The Impact of high-performance work system perceived by medical staff on job satisfaction: the mediating role of self-efficacy.

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS.

Non-Pharmacological Interventions in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023. STUDY SELECTION: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method. DATA SYNTHESIS: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (6MWD; 68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO2; 3.48 mL/kg•min [2.84, 4.12]), quality of life (QOL; -17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO2, 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events. CONCLUSIONS: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL.

Non-pharmacological interventions for older patients with hypertension: A systematic review and network meta-analysis.

OBJECTIVE: To determine the most effective non-pharmacological interventions to control the blood pressure variation in older hypertensive patients. METHODS: Primary endpoints were office systolic blood pressure (SBP) and diastolic blood pressure (DBP). The quality of evidence was assessed using the "risk of bias 2″ tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. We performed a Bayesian network meta-analysis using R-4.0.2 software to compare the efficacy of interventions. RESULTS: 36 eligible studies (3,531 patients) with a median follow-up of 12 weeks, assessing 18 non-pharmacological interventions, were included. The percentages of high, moderate, low, and very low certainty evidence were 16.7%, 38.9%, 33.3%, and 11.1%, respectively. CONCLUSION: High certainty evidence suggests that self-management education is most effective in lowering SBP and DBP in older patients with hypertension, followed by moderate-intensity aerobic exercise. Moderate-intensity resistance training is the most effective exercise for lowering SBP. REGISTRATION: PROSPERO, #CRD42020209850.

A new prenylated coumestan from the roots of Campylotropis hirtella.

A new prenylated coumestan, campylohirtin A (1), along with fifteen phenolic known compounds (2‒16) and four other known compounds (17‒20), was obtained from the 95% ethanol extract of roots of Campylotropis hirtella. Their structures were elucidated based on extensive spectroscopic analysis (1 D and 2 D-NMR, MS, UV and IR). In vitro antimalarial activities of compounds 1-3, 5-14 and 16 were evaluated by ß-hematin formation inhibition assay. Compared with the positive control chloroquine diphosphate, compounds 8, 11 and 16 exhibited strong antimalarial activity with the IC50 values of 69.9, 33.2 and 75.4 µM, respectively. Compounds 1-3, 5-7 and 12 showed moderate antimalarial activities with IC50 values ranging from 134.6 µM to 578.6 µM.[Formula: see text].

Integrated Bioinformatics Analysis for the Identification of Key Molecules and Pathways in the Hippocampus of Rats After Traumatic Brain Injury.

High-throughput and bioinformatics technology have been broadly applied to demonstrate the key molecules involved in traumatic brain injury (TBI), while no study has integrated the available TBI-related datasets for analysis. In this study, four available expression datasets of fluid percussion injury (FPI) and sham samples from the hippocampus of rats were analysed. A total of 248 differentially expressed genes (DEGs) and 10 differentially expressed microRNAs (DEMIs) were identified. Then, functional annotation was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Most of the DEGs were enriched for the term inflammatory immune response. The MCODE plug-in in the Cytoscape software was applied to build a protein-protein interaction (PPI) network, and 18 hub genes were demonstrated to be enriched in the cell cycle pathway. Besides, time sequence (3 h, 6 h, 12 h, 24 h, and 48 h) profile analysis was performed using short time-series expression miner (STEM). The significantly expressed genes were assigned into 24 pattern clusters with four significant uptrend clusters. Four DEGs, Fcgr2a, Bcl2a1, Cxcl16, and Gbp2, were found to be differentially expressed at all time-points. Fifty-three DEGs and eight DEMIs were identified to form a miRNA-mRNA negative regulatory network using miRWalk3.0 and Cytoscape. Moreover, the mRNA levels of eight hub genes were validated by qRT-PCR. These DEGs, DEMIs, and time-dependent expression patterns facilitate our knowledge of the molecular mechanisms underlying the process of TBI in the hippocampus of rats and have the potential to improve the diagnosis and treatment of TBI.

A functional variant in the flanking region of pri-let-7f contributes to colorectal cancer risk in a Chinese population.

Let-7f was reported to be downregulated in patients with colorectal cancer (CRC). However, little is known about the role of let-7f in CRC carcinogenesis. The aim of this study was to investigate the correlation between genetic polymorphisms in the flanking region of pri-let-7f and CRC risk, as well as the potential role of let-7f in CRC cell migration and invasion. The pri-let-7f-1 rs10739971 and pri-let-7f-2 rs17276588 were genotyped using TaqMan (Applied Biosystems, Foster City, CA) assay. The luciferase activity was detected using Dual-Luciferase Reporter Assay. CRC cell migration and invasion were evaluated using transwell chamber assay. The rs17276588 AG and AG/AA genotypes had a significantly increased CRC risk (AG vs. GG: adjusted odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.19-1.83, p < 0.001; AG/AA vs. GG: adjusted OR = 1.43, 95% CI = 1.17-1.75, p < 0.001). Stratification analyses showed that the increased risk was observed in CRC patients with well-moderately differential status, patients with clinical Stages I-II, and patients without lymph node metastasis. The rs17276588A allele displayed a decreased transcriptional activity and low levels of let-7f. Moreover, let-7f inhibited migration and invasion in Caco-2 and Lovo cells. These findings indicate that the rs17276588 AG/AA genotypes increased CRC risk by reducing the expression of tumor suppressor let-7f.

Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor.

Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although PEDV was long believed to replicate in the intestinal epithelium by using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells results in disruption of the tight junctional distribution of occludin to its intracellular location. Overexpression of occludin in target cells makes them more susceptible to PEDV infection, whereas ablation of occludin expression by use of small interfering RNA (siRNA) in target cells significantly reduces their susceptibility to virus infection. However, the results observed with occludin siRNA indicate that occludin is not required for virus attachment. We conclude that occludin plays an essential role in PEDV infection at the postbinding stages. Furthermore, we observed that macropinocytosis inhibitors blocked occludin internalization and virus entry, indicating that virus entry and occludin internalization are closely coupled. However, the macropinocytosis inhibitors could not impede virus replication once the virus had entered host cells. This suggests that occludin internalization by macropinocytosis or a macropinocytosis-like process is involved in the virus entry events. Immunofluorescence confocal microscopy showed that PEDV was trapped at cellular junctional regions upon macropinocytosis inhibitor treatment, indicating that occludin may serve as a scaffold in the vicinity of virus entry. Collectively, these data show that occludin plays an essential role in PEDV infection during late entry events. Our observation may provide novel insights into PEDV infection and related pathogenesis.IMPORTANCE Tight junctions are highly specialized membrane domains whose main function is to attach adjacent cells to each other, thereby forming intercellular seals. Here we investigate, for the first time, the role of the tight junction protein occludin in PEDV infection. We observed that PEDV infection induced the internalization of occludin. By using genetic modification methods, we demonstrate that occludin plays an essential role in PEDV infection. Moreover, PEDV entry and occludin internalization seem to be closely coupled. Our findings reveal a new mechanism of PEDV infection.

Porcine Epidemic Diarrhea Virus Infection Inhibits Interferon Signaling by Targeted Degradation of STAT1.

UNLABELLED: Porcine epidemic diarrhea virus (PEDV) is a worldwide-distributed alphacoronavirus, but the pathogenesis of PEDV infection is not fully characterized. During virus infection, type I interferon (IFN) is a key mediator of innate antiviral responses. Most coronaviruses develop some strategy for at least partially circumventing the IFN response by limiting the production of IFN and by delaying the activation of the IFN response. However, the molecular mechanisms by which PEDV antagonizes the antiviral effects of interferon have not been fully characterized. Especially, how PEDV impacts IFN signaling components has yet to be elucidated. In this study, we observed that PEDV was relatively resistant to treatment with type I IFN. Western blot analysis showed that STAT1 expression was markedly reduced in PEDV-infected cells and that this reduction was not due to inhibition of STAT1 transcription. STAT1 downregulation was blocked by a proteasome inhibitor but not by an autophagy inhibitor, strongly implicating the ubiquitin-proteasome targeting degradation system. Since PEDV infection-induced STAT1 degradation was evident in cells pretreated with the general tyrosine kinase inhibitor, we conclude that STAT1 degradation is independent of the IFN signaling pathway. Furthermore, we report that PEDV-induced STAT1 degradation inhibits IFN-α signal transduction pathways. Pharmacological inhibition of STAT1 degradation rescued the ability of the host to suppress virus replication. Collectively, these data show that PEDV is capable of subverting the type I interferon response by inducing STAT1 degradation. IMPORTANCE: In this study, we show that PEDV is resistant to the antiviral effect of IFN. The molecular mechanism is the degradation of STAT1 by PEDV infection in a proteasome-dependent manner. This PEDV infection-induced STAT1 degradation contributes to PEDV replication. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response.

Elevated plasma-soluble CD16 levels in porcine reproductive and respiratory syndrome virus-infected pigs: correlation with ADAM17-mediated shedding.

Soluble CD16 (sCD16) is closely correlated with chronic diseases in humans. Here, plasma sCD16 levels in pigs were increased by infection with porcine reproductive and respiratory syndrome virus (PRRSV) but not with porcine epidemic diarrhea virus, porcine circovirus type 2 and pseudorabies virus. Of interest, PRRSV attached to blood neutrophils and reduced surface CD16 expression on neutrophils. In vitro data confirmed that PRRSV caused CD16 shedding in neutrophils. Further analyses revealed that ADAM17 was involved in porcine CD16 shedding. Thus, our findings suggest that increase in sCD16 levels may be an indicator of PRRSV infection.

Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection.

The immunological effect of porcine reproductive and respiratory syndrome disease virus (PRRSV) vaccines is thought to be influenced by a variety of host factors, in which antibody-dependent enhancement (ADE) of infection is one crucial factor. Here, we assessed the mechanism of ADE of PRRSV infection. First, we found that subneutralizing serum could induce ADE of PRRSV infection in porcine alveolar macrophages (PAMs). Quantitative PCR, Western blotting and flow cytometry revealed that CD16 is the most abundant Fcγ receptor (FcγR) expressed on the surface of PAMs; thus, the role of CD16 in ADE of PRRSV infection was examined in PAMs. By using functional blocking antibodies, we demonstrated that CD16 is involved in enhanced virus production in PRRSV-antibody immune complex-infected PAMs. Because PAMs co-express different FcγR isoforms, we evaluated the effects of CD16 in FcγR-non-bearing cells by transfection. Using these engineered cells, we found that CD16 could specifically bind to the PRRSV-antibody immune complex and subsequently mediate internalization of the virus, resulting in the generation of progeny virus. We also showed that efficient expression of CD16 required association of the FcR γ-chain. Together, our findings provide significant new insights into PRRSV infection, which can be enhanced by CD16-mediated PRRSV-antibody immune complexes. This CD16-mediated ADE may induce a shift in PRRSV tropism towards CD16-expressing cells, distributing virus to more organs during virus infection.

Modulation of CD163 expression by metalloprotease ADAM17 regulates porcine reproductive and respiratory syndrome virus entry.

UNLABELLED: As a consequence of their effects on ectodomain shedding, members of the A disintegrin and metalloprotease (ADAM) family have been implicated in the control of various cellular processes. Although ADAM family members are also involved in cancer, inflammation, and other pathologies, it is unclear whether they affect porcine reproductive and respiratory syndrome virus (PRRSV) infection. Here, we demonstrate for the first time that inhibition of ADAM17 enhances PRRSV entry in Marc-145 and porcine alveolar macrophages (PAMs). We also demonstrate that the inhibition of ADAM17 upregulates membrane CD163 expression, a putative PRRSV receptor that is exogenously expressed in BHK-21 and endogenously expressed in Marc-145 and PAMs. Furthermore, overexpression of ADAM17 induced downregulation of CD163 expression and a reduction in PRRSV infection, whereas ablation of ADAM17 expression using specific small interfering RNA resulted in upregulation of CD163 expression with a corresponding increase in PRRSV infection. These ADAM17-mediated effects were confirmed with PRRSV nonpermissive BHK-21 cells transfected with CD163 cDNA. Overall, these findings indicate that ADAM17 downregulates CD163 expression and hinders PRRSV entry. Hence, downregulation of ADAM17 particular substrates may be an additional component of the anti-infection defenses. IMPORTANCE: ADAM17 is one of the important membrane-associated metalloproteases that mediate various cellular events, as well as inflammation, cancer, and other pathologies. Here, we investigate for the first time the role of the metalloprotease ADAM17 in PRRSV infection. By using inhibitor and genetic modification methods, we demonstrate that ADAM17 negatively regulate PRRSV entry by regulating its substrate(s). More specifically, ADAM 17 mediates the downregulation of the PRRSV cellular receptor CD163. The reduction in CD163 expression represents another component of the anti-infection response initiated by ADAM17.

Purification and partial characterization of a thermostable antimicrobial protein from Bacillus subtilis FB123.

Antimicrobial proteins/peptides have attracted much attention because of their potential use in the industrial setting. In the present study, a thermostable antimicrobial protein (BSAMP) was purified from the culture supernatant of Bacillus subtilis FB123 by ammonium sulfate precipitation, gel chromatography on Sephacryl S-200 High Resolution, and ion exchange chromatography on DEAE Sepharose Fast Flow column. The molecular weight of the purified BSAMP was 54 kDa, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis both in the absence and presence of ß-mercaptoethanol. Its isoelectric point was determined to be 5.24 by isoelectric focusing electrophoresis. Periodic acid-Schiff staining revealed BSAMP to be a glycoprotein. Maximum activity was obtained at pH 6.0, with over 79% maximum activity retained at pH 3.0-5.0 and pH 7.0-9.0, respectively. BSAMP was shown to be highly thermostable, as its activity did not change obviously after treatment at 100 °C. However, it was partially sensitive to papain, trypsin, and alkali proteases. Finally, the bacterial protein exhibited broad-spectrum antimicrobial activity against several pathogenic organisms. These findings suggested that BSAMP should be further developed as a natural antibacterial agent for disease prevention in aquiculture and agriculture.

Facile Preparation of Cellulose Beads with Tunable Graded Pores and High Mechanical Strength.

Cellulose-based hierarchical porous beads exhibit significant application potential in adsorption and separation systems due to their degradation and biocompatibility. However, the current fabrications of cellulose beads show poor mechanical properties and a difficult-to-regulate hierarchical porous structure, reducing their lifespan of use and limiting their application in fine separation. Here, we reported the facile creep-drop method to prepare cellulose beads that enabled systemic regulation of the macro-size, micropore structures, and mechanical properties by optimizing injection nozzle diameter, the composition of the coagulation bath, the temperature of the coagulation bath, and cellulose concentration. Notably, during the molding process, the H2SO4-Na2SO4 composite solidification bath endowed cellulose beads with a dense shell layer and a loose core layer, which achieved the integration of mechanical properties and high porosity. The cellulose beads exhibited high porosity (93.38-96.18%) and high sphericity (86.78-94.44%) by modulating the shell thickness of the cellulose beads. In particular, the cellulose beads exhibited excellent mechanical properties with a high compressive strength of 544.24 kPa at a 5% cellulose concentration. It is expected that these cellulose beads with tunable microstructures can realize their potential for applications in the fields of wastewater treatment, chemical engineering, bioengineering, medicine, and pharmaceuticals.

Farnesane sesquiterpenoids from Rubus delavayi and their anti-Trichinella spiralis activities.

Two new farnesane sesquiterpenoid glycosides, rubusdelosides A and B (1 and 4), together with five known farnesane sesquiterpenoids (2, 3, and 5-7), and two known meroterpenoids (8 and 9), were isolated from water extract of the herbs of R. delavayi. Their structures were identified by the comprehensive analyses of physicochemical properties and spectroscopic data (NMR and HR-ESI-MS). Compounds 1-8 showed moderate in vivo anti-T. spiralis activities.

Genetic predisposition to papillary thyroid carcinoma is mediated by a long non-coding RNA TINCR enhancer polymorphism.

Single nucleotide polymorphisms (SNPs) in the enhancer region have been demonstrated to confer to altered enhancer activities, aberrant gene expression, and cancer susceptibility. In this study, we aimed to examine the association between an SNP, rs8101923, within terminal differentiation-induced non-coding RNA (TINCR) and the risk of papillary thyroid carcinoma (PTC). Blood samples from 559 patients with PTC and 445 healthy individuals were collected. The rs8101923 was genotyped by using polymerase chain reaction-restriction fragment length polymorphism assay. The impact of the rs8101923 on TINCR expression and enhancer activity was evaluated by quantitative real-time PCR and dual-luciferase reporter assay. The binding of AP-2α to TINCR enhancer was determined by chromatin immunoprecipitation. The rs8101923 G allele was significantly associated with a higher risk of PTC (adjusted OR = 1.37; 95% CI: 1.15-1.64). Mechanistically, the rs8101923 was related to increased transcriptional levels and enhancer activities (P < 0.05). Transcription factor AP-2α binds to the enhancer region of TINCR containing the rs8101923 locus, and promotes cell proliferation in PTC. These findings suggest the rs8101923 as a risk factor in the pathogenesis of PTC, which provides evidence for explaining the mechanism of the rs8101923 risk allele predisposing to PTC.

Adipsin of the Alternative Complement Pathway Is a Potential Predictor for Preeclampsia in Early Pregnancy.

Objective: The concentrations of complement proteins (adipsin, C3a, and C5a) and soluble endoglin (sENG) in the plasma were measured in this study, and their value as early-pregnancy predictors and potential diagnostic marker of preeclampsia was assessed, respectively. Experimental Design: Plasma samples were obtained from healthy and preeclampsia pregnant women before delivery for a cross-sectional study. Plasma samples were collected from healthy and preeclampsia pregnant women throughout pregnancy and postpartum for a follow-up study. Enzyme-linked immunosorbent assays were used to detect plasma levels of several complement proteins (adipsin, C3a, and C5a) and sENG. Results: The plasma levels of adipsin, C5a, and sENG were significantly increased before delivery in pregnant women with preeclampsia. During pregnancy, the plasma adipsin, C5a, and sENG levels were increased from the third trimester in healthy pregnant women; plasma adipsin levels remained stable after delivery, while C3a levels increased in the second trimester and remained stable afterward. Furthermore, levels of adipsin, C5a, and sENG were higher in preeclampsia patients at different stages of pregnancy; the C3a level presents a similar change and no difference was found in the third trimester. In the first trimester, receiver-operating curve (ROC) curve analysis showed that adipsin (AUC, 0.83 ± 0.06, P=0.001) and sENG (AUC, 0.74 ± 0.09, P=0.021) presented high value as predictors of early pregnancy. Conclusions: Adipsin is likely a novel plasma biomarker to monitor the increased risk of preeclampsia in early pregnancy. Moreover, the increased plasma levels of adipsin, C5a, and sENG before delivery may be associated with preeclampsia.

N6-methyladenosine RNA modification: A promising regulator in central nervous system injury.

In addition to DNA methylation, reversible epigenetic modification occurring in RNA has been discovered recently. The most abundant type of RNA methylation is N6-methyladenosine (m6A) modification, which is dynamically regulated by methylases ("writers"), demethylases ("erasers") and m6A-binding proteins ("readers"). As an essential posttranscriptional regulator, m6A can control mRNA splicing, processing, stability, export and translation. Recent studies have revealed that m6A modification has the strongest tissue specificity for brain tissue and plays crucial roles in central nervous system (CNS) injures by affecting its downstream target genes or non-coding RNAs. This review focuses on the expression and function of m6A regulatory proteins in CNS trauma in vitro and in vivo. We also highlight the latest insights into the molecular mechanisms of pathological damage in the CNS. Understanding m6A dynamics, functions, and machinery will yield an opportunity for designing and developing novel therapeutic agents for CNS injuries.

Robust, sustainable cellulose composite aerogels with outstanding flame retardancy and thermal insulation.

Robust and sustainable cellulose composite aerogels were prepared by incorporating MgAl-layered double hydroxide (MgAl-LDH) as green nanofillers and flame retardants. Two series of aerogels combining MgAl-CO3 LDH (MA-C) and MgAl-H2PO4 LDH (MA-P) were achieved, in which both MA-C and MA-P were uniformly dispersed in cellulose substances. The cellulose composite aerogels with 1.8 wt% of MA-C (denoted as CAC) and MA-P (denoted as CAP) displayed excellent mechanical properties, increased by 2.6 and 2.8 times compared with neat cellulose aerogels (CA), respectively. The peak of heat release rate (PHRR) of CAC and CAP reduced by 41 % and 50 % compared with the neat one, respectively, demonstrating the outstanding flame retardancy. The reduction in smoke production ratio (SPR) was 79 % for CAC and 75 % for CAP, respectively, indicating enhanced smoke suppression performance. Therefore, the high performance flame-retardant cellulose composite aerogels exhibit an application prospect in green advanced engineering field.

A New Antimalarial Noreudesmane Sesquiterpenoid from Dobinea delavayi.

One previously undescribed angeloylated noreudesmane sesquiterpenoid, dobinin O (1), along with four known eudesmane sesquiterpenoids (2-5) were isolated from the peeled roots of Dobinea delavayi. Their structures were elucidated by extensive spectroscopic data analyses. In addition, compound 1 exhibited moderate antimalarial activity against Plasmodium yoelii BY265RFP with the inhibition ratio of 17.8 ± 13.3% at the dose of 30 mg/kg/day.