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Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.
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Secuenciación de Nucleótidos de Alto Rendimiento , Pulmón , Musarañas , Viroma , Animales , Musarañas/virología , China , Pulmón/virología , Viroma/genética , Filogenia , Virus ARN/genética , Virus ARN/clasificación , Virus ARN/aislamiento & purificación , ARN Viral/genética , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/aislamiento & purificación , Virus de la Rabia/genética , Virus de la Rabia/clasificación , Virus de la Rabia/aislamiento & purificación , Reservorios de Enfermedades/virologíaRESUMEN
BACKGROUND: Nonsuicidal self-injury (NSSI) is a serious problem in the adolescent population worldwide. Childhood trauma and bullying have been identified as risk factors for NSSI. We explored the relationships among Childhood trauma, Bullying victimization and the severity of NSSI behaviours, and test the effect of Bullying victimization in mediating the association between Childhood trauma and the NSSI behaviours. METHODS: A total of 123 adolescents were recruited. They were diagnosed with depression or depressive episodes of bipolar disorder and had experienced NSSI in the last year. They were assessed using the Chinese version of the Childhood Trauma Questionnaire (CTQ-C), the Revised Olweus Bullying Victimization Questionnaire (OBVQ-R), and the Adolescent Self-Harm Questionnaire (ASHQ). RESULTS: Females presented a significantly greater prevalence of sexual abuse and relationship bullying than boys. Individuals in the younger age group (10-14 years) presented a greater incidence of emotional neglect, verbal bullying, relationship bullying, and total bullying, and their NSSI score was also higher than that of those in the older age group (15-19 years). Only children show a greater prevalence of sexual abuse than nononly children. Single-parent families scored higher on emotional abuse, emotional neglect, physical neglect and physical bullying than two-parent families. There was a significant positive correlation between each dimension of childhood trauma and all the dimensions of bullying, between childhood trauma and NSSI, and between bullying and NSSI. Childhood trauma can not only directly affect the severity of NSSI but also indirectly aggravate the severity of NSSI through bullying victimization. The mediating effects of bullying victimization on emotional abuse, physical abuse, emotional neglect and physical neglect were 14%, 21%, 20%, 13% and 20%, respectively. CONCLUSION: There was a significant positive correlation between childhood trauma and bullying, between childhood trauma and NSSI, and between bullying and NSSI. Childhood trauma can not only directly affect the severity of NSSI but also indirectly aggravate the severity of NSSI through bullying victimization. Bullying victimization played the partial mediating effects between Childhood trauma and NSSI.
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Acoso Escolar , Víctimas de Crimen , Conducta Autodestructiva , Humanos , Adolescente , Acoso Escolar/psicología , Masculino , Femenino , Niño , Víctimas de Crimen/psicología , Conducta Autodestructiva/psicología , Conducta Autodestructiva/epidemiología , Experiencias Adversas de la Infancia/psicología , Factores de Riesgo , Adulto Joven , Maltrato a los Niños/psicología , China/epidemiología , Prevalencia , Encuestas y CuestionariosRESUMEN
The present study aims to investigate the role of interferon regulatory factor 4 (IRF4) in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and analyze the underlying signaling of these processes. In this study, IRF4 is upregulated in periodontitis periodontal ligament tissues, as compared to healthy periodontal ligament tissues. IRF4 knockdown increases cell proliferation, decreases levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-8, enhances osteogenic activity, and increases the expression of RUNX family transcription factor 2, Collagen I, and Osteocalcin in PDLSCs. The opposite results are observed in IRF4 overexpressed PDLSCs. Additionally, GSEA shows that IRF4 activates the interleukin-18 (IL-18) signaling pathway. The expressions of IL-18, B-cell translocation gene 2, interleukin-1beta, and caspase-3 are decreased by IRF4 knockdown, while increased by IRF4 overexpression. IL-18 overexpression eliminates the promoting effect of IRF4 knockdown on osteogenic differentiation of PDLSCs. In conclusion, IRF4 suppresses osteogenic differentiation of PDLSCs by activating the IL-18 signaling pathway.
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The power conversion efficiency (PCE) of perovskite solar cells (PSCs) has exceeded those of conventional thin-film solar cell technologies, and the speed at which this increase has been achieved is unprecedented in the history of photovoltaics. Despite the significant progress achieved by PSCs at the laboratory level, their commercial prospects still face two significant challenges: scaling up in size and ensuring long-term stability. Small-area devices (~1 cm2) are typically fabricated using spin-coating. However, this approach may not be suitable for preparing the large-area (>100 cm2) substrates required for commercialization. Thus, new materials and methods must be developed to facilitate the coating of large-area PSCs. This review will discuss the development of scaling up organic-inorganic hybrid PSCs and the challenges of increasing the device area. Furthermore, it will provide an overview of the methodologies for achieving high-efficiency perovskite solar modules.
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The aqueous zinc ion battery (AZIB) has been widely studied due to its rapid kinetics and high specific capacity attributed to the chemical insertion of H+ protons. However, the current research landscape lacks comprehensive investigations into copper-based sulfide materials and the intricate co-embedding/extraction mechanism of H+/Zn2+. In this study, we employed an innovative in-situ etching method to synthesize a current collector-integrated Cu@Cu31S16 cathode material. Cu31S16 not only exhibits excellent stability and conductivity but also activates proton insertion chemistry. Consequently, we have demonstrated, for the first time, efficient and reversible co-embedding/extraction behavior of H+/Zn2+ in Zn-Cu31S16 batteries. Specifically, owing to the lower charging and discharging plateaus of zinc ions (0.65 V, 0.45 V) compared to H+ (0.97 V, 0.84 V) in Zn-Cu31S16 batteries, two distinct plateaus were observed. Moreover, we delved into the mechanism of ion co-embedding/extraction by exploring different ions (Zn2+, H+/Zn2+, H+) within varying voltage ranges. This exploration led to the development of three types of ion batteries, where Zn2+, H+/Zn2+, and H+ exhibit co-embedding/extraction within voltage ranges of 0.3-0.9 V, 0.3-1.05 V, and 0.5-1.05 V, respectively. These batteries have achieved impressive performance with specific capacities of 282.74 mAh g-1, 587.4 mAh g-1 and 687.3 mAh g-1, respectively. Introducing the concept of "Voltage-Selective Ion Co-Embedding/Extraction", this study broadens the research scope of AZIBs. This research not only offers a feasible solution and theoretical guidance for future proton batteries but also underscores the tremendous potential of AHPB.
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BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.
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Corticoesteroides , Anticuerpos Monoclonales Humanizados , Quimioterapia Combinada , Síndrome de Trombocitopenia Febril Grave , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Síndrome de Trombocitopenia Febril Grave/tratamiento farmacológico , Síndrome de Trombocitopenia Febril Grave/mortalidad , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Anciano , Resultado del Tratamiento , Hospitalización/estadística & datos numéricos , China , AdultoRESUMEN
BACKGROUND AND PURPOSE: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA-derived small ribonucleic acids (tsRNAs) have been established as promising non-invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development. EXPERIMENTAL APPROACH: Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA-Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed. KEY RESULTS: In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up-regulated and 4 down-regulated). qRT-PCR was used to validate the expression of six tsRNAs that were up-regulated in MDD (tiRNA-1:20-chrM.Ser-GCT, tiRNA-1:33-Gly-GCC-1, tRF-1:22-chrM.Ser-GCT, tRF-1:31-Ala-AGC-4-M6, tRF-1:31-Pro-TGG-2 and tRF-1:32-chrM.Gln-TTG). Interestingly, serum tiRNA-Gly-GCC-001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA-Gly-GCC-001 is predicted to suppress brain-derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA-Gly-GCC-001 down-regulation was evident following an 8-week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy. CONCLUSION AND IMPLICATIONS: Our current work reports for the first time that tiRNA-Gly-GCC-001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy.
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Antidepresivos , Biomarcadores , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/genética , Biomarcadores/sangre , Masculino , Femenino , Adulto , Antidepresivos/uso terapéutico , Antidepresivos/farmacología , Persona de Mediana Edad , ARN de Transferencia/genéticaRESUMEN
System-level fault diagnosis model, namely, the PMC model, detects fault nodes only through the mutual testing of nodes in the system without physical equipment. In order to achieve server nodes fault diagnosis in large-scale data center networks (DCNs), the traditional algorithm based on the PMC model cannot meet the characteristics of high diagnosability, high accuracy and high efficiency due to its inability to ensure that the test nodes are fault-free. This paper first proposed a fault-tolerant Hamiltonian cycle fault diagnosis (FHFD) algorithm, which tests nodes in the order of the Hamiltonian cycle to ensure that the test nodes are faultless. In order to improve testing efficiency, a hierarchical diagnosis mechanism was further proposed, which recursively divides high scale structures into a large number of low scale structures based on the recursive structure characteristics of DCNs. Additionally, we proved that $ 2(n-2){n^{k-1}} $ and $ (n-2){t_{n, k}}/{t_{n, 1}} $ faulty nodes could be detected for $ BCub{e_{n, k}} $ and $ DCel{l_{n, k}} $ within a limited time for the proposed diagnosis strategy. Simulation experiments have also shown that our proposed strategy has improved the diagnosability and test efficiency dramatically.
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BACKGROUND: Acute lung injury (ALI) is a devastating clinical disorder with a high mortality rate, and there is an urgent need for more effective therapies. Fibroblast growth factor 18 (FGF18) has potent anti-inflammatory properties and therefore has become a focus of research for the treatment of lung injury. However, the precise role of FGF18 in the pathological process of ALI and the underlying mechanisms have not been fully elucidated. METHODS: A mouse model of ALI and human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS) was established in vivo and in vitro. AAV-FGF18 and FGF18 proteins were used in C57BL/6J mice and HUVEC, respectively. Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and p65 protein levels were determined by western blotting or immunofluorescent staining. Afterward, related inhibitors were used to explore the potential mechanism by which FGF18 relieves inflammation. RESULTS: In this study, we found that FGF18 was significantly upregulated in LPS-induced ALI mouse lung tissues and LPS-stimulated HUVECs. Furthermore, our studies demonstrated that overexpressing FGF18 in the lung or HUVEC could significantly alleviate LPS-induced lung injury and inhibit vascular leakage. CONCLUSIONS: Mechanically, FGF18 treatment dramatically inhibited the NF-κB signaling pathway both in vivo and in vitro. In conclusion, these results indicate that FGF18 attenuates lung injury, at least partially, via the NF-κB signaling pathway and therefore may be a potential therapeutic target for ALI.
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Lesión Pulmonar Aguda , Factores de Crecimiento de Fibroblastos , Sepsis , Ratones , Humanos , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/toxicidad , Ratones Endogámicos C57BL , Lesión Pulmonar Aguda/metabolismo , Pulmón/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Sepsis/metabolismoRESUMEN
Background: Non-suicidal self-injury (NSSI), of which the predisposing factors are complex and diverse, profoundly affects the physical and mental health of young people. Therefore, this work established an NSSI intermediary network model considering the interaction of multiple factors. A mediating effect between attention-deficit/hyperactivity disorder (ADHD) and NSSI, considering the influence of comorbidities, such as depression, anxiety, and impulsive personality, was proposed based on sex differences. Methods: A total of 2,689 middle school students in Ningbo City, Zhejiang Province, China, were randomly sampled and participated in this study. Data regarding their demographic characteristics, attention deficit, hyperactivity/impulsivity, NSSI, anxiety, depression, internet addiction, and other comorbid symptoms were collected and analyzed. After initially screening the data, variables were assessed for significance using a single-factor inter-group difference analytic method, and a binary logistic regression analysis was performed. The intermediary effect of factors influencing NSSI in males and females was also analyzed. Results: The overall NSSI rate was 15.16%. The results showed that the impact of individual impulsivity characteristics (impulsiveness, the ADHD with hyperactivity/impulsivity subtype) on NSSI behavior was not significant (regression results, P > 0.05). The degree of association between ADHD with attention deficit and ADHD with comprehension deficit subtypes, and other comorbid symptoms (depression, anxiety, and internet addiction disorder) and NSSI, with odds ratios (ORs) of 7.6/6.42/436.68/3.82/1.86, and 95% bootstrap confidence intervals (CIs) of 4.64, 12.87/3.46, 12.67/137.42, 2659.13/2.32, 6.37/1.31, 2.82, respectively. The results also showed significant effects of ADHD subtypes on comorbid symptoms and the path effects of NSSI (P < 0.01). Among them, the mediating effect was the strongest when anxiety was the mediating variable, and the mediating effect of girls was higher than that of boys. Conclusion: The results of this work demonstrated the influence of ADHD symptoms on NSSI behavior. Among patients with ADHD, patients with subtypes with obvious attention deficit characteristics were more likely to exhibit NSSI behavior, whereas the hyperactive impulse subtype had no direct impact on NSSI. We conclude that adolescent impulsivity may not be directly related to NSSI behavior and that impulsive characteristics jointly affect NSSI behavior through a series of NSSI comorbid symptoms. Notably, the probability of symptom onset and the degree of comorbidity was significantly higher in girls than in boys of the same age, and girls were more prone to NSSI behavior. These findings provide effective theoretical support for the prevention and treatment of adolescent NSSI behavior.
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Trastorno por Déficit de Atención con Hiperactividad , Conducta Autodestructiva , Adolescente , Humanos , Masculino , Femenino , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Conducta Autodestructiva/psicología , Salud Mental , Comorbilidad , Ansiedad/epidemiologíaRESUMEN
Highly stretchable porous materials are promising for flexible electronics but their fabrication is a great challenge. Herein, several kinds of highly stretchable conductive porous elastomers with low or negative Poisson's ratios are achieved by uniaxial, biaxial, and triaxial hot-pressing strategies. The reduced graphene oxide/polymer nanocomposite elastomers with folded porous structures obtained by uniaxial hot pressing exhibit high stretchability up to 1200% strain. Furthermore, the meta-elastomers with reentrant porous structures combining high biaxial (or triaxial) stretchability and negative Poisson's ratios are achieved by biaxial (or triaxial) hot pressing. The resulting elastomer-based wearable strain sensors exhibit an ultrawide response range (0-1200%). The materials can be applied for smart thermal management and electromagnetic interference shielding, which are achieved by regulating the porous microstructures via stretching. This work provides a versatile strategy to highly stretchable and negative-Poisson-ratio porous materials with promising features for various applications such as flexible electronics, thermal management, electromagnetic shielding, and energy storage.
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Highly sensitive self-powered stretchable electronic skins with the capability of detecting broad-range dynamic and static pressures are urgently needed with the increasing demands for miniaturized wearable electronics, robots, artificial intelligence, etc. However, it remains a great challenge to achieve this kind of electronic skins. Here, unprecedented battery-type all-in-one self-powered stretchable electronic skins with a novel structure composed of pressure-sensitive elastic vanadium pentoxide (V2 O5 ) nanowire-based porous cathode, elastic porous polyurethane /carbon nanotube/polypyrrole anode, and polyacrylamide ionic gel electrolyte are reported. A new battery-type self-powered pressure sensing mechanism involving the output current variation caused by the resistance variation of the electrodes and electrolytes under external pressure is revealed. The battery-type self-powered electronic skins combining high sensitivity, broad response range (1.8 Pa-1.5 MPa), high fatigue resistance, and excellent stability against stretching (50% tensile strain) are achieved for the first time. This work provides a new and versatile battery-type sensing strategy for the design of next-generation all-in-one self-powered miniaturized sensors and electronic skins.
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Transparent aerogels are ideal candidates for thermally insulating windows, solar thermal receivers, electronics, etc. However, they are usually prepared via energy-consuming supercritical drying and show brittleness and low tensile strength, significantly restricting their practical applications. It remains a great challenge to prepare transparent aerogels with high tensile strength and toughness. Herein, biomimetic transparent tough cellulose nanofiber-based nanocomposite aerogels with a layered nanofibrous structure are achieved by vacuum-assisted self-assembly combined with ambient pressure drying. The nacre-like layered homogeneous nanoporous structures can reduce light scattering and effectively transfer stress and prevent stress concentration under external forces. The aerogels exhibit an attractive combination of excellent transparency and hydrophobicity, high compressive and tensile strengths, high toughness, excellent machinability, thermal superinsulation, and wide working temperature range (-196 to 230 °C). It is demonstrated that they can be used for superinsulating windows of buildings and high-efficient thermal management for electronics and human bodies. In addition, a prototype of transparent flexible aerogel-based triboelectric nanogenerator is developed. This work provides a promising pathway toward transparent tough porous materials for energy saving/harvesting, thermal management, electronics, sensors, etc.
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The present study attempts to explore the direct recyclability of glyceroborate from medicine pharmaceutical production wastewater into an aqueous lubricant instead of conventional waste processing methods from the tribological view. In order to determine the tribological feasibility, the physicochemical properties of crude pharmaceutical wastewater are investigated and compared with those of pure glycerol to access their potential lubrication properties. The results demonstrated that the crude pharmaceutical wastewater has better friction-reducing and antiwear properties under the same working conditions. Besides outstanding lubricating properties, the friction-induced formation of borate tribo-film and intermediate FeOOH compound favors lowering of the shear stress between the rubbing surfaces. This finding better provides an alternative to transform glyceroborate from medicine pharmaceutical production wastewater after simple distillation processing to a potential aqueous lubricant.
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Complex microbial ecosystems in both gastrointestinal and respiratory systems have been found to have a significant impact on human health. Growing evidence has demonstrated that intestinal dysbiosis can increase vulnerability to pulmonary infections. However, changes in the composition and activity of the intestinal flora after probiotic supplementation may alter the disease state of the host. The effects of probiotics on the improvement of diseases, such as severe pneumonia (SP), in intensive care units (ICUs) remain controversial. We retrospectively included 88 patients diagnosed with severe pneumonia between April 2021 and June 2022. The patients were divided into 2 groups: a probiotic group (nâ =â 40) and a control group (nâ =â 48). In addition, changes in CRP, PCT, WBC, IL-6, Clostridium difficile toxin, and PSI pneumonia scores were assessed. Changes in the gut microbiome of the patients were assessed using amplicon sequencing. Compared to the control group, a significant reduction in the incidence of length of hospital stay was observed in the probiotic group, but there were no significant differences in the mortality rate, duration of fever, diarrhea, and constipation. After probiotic treatment, CRP, PCT, WBC, and PSI score were significantly lower than before, and better clinical efficacy was achieved in the probiotic group for the duration of antibiotic therapy. Gut microbiota analysis revealed that the abundance of opportunistic pathogens (e.g., Massilia) increased remarkably at the genus level in the control group, and a significant increase in Erysipelotrichaceae_ge was observed after probiotic intervention. The control group showed an increase in opportunistic pathogens (Citrobacter, Massilia) during the antibiotic treatment. Probiotics interventions inhibit the growth of opportunistic pathogens. In addition, we found that the population of butyrate-producing bacteria (e.g., Ruminococcaceae UCG-005) increased following probiotic treatment.
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Microbioma Gastrointestinal , Neumonía , Probióticos , Humanos , Anciano , Ecosistema , Estudios Retrospectivos , Probióticos/uso terapéutico , Neumonía/tratamiento farmacológico , Resultado del Tratamiento , Antibacterianos/uso terapéuticoRESUMEN
Mudanjiang phlebovirus (MJPV) is a newly discovered phlebovirus, initially detected from Ixodes persulcatus ticks in China in 2022. In this study, by next-generation sequencing (NGS) on a wide variety of ticks and wild small animals in China, we detected MJPV from I. persulcatus and Meriones meridianus. Additionally, we conducted RT-PCR and sequencing on 1815 adult ticks and 805 wild small mammals collected from eight provinces in China between 2017 and 2021. MJPV RNA-positive results were found in 0.22% (4/1815) of tick samples, as well as in 0.12% (1/805) of rodent samples. All positive detections were obtained from Heilongjiang and Inner Mongolia. Sequencing analysis revealed nucleotide similarities ranging from 98.23% to 99.11%, as well as amino acid similarities ranging from 99.12% to100%, between the current MJPV strain and previously reported strains of MJPV. Phylogenetic tree analysis demonstrated that the previously reported MJPV strain along with our two variants clustered together with other tick-borne phenuiviruses, indicating their close relationship within this viral group. This study represents the first detection of MJPV infection in wild rodents, expanding the known host range for this virus in the endemic regions.
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Ixodes , Phlebovirus , Virus , Animales , Phlebovirus/genética , Filogenia , Animales Salvajes , Roedores , China/epidemiologíaRESUMEN
Hepatic ischemia-reperfusion injury (IRI) is a common complication occurs during hepatic resection and transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Here, we aim to explore the role of fibroblast growth factor 18 (FGF18) in hepatic IRI. In this work, we find that Hepatic stellate cells (HSCs) secrete FGF18 and alleviates hepatocytes injury. HSCs-specific FGF18 deletion largely aggravates hepatic IRI. Mechanistically, FGF18 treatment reduces the levels of ubiquitin carboxyl-terminal hydrolase 16 (USP16), leading to increased ubiquitination levels of Kelch Like ECH Associated Protein 1 (KEAP1) and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, USP16 interacts and deubiquitinates KEAP1. More importantly, Nrf2 directly binds to the promoter of USP16 and forms a negative feedback loop with USP16. Collectively, our results show FGF18 alleviates hepatic IRI by USP16/KEAP1/Nrf2 signaling pathway in male mice, suggesting that FGF18 represents a promising therapeutic approach for hepatic IRI.
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Factor 2 Relacionado con NF-E2 , Daño por Reperfusión , Animales , Masculino , Ratones , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Daño por Reperfusión/etiología , Daño por Reperfusión/genética , Transducción de SeñalRESUMEN
Purpose: To investigate changes and links of stress and high sleep reactivity (H-SR) on the macro-structure and orderliness of sleep and cortisol levels in good sleepers (GS). Patients and Methods: Sixty-two GS (18-40 years old) were recruited, with 32 in the stress group and 30 in the control group. Each group was further divided into H-SR and low SR subgroups based on the Ford Insomnia Response to Stress Test. All participants completed two nights of polysomnography in a sleep laboratory. Before conducting polysomnography on the second night, the stress group completed the Trier Social Stress Test and saliva was collected. Results: The duration of NREM sleep stages 1, 2 (N1, N2) and rapid eye movement sleep (REM) decreased, and the values of approximate entropy, sample entropy, fuzzy entropy, and multiscale entropy increased under stress and SR effects. Stress increased rapid eye movement density, and H-SR increased cortisol reactivity. Conclusion: Stress can damage the sleep and increase cortisol release in GS, especially those with H-SR. N1, N2 and REM sleep are more easily affected, while NREM sleep stage 3 sleep is relatively stable.
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Introduction: The potentially unlimited number of cardiomyocyte (CMs) derived from human induced pluripotent stem cells (hiPSCs) in vitro facilitates high throughput applications like cell transplantation for myocardial repair, disease modelling, and cardiotoxicity testing during drug development. Despite promising progress in these areas, a major disadvantage that limits the use of hiPSC derived CMs (hiPSC-CMs) is their immaturity. Methods: Three hiPSC lines (PCBC-hiPSC, DP3-hiPSCs, and MLC2v-mEGFP hiPSC) were differentiated into CMs (PCBC-CMs, DP3-CMs, and MLC2v-CMs, respectively) with or without retinoic acid (RA). hiPSC-CMs were either maintained up to day 30 of contraction (D30C), or D60C, or purified using lactate acid and used for experiments. Purified hiPSC-CMs were cultured in basal maturation medium (BMM) or BMM supplemented with ascorbic acid (AA) for 14 days. The AA treated and non-treated hiPSC-CMs were characterized for sarcomeric proteins (MLC2v, TNNI3, and MYH7), ion channel proteins (Kir2.1, Nav1.5, Cav1.2, SERCA2a, and RyR), mitochondrial membrane potential, metabolomics, and action potential. Bobcat339, a selective and potent inhibitor of DNA demethylation, was used to determine whether AA promoted hiPSC-CM maturation through modulating DNA demethylation. Results: AA significantly increased MLC2v expression in PCBC-CMs, DP3-CMs, MLC2v-CMs, and RA induced atrial-like PCBC-CMs. AA treatment significantly increased mitochondrial mass, membrane potential, and amino acid and fatty acid metabolism in PCBC-CMs. Patch clamp studies showed that AA treatment induced PCBC-CMs and DP3-CMs adaptation to a ventricular-like phenotype. Bobcat339 inhibited MLC2v protein expression in AA treated PCBC-CMs and DP3-CMs. DNA demethylation inhibition was also associated with reduced TET1 and TET2 protein expressions and reduced accumulation of the oxidative product, 5 hmC, in both PCBC-CMs and DP3-CMs, in the presence of AA. Conclusions: Ascorbic acid induced MLC2v protein expression and promoted ventricular-like CM subtype in hiPSC-CMs. The effect of AA on hiPSC-CM was attenuated with inhibition of TET1/TET2 mediated DNA demethylation.
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Células Madre Pluripotentes Inducidas , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Ácido Ascórbico/farmacología , Miocitos Cardíacos/metabolismo , Diferenciación Celular , Tretinoina/farmacología , Tretinoina/metabolismo , Células Cultivadas , Oxigenasas de Función Mixta/metabolismo , Proteínas Proto-Oncogénicas/metabolismoRESUMEN
OBJECTIVES: To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment. METHODS: A retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models. RESULTS: A total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log10(lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts. CONCLUSION: Glucocorticoids are not recommended for mild patients defined by L-index <3.823; however, patients with severe SFTS may benefit from low-moderate doses of glucocorticoids.