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Background. Exosomes derived from cardiac microvascular endothelial cells (CMECs) under hypoxia can mediate cardiac repair functions and alleviate pyroptosis and oxidative stress during ischemia-reperfusion (I/R) injury. This study is aimed at investigating the effect and mechanism of miR-27b-3p underlying hypoxic CMECs-derived exosomes against I/R injury. Methods. CMECs were isolated from the left ventricle of Sprague-Dawley rats, followed by culturing under hypoxic conditions or pretreatment with the miR-27b-3p inhibitor. CMECs-derived exosomes were added into H9C2 cells before hypoxia/reoxygenation (H/R) or injected into the rat heart before I/R injury. An in vivo I/R injury model was established by ligating and releasing the left anterior descending coronary artery. Expression of pyroptosis-related factors was detected using Western blot, and heart infarcted size was determined by the 2,3,5-triphenyl-2H-tetrazpinolium chloride staining method. Dual-Luciferase Reporter assays were performed to analyze the interactions of nmiR-27b-3p-forkhead box O1 (Foxo1) and Gasdermin D- (GSDMD-) Foxo1. Chromatin-immunoprecipitation (ChIP) assays were performed to validate the interactions between forkhead box O1 (Foxo1) and Gasdermin D (GSDMD) and Foxo1-mediated histone acetylation of GSDMD. Results. CMECs were successfully identified from left ventricle of Sprague-Dawley rats. The expressions of Foxo1 and pyroptosis-related proteins (GSDMD, NLPR3, cleaved caspase 1, IL-1β, and IL-18) were upregulated in the rat heart after I/R injury. Treatment of CMEC-derived exosomes, especially that under hypoxic conditions, significantly reduced pyroptosis in the rat heart. miR-27b-3p was significantly upregulated in CMEC-derived exosomes under hypoxic conditions, and miR-27b-3p inhibition in exosomes alleviated its cytoprotection and inhibited oxidative stress in H9C2 cells. Treatment with Foxo1 overexpression plasmids aggravated in vitro H/R and in vivo I/R injury by upregulating pyroptosis-related proteins. Further experiments validated that miR-27b-3p negatively targeted Foxo1, which bound to the promoter region of GSDMD. Conclusions. These results demonstrated a great therapeutic efficacy of miR-27b-3p overexpression in hypoxic CMEC-derived exosomes in preventing the development of myocardial damage post I/R injury through inhibiting Foxo1/GSDMD signaling-induced oxidative stress and pyroptosis.

The rebound-competent viral reservoir (RCVR), comprised of virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after antiretroviral therapy interruption (ATI), remains the biggest obstacle to the eradication of HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop targeted therapeutic strategies for reducing the RCVR. In this study, barcoded SIVmac239M was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood, lymphoid tissues (LTs, spleen, mesenteric and inguinal lymph nodes), and non-lymphoid tissues (NLTs, colon, ileum, lung, liver, and brain) were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX/RNAscope/ in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy although plasma viral RNA remained < 22 copies/mL. Among the tissues studied, mesenteric and inguinal lymph nodes, and spleen contained viral barcodes detected in plasma, and trended to have higher cell-associated viral loads, higher intact provirus levels, and greater diversity of viral barcodes. CD4+ T cells were the main cell type harboring viral RNA (vRNA) after ATI. Further, T cell zones in LTs showed higher vRNA levels than B cell zones for most animals. These findings are consistent with LTs contributing to virus present in plasma early after ATI. ONE SENTENCE SUMMARY: The reemerging of SIV clonotypes at early post-ATI are likely from the secondary lymphoid tissues.

Purpose: Novel, effective, and safe preventive therapy targets for AF are still warranted. Circulating proteins with causal genetic evidence represents promising candidates. We aimed to systematically screen circulating proteins for AF drug targets and determine their safety and efficacy using genetic methods. Methods: The protein quantitative trait loci (pQTL) of up to 1,949 circulating proteins were retrieved from nine large genome-proteome-wide association studies. Two-sample Mendelian Randomization (MR) and colocalization analyses were used to estimate the causal effects of proteins on the risk of AF. Further, phenome-wide MR was conducted to depict side effects and the drug-targets databases were searched for drug validation and repurposing. Results: Systematic MR screen identified 30 proteins as promising drug targets. Genetically predicted 12 proteins increased AF risk (TES, CFL2, MTHFD1, RAB1A, DUSP13, SRL, ANXA4, NEO1, FKBP7, SPON1, LPA, MANBA); 18 proteins decreased AF risk (PMVK, UBE2F, SYT11, CHMP3, PFKM, FBP1, TNFSF12, CTSZ, QSOX2, ALAD, EFEMP1, FLRT2, LRIG1, OLA1, SH3BGRL3, IL6R, B3GNT8, FCGR2A). DUSP13 and TNFSF12 possess strong colocalization evidence. For these identified proteins, extended phe-MR conducted side-effect profiles, whereas drug targets databases presented the approved or investigated indications. Conclusion: We identified 30 circulating proteins as potential preventive targets for AF.

The present paper focused on how a third party's social status affects third-party intervention to maintain social fairness. Study 1 adopted a quasi-experimental design. Selecting high and low-status members of real social groups, we observed that high-status individuals intervened more forcibly and more frequently when assessing the fairness of players' behavior in a dictator game (DG). The manifestation of social status is generally divided into power and economic capital. In Study 2a, using the same DG punishment-compensation paradigm we randomly assigned the third party in the lab to high, medium, and low impact conditions, where their actions had relative multiplier effects on the resources retained by dictators and recipients. This tested whether the power to influence the situation would systematically affect third party's behavior. We found that greater influence predicted increased interventions. Study 2b investigated the influence of economic capital or intrinsic wealth on a third party's altruistic behavior by varying how much capital the third party had at their disposal to spend on punishment or recompensing. Having high capital predicted an increase in the size of penalty inflicted or compensation offered, but resource abundance had no effect on the likelihood that the third party would intervene. In conclusion, the paper showed that the social status of the third party truly does affect their altruistic interventions and the impact of social status on altruistic behaviors for maintaining fairness by the third party occurred primarily through the third parties' perception of their power. Furthermore, the influence of gain and loss contexts and social status on third-party punishment and compensation were independent of each other. This paper provided a new perspective for third-party altruistic behaviors and help to clarify the view of social fairness.

Nicotinamide adenine dinucleotide (NAD) plays pivotal roles in controlling many biochemical processes. 'NAD' refers to the chemical backbone irrespective of charge, whereas 'NAD+' and 'NADH' refers to oxidized and reduced forms, respectively. NAD+/NADH ratio is essential for maintaining cellular reduction-oxidation (redox) homeostasis and for modulating energy metabolism. As a sensing or consuming enzyme of the poly (ADP-ribose) polymerase 1 (PARP1), the cyclic ADP-ribose (cADPR) synthases (CD38 and CD157), and sirtuin protein deacetylases (sirtuins, SIRTs), NAD+ participates in several key processes in cardiovascular disease. For example, NAD+ protects against metabolic syndrome, heart failure, ischemia-reperfusion (IR) injury, arrhythmia and hypertension. Accordingly, the subsequent loss of NAD+ in aging or during stress results in altered metabolic status and potentially increased disease susceptibility. Therefore, it is essential to maintain NAD+ or reduce loss in the heart. This review focuses on the involvement of NAD+ in the pathogenesis of cardiovascular disease and explores the effects of NAD+ boosting strategies in cardiovascular health.

The relationship between mitochondrial dysfunction or ER stress with pathogenesis of cardiovascular disease is well documented, but the crosstalk between them in cardiovascular diseases is not clear. Adiponectin (APN) is reported to become a potential cardioprotective molecule, but whether and how APN regulates mitochondrial dysfunction and ER stress is not clear. In this study, we used rotenone-treated HL-1 atrial cardiomyocytes as an in vitro model of mitochondrial dysfunction to investigate the possible interactions between mitochondrial dysfunction and ER stress and explore the effects of APN on rotenone-induced cytotoxicity and the underlying mechanisms. It found that rotenone treatment significantly activated the ER stress PRK-like endoplasmic reticulum kinase (PERK)-dependent pathway, decreased autophagic flux and APN expression in a dose-dependent manner. Pretreatment of GSK2606414, an inhibitor of PERK kinase activity, attenuated the rotenone-induced decrease of APN expression. In return exogenous APN pretreatment inhibited rotenone-induced ER stress and activated autophagy via AMP-activated protein kinase (AMPK) activation and protected HL-1 cells against apoptosis and enhanced the viability after rotenone treatment. In conclusion, rotenone treatment induced significant cardiomyocyte cytotoxicity and ER stress, suppressed autophagy, and decreased APN expression in HL-1 cells. APN in return inhibited ER stress and activated autophagy through AMPK activation, thus alleviating rotenone induced HL-1 apoptosis.

Celiac disease (CD) refers to a chronic bowel disorder related to the disturbance of immune systems and intolerance to gluten. Globally, CD affects about 1.4% of the total population with various gastrointestinal and extraintestinal symptoms1 . While genetical background plays significant roles in the occurrence of CD, emerging evidence from observational studies demonstrate strong associations of CD with other chronic diseases, indicating shared etiology or risk factors.

Substantial research has demonstrated the association between cardiovascular disease and the dysregulation of intracellular calcium, ageing, reduction in nicotinamide adenine dinucleotide NAD+ content, and decrease in sirtuin activity. CD38, which comprises the soluble type, type II, and type III, is the main NADase in mammals. This molecule catalyses the production of cyclic adenosine diphosphate ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and adenosine diphosphate ribose (ADPR), which stimulate the release of Ca2+, accompanied by NAD+ consumption and decreased sirtuin activity. Therefore, the relationship between cardiovascular disease and CD38 has been attracting increased attention. In this review, we summarize the structure, regulation, function, targeted drug development, and current research on CD38 in the cardiac context. More importantly, we provide original views about the as yet elusive mechanisms of CD38 action in certain cardiovascular disease models. Based on our review, we predict that CD38 may serve as a novel therapeutic target in cardiovascular disease in the future.

Purpose Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo. Patients and methods The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo. Results We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX. Conclusion We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer.

How work stress affects creativity has attracted the attention of both enterprises and scholars. Hindrance work stress and Excessive challenge work stress usually impair creativity. However, how to buffer the impairment of work stress on creativity has not been studied in depth. Based on the Job Demands-Resources Model, this study proposes that available resources of employees can buffer the harmful impact of work stress on creativity. Available resources can buffer the negative impact of work stress by supplementing the depleted resources of motivation, cognition, emotion. Future research should explore other moderators that can buffer the impact of stress on creativity, how to buffer the influence of stress on creativity when multiple resources coexist and the boundary conditions under which available resources can play a buffering role, and finally carry out field study to apply the research results to management practice.

In this study, the improved masking detection paradigm was adopted to form stimulus picture pairs with pictures of different emotional faces and household items, to explore the attention preference characteristics of individuals with social anxiety under the threshold of consciousness. The results showed that the threshold of consciousness, under the condition of consistency, detects the target in the reaction on the negative emotions. Face images are much smaller than to detect the target in household items to the reaction time on the images, and also appear less than to detect the target in the reaction on the positive mood face images, namely high social anxiety group compared with low social anxiety, attention to negative emotional faces that exist. The results are consistent with the alertness model in the cognitive processing theory model of social anxiety.

The effect of occupational delayed gratification is that it can prompt individuals to postpone short-term instant gratification in order to pursue more valuable long-term career goals when they encounter a choice of interests, which is very beneficial to the career development of the new generation of employees. Based on extensive literature review and interviews, this paper compiles a pretest questionnaire for investigation and proposes models and hypotheses. For the data of the pretest questionnaire, big data item discrimination analysis, Cronbach’s alpha internal consistency reliability test, and exploratory factor analysis were used to eliminate unreasonable items. From the four aspects of self-evaluation, self-efficacy, self-esteem, and social support, it explains how to cultivate and improve the career delayed gratification of the new generation of employees, so that they can make the right choice between short-term and long-term benefits, setbacks, and success, thereby improving the organizational socialization outcome relationship.

Atrial fibrillation (AF) is the most common sustained arrhythmia. Atrial remodeling, including electrical/structural/autonomic remodeling, plays a vital role in AF pathogenesis. All of these have been shown to contribute continuously to the self-perpetuating nature of AF. The Warburg effect was found to play important roles in tumor and non-tumor disease. Recently, lots of studies documented altered atrial metabolism in AF, but the specific mechanism and the impact of these changes upon AF initiation/progression remain unclear. In this article, we review the metabolic consideration in AF comprehensively and observe the footprints of the Warburg effect. We also summarize the signaling pathway involved in the Warburg effect during AF-HIF-1α and AMPK, and discuss their potential roles in AF maintenance and progression. In conclusion, we give the innovative idea that the Warburg effect exists in AF and promotes the progression of AF. Targeting it may provide new therapies for AF treatment.

Aim: To evaluate the genetic associations of visceral adipose tissue (VAT) mass with metabolic risk factors and cardiovascular disease (CVD) endpoints and to construct a network analysis about the underlying mechanism using Mendelian randomization (MR) analysis.Methods and Results: Using summary statistics from genome-wide association studies (GWAS), we conducted the two-sample MR to assess the effects of VAT mass on 10 metabolic risk factors and 53 CVD endpoints. Genetically predicted VAT mass was associated with metabolic risk factors, including triglyceride (odds ratio, OR, 1.263 [95% confidence interval, CI, 1.203–1.326]), high-density lipoprotein cholesterol (OR, 0.719 [95% CI, 0.678–0.763]), type 2 diabetes (OR, 2.397 [95% CI, 1.965–2.923]), fasting glucose (OR, 1.079 [95% CI, 1.046–1.113]), fasting insulin (OR, 1.194 [95% CI, 1.16–1.229]), and insulin resistance (OR, 1.204 [95% CI, 1.16–1.25]). Genetically predicted VAT mass was associated with CVD endpoints, including atrial fibrillation (OR, 1.414 [95% CI, 1.332 = 1.5]), coronary artery disease (OR, 1.573 [95% CI, 1.439 = 1.72]), myocardial infarction (OR, 1.633 [95% CI, 1.484 =1.796]), heart failure (OR, 1.711 [95% CI, 1.599–1.832]), any stroke (OR, 1.29 [1.193–1.394]), ischemic stroke (OR, 1.292 [1.189–1.404]), large artery stroke (OR, 1.483 [1.206–1.823]), cardioembolic stroke (OR, 1.261 [1.096–1.452]), and intracranial aneurysm (OR, 1.475 [1.235–1.762]). In the FinnGen study, the relevance of VAT mass to coronary heart disease, stroke, cardiac arrhythmia, vascular diseases, hypertensive heart disease, and cardiac death was found. In network analysis to identify the underlying mechanism between VAT and CVDs, VAT mass was positively associated with 23 cardiovascular-related proteins (e.g., Leptin, Hepatocyte growth factor, interleukin-16), and inversely with 6 proteins (e.g., Galanin peptides, Endothelial cell-specific molecule 1). These proteins were further associated with 32 CVD outcomes.Conclusion: Mendelian randomization analysis has shown that VAT mass was associated with a wide range of CVD outcomes including coronary heart disease, cardiac arrhythmia, vascular diseases, and stroke. A few circulating proteins may be the mediators between VAT and CVDs.

Event-related potential (ERP) technology and the dictator game paradigm are used to explore the formation mechanism of upstream indirect reciprocity behaviors. We design a within subject experiment of 3 (social comparison: upward versus parallel versus downward) × 2 (treatment: fair versus unfair) involving 49 subjects. In the first round of allocations, subjects are forced to accept a monetary amount allocated to them by another player. In the second round, subjects assume the role of allocator and divide a monetary amount between themselves and a third party. Our results show the following: 1) Having received fair treatment from someone else, individuals engaged in downward comparison are more inclined to reciprocate the fairness they had received to a third party compared to individuals in parallel and upward comparison conditions. If individuals receive unfair treatment, they tend to repeat this behavior to a third party regardless of which social comparison condition they are in; 2) Under the condition of upward comparison, individuals receiving unfair treatment exhibit greater FRN amplitude and less P300 amplitude, but in parallel and downward comparison conditions, there is no significance in FRN and P300 amplitude between individuals receiving fair and unfair treatment.

[Figure: see text].

Genetic evidence based on two-sample Mendelian randomization approaches suggested that visceral adipose tissue had a causal, independent role in lowering the risk of Parkinson's disease. Further studies are needed to explore the underlying mechanism.

Background: Atrial fibrillation (AF) is the most common arrhythmia. We aimed to construct competing endogenous RNA (ceRNA) networks associated with the susceptibility and persistence of AF by applying the weighted gene co-expression network analysis (WGCNA) and prioritize key genes using the random walk with restart on multiplex networks (RWR-M) algorithm.Methods: RNA sequencing results from 235 left atrial appendage samples were downloaded from the GEO database. The top 5,000 lncRNAs/mRNAs with the highest variance were used to construct a gene co-expression network using the WGCNA method. AF susceptibility- or persistence-associated modules were identified by correlating the module eigengene with the atrial rhythm phenotype. Using a module-specific manner, ceRNA pairs of lncRNA–mRNA were predicted. The RWR-M algorithm was applied to calculate the proximity between lncRNAs and known AF protein-coding genes. Random forest classifiers, based on the expression value of key lncRNA-associated ceRNA pairs, were constructed and validated against an independent data set.Results: From the 21 identified modules, magenta and tan modules were associated with AF susceptibility, whereas turquoise and yellow modules were associated with AF persistence. ceRNA networks in magenta and tan modules were primarily involved in the inflammatory process, whereas ceRNA networks in turquoise and yellow modules were primarily associated with electrical remodeling. A total of 106 previously identified AF-associated protein-coding genes were found in the ceRNA networks, including 16 that were previously implicated in the genome-wide association study. Myocardial infarction–associated transcript (MIAT) and LINC00964 were prioritized as key lncRNAs through RWR-M. The classifiers based on their associated ceRNA pairs were able to distinguish AF from sinus rhythm with respective AUC values of 0.810 and 0.940 in the training set and 0.870 and 0.922 in the independent test set. The AF-related single-nucleotide polymorphism rs35006907 was found in the intronic region of LINC00964 and negatively regulated the LINC00964 expression.Conclusion: Our study constructed AF susceptibility- and persistence-associated ceRNA networks, linked genetics with epigenetics, identified MIAT and LINC00964 as key lncRNAs, and constructed random forest classifiers based on their associated ceRNA pairs. These results will help us to better understand the mechanisms underlying AF from the ceRNA perspective and provide candidate therapeutic and diagnostic tools.

Power is the basic component of our society. In social psychology, the study of power usually focuses on the sense of power. Early research always focused on the negative effects of power, but it is difficult to explain the complex effects of sense of power. Therefore, from the perspective of moral self-image, this study attempts to integrate the differential effects of sense of power and explores its potential moderating and mediating role. Therefore, we use three studies to explore these effects and find that individual’s sense of power can reduce their pro-social behavior, while moral self-image can moderate this effect. In addition, the moderating effect of moral self-image is mediated by perceived responsibility.

Leader’s emotion is one of the most influential factors of employee behavior in the workplace. The expression or of a leader’s positive emotion can directly or indirectly affect the employee’s work performance, especially the employee’s Counterproductive Work Behavior (CWB). This paper systematically explains the internal mechanism how the leader’s positive emotion affects employees’ CWB through experimental methods, and uses the Emotions As Social Information Modle (EASI) to analyze and explain the research results. Finally, this study exposes the inner psychological process of Leader’s positive emotion affecting employees’ CWB through their own positive emotions, proving the moderating effect of leadership justice in this process, and this study enriches the results of the research field of CWB.

In recent years, related research on materialism has been widely concerned by scholars at home and abroad, but most of the research is based on its negative influence. Will materialism have a positive impact? How to deal with the negative effects of materialism? It should also cause our concern. This paper introduces the positive and negative effects of materialism from four levels of individual, consumption, organization and society, and summarizes the interventions of materialism. Future research should continue to improve the concept of materialism, expand research levels, and develop effective intervention strategies.

Delay discounting is an important part of intertemporal decision-making. This decision involves information about the costs and benefits of future possibilities,which affect people making decision. Episodic foresight therefore has a capacity to organize current action in view of anticipated events and concerns the imaginative of thinking about future events that often draw on the visual modality. In the clinic research,episodic foresight could improve maladaptive behaviors,including pathological gambling,obesity,drug and alcohol abuse. Our study explores the psychological mechanism and brain mechanism. We proposed that future research should further explore how the episodic foresight affects delay discounting and how episodic foresight is applied to clinic and behaviour modification.

Self-affirmation is helpful for reducing the individual’s defensive response to threats, harvesting and growing from threatening but valuable information. This study examines whether viewing personal WeChat moments is self-affirmative. Browsing WeChat moments of other people that better than yourself will lead to an upward social comparison, but the effect of browsing your own moments is rarely discussed. This study conducts an experiment, and the result proves that browsing WeChat moments is an effective self-affirmation intervention paradigm. The self-affirmation paradigm which is close to daily life deserves further promotion and research.

Background Atrial fibrillation (AF) is the most common arrhythmia with poorly understood mechanisms. We aimed to investigate the biological mechanism of AF and to discover feature genes by analyzing multi-omics data and by applying a machine learning approach. Methods At the transcriptomic level, four microarray datasets (GSE41177, GSE79768, GSE115574, GSE14975) were downloaded from the Gene Expression Omnibus database, which included 130 available atrial samples from AF and sinus rhythm (SR) patients with valvular heart disease. Microarray meta-analysis was adopted to identified differentially expressed genes (DEGs). At the proteomic level, a qualitative and quantitative analysis of proteomics in the left atrial appendage of 18 patients (9 with AF and 9 with SR) who underwent cardiac valvular surgery was conducted. The machine learning correlation-based feature selection (CFS) method was introduced to selected feature genes of AF using the training set of 130 samples involved in the microarray meta-analysis. The Naive Bayes (NB) based classifier constructed using training set was evaluated on an independent validation test set GSE2240. Results 863 DEGs with FDR 1.2 were obtained from the transcriptomic and proteomic study, respectively. The DEGs and DEPs were then analyzed together which identified 30 biomarkers with consistent trends. Further, 10 features, including 8 upregulated genes (CD44, CHGB, FHL2, GGT5, IGFBP2, NRAP, SEPTIN6, YWHAQ) and 2 downregulated genes (TNNI1, TRDN) were selected from the 30 biomarkers through machine learning CFS method using training set. The NB based classifier constructed using the training set accurately and reliably classify AF from SR samples in the validation test set with a precision of 87.5% and AUC of 0.995. Conclusion Taken together, our present work might provide novel insights into the molecular mechanism and provide some promising diagnostic and therapeutic targets of AF.

Additional file 1. Detailed procedure of the proteomic study.