Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations.

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 ∼ 50-100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 ∼ 40-60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation.

Multilocus Sequence Analysis and Detection of Copper Ion Resistance of Xanthomonas phaseoli pv. manihotis Causing Bacterial Blight in Cassava.

Cassava (Manihot esculenta Crantz) is an important tropical tuber crop around the world. Cassava bacterial blight, caused by Xanthomonas phaseoli pv. manihotis, is a key disease that influences cassava production worldwide. Between 2008 and 2020, 50 X. phaseoli pv. manihotis strains were isolated from diseased plant samples or acquired from China, Uganda, Cambodia, Colombia, Malaysia, and Micronesia. Using multilocus sequence analysis, the genetic diversity of X. phaseoli pv. manihotis strains was evaluated. A neighbor-joining phylogenetic dendrogram was constructed based on partial sequences of five housekeeping genes (atpD-dnaK-gyrB-efp-rpoD). The strains clustered into three groups whose clusters were consistent with atpD and RpoD gene sequences. Group I contained 46 strains from China, Uganda, Cambodia, and Micronesia, and the other two groups were comprised of strains from Colombia and Malaysia, respectively. The resistance of all these strains to copper ion (Cu2+) was determined, the minimal inhibitory concentration was between 1.3 and 1.7 mM, and there was no significant difference between strains from different geographic region. During genome annotation of the X. phaseoli pv. manihotis strain CHN01, homologous gene clusters of copLAB and xmeRSA were identified. The predicted amino acid sequences of two gene clusters were highly homologous with the copper-resistant protein from Xanthomonas strains. CopLAB and xmeRSA were amplified from all these strains, suggesting that the regulation of copper resistance is associated with two distinct metabolic pathways. CopLAB and xmeRSA were highly conserved among strains from different geographic regions, possibly associated with other conserved function.

Analyzing the Relationship between Supervisors and Post-Graduates Based on Differential Game Theory.

A healthy relationship between supervisors and postgraduates is critical for their academic achievements and personal development. This paper quantitatively discusses such a relationship from the viewpoint of differential game theory. First, a mathematic model was established to describe the evolutionary dynamics of the academic level of the supervisor-postgraduate community, which is related to the two parties' positive and negative efforts. Then, the objective function aimed at maximizing the individual and total benefit of the community was constructed. After that, the differential game relationships in the non-cooperative, cooperative and Stackelberg scenarios were formulated and solved. A comparison of the three game scenarios showed that the optimal academic level and total benefit of the community were 22% higher in the cooperative scenario than in the non-cooperative and Stackelberg game scenarios. Moreover, the influence of model parameters on the game results was analyzed. The results indicate that, for the supervisor-led Stackelberg game, when the sharing cost ratio is increased to a specific level, the supervisor's optimal benefit will not be further improved.

Non-Targeted Analytical Technology in Herbal Medicines: Applications, Challenges, and Perspectives.

Herbal medicines (HMs) have been utilized to prevent and treat human ailments for thousands of years. Especially, HMs have recently played a crucial role in the treatment of COVID-19 in China. However, HMs are susceptible to various factors during harvesting, processing, and marketing, affecting their clinical efficacy. Therefore, it is necessary to conclude a rapid and effective method to study HMs so that they can be used in the clinical setting with maximum medicinal value. Non-targeted analytical technology is a reliable analytical method for studying HMs because of its unique advantages in analyzing unknown components. Based on the extensive literature, the paper summarizes the benefits, limitations, and applicability of non-targeted analytical technology. Moreover, the article describes the application of non-targeted analytical technology in HMs from four aspects: structure analysis, authentication, real-time monitoring, and quality assessment. Finally, the review has prospected the development trend and challenges of non-targeted analytical technology. It can assist HMs industry researchers and engineers select non-targeted analytical technology to analyze HMs' quality and authenticity.

How Does Employees' Narcissism Influence Organizational Commitment? The Role of Perceived Supervisor Support and Abusive Supervision.

Narcissism has an important influence on employees' attitudes and behavior. However, research on the mechanism of this process is still relatively scarce. Based on the conservation of resources (COR) theory, this study constructed a conceptual model of the relationship between narcissism and organizational commitment and explored the role of perceived supervisor support and abusive supervision in this process. Data were collected in three waves from 288 participants through an online data collection platform in China. The results indicated that employee narcissism negatively predicts organizational commitment, and this process is mediated by perceived supervisor support. We also discuss the moderating role of abusive supervisors on perceived supervisor support, confirming that external self-value threat affects perceived support of narcissistic individuals. These results contribute to our understanding of the role of narcissism in organizations.

Psychometric Properties of the Chinese Version of the Organization Big Five Scale.

This study translates the Organization Big Five Scale (ORG-B5) into Chinese and tests its reliability and validity. In Study 1 (N=406), the ORG-B5 was translated into Chinese, and an exploratory factor analysis established the scale's factorial validity. In Study 2 (N=391), confirmatory factor analyses found that the five-factor correlation model fit the data best. The results from the configural, metric, and scalar invariance models also demonstrate that the ORG-B5 is equivalent across gender, age, and work tenure. The relationship between ORG-B5 and related constructs was also explored further. This study argues that the Chinese version of ORG-B5 provides researchers with a psychometrically sound and efficient tool to assess the Big Five personality traits within organizations in the Chinese context.

How Servant Leadership Sparks Feedback-Seeking Behavior: A Moderated Mediation Model.

Drawing upon social information processing theory, we propose that moqi with supervisors mediates the relationship between servant leadership and follower feedback-seeking behavior. Subordinates' traditionality plays a moderating role in this process. A total of 440 Chinese working adults responded to the two-wave questionnaire survey in paper and pencil forms. Correlation analyses, mediation analysis, and moderated mediation analysis was performed through R and SPSS PROCESS Macro. The results revealed that servant leadership positively correlates with followers' feedback-seeking behavior via moqi with supervisors. Moreover, these indirect effects of servant leadership were moderated by traditionality, such that servant leadership had weaker relations with feedback-seeking behavior when traditionality was higher (vs. lower). Theoretical contributions and practical implications, limitations and suggestions for further study were discussed.

Validation of the Chinese Version of the Procrastination at Work Scale.

The purpose of this study was to validate the Chinese version of the Procrastination at Work Scale (PAWS), a recently developed scale aimed at assessing procrastination in the work context. We translated the PAWS into Chinese and conducted exploratory factor analysis on participants in sample A (N = 236), resulting in a two-factor solution consistent with the original PAWS. In sample B (N = 227), confirmatory factor analysis showed that a two-factor, bifactor model fit the data best. Configural, metric, and scalar invariance models were tested, which demonstrated that the Chinese version of the PAWS did not differ across groups by gender, age, education, or job position. Validity testing demonstrated that the scale relates to work engagement, counterproductive work behavior, task performance, workplace well-being, and organizational commitment. This study indicated that the Chinese version of the PAWS could be used in future research to measure procrastination at work in China.

Genomic Characteristics and Comparative Genomics Analysis of Two Chinese Corynespora cassiicola Strains Causing Corynespora Leaf Fall (CLF) Disease.

Rubber tree Corynespora leaf fall (CLF) disease, caused by the fungus Corynespora cassiicola, is one of the most damaging diseases in rubber tree plantations in Asia and Africa, and this disease also threatens rubber nurseries and young rubber plantations in China. C. cassiicola isolates display high genetic diversity, and virulence profiles vary significantly depending on cultivar. Although one phytotoxin (cassicolin) has been identified, it cannot fully explain the diversity in pathogenicity between C. cassiicola species, and some virulent C. cassiicola strains do not contain the cassiicolin gene. In the present study, we report high-quality gapless genome sequences, obtained using short-read sequencing and single-molecule long-read sequencing, of two Chinese C. cassiicola virulent strains. Comparative genomics of gene families in these two stains and a virulent CPP strain from the Philippines showed that all three strains experienced different selective pressures, and metabolism-related gene families vary between the strains. Secreted protein analysis indicated that the quantities of secreted cell wall-degrading enzymes were correlated with pathogenesis, and the most aggressive CCP strain (cassiicolin toxin type 1) encoded 27.34% and 39.74% more secreted carbohydrate-active enzymes (CAZymes) than Chinese strains YN49 and CC01, respectively, both of which can only infect rubber tree saplings. The results of antiSMASH analysis showed that all three strains encode ~60 secondary metabolite biosynthesis gene clusters (SM BGCs). Phylogenomic and domain structure analyses of core synthesis genes, together with synteny analysis of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) gene clusters, revealed diversity in the distribution of SM BGCs between strains, as well as SM polymorphisms, which may play an important role in pathogenic progress. The results expand our understanding of the C. cassiicola genome. Further comparative genomic analysis indicates that secreted CAZymes and SMs may influence pathogenicity in rubber tree plantations. The findings facilitate future exploration of the molecular pathogenic mechanism of C. cassiicola.

Epidemiology and Outcomes of Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: A Multicenter Retrospective Study.

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). However, the epidemiological features and outcomes of AKI among COVID-19 patients with ARDS are unknown. METHODS: We retrospectively recruited consecutive adult COVID-19 patients who were diagnosed with ARDS according to Berlin definition from 13 designated intensive care units in the city of Wuhan, China. Potential risk factors of AKI as well as the relation between AKI and in-hospital mortality were investigated. RESULTS: A total of 275 COVID-19 patients with ARDS were included in the study, and 49.5% of them developed AKI during their hospital stay. In comparison with patients without AKI, patients who developed AKI were older, tended to have chronic kidney disease, had higher Sepsis-Related Organ Failure Assessment score on day 1, and were more likely to receive invasive ventilation and develop acute organ dysfunction. Multivariate analysis showed that age, history of chronic kidney disease, neutrophil-to-lymphocyte ratio, and albumin level were independently associated with the occurrence of AKI. Importantly, increasing AKI severity was associated with increased in-hospital mortality when adjusted for other potential variables: odds ratio of stage 1 = 5.374 (95% CI: 2.147-13.452; p < 0.001), stage 2 = 6.216 (95% CI: 2.011-19.210; p = 0.002), and stage 3 = 34.033 (95% CI: 9.723-119.129; p < 0.001). CONCLUSION: In this multicenter retrospective study, we found that nearly half of COVID-19 patients with ARDS experienced AKI during their hospital stay. The coexistence of AKI significantly increased the mortality of these patients.

A Noise-Robust Framework for Automatic Segmentation of COVID-19 Pneumonia Lesions From CT Images.

Segmentation of pneumonia lesions from CT scans of COVID-19 patients is important for accurate diagnosis and follow-up. Deep learning has a potential to automate this task but requires a large set of high-quality annotations that are difficult to collect. Learning from noisy training labels that are easier to obtain has a potential to alleviate this problem. To this end, we propose a novel noise-robust framework to learn from noisy labels for the segmentation task. We first introduce a noise-robust Dice loss that is a generalization of Dice loss for segmentation and Mean Absolute Error (MAE) loss for robustness against noise, then propose a novel COVID-19 Pneumonia Lesion segmentation network (COPLE-Net) to better deal with the lesions with various scales and appearances. The noise-robust Dice loss and COPLE-Net are combined with an adaptive self-ensembling framework for training, where an Exponential Moving Average (EMA) of a student model is used as a teacher model that is adaptively updated by suppressing the contribution of the student to EMA when the student has a large training loss. The student model is also adaptive by learning from the teacher only when the teacher outperforms the student. Experimental results showed that: (1) our noise-robust Dice loss outperforms existing noise-robust loss functions, (2) the proposed COPLE-Net achieves higher performance than state-of-the-art image segmentation networks, and (3) our framework with adaptive self-ensembling significantly outperforms a standard training process and surpasses other noise-robust training approaches in the scenario of learning from noisy labels for COVID-19 pneumonia lesion segmentation.

Light-controlled cooperative catalysis of asymmetric sulfoxidation based on azobenzene-bridged chiral salen TiIV catalysts.

Incorporation of azobenzene into the linker of bimetallic chiral salen TiIV catalysts allowed the photoswitchable arrangement of the two Ti(salen) units through cis/trans photoisomerization of azobenzene. The differently arranged Ti(salen) units changed their cooperative function to reflect the positional relationships, as a result, their efficiency as cooperative catalysts in asymmetric sulfoxidation could be readily controlled by light stimuli.

Low Expression of 14-3-3beta Is Associated With Adverse Survival of Diffuse Large B-Cell Lymphoma Patients.

Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma in the world, is highly heterogeneous. Although current therapies have improved the clinical outcome, 30-40% of the patients are still not cured. Thus, novel treatment options such as targeted therapy is urgently needed. Accumulating evidence suggests that 14-3-3beta protein plays an important role in tumorigenesis and tumor progression. However, the specific roles of 14-3-3beta in DLBCL are still poorly understood. In this study, we retrospectively analyzed 120 archived wax blocks obtained from patients with DLBCL (n = 70) and non-neoplastic lymph nodes (n = 50). Immunohistochemical staining showed that 14-3-3beta gene expression was significantly decreased in DLBCL tissues (P < 0.001) compared to that in non-neoplastic lymph nodes. Low 14-3-3beta expression was significantly correlated with extra-nodal status (P = 0.026), serum LDH level (P = 0.023) and adverse survival of DLBCL patients. In survival analyses, low 14-3-3beta expression was significantly associated with adverse overall survival of the DLBCL patients (P = 0.003). Using the Kaplan-Meier analysis module of the R2 microarray analysis and visualization platform (http://r2.amc.nl), we also confirmed that low expression of 14-3-3beta gene had inferior overall survival in DLBCL patients. Based on our results, we conclude that low expression of 14-3-3beta is associated with adverse survival of diffuse large B-cell lymphoma patients, suggesting a novel prognostic marker and potential therapeutic target.

Recurrent GNAQ mutation encoding T96S in natural killer/T cell lymphoma.

Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive malignancy with a higher prevalence in Asia and South America. However, the molecular genetic mechanisms underlying NKTCL remain unclear. Here, we identify somatic mutations of GNAQ (encoding the T96S alteration of Gαq protein) in 8.7% (11/127) of NKTCL patients, through whole-exome/targeted deep sequencing. Using conditional knockout mice (Ncr1-Cre-Gnaqfl/fl), we demonstrate that Gαq deficiency leads to enhanced NK cell survival. We also find that Gαq suppresses tumor growth of NKTCL via inhibition of the AKT and MAPK signaling pathways. Moreover, the Gαq T96S mutant may act in a dominant negative manner to promote tumor growth in NKTCL. Clinically, patients with GNAQ T96S mutations have inferior survival. Taken together, we identify recurrent somatic GNAQ T96S mutations that may contribute to the pathogenesis of NKTCL. Our work thus has implications for refining our understanding of the genetic mechanisms of NKTCL and for the development of therapies.

Validation of a Short-Form Five Facet Mindfulness Questionnaire Instrument in China.

The Five Facet Mindfulness Questionnaire (FFMQ) developed by Baer and colleagues has been widely used owing to its satisfactory psychometric properties. Because there was not yet a short-form version of the FFMQ (SF-FFMQ) that could be utilized in work settings available in China, we developed a Chinese SF-FFMQ. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) supported a five-factor structure of our Chinese SF-FFMQ in two Chinese samples (Sample 1, N = 535; Sample 2, N = 391). The internal consistencies of the facets and the whole scale were acceptable. The predictive validity of this questionnaire was affirmed. Overall, the mindfulness facets correlated with related constructs including depression symptoms, anxiety symptoms, employee life well-being, employee workplace well-being, and employee psychological well-being. In sample 2, which consisted of participants employed by local companies, we found that mindfulness mediated a positive relationship between servant leadership and employees' satisfaction with work-family balance. In conclusion, our Chinese SF-FFMQ was found to be a valid and reliable measurement tool and our results support its use in both research and practice in clinical and work settings in China.

IL-13 and IL-13Rα1 are overexpressed in extranodal natural killer/T cell lymphoma and mediate tumor cell proliferation.

Extranodal NK/T cell lymphoma (NKTCL) is a rare but aggressive subtype of non-Hodgkin lymphoma. Multi-agent chemotherapy and involved-field radiotherapy are used to treat this disease, but the prognosis remains poor. Interleukin 13 and its receptors (IL-13Rs) are correlated with the pathogenesis and progression of various malignances. However, their roles in NKTCL have not been evaluated. In this study, we examined the roles of IL-13 and IL-13Rs in NKTCL and the underlying mechanisms. We found significantly higher serum IL-13 levels (p < 0.001) and IL-13Rα1 expression in tumor tissues (36 of 40, p < 0.001) in patients with NKTCL than in control cohort. IL-13 secretion was observed in tumor tissues (30 of 40, p < 0.001) and several cell lines of NKTCL. However, we did not detect significant associations between clinical characteristics and the expression levels of IL-13 or IL-13Rs. In vitro, IL-13 activated Stat6 and promoted cell proliferation in a dose-dependent manner. In addition, blocking IL-13 exerted a negative effect on tumor cell growth. We conclude that IL-13 functions as an autocrine growth factor in NKTCL and contributes to its pathogenesis. Blocking IL-13 is thus a potential therapeutic approach for NKTCL.

Frequent Mutations in Natural Killer/T Cell Lymphoma.

Extranodal natural killer (NK)/T cell lymphoma (ENKTL-NT or NKTCL), with its aggressive nature and poor prognosis, has been widely studied to discover more effective treatment options. Various somatic gene alterations have been identified by traditional Sanger sequencing. However, recently, novel gene mutations in NKTCL have been revealed by next-generation sequencing (NGS) technology, suggesting the potential for novel targeted therapies. This review discusses recurrent aberrations in NKTCL detected by NGS, which can be categorized into three main groups, specifically, tumor suppressors (TP53, DDX3X, and MGA), the JAK/STAT cascade, and epigenetic modifiers (KMT2D, BCOR, ARID1A, and EP300). Some epigenetic dysregulation and DDX3X mutation, which have been rarely identified by traditional sequencing technology, were recently uncovered with high frequencies by NGS. In this review, we summarize the mutational frequencies of various genes in NKTCL. In general, based on our analysis, BCOR is the most frequently mutated gene (16.9%), followed by TP53 (14.7%), and DDX3X (13.6%). The characterization of such genes provides new insight into the pathogenesis of this disease and indicates new biomarkers or therapeutic targets.

Overweight and obesity associated with increased total serum calcium level: comparison of cross-sectional data in the health screening for teaching faculty.

Obesity is a risk of cardiovascular diseases. Our previous studies revealed that serum calcium level may have influence in the blood pressure to older male subjects. The aim of this study was to evaluate the relationship between total serum calcium level and overweight and obesity subjects. In our study, overweight and obesity status and total serum calcium level were measured among 2,503 subjects, at age range of 22-94 years, who were recruited for the routine health screening in 2006. The estimated mean for age (p < 0.001), white blood cell count (p = 0.037), hemoglobin concentration (p < 0.001), red blood cell count (p < 0.001), total serum calcium level (p < 0.001), total cholesterol weight (p < 0.001), HDL-cholesterol (p < 0.001), LDL-cholesterol (p < 0.001), and triglyceride (p < 0.001) of overweight and obesity subjects were significantly higher than those of non-overweight subjects. The prevalence of overweight/obesity in subjects according to the log-transformed total serum calcium level quartiles was 16.3-30.5 %. The prevalence of overweight/obesity subjects showed trends that were significant according to the total serum calcium level quartiles (p < 0.001). The odds ratios (ORs) and 95 % confidence intervals (CIs) for overweight/obesity of the second, third, and fourth quartiles compared to the lowest quartile were 1.407 (1.050-1.883), 1.543 (1.136-2.095), and 1.360 (0.995-1.859), respectively, after adjusting for sex and age (p < 0.001). These findings suggest that a higher prevalence of adult overweight/obesity is weakly associated with higher total serum calcium level in the Chinese population.