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BACKGROUND: Vesicular stomatitis virus (VSV) is a typical non-segmented negative-sense RNA virus of the genus Vesiculovirus in the family Rhabdoviridae. VSV can infect a wide range of animals, including humans, with oral blister epithelial lesions. VSV is an excellent model virus with a wide range of applications as a molecular tool, a vaccine vector, and an oncolytic vector. To further understand the interaction between VSV and host cells and to provide a theoretical basis for the application prospects of VSV, we analyzed the expression of host differentially expressed genes (DEGs) during VSV infection using RNA-Seq. RESULTS: Our analyses found a total of 1015 differentially expressed mRNAs and 161 differentially expressed LncRNAs in BHK-21 cells infected with VSV for 24 h compared with controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment showed that the differentially expressed lncRNAs and their target genes were mainly concentrated in pathways related to apoptosis, cancer, disease, and immune system activation, including the TNF, P53, MAPK, and NF-kappaB signaling pathways. The differentially expressed lncRNA can modulate immune processes by regulating genes involved in these signaling transmissions. Ten randomly selected DEGs, namely, Il12rb2, F2, Masp2, Mcl1, FGF18, Ripk1, Fas, BMF, POLK, and JAG1, were validated using RT-qPCR. As predicted through RNA-Seq analysis, these DEGs underwent either up- or downregulation, suggesting that they may play key regulatory roles in the pathways mentioned previously. CONCLUSIONS: Our study showed that VSV infection alters the host metabolic network and activates immune-related pathways, such as MAPK and TNF. The above findings provide unique insights for further study of the mechanism of VSV-host interactions and, more importantly, provide a theoretical basis for VSV as an excellent vaccine carrier.
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RNA Longo não Codificante , Vacinas , Animais , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica , RNA-Seq , TranscriptomaRESUMO
Developing 3D hosts is one of the most promising strategies for putting forward the practical application of lithium(Li)-based anodes. However, the concentration polarization and uniform electric field of the traditional 3D hosts result in undesirable "top growth" of Li, reduced space utilization, and obnoxious dendrites. Herein, a novel dual-gradient 3D host (GDPL-3DH) simultaneously possessing gradient-distributed pore structure and lithiophilic sites is constructed by an electrospinning route. Under the synergistic effect of the gradient-distributed pore and lithiophilic sites, the GDPL-3DH exhibits the gradient-increased electrical conductivity from top to bottom. Also, Li is preferentially and uniformly deposited at the bottom of the GDPL-3DH with a typical "bottom-top" mode confirmed by the optical and SEM images, without Li dendrites. Consequently, an ultra-long lifespan of 5250 h of a symmetrical cell at 2 mA cm-2 with a fixed capacity of 2 mAh cm-2 is achieved. Also, the full cells based on the LiFePO4, S/C, and LiNi0.8Co0.1Mn0.1O2 cathodes all exhibit excellent performances. Specifically, the LiFePO4-based cell maintains a high capacity of 136.8 mAh g-1 after 700 cycles at 1 C (1 C = 170 mA g-1) with 94.7% capacity retention. The novel dual-gradient strategy broadens the perspective of regulating the mechanism of lithium deposition.
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The inhomogeneous nucleation and growth of Li dendrite combined with the spontaneous side reactions with the electrolytes dramatically challenge the stability and safety of Li metal anode (LMA). Despite tremendous endeavors, current success relies on the use of significant excess of Li to compensate the loss of active Li during cycling. Herein, a near-surface Li+ irrigation strategy is developed to regulate the inhomogeneous Li deposition behavior and suppress the consequent side reactions under limited Li excess condition. The conformal polypyrrole (PPy) coating layer on Cu surface via oxidative chemical vapor deposition technique can induce the migration of Li+ to the interregional space between PPy and Cu, creating a near-surface Li+-rich region to smooth diffusion of ion flux and uniform the deposition. Moreover, as evidenced by multiscale characterizations including synchrotron high-energy X-ray diffraction scanning, a robust N-rich solid-electrolyte interface (SEI) is formed on the PPy skeleton to effectively suppress the undesired SEI formation/dissolution process. Strikingly, stable Li metal cycling performance under a high areal capacity of 10 mAh cm-2 at 2.0 mA cm-2 with merely 0.5 × Li excess is achieved. The findings not only resolve the long-standing poor LMA stability/safety issues, but also deepen the mechanism understanding of Li deposition process.
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The monkeypox epidemic has attracted global attention to poxviruses. The cytoplasmic replication of poxviruses requires extensive protein synthesis, challenging the capacity of the endoplasmic reticulum (ER). However, the role of the ER in the life cycle of poxviruses is unclear. In this study, we demonstrate that infection with the lumpy skin disease virus (LSDV), a member of the poxvirus family, causes ER stress in vivo and in vitro, further facilitating the activation of the unfolded protein response (UPR). Although UPR activation aids in the restoration of the cellular environment, its significance in the LSDV life cycle remains unclear. Furthermore, the significance of ER imbalance for viral replication is also unknown. We show that LSDV replication is hampered by an unbalanced ER environment. In addition, we verify that the LSDV replication depends on the activation of PERK-eIF2α and IRE1-XBP1 signaling cascades rather than ATF6, implying that global translation and reduced XBP1 cleavage are deleterious to LSDV replication. Taken together, these findings indicate that LSDV is involved in the repression of global translational signaling, ER chaperone transcription, and ATF6 cleavage from the Golgi into the nucleus, thereby maintaining cell homeostasis; moreover, PERK and IRE1 activation contribute to LSDV replication. Our findings suggest that targeting UPR elements may be applied in response to infection from LSDV or even other poxviruses, such as monkeypox.
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Vírus da Doença Nodular Cutânea , Mpox , Animais , Bovinos , Humanos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Vírus da Doença Nodular Cutânea/metabolismo , Mpox/metabolismo , Transdução de Sinais , Resposta a Proteínas não Dobradas , Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/metabolismo , Fator 6 Ativador da Transcrição/metabolismoRESUMO
Goatpoxvirus (GTPV), sheeppoxvius (SPPV), and the Lumpy skin disease virus (LSDV) is a Capripoxvirus belonging to the family poxviridae. They can cause significant economic losses in countries where this disease are endemic. However, effective and convenient diagnostic tools against sera antibody are not readily available until now. Toward this goal, a polyclonal antibody competitive enzyme-linked immunosorbent assay (c-ELISA) of detecting serogroup-specific antibody is established based on major LSDV antigen A33. Serum samples (n = 605) were collected to optimize the c-ELISA from different areas. The cut-off value for the c-ELISA was estimate using percent inhibition (PI) values. The diagnostic performance of test including sensitivity (sn) and specificity (sp) were obtained by receiver operator characteristic (ROC) analysis. Among these analysis, > 57.61% PI value was accepted as cut-off of the c-ELISA, the diagnostic sn an diagnostic sp were reached to 96.4% and 98.5%, at > 95% confidence interval. These results show that the developed competitive ELISA is sensitive, specific, and reliable, which make it appropriate for serological investigation.
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Anticorpos Antivirais , Antígenos Virais , Ensaio de Imunoadsorção Enzimática , Sensibilidade e Especificidade , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Antivirais/sangue , Animais , Antígenos Virais/imunologia , Capripoxvirus/imunologia , Curva ROC , Cabras , Infecções por Poxviridae/diagnóstico , Infecções por Poxviridae/veterinária , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/virologiaRESUMO
PURPOSE: Whether chronotype affects the health outcomes of night shift work populations is unknown. This study aimed to assess the influence of different chronotypes in the rotating night shift population on sleep status, mood, blood pressure (BP), and heart rate variability (HRV), as well as the circadian rhythm of BP and HRV. METHODS: A total of 208 rotating night shift workers were included. All participants completed structured questionnaires to assess chronotype, mood and sleep status. During their daily lives outside of the night shift, they underwent 24-hour Holter electrocardiogram monitoring and 24-hour ambulatory blood pressure monitoring. Day-time and night-time BP and BP dipping were obtained. Day-time and night-time HRV values (SDNN, RMSSD, LF, HF, LF nu, SD1, SD2 and SD2/SD1) were calculated and fitted to the cosine period curve. Three circandian parameters (mesor, amplitude and acrophase) were extracted to quantify the circadian rhythm of the HRV indices. RESULTS: Among all three groups, E-type showed more fatigue and sleepiness. In addition, E-type showed blunted diastolic BP dipping. Notably, E-type showed association with higher RMSSD, LF, HF and SD1 in the night time, and higher mesors of RMSSD and LF and amplitude of SD2/SD1 in circadian analysis. CONCLUSION: Chronotype is a factor affecting fatigue, sleepiness and cardiovascular circadian rhythms of rotating night shift workers. Chronotype should be taken into consideration for managing night-shift rotation to promote occupational health.
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Monitorização Ambulatorial da Pressão Arterial , Cronotipo , Sindactilia , Humanos , Sonolência , Sono/fisiologia , Ritmo Circadiano/fisiologia , Fadiga , Tolerância ao Trabalho Programado/fisiologiaRESUMO
BACKGROUND: Health care workers (HCWs) frequently face multiple stressors at work, particularly those working night shifts. HCWs who have experienced distress may find it difficult to adopt stress management approaches, even if they are aware of the effects of stress and coping processes. Therefore, an individualized intervention may be required to assist distressed HCWs in bridging the "knowledge-practice" gap in stress management and effectively alleviating stress symptoms. OBJECTIVE: The main objective of this research was to compare the effects of a complex interactive multimodal intervention (CIMI) to self-guided stress management interventions on stress symptoms of distressed HCWs, as measured by physiological (heart rate variability), psychological (perceived stress, mental distress, and subjective happiness), and sleep disorder (fatigue and sleepiness) indicators. METHODS: We conducted a nonrandomized, controlled study in 2 Chinese general hospitals. The participants in this study were 245 HCWs who fulfilled at least 1 of the 3 dimensions on the Depression, Anxiety, and Stress Scale. All eligible individuals were required to complete a questionnaire and wear a 24-hour Holter device to determine the physiological signs of stress as indexed by heart rate variability at both baseline and after the intervention. The CIMI group received a 12-week online intervention with 4 components-mobile stress management instruction, a web-based WeChat social network, personalized feedback, and a nurse coach, whereas the control group simply received a self-guided intervention. RESULTS: After a 12-week intervention, the Perceived Stress Scale (PSS) scores reduced significantly in the CIMI group (mean difference [MD] -5.31, 95% CI -6.26 to -4.37; P<.001) compared to the baseline levels. The changes in PSS scores before and after the intervention exhibited a significant difference between the CIMI and control groups (d=-0.64; MD -4.03, 95% CI -5.91 to -2.14; P<.001), and the effect was medium. In terms of physiological measures, both the control group (MD -9.56, 95% CI -16.9 to -2.2; P=.01) and the CIMI group (MD -8.45, 95% CI -12.68 to -4.22; P<.001) demonstrated a significant decrease in the standard deviation of normal-to-normal intervals (SDNN) within the normal clinical range; however, there were no significant differences between the 2 groups (d=0.03; MD 1.11, 95% CI -7.38 to 9.59; P=.80). CONCLUSIONS: The CIMI was an effective intervention for improving sleep disorders, as well as parts of the psychological stress measures in distressed HCWs. The findings provide objective evidence for developing a mobile stress management intervention that is adaptable and accessible to distressed HCWs, but its long-term effects should be investigated in future research. TRIAL REGISTRATION: ClinicalTrials.gov NCT05239065; https://clinicaltrials.gov/ct2/show/NCT05239065.
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Pessoal de Saúde , Humanos , China , Feminino , Masculino , Adulto , Pessoal de Saúde/psicologia , Estresse Psicológico/terapia , Estresse Psicológico/psicologia , Pessoa de Meia-Idade , Estresse Ocupacional/terapia , Estresse Ocupacional/psicologia , Frequência Cardíaca , Inquéritos e QuestionáriosRESUMO
Insecticides are an indispensable and important tool for agricultural production. However, the inappropriate application of insecticides can cause damage to the food chain and ecosystem. Orius similis is an important predatory and natural enemy of Frankliniella occidentalis. Imidacloprid is widely used to control pests, but will inevitably exert adverse effects on O. similis. In order to determine the effect of different imidacloprid treatments on the ability of O. similis to prey on the 2nd-instar nymphs of F. occidentalis, we determined the toxicity and predation of imidacloprid on different stages of O. similis under contact and ingestion treatments. In addition, we used the Holling disc equation to evaluate the ability of O. similis to search and exhibit predatory activity following contact and ingestion treatments. Analysis showed that the highest LC10 and LC20 values for imidacloprid contact and ingestion toxicity treatment were 17.06 mg/L and 23.74 mg/L, respectively. Both imidacloprid treatments led toa reduction in the predatory of O. similis on prey. The functional responses of the 3rd to 5th instar nymphs, along with female and male O. similis adults to the 2nd-instar nymphs of F. occidentalis were consistent with the Holling type II response following contact and ingestion with imidacloprid. However, following imidacloprid treatment, the handing time (Th) of O. similis with single F. occidentalis was prolonged and the instantaneous attack rate (a) was reduced after imidacloprid treatment. The predatory capacity (a/Th) of female O. similis adults when treated with the LC10 concentration of imidacloprid by ingestion was 52.85; this was lower than that of the LC10 concentration of imidacloprid in the contact treatment (57.67). The extent of predation of O. similis on the 2nd-instar nymphs of F. occidentalis was positively correlated with prey density, although the search effect was negatively correlated with prey density. The most extensive search effect was exhibited by adult O. similis females. Simulations with the Hessell-Varley interference model showed that an increase in the number of O. similis would reduce search efficiency regardless of whether they were treated with imidacloprid or not. Thus, O. similis, especially female adults, exhibited strong potential for controlling the 2nd-instar nymphs of F. occidentalis. The toxicity of ingestion following treatment with the same concentration of imidacloprid in O. similis was greater than that of contact treatment. When using O. similis to control F. occidentalis in the field, we should increase the number of female adults released, and prolong the interval between imidacloprid treatment and O. similis exposure. This strategy will improve the control ability of O. similis, coordinate both chemical and biological control, reduce the impact of pesticides on the environment, and improve the efficiency of agricultural production.
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Inseticidas , Neonicotinoides , Nitrocompostos , Animais , Feminino , Masculino , Inseticidas/toxicidade , Cadeia Alimentar , Comportamento Predatório , Ecossistema , Comportamento Alimentar , NinfaRESUMO
BACKGROUND: Poststroke cognitive impairment (PSCI) is highly prevalent in stroke survivors and correlated with unfavorable clinical outcomes. This study aimed to identify the neural substrate of PSCI using atlas-based disconnectome analysis and assess the value of disconnection score, a baseline measure for stroke-induced structural disconnection, in PSCI prediction. METHODS: A multicenter prospective cohort of 676 first-ever patients with acute ischemic stroke was enrolled from 3 independent hospitals in China. Sociodemographic, clinical, and neuroimaging data were collected at acute stage of stroke. Cognitive assessment was performed at 3 months after stroke. Voxel-wise and tract-wise disconnectome analysis were performed to uncover the strategic structural disconnection pattern for global PSCI. Disconnection score was calculated for each participant in leave-one-dataset-out cross-validation. Multivariable logistic regression was performed for the association between disconnection score and PSCI. Prediction models with and without disconnection score were developed, cross-validated, and compared in terms of discrimination and goodness-of-fit. RESULTS: Compared with lesions of non-PSCI, those of PSCI were more likely to have fiber connections with left prefrontal cortex and left deep structures (thalamus and basal ganglia). Disconnection score could predict the risk and severity of PSCI during cross-validation, and was independently associated with PSCI after controlling for all baseline covariates (odds ratio, 1.38 [95% CI, 1.17-1.64]; P<0.001). Incorporating disconnection score into a reference model with 6 known predictors resulted in significant improvement in both discrimination and goodness-of-fit throughout cross-validation. CONCLUSIONS: A strategic structural disconnection pattern centered on left prefrontal cortex, thalamus, and basal ganglia is identified for global PSCI using indirect disconnectome analysis. The baseline disconnection score is independently predictive of PSCI and has significant incremental value to preexisting sociodemographic, clinical, and neuroimaging predictors. REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.
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Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/psicologia , Modelos LogísticosRESUMO
Realgar-Indigo naturalis formula (RIF), with A4S4 as a major ingredient, is an oral arsenic used in China to treat pediatric acute promyelocytic leukemia (APL). The efficacy of RIF is similar to that of arsenic trioxide (ATO). However, the effects of these two arsenicals on differentiation syndrome (DS) and coagulation disorders, the two main life-threatening events in children with APL, remain unclear. We retrospectively analyzed 68 consecutive children with APL from South China Children Leukemia Group-APL (SCCLG-APL) study. Patients received all-trans retinoic acid (ATRA) on day 1 of induction therapy. ATO 0.16 mg/kg day or RIF 135 mg/kg·day was administrated on day 5, while mitoxantrone was administered on day 3 (non-high-risk) or days 2-4 (high-risk). The incidences of DS were 3.0% and 5.7% in ATO (n = 33) and RIF (n = 35) arms (p = 0.590), and 10.3% and 0% in patients with and without differentiation-related hyperleukocytosis (p = 0.04), respectively. Moreover, in patients with differentiation-related hyperleukocytosis, the incidence of DS was not significantly different between ATO and RIF arms. The dynamic changes of leukocyte count between arms were not statistically different. However, patients with leukocyte count > 2.61 × 109/L or percentage of promyelocytes in peripheral blood > 26.5% tended to develop hyperleukocytosis. The improvement of coagulation indexes in ATO and RIF arms was similar, with fibrinogen and prothrombin time having the quickest recovery rate. This study showed that the incidence of DS and recovery of coagulopathy are similar when treating pediatric APL with RIF or ATO.
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Arsênio , Arsenicais , Transtornos da Coagulação Sanguínea , Leucemia Promielocítica Aguda , Criança , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Arsênio/uso terapêutico , Estudos Retrospectivos , Trióxido de Arsênio , Tretinoína , Protocolos de Quimioterapia Combinada Antineoplásica , Óxidos , Resultado do TratamentoRESUMO
Intestinal organoids have emerged as powerful model systems for studying the complex structure and function of the intestine. However, there is a lack of widely applicable methods for the collection, labeling, and imaging of intestinal organoids. In this study, we developed a novel method for loading and labeling intestinal organoids, a method that efficiently collects the organoids and facilitates imaging of their three-dimensional (3D) structure. Based on this strainer platform, mouse intestinal organoids were adequately collected and immobilized, facilitating the immunolabeling workflow to target proteins of the organoids. After evaluation, the strainer size of 40 µm was considered to be more conducive to the collection and labeling of mouse intestinal organoids. More extensive research on organoids of multiple types and species origins will contribute to broadening the applicability of the methodology. Overall, our study proposes an innovative workflow for loading and analyzing intestinal organoids. The combination of a strainer-based collection method, fluorescent labeling, and 3D reconstruction provides valuable insights into the organization and complexity of these tissue models, thereby offering new avenues for investigating intestinal development, disease modeling, and drug discovery.
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Corantes , Descoberta de Drogas , Animais , Camundongos , Modelos Biológicos , Organoides , Fluxo de TrabalhoRESUMO
The recent spread of the monkeypox virus among humans has heightened concerns regarding orthopoxvirus infections. Consequently, conducting a comprehensive study on the immunobiology of the monkeypox virus is imperative for the development of effective therapeutics. Ectromelia virus (ECTV) closely resembles the genetic and disease characteristics of monkeypox virus, making it a valuable research tool for studying orthopoxvirus-host interactions. Guanylate-binding proteins (GBPs), highly expressed interferon-stimulated genes (ISGs), have antagonistic effects against various intracellular pathogenic microorganisms. Our previous research has shown that GBP2 has a mild but statistically significant inhibitory effect on ECTV infection. The presence of a significant number of molecules in the poxvirus genome that encode the host immune response raises questions about whether it also includes proteins that counteract the antiviral activity of GBP2. Using IP/MS and co-IP technology, we discovered that the poly(A) polymerase catalytic subunit (PAPL) protein of ECTV is a viral regulatory molecule that interacts with GBP2. Further studies have shown that PAPL antagonizes the antiviral activity of GBP2 by reducing its protein levels. Knocking out the PAPL gene of ECTV with the CRISPR/Cas9 system significantly diminishes the replication ability of the virus, indicating the indispensable role of PAPL in the replication process of ECTV. In conclusion, our study presents preliminary evidence supporting the significance of PAPL as a virulence factor that can interact with GBP2.
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Vírus da Ectromelia , Ectromelia Infecciosa , Animais , Camundongos , Humanos , Vírus da Ectromelia/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Polinucleotídeo Adenililtransferase/metabolismo , Domínio Catalítico , Antivirais/farmacologiaRESUMO
Objective: To analyze the electroencephalogram (EEG) features of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) and to study the clinical assessment value of the degree of EEG background slowing and the presence of δ brush. Methods: We enrolled 52 patients with anti-NMDARE and collected their clinical data, including age, sex, form of disease onset, status of tumor comorbidity, auxiliary examination findings (cerebrospinal fluid [CSF] anti-methyl-D-aspartate receptor antibody titers, magnetic resonance imaging [MRI] reports, and EEG results), treatment status, and follow-up after discharge. The degree of EEG background abnormality and the presence of δ brush in the EEG of patients with different clinical features were analyzed. Results: Among the 52 patients, 7 (14%) had normal EEG, and 45 (87%), abnormal EEG, including 25 (48%) with mild abnormalities, 11 (21%) with moderate abnormalities, and 9 (17%) with severe abnormalities. δ brush was seen in 6 (12%) patients. At the time of EEG, 32 (62%) patients were in the mild condition group and 20 (38%) patients were in the severe condition group. After 1 year of follow-up, there were 45 (86%) patients in the good prognosis group and 7 (14%) patients in the poor prognosis group. The exacerbation of EEG background abnormalities and the presence of δ brush were indications for an increase in the proportion of patients who were in severe condition, who needed ICU admission, and who had poor prognosis ( P<0.01). The worse the EEG background abnormalities, the higher the proportion of CSF antibody titers>1â¶10 ( P=0.035), and the higher the proportion of patients initiating second-line immunotherapy ( P=0.008). The δ brush was seen a higher proportion in patients with comorbid tumors ( P=0.012). The probability of δ brush presence was higher in the first-time diagnosis cases than that in recurrent cases ( P=0.023). Conclusions: The degree of EEG slowing and the presence of δ brush have shown consistent performance in assessing patients' condition and predicting prognosis. The slower the EEG, the more severe the disease, and the worse the prognosis. The presence of δ brush indicates severe disease and poor prognosis. EEG slowing is correlated with the immune status of patients with anti-NMDARE. The slower the EEG, the more severe the immune abnormalities. In clinical practice, patient EEG should be under dynamic monitoring in order to evaluate the effect of immunotherapy. If EEG slowing is not improved, enhanced immunotherapy should be considered as early as possible. The δ brush is seen at a higher proportion in patients with comorbid tumors. Therefore, active efforts should be made to screen for tumors when δ brush is present.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Eletroencefalografia/métodos , HospitalizaçãoRESUMO
The universal cathode crossover such as chemical and oxygen has been significantly overlooked in lithium metal batteries using high-energy cathodes which leads to severe capacity degradation and raises serious safety concerns. Herein, a versatile and thin (≈25â µm) interlayer composed of multifunctional active sites was developed to simultaneously regulate the Li deposition process and suppress the cathode crossover. The as-induced dual-gradient solid-electrolyte interphase combined with abundant lithiophilic sites enable stable Li stripping/plating process even under high current density of 10â mA cm-2 . Moreover, X-ray photoelectron spectroscopy and synchrotron X-ray experiments revealed that N-rich framework and CoZn dual active sites can effectively mitigate the undesired cathode crossover, hence significantly minimizing Li corrosion. Therefore, assembled lithium metal cells using various high-energy cathode materials including LiNi0.7 Mn0.2 Co0.1 O2 , Li1.2 Co0.1 Mn0.55 Ni0.15 O2 , and sulfur demonstrate significantly improved cycling stability with high cathode loading.
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ABHD5 is an essential coactivator of ATGL, the rate-limiting triglyceride (TG) lipase in many cell types. Importantly, ABHD5 also functions as a tumor suppressor, and ABHD5 mRNA expression levels correlate with patient survival for several cancers. Nevertheless, the mechanisms involved in ABHD5-dependent tumor suppression are not known. We found that overexpression of ABHD5 induces cell cycle arrest at the G1 phase and causes growth retardation in a panel of prostate cancer cells. Transcriptomic profiling and biochemical analysis revealed that genetic or pharmacological activation of lipolysis by ABHD5 potently inhibits mTORC1 signaling, leading to a significant downregulation of protein synthesis. Mechanistically, we found that ABHD5 elevates intracellular AMP content, which activates AMPK, leading to inhibition of mTORC1. Interestingly, ABHD5-dependent suppression of mTORC1 was abrogated by pharmacological inhibition of DGAT1 or DGAT2, isoenzymes that re-esterify fatty acids in a process that consumes ATP. Collectively, this study maps out a novel molecular pathway crucial for limiting cancer cell proliferation, in which ABHD5-mediated lipolysis creates an energy-consuming futile cycle between TG hydrolysis and resynthesis, leading to inhibition of mTORC1 and cancer cell growth arrest.
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1-Acilglicerol-3-Fosfato O-Aciltransferase/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , 1-Acilglicerol-3-Fosfato O-Aciltransferase/genética , Monofosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Western Blotting , Ciclo Celular/genética , Ciclo Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Humanos , Lipólise/fisiologia , Metabolismo/fisiologia , RNA-SeqRESUMO
In this work, electrocatalytic upgrade of n-valeraldehyde to octane with higher activity and selectivity is achieved over Au single-atom catalysts (SACs)-NiMn2 O4 spinel synergetic composites. Experiments combined with density functional theory calculation collaboratively demonstrate that Au single-atoms occupy surface Ni2+ vacancies of NiMn2 O4 , which play a dominant role in n-valeraldehyde selective oxidation. A detailed investigation reveals that the initial n-valeraldehyde molecule preferentially adsorbs on the Mn tetrahedral site of NiMn2 O4 spinel synergetic structures, and the subsequent n-valeraldehyde molecule easily adsorbs on the Ni site. Specifically, Au single-atom surficial derivation over spinel lowers the adsorption energy (Eads ) of the initial n-valeraldehyde molecule, which will facilitate its adsorption on the Mn site of Au SACs-NiMn2 O4 . Furthermore, the single-atom Au surficial derivation not only alters the electronic structure of Au SACs-NiMn2 O4 but also lower the Eads of subsequent n-valeraldehyde molecule. Hence, the subsequent n-valeraldehyde molecules prefer adsorption on Au sites rather than Ni sites, and the process of two alkyl radicals originating from Mn-C4 H9 and Au-C4 H9 dimerization into an octane is accordingly accelerated. This work will provide an avenue for the rational design of SACs and supply a vital mechanism for understanding the electrocatalytic upgrade of n-valeraldehyde to octane.
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Óxido de Magnésio , Octanos , Aldeídos , Óxido de Alumínio , CatáliseRESUMO
Capacity degradation and destructive hazards are two major challenges for the operation of lithium-ion batteries at high temperatures. Although adding flame retardants or fire extinguishing agents can provide one-off self-protection in case of emergency overheating, it is desirable to directly regulate battery operation according to the temperature. Herein, smart self-protecting aqueous lithium-ion batteries are developed using thermos-responsive separators prepared through in situ polymerization on the hydrophilic separator. The thermos-responsive separator blocks the lithium ion transport channels at high temperature and reopens when the battery cools down; more importantly, this transition is reversible. The influence of lithium salts on the thermos-responsive behaviors of the hydrogels is investigated. Then suitable lithium salt (LiNO3 ) and concentration (1 m) are selected in the electrolyte to achieve self-protection without sacrificing battery performance. The shut-off temperature can be tuned from 30 to 80 °C by adjusting the hydrophilic and hydrophobic moiety ratio in the hydrogel for targeted applications. This self-protecting LiMn2 O4 /carbon coated LiTi2 (PO4 )3 (LMO/C-LTP) battery shows promise for smart energy storage devices with high safety and extended lifespan in case of high operating temperatures.
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Ammonia electro-oxidation is an extremely significant reaction with regards to the nitrogen cycle, hydrogen economy, and wastewater remediation. The design of efficient electrocatalysts for use in the ammonia electro-oxidation reaction (AOR) requires comprehensive understanding of the mechanism and intermediates involved. In this study, aggregation-induced emission (AIE), a robust fluorescence sensing platform, is employed for the sensitive and qualitative detection of hydrazine (N2H4), one of the important intermediates during the AOR. Here, we successfully identified N2H4 as a main intermediate during the AOR on the model Pt/C electrocatalyst using 4-(1,2,2-triphenylvinyl)benzaldehyde (TPE-CHO), an aggregation-induced emission luminogen (AIEgen). We propose the AOR mechanism for Pt with N2H4 being formed during the dimerization process (NH2 coupling) within the framework of the Gerischer and Mauerer mechanism. The unique chemodosimeter approach demonstrated in this study opens a novel pathway for understanding electrochemical reactions in depth.
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BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.
Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Fígado/fisiopatologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores , COVID-19 , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Orf virus (ORFV) is a member of the genus Parapoxvirus and family Poxviridae. The virus has a worldwide distribution and infects sheep, goats, humans, and wild animals. However, due to the complex structure of the poxvirus, the underlying mechanism of the entry and infection by ORFV remains largely unknown. ORFV ORF047 encodes a protein named L1R. Poxviral L1R serves as the receptor-binding protein and blocks virus binding and entry independently of glycosaminoglycans (GAGs). The study aimed to identify the host interaction partners of ORFV ORF047. METHODS: Yeast two-hybrid cDNA library of sheep testicular cells was applied to screen the host targets with ORF047 as the bait. ORF047 was cloned into a pBT3-N vector and expressed in the NMY51 yeast strain. Then, the expression of bait proteins was validated by Western blot analysis. RESULTS: Sheep SERP1and PABPC4 were identified as host target proteins of ORFV ORF047, and a Co-IP assay further verified their interaction. CONCLUSIONS: New host cell proteins SERP1and PABPC4 were found to interact with ORFV ORF047 and might involve viral mRNA translation and replication.