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To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.

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Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

Asunto(s)

Aflatoxina B1 , Vesículas Extracelulares , Células Estrelladas Hepáticas , Hepatocitos , Cirrosis Hepática , Mitofagia , Proteína p53 Supresora de Tumor , Ubiquitina-Proteína Ligasas , Aflatoxina B1/toxicidad , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/metabolismo , Mitofagia/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Animales , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ratones , Masculino , Humanos , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos

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BACKGROUND: Human herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series. CASE PRESENTATION: In this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively. CONCLUSION: This case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

Asunto(s)

Herpesvirus Humano 6 , Linfohistiocitosis Hemofagocítica , Trastornos Mentales , Adulto , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/complicaciones , Enfermedad Crítica , Reacción en Cadena de la Polimerasa , Herpesvirus Humano 6/genética , Trastornos Mentales/complicaciones

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OBJECTIVE: To predict the influencing factors of neonatal pneumonia in pregnant women with diabetes mellitus using a Bayesian network model. By examining the intricate network connections between the numerous variables given by Bayesian networks (BN), this study aims to compare the prediction effect of the Bayesian network model and to analyze the influencing factors directly associated to neonatal pneumonia. METHOD: Through the structure learning algorithms of BN, Naive Bayesian (NB), Tree Augmented Naive Bayes (TAN), and k-Dependence Bayesian Classifier (KDB), complex networks connecting variables were presented and their predictive abilities were tested. The BN model and three machine learning models computed using the R bnlean package were also compared in the data set. RESULTS: In constraint-based algorithms, three algorithms had different presentation DAGs. KDB had a better prediction effect than NB and TAN, and it achieved higher AUC compared with TAN. Among three machine learning modes, Support Vector Machine showed a accuracy rate of 91.04% and 67.88% of precision, which was lower than TAN (92.70%; 72.10%). CONCLUSION: KDB was applicable, and it can detect the dependencies between variables, identify more potential associations and track changes between variables and outcome.

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Diabetes Mellitus , Mujeres Embarazadas , Embarazo , Recién Nacido , Femenino , Humanos , Teorema de Bayes , Algoritmos , Aprendizaje Automático

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Thermally conductive materials (TCMs) are highly desirable for thermal management applications to tackle the "overheating" concerns in the electronics industry. Despite recent progress, the development of high performance TCMs integrated with an in-plane thermal conductivity (TC) higher than 50.0 W (m K)-1 and a through-plane TC greater than 10.0 W (m K)-1 is still challenging. Herein, self-standing liquid metal@boron nitride (LM@BN) bulks with ultrahigh in-plane TC and through-plane TC were reported for the first time. In the LM@BN bulks, LM could serve as a bonding and thermal linker among the oriented BN platelets, thus remarkably accelerating heat transfer across the whole system. Benefiting from the formation of a unique structure, the LM@BN bulk achieved an ultrahigh in-plane TC of 82.2 W (m K)-1 and a through-plane TC of 20.6 W (m K)-1, which were among the highest values ever reported for TCMs. Furthermore, the LM@BN bulks exhibited superior compressive and leakage-free performances, with a high compressive strength (5.2 MPa) and without any LM leakage even after being crushed. It was also demonstrated that the excellent TCs of the LM@BN bulks made them effectively cool high-power light emitting diode modules. This work opens up one promising pathway for the development of high-performance TCMs for thermal management in the electronics industry.

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As a vulnerable species identified by the International Union for Conservation of Nature (IUCN), Lepidochelys olivacea has attracted extensive attention in recent years. To examine its current distribution and that under future climate change scenarios, we compiled the occurrence data of L. olivacea. With eight predictor variables, including depth, offshore distance, mean primary productivity, minimum primary productivity, mean sea surface temperature, minimum sea surface temperature, mean sea surface salinity, and minimum sea surface salinity, we predicted its distribution in an ensemble species distribution model. The accuracy of the model was evaluated with the parameters of areas under curves (AUC) and true skill statistics (TSS). The results showed that the AUC and TSS values were 0.96 and 0.81, respectively, indicating a good predictive performance of the ensemble model. Sea surface temperature and salinity were the two most important variables determining the distribution of L. olivacea, with the suitable temperature ranging from 23 to 29 ℃ and salinity below 34. The current distribution range of L. olivacea was between 30° N-25° S. Under future climate scenarios, its distribution range would decrease, especially under the RCP85 scenario in the 2100s (with a 28% reduction in the suitable survival range). The results of model validation showed that it had high accuracy and could make accurate predictions of the distribution. This study would provide references for the development of more rational conservation measures and management strategies.

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Cambio Climático , Salinidad , Temperatura

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Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins widely found in food contaminants, and its target organ is the liver. It poses a major food security and public health threat worldwide. However, the lipotoxicity mechanism of AFB1 exposure-induced liver injury remains unclear and requires further elucidation. Herein, we investigated the potential hepatic lipotoxicity of AFB1 exposure using in vitro and in vivo models to assess the public health hazards of high dietary AFB1 exposure. We demonstrated that low-dose of AFB1 (1.25 µM for 48 h, about one-fifth of the IC50 in HepG2 and HepaRG cells, IC50 are 5.995 µM and 5.266 µM, respectively) exposure significantly induced hepatic lipotoxicity, including abnormal lipid droplets (LDs) growth, mitochondria-LDs contacts increase, lipophagy disruption, and lipid accumulation. Mechanistically, we showed that AFB1 exposure promoted the mitochondrial p53 (mito-p53) and LDs-associated protein perilipin 2 (PLIN2) interaction-mediated mitochondria-LDs contacts, resulting in lipid accumulation in hepatocytes. Mito-p53-targeted inhibition, knockdown of PLIN2, and rapamycin application efficiently promoted the lysosome-dependent lipophagy and alleviated the hepatic lipotoxicity and liver injury induced by AFB1 exposure. Overall, our study found that mito-p53 and PLIN2 interaction mediates three organelles-mitochondria, LDs, and lysosomal networks to regulate lipid homeostasis in AFB1 exposure-induced hepatotoxicity, revealing how this unique trio of organelles works together and provides a novel insight into the targeted intervention in inter-organelle lipid sensing and trafficking for alleviating hazardous materials-induced hepatic lipotoxicity.

Asunto(s)

Aflatoxina B1 , Gotas Lipídicas , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Perilipina-2/metabolismo , Gotas Lipídicas/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Hígado/metabolismo , Mitocondrias/metabolismo , Lípidos

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Objective: To summarize the outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting. Methods: This study was a retrospective cohort study. A total of 19 neonates who had pulmonary atresia treated by ductus arteriosus stenting in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to June 2021 were included. They were divided into the intact ventricular septum (PA-IVS) group and the ventricular septal defect (PA-VSD) group. Ductus arteriosus stents were implanted by different approaches. These children were followed up regularly at the 1, 3, 6, and 12 months after the surgery and annually since then to evaluate the outcome. Independent sample t-test was used for the statistical analysis. Results: There were 12 children in PA-IVS group and 7 in PA-VSD group. All of them were full term in fants. The gestational age of the PA-IVS group and the PA-VSD group was (38.8±1.1) and (37.7±1.8) weeks, the birth weights were (3.2±0.4) and (3.4±1.1) kg, and the age at operation was (10±9) and (12±7) days, respectively, without significant difference (all P>0.05). Among the 12 children with PA-IVS, 9 had stents successfully implanted through the femoral artery and 3 through the femoral vein. Of the 7 children with PA-VSD, 2 had the stents successfully implanted via the femoral artery and 2 failed, and the remaining 3 had stents successfully implanted via the left carotid artery. There was no postoperative thromboembolism, arteriovenous fistula, pseudoaneurysm or other vascular complications. Five children with PA-VSD who had successful operations were followed up at 6 months of age. They all had the operation for pulmonary atresia, repair of the ventricular septal defect, removal of arterial duct stents, and ligation of the arterial duct. All children survived without any stent displacement or stenosis and biventricular circulation was achieved during the follow-up. Conclusions: Ductus arteriosous stenting can be the first-stage treatment for children with PA-IVS and PA-VSD. In addition to the traditional femoral vein and femoral artery approach, the carotid artery can be used as a route for stent placement.

Asunto(s)

Niño , Recién Nacido , Humanos , Lactante , Atresia Pulmonar/cirugía , Conducto Arterial , Estudios Retrospectivos , China , Cardiopatías Congénitas , Conducto Arterioso Permeable/cirugía , Defectos del Tabique Interventricular , Stents

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Stroke has become a major health issue worldwide, bringing a heavy burden to patients, families, and society. Effective reperfusion therapy can significantly improve the outcomes of patients with acute ischemic stroke (AIS). The secondary prevention guidelines in various countries recommend reducing stroke risk by strictly controlling blood pressure. With the widespread application of 24-hour ambulatory blood pressure monitoring, the study of blood pressure variability (BPV) has gradually become a hot topic in the field of stroke prevention and treatment. However, the impact of BPV on the outcomes of patients with AIS receiving reperfusion therapy remains controversial. This article mainly reviews the concept and the related parameters of BPV, as well as the relationship and possible mechanisms between BPV and the outcomes of patients with AIS receiving reperfusion therapy.

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Abstract@#With the increasing prevalence of overweight and obesity in children, the influence of overweight and obesity on pubertal timing has attracted the attention of scholars. This paper reviewed the correlation and mechanism between childhood obesity and pubertal timing, especially for earlier pubertal timing, and found that the regulation of hypothalamic-pituitary-gonadal axis function by nutrition and metabolic signals might under lie those associations. Obesity in girls was positively correlated with early pubertal timing, while the conclusions in boys were inconsistent. Overweight in boys was related to early pubertal timing, obesity in boys could lead to both earlier and later onset of puberty, which warrents further investigation.

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OBJECTIVES: Hepatitis B virus X (HBx) is closely associated with HBV-related hepatocarcinogenesis via the inactivation of tumour suppressors. Protein phosphatase 2A (PP2A) regulatory subunit B56 gamma (B56γ), as a tumour suppressor, plays a critical role in regulating cellular phosphorylation signals via dephosphorylation of signalling proteins. However, the underlying mechanism that B56γ involved in regulating HBx-associated hepatocarcinogenesis phenotypes and mediating anti-HBx antibody-mediated tumour suppression remains unknown. MATERIALS AND METHODS: We used bioinformatics analysis, paired HCC patient specimens, HBx transgenic (HBx-Tg) mice, xenograft nude mice, HBV stable replication in the HepG2.2.15 cells, and anti-HBx antibody intervention to systematically evaluate the biological function of protein kinase B (AKT) dephosphorylation through B56γ in HBx-associated hepatocarcinogenesis. RESULTS: Bioinformatics analysis revealed that AKT, matrix metalloproteinase 2 (MMP2), and MMP9 were markedly upregulated, while cell migration and viral carcinogenesis pathways were activated in HBV-infected liver tissues and HBV-associated HCC tissues. Our results demonstrated that HBx-expression promotes AKT phosphorylation (p-AKTThr308/Ser473 ), mediating the migration and invasion phenotypes in vivo and in vitro. Importantly, in clinical samples, HBx and B56γ were downregulated in HBV-associated HCC tumour tissues compared with peritumor tissues. Moreover, intervention with site-directed mutagenesis (AKTT308A , AKTS473A ) of p-AKTThr308/Ser473 mimics dephosphorylation, genetics-based B56γ overexpression, and intracellular anti-HBx antibody inhibited cell growth, migration, and invasion in HBx-expressing HCC cells. CONCLUSIONS: Our results demonstrated that B56γ inhibited HBV/HBx-dependent hepatocarcinogenesis by regulating the dephosphorylation of p-AKTThr308/Ser473 in HCC cells. The intracellular anti-HBx antibody and the activator of B56γ may provide a multipattern chemopreventive strategy against HBV-related HCC.

Asunto(s)

Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Ratones , Animales , Humanos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Proteína Fosfatasa 2/metabolismo , Ratones Desnudos , Carcinogénesis/genética , Hepatitis B/complicaciones , Hepatitis B/genética , Hepatitis B/metabolismo

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Mitochondria-lysosome crosstalk is an intercellular communication platform regulating mitochondrial quality control (MQC). Activated dynamin-related protein 1 (Drp1) with phosphorylation at serine 616 (p-Drp1Ser616) plays a critical role in mitophagy-dependent cell survival and anti-cancer therapy for hepatocellular carcinoma (HCC). However, the underlying mechanisms that p-Drp1Ser616 involved in regulating mitochondria-lysosome crosstalk and mediating anti-HCC therapy remain unknown. HCC cells and mouse xenograft models were conducted to evaluate the relationship between p-Drp1Ser616 and Ras-associated protein 7 (Rab7) and the underlying mechanism by protein phosphatase 2A (PP2A)-B56γ regulating mitophagy via dephosphorylation of p-Drp1Ser616 in HCC. Herein, we found that Drp1 was frequently upregulated and was associated with poor prognosis in HCC. Mitochondrial p-Drp1Ser616 was a novel inter-organelle tethering protein localized to mitochondrion and lysosome membrane contact sites (MCSs) via interaction with Rab7 to trigger an increase in the mitochondria-lysosome crosstalk, resulting in PINK1-Parkin-dependent mitophagy and anti-apoptosis in HCC cells under the treatment of chemotherapy drugs. Moreover, we demonstrate that B56γ-mediated direct dephosphorylation of p-Drp1Ser616 inhibited mitophagy and thus increased mitochondria-dependent apoptosis. Overall, our findings demonstrated that activation of B56γ sensitizes the anti-cancer effect of HCC chemoprevention via dephosphorylated regulation of p-Drp1Ser616 in inhibiting the interaction between p-Drp1Ser616 and Rab7, which may provide a novel mechanism underlying the theranostics for targeting intervention in HCC.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Lisosomas/metabolismo , Ratones , Mitocondrias/metabolismo , Dinámicas Mitocondriales , Proteína Fosfatasa 2/metabolismo

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To clarify the consistency and efficiency of four methods for myocardial extracellular volume (ECV) measurement (manual method using dual-energy iodine [manual ECViodine], manual method using subtraction [manual ECVsub], automatic ECViodine, automatic ECVsub) in patients with ischaemic cardiomyopathy. Fifty patients with ischaemic cardiomyopathy who underwent coronary computed tomography angiography (CCTA) following dual-energy computed tomography (CT) with late iodine enhancement (LIE-DECT) were included. LIE with ischaemic patterns representing scarring could be detected using iodine maps in all patients. The global and remote ECVs of non-scarred myocardium were measured using four methods (manual ECViodine, automatic ECViodine, manual ECVsub, and automatic ECVsub). The consistency and time cost of the four methods were analysed. There were no significant differences in the mean global ECVs or remote ECVs among the four methods (p > 0.05). ECViodine resulted in a lower Bland-Altman limit of agreement than that of ECVsub for both global and remote measurements. Intraclass correlation coefficients of the automatic and manual ECViodine measurements demonstrated better concordance (0.804 and 0.859, respectively) than those of automatic and manual ECVsub (0.607 and 0.669, respectively) for both global and remote measurements. The measurement time for automatic ECV was less than that for manual ECV for both global and remote ECV measurements (all p < 0.001). ECV measurement using dual-energy iodine yielded good concordance, and the automatic method has the advantages of being simple and convenient, which can become a useful tool for quantification of myocardial fibrosis.

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Mitochondria are highly dynamic organelles and undergo constant fission and fusion, which are both essential for the maintenance of cell physiological functions. Dysregulation of dynamin-related protein 1 (Drp1)-dependent mitochondrial dynamics is associated with tumorigenesis and the chemotherapeutic response in hepatocellular carcinoma (HCC). The enzyme cyclooxygenase-2 (COX-2) is overexpressed in most cancer types and correlates with a poor prognosis. However, the roles played by the translocation of mitochondrial COX-2 (mito-COX-2) and the interaction between mito-COX-2 and Drp1 in chemotherapeutic responses remain to be elucidated in the context of HCC. Bioinformatics analysis, paired HCC patient specimens, xenograft nude mice, immunofluorescence, transmission electron microscopy, molecular docking, CRISPR/Cas9 gene editing, proximity ligation assay, cytoplasmic and mitochondrial fractions, mitochondrial immunoprecipitation assay, and flow cytometry analysis were performed to evaluate the underlying mechanism of how mito-COX-2 and p-Drp1Ser616 interaction regulates the chemotherapeutic response via mitochondrial dynamics in vitro and in vivo. We found that COX-2 and Drp1 were frequently upregulated and confer a poor prognosis in HCC. We also found that the proportion of mito-COX-2 and p-Drp1Ser616 was increased in HCC cell lines. In vitro, we demonstrated that the enhanced mitochondrial translocation of COX-2 promotes its interaction with p-Drp1Ser616 via PTEN-induced putative kinase 1 (PINK1)-mediated Drp1 phosphorylation activation. This increase was associated with higher colony formation, cell proliferation, and mitochondrial fission. These findings were confirmed by knocking down COX-2 in HCC cells using CRISPR/Cas9 technology. Furthermore, inhibition of Drp1 using pharmacologic inhibitors (Mdivi-1) or RNA interference (siDNM1L) decreased mito-COX-2/p-Drp1Ser616 interaction-mediated mitochondrial fission, and increased apoptosis in HCC cells treated with platinum drugs. Moreover, inhibiting mito-COX-2 acetylation with the natural phytochemical resveratrol resulted in reducing cell proliferation and mitochondrial fission, occurring through upregulation of mitochondrial deacetylase sirtuin 3 (SIRT3), which, in turn, increased the chemosensitivity of HCC to platinum drugs in vitro and in vivo. Our results suggest that targeting interventions to PINK1-mediated mito-COX-2/p-Drp1Ser616-dependent mitochondrial dynamics increases the chemosensitivity of HCC and might help us to understand how to use the SIRT3-modulated mito-COX-2/p-Drp1Ser616 signaling axis to develop an effective clinical intervention in hepatocarcinogenesis.

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OBJECTIVES: To measure the myocardial extracellular volume (ECV) in patients with heart failure with preserved ejection fraction (HFpEF) using dual-energy computed tomography with late iodine enhancement (LIE-DECT) and to evaluate the relationship between ECV and risk of HFpEF and cardiac structure and function. METHODS: A total of 112 consecutive patients with HFpEF and 80 consecutive subjects without heart disease (control group) who underwent LIE-DECT were included. All patients were divided into ischaemic and non-ischaemic groups according to the LIE patterns detected using iodine maps. The ischaemic scar burden was calculated in the ischaemic HFpEF group. Iodine maps and haematocrit were used to measure ECV in the non-ischaemic HFpEF group and remote ECV of the non-scarred myocardium in the ischaemic HFpEF group, respectively. Cardiac structural and functional variables were collected. RESULTS: ECV in patients with non-ischaemic HFpEF (n = 77) and remote ECV in patients with ischaemic HFpEF (n = 35) were significantly higher than those in control subjects (p < 0.001). Multivariate logistic regression analysis revealed that after adjusting for age, sex, body mass index, smoking, and drinking, a higher ECV/remote ECV was still associated with non-ischaemic HFpEF and ischaemic HFpEF (p < 0.001). A positive correlation was established between ECV and cardiac structural and functional variables (p < 0.05) in all participants. Subgroup analysis showed that ECV/remote ECV and ischaemic scar burden positively correlated with heart failure classification in the HFpEF subgroup (p < 0.05). CONCLUSION: ECV/remote ECV elevation was significantly associated with non-ischaemic and ischaemic HFpEF. Remote ECV and LIE may have synergistic effects in the risk assessment of ischaemic HFpEF. KEY POINTS: • ECV/remote ECV elevation is associated not only with non-ischaemic HFpEF but also with ischaemic HFpEF. • ECV/remote ECV and ischaemic scar burden are correlated with cardiac structure and function.

Asunto(s)

Insuficiencia Cardíaca , Yodo , Cicatriz/patología , Humanos , Miocardio/patología , Valor Predictivo de las Pruebas , Volumen Sistólico , Tomografía Computarizada por Rayos X , Función Ventricular Izquierda

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@#BACKGROUND: Sepsis-induced liver injury is a fatal complication of sepsis. Trichostatin A (TSA) regulates inflammation and autophagy in some human diseases, and forkhead box O3a (FoxO3a) has been shown to regulate autophagy. The present study aims to investigate whether TSA exerts its effects on septic liver injury through the FoxO3a/autophagy signaling pathway. METHODS: A sepsis mouse model was constructed by the cecal ligation and puncture (CLP) method, and AML12 cells were pretreated with lipopolysaccharide (LPS) (1 μg/mL) to establish a sepsis cell model. Forty mice were divided into four groups, namely control group, TSA group, CLP group, and CLP+TSA group, with 10 mice in each group. Cells were divided into control group, TSA group, LPS group, and LPS+TSA group. Hematoxylin-eosin (H&E) staining and biochemical methods were used to evaluate liver tissue injury. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the expression of proinflammatory cytokines, and Western blotting and immunofluorescence were used to measure autophagy-related protein expression. RESULTS: Compared with the CLP group (mice), the proinflammatory cytokines (interleukin-β [IL-β] 2,665.27±324.90 pg/mL to 2,080.26±373.66 pg/mL; interleukin-6 [IL-6] 399.01±60.98 pg/mL to 221.90±46.89 pg/mL) and the hepatocyte injury markers (aspartate transaminase [AST] from 198.18±27.07 U/L to 128.42±20.55 U/L; alanine aminotransferase [ALT] from 634.98±74.10 U/L to 478.60±32.56 U/L) were notably decreased after TSA intervention. Moreover, LC3 II and FoxO3a showed an obvious increase and P62 showed an obvious decrease in the CLP+TSA group. Cell experiment results showed the similar trend. After FoxO3a gene was knocked down in AML12 cells, the promotion of autophagy and the improvement of liver enzyme index and inflammation by TSA were weakened. CONCLUSION: TSA may improve the inflammatory response and liver injury in septic mice through FoxO3a/autophagy.

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Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.

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Non-small cell lung cancer (NSCLC) is one of the most severe malignant tumors worldwide. Lobectomy and systematic nodal dissection remain the standard treatment for stageⅠNSCLC. Stereotactic body radiotherapy (SBRT) has become the standard treatment for medically inoperable patients. Though the prognosis of stage Ⅰ NSCLC patients is generally good, there are still about 20% of patients with local recurrence and distant metastasis. There is significant heterogeneity in the prognosis and failure phenotype of patients, which cannot be precisely distinguished by the pathological TNM classification system. Identification of the risk factors for the prognosis of patients with stage Ⅰ NSCLC is a key step to realize the treatment from experience to precision. Screening the high-risk patients will facilitate to individually develop the adjuvant therapy strategy after surgery or SBRT and improve the overall curative effect. There are many factors that are significantly related to the prognosis of stage Ⅰ NSCLC including individual factors such as gender, age, and systemic inflammatory biomarkers; treatment-related factors such as the extent of surgical resection of the primary tumor and lymph nodes, the choice of different radiation rays, and different dose fractionation; and tumor-related factors such as imaging information, pathology information; and molecular biology information. This review will analyze the treatment failure phenotype and prognostic factors of stageⅠ NSCLC in various perspectives such as individual-, tumor- and treatment-related factors.

Asunto(s)

Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/patología , Fenotipo , Pronóstico , Insuficiencia del Tratamiento

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Multiple sclerosis ( MS) is an immune-mediated chro¬nic inflammatory disease of the central nervous system (CNS) , which is regulated by multiple pathophysiological mechanisms.There are four clinical phenotypes of MS, including relapsing-re- mitting MS ( RRMS) , primary progressive MS ( PPMS) , sec- ondary-pmgressive MS ( SPMS) , and progressive relapsing MS ( PRMS) , among which RRMS is the main type.'Hie pathogen¬esis of MS is not clear and it could not he cured, so long-term drug treatment is needed for the MS patients.Nowadays, animal models play an important role in the preclinical research of MS drugs.'Hie MS animal models are mainly divided into experi¬mental autoimmune encephalomyelitis (EAE) model, toxin in¬ duced demyelination model, and vims induced demyelination model, among which EAE model is most widely used.'Hie three types of MS animal models demonstrate specific characteristics due to the different induction methods and animal species, and they correspond to specific clinical types of MS.According to the different clinical types of MS, the use of appropriate animal models for drug research and development will help us develop more targeted and potential therapeutic dnrgs, making it possible to cure MS.

RESUMEN

A hermetic Micro-Electro-Mechanical Systems (MEMS) package with a metal lid is investigated to prevent lid-off failure and improve its reliability during the precondition test. While the MEMS package benefits from miniaturization and low cost, a hermetic version is highly sensitive to internal pressure caused by moisture penetration and the reflow process, thus affecting its reliability. In this research, the finite element method is applied to analyze the contact stress between the metal lid and the silver epoxy by applying the cohesive zone model (CZM). Moreover, the red dye penetration test is applied, revealing a microcrack at the metal lid/silver epoxy interface. Further analyses indicate that the crack is caused by internal pressure. According to the experimental testing and simulation results, the silver epoxy material, the curing process, the metal lid geometry, and the bonding layer contact area can enhance the bonding strength between the metal lid and the substrate.