospital wards, is effective in identifying older patients nearing the end of life, as well as in providing advance care planning for patients., Patient or Public Contribution: Patients' palliative care needs at admission were assessed by general nurses using the SQ and PCST., (© 2024 John Wiley & Sons Ltd.)

Background: Erectile dysfunction is now a common disorder of sexual function, and its relationship to dietary calcium, phosphorus, and potassium has not been well studied. We set out to determine if dietary intakes of calcium, phosphorus, and potassium are related to erectile dysfunction in U.S. men., Methods: For this cross-sectional investigation, we used data from NHANES 2001-2004. To investigate the connection of dietary calcium, phosphorus, and potassium intake with erectile dysfunction, we employed multivariate logistic regression, smoothed curve fitting, and subgroup analysis., Results: This cross-sectional study comprised 3,556 eligible male subjects in total, with a weighted mean age of 49.93±18.13 years. After controlling for race and age, the greatest tertile of calcium consumption was found to have a 34% lower risk of erectile dysfunction than the lowest tertile (OR = 0.66; 95% CI = 0.52-0.84; p = 0.0006). The risk of erectile dysfunction was found to be reduced by 33% (OR = 0.67; 95% CI = 0.52-0.87; p = 0.0024) for the highest tertile of phosphorus intake compared to the lowest tertile of phosphorus intake and by 35% (OR = 0.65; 95% CI = 0.50-0.83; p = 0.0006) for the highest tertile of potassium intake compared to the lowest tertile of potassium intake in the fully adjusted model., Conclusion: Erectile dysfunction and dietary consumption of calcium, phosphorus, and potassium are inversely associated with the U.S. population. To confirm the accuracy of our findings, additional prospective studies are necessary. Furthermore, it is imperative to do further fundamental research at the molecular level to gain a deeper understanding of the underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pyroptosis plays a crucial role in sepsis, and the abnormal handling of myocyte calcium (Ca 2+ ) has been associated with cardiomyocyte pyroptosis. Specifically, the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is a Ca 2+ release channel in the endoplasmic reticulum (ER). However, the specific role of IP3R2 in sepsis-induced cardiomyopathy (SIC) has not yet been determined. Thus, this study aimed to investigate the underlying mechanism by which IP3R2 channel-mediated Ca 2+ signaling contributes to lipopolysaccharide (LPS)-induced cardiac pyroptosis. The SIC model was established in rats by intraperitoneal injection of LPS (10 mg/kg). Cardiac dysfunction was assessed using echocardiography, and the protein expression of relevant signaling pathways was analyzed using ELISA, RT-qPCR, and western blot. Small interfering RNAs (siRNA) and an inhibitor were used to explore the role of IP3R2 in neonatal rat cardiomyocytes (NRCMs) stimulated by LPS in vitro. LPS-induced NLRP3 overexpression and GSDMD-mediated pyroptosis in the rats' heart. Treatment with the NLRP3 inhibitor MCC950 alleviated LPS-induced cardiomyocyte pyroptosis. Furthermore, LPS increased ATP-induced intracellular Ca 2+ release and IP3R2 expression in NRCMs. Inhibiting IP3R activity with xestospongin C (XeC) or knocking down IP3R2 reversed LPS-induced intracellular Ca 2+ release. Additionally, inhibiting IP3R2 reversed LPS-induced pyroptosis by suppressing the NLRP3/Caspase-1/GSDMD pathway. We also found that ER stress and IP3R2-mediated Ca 2+ release mutually regulated each other, contributing to cardiomyocyte pyroptosis. IP3R2 promotes NLRP3-mediated pyroptosis by regulating ER Ca 2+ release, and the mutual regulation of IP3R2 and ER stress further promotes LPS-induced pyroptosis in cardiomyocytes., (© 2024. The Author(s).)

A phosphorescence enhancement of pyridinium macrocycle/monomer phosphors is realized with up to 14.7-fold prolonging of the phosphorescence lifetimes and visible afterglow by doping into a poly(vinylalcohol) (PVA) matrix. The abundant hydrogen-bonding interactions and electrostatic interactions between the phosphors and the PVA suppressed the nonradiative decay processes, slowed down the radiative decay and nonradiative decay of triplet states, and therefore promoted the long-lived RTP.

Microdissection testicular sperm extraction (micro-TESE) is widely used to treat nonobstructive azoospermia. However, a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE. This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021. The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval. The prediction model was constructed using acquired regression coefficients, and its predictive performance was assessed using the receiver operating characteristic curve. In all, 67 patients (sperm retrieval rate: 33.5%) underwent successful micro-TESE. Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE. Binary logistic regression analysis yielded the following six predictors: anti-Müllerian hormone (odds ratio [OR] = 0.902, 95% confidence interval [CI]: 0.821-0.990), inhibin B (OR = 1.012, 95% CI: 1.001-1.024), Klinefelter's syndrome (OR = 0.022, 95% CI: 0.002-0.243), Y chromosome microdeletion (OR = 0.050, 95% CI: 0.005-0.504), cryptorchidism with orchiopexy (OR = 0.085, 95% CI: 0.008-0.929), and idiopathic nonobstructive azoospermia (OR = 0.031, 95% CI: 0.003-0.277). The prediction model had an area under the curve of 0.720 (95% CI: 0.645-0.794), sensitivity of 65.7%, specificity of 72.2%, Youden index of 0.379, and cut-off value of 0.305 overall, indicating good predictive value and accuracy. This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Aim: Sacubitril/valsartan (Sac/Val, LCZ696), the world's first angiotensin receptor-neprilysin inhibitor (ARNi), has been widely used in the treatment of heart failure. However, the use of Sac/Val in the treatment of atrial fibrillation (AF), especially AF with hypertension, has been less reported. We investigated the effect of Sac/Val on atrial remodeling and hypertension-related AF., Methods: The AF induction rate and electrophysiological characteristics of spontaneously hypertensive rats (SHRs) treated with Sac/Val or Val were detected by rapid atrial pacing and electrical mapping/optical mapping. The whole-cell patch-clamp and Western blot were used to observe electrical/structural remodeling of atrial myocytes/tissue of rats and atrium-derived HL-1 cells cultured under 40 mmHg in vitro., Results: Sac/Val was superior to Val in reducing blood pressure, myocardial hypertrophy and susceptibility of AF in SHRs. The shorten action potentials duration (APD), decreased L type calcium channel current (I Ca,L ) and Cav1.2, increased ultrarapid delayed rectified potassium current (I kur ) and Kv1.5 in atrial myocytes/tissue of SHRs could be better improved by Sac/Val, as well as the levels of atrial fibrosis. While the protein expression of angiotensin-converting enzyme-1 (ACE-1), angiotensin, angiotensin II type I AT1 receptor (AT1R) and neprilysin (NEP) were increased, which could be more effective ameliorated by Sac/Val than Val. Furthermore, Val + Sacubitrilat (LBQ657) (an active NEP inhibitor) was also superior to LBQ657 or Val in improving the electrical and structural remodeling of HL-1 cells through inhibiting NEP., Conclusion: Sac/Val can improve atrial structural and electrical remodeling induced by hypertension and reduce the AF susceptibility by inhibiting RAS and NEP. The above effects of Sac/Val were superior to Val alone., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU., Research Question: Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury?, Study Design and Methods: This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission., Results: Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy., Interpretation: VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU., (Published by Elsevier Inc.)

A new oxygenated lanostane-type triterpenoid, 20 S ,24 S -epoxy-lanosta-7,9(11)-dien-3 β ,15 α ,25 R ,26-tetraol ( 1 ), together with three known compounds ( 2 - 4 ) were isolated from the fruiting bodies of Ganoderma weberianum . Extensive NMR spectrometry and HRESIMS analysis, as well as NMR and ECD calculations elucidated the structure of the new compound. 27-nor-3 β -hydroxylanosta-7,9(11),23 E -trien-25-one ( 2 ) showed superior α -glucosidase inhibitory activity with IC 50 value of 122.1 μM to that of positive control acarbose (304.6 μM).

This study aimed to investigate the association between bedtime and cardiac autonomic function in older adults. This cross-sectional study included community-dwelling older adults aged ≥ 65 years. Self-reported bedtime was categorized as early (< 21:30), intermediate (21:30-22:30), and late (> 22:30). Cardiac autonomic function was evaluated by HRV. The lowest tertiles for each HRV parameter were defined as unhealthy indicators. A total of 3,729 individuals participated, with mean age of 76.3 ± 6.6 years. After controlling for various covariates, late bedtime was associated with a lower risk for unhealthy total power [Odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.59-0.93] and low frequency power (OR = 0.69, 95% CI = 0.55-0.87) than intermediate bedtime. In contrast, early bedtime was correlated with a higher risk of poor total power (OR = 1.23, 95% CI: 1.05-1.45) and high frequency power (OR = 1.18, 95% CI = 1.00-1.39). When further specifying sleep duration and physical disability into the regression models, the inverse association between late bedtime and unhealthy HRV remained; however, the association between early bedtime and HRV disappeared. Accordingly, we concluded that in terms of cardiac autonomic function, early bedtime in older adults is not necessarily beneficial for their health outcomes, whereas late bedtime may not be detrimental. Abbreviations: ADL: activity of daily living; BMI: body mass index; CI: confidence interval; GARS: the Groningen Activity Restriction Scale; HADS: The Hospital Anxiety and Depression Scale; HF: high frequency power; HRV: heart rate variability; LF: low frequency power; LF/HF: low frequency to high frequency ratio; OR: odds ratios; TP: total power.

Introduction: Objective: to conduct a systematic review of the observational studies analyzing the association between ultra-processed food (UPF) intake and the risk of depression. Design: the search adhered to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); a search for observational studies published until June 2020 was performed in PubMed, Embase, Cochrane Library, and Web of Science databases, followed by additional manual searches. Eight reviewers, working independently in teams of two, screened studies for eligibility, extracted data, and assessed risk of bias. We resolved disagreements through discussion or, if necessary, through adjudication by a third (LH). And the study assessed cross-sectional studies using the Agency for Healthcare Research and Quality (AHRQ) methodological checklist and cohort and case-control studies using the Newcastle-Ottawa Scale (NOS) for quality. We used a tabular format to summarize the articles. Results: twenty-eight studies evaluating UPF intake and risk of depression were finally selected, 21 of which had a cross-sectional design, 6 studies had a cohort design, and 1 had a case-control design. Of these, 4 cohort studies and 17 cross-sectional studies found that consumption of UPF were positively associated with depression or depressive symptoms. Conclusions: our review demonstrated that most studies included in the systematic review showed that UPF consumption is associated with the risk of depression. Future studies should consider the use of validated food intake assessments and standardized depression assessment methods to promote comparability between studies.

Four new species of Russula subsection Sardoninae from northern and southwestern China under coniferous and deciduous trees are proposed as R. begonia , R. photinia , R. rhodochroa , and R. rufa . Illustrations and descriptions of R. gracillima , R. leucomarginata , R. roseola , and the above four new species are provided based on evidence of morphological characters and phylogenetic analyses of the internal transcribed spacer (ITS), as well as the multi-locus of mtSSU, nLSU, rpb1 , rpb2 and tef1 -α. The relationships between these new species and allied taxa are discussed.

Diabetic coronary artery injury is closely associated with Ca 2+ dysregulation, although the underlying mechanism remains unclear. This study explored the role and mechanism of Ca 2+ handling in coronary artery dysfunction in type 2 diabetic rats. Zucker diabetic fatty (ZDF) rats were used as the type 2 diabetes mellitus model. The contractility of coronary artery rings induced by KCl, CaCl 2 , 5-HT and U46619 was significantly lower in ZDF rats than in Zucker lean rats. Vasoconstriction induced by 5-HT and U46619 was greatly inhibited by nifedipine. However, in the presence of 1 μM nifedipine or in the Ca 2+ -free KH solution containing 1 μM nifedipine, there was no difference in the vasoconstriction between Zucker lean and ZDF rats. Store-operated calcium channels (SOCs) were not involved in coronary vasoconstriction. The downregulation of contractile proteins and the upregulation of synthesized proteins were in coronary artery smooth muscle cells (CASMCs) from ZDF rats. Metformin reversed the reduction of vasoconstriction in ZDF rats. Taken together, L-type calcium channel is important for regulating the excitation-contraction coupling of VSMCs in coronary arteries, and dysregulation of this channel contributes to the decreased contractility of coronary arteries in T2DM., (© 2022 John Wiley & Sons Australia, Ltd.)

Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome, the azoospermia factor region (AZF). AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility. Assisted reproductive technology (ART) has been used to overcome natural fertilization barriers, allowing infertile couples to have children. However, these techniques increase the risk of vertical transmission of genetic defects. Despite widespread awareness of AZF microdeletions, the occurrence of de novo deletions and overexpression, as well as the expansion of AZF microdeletion vertical transmission, remains unknown. This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes. Moreover, vertical transmission cases of AZF microdeletions, the impact of vertical inheritance on male fertility, and the prospective direction of research in this field are also outlined., Competing Interests: None

Atrial fibrosis induced by aging is one of the main causes of atrial fibrillation (AF), but the potential molecular mechanism is not clear. Acetyltransferase p300 participates in the cellular senescence and fibrosis, which might be involved in the age-related atrial fibrosis. Four microarray datasets generated from atrial tissue of AF patients and sinus rhythm (SR) controls were analyzed to find the possible relationship of p300 (EP300) with senescence and fibrosis. And then, biochemical assays and in vivo electrophysiological examination were performed on older AF patients, aging mice, and senescent atrial fibroblasts. The results showed that (1) the left atrial tissues of older AF patients, aging mouse, and senescence human atrial fibroblasts had more severe atrial fibrosis and higher protein expression levels of p300, p53/acetylated p53 (ac-p53)/p21, Smad3/p-Smads, and fibrosis-related factors. (2) p300 inhibitor curcumin and p300 knockdown treated aging mouse and senescence human atrial fibroblasts reduced the senescence ratio of atrial fibroblasts, ameliorated the atrial fibrosis, and decreased the AF inducibility. In contrast, over-expression of p300 can lead to the senescence of atrial fibroblasts and atrial fibrosis. (3) p53 knockdown decreased the expression of aging and fibrosis-related proteins. (4) Co-immunoprecipitation and immunofluorescence showed that p53 forms a complex with smad3 and directly regulates the expression of smad3 in atrial fibroblasts. Our findings suggest that the mechanism of atrial fibrosis induced by aging is, at least, partially dependent on the regulation of p300, which provides new sights into the AF treatment, especially for the elderly., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Calcium (Ca 2+ ) dysregulation contributes to various vascular diseases, but the role and underlying mechanism of stromal interaction molecule-1 (STIM1) in Ca 2+ signaling and vasocontraction remain elusive. By using smooth muscle-specific STIM1 knockout (sm-STIM1 KO) mice and a multi myograph system, we investigated the differential role of STIM1 in Ca 2+ handling between coronary and intrarenal arterial smooth muscles. After STIM1 deletion, contractile responses to 5-HT were obviously reduced in coronary and intrarenal arteries in the sm-STIM1 KO mice, but not altered in U46619. Phenylephrine barely induced the contraction of coronary arteries, we only detected an effect on the contraction of intrarenal arteries, which was also reduced in the sm-STIM1 KO mice. Then, L-type Ca 2+ channel (Cav1.2)- mediated vasocontractions were significantly enhanced in coronary and intrarenal arteries in sm-STIM1 KO mice, similar to treatment with the Cav1.2 agonist Bay K8644 in coronary arteries. However, non-Cav1.2-mediated vasocontractions were remarkably reduced. IP 3 receptor- and ryanodine receptor-mediated vasocontractions were both obviously decreased in coronary and intrarenal arteries in sm-STIM1 KO mice. Moreover, STIM1-mediated store operated Ca 2+ entry (SOCE) only participated in the contraction of intrarenal arteries. In conclusion, we demonstrate that STIM1 participates in Cav1.2, sarcoplasmic reticulum (SR) Ca 2+ release and store-operated Ca 2+ (SOC) channels-mediated vasocontraction, which exhibits obvious organ-specificity between coronary and intrarenal arteries., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest, (Copyright © 2022 Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) is a common chronic metabolic disease caused by significant accumulation of advanced glycation end products (AGEs). Atrial fibrillation (AF) is a common cardiovascular complication of DM. Here, we aim to clarify the role and mechanism of atrial myocyte senescence in the susceptibility of AF in diabetes. Rapid transesophageal atrial pacing was used to monitor the susceptibility of mice to AF. Whole-cell patch-clamp was employed to record the action potential (AP) and ion channels in single HL-1 cell and mouse atrial myocytes. More importantly, anti-RAGE antibody and RAGE-siRNA AAV9 were used to investigate the relationship among diabetes, aging, and AF. The results showed that elevated levels of p16 and retinoblastoma (Rb) protein in the atrium were associated with increased susceptibility to AF in diabetic mice. Mechanistically, AGEs increased p16/Rb protein expression and the number of SA-β-gal-positive cells, prolonged the action potential duration (APD), reduced protein levels of Cav1.2, Kv1.5, and current density of I Ca,L , I Kur in HL-1 cells. Anti-RAGE antibody or RAGE-siRNA AAV9 reversed these effects in vitro and in vivo, respectively. Furthermore, downregulating p16 or Rb by siRNA prevented AGEs-mediated reduction of Cav1.2 and Kv1.5 proteins expression. In conclusion, AGEs accelerated atrial electrical remodeling and cellular senescence, contributing to increased AF susceptibility by activating the p16/Rb pathway. Inhibition of RAGE or the p16/Rb pathway may be a potential therapeutic target for AF in diabetes., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Long snake moxibustion, a kind of indirect moxibustion therapy for stimulating the midline part of the back of the patient's body after playing a layer of ginger or garlic mud, is frequently used to treat spine disorders and deficiency-cold type syndromes. In the present paper, we introduced our newly made moxibustion box for applying long snake moxibustion which is safe and easy to operate and can be freely moved at any time in the treatment of vertebral diseases, and conveniently makes the ignited-moxa close to the locus. This newly-designed moxibustion box is made of two lines of paralleled flexible connection side plates hinged ends to ends and two U-like connection plates at the opposite two ends to construct a rectangular frame device. The hinged design makes the long snake moxibustion box conform to the physiological curvature of human body and its length can be adjusted according to the height of patients. When used in clinical practice, it can enhance the patients' safety and reduce the operator's working intensity, and may be helpful to the popularization and development of long snake moxibustion therapy.

Objective: To investigate the change trends of sperm quality with seasonal variations among the volunteers of sperm donors in Beijing area, as well as the relationship between two parameters., Methods: Semen data from the volunteers of sperm donors in Human Sperm Bank of Peking University Third Hospital were collected using a retrospective study method. The subjects were divided into 4 seasonal groups based on the lunar solar terms and the time of sperm donation. The data were assessed to find whether there were differences in semen parameters among different seasonal groups, and to analyze the change trends and the influence of seasonal factors on semen parameters., Results: A total of 21 174 semen parameter data were analyzed. Firstly, to analyze all data as a whole, in spring, summer, autumn and winter groups, sperm concentration was (106.04±59.67)×10 6 /mL, (97.61±47.41)×10 6 /mL, (100.18±47.17)×10 6 /mL, (100.59±38.68)×10 6 /mL, respectively, and the spring group was significantly higher than the other 3 seasonal groups ( P < 0.001); proportion of progressive motility sperm (PR) was 56.49%±12.76%, 58.02%±13.65%, 58.05%±12.36%, and 57.66%±12.61%, respectively, spring group was lower than the other three seasonal groups, and summer group was better among the latter ( P < 0.001). There was no difference in normal rate of sperm morphology among the four seasonal groups. The qualified rate of sperm donors in the winter group was higher than that in the other three seasons groups ( P < 0.01), while the qualified rate in the summer group was lower than that in the other three seasons groups. In addition, the semen parameters of the volunteers during the screening period and the official sperm donation period were analyzed respectively, which revealed that sperm concentration of spring group was higher than that of summer and winter groups, and PR was lower than that of summer and autumn groups. On account of the semen parameters of official sperm donation period, multiple linear regression analysis found that season was the main factor affecting sperm concentration, the average sperm concentration in spring group was about 6×10 6 /mL higher than in winter group, but PR was 2.9% lower in spring group compared with autumn group (all P < 0.05)., Conclusion: Season was the influencing factor of semen quality of sperm donors in Beijing area. We recommend spring and winter may be the preferred seasons for sperm donation.

Eleven undescribed limonoids, cipacinerasins A-K, involving of four diverse carbon skeletal types, along with fifteen known analogues, were isolated from the branches and leaves of Cipadessa baccifera. Within them, cipacinerasins A and B feature a rearranged tetrahydropyranyl ring B formed between C-8 and C-30, are unusual miscellaneous-type limonoids. Cipacinerasins E and F are rare trijugin-type limonoids, of which the D-ring δ-lactone is cleaved. Their structures were elucidated on the basis of extensive spectroscopic data (HRESIMS, NMR, UV and IR), electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. All compounds were evaluated in vitro cytotoxicity against five human tumor cell lines (K562, HeLa, PC3, LN-Cap and Hell), and cipacinerasin E showed moderate antitumor activity with IC 50 values ranging from 8.0 to 24.8 μM., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Valvular heart disease (VHD) is a major precipitating factor of atrial fibrillation (AF) that contributes to decreased cardiac function, heart failure, and stroke. Stroke induced by VHD combined with atrial fibrillation (AF-VHD) is a much more serious condition in comparison to VHD alone. The aim of this study was to explore the molecular mechanism governing VHD progression and to provide candidate treatment targets for AF-VHD., Methods: Four public mRNA microarray datasets were downloaded and differentially expressed genes (DEGs) screening was performed. Weighted gene correlation network analysis was carried out to detect key modules and explore their relationships and disease status. Candidate hub signature genes were then screened within the key module using machine learning methods. The receiver operating characteristic curve and nomogram model analysis were used to determine the potential clinical significance of the hub genes. Subsequently, target gene protein levels in independent human atrial tissue samples were detected using western blotting. Specific expression analysis of the hub genes in the tissue and cell samples was performed using single-cell sequencing analysis in the Human Protein Atlas tool., Results: A total of 819 common DEGs in combined datasets were screened. Fourteen modules were identified using the cut tree dynamic function. The cyan and purple modules were considered the most clinically significant for AF-VHD. Then, 25 hub genes in the cyan and purple modules were selected for further analysis. The pathways related to dilated cardiomyopathy, hypertrophic cardiomyopathy, and heart contraction were concentrated in the purple and cyan modules of the AF-VHD. Genes of importance ( CSRP3 , MCOLN3 , SLC25A5 , and FIBP ) were then identified based on machine learning. Of these, CSRP3 had a potential clinical significance and was specifically expressed in the heart tissue., Conclusions: The identified genes may play critical roles in the pathophysiological process of AF-VHD, providing new insights into VHD development to AF and helping to determine potential biomarkers and therapeutic targets for treating AF-VHD., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Purpose: Symptoms are vital outcomes for cancer clinical trials, observational research, and population-level surveillance. Patient-reported outcomes (PROs) are valuable for monitoring symptoms, yet there are many challenges to collecting PROs at scale. We sought to develop, test, and externally validate a deep learning model to extract symptoms from unstructured clinical notes in the electronic health record., Methods: We randomly selected 1,225 outpatient progress notes from among patients treated at the Dana-Farber Cancer Institute between January 2016 and December 2019 and used 1,125 notes as our training/validation data set and 100 notes as our test data set. We evaluated the performance of 10 deep learning models for detecting 80 symptoms included in the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) framework. Model performance as compared with manual chart abstraction was assessed using standard metrics, and the highest performer was externally validated on a sample of 100 physician notes from a different clinical context., Results: In our training and test data sets, 75 of the 80 candidate symptoms were identified. The ELECTRA-small model had the highest performance for symptom identification at the token level (ie, at the individual symptom level), with an F1 of 0.87 and a processing time of 3.95 seconds per note. For the 10 most common symptoms in the test data set, the F1 score ranged from 0.98 for anxious to 0.86 for fatigue. For external validation of the same symptoms, the note-level performance ranged from F1 = 0.97 for diarrhea and dizziness to F1 = 0.73 for swelling., Conclusion: Training a deep learning model to identify a wide range of electronic health record-documented symptoms relevant to cancer care is feasible. This approach could be used at the health system scale to complement to electronic PROs.

Objective: To explore the time-effect relationship of long snake moxibustion in intervening recurrent exopathogenic diseases of patients with yang-deficiency constitution in different moxibustion periods and provide a scientific basis for the selection of long snake moxibustion in preventing and treating recurrent exopathogenic diseases of patients with yang-deficiency constitution., Methods: Ninety patients with yang-deficiency constitution who met the inclusion criteria of recurrent exopathogenic diseases were randomly divided into a 30 min group, a 60 min group, and a 90 min group, with 30 cases in each group. Long snake moxibustion was applied once a week from Dazhui (GV14) to Yaoshu (GV2) for different periods (30, 60, and 90 min), 12 times (12 weeks) in total. The scores of yang-deficiency constitution quality scale and Fatigue Severity Scale (FSS) before treatment, after treatment, and six months after treatment, as well as attack times of exopathogenic diseases within one year before treatment and after treatment in the three groups, were observed and recorded., Results: After treatment and 6 months after treatment, the yang-deficiency quality scale scores and FSS scores of the three groups were lower than those before treatment ( P <0.01), which decreased in the sequence of the 30 min group, the 90 min group, and the 60 min group ( P <0.05). Within one year after treatment, the attack times of exopathogenic diseases in the three groups was lower than that within one year before treatment ( P <0.01), which decreased in the sequence of the 30 min group, the 90 min group, and the 60 min group ( P <0.05)., Conclusion: The optimal moxibustion time of long snake moxibustion on the recurrent exopathogenic diseases of patients with yang-deficiency constitution is 60 min.

Objective: To investigate the effect of internal external fixator assisted O-arm navigation imaging in the treatment of unstable pelvic fractures., Methods: From May 2019 to November 2019, 15 patients with unstable pelvic fractures were treated by intraoperative O-arm navigation imaging using INFIX technology. There were 6 males and 9 females. The age ranged from 24 to 66 years old. The course of disease ranged from 2 to 14 days. According to Tile classification, there were 1 case of B1 type, 8 cases of B2 type, 3 cases of C1 type, and 3 cases of C2 type. According to Young-Burgess classification, there were 8 cases of LC, 1 case of APC, 4 cases of VS, 2 cases of CM. Preoperative routine pelvic anteroposterior film, entrance position, exit position and pelvic CT three-dimensional reconstruction were performed. Intraoperative O-arm navigation system three-dimensional reconstruction and triplane scanning imaging were used to evaluate the effect of intraoperative reduction. The anterior pelvic ring was fixed with internal external fixator, and the posterior ring was fixed with sacroiliac screw, plate screw or lumbar iliac screw. The operation time, intraoperative bleeding and nail placement were observed and recorded. The quality of fracture reduction was evaluated by Matta standard, and the postoperative function was evaluated by Majeed function score., Results: Wound healing was good in all patients without vascular, nerve and local irritation complications. All the 15 patients were followed up for 10 to 16 months. The fracture reduction was evaluated according to the Matta scoring standard, 9 cases were excellent results, 5 cases were good, and 1 case was medium. The Majeed functional score was 0 to 95 points., Conclusion: The built-in external fixator assisted O-arm navigation imaging system in the treatment of unstable pelvic fractures. The reduction effect is evaluated in advance, the operation time is shortened, and the accuracy of internal fixation is improved. The operation is simple, safe and less bleeding. The operation is in line with the principles of minimally invasive medical treatment and precision medical treatment in orthopedics, which is conducive to the recovery of patients' postoperative function and rapid recovery.

Nine collections of gymnopoid fungi were studied based on morpho-molecular characteristics. The macromorphology was made according to the photograph of fresh basidiomata and field notes, while the micromorphology was examined via an optical microscope. Simultaneously, the phylogenetic analyses were performed by maximum likelihood and Bayesian inference methods based on a combined dataset of nrITS1-nr5.8S-nrITS2-nrLSU sequences. Integrated analysis of these results was therefore, G. efibulatus belonging to sect. Androsacei , G. iodes and G. sinopolyphyllus belonging to sect. Impudicae and G. strigosipes belonging to sect. Levipedes are proposed as new to science. The detailed descriptions, colour photos of basidiomata and line-drawings of microscopic structures are provided. The comparisons with closely related species and a key to known species of Gymnopus s. str. reported with morpho-molecular evidence in China is also given.

The timing of death in patients with coronavirus disease 2019 (COVID-19) varied by their comorbidities and severity of illness. However, few studies have determined predictors of mortality with respect to the timing of death in infectious patients. This cohort study aimed to identify the factors associated with early and late death in hospitalized COVID-19 patients. From 14 May to 31 July 2021, this study consecutively recruited laboratory-confirmed COVID-19 patients admitted to Taipei City Hospital. All patients with COVID-19 were followed up until death or discharge from the hospital or till 13 August 2021. Mortality in such patients was categorized as early death (death within the first two weeks of hospitalization) or late death (mortality later than two weeks after hospitalization), based on the timing of death. Multinomial logistic regression was used to determine the factors associated with early and late death among such patients. Of 831 recruited patients, the overall mean age was 59.3 years, and 12.2% died during hospitalization. Of the 101 deceased, 66 (65.3%) and 35 (34.7%) died early and late, respectively. After adjusting for demographics and comorbidities, independent predictors for early death included age ≥ 65 years (adjusted odds ratio (AOR) = 5.27; 95% confidence interval (CI): 2.88-9.65), heart failure (AOR = 10.32; 95% CI: 2.28-46.65), and end-stage renal disease (AOR = 11.97; 95% CI: 3.53-40.55). This study found that two thirds of COVID-19 deaths occurred within two weeks of hospitalization. It suggests that hospitalized patients with COVID-19 should be treated carefully and monitored closely for the progression of clinical conditions during treatment, particularly in older patients and in those with comorbidities.

Introduction: Hypoxia is a common pathological condition after spinal cord injury. Oestrogen-related receptor alpha (ERRα), as a key regulator of energy metabolism and mitochondrial functions, plays an important role in maintaining cell homeostasis. However, its role in hypoxic spinal microglia has not been fully elaborated. This study investigated the receptor's activity when these cells are hypoxic and used as an in vitro model., Material and Methods: In this study, microglia (BV2) were exposed to cobalt chloride as a hypoxic model, and the inverse agonist of ERRα, XCT790, and pyrido[1,2-α]-pyrimidin-4-one were used to regulate the expression of the receptor to explore the ERRα-related mechanisms involved in hypoxic spinal cord injury (SCI)., Results: ERRα promoted autophagy in BV2 cells and inhibited the activation of the p38 mitogen-activated protein kinase (MAPK) pathway and the expression of anti-inflammatory factors under hypoxic conditions. It also promoted the expression of fibronectin type III domain containing protein 5 (FNDC5)., Conclusion: When a hypoxic SCI occurs, ERRα may maintain the homeostasis of spinal cord nerve cells by regulating autophagy and the p38MAPK/nuclear factor-kappa B cell and FNDC5/brain-derived neurotrophic factor signalling pathways, which are beneficial to the recovery of these cells., Competing Interests: Conflict of Interest Conflict of Interests Statement. The authors declare that there is no conflict of interests regarding the publication of this article., (© 2022 C.Y. Deng et al., published by Sciendo.)

Based on phylogenetic analyses, some newly studied Chinese mushroom specimens were found to represent two distinct species within the genus Gymnopus . Along with G.fusipes (sect. Gymnopus) they form a distinct clade with high support, although their macromorphological characters seem to be closer to members of Gymnopus sect. Levipedes or sect. Vestipedes (Collybiopsis). When examined in detail, their micromorphological characters, especially the type of pileipellis, support them as new members of G. sect. Gymnopus. Therefore, two new species, G.omphalinoides and G.schizophyllus , and the emended circumscription of sect. Gymnopus are proposed in this paper. Detailed morphological descriptions, colour photos, illustrations of the two new species, morphological comparisons with similar taxa and the molecular-phylogenetic analyses of the combined nrITS and nrLSU data are presented. A key to the known species of G. sect. Gymnopus is also presented., (Ji-Peng Li, Vladimír Antonín, Genevieve Gates, Lu Jiang, Tai-Hui Li, Yu Li, Bin Song, Chun-Ying Deng.)

Hypertension is a major cardiovascular risk factor for atrial fibrillation (AF) worldwide. However, the role of mechanical stress caused by hypertension on downregulating the L-type calcium current (I Ca,L ), which is vital for AF occurrence, remains unclear. Therefore, the aim of the present study was to investigate the role of Piezo1, a mechanically activated ion channel, in the decrease of I Ca,L in response to high hydrostatic pressure (HHP, one of the principal mechanical stresses) at 40 mmHg, and to elucidate the underlying pathways. Experiments were conducted using left atrial appendages from patients with AF, spontaneously hypertensive rats (SHRs) treated with valsartan (Val) at 30 mg/kg/day and atrium-derived HL-1 cells exposed to HHP. The protein expression levels of Piezo1, Calmodulin (CaM), and Src increased, while that of the L-type calcium channel a1c subunit protein (Cav1.2) decreased in the left atrial tissue of AF patients and SHRs. SHRs were more vulnerable to AF, with decreased I Ca,L and shortened action potential duration, which were ameliorated by Val treatment. Validation of these results in HL-1 cells in the context of HHP also demonstrated that Piezo1 is required for the decrease of I Ca,L by regulating Ca 2+ transient and activating CaM/Src pathway to increase the expression of paired like homeodomain-2 (Pitx2) in atrial myocytes. Together, these data demonstrate that HHP stimulation increases AF susceptibility through Piezo1 activation, which is required for the decrease of I Ca,L via . the CaM/Src/Pitx2 pathway in atrial myocytes., 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 © 2022 Fang, Li, Li, Luo, Kuang, Luo, Li, Yang, Liu, Deng, Xue, Wu and Rao.)

Hierarchical, ultrathin, and porous NiMoO 4 @CoMoO 4 on Co 3 O 4 hollow bones were successfully designed and synthesized by a hydrothermal route from the Co-precursor, followed by a KOH (potassium hydroxide) activation process. The hydrothermally synthesized Co 3 O 4 nanowires act as the scaffold for anchoring the NiMoO 4 @CoMoO 4 units but also show more compatibility with NiMoO 4 , leading to high conductivity in the heterojunction. The intriguing morphological features endow the hierarchical Co 3 O 4 @NiMoO 4 @CoMoO 4 better electrochemical performance where the capacity of the Co 3 O 4 @NiMoO 4 @CoMoO 4 heterojunction being 272 mA·h·g -1 at 1 A·g -1 can be achieved with a superior retention of 84.5% over 1000 cycles. The enhanced utilization of single/few NiMoO 4 @CoMoO 4 shell layers on the Co 3 O 4 core make it easy to accept extra electrons, enhancing the adsorption of OH - at the shell surface, which contribute to the high capacity. In our work, an asymmetric supercapacitor utilizing the optimized Co 3 O 4 @NiMoO 4 @CoMoO 4 activated carbon (AC) as electrode materials was assembled, namely, Co 3 O 4 @NiMoO 4 @CoMoO 4 //AC device, yielding a maximum high energy density of 53.9 W·h·kg -1 at 1000 W·kg -1 . It can retain 25.92 W·h·kg -1 even at 8100 W·kg -1 , revealing its potential and viability for applications. The good power densities are ascribed to the porous feature from the robust architecture with recreated abundant mesopores on the composite, which assure improved conductivity and enhanced diffusion of OH - and also the electron transport. The work demonstrated here holds great promise for synthesizing other heterojunction materials M 3 O 4 @MMoO 4 @MMoO 4 (M = Fe, Ni, Sn, etc).

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by electrical and/or structural remodelling. In the present study, we hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.2 and connexin 43 (Cx43) and basal I Ca , L were decreased in AF subjects compared to sinus rhythm (SR) controls. In cultured atrium-derived myocytes (HL-1 cells), knocking-down of Cx43 or incubation with 30 mmol/L glycyrrhetinic acid significantly inhibited protein levels of Cav1.2 and Cav3.1 and the current density of I Ca , L and I Ca , T . Incubation with nifedipine or mibefradil decreased the protein level of Cx43 in HL-1 cells. Moreover, Cx43 was colocalized with Cav1.2 and Cav3.1 in atrial myocytes. Therefore, Cx43 might regulate the I Ca , L and I Ca , T through colocalization with calcium channel subunits in atrial myocytes, representing a potential pathogenic mechanism in AF., (© 2021 John Wiley & Sons Australia, Ltd.)