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In the past, hepatic stellate cells (HSCs) were considered to be noninflammatory cells and to contribute to liver fibrosis by producing extracellular matrix. Recently, it was found that HSCs can also secrete cytokines and chemokines and therefore participate in hepatic inflammation. Autophagy participates in many immune response processes in immune cells. It is unclear whether autophagy is involved in inflammatory cytokine induction in HSCs. MAPK p38, Ulk1 phosphorylation, and the Ulk1-Atg13 complex were analyzed in HSC-T6 cells after LPS treatment. The relationship between autophagy inhibition and inflammation was investigated in primary rat HSCs. We discovered that LPS inhibited autophagy through MAPK p38. The activation of MAPK p38 induced Ulk1 phosphorylation, which disrupted the Ulk1-Atg13 complex and therefore inhibited autophagy. Furthermore, in primary rat HSCs, we demonstrated that autophagy inhibition regulated IL-1ß induction, which depended on the MAPK p38/Ulk1 pathway. Our results reveal a continuous signaling pathway, MAPK p38-Ulk1 phosphorylation-Ulk1-Atg13 disruption, which inhibits autophagy and induces IL-1ß expression in HSCs.NEW & NOTEWORTHY LPS inhibits autophagy in a concentration- and dose-dependent manner in HSC-T6 cells. MAPK p38 induces phosphorylation of Ulk1, which disrupts the Ulk1-Atg13 complex and is therefore required for the inhibition of autophagy by LPS. LPS induces IL-1ß expression via the MAPK p38/Ulk1 pathway in HSCs.
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Células Estrelladas Hepáticas , Lipopolisacáridos , Animales , Autofagia , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Citocinas/metabolismo , Células Estrelladas Hepáticas/metabolismo , Inflamación/metabolismo , Interleucina-1beta , Lipopolisacáridos/metabolismo , Lipopolisacáridos/farmacología , Fosforilación , Ratas , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND & AIMS: There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. METHODS: Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. RESULTS: Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. CONCLUSIONS: TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. TRIAL REGISTRATION: This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019).
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Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/uso terapéutico , Adulto , Alanina , Guanina/análogos & derivados , Guanina/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Humanos , Masculino , Persona de Mediana Edad , Tenofovir/uso terapéutico , Resultado del TratamientoRESUMEN
Quantum steering is an important quantum resource, which is intermediate between entanglement and Bell nonlocality. In this paper, we study steering witnesses for Gaussian states in continuous-variable systems. We give a definition of steering witnesses by covariance matrices of Gaussian states, and then obtain a steering criterion by steering witnesses to detect steerability of any (m+n)-mode Gaussian states. In addition, the conditions for two steering witnesses to be comparable and the optimality of steering witnesses are also discussed.
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BACKGROUND: HBV-resistant mutants in treatment-naïve patients may lead to antiviral treatment failure. It is not clear if HBV mutants are present in pregnant women and about the influence of the preexisting mutants on the short-term antiviral therapy during pregnancy. METHOD: We enrolled 73 pregnant women with high HBV DNA load and telbivudine (TBV) treatment during pregnancy in this retrospective study. The UDPS was used to detect the HBV mutations before and after the TBV treatment. RESULTS: Before TBV treatment, the complexity of HBV quasispecies of all subjects was 0.40 ± 0.09; 41.1% (30/73) and 53.4% (39/73) subjects had rtM204I/V and rtN236 T/A detected, respectively; and 9.6% (7/73) patients had more than 20% frequency mutation of rtM204I/V, which was also similar with high frequency of rtN236 T/A mutation (41.1% vs. 53.4%, P=0.136; frequencies >20%: 9.6% vs. 5.5%, P=0.347). After TBV treatment, 71.2% (52/73) subjects had HBV DNA load ≥ 103 IU/mL at delivery. Among them, 75.0% of patients with rtM204I positive had HBV DNA load ≥103 IU/mL at delivery, which was comparable with the subjects without rtM204I (75.0% vs. 70.8%, P=0.710). No changes were found in the frequencies and the complexity of HBV quasispecies of rtM204I mutation after the TVB treatment. CONCLUSION: The prevalence of preexisting drug-resistant mutations among pregnant women was high using UPDS. However, the preexisting HBV mutation had limited influence on the efficacy of short-term TBV treatment, and TBV treatment during late pregnancy seemed not to increase the risk of emerging HBV-resistant mutants.
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Mother-to-child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow-up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention-to-treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log10 IU/mL.
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Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Telbivudina/uso terapéutico , Tenofovir/uso terapéutico , Adulto , Antivirales/efectos adversos , ADN Viral/sangre , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Estudios Prospectivos , Telbivudina/efectos adversos , Tenofovir/efectos adversos , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Sofosbuvir is the keystone of direct antiviral agents for the chronic hepatitis C (CHC). The safety of sofosbuvir in patients with stage 4-5 chronic kidney disease (CKD) needs further observation in real world. CASE PRESENTATION: Thirty-three patients with stage 5 CKD and hepatitis C virus (HCV) infection from 2 hemodialysis centers accepted sofosbuvir based treatment as we reported previously. Serum potassium concentrations were tested every 4 weeks or on demand. Ten of 33 patients showed recurrence of hyperkalemia. We summarized the characteristics of hyperkalemia occurrence in these 10 patients. Overall, 24 episodes of hyperkalemia were observed in these 10 patients, 21 were under treatment and 3 were after treatment. Patients with or without hyperkalemia before sofosbuvir treatment didn't show significantly differences in the median frequencies of hyperkalemia episodes during the observation period (3.5 vs. 2, p = 0.264). CONCLUSIONS: Patients with stage 5 CKD and HCV infection treated with sofosbuvir based regimens, even halved sofosbuvir, should be taken caution and closely monitoring serum potassium and renal function is necessary.
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Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hiperpotasemia/inducido químicamente , Hiperpotasemia/epidemiología , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Sofosbuvir/uso terapéutico , Respuesta Virológica SostenidaRESUMEN
The C-terminal domain (CTD) of hepadnavirus core protein is involved in multiple steps of viral replication. In particular, the CTD is initially phosphorylated at multiple sites to facilitate viral RNA packaging into immature nucleocapsids (NCs) and the early stage of viral DNA synthesis. For the avian hepadnavirus duck hepatitis B virus (DHBV), CTD is dephosphorylated subsequently to facilitate the late stage of viral DNA synthesis and to stabilize NCs containing mature viral DNA. The role of CTD phosphorylation in virion secretion, if any, has remained unclear. Here, the CTD from the human hepatitis B virus (HBV) was found to be dephosphorylated in association with NC maturation and secretion of DNA-containing virions, as in DHBV. In contrast, the CTD in empty HBV virions (i.e., enveloped capsids with no RNA or DNA) was found to be phosphorylated. The potential role of CTD dephosphorylation in virion secretion was analyzed through mutagenesis. For secretion of empty HBV virions, which is independent of either viral RNA packaging or DNA synthesis, multiple substitutions in the CTD to mimic either phosphorylation or dephosphorylation showed little detrimental effect. Similarly, phospho-mimetic substitutions in the DHBV CTD did not block the secretion of DNA-containing virions. These results indicate that CTD dephosphorylation, though associated with NC maturation in both HBV and DHBV, is not essential for the subsequent NC-envelope interaction to secrete DNA-containing virions, and the CTD state of phosphorylation also does not play an essential role in the interaction between empty capsids and the envelope for secretion of empty virions.IMPORTANCE The phosphorylation state of the C-terminal domain (CTD) of hepatitis B virus (HBV) core or capsid protein is highly dynamic and plays multiple roles in the viral life cycle. To study the potential role of the state of phosphorylation of CTD in virion secretion, we have analyzed the CTD phosphorylation state in complete (containing the genomic DNA) versus empty (genome-free) HBV virions. Whereas CTD is unphosphorylated in complete virions, it is phosphorylated in empty virions. Mutational analyses indicate that neither phosphorylation nor dephosphorylation of CTD is required for virion secretion. These results demonstrate that while CTD dephosphorylation is associated with HBV DNA synthesis, the CTD state of phosphorylation may not regulate virion secretion.
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Proteínas de la Cápside/metabolismo , Cápside/metabolismo , Virus de la Hepatitis B del Pato/metabolismo , Virus de la Hepatitis B/metabolismo , Ensamble de Virus/genética , Animales , Línea Celular Tumoral , Pollos , Células Hep G2 , Virus de la Hepatitis B del Pato/genética , Virus de la Hepatitis B/genética , Humanos , Fosforilación , Estructura Terciaria de Proteína , ARN Viral/metabolismo , Replicación Viral , Esparcimiento de VirusRESUMEN
BACKGROUND AND GOALS: A series of changes in the immune system occur during pregnancy and puerperium. Currently, we aim to characterize both the natural changes in liver inflammation and its association with hepatitis B viremia during this special period. PATIENTS AND METHODS: Chronic hepatitis B (CHB) gravidas were recruited and followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed throughout the period. RESULTS: A total of 1097 CHB mothers had finished the entire follow-up including 451 accepting telbivudine, 178 accepting tenofovir, and 468 without antiviral therapy. Among the mothers, 11.94% went through hepatic flare in the first trimester and the rate decreased to 2.1% at the time of delivery. Nevertheless, a much higher frequency (19.78%) was observed in the early postpartum. Interestingly, alanine aminotransferase level decreased along with the development of pregnancy and then suddenly increased in the first month of puerperium. In addition, a downward trend was observed on the titer of HBsAg and HBeAg after delivery. Of note, an obvious higher frequency of alanine aminotransferase flare was revealed in mothers with high viremia (>6 log10 IU/mL). With multivariate analysis, only hepatitis B virus titer at baseline was strongly associated with hepatic flare during early postpartum (95% confidence interval, 1.012-3.049, P=0.045). The predictive rates of hepatic flare at baseline viral load of 6, 7, and 8 log10 IU/mL were 16.67%, 28.30%, and 30.60%, respectively. CONCLUSIONS: CHB gravidas with high viremia should be monitored closely during entire pregnancy, and extended antiviral therapy is recommend to those mothers with baseline viremia >7 log10 IU/mL.
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Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B/diagnóstico , Atención Perinatal , Complicaciones Infecciosas del Embarazo/diagnóstico , Trastornos Puerperales/diagnóstico , Adulto , Alanina Transaminasa/sangre , Antivirales/administración & dosificación , Antivirales/uso terapéutico , China , Femenino , Hepatitis B/sangre , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Trastornos Puerperales/sangre , Trastornos Puerperales/tratamiento farmacológico , Trastornos Puerperales/virología , Carga Viral , Adulto JovenRESUMEN
BACKGROUND & AIMS: We previously found that hepatic stellate cell activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure. Nitric oxide has shown to induce hepatic stellate cell apoptosis. Whether and how nitric oxide is involved in acute liver failure and autophagy remains unclear. METHODS: Acute liver failure patients were recruited to investigate the correlation between plasma nitric oxide levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from acute liver failure patients who had undergone liver transplantation. The expression of nitric oxide synthases and hepatic stellate cell activation (alpha-SMA), and autophagic activity (LC3) were investigated by immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot analysis, confocal microscopy, and flow cytometry in hepatic stellate cells treated with nitric oxide donors. RESULTS: Plasma nitric oxide level was significantly increased in patients with acute liver failure compared to those with cirrhosis (53.60±19.74 µM vs 19.40±9.03 µM, Z=-7.384, P<.001) and positively correlated with MELD-Na score (r=.539, P<.001), implicating nitric oxide in acute liver failure. At least some Nitric oxide was produced by overexpression of inducible nitric oxide synthases and endothelial nitric oxide synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo observation revealed that autophagy was inhibited in hepatic stellate cells based on decreased LC3 immunostaining, and in vitro experiments demonstrated that Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic stellate cell apoptosis, which was rescued by an autophagy inducer. CONCLUSIONS: Increased nitric oxide synthases/ nitric oxide promotes apoptosis through autophagy inhibition in hepatic stellate cells during acute liver failure, providing a novel strategy for the treatment of patients with acute liver failure.
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Apoptosis , Autofagia , Células Estrelladas Hepáticas/citología , Fallo Hepático Agudo/sangre , Óxido Nítrico/sangre , Adulto , Animales , Femenino , Hepatitis Crónica/complicaciones , Humanos , Hígado/patología , Cirrosis Hepática/complicaciones , Fallo Hepático Agudo/patología , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/metabolismoRESUMEN
BACKGROUND AND AIM: The efficacy of telbivudine for breaking vertical transmission of hepatitis B virus has been well established. Data on the risk of postpartum flare after telbivudine withdrawal and efficacy of extended antiviral therapy after delivery are limited. METHODS: Chronic hepatitis B virus-infected women who received telbivudine beginning at week 24 or 28 of gestation were enrolled and then followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed. RESULTS: Of the 241 women who finished 52 weeks of follow-up, 33.6% had elevated serum alanine aminotransferase (ALT) during pregnancy. Telbivudine administration resulted in ALT normalization in 85.2% before delivery. Compared with women having a normal ALT level throughout pregnancy, those with elevated ALT had a significantly higher rate of ALT flare after telbivudine withdrawal (25.0% vs 11.9%; χ2 = 4.273, P = 0.039). Multivariate analysis indicated that only ALT elevation during pregnancy correlated with postpartum flare after telbivudine withdrawal. Those women with elevated ALT during pregnancy continued antiviral treatment to 52 weeks postpartum and had a significantly higher HBeAg seroconversion rate (P = 0.001) and a notable decrease in HBsAg titers (P = 0.001). CONCLUSION: It is safe for the majority of women to withdraw telbivudine after delivery, whereas exciting serological response encourages extended antiviral therapy for mother with ALT elevation during pregnancy.
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Antivirales/administración & dosificación , Hepatitis B Crónica/tratamiento farmacológico , Periodo Posparto , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Timidina/análogos & derivados , Adulto , Alanina Transaminasa/sangre , Esquema de Medicación , Femenino , Estudios de Seguimiento , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/transmisión , Hepatitis B Crónica/virología , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Telbivudina , Timidina/administración & dosificación , Adulto JovenRESUMEN
The evaluation of a favorable area is crucial for the exploration and exploitation of coalbed methane (CBM) resources. In traditional evaluation methods, the weight of controlling factors for the evaluation of favorable area is often obtained from different models and calculation methods, and the constant weight is commonly used in the entire target area. The influence of the index value of controlling factors and the combination state of these values on the weight is consistently overlooked during the evaluation process. In view of this phenomenon, a new evaluation method based on variable weight theory was introduced to enhance the accuracy of the result from evaluation (i.e., favorable area for CBM development) in this paper. Based on the raw data of controlling factors, the evaluation area was divided into a finite number of regular grids; each grid could be seen as an evaluation unit, and different attribute values were assigned to them. The constant weights are determined by the analytic hierarchy process (AHP), while the variable weight of controlling factors in each unit was calculated by a partitioned variable weight model (VWM) which constructed based on variable weight theory. Finally, the VWM for the evaluation of favorable area was constructed and applied in the Weibei CBM field. The influence of variability in index values on the weight was taken into consideration in this model, which can complement the disadvantage of the constant weight model (CWM). The accuracy of the result from the evaluation of favorable areas for CBM development could be improved by using this VWM, which provides a reasonable idea and method for the selection of target areas in CBM fields.
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The melanocortin 4 receptor (MC4R) gene plays a central role in regulating energy homeostasis and food intake in livestock, thereby affecting their economic worth and growth. In a previous study, the p.T117M mutation in the sheep MC4R gene, which leads to the transition of threonine to methionine, was found to affect the body weight at six months and the average daily gain in Hu sheep. However, there are still limited studies on the frequency of the sheep p.T117M missense mutation globally, and the underlying cellular mechanism remains elusive. Therefore, this study first used WGS to investigate the distribution of the MC4R gene p.T117M mutation in 652 individuals across 22 breeds worldwide. The results showed that the mutation frequency was higher in European breeds compared with Chinese sheep breeds, particularly in Poll Dorset sheep (mutation frequency > 0.5). The p.T117M mutation occurs in the first extracellular loop of MC4R. Mechanistically, the basal activity of the mutated receptor is significantly increased. Specifically, upon treatment with α-MSH and ACTH ligands, the cAMP and MAPK/ERK signaling activation of M117 MC4R is enhanced. These results indicate that the T117M mutation may change the function of the gene by increasing the constitutive activity and signaling activation of cAMP and MAPK/ERK, and, thus, may regulate the growth traits of sheep. In conclusion, this study delved into the global distribution and underlying cellular mechanisms of the T117M mutation of the MC4R gene, establishing a scientific foundation for breeding sheep with superior growth, thereby contributing to the advancement of the sheep industry.
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There is an increasing evidence indicating the involvement of the sympathetic nervous system (SNS) in liver disease development. To achieve an extensive comprehension of the obscure process by which the SNS alleviates inflammatory damage in non-parenchymal liver cells (NPCs) during acute liver failure (ALF), we employ isoproterenol (ISO), a beta-adrenoceptor agonist, to mimic SNS signaling. ISO was administered to C57BL/6J mice to establish an acute liver failure (ALF) model using LPS/D-GalN, which was defined as ISO + ALF. Non-parenchymal cells (NPCs) were isolated from liver tissues and digested for tandem mass tag (TMT) labeled proteomics to identify differentially expressed proteins (DEPs). The administration of ISO resulted in a decreased serum levels of pro-inflammatory cytokines, e.g., TNF-α, IL-1ß, and IL-6 in ALF mice, which alleviated liver damage. By using TMT analysis, it was possible to identify 1587 differentially expressed proteins (DEPs) in isolated NPCs. Notably, over 60% of the DEPs in the ISO + ALF vs. ALF comparison were shared in the Con vs. ALF comparison. According to enrichment analysis, the DEPs influenced by ISO in ALF mice were linked to biological functions of heme and fatty acid metabolism, interferon gamma response, TNFA signaling pathway, and mitochondrial oxidation function. Protein-protein interaction network analysis indicated Mapk14 and Caspase3 may serve as potentially valuable indicators of ISO intervention. In addition, the markers on activated macrophages, such as Mapk14, Casp1, Casp8, and Mrc1, were identified downregulated after ISO initiation. ISO treatment increased the abundance of anti-inflammatory markers in mouse macrophages, as evidenced by the immunohistochemistry (IHC) slides showing an increase in Arg + staining and a reduction in iNOS + staining. Furthermore, pretreatment with ISO also resulted in a reduction of LPS-stimulated inflammation signaling markers, Mapk14 and NF-κB, in human THP-1 cells. Prior treatment with ISO may have the potential to modify the biological functions of NPCs and could serve as an innovative pharmacotherapy for delaying the pathogenesis and progression of ALF.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Isoproterenol , Animales , Ratones , Agonistas Adrenérgicos beta/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Citocinas/metabolismo , Galactosamina , Isoproterenol/farmacología , Lipopolisacáridos/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Fallo Hepático Agudo/tratamiento farmacológico , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/metabolismo , Ratones Endogámicos C57BLRESUMEN
The soluble and fermentable carbohydrate contents was detected over 47% of glucose and fructose in Chinese Elaeagnus angustifolia fruit powder (EAF), being over 47 wt% sugar content more than that of grape. Ethanol was therefore fermented directly from EAF, and different submerged fermentation modes were comparatively employed to optimize ethanol harvest. The results indicated that glucose has certain competitive inhibition on fructose bio-utilization, as well as the EAF solid residue involved fermentation mode also hindered the fermented-ethanol titer. Pectinase addition and in situ hydrolysis seemed to assist somewhat the fermentation. The water-solute fermentation mode is preferable, and glucose and fructose components were completely consumed and converted to 80.96 g/L ethanol at 87.6% ethanol yield even under tannin and pectin inhibition. The fermentation result could provide some experimental data and an approach to not only new biomass resource explores of bioethanol and alcohol beverage production, but also the technological development on valorization commercials of EAF in global draught areas.
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Elaeagnaceae , Etanol , Fermentación , Fructosa , Glucosa , Carbohidratos/química , Frutas , Hidrólisis , Elaeagnaceae/químicaRESUMEN
Anthrax is caused by Bacillus anthracis. Humans are mainly infected through contact with the fur and meat of livestock. The cutaneous form is the most common form. The skin lesions of typical cutaneous anthrax are characterized by shallow ulcers with black crusts, surrounded by small blisters and nonpitting edema of nearby tissues. Metagenomic next-generation sequencing (mNGS) is a new pathogenic detection method which is rapid and unbiased. We reported the first case of cutaneous anthrax diagnosed by mNGS. Ultimately, the man received prompt antibiotic therapy and had a good prognosis. In conclusion, mNGS is proved to be a good method for etiological diagnosis, especially for rare infectious diseases.
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Background and aim: Sepsis is a syndromic response to infection and is associated with high mortality, thus imposing a significant global burden of disease. Although low-molecular-weight heparin (LMWH) has been recommended to prevent venous thromboembolism, its anticoagulant and anti-inflammatory effects in sepsis remain controversial. Owing to the modification of the Sepsis-3 definition and diagnostic criteria, further evaluation of the efficacy and benefit population of LMWH is required. Methods: We performed a retrospective cohort study to assess whether LMWH improved the inflammation, coagulopathy, and clinical outcomes against Sepsis-3 and to identify the target patients. All patients diagnosed with sepsis at the First Affiliated Hospital of Xi'an Jiaotong University (the largest general hospital in northwest China) from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria. Results: After 1:1 propensity score matching, 88 pairs of patients were categorized into the treatment and control groups based on subcutaneous LMWH administration. Compared with the control group, a significantly lower 28-day mortality was observed in the LMWH group (26.1 vs. 42.0%, p = 0.026) with a comparable incidence of major bleeding events (6.8 vs. 8.0%, p = 0.773). Cox regression analysis showed that LMWH administration was the independent protective factor for septic patients (aHR, 0.48; 95% CI, 0.29-0.81; p = 0.006). Correspondingly, the LMWH treatment group showed a significant improvement in inflammation and coagulopathy. Further subgroup analysis showed that LMWH therapy was associated with favorable outcomes in patients younger than 60 years and diagnosed with sepsis-induced coagulopathy (SIC), ISTH overt DIC, non-septic shock, or non-diabetics and in patients included in the moderate-risk group (APACHE II score 20-35 or SOFA score 8-12). Conclusion: Our study results showed that LMWH improves 28-day mortality by improving inflammatory response and coagulopathy in patients meeting Sepsis-3 criteria. The SIC and ISTH overt DIC scoring systems can better identify septic patients who are likely to benefit more from LMWH administration.
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Pregnant women with hemorrhagic fever with renal syndrome (HFRS) are a significant challenge for clinicians. The clinical characteristics of HFRS in pregnant women and its influence on both the pregnant women and fetus have yet to be clarified clearly. To highlight the specific clinical features of HFRS in pregnant women and the outcomes of pregnant women with HFRS and their fetuses, we screened pregnant women with HFRS from inception to May 1st 2021. We also conducted a comparison with non-pregnant women complicated with HFRS. Twenty-seven pregnant women and 87 non-pregnant women with complete electronic medical records were enrolled for final analyses; 55.6% (15/27) and 21.8% (19/87) were diagnosed as critical type in pregnant women and non-pregnant women, respectively. Compared with non-pregnant patients, there was a significantly higher likelihood of critical status in pregnant patients; the risk was significantly higher in late trimester (p <0.001). In addition, hypoalbuminemia and anemia were also evident in pregnant patients (p = 0.04, p <0.001, respectively). Leukocyte count, especially when higher than 15 × 109/L, was significantly correlated with disease severity (p = 0.009). After comprehensive therapy, 26 pregnant patients recovered without sequelae. Five fetal adverse events were reported during hospitalization. All adverse events were observed in mothers with critical types (p = 0.047, X2 = 4.909) and occurred in the later trimester. Collectively, our data show that pregnant woman with HFRS during the third trimester presents a more severe condition, especially those with leukocytosis. However, the majority of those pregnant patients could recover with comprehensive treatment and undergo normal labor.
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Biochar-based fertilizer amendment can improve soil properties partly due to stimulated microbial activities and growths. The karst ecosystem is prone to degradation and accounts for a large proportion of southwest China. Understanding of the response of the microbial community structure to biochar-based fertilizer application is of great significance in karst soil restoration. A field experiment located in southwest China was conducted in typical karst soil, and a high-throughput sequencing approach was used to investigate the effect of biochar-based fertilizer application on microbial community structure in karst soil. Field trials were set up for 24 months using the following treatments: control (CK), compost plus NPK fertilizer (MF), biochar (B), less biochar (half the quantity of biochar in B) plus compost and NPK fertilizer (B1MF), biochar plus compost and NPK fertilizer (BMF), and more biochar (double the quantity of biochar in B) plus compost and NPK fertilizer (B4MF). The results elucidated that BMF and B4MF treatments had higher contents of soil carbon and soil nutrients N, P, and K than the other treatments. Soil microbial abundance and diversity were significantly increased by biochar-based fertilizer amendments (BMF and B4MF), compared to CK (P < 0.05). BMF and B4MF treatments significantly increased the relative abundance of dominant microorganisms, compared to CK (P < 0.05). The difference in the composition of indicator microbes between each treated group indicated that soil amendments altered the microbial community structure. There was a strong correlation between soil properties (soil C-, N-, and P-fractions) and microbial community structure. Furthermore, network analysis revealed that the addition of biochar-based fertilizer increased the scale and complexity of the microbial co-occurrence network. To summarize, the application of biochar-based fertilizer enabled more keystone species in the soil microbial network to participate in soil carbon resource management and soil nutrient cycling, indicating that biochar-based fertilizer is beneficial for the restoration of karst-degraded soils.
Asunto(s)
Fertilizantes , Microbiota , Carbón Orgánico , Fertilizantes/análisis , Suelo , Microbiología del SueloRESUMEN
The application of biochar-based fertilizer can improve soil properties in part by stimulating microbial activity and growth. Karst ecosystems, which make up large areas of Southwest China, are prone to degradation. Understanding the response of arbuscular mycorrhizal fungal (AMF) community structure to biochar-based fertilizer application is of great significance to karst soil restoration. A field experiment was conducted in a typical karst soil (calcareous sandy loam) in Southwest China. A high-throughput sequencing approach was used to investigate the effect of biochar-based fertilization on AMF community structure in the karst soil. With the control (CK), compost with NPK fertilizer (MF), biochar (B), a lower amount of biochar with compost and NPK fertilizer (B1MF), biochar with compost and NPK fertilizer (BMF), and a higher amount of biochar with compost and NPK fertilizer (B4MF), the field trials were set up for 24 months. Soil amendments increased soil nutrient content and AMF diversity. The composition and structure of the AMF community varied among the treatments. AMF community composition was significantly impacted by soil chemical properties such as TC (total carbon), TN (total nitrogen), TP (total phosphorus), and AP (available phosphorus). Furthermore, network analysis showed that biochar-based fertilization increased the scale and complexity of the microbial co-occurrence network. Biochar-based fertilization enabled more keystone species (such as order Diversisporales and Glomerales) in the soil AMF network to participate in soil carbon resource management and soil nutrient cycling, indicating that biochar-based fertilizer is beneficial for the restoration of degraded karst soils.
Asunto(s)
Micobioma , Micorrizas , Carbón Orgánico , Ecosistema , Fertilización , Fertilizantes/análisis , Micorrizas/química , Suelo , Microbiología del SueloRESUMEN
OBJECTIVES: A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. RESULTS: 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.