Berbamine inhibits porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) is a significant contributor to high mortality rates in piglets, posing a serious threat to the global pig industry. The absence of effective control measures and vaccines against circulating PEDV variants underscores the urgent need for new treatment strategies. In this study, we screened a compound library and identified Berbamine as a potential anti-PEDV drug through molecular docking techniques. In vitro experiments demonstrated that Berbamine significantly inhibits PEDV proliferation in Vero and IPEC-J2 cells in a dose-dependent manner, primarily targeting the replication phase of the PEDV life cycle. Furthermore, in vivo experiments revealed that Berbamine effectively alleviates intestinal damage caused by PEDV infection in piglets, leading to a reduction in viral load and cytokine levels, including IL-6, IL-8, IL-1ß, and TNF-α. Additionally, autodock predictions indicate that viral non-structural proteins 3 and 16 (Nsp3 and Nsp16) are potential targets for Berbamine. Consequently, Berbamine holds significant promise for application and development as an antiviral treatment against PEDV.

Evidence of Higher Order Phonon Anharmonicity in Gray Arsenic Crystal.

Phonons play a key role in the heat transport process of quantum materials. The understanding of thermal behaviors of phonons will be beneficial for designing modern electronic devices. In this study, we utilize specific heat, Raman spectroscopy, and first-principles calculations combined with the phonon Boltzmann transport equation to explore the thermal transport of gray arsenic. Our specific heat data indicate the presence of the phonon anharmonicity at high temperature. This is further supported by temperature-dependent Raman data showing evident phonon softening and line width broadening. More interestingly, from the analysis of temperature-dependent Raman modes, we found that the four-phonon scattering process is indispensable for interpreting the line width broadening at high temperatures. Moreover, we evaluate the importance of the four-phonon scattering process in the heat transport of gray arsenic using the moment tensor potential method. Our work sheds light on the importance of a higher order phonon scattering process in heat transport of the materials with moderate thermal conductivity.

Effect of Negative Pulse on the Stability of Black Electrolytes for Magnesium Alloy Microarc Oxidation.

The correlation between negative pulse and the black electrolyte properties of magnesium alloy micro-arc oxidation and the treated area was investigated by introducing a negative pulse electric field. The physical phase composition, microstructure, elemental distribution, and content of the coating were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The results showed that the introduction of negative pulses favored the generation of MgO and MgSiO3 contents in the coatings, and an increase in the MgO phase was found in the coatings formed in the failed electrolytes; the microporous size and microcracks of the coatings were gradually and significantly reduced; the average consumption of Cu ions was 0.0453 g/L·dm2, which is only 26% of that in the unipolar condition; the introduction of the negative pulses significantly improved the "anomalous consumption" of Cu ions. The introduction of negative pulse can significantly improve the "abnormal consumption" of copper ions, which is attributed to the change in the electric field by negative pulse, which makes the cathode-enriched Cu ions migrate to the anode and reduces the reduction and precipitation of Cu ions at the cathode.

Study of Coating Growth Direction of 6061 Aluminum Alloy in Soft Spark Discharge of Plasma Electrolytic Oxidation.

Conventional plasma electrolytic oxidation treatments produce oxide coatings with micron-scale discharge pores, resulting in insulation and wear and corrosion resistance far below that expected of highly dense Al2O3 coatings. The introduction of cathodic polarization during the plasma electrolytic oxidation process, especially when the applied cathode-to-anode current ratio (Rpn) is greater than 1, triggers a unique plasma discharge phenomenon known as "soft sparking". The soft spark discharge mode significantly improves the densification of the anode ceramic layer and facilitates the formation of the high-temperature α-Al2O3 phase within the coating. Although the soft spark discharge phenomenon has been known for a long time, the growth behavior of the coating under its discharge mode still needs to be studied and improved. In this paper, the growth behavior of the coating before and after soft spark discharge is investigated with the help of the micro-morphology, phase composition and element distribution of a homemade fixture. The results show that the ceramic layer grows mainly along the oxide-electrolyte direction before the soft spark discharge transformation; after the soft spark discharge, the ceramic layer grows along the oxide-substrate direction. It was also unexpectedly found that, under soft spark discharge, the silicon element only exists on the outside of the coating, which is caused by the large size and slow migration of SiO32-, which can only enter the ceramic layer and participate in the reaction through the discharge channel generated by the strong discharge. In addition, it was also found that the relative phase content of α-Al2O3 in the coating increased from 0.487 to 0.634 after 10 min of rotary spark discharge, which is an increase of 30.2% compared with that before the soft spark discharge transition. On the other hand, the relative phase content of α-Al2O3 in the coating decreased from 0.487 to 0.313 after 20 min of transfer spark discharge, which was a 55.6% decrease compared to that before the soft spark discharge transformation.

Comparative efficacy of five approved Janus kinase inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis: a systematic review and network meta-analysis of randomized controlled trials.

Background: The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are insensitive or under-responsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). But there was no recommendation for which one was preferred in five currently approved JAK inhibitors. The objective of this network meta-analysis study was to evaluate the efficacy of five JAK inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis. Methods: The randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. The control group included placebo or csDMARD. Outcome indicators included American College of Rheumatology 20% response (ACR20), ACR50, ACR70 and the percentage of patients achieving 28-joint disease activity score using C-reactive protein (DAS28(CRP))<2.6 at 12 weeks and 24 weeks. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95%CI) as effect sizes to analyze the statistics. Results: This study included thirty-six RCTs with 16,713 patients. All JAK inhibitors were more effective than placebo in ACR20 (RRs ranging between 1.74 and 3.08), ACR50 (RRs ranging between 2.02 and 7.47), ACR70 (RRs ranging between 2.68 and 18.13), DAS28(CRP) < 2.6 (RRs ranging between 2.70 and 7.09) at 12 weeks. Upadacitinib 30 mg and upadacitinib 15 mg showed relatively good efficacy according to their relative SUCRA ranking. All JAK inhibitors were more effective than csDMARD or placebo in ACR20 (RRs ranging between 1.16 and 1.86), ACR50 (RRs ranging between 1.69 and 2.84), ACR70 (RRs ranging between 1.50 and 4.47), DAS28(CRP) < 2.6 (RRs ranging between 2.28 and 7.56) at 24 weeks. Upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD showed relatively good efficacy according to their relative SUCRA ranking. The safety analysis results such as serious infection, malignancy, major adverse cardiovascular event (MACE), and venous thromboembolic events (VTE) showed no statistical difference. Conclusion: This NMA study indicated that all JAK inhibitors performed better than placebo. Based on the results of this study, upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD were recommended treatment options with relatively good efficacy and safety. However, attention should be paid to monitoring the occurrence of adverse events in high-risk RA patients with medication. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation.

Up-regulated novel-miR-17 promotes hypothermic reperfusion arrhythmias by negatively targeting Gja1 and mediating activation of the PKC/c-Jun signaling pathway.

BACKGROUND: Hypothermic ischemia-reperfusion arrhythmia is a common complication of cardiothoracic surgery under cardiopulmonary bypass, but few studies have focused on this type of arrhythmia. Our prior study discovered reduced myocardial Cx43 protein levels may be linked to hypothermic reperfusion arrhythmias. However, more detailed molecular mechanism research is required. METHOD: The microRNA and mRNA expression levels in myocardial tissues were detected by real-time quantitative PCR (RT-qPCR). Besides, the occurrence of hypothermic reperfusion arrhythmias and changes in myocardial electrical conduction were assessed by electrocardiography and ventricular epicardial activation mapping. Furthermore, bioinformatics analysis, applying antagonists of miRNA, western blotting, immunohistochemistry, a dual luciferase assay, and pearson correlation analysis were performed to investigate the underlying molecular mechanisms. RESULTS: The expression level of novel-miR-17 was up-regulated in hypothermic ischemia-reperfusion myocardial tissues. Inhibition of novel-miR-17 upregulation ameliorated cardiomyocyte edema, reduced apoptosis, increased myocardial electrical conduction velocity, and shortened the duration of reperfusion arrhythmias. Mechanistic studies showed that novel-miR-17 reduced the expression of Cx43 by directly targeting Gja1 while mediating the activation of the PKC/c-Jun signaling pathway. CONCLUSION: Up-regulated novel-miR-17 is a newly discovered pro-arrhythmic microRNA that may serve as a potential therapeutic target and biomarker for hypothermic reperfusion arrhythmias.

Dynamic Molecular Interphases Regulated by Trace Dual Electrolyte Additives for Ultralong-Lifespan and Dendrite-Free Zinc Metal Anode.

Metallic zinc is a promising anode material for rechargeable aqueous multivalent metal-ion batteries due to its high capacity and low cost. However, the practical use is always beset by severe dendrite growth and parasitic side reactions occurring at anode/electrolyte interface. Here we demonstrate dynamic molecular interphases caused by trace dual electrolyte additives of D-mannose and sodium lignosulfonate for ultralong-lifespan and dendrite-free zinc anode. Triggered by plating and stripping electric fields, the D-mannose and lignosulfonate species are alternately and reversibly (de-)adsorbed on Zn metal, respectively, to accelerate Zn2+ transportation for uniform Zn nucleation and deposition and inhibit side reactions for high Coulombic efficiency. As a result, Zn anode in such dual-additive electrolyte exhibits highly reversible and dendrite-free Zn stripping/plating behaviors for >6400 hours at 1 mA cm-2, which enables long-term cycling stability of Zn||ZnxMnO2 full cell for more than 2000 cycles.

Binder-Free MOF-Based and MOF-Derived Nanoarrays for Flexible Electrochemical Energy Storage: Progress and Perspectives.

The fast development of Internet of Things and the rapid advent of next-generation versatile wearable electronics require cost-effective and highly-efficient electroactive materials for flexible electrochemical energy storage devices. Among various electroactive materials, binder-free nanostructured arrays have attracted widespread attention. Featured with growing on a conductive and flexible substrate without using inactive and insulating binders, binder-free 3D nanoarray electrodes facilitate fast electron/ion transportation and rapid reaction kinetics with more exposed active sites, maintain structure integrity of electrodes even under bending or twisted conditions, readily release generated joule heat during charge/discharge cycles and achieve enhanced gravimetric capacity of the whole device. Binder-free metal-organic framework (MOF) nanoarrays and/or MOF-derived nanoarrays with high surface area and unique porous structure have emerged with great potential in energy storage field and been extensively exploited in recent years. In this review, common substrates used for binder-free nanoarrays are compared and discussed. Various MOF-based and MOF-derived nanoarrays, including metal oxides, sulfides, selenides, nitrides, phosphides and nitrogen-doped carbons, are surveyed and their electrochemical performance along with their applications in flexible energy storage are analyzed and overviewed. In addition, key technical issues and outlooks on future development of MOF-based and MOF-derived nanoarrays toward flexible energy storage are also offered.

Magnetic susceptibility and R2*-based texture analysis for evaluating liver fibrosis in chronic liver disease.

PURPOSE: To explore potential feasibility of texture features in magnetic susceptibility and R2* maps for evaluating liver fibrosis. METHODS: Thirty-one patients (median age 46 years; 22 male) with chronic liver disease were prospectively recruited and underwent magnetic resonance imaging (MRI), blood tests, and liver biopsy. Susceptibility and R2* maps were obtained using a 3-dimensional volumetric interpolated breath-hold examination sequence with a 3T MRI scanner. Texture features, including histogram, gray-level co-occurrence matrix (GLCM), gray-level dependence matrix (GLDM), gray-level run length matrix (GLRLM), gray-level size zone matrix (GLSZM), and neighboring gray tone difference matrix (NGTDM) features, were extracted. Texture features and blood test results of non-significant (Ishak-F < 3) and significant fibrosis patients (Ishak-F ≥ 3) were compared, and correlations with Ishak-F stages were analyzed. Areas under the curve (AUCs) were calculated to determine the efficacy for evaluating liver fibrosis. RESULTS: Nine texture features of susceptibility maps and 19 features of R2* maps were significantly different between non-significant and significant fibrosis groups (all P < 0.05). Large dependence high gray-level emphasis (LDHGLE) of GLDM and long run high gray-level emphasis (LRHGLE) of GLRLM in R2* maps showed significantly negative and good correlations with Ishak-F stages (r = -0.616, P < 0.001; r = -0.637, P < 0.001). Busyness (NGTDM) in susceptibility maps, LDHGLE of GLDM and LRHGLE of GLRLM in R2* maps yield the highest AUCs (AUC = 0.786, P = 0.007; AUC = 0.807, P = 0.004; AUC = 0.819, P = 0.003). CONCLUSION: Texture characteristics of susceptibility and R2* maps revealed possible staging values for liver fibrosis. Susceptibility and R2*-based texture analysis may be a useful and noninvasive method for staging liver fibrosis.

Effects of exogenous melatonin on growth and physiological characteristics of Agropyron mongolicum seedlings under drought stress.

To clarify the alleviation effect of exogenous melatonin (MT) on Agropyron mongolicum under drought stress, we examined the response of A. mongolicum 'Yanchi' seedlings to simulated drought stress with polyethylene glycol 6000 (PEG-6000), by investigating the effects of exogenous addition of different concentrations (0, 1, 10, 50, 100, 150 and 200 mg·L-1) of MT on seedlings growth and physiological characteristics under drought stress. The results showed that drought stress significantly inhibited the growth of A. mongolicum seedlings, and that exogenous addition of different concentrations of MT could alleviate the growth inhibition caused by drought stress, with the strongest mitigation effect observed at MT concentration of 100 mg·L-1. Compared with the drought stress treatment alone, exogenous addition of 100 mg·L-1 MT under drought stress increased plant height, aboveground dry weight, and leaf relative water content by 58.2%, 121.2% and 48.1%. The contents of chlorophyll a, chlorophyll b, carotenoids increased by 48.7%, 80.8% and 38.3%, superoxide dismutase, peroxidase and root activity increased by 12.6%, 33.9% and 39.1%, and the contents of ascorbic acid and glutathione increased by 19.5% and 18.3%, respectively. The contents of proline, soluble sugar and soluble protein were increased by 16.2%, 32.6% and 14.3%, while that of malondialdehyde, hydrogen peroxide and superoxide anion radical were decreased by 45.8%, 65.8% and 30.8%, respectively. In summary, exogenous addition of 100 mg·L-1 MT could improve drought tolerance of A. mongolicum seedlings by promoting growth, enhancing antioxidant capacity, increasing the content of osmoregulation substances, inhibiting the excessive production of reactive oxygen, and reducing membrane peroxide level.

The potential roles of stress-induced phosphoprotein 1 and connexin 43 in rats with reperfusion arrhythmia.

OBJECTIVE: Connexin 43 (Cx43) is a critical gene for maintaining myocardial homeostasis. Interestingly, Cx43 and stress-induced phosphoprotein 1 (STIP1) were recorded to be lowly expressed in ischemia/reperfusion (I/R). However, their impacts on reperfusion arrhythmia (RA) remain to be explored. Our study aimed to find out the related underlying mechanisms. METHODS: After the establishment of an isolated heart model through Langendorff perfusion, the heart rate, conduction activation time, conduction velocity, and conduction direction of the left ventricle were evaluated, along with the apoptotic rate detection in the collected myocardial tissues. After the construction of a hypoxia/reoxygenation (H/R)-induced cellular model, cell apoptosis, intercellular communication, cell viability, and the content of reactive oxygen species, superoxide dismutase, malondialdehyde, and lactic dehydrogenase were measured. The expression of Cx43 and STIP1 was determined in both rat heart and cell models. The bindings of STIP3 and Cx43 to  heat shock protein 90 (HSP90) and heat shock protein 70 (HSP70) were verified. RESULTS: Relative to the corresponding controls, Cx43 and STIP1 were decreased in myocardial tissues of RA rats and H/R-stimulated H9C2 cells, where Cx43-binding HSP70 and HSP90 were respectively increased and decreased, and ubiquitination level of Cx43 was enhanced. STIP1 overexpression promoted protein expression of Cx43, intercellular communication, and cell viability, and reduced cell apoptosis and oxidative stress in H/R-stimulated H9C2 cells. CONCLUSION: STIP1 promoted Cx43 expression to improve intercellular communication and reduce oxidative stress in H/R-stimulated H9C2 cells.

[Relationship between coronavirus disease 2019 vaccination and the risk of immune thrombocytopenia]. / æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“ç–«è‹—æŽ¥ç§ä¸Žå ç–«æ€§è¡€å°æ¿å‡å°‘ç—‡å‘ç”Ÿé£Žé™©çš„å ³ç³».

OBJECTIVES: To study the relationship between coronavirus disease 2019 (COVID-19) vaccination and the risk of immune thrombocytopenia (ITP). METHODS: A retrospective analysis was conducted on children aged 3-17 years with newly diagnosed ITP who were hospitalized in Children's Hospital Affiliated to Zhengzhou University from November 2021 to December 2022. Clinical data and COVID-19 vaccination status were compared among three groups: ITP patients vaccinated within 12 weeks before onset, vaccinated more than 12 weeks before onset, and unvaccinated. Changes in serum immunoglobulin and complement levels were analyzed among five groups: ITP patients vaccinated <4 weeks before onset, 4-<8 weeks before onset, 8-<12 weeks before onset, ≥12 weeks before onset, and unvaccinated. A case-control design was used to estimate the risk of ITP: 387 children aged 3-17 years with fractures hospitalized during the same period in the emergency department of the hospital were selected as the control group, and the exposure to COVID-19 vaccination within 12, 8, and 4 weeks before onset in ITP children was compared to estimate the risk of ITP. RESULTS: Among 129 ITP children, there were no statistically significant differences in age, gender, rate of preceding infections, absolute platelet count at initial diagnosis, absolute lymphocyte count at initial diagnosis, bleeding score, positive anti-nuclear antibody rate, absolute platelet count after 4 days of treatment, recurrence rate, and proportion of patients with disease duration ≥3 months among the three groups vaccinated within 12 weeks before onset, vaccinated more than 12 weeks before onset, and unvaccinated (P>0.05). There was a statistically significant difference in serum immunoglobulin G, immunoglobulin A, and complement component 3 levels among the groups vaccinated <4 weeks, 4-<8 weeks, 8-<12 weeks, and ≥12 weeks before onset, and unvaccinated (P<0.05). The risk estimation results showed that COVID-19 vaccination within 12 weeks, 8 weeks, and 4 weeks before onset did not increase the risk of ITP (P>0.05). CONCLUSIONS: COVID-19 vaccination does not increase the risk of ITP.

Imaging feature-based clustering of financial time series.

Timeseries representation underpin our ability to understand and predict the change of natural system. Series are often predicated on our choice of highly redundant factors, and in fact, the system is driven by a much smaller set of latent intrinsic keys. It means that a better representation of data makes points in phase space clearly for researchers. Specially, a 2D structure of timeseries could combine the trend and correlation characters of different periods in timeseries together, which provides more clear information for top tasks. In this work, the effectiveness of 2D structure of timeseries is investigated in clustering tasks. There are 4 kinds of methods that the Recurrent Plot (RP), the Gramian Angular Summation Field (GASF), the Gramian Angular Differential Field (GADF) and the Markov Transition Field (MTF) have been adopted in the analysis. By classifying the CSI300 and S&P500 indexes, we found that the RP imaging series are valid in recognizing abnormal fluctuations of financial timeseries, as the silhouette values of clusters are over 0.6 to 1. Compared with segment methods, the 2D models have the lowest instability value of 0. It verifies that the SIFT features of RP images take advantage of the volatility of financial series for clustering tasks.

ELL associated factor 2 is a potential diagnostic and prognostic indicator: evidence from the in silico and in vitro experiments.

Due to the lack of sensitive biomarkers, cancer disease kill 9.6 million individuals each year around the globe. The present study aimed to explore the association between ELL Associated Factor 2 (EAF2) expression and its diagnostic and prognostic landscape across different human cancers using an in silico and in vitro approach. To achieve the defined goals of this study, we used the following online sources: UALCAN, KM plotter, TNMplot, cBioPortal, STRING, DAVID, MuTarget, Cytoscape, and CTD. In addition to this, we also used additional The Cancer Genome Atlas (TCGA) datasets via TIMER2, GENT2, and GEPIA to confirm the expression of EAF2 on additional cohorts. Finally, we performed RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) techniques-based analysis using A549, ABC-1, EBC-1, LK-2 lung cancer cell lines, and MRC-9 normal control lung cell line for further validation of the results. On balance, EAF2 was elevated in 19 types of human cancers and its up-regulation was significantly correlated with shorter overall survival (OS), relapse-free survival (RFS), and metastasis in Liver Hepatocellular Carcinoma (LIHC) and Lung Squamous Cell Carcinoma (LUSC) patients. We further evaluated that EAF2 expression was also elevated across LIHC and LUSC patients belonging to different clinicopathological features. Through pathway analysis, EAF2 associations were observed with four important pathways. Moreover, some worth noticing correlations were also documented between EAF2 expression and its promoter methylation level, genetic alterations, other mutant genes, tumor purity, and different immune cells infiltration. The higher EAF2 expression contributes significantly to the tumorigenesis and metastasis of LIHC and LUSC. Therefore, it can be used as a common biomarker in these cancers.

Sevoflurane Improves Ventricular Conduction by Exosomes Derived from Rat Cardiac Fibroblasts After Hypothermic Global Ischemia-Reperfusion Injury.

Purpose: This study investigated the effect of exosomes derived from sevoflurane-treated cardiac fibroblasts (Sev-CFs-Exo) on reperfusion arrhythmias (RA), ventricular conduction, and myocardial ischemia-reperfusion injury (MIRI). Methods: Primary cardiac fibroblasts (CFs) were isolated from the hearts of neonatal rats and identified by morphology and immunofluorescence. Exosomes were isolated from CFs at passages 2-3 after they had been treated with 2.5% sevoflurane for an hour and cultivated for 24-48 hours. The control group was CFs that did not receive any treatment. The hypothermic global ischemia-reperfusion injury model was established using the Langendorff perfusion technique following injection with exosomes through the caudal vein. Multi-electrode array (MEA) mapping was used to investigate the changes in RA and ventricular conduction in isolated hearts. Western blots and immunofluorescence were used to examine the relative expression and location of connexin 43 (Cx43). In addition, the MIRI was evaluated with triphenyl tetrazolium chloride and Hematoxylin-Eosin staining. Results: The primary CFs had a variety of morphologies, no spontaneous pulsation, and were vimentin-positive, which confirmed their successful isolation. Sev-CFs-Exo increased the heart rate (HR) at reperfusion for 15 minutes (T2) and 30 minutes (T3) and lowered the score and duration of RA and the time for restoration of heartbeat in reperfusion. Meanwhile, Sev-CFs-Exo increased conduction velocity (CV), decreased absolute inhomogeneity (P5-95) and inhomogeneity index (P5-95/P50) at T2 and T3, as well as promoted the recovery of HR, CV, P5-95 and P5-95/P50 after hypothermic global ischemia-reperfusion injury. Furthermore, Sev-CFs-Exo raised expression and reduced lateralization of Cx43, and improved myocardial infarct sizes and cellular necrosis. However, while cardiac fibroblast-derived exosomes (CFs-Exo) showed similar cardioprotective effects, the outcomes were not as significant. Conclusion: Sevoflurane reduces the risk of RA and improves ventricular conduction and MIRI by CFs-Exo, and this may be driven by the expression and location of Cx43.

Molecular chaperones HSP40, HSP70, STIP1, and HSP90 are involved in stabilization of Cx43.

To investigate the involvement of stress induced phosphoprotein 1 (STIP1), heat shock protein (HSP) 70, and HSP90 in ubiquitination of connexin 43 (Cx43) in rat H9c2 cardiomyocytes. Co-immunoprecipitation was used to detect protein-protein interactions and Cx43 ubiquitination. Immunofluorescence was used for protein co-localization. The protein binding, Cx43 protein expression, and Cx43 ubiquitination were reanalyzed in H9c2 cells with modified STIP1 and/or HSP90 expression. STIP1 bound to HSP70 and HSP90, and Cx43 bound to HSP40, HSP70, and HSP90 in normal H9c2 cardiomyocytes. Overexpression of STIP1 promoted the transition of Cx43-HSP70 to Cx43-HSP90 and inhibited Cx43 ubiquitination; knockdown of STIP1 resulted in the opposite effects. Inhibition of HSP90 counteracted the inhibitory effect of STIP1 overexpression on Cx43 ubiquitination. STIP1 suppresses Cx43 ubiquitination in H9c2 cardiomyocytes by promoting the transition of Cx43-HSP70 to Cx43-HSP90.

TEAD4 predicts poor prognosis and transcriptionally targets PLAGL2 in serous ovarian cancer.

The oncogenic function of TEA domain transcription factor 4 (TEAD4) has been confirmed in multiple human malignancies, while its potential role and regulatory mechanism in serous ovarian cancer progression are left unknown. By the gene expression analyses from Gene Expression Profiling Interactive Analysis (GEPIA) database, TEAD4 expression is shown to be up-regulated in serous ovarian cancer samples. Here, we confirmed the high expression of TEAD4 in clinical serous ovarian cancer specimens. In the following functional experiments, we found that TEAD4 overexpression promoted serous ovarian cancer malignant phenotypes, including proliferation, migration and invasion in serous ovarian cancer SK-OV-3 and OVCAR-3 cells, while TEAD4 knockout exerted the opposite function. The tumor growth inhibition of TEAD4 depletion was also affirmed by a Xenograft model in mice. In addition, this phenotypic deterioration induced by TEAD4 overexpression was diminished by PLAG1 like zinc finger 2 (PLAGL2) silencing. More importantly, combined with the results of the dual-luciferase assay, the transcriptional regulation of TEAD4 on PLAGL2 promoter was evidenced. Our results showed that the cancer-promoting gene TEAD4 was involved in serous ovarian cancer progression via targeting PLAGL2 at the transcriptional level.

Comparison of linear and non-linear machine learning models for time-dependent readmission or mortality prediction among hospitalized heart failure patients.

Although many models are available to predict prognosis of heart failure patients, most tools combining survival analysis are based on proportional hazard model. Non-linear machine learning algorithms would overcome the limitation of the time-independent hazard ratio assumption and provide more information in readmission or mortality prediction among heart failure patients. The present study collected the clinical information of 1796 hospitalized heart failure patients surviving during hospitalization in a Chinese clinical center from December 2016 to June 2019. A traditional multivariate Cox regression model and three machine learning survival models were developed in derivation cohort. Uno's concordance index and integrated Brier score in validation cohort were calculated to evaluate the discrimination and calibration of different models. Time-dependent AUC and Brier score curves were plotted to assess the performance of models at different time phases.

Symmetry breaking and competition effect in phase transitions.

This study is started from a photon-magnon model with a competition effect of the level attraction and repulsion, its Hermiticity is mainly decided by a phase-dependent and asymmetric coupling factor, namelyφ = 0 for Hermitian andϕ=πfor non-Hermitian. Then an extensional study predicts the quantum critical behaviors using an Hermitian and even no-Hermitian photon-spins model with an additional second-order drive. The numerical results firstly indicate that this coupling phaseφcan function the protective effect on quantum phase transitions (QPTs), and the new tricritical points can not only be modulated by this nonlinear drive, but also be influenced by the dissipation and the collective decoherence. Secondly, this competition effect can also induce a reversal of the value of order parameters between the positive and negative. This study can also bring more important results of QPTs toward the issue of symmetry breaking and non-Hermiticity.

Comparison of remimazolam and propofol about safety outcome indicators during general anesthesia in surgical patients: a systematic review and meta-analysis.

INTRODUCTION: Remimazolam is a novel sedative drug that has been successively approved for procedural sedation and general anesthesia, however, which has not been fully explored due to limited clinical studies and a small sample size. Current clinical studies have focused on the use of remimazolam and propofol for general anesthesia (GA) as indicators of safety outcomes in surgical patients, but different studies have reached different conclusions. The aim of this study was to investigate whether the safety-related outcome indicators in GA were superior to propofol in surgical patients. EVIDENCE ACQUISITION: We systematically searched PubMed, Cochrane Library, Embase, and Web of Science databases for all published randomized controlled trials comparing remimazolam with propofol for general anesthesia. Data from eligible studies were pooled with relative risk or mean differences to analyze the differences in hemodynamic stability and adverse effects of the two medications. EVIDENCE SYNTHESIS: Eight randomized controlled trials involving 998 participants were included. Compared with propofol, remimazolam had better hemodynamic stability with a lower incidence of hypotension (RR=0.43, 95% CI: [0.34, 0.55], I2=0%, P<0.00001), a higher preintubation, and immediate postintubation mean arterial pressure (MAP, MD=5.41, 95% CI: [5.26,11.24], Z=5.41, P<0.00001<0.05); (MD=1.60, 95% CI: [-0.20, 3.41], Z=1.74, P<0.08>0.05). Regarding other adverse events, the incidence of hypoxemia, nausea and vomiting, dizziness and injection site pain was lower in the remimazolam group compared to the propofol group. CONCLUSIONS: In this Meta-analysis, compared with propofol, remimazolam for GA reduced the incidence of hypotension, hypoxemia, nausea and vomiting, dizziness and injection site pain, and had a more stable MAP before and after intubation, which supported that remimazolam is a safer sedative. However, a large sample is needed to validate this finding.