The Impacts of Nirmatrelvir-Ritonavir on Myocardial Injury and Long-Term Cardiovascular Outcomes in Hospitalized Patients with COVID-19 amid the Omicron Wave of the Pandemic.

PURPOSE: Even though nirmatrelvir-ritonavir can improve the short-term morbidity and mortality in COVID-19 patients, the effects of this treatment on long-term major adverse cardiovascular events (MACEs), especially myocardial injury, remains undetermined. METHODS: This prospective cohort study identified hospitalized adult patients with COVID-19 between April 19, 2022, and June 9, 2022, amid the omicron wave of the pandemic. Matched nirmatrelvir-ritonavir-treated and non-treated cohorts were formed using the propensity score matching method. The primary outcome of this study was the incidence of MACEs (cardiovascular death, myocardial infarction, stroke, new-onset heart failure or heart failure hospitalization or ventricular arrhythmia) from 30 days to 16 months after the diagnosis of COVID-19. RESULTS: Two 949-patient cohorts with balanced baseline characteristics were formed by propensity score matching. Patients with nirmatrelvir-ritonavir, compared to those untreated, had a lower level of troponin I peak as well as the incidence of troponin I elevation. During the follow-up period, 59 patients in the nirmatrelvir-ritonavir group and 86 patients in the control group developed MACEs (P = 0.020). Regarding specific constituents of MACEs, the differences are mainly reflected in new-onset heart failure or heart failure hospitalization. COVID-19 clinical severity and troponin I peak were the independent predictors, while nirmatrelvir-ritonavir was the independent protective factor for the occurrence of MACEs in this population. CONCLUSION: Nirmatrelvir-ritonavir was effective in reducing myocardial injury as well as long-term adverse cardiovascular outcomes among hospitalized patients with COVID-19 amid the omicron wave of the pandemic.

Direct solar energy conversion on zinc-air battery.

A concept of solar energy convertible zinc-air battery (SZAB) is demonstrated through rational design of an electrode coupled with multifunction. The multifunctional electrode is fabricated using nitrogen-substituted graphdiyne (N-GDY) with large π-conjugated carbonous network, which can work as photoresponsive bifunctional electrocatalyst, enabling a sunlight-promoted process through efficient injection of photoelectrons into the conduction band of N-GDY. SZAB enables direct conversion and storage of solar energy during the charging process. Such a battery exhibits a lowered charge voltage under illumination, corresponding to a high energy efficiency of 90.4% and electric energy saving of 30.3%. The battery can display a power conversion efficiency as high as 1.02%. Density functional theory calculations reveal that the photopromoted oxygen evolution reaction kinetics originates from the transition from the alkyne bonds to double bonds caused by the transfer of excited electrons, which changes the position of highest occupied molecular orbital and lowest unoccupied molecular orbital, thus greatly promoting the formation of intermediates to the conversion process. Our findings provide conceptual and experimental confirmation that batteries are charged directly from solar energy without the external solar cells, providing a way to manufacture future energy devices.

The impacts of prophylactic anticoagulation therapy during hospitalization on long-term cardiovascular outcomes in high-risk COVID-19 patients amid the omicron wave of the pandemic.

Background: Although prophylactic anticoagulation therapy is suggested to be adopted in severe COVID-19 patients, its effects on the long-term cardiovascular (CV) outcomes, namely the risk of major adverse CV events(MACEs) in high-risk CV patients amid the omicron wave of the pandemic, remain unknown. Methods: We conducted this prospective cohort study of consecutive adults hospitalized COVID-19 between 19 April and 12 June 2022, COVID-19 patients with at least two CV risk factors or pre-existing CV diseases were enrolled. A propensity score matching(PSM) method was used to evaluated the effects of prophylactic anticoagulation therapy in hospital on long-term MACEs, including CV death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina pectoris, coronary revascularization and arterial or venous thrombosis. Results: Two cohorts (with or without anticoagulants during hospitalization) of each 230 patients with balanced baseline characteristics were formed using PSM. During the 15-month follow-up period, 13 patients with anticoagulants and 29 patients without anticoagulants developed MACEs. Overall, the anticoagulation group had a significantly lower risk of MACEs than the control group (hazard ratio [HR] 0.431; 95 % confidence interval [CI]: 0.224-0.830, P = 0.010). Regarding specific constituents of MACEs, the differences were mainly reflected in arterial or venous thrombosis. The significantly lower HRs of overall MACEs were significantly observed in subgroup of age > 75 years, women, higher D dimer level, unvaccinated and non-nirmatrelvir-ritonavir prescribed patients. Conclusions: Prophylactic anticoagulation therapy during hospitalization was effective in reducing long-term MACEs among COVID-19 patients with CV risk factors or pre-existing CV diseases amid the omicron wave of the pandemic.

Graph global attention network with memory: A deep learning approach for fake news detection.

With the proliferation of social media, the detection of fake news has become a critical issue that poses a significant threat to society. The dissemination of fake information can lead to social harm and damage the credibility of information. To address this issue, deep learning has emerged as a promising approach, especially with the development of Natural Language Processing (NLP). This study introduces a novel approach called Graph Global Attention Network with Memory (GANM) for detecting fake news. This approach leverages NLP techniques to encode nodes with news context and user content. It employs three graph convolutional networks to extract informative features from the news propagation network and aggregates endogenous and exogenous user information. This methodology aims to address the challenge of identifying fake news within the context of social media. Innovatively, the GANM combines two strategies. First, a novel global attention mechanism with memory is employed in the GANM to learn the structural homogeneity of news propagation networks, which is the attention mechanism of a single graph with a history of all graphs. Second, we design a module for partial key information learning aggregation to emphasize the acquisition of partial key information in the graph and merge node-level embeddings with graph-level embeddings into fine-grained joint information. Our proposed method provides a new direction in news detection research with a combination of global and partial information and achieves promising performance on real-world datasets.

Advanced Multilayered Electrode with Planar Building Blocks Structure for High-Performance Lithium-Ion Storage.

To achieve the high-performance of lithium-ion battery, the optimization of electrode materials has generally been considered as the one of the important methods. But most of those works pay attention to the new materials preparation or interface modification rather than the structural innovation. Here, an advanced electrode (GDY/BP/GDY-E) with multilevel layered architecture constructed by planar building blocks stacking structure has been designed and fabricated to explore the structure design of the electrode. This new structure is assembled by graphdiyne (GDY) and black phosphorus (BP) in parallel to form a building block (GDY/BP/GDY). The electric fields between the two GDY sides of the planar building block structure contribute to the superior migration dynamics of lithium ions and desirable pseudocapacitance behavior. Meanwhile, the planar stacking structure of GDY/BP/GDY can efficiently inhibit volume expansion of BP and a series of parasitic reactions of electrolytes during the long-term cycling. The advanced GDY/BP/GDY-E exhibits excellent high-rate performance (1418.8 mAh g-1 at 0.1 A g-1 ) and cycling stability (391.7 mAh g-1 after 5000 cycles at 10 A g-1 ). Such structural design of electrode materials shows a new way to develop high-performance electrodes.

Boosting Fe Cationic Vacancies with Graphdiyne to Enhance Exceptional Pseudocapacitive Lithium Intercalation.

Modulating the electronic structure of electrode materials at atomic level is the key to controlling electrodes with outstanding rate capability. On the basis of modulating the iron cationic vacancies (IV) and electronic structure of materials, we proposed the method of preparing graphdiyne/ferroferric oxide heterostructure (IV-GDY-FO) as anode materials. The goal is to motivate lithium-ion batteries (LIBs) toward ultra-high capacity, superior cyclic stability, and excellent rate performance. The graphdiyne is used as carriers to disperse Fe3 O4 uniformly without agglomeration and induce high valence of Fe with reducing the energy in the system. The presence of Fe vacancy could regulate the charge distribution around vacancies and adjacent atoms, leading to facilitate electronic transportation, enlarge the lithium-ion diffusion, and decrease Li+ diffusion barriers, and thus displaying significant pseudocapacitive process and advantageous lithium-ion storage. The optimized electrode IV-GDY-FO reveals a capacity of 2084.1 mAh g-1 at 0.1 C, superior cycle stability and rate performance with a high specific capacity of 1057.4 mAh g-1 even at 10 C.

Tumor microenvironment-mediated NIR-I-to-NIR-II transformation of Au self-assembly for theranostics.

The misdiagnosis of tumors due to insufficient penetration depth or signal interference and damage to normal tissues due to indiscriminate treatment are the biggest challenges in using photothermal agents for clinical translation. To overcome these limitations, a strategy of switching from the near-infrared (NIR)-I region to the NIR-II region was developed based on tumor microenvironment (TME)-mediated gold (Au) self-assembly. Using zeolitic imidazolate framework-8 (ZIF-8) metal-organic framework-coated gold nanorods (AuNRs@ZIF-8) as a model photothermal agent, we demonstrated that only a NIR-I photoacoustic imaging signal was observed in normal tissue because ZIF-8 could prevent the aggregation of AuNRs. However, when ZIF-8 dissociated in the TME, the AuNRs aggregated to activate NIR-II photoacoustic imaging and attenuate the NIR-I signal, thereby allowing an accurate diagnosis of tumors based on signal transformation. Notably, TME-activated NIR-II photothermal therapy could also inhibit tumor growth. Therefore, this TME-activated NIR-I-to-NIR-II switching strategy could improve the accuracy of deep-tumor diagnoses and avoid the injury caused by undifferentiated treatment. STATEMENT OF SIGNIFICANCE: Photothermal agents used for photoacoustic imaging and photothermal therapy have garnered great attention for tumor theranostics. However, always "turned on" near-infrared (NIR)-I laser (700-1000 nm)-responsive photothermal agents face issues of penetration depth and damage to normal tissues. In contrast, tumor microenvironment-activated NIR-II "smart" photothermal agents exhibit deeper penetration depth and tumor selectivity. Therefore, a NIR-I-to-NIR-II switching strategy was developed based on tumor microenvironment-mediated Au self-assembly. This work provides a new strategy for developing tumor microenvironment-activated NIR-II smart photothermal agents.

Evaluating the quality consistency of antiviral oral liquid by high-performance liquid chromatography five-wavelength matched average fusion fingerprint combined with electrochemical fingerprint and ultraviolet spectral quantum fingerprint.

The antiviral oral liquid (AOL) was an antiviral drug currently in clinical trials against coronavirus disease 2019. This study aimed to improve its quality consistency evaluation method using fingerprint techniques from several aspects. First, the five-wavelength matched average fusion fingerprint (FMAFFP) for HPLC, electrochemical fingerprint (ECFP), and ultraviolet spectral quantum fingerprint (UVFP) was established for 22 samples, respectively. Their quality was then assessed using the average linear quantitative fingerprint method, and 22 samples were classified into eight quality grades. OPLS and PCA were then used further to explore the characteristic parameters of these three fingerprints. Five compounds were quantified simultaneously for the first time, and then the relationship between the average linear quantitative similarity (PL) and the sum of the five quantitative components (P5c) was investigated. A linear correlation (r ≥ 0.9735) between PL and P5c suggested that PL may be used to predict chemical content. Finally, to investigate the antioxidant potential of the AOL, correlation analyses were performed for FMAFFP peaks-PEC and UVFP peaks-PEC, respectively, where the PEC value was defined as the quantitative similarity of ECFP. The Pearson correlation coefficient and gray correlation analysis were consistent, allowing us to initially explore the antioxidant capacity of the unidentified components of the samples. This study researched AOL using multidimensional fingerprints to provide a comprehensive and reliable method for quality consistency control of herbal compound preparations.

The initial timing and dosage pattern of sacubitril/valsartan in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: In real-world clinical practice, the initiation and up-titration of sacubitril/valsartan remain challenging due to symptomatic hypotension in patients with acute myocardial infarction(AMI). The purpose of this study was to investigate the efficacy of different initial timing and dosage of sacubitril/valsartan in AMI patients. METHODS: This prospective and observational cohort study enrolled AMI patients treated with percutaneous coronary intervention(PCI), and were categorized according to the initial timing and average daily doses of sacubitril/valsartan prescription. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, coronary revascularization, heart failure(HF) hospitalization and ischaemic stroke. Secondary outcomes included the new-onset HF, and the composite endpoints in AMI patients complicated with HF at baseline. RESULTS: The study population consisted of 915 AMI patients. After a median follow-up of 38 months, early use or high dosage of sacubitril/valsartan was associated with an improvement in primary endpoint as well as the incidence of new-onset HF. Early use of sacubitril/valsartan also ameliorated the primary endpoint in AMI patients with left ventricular ejection fraction(LVEF) ≤50% as well as LVEF>50%. Besides, early use of sacubitril/valsartan improved the clinical outcomes in AMI patients complicated with HF at baseline. The low dose was well tolerated and may be associated with similar outcomes compared with high dose under some circumstances(LVEF>50% or HF at baseline). CONCLUSIONS: Early use or high dosage of sacubitril/valsartan medication is associated with an improvement in clinical outcome. The low dose of sacubitril/valsartan is well tolerated and may be an acceptable alternative strategy.

Structurally diverse glycosides with α-glucosidase inhibitory properties from water extract of the leaves of Cyclocarya paliurus.

In this work we investigated the chemical constituents of water extract of the leaves of Cyclocarya paliurus. Two new megastigmane glycosides (3 and 8), three aliphatic alcohol glycosides (9-11), and two aromatic glycosides (12 and 13), along with fourteen known compounds were isolated, and their in vitro inhibitory activity against α-glucosidase was evaluated. Compounds 13 and 15-18 displayed inhibitory activity with IC50 values varying from 27.05 to 96.58 µM, and the structure-activity relationship among isolated compounds was discussed.

Roles of oral microbiota and oral-gut microbial transmission in hypertension.

INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered. OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN. METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN. RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition. CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.

Directly Growing Graphdiyne Nanoarray Cathode to Integrate an Intelligent Solid Mg-Moisture Battery.

A continuous humidity and solar-light dual responsive intelligent solid Mg-moisture battery (SMB) with a graphdiyne nanosheets array was fabricated. The integrated battery works based on a new concept of chemical bond conversion on the surface of the graphdiyne nanosheets array that is grown in situ on a 3D melamine sponge (GDY/MS). The unique structure, excellent catalytic, and semiconductor performance of GDY endows the GDY/MS with some outstanding characteristics on trapping and transferring water molecules, catalyzing HER, and utilizing solar energy, making the GDY/MS a new generation cathode for a high-performance intelligent SMB. The performance of the GDY/MS-based smart SMB (GSMB) can be continuously tuned by humidity and solar-light. The GSMB shows a significant positive correlation between open circuit potential (OCP) and humidity, while the natural band gap of GDY makes it further act as a photoelectrode to capture light and generate photoelectrons. The GSMB can be applied as a self-power humidity monitor with an ultrafast response time of <0.24 s, a recovery time of <0.16 s, and a sensitive (36,600%) respiratory sensing performance. This simple and efficient battery-made strategy represents the future development direction of self-power supply equipment, intelligent electronic devices, and intelligent battery integration.

Dual control system for comprehensive evaluation of quality consistency of herbal preparations.

This study was undertaken to establish an integrated quality control method based on the fingerprint of different testing instruments and a four-dimensional antioxidant activity profile. Firstly, the comprehensive ratio quantitative fingerprint method was used to rapidly calculate the similarity of GC fingerprint, UV-vis quantized fingerprint, HPLC fingerprint and ATR-FT-IR quantized fingerprint. In addition, a comprehensive evaluation strategy was proposed using the variation coefficient weighting algorithm, incorporating four complementary inputs, to achieve highly accurate analysis. At the same time, multi-markers assay by monolinear method was used for the first time for the quantitative analysis of multiple components. Based on this, the fingerprint-efficacy relationship was investigated, and substances that might be biologically active and the wavelength range of their distribution were predicted using the online-HPLC-DPPH-FIA method in conjunction with a PLS model built from individual and combined data matrices. The results showed that all 20 batches of samples were within 1-3 grades, with good quality consistency. According to index E, the samples' overall antioxidant capacity was also highly correlated with the year of production. The four-dimensional antioxidant activity profile also led to the conclusion that variations in antioxidant characteristics were caused by differences in the concentration and volatility of particular bioactive chemicals. Finally, mid-level data fusion produced better classification results than a single technique, further demonstrating the synergistic effects that may occur when the four types of data were combined. This study demonstrated that the combination of GC, UV-vis, ATR-FT-IR and HPLC can be used for the consistency control of herbal preparations and can elucidate the potential in predicting the antioxidant capacity of herbal preparations.

Factors affecting physical examinations among patients with severe mental disorders in Shaoxing City / 预防医学

Objective@#To investigate the proportion of physical examinations among patients with severe mental disorders and its influencing factors in Shaoxing City, Zhejiang Province, so as to provide the evidence for improving the proportion of physical examinations among patients with severe mental disorders. @*Methods @#The epidemiological and clinical features of patients with severe mental disorders included in community management in Shaoxing City in 2022 were collected from Zhejiang Provincial Severe Mental Disorder Management Information System, including demographics, disease diagnosis and treatment, physical examination, and rescue and assistance. Factors affecting the physical examination were identified among patients with severe mental disorders using a multivariable logistic regression model. @*Results@#A total of 25 468 patients with severe mental disorders were enrolled in Shaoxing City in 2022, including 12 151 males and 13 317 females, with a male to female ratio of 0.91∶1, and the participants had a mean age of (54.34±14.71) years. Schizophrenia was the predominant type of severe mental disorders (15 419 cases, 60.54%), and 21 374 subjects participating in the physical examinations in 2022 (83.92%). Multivariable logistic regression analysis showed that female (OR=0.901, 95%CI: 0.832-0.975), urban areas (OR=0.506, 95%CI: 0.468-0.547), mental disorders due to epilepsy (OR=1.779, 95%CI: 1.104-2.866), hospitalized treatment (6 to 10 times, OR=0.523, 95%CI: 0.401-0.681; 11 times and more, OR=0.177, 95%CI: 0.108-0.288), special diseases in outpatient (OR=1.738, 95%CI: 1.597-1.891), receiving medical assistance (OR=2.851, 95%CI: 2.616-3.107), targets of the community care and assistance groups (OR=1.653, 95%CI: 1.471-1.857) and guardian (spouse, OR=1.777, 95%CI: 1.513-2.086; children, OR=1.277, 95%CI: 1.069-1.526; parents, OR=1.342, 95%CI: 1.143-1.576) were statistically associated with the proportion of physical examinations. @*Conclusions@#The proportion of health examinations was 83.92% among patients with severe mental disorders in Shaoxing City in 2022. Gender, residence, guardian, disease diagnosis, times of hospitalized treatment, medical assistance, special diseases in outpatients and target of community care and assistance groups were factors affecting health examinations among patients with severe mental disorders.

DLGAP1-AS2 promotes human colorectal cancer progression through trans-activation of Myc.

Substantial evidence suggests that non-coding RNA plays a vital role in human cancer, especially long non-coding RNA (lncRNA) with a length greater than 200nt. Herein, we found a lncRNA facilitating human colorectal cancer (CRC) progression. DLGAP1-AS2 was significantly increased in CRC tissues and cell lines. Knockdown of DLGAP1-AS2 inhibited CRC cell proliferation, migration, invasion in vitro, and tumor growth in vivo. The subcellular localization of DLGAP1-AS2 was translocated from the cytoplasm of normal cells to the nucleus of CRC cells due to reduced levels of N6-methyladenosine (m6A) modification. Further, through the screening of a series of signal pathways, we found that Myc pathway was involved in the effect of DLGAP1-AS2. Silencing of DLGAP1-AS2 markedly reduced Myc mRNA and protein levels. Blockade of Myc effectively abolished the enhanced aggressive behaviors of CRC cells caused by DLGAP1-AS2 overexpression. Mechanistically, DLGAP1-AS2 directly bound CTCF, a well-known transcriptional repressor of Myc, resulting in reduced binding of CTCF on Myc promoter and activating Myc transcription. The second hairpin structure of DLGAP1-AS2 was critical for the interaction between DLGAP1-AS2 and CTCF in the nucleus. Taken together, our study reveals the oncogenic regulatory axis of DLGAP1-AS2/CTCF/Myc in CRC, implying a promising targeted therapy for clinical application.

Determining the Efficiency of the Sponge City Construction Pilots in China Based on the DEA-Malmquist Model.

Sponge city construction (SCC) has improved the quality of the urban water ecological environment, and the policy implementation effect of SCC pilots is particularly remarkable. Based on the data envelopment analysis (DEA) model, this study employed the related index factors such as economy, ecology, infrastructure, and the population of the pilot city as the input, and the macro factors of SCC as the output, to scientifically evaluate the relative efficiency between the SCC pilots in China. Eleven representative SCC pilots were selected for analysis from the perspectives of static and dynamic approaches, and comparisons based on the horizontal analysis of the efficiency of SCC pilots were conducted and some targeted policy suggestions are put forward, which provide a reliable theoretical model and data support for the efficiency evaluation of SCC. This paper can be used as a reference for construction by providing a DEA model for efficiency evaluation methods and thus helps public sector decision makers choose the appropriate construction scale for SCC pilots.

Characteristics, prognosis, and treatment response in HFpEF patients with high vs. normal ejection fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) patients varied by left ventricular ejection fraction (LVEF) have different clinical characteristics, prognosis, and treatment response. With data from our prospective HFpEF cohort, we assessed the possible relationship between clinical characteristics, outcome as well as treatment response and LVEF. Methods: We compared differences in baseline characteristics and clinical outcomes across LVEF categories (50%≤LVEF <60% vs. LVEF≥60%) in 1,502 HFpEF patients, and determined whether LVEF modified the treatment response. During 5-year follow-up, all-cause mortality was used as the primary endpoints, and composite endpoints (all-cause mortality or HF hospitalization) were set as the secondary endpoint. Results: Patients with higher LVEF were statistically older, more likely to be women and have a history of atrial fibrillation. Patients with lower LVEF category were more likely to have a history of coronary artery disease. The incidences of all-cause mortality and composite endpoints were higher in patients with higher LVEF. Also, LVEF modified the spironolactone treatment effect for the primary outcome and secondary endpoint with stronger estimated benefits at the lower LVEF category with respect to all-cause mortality (HR 0.734, 95% CI 0.541-0.997, P = 0.048) and all-cause mortality or HF hospitalization (HR 0.767, 95% CI 0.604-0.972, P = 0.029). Conclusion: The characteristics and outcomes of HFpEF patients varied substantially by LVEF. Patients with higher LVEF encountered more adverse events than those with lower LVEF. The potential efficacy of spironolactone was greatest at the lower category of LVEF spectrum in HFpEF.

Research Progress of Exosomal microRNA in Cardiovascular Disease and Its Forensic Application Prospects.

Exosomal microRNAs (miRNAs) are miRNAs that are mediated by exosomes to achieve cell-to-cell communication, and they are widespread in organisms. In recent years, the key role of the multiple biological functions of exosomal miRNAs in the occurrence and development of cardiovascular diseases has been confirmed by a large number of studies, which has become a hot spot in clinical and basic research. Sudden cardiac death caused by cardiovascular disease is one of the important contents in forensic medical identification. This article introduces the research progress of cardiovascular disease prediction, treatment and prognosis on exosomal miRNA. The prospects of the application in forensic medical identification are discussed.

Extracellular vesicles from hypoxia-preconditioned mesenchymal stem cells alleviates myocardial injury by targeting thioredoxin-interacting protein-mediated hypoxia-inducible factor-1α pathway.

BACKGROUND: Extracellular vesicles (EVs) derived from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) have better cardioprotective effects against myocardial infarction (MI) in the early stage than EVs isolated from normoxic (NC)-MSCs. However, the cardioprotective mechanisms of HP-EVs are not fully understood. AIM: To explore the cardioprotective mechanism of EVs derived from HP MSCs. METHODS: We evaluated the cardioprotective effects of HP-EVs or NC-EVs from mouse adipose-derived MSCs (ADSCs) following hypoxia in vitro or MI in vivo, in order to improve the survival of cardiomyocytes (CMs) and restore cardiac function. The degree of CM apoptosis in each group was assessed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/PI assays. MicroRNA (miRNA) sequencing was used to investigate the functional RNA diversity between HP-EVs and NC-EVs from mouse ADSCs. The molecular mechanism of EVs in mediating thioredoxin-interacting protein (TXNIP) was verified by the dual-luciferase reporter assay. Co-immunoprecipitation, western blotting, and immunofluorescence were performed to determine if TXNIP is involved in hypoxia-inducible factor-1 alpha (HIF-1α) ubiquitination and degradation via the chromosomal region maintenance-1 (CRM-1)-dependent nuclear transport pathway. RESULTS: HP-EVs derived from MSCs reduced both infarct size (necrosis area) and apoptotic degree to a greater extent than NC-EVs from CMs subjected to hypoxia in vitro and mice with MI in vivo. Sequencing of EV-associated miRNAs showed the upregulation of 10 miRNAs predicted to bind TXNIP, an oxidative stress-associated protein. We showed miRNA224-5p, the most upregulated miRNA in HP-EVs, directly combined the 3' untranslated region of TXNIP and demonstrated its critical protective role against hypoxia-mediated CM injury. Our results demonstrated that MI triggered TXNIP-mediated HIF-1α ubiquitination and degradation in the CRM-1-mediated nuclear transport pathway in CMs, which led to aggravated injury and hypoxia tolerance in CMs in the early stage of MI. CONCLUSION: The anti-apoptotic effects of HP-EVs in alleviating MI and the hypoxic conditions of CMs until reperfusion therapy may partly result from EV miR-224-5p targeting TXNIP.

Controlled Growth of 3D Interpenetrated Networks by NiCo2O4 and Graphdiyne for High-Performance Supercapacitor.

In this paper, the 2D all-carbon graphdiyne, which possesses superior 2D strength and high mixed conductivities for both electrons and ions, is used to protect nickel cobalt oxide nanostructures with multidimensions. The in situ grown graphdiyne seamlessly wraps on nanostructures to form 3D interpenetrating networks, leading to significant improvement in the conductivity and avoidance of the structural degradation. The assembled hybrid asymmetric supercapacitor showed a high specific capacitance of 200.9 F g-1 at 1 A g-1 with an energy density of 62.8 Wh kg-1 and a power density of 747.9 W kg-1. The device also showed a preeminent rate capability (86.4% capacitance retention, while the current density was increased from 1 to 20 A g-1) and an ultrastable long-term cycling performance (the capacitance retention is about 97.7% after 10 000 cycles at a high current density of 20 A g-1).