Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways.

Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.IMPORTANCEHyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.

Nickel-Catalyzed Atroposelective C-H Alkylation Enabled by Bimetallic Catalysis with Air-Stable Heteroatom-Substituted Secondary Phosphine Oxide Preligands.

The catalytic asymmetric construction of axially chiral C-N atropisomers remains a formidable challenge due to their low rotational barriers and is largely reliant on toxic, cost-intensive, and precious metal catalysts. In sharp contrast, we herein describe the first nickel-catalyzed atroposelective C-H alkylation for the construction of C-N axially chiral compounds with the aid of a chiral heteroatom-substituted secondary phosphine oxide (HASPO)-ligated Ni-Al bimetallic catalyst. A wide range of alkenes, including terminal and internal alkenes, were well compatible with the reaction, providing a variety of benzimidazole derivatives in high yields and enantioselectivities (up to 97:3 e.r.). The key to success was the identification of novel HASPOs as highly effective chiral preligands. Mechanistic studies revealed the catalyst mode of action, and in-depth data science analysis elucidated the key features of the responsible chiral preligands in controlling the enantioselectivity.

Unveiling facial kinship: The BioKinVis dataset for facial kinship verification and genetic association studies.

Facial image-based kinship verification represents a burgeoning frontier within the realms of computer vision and biomedicine. Recent genome-wide association studies have underscored the heritability of human facial morphology, revealing its predictability based on genetic information. These revelations form a robust foundation for advancing facial image-based kinship verification. Despite strides in computer vision, there remains a discernible gap between the biomedical and computer vision domains. Notably, the absence of family photo datasets established through biological paternity testing methods poses a significant challenge. This study addresses this gap by introducing the biological kinship visualization dataset, encompassing 5773 individuals from 2412 families with biologically confirmed kinship. Our analysis delves into the distribution and influencing factors of facial similarity among parent-child pairs, probing the potential association between forensic short tandem repeat polymorphisms and facial similarity. Additionally, we have developed a machine learning model for facial image-based kinship verification, achieving an accuracy of 0.80 in the dataset. To facilitate further exploration, we have established an online tool and database, accessible at http://120.55.161.230:88/.

Pathogenicity and host cytokines response of EqHV-8 infection in C57BL/6J mice.

Equid herpesvirus type 8 (EqHV-8) is known to cause abortion, respiratory signs, and viral encephalitis in equines. EqHV-8 has been reported to cause serious economic losses in large-scale donkey farms in China. However, little is known about the viral replication and immune reaction in the brains and lungs of EqHV-8-induced C57BL/6J mice. We determined the pathogenicity and immune status in a mice model. The C57BL/6J mice were infected with the EqHV-8 donkey/Shandong/10/2021 strain, and the clinical signs and body weights were evaluated every day. In addition, viremia, virus loads, and the expression of pro-inflammatory cytokines in mice brains and lungs were assessed at 1, 3, 5, and 7 days post infection (dpi). Our results demonstrated that mice in the EqHV-8 infected group displayed body weight loss, dyspnea signs, and viremia. The expression of interleukin (IL)-1ß, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 mRNA was increased in the brains and lungs of EqHV-8-infected mice than that in control group at 5 dpi and 7 dpi, and IL-12a expression was increased at 7 dpi. These data indicated that EqHV-8 elicited a strong cytokines response, caused neurogenic disease and respiratory signs in C57BL/6J mice, thus revealing the pathogenicity of EqHV-8.

Relationship Between Preoperative Nutritional Indicators and Postoperative Complications in Patients with Oesophageal Cancer: A Meta-Analysis.

Nutritional status is an essential factor in the occurrence of complications in patients with esophageal cancer. We sought to assess the relationship between malnutrition and complications using various nutritional assessment indicators. We conducted a comprehensive literature search of medical databases for articles published up to July 2023. The primary outcome indicator is the occurrence of complications, for which we combined 95% confidence intervals (CIs) and odds ratios (ORs) for postoperative complications and analyzed them using a random effects model. The analysis was carried out using STATA15.0 software. A total of 33 study groups from 22 publications with 5,675 subjects were included. Pooled results show that nutritional indicators are strongly correlated with the occurrence of postoperative complications (OR = 1.45, 95% CI: 1.30-1.62). In the subgroup analyses, comprehensive indicators and the skeletal muscle index were significantly associated with complications, whereas laboratory indicators were not associated with complications (comprehensive indicators OR = 2.68, 95% CI: 1.80-4.00; skeletal muscle index OR = 2.93, 95% CI: 1.44-5.99; laboratory indicators OR = 1.05, 95% CI: 0.96-1.16). Patients with normal body mass index and hospitalized patients were more likely to develop complications. Malnutrition is strongly associated with the development of complications. Nutritional indicators and patient characteristics influenced this relationship.

Application of TCM Rehabilitation in Joint Function Recovery After Treatment of Distal Radius Fractures: A Meta-Analysis.

Objective: To evaluate the effect of traditional Chinese medicine (TCM) rehabilitation on the postoperative function of patients with distal radius fractures by Meta-analysis. Methods: PubMed, Embase, CNKI, Wanfang, and other databases were searched for retrospective controlled trials and prospective randomized controlled trials on the effect of traditional Chinese medicine rehabilitation on the function of patients with distal radius fractures after surgery from the establishment of the database to May 2023. Revman version 5.3 software was used to analyze the extracted and screened index data. Results: Eight studies involving 455 patients were included. Meta-analysis results showed Overall analysis showed that there was a significant difference in wrist function between the TCM rehabilitation group and the control group (MD = -12.16, 95%CI:-17.21 to -7.11, P < .00001), low heterogeneity (I2=40%, P = .17), the difference in dorsiflexion function between the TCM rehabilitation group and the control group was statistically significant (MD = -1.16, 95%CI:-2.24 to -0.08, P = .04), with high heterogeneity (I2=79%, P = .003), that there was a significant difference in grip strength between the TCM rehabilitation group and the control group at 6 weeks (MD= 0.48, 95%CI: 0.24 to 0.71, P < .0001) with low heterogeneity (I2=45%, P = .12), there was no significant difference between the TCM rehabilitation group and the control group (OR= -0.00, 95%CI: -0.08 to 0.08, P = .99), and there was no heterogeneity (I2=0%, P = .66). Conclusion: Traditional Chinese medicine rehabilitation treatment of distal radius fractures can increase the range of motion of wrist joints, reduce pain, shorten the rehabilitation time of patients, improve the quality of life, and is conducive to the standardized treatment of patients.

Universal screening and treatment towards the elimination of chronic hepatitis C in China: an economic evaluation.

OBJECTIVES: China has the largest number of hepatitis C virus (HCV) infection in the world, but current levels of diagnosis and treatment are low. The objective of this study was to assess the cost-effectiveness of various universal HCV screening and treatment strategies in China and inform decisions on health policy. STUDY DESIGN: A cost-effectiveness analytical study. METHODS: We developed a Markov model to investigate cost-effectiveness of different HCV screening and treatment strategies in China. We simulated several screening scenarios for Chinese people aged 18-70 years. We estimated incremental cost-effectiveness ratios (ICERs) of different intervention scenarios compared with status quo. RESULTS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups (Scenario S5) was the most cost-effective strategy (ICER: USD $11,667.71/quality-adjusted life-year [QALY] gained), which resulted in great reduction in HCV-related diseases and deaths, with a 67.11% reduction in cases of chronic HCV. Universal HCV screening and treatment implementation remains a cost-effective strategy when delayed until 2025 (ICER: USD $17,093.69/QALY), yet the delayed strategy is less effective in reducing HCV-related deaths. CONCLUSIONS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups is the most cost-effective strategy and has lead to a significant reduction in both HCV morbidity and mortality in China, which would essentially eliminate HCV as a public threat.

Health characteristics and factors associated with transition shock in newly graduated registered nurses: a latent class analysis.

BACKGROUND: Transition shock occurs at a vulnerable time in newly graduated registered nurses' careers and has a clear impact on both newly graduated registered nurses' productivity and patient recovery outcomes. Identifying classification features of transition shock and targeting interventions to support newly graduated registered nurses is imperative. The study aimed to explore potential transition shock subgroups of newly graduated registered nurses and further explore the impact of population characteristics and two indices of health on transition shock. METHODS: A descriptive, cross-sectional design was conducted. An online questionnaire was sent via WeChat to newly graduated registered nurses who started work in 2021 at seven hospitals between August and November 2021, and 331 nurses filled out the questionnaire. Latent class analysis was used to identify the potential class of the transition shock of newly graduated registered nurses, and multinomial logistic regression analyses were used to determine the factors of potential classification. RESULTS: The study identified four classes of transition shock in newly graduated registered nurses, namely, "high transition shock", "physical fatigue-lack of knowledge", "development adaptation" and "low transition shock-worry" groups. Newly graduated registered nurses who urinated less than 4 times per day (OR = 0.051, 95% CI = 0.005-0.502) were likely to be in the "high transition shock" group. Newly graduated registered nurses who did not delay urination (OR = 4.267, 95% CI = 1.162-11.236) were more likely to belong to the "low transition shock-worry" group. Newly graduated registered nurses without sleep disturbance were more likely to be in the "physical fatigue - lack of knowledge" (OR = 3.109, 95% CI = 1.283-7.532), "development adaptation" (OR = 8.183, 95% CI = 2.447-27.066), and "low transition shock-worry" (OR = 8.749, 95% CI = 1.619-47.288) groups than in the 'high transition shock' group. CONCLUSIONS: This study highlights potential patterns of transition shock among newly graduated registered nurses. Two indices of health, namely, delayed urination and sleep disturbance, can predict the subgroups of newly graduated registered nurses with transition shock.

The biosafety incident response competence scale for clinical nursing staff: a development and validation study.

AIMS: This study was designed to develop a biosafety incident response competence scale and evaluate its validity and reliability among clinical nurses. DESIGN: This study employed a sequential approach, comprising four phases: (1) the establishment of a multidimensional conceptual model, (2) the preliminary selection of the items, (3) further exploration and psychometric testing of the items, (4) the application of the scale among clinical nurses. METHODS: The biosafety incident response competence conceptual model was developed through literature review and the Delphi method. A total of 1,712 clinical nurses participated in the preliminary items selection, while 1,027 clinical nurses were involved in the further psychometric testing from July 2023 to August 2023. The item analysis, exploratory factor analysis and confirmatory factor analysis were conducted to evaluate the construct validity. Reliability was measured using Cronbach's alpha, split-half reliability, and test-retest reliability, while validity analysis included content validity, structural validity, convergent validity, and discriminant validity. From September to November 2023, we conducted a survey using the established scale with a total of 4338 valid questionnaires collected. T-test and variance analysis was employed to determine potential variations in biosafety incident response competence based on participants characteristics. RESULTS: The final scale is composed of 4 factors and 29 items, including monitoring and warning abilities, nursing disposal abilities, biosafety knowledge preparedness, and infection protection abilities. The explanatory variance of the 4 factors was 75.100%. The Cronbach's alpha, split-half reliability and test-retest reliability were 0.974, 0.945 and 0.840 respectively. The Scale-level content validity index was 0.866. The Average Variance Extracted of the 4 factors was larger than 0.5, the Construct Reliability was larger than 0.7, and the Heterotrait-Monotrait ratio were less than 0.9. There were significant differences in the scores of response competence among nurses of different ages, working years, titles, positions, departments, marital status and participation in biosafety training (all P < 0.05). CONCLUSIONS: The biosafety incident response competence scale for nurses exhibits satisfactory reliability and validity, making it a valuable tool for assessing clinical nurses' abilities in responding to biosafety incidents.

Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN. METHODS: DN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein-protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes. RESULTS: A total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes. CONCLUSION: We identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.

Bridging Chemical Knowledge and Machine Learning for Performance Prediction of Organic Synthesis.

Recent years have witnessed a boom of machine learning (ML) applications in chemistry, which reveals the potential of data-driven prediction of synthesis performance. Digitalization and ML modelling are the key strategies to fully exploit the unique potential within the synergistic interplay between experimental data and the robust prediction of performance and selectivity. A series of exciting studies have demonstrated the importance of chemical knowledge implementation in ML, which improves the model's capability for making predictions that are challenging and often go beyond the abilities of human beings. This Minireview summarizes the cutting-edge embedding techniques and model designs in synthetic performance prediction, elaborating how chemical knowledge can be incorporated into machine learning until June 2022. By merging organic synthesis tactics and chemical informatics, we hope this Review can provide a guide map and intrigue chemists to revisit the digitalization and computerization of organic chemistry principles.

Synergistic Effects of Lewis Acid-Base Pair Sites─Hf-MOFs with Functional Groups as Distinguished Catalysts for the Cycloaddition of Epoxides with CO2.

The incorporation of Lewis acid-base sites in catalysts has been considered as a significant approach to fabricating bifunctional catalysts with efficient catalytic activity for CO2 fixation. In this paper, a series of Hafnium-based metal-organic frameworks (Hf-MOFs), NU-912(Hf) and NU-912-X(Hf)-X (X = -NH2, -Br, -CN, and -I) derivatives assembled by Lewis acidic Hf6(µ3-O)4(µ3-OH)4(H2O)4(OH)4 (Hf6) clusters and Lewis base-attached organic linkers, are successfully synthesized by a facile ligand functionalization method. These isostructural Hf-MOFs, which exhibit diamond channels of 1.3 nm diameter, great chemical stability, and CO2 adsorption capacity, have been evaluated as catalysts for the CO2 cycloaddition reaction with epoxides. Catalytic experiments reveal that the micropore environments of these MOFs have an outstanding impact on catalytic activity. Remarkably, NU-912(Hf)-I serves as an efficient heterogeneous catalyst for this catalytic reaction under mild conditions due to the high density of Lewis acid Hf6 cluster centers and strong Lewis base functional groups, surpassing most of the reported MOF-based catalysts.

Field Evidence for Asian Outflow and Fast Depletion of Total Gaseous Mercury in the Polluted Coastal Atmosphere.

Atmospheric mercury (Hg) cycling in polluted coastal atmosphere is complicated and not fully understood. Here, we present measurements of total gaseous mercury (TGM) monitored at a coastal mountaintop in Hong Kong downwind of mainland China. Sharp TGM peaks during cold front passages were frequently observed due to Asian pollution outflow with typical TGM/CO slopes of 6.8 ± 2.2 pg m-3 ppbv-1. Contrary to the daytime maximums of other air pollutants, TGM exhibited a distinct diurnal variation with a midday minimum. Moreover, we observed four cases of extremely fast TGM depletion after sunrise, during which TGM concentrations rapidly dipped to 0.3-0.6 ng m-3 accompanied by other pollutants on the rise. Simulated meteorological fields revealed that morning upslope flow transporting anthropogenically polluted but TGM-depleted air masses from the mixed layer caused morning TGM depletion at the mountaintop location. The TGM-depleted air masses were hypothesized to result mainly from fast photooxidation of Hg after sunrise with minor contributions from dry deposition (5.0%) and nocturnal oxidation (0.6%). A bromine-induced two-step oxidation mechanism involving abundant pollutants (NO2, O3, etc.) was estimated to play a dominant role, contributing 55%-60% of depleted TGM and requiring 0.20-0.26 pptv Br, an amount potentially available through sea salt aerosol debromination. Our findings suggest significant effects of the interaction between anthropogenic pollution and marine halogen chemistry on atmospheric Hg cycling in the coastal areas.

Survival experience of patients undergoing oesophagectomy during the recovery period: A meta-synthesis of qualitative studies.

AIMS AND OBJECTIVE: To systematically review and synthesise existing qualitative research evidence describing the survival experience of patients undergoing oesophagectomy during recovery. BACKGROUND: Patients with oesophageal cancer undergoing surgical treatment have severe physical and psychological burdens during the recovery period. Qualitative studies on the survival experience of patients undergoing oesophagectomy are increasing annually, but there is no integration of qualitative evidence. DESIGN: A systematic review and synthesis of qualitative studies were conducted following the ENTREQ. METHODS: Five English (CINAHL, Embase, PubMed, Web of Science and Cochrane Library) and three Chinese (Wanfang, CNKI and VIP) databases were searched for literature on the survival of patients undergoing oesophagectomy during the recovery period from its establishment in April 2022. The quality of the literature was evaluated by the 'Qualitative Research Quality Evaluation Criteria for the JBI Evidence-Based Health Care Centre in Australia', and the data were synthesised by the thematic synthesis method of Thomas and Harden. RESULTS: A total of 18 studies were included, and four themes were identified: physical and mental dual challenges, impaired social functioning, efforts to return to normal life, lack of knowledge and skills in post-discharge care, and thirst for external support. CONCLUSIONS: Future research should focus on the problem of reduced social interaction during the recovery of patients with oesophageal cancer, formulating individualised exercise intervention programs and establishing a sound social support system. RELEVANCE TO CLINICAL PRACTICE: The results of this study provide evidence-based support for nurses to carry out targeted interventions and reference methods for patients with oesophageal cancer to rebuild their lives. NO PATIENT OR PUBLIC CONTRIBUTION: The report was a systematic review and did not involve a population study.

A randomised controlled trial to improve the resilience of oesophageal cancer survivors in rural China: A study protocol.

AIM: To design a protocol based on the experiences of long-term survivors to facilitate resilience for oesophageal cancer patients in rural China. BACKGROUND: According to the latest Global Cancer Statistics Report, 604,000 new cases of oesophageal cancer were reported, of which over 60% of the disease burden is distributed in China. The incidence of oesophageal cancer in rural China (15.95/100,000) is twice as high as those in urban areas (7.59/100,000). To be sure, resilience can help patients better adapt to post-cancer life. But universal interventions involving improving the resilience of oesophageal cancer patients have much less been explored, especially for rural patients. METHODS: The two-arm, parallel design, non-blinded, randomised controlled trial will be implemented in 86 adults diagnosed with oesophageal cancer and will be randomly assigned to the control group or the intervention group via the blocked randomisation. The intervention group will undergo an intervention with one-on-one guidance from a nurse while viewing a CD of the experiences of long-term survivors with oesophageal cancer in rural areas. Every 2 weeks, a theme session will be introduced, and the entire intervention will continue for 12 weeks. Psychosocial variables (resilience, self-efficacy, coping mode and family support) will be surveyed at baseline, post-intervention and 3 months after the intervention. The paper complies with the Standard Protocol Items: Recommendations for Intervention Trials 2013 and Consolidated Standards of Reporting Trials guidelines for study protocols adapted for designing and reporting parallel group randomised trials. CONCLUSION: The intervention programme transitions from hospitalisation to discharge, which includes one-on-one interventions by medical personnel and a portable CD describing the experiences of long-term survivors with rural oesophageal cancer. Once the intervention's effectiveness is proven, this protocol will provide psychological support for massive oesophageal cancer patients. RELEVANCE TO CLINICAL PRACTICE: The intervention programme may be used as an auxiliary therapy to promote patients' postoperative psychological rehabilitation. This programme has the advantages of being cost-effective, flexible, accessible, and convenient and can be implemented without the limitation of time, place and clinical medical staff. TRIAL REGISTRATION: The Chinese Clinical Trial Registration number is ChiCTR2100050047. Registered on 16 August 2021.

The mediating role of cognitive emotion regulation in the relationship between self-concealment and quality of life among breast cancer chemotherapy patients.

PURPOSE: This study aimed to explore whether self-concealment (SC) affects the quality of life (QOL), and whether cognitive emotion regulation (CER) mediates the relationship between SC and QOL among breast cancer chemotherapy patients. METHODS: This cross-sectional study was conducted among 228 breast cancer chemotherapy patients from November 2021 to March 2022 in Anhui Province, China. Data were collected using the Self-Concealment Scale, Cognitive Emotion Regulation Questionnaire, and Short Form 36 Questionnaire. Descriptive statistics, independent-sample t test, one-way analysis of variance, and structural equation modeling were used to explore associations among SC, CER, and QOL. RESULTS: QOL levels differed significantly by participant age, monthly per capita household income and home location. SC was negatively correlated with QOL. SSC was negatively correlated with adaptive-CER strategies and positively correlated with maladaptive-CER strategies. Adaptive-CER strategies were positively correlated with QOL. Maladaptive-CER strategies were negatively correlated with QOL. CER fully mediated the association between SC and QOL in breast cancer chemotherapy patients. CONCLUSION: Nursing staff should help breast cancer chemotherapy patients reduce the use of maladaptive-CER strategies in the care of patients in the future. Helping patients reduce SC is more conductive to improving the QOL of breast cancer chemotherapy patients.

The association between stroke and COVID-19-related mortality: a systematic review and meta-analysis based on adjusted effect estimates.

OBJECTIVE: To investigate the association between stroke and the risk for mortality among coronavirus disease 2019 (COVID-19) patients. METHODS: We performed systematic searches through electronic databases including PubMed, Embase, Scopus, and Web of Science to identify potential articles reporting adjusted effect estimates on the association of stroke with COVID-19-related mortality. To estimate pooled effects, the random-effects model was applied. Subgroup analyses and meta-regression were performed to explore the possible sources of heterogeneity. The stability of the results was assessed by sensitivity analysis. Publication bias was evaluated by Begg's test and Egger's test. RESULTS: This meta-analysis included 47 studies involving 7,267,055 patients. The stroke was associated with higher COVID-19 mortality (pooled effect = 1.30, 95% confidence interval (CI): 1.16-1.44; I2 = 89%, P < 0.01; random-effects model). Subgroup analyses yielded consistent results among area, age, proportion of males, setting, cases, effect type, and proportion of severe COVID-19 cases. Statistical heterogeneity might result from the different effect type according to the meta-regression (P = 0.0105). Sensitivity analysis suggested that our results were stable and robust. Both Begg's test and Egger's test indicated that potential publication bias did not exist. CONCLUSION: Stroke was independently associated with a significantly increased risk for mortality in COVID-19 patients.

Linalool Activates Oxidative and Calcium Burst and CAM3-ACA8 Participates in Calcium Recovery in Arabidopsis Leaves.

Plants produce linalool to respond to biotic stress, but the linalool-induced early signal remains unclear. In wild-type Arabidopsis, plant resistance to diamondback moth (Plutella xylostella) increased more strongly in a linalool-treated group than in an untreated control group. H2O2 and Ca2+, two important early signals that participated in biotic stress, burst after being treated with linalool in Arabidopsis mesophyll cells. Linalool treatment increased H2O2 and intracellular calcium concentrations in mesophyll cells, observed using a confocal microscope with laser scanning, and H2O2 signaling functions upstream of Ca2+ signaling by using inhibitors and mutants. Ca2+ efflux was detected using non-invasive micro-test technology (NMT), and Ca2+ efflux was also inhibited by NADPH oxidase inhibitor DPI (diphenyleneiodonium chloride) and in cells of the NADPH oxidase mutant rbohd. To restore intracellular calcium levels, Ca2+-ATPase was activated, and calmodulin 3 (CAM3) participated in Ca2+-ATPase activation. This result is consistent with the interaction between CAM7 and Ca2+-ATPase isoform 8 (ACA8). In addition, a yeast two-hybrid assay, firefly luciferase complementation imaging assay, and an in vitro pulldown assay showed that CAM3 interacts with the N-terminus of ACA8, and qRT-PCR showed that some JA-related genes and defense genes expressions were enhanced when treated with linalool in Arabidopsis leaves. This study reveals that linalool enhances H2O2 and intracellular calcium concentrations in Arabidopsis mesophyll cells; CAM3-ACA8 reduces intracellular calcium concentrations, allowing cells to resume their resting state. Additionally, JA-related genes and defense genes' expression may enhance plants' defense when treated with linalool.

Ethyl Vinyl Ketone Activates K+ Efflux to Regulate Stomatal Closure by MRP4-Dependent eATP Accumulation Working Upstream of H2O2 Burst in Arabidopsis.

Plants regulate stomatal mobility to limit water loss and improve pathogen resistance. Ethyl vinyl ketone (evk) is referred to as a reactive electrophilic substance (RES). In this paper, we found that evk can mediate stomatal closure and that evk-induced stomatal closure by increasing guard cell K+ efflux. To investigate the role of eATP, and H2O2 in evk-regulated K+ efflux, we used Arabidopsis wild-type (WT), mutant lines of mrp4, mrp5, dorn1.3 and rbohd/f. Non-invasive micro-test technology (NMT) data showed that evk-induced K+ efflux was diminished in mrp4, rbohd/f, and dorn1.3 mutant, which means eATP and H2O2 work upstream of evk-induced K+ efflux. According to the eATP content assay, evk stimulated eATP production mainly by MRP4. In mrp4 and mrp5 mutant groups and the ABC transporter inhibitor glibenclamide (Gli)-pretreated group, evk-regulated stomatal closure and eATP buildup were diminished, especially in the mrp4 group. According to qRT-PCR and eATP concentration results, evk regulates both relative gene expressions of MRP4/5 and eATP concentration in rbohd/f and WT group. According to the confocal data, evk-induced H2O2 production was lower in mrp4, mrp5 mutants, which implied that eATP works upstream of H2O2. Moreover, NADPH-dependent H2O2 burst is regulated by DORN1. A yeast two-hybrid assay, firefly luciferase complementation imaging assay, bimolecular fluorescence complementation assay, and pulldown assay showed that the interaction between DORN1 and RBOHF can be realized, which means DORN1 may control H2O2 burst by regulating RBOHF through interaction. This study reveals that evk-induced stomatal closure requires MRP4-dependent eATP accumulation and subsequent H2O2 accumulation to regulate K+ efflux.

Expression of a Chlorophyll b Reductase Gene from Zoysia japonica Causes Changes in Leaf Color and Chlorophyll Morphology in Agrostis stolonifera.

The NYC-like (NOL) enzyme is considered as an essential enzyme for chlorophyll b degradation, which catalyzes the formation of 7-hydroxymethyl chlorophyll a from chlorophyll b. The ZjNOL gene was cloned from Zoysia japonica with a completed coding sequence of 981-bp in length, encoding 326 amino acids. ZjNOL was localized on the stroma side of the thylakoid membrane, and co-localized with ZjNYC in the chloroplasts. Multiple photoregulatory elements and hormone regulatory elements were identified in the promoter region of the ZjNOL gene, and the expression level of the ZjNOL gene was dramatically up-regulated in senescence leaves, which were regulated by a variety of plant hormones. ZjNOL's ectopic expression in creeping bentgrass produced yellow leaves, thicker cortex, and smaller vascular column cells. Additionally, transgenic plants exhibited morphological alterations in their chloroplast structure, and the number of grana and thylakoids per grana stack reduced dramatically. Transgenic plants also had a lower photosynthetic rate and Fm/Fv than the control. The transgenic plants displayed a decreased chlorophyll content and a greater rate of ion leakage. The properties and activities of ZjNOL will serve as a foundation for future research into gene functions and regulatory processes.