RESUMEN
BACKGROUND AND AIMS: Heart failure (HF) is a leading cause of mortality worldwide and characterized by significant co-morbidities and dismal prognosis. Neutrophil extracellular traps (NETs) aggravate inflammation in various cardiovascular diseases; however, their function and mechanism of action in HF pathogenesis remain underexplored. This study aimed to investigate the involvement of a novel VWF-SLC44A2-NET axis in HF progression. METHODS: NET levels were examined in patients with HF and mouse models of transverse aortic constriction (TAC) HF. PAD4 knockout mice and NET inhibitors (GSK-484, DNase I, NEi) were used to evaluate the role of NETs in HF. RNA sequencing was used to investigate the downstream mechanisms. Recombinant human ADAMTS13 (rhADAMTS13), ADAMTS13, and SLC44A2 knockouts were used to identify novel upstream factors of NETs. RESULTS: Elevated NET levels were observed in patients with HF and TAC mouse models of HF. PAD4 knockout and NET inhibitors improved the cardiac function. Mechanistically, NETs induced mitochondrial dysfunction in cardiomyocytes, inhibiting mitochondrial biogenesis via the NE-TLR4-mediated suppression of PGC-1α. Furthermore, VWF/ADAMTS13 regulated NET formation via SLC44A2. Additionally, sacubitril/valsartan amplifies the cardioprotective effects of the VWF-SLC44A2-NET axis blockade. CONCLUSIONS: This study established the role of a novel VWF-SLC44A2-NET axis in regulating mitochondrial homeostasis and function, leading to cardiac apoptosis and contributing to HF pathogenesis. Targeting this axis may offer a potential therapeutic approach for HF treatment.
RESUMEN
BACKGROUND: Inflammation resolution and cardiac repair initiation after myocardial infarction (MI) require timely activation of reparative signals. Histone lactylation confers macrophage homeostatic gene expression signatures via transcriptional regulation. However, the role of histone lactylation in the repair response post-MI remains unclear. We aimed to investigate whether histone lactylation induces reparative gene expression in monocytes early and remotely post-MI. METHODS: Single-cell transcriptome data indicated that reparative genes were activated early and remotely in bone marrow and circulating monocytes before cardiac recruitment. Western blotting and immunofluorescence staining revealed increases in histone lactylation levels, including the previously identified histone H3K18 lactylation in monocyte-macrophages early post-MI. Through joint CUT&Tag and RNA-sequencing analyses, we identified Lrg1, Vegf-a, and IL-10 as histone H3K18 lactylation target genes. The increased modification and expression levels of these target genes post-MI were verified by chromatin immunoprecipitation-qPCR and reverse transcription-qPCR. RESULTS: We demonstrated that histone lactylation regulates the anti-inflammatory and pro-angiogenic dual activities of monocyte-macrophages by facilitating reparative gene transcription and confirmed that histone lactylation favors a reparative environment and improves cardiac function post-MI. Furthermore, we explored the potential positive role of monocyte histone lactylation in reperfused MI. Mechanistically, we provided new evidence that monocytes undergo metabolic reprogramming in the early stage of MI and demonstrated that dysregulated glycolysis and MCT1 (monocarboxylate transporter 1)-mediated lactate transport promote histone lactylation. Finally, we revealed the catalytic effect of IL (interleukin)-1ß-dependent GCN5 (general control non-depressible 5) recruitment on histone H3K18 lactylation and elucidated its potential role as an upstream regulatory element in the regulation of monocyte histone lactylation and downstream reparative gene expression post-MI. CONCLUSIONS: Histone lactylation promotes early remote activation of the reparative transcriptional response in monocytes, which is essential for the establishment of immune homeostasis and timely activation of the cardiac repair process post-MI.
Asunto(s)
Histonas , Infarto del Miocardio , Humanos , Histonas/metabolismo , Activación Transcripcional , Infarto del Miocardio/metabolismo , Macrófagos/metabolismo , Monocitos/metabolismoRESUMEN
BACKGROUND: The mpox pandemic has caused widespread public concern around the world. The spread of misinformation through the internet and social media could lead to an infodemic that poses challenges to mpox control. OBJECTIVE: This review aims to summarize mpox-related infodemiology studies to determine the characteristics, influence, prevention, and control measures of the mpox infodemic and propose prospects for future research. METHODS: The scoping review was conducted based on a structured 5-step methodological framework. A comprehensive search for mpox-related infodemiology studies was performed using PubMed, Web of Science, Embase, and Scopus, with searches completed by April 30, 2024. After study selection and data extraction, the main topics of the mpox infodemic were categorized and summarized in 4 aspects, including a trend analysis of online information search volume, content topics of mpox-related online posts and comments, emotional and sentiment characteristics of online content, and prevention and control measures for the mpox infodemic. RESULTS: A total of 1607 articles were retrieved from the databases according to the keywords, and 61 studies were included in the final analysis. After the World Health Organization's declaration of an mpox public health emergency of international concern in July 2022, the number of related studies began growing rapidly. Google was the most widely used search engine platform (9/61, 15%), and Twitter was the most used social media app (32/61, 52%) for researchers. Researchers from 33 countries were concerned about mpox infodemic-related topics. Among them, the top 3 countries for article publication were the United States (27 studies), India (9 studies), and the United Kingdom (7 studies). Studies of online information search trends showed that mpox-related online search volume skyrocketed at the beginning of the mpox outbreak, especially when the World Health Organization provided important declarations. There was a large amount of misinformation with negative sentiment and discriminatory and hostile content against gay, bisexual, and other men who have sex with men. Given the characteristics of the mpox infodemic, the studies provided several positive prevention and control measures, including the timely and active publishing of professional, high-quality, and easy-to-understand information online; strengthening surveillance and early warning for the infodemic based on internet data; and taking measures to protect key populations from the harm of the mpox infodemic. CONCLUSIONS: This comprehensive summary of evidence from previous mpox infodemiology studies is valuable for understanding the characteristics of the mpox infodemic and for formulating prevention and control measures. It is essential for researchers and policy makers to establish prediction and early warning approaches and targeted intervention methods for dealing with the mpox infodemic in the future.
Asunto(s)
Medios de Comunicación Sociales , Humanos , Medios de Comunicación Sociales/estadística & datos numéricos , Pandemias/prevención & control , InternetRESUMEN
Anaerobic co-digestion was conducted on the solid residues after three-phase separation of kitchen waste (KWS) and waste-activated sludge (WAS), the synergistic effects and process performance were studied during co-digestion at different ratios of KWS to WAS. KWS and WAS mix ratios of 0:1, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1 and 1:0 (based on TS). The results showed that a ratio of KWS to WAS of 1:1 got a very high methane recovery with a methane yield of 310.45 ± 30.05 mL/g VSadded. The highest concentration of free ammonia among all reaction systems was only 70.23 ± 5.53 mg/L, which was not enough to produce ammonia inhibition in the anaerobic co-digestion system. However, when the KWS content exceeded 50%, methane inhibition and prolongation of the lag phase were observed due to the accumulation of volatile fatty acids (VFAs), and during the lag phase. Microbial community analysis showed that various bacterial groups involved in acid production and hydrolysis were mainly dominated by phylum Firmicutes, Chloroflexi, Proteobacteria and Bacteroidetes. Hydrogenotrophic methanogen was found to dominate all archaeal communities in the digesters. Co-digestion of KWS with WAS significantly increased the relative abundance of Methanobacterium compared with anaerobic digestion of WAS alone.
Asunto(s)
Reactores Biológicos , Metano , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , Anaerobiosis , Metano/metabolismo , Bacterias/metabolismo , Bacterias/clasificación , Amoníaco/metabolismo , Eliminación de Residuos/métodos , Residuos Sólidos , Eliminación de Residuos Líquidos/métodos , Residuos de AlimentosRESUMEN
Manipulation of the chirality at all scales has a cross-disciplinary importance and may address key challenges at the heart of physical sciences. One critical question in this field is how the chirality of one entity can be transferred to the asymmetry of another entity. Here, we find that small molecules play a crucial role in the chirality transfer from chiral organic molecules to CdSe/CdS nanorods, where the handedness of the nanorod assemblies either agrees or disagrees with that of the molecular assemblies, leading to the positive or inverse chirality transfer. The assembling mode of nanorods on the molecular assemblies, where the nanorods are either lying or standing, is closely associated with the handedness of the nanorod assemblies, resulting in opposite chirality. Furthermore, we have found that circularly polarized emission from chiral assemblies of nanorods is dependent on molecular additives. The promoted luminescence dissymmetry factor (glum) of the nanocomposites with a high value of â¼0.3 could be attained under optimal conditions.
RESUMEN
The poor cycling performance of Li-rich cathode Li2MnO3, a promising cathode for next-generation Li-ion batteries, limits its commercial applications. Transition metal (TM) doping is widely applied to optimize the electrochemical performance of Li2MnO3, where the d valence electrons of the TM play a crucial role. Nevertheless, the rule of the doping effect of TM with various numbers of d electrons has not been well summarized. In this work, 4d-TMs (Zr, Nb, Mo, Ru and Rh) are selected as dilute doping elements for Li2MnO3 to evaluate their effect on the performance of Li2MnO3 through first-principles calculations. The calculations indicate that as the number of 4d electrons increases, the doped TM transforms from an electrochemically inert state (Zr and Nb) to an electrochemically active state (Mo, Ru and Rh) in Li2MnO3. Meanwhile, the orbital hybridization between the 4d electrons of the TM and the 2p electrons of O becomes stronger from Zr to Rh, which promotes the co-oxidation of the TM and O for charge compensation and alleviates the excessive oxidation of O, thus enhancing the stability of O. Moreover, the oxidation of the doped TM and lattice Mn during charging can trigger a decrease in the initial average delithiation potential. Although the 4d-TMs exhibit slight promoting or inhibiting effects on Li diffusion, no obvious rule related to the number of d electrons has been found. Our work highlights the rule of the doping effect of TMs with different 4d electrons on the electrochemical performance of Li2MnO3 and would facilitate a better design of Li2MnO3 cathode materials.
RESUMEN
The effects of mammalian target of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVL]) on survival in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) remain the subject of intense research. Therefore, we performed this systematic review and meta-analysis to investigate the potential survival benefits of mTOR inhibitors (mTORis). Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for all randomized controlled trials (RCTs) and cohort studies investigating effects of SRL or EVL on LT recipients for HCC. The primary outcomes were 1-, 2-, 3-, and 5-year overall survival (OS), and the secondary outcomes were 1-, 2-, and 3-year recurrence-free survival (RFS) and adverse effects. Pooled relative risks (RRs) with 95% confidence interval (CI) were calculated by a fixed or random effects model with Mantel-Haenszel weighting. Subgroup analyses were performed according to crucial clinical characteristics. We also conducted sensitivity analyses to assess the reliability of our findings. A total of 17 studies were included. OS was improved in both RCTs (1 year: RR, 1.04; 95% CI, 1.00-1.08; 2 years: RR, 1.09; 95% CI, 1.02-1.16; 3 years: RR, 1.13; 95% CI, 1.04-1.24; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 2 years: RR, 1.24; 95% CI, 1.16-1.32; 3 years: RR, 1.24; 95% CI, 1.15-1.34; 5 years: RR, 1.17; 95% CI, 1.10-1.24), with a lower risk of renal toxicity (RR, 0.75; 95% CI, 0.60 to 0.93). The 1-, 2-, and 3-year RFS were also improved. Current evidence indicates that SRL- or EVL-based immunosuppression improves OS and RFS with a lower risk of renal toxicity compared with mTORi-free immunosuppression. Nevertheless, results must be interpreted with caution.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Everolimus/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/efectos adversos , Sirolimus/efectos adversosRESUMEN
BACKGROUND: Biliary tract cancers (BTCs) are a series of heterogeneous malignancies that are broadly grouped based on the anatomical site where they arise into subtypes including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). METHODS AND RESULTS: The present study provides an overview of the epidemiology of the various BTCs based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018. Distinct differences in both incidence and mortality rates were observed for these BTCs as a function of age, sex, ethnicity, and calendar year. In 2018, BTCs emerged as the fifth most prevalent form of alimentary tract cancer in the USA. While the incidence and mortality of ICC appear to be increasing, the incidence rates of GBC, ECC, and AVC have remained stable, as have the corresponding mortality rates. The most common and deadliest BTCs in 2018 were ICC and GBC among males and females, respectively. The ethnic groups exhibiting the highest incidence rates of these different BTCs were American Indians and Alaska Natives for GBC, and Asian and Pacific Islanders for ICC, ECC, and AVC. The incidence of all of these forms of BTC rose with age. There were some variations in BTCs in terms of staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes from 2000 to 2018. CONCLUSIONS: The epidemiological characteristics, staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes were distinct for each of these BTCs.
Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Neoplasias de la Vesícula Biliar , Masculino , Femenino , Humanos , Estados Unidos/epidemiología , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/patología , Neoplasias del Sistema Biliar/epidemiología , Neoplasias del Sistema Biliar/patología , Colangiocarcinoma/epidemiología , Colangiocarcinoma/patología , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/patología , Conductos Biliares IntrahepáticosRESUMEN
Unsaturated environment is the key to affect catalytic activity of the oxygen reduction reaction (ORR). Unveiling the effect of unsaturated sites toward ORR activity is of importance due to the vague unsaturated states. Reported here is a proof-of-concept strategy on the evaluation of unsaturated bonds (UBs) on adjacent carbon environment by precisely developing two metal-free vinyl-/azo-decorated covalent organic frameworks (Vinyl-COF and Azo-COF) as catalysts. The as-prepared UB-COFs exhibit good performance than the control Py-COF and comparable to the most reported carbon catalysts. Supported by theory calculations and in situ Raman spectra-electrochemistry, it is revealed that the UBs in organic catalysts can produce para-activation, identifying the para C=N groups as active centers. Importantly, the intrinsic UBs can induce local charge redistribution, and make the molecular skeleton possess high isosurface map distribution, with an efficient affinity for oxygen intermediates.
RESUMEN
BACKGROUND: Studies have suggested that the injection drug use (IDU) was no longer the main transmission route of HIV/AIDS in China. However, there has never been a study to assess the national HIV epidemic among persons who inject drugs (PWIDs) based on a nationwide database. METHODS: PWIDs among new entrants in detoxification centers with HIV test results were extracted from the 2008-2016 National Dynamic Management and Control Database for Persons Who Use Drugs (NDMCD). Logistic regressions were used to analyze factors associated with HIV infection, and joinpoint regression were used to examine trends in the HIV prevalence. RESULTS: A total of 103,619 PWIDs among new entrants tested for HIV in detoxification centers between 2008 and 2016 were included in the analysis. The HIV prevalence was 5.0% (n = 5167) among PWIDs. A U-shaped curve of the HIV prevalence decreased from 4.9% in 2008 to 3.3% in 2010 (Annual Percent Change [APC] - 20.6, 95% CI - 32.5 to - 6.7, p < 0.05) and subsequently increased from 3.3% in 2010 to 8.6% in 2016 (APC 17.9, 95% CI 14.5-21.4, p < 0.05) was observed. The HIV prevalence in west regions in China all presented decreased trends, while central and eastern regions presented increased trends. CONCLUSIONS: Although the HIV prevalence has been declining in general population, the HIV prevalence among PWIDs has shown an increasing trend since 2010. Current policies on HIV control in PWIDs should be reassessed.
Asunto(s)
Consumidores de Drogas , Epidemias , Infecciones por VIH , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa , China/epidemiología , Estudios Transversales , Infecciones por VIH/epidemiología , Humanos , Abuso de Sustancias por Vía Intravenosa/epidemiologíaRESUMEN
BACKGROUND: Recently, more and more men who have sex with men (MSM) look for casual partners through online dating platforms in China. However, most are unable to know their partners' HIV and other sexually transmitted diseases (STD) statuses, leading to the rapid increase in HIV infection among Chinese MSM. Effective partner notification is urgently needed to increase the risk awareness of MSM and prevent HIV and other STDs transmission. However, the traditional intervention mainly targets to the HIV-positive MSM and the effect is not promising. Our study aims to provide Internet-based partner notification, along with a series of health services for HIV-negative MSM to protect them from HIV and other STDs. METHODS: A pragmatic stepped wedge cluster randomized controlled trial design is used to evaluate the effectiveness of a new intervention paradigm, which aims to reduce HIV and other STDs incidences among MSM in China. Through integrating a mobile health (mHealth) service application (app) to the current HIV and other STDs prevention and control methods, the new paradigm provides partner notification of HIV, syphilis, hepatitis B, and hepatitis C statuses. A total of 6172 MSM in 16 districts of Beijing, China will be recruited and randomized to sequentially receive partner notification intervention through the app at 6-month intervals. The primary outcomes are HIV incidence and the additional cost of the intervention. The secondary outcomes include incidences of syphilis, hepatitis B, and hepatitis C, disease transmission social networks, testing adherence, knowledge of HIV and STDs control, health self-responsibility awareness, changes of high risk behaviors and other related outcomes. The generalized linear mixed models (GLMM) will be used to analyze the differences of outcomes in the control period and in the intervention period. DISCUSSION: We expect that the HIV incidence will be significantly lower and the secondary outcomes will also be improved with providing health service of partner notification through mhealth intervention. The feasible and affordable public health intervention paradigm will have implications for HIV and STDs prevention and control among MSM and other key populations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04349748 . Registered on 16 April 2020.
Asunto(s)
Trazado de Contacto/métodos , Infecciones por VIH/prevención & control , Homosexualidad Masculina/estadística & datos numéricos , Aplicaciones Móviles , Enfermedades de Transmisión Sexual/prevención & control , Red Social , Telemedicina/organización & administración , Adolescente , Adulto , Beijing/epidemiología , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: The World Health Organization recommended HIV self-testing (HIVST) for individuals practicing unsafe sexual behaviors; however, the adherence to HIV testing has not been reported. OBJECTIVE: In this study, we attempted to determine the adherence to HIVST among men who have sex with men (MSM), as well as the impact factors and potential effects of their adherence. METHODS: We conducted a longitudinal study among MSM in Harbin, Heilongjiang province, China from July 1, 2017 to June 30, 2018. A mobile app system was used to provide the "Mailing rapid test reagent kit" for the HIVST service. The proportion of those who adhered to HIV testing every 3 months was calculated. Logistic regression was used to explore the impact factors related to adherence to HIVST. Rates of HIV infection between MSM who adhered to HIVST and those who did not were compared using Cox proportional hazards regression. Changes of condom use behaviors between the two groups were also compared using the chi-square test. RESULTS: A total of 1315 MSM who received the HIVST service through the app were included in the study. Overall, 10% of the MSM adhered to HIVST, and the proportion of adhering tests was only 34.9%. Adherence of HIVST was associated with marital status (adjusted odds ratio [OR]unmarried vs married 2.31, 95% CI 1.13-4.71) and the number of HIV tests they received (adjusted OR3 times vs 2 times or below 3.36, 95% CI 2.01-5.63; adjusted OR4 times or above vs 2 times or below 7.30, 95% CI 4.67-11.42). Twenty HIV seroconversions were observed during 1-year follow up. The rate of HIV infection in the adherence group (17.10 per 100 person years, 95% CI 8.80-30.84) was significantly higher than that in the nonadherence group (4.80 per 100 person years, 95% CI 2.77-7.88; adjusted hazard ratio 3.33, 95% CI 1.35-8.20). Those who adhered to HIV testing were more likely to improve condom use behaviors, although the difference was not statistically significant. CONCLUSIONS: Regular HIV testing is necessary for early detection of HIV infection among MSM. Given the poor adherence, a new internet-based management paradigm for MSM is needed to raise their health awareness to optimize the implementation of HIVST.
Asunto(s)
Infecciones por VIH/diagnóstico , Prueba de VIH/métodos , Homosexualidad Masculina/estadística & datos numéricos , Autoevaluación , Minorías Sexuales y de Género/estadística & datos numéricos , Adulto , China , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: The mechanistic target of rapamycin (mTOR) signal pathway plays a crucial role in the development of nonalcoholic fatty liver disease (NAFLD). However, the causal effect of mTOR downstream proteins on NAFLD remains unknown. AIMS: We conducted a two-sample Mendelian randomization (MR) study to investigate whether the mTOR-dependent circulating proteins, including Eukaryotic Initiation Factor 4E Binding Proteins (eIF4EBPs), Ribosomal Protein S6K kinase 1 (RP-S6K), Eukaryotic Initiation Factor 4E (eIF4E), Eukaryotic Initiation Factor 4A (eIF4A) and Eukaryotic Initiation Factor 4 G (eIF4G), have causal effects on the risk of NAFLD. METHODS: The causal estimate was evaluated with the inverse-variance weighted (IVW) method in discovery stage and validation stage. The single-nucleotide polymorphisms (SNPs) were selected to genetically predict exposures from Genome-Wide Association Studies (GWAS). Exposures with statistically significant effects in the discovery dataset would be further validated in the validation dataset. RESULTS: MR study revealed that eIF4E had a causal effect on NAFLD in both discovery stage (OR = 1.339, P = 0.037) and validation stage (OR = 1.0007, P = 0.022). Sensitivity analyses confirmed robustness of the results. CONCLUSION: The genetically predicted higher level of mTOR-dependent eIF4E in plasma might have a causal effect on the occurrence of NAFLD.
Asunto(s)
Factor 4E Eucariótico de Iniciación , Enfermedad del Hígado Graso no Alcohólico , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Serina-Treonina Quinasas TOR/genética , SirolimusRESUMEN
Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications.
Asunto(s)
Ferroptosis , Nitritos , Elementos de Transición , Neoplasias de la Mama Triple Negativas , Humanos , Adenosina Trifosfatasas , Factor 2 Relacionado con NF-E2 , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose-dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti-inflammatory compound derived from hematoxylin, shows potential against DOX-induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX-induced ferroptosis and maintaining mitochondrial homeostasis. Subsequently, the molecular target of PrA through proteome microarray, molecular docking, and dynamics simulation is identified. Mechanistically, PrA physically binds with ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation and subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation and subsequent release of ferrous ions (Fe2+) release. Given the critical role of ferroptosis in the pathogenesis of ischemia-reperfusion (IR) injury, this further investigation posits that PrA can confer a protective effect against IR-induced cardiac damage by inhibiting ferroptosis. Overall, a novel pharmacological inhibitor is unveiled that targets ferroptosis and uncover a dual-regulated mechanism for cardiomyocyte ferroptosis in DIC, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.
RESUMEN
Background: Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease. Methods: In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010. Findings: We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02-21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97-4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%-8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda, while 34 species fell under Chordata, comprising 27 Mammalia and 7 Aves. Interpretation: This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale. Funding: None.
RESUMEN
This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.
RESUMEN
Aim: This study aimed to explore the spatial and temporal characteristics of emerging airborne viral infectious diseases outbreaks worldwide. Subject and methods: We conducted a systematic literature review on outbreaks of emerging airborne viral infectious diseases and calculated outbreak number and intensity at the country level. Fisher's exact test was used to compare the viral infectious diseases outbreaks in different income-level regions. To identify the major airborne viral infectious diseases outbreaks, we ranked and extracted the leading viral infectious diseases in outbreak number and intensity in each country by year. Results: A total of 2505 outbreaks were reported from 1873 to 2021 across 2010 studies. There were 47 countries (47/130, 36.15%) with more frequent emerging airborne viral infectious disease outbreaks (more than nine outbreaks), and these countries mainly distributed in high-income regions (22/47 countries, 46.81%, p < 0.05), especially in Western Europe (14/47 countries, 29.79%, p < 0.05). The number of overall outbreaks was more in the United States and China than in other countries in different years. Outbreaks of measles and influenza are always frequent and intense. Highly pathogenic human coronaviruses infection caused short-term pandemics during which their outbreak number and intensity exceeded other viruses. Rift valley fever outbreaks in the human population are spreading outside of Africa through the flow of goods and travelers. Conclusion: Countries in high-income regions reported more emerging airborne viral infectious diseases outbreaks, especially in the Western European region, the United States, and China. It is urgent to strengthen collaborative surveillance of emerging airborne viruses, cross-border flow of goods and travelers, and ecological environment to avoid the spread of viral infectious diseases outbreaks worldwide. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01850-3.
RESUMEN
BACKGROUND: As one of the major constituents of the cannabis sativa plant, cannabidiol (CBD) is approved for use in medical treatment and cosmetics because of its potential health benefits. With the rapid growth of the CBD market, customers purchase these products, and relevant discussions are becoming more active on social media. OBJECTIVE: In this study, we aimed to understand the users' attitudes toward CBD products in various countries by conducting text mining on social media in countries with different substance management policies. METHODS: We collected posts from Reddit and Xiaohongshu, conducted topic mining using the latent Dirichlet allocation model, and analyzed the characteristics of topics on different social media. Subsequently, a co-occurrence network of high-frequency keywords was constructed to explore potential relationships among topics. Moreover, we conducted sentiment analysis on the posts' comments and compared users' attitudes toward CBD products on Reddit and Xiaohongshu using chi-square test. RESULTS: CBD-related posts on social media have been rapidly increasing, especially on Xiaohongshu since 2019. A total of 1790 posts from Reddit and 1951 posts from Xiaohongshu were included in the final analysis. The posts on the 2 social media platforms, Reddit and Xiaohongshu, were categorized into 7 and 8 topics, respectively, by the latent Dirichlet allocation model, and these topics on the 2 social media were grouped into 5 themes. Our study showed that the themes on Reddit were mainly related to the therapeutic effects of CBD, whereas the themes on Xiaohongshu concentrated on cosmetics, such as facial masks. Theme 2 (CBD market information) and theme 3 (attitudes toward CBD) on Reddit had more connections with other themes in the co-occurrence network, and theme 3 and theme 1 (CBD therapeutic effects) had a high co-occurrence frequency (22,803/73,865, 30.87%). Meanwhile, theme 1 (CBD cosmetics) on Xiaohongshu had various connections with others (169,961/384,575, 44.19%), and the co-occurrence frequency of theme 4 (CBD ingredients) and theme 1 was relatively prominent (27,128/49,312, 55.01%). Overall, users' comments tended to be positive for CBD-related information on both Reddit and Xiaohongshu, but the percentage was higher on Xiaohongshu (82.25% vs 86.18%; P<.001), especially in cosmetics and medical health care products. CONCLUSIONS: The CBD market has grown rapidly, and the topics related to CBD on social media have become active. There are apparent differences in users' attitudes toward CBD in countries with different substance management policies. Targeted CBD management measures should be formulated to suit the prevalence of CBD use of each country.