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The pathophysiological mechanisms of schizophrenia are still unclear. Converging evidence suggests that energy metabolism abnormalities are involved in schizophrenia, and support its role in the pathophysiology of this disease. Lactate plays an important role in energy metabolism. Many studies have reported changes in the levels of lactate in the brain and serum of schizophrenia patients; however, the results from these studies are not consistent. To overcome this limitation, the goal of the present meta-analysis is to analyze the changes in lactate levels in the brain and blood of schizophrenia patients. For this systematic review and meta-analysis, we performed a thorough search of relevant literature in the English language, using the MEDLINE, Cochrane, and Embase databases. In the present meta-analysis, 20 studies were scrutinized, including 13 studies on brain lactate levels, which involved 322 schizophrenia patients and 324 healthy individuals as controls. 7 studies on blood lactate levels, involving 234 schizophrenia patients and 238 healthy individuals, were also included. Brain lactate levels were elevated in schizophrenia patients, both in vivo and in post-mortem studies. Nevertheless, blood lactate levels in schizophrenia patients have revealed no statistically significant difference, as compared with control individuals. In comparison with healthy individuals, schizophrenia patients had higher lactate levels in the brain, rather than in the blood. These findings suggest independent regulatory mechanisms of lactate levels in the brain and peripheral tissues. Abnormal lactate metabolism in the brain may be an important pathological mechanism in schizophrenia. [ABSTRACT FROM AUTHOR]

In this work, vermicompost was prepared with maize stover and cattle dung in ratios of 60:40 (VC1), 50:50 (VC2) and 40:60 (VC3), and the physicochemical properties of the vermicompost were related to the ratio of the raw materials used. The effect of the vermicomposts on the adsorption kinetics, adsorption isotherms and desorption of atrazine were investigated in unamended soil (S) and soil amended with 4% (w/w) of VC1(S-VC1), VC2(S-VC2) and VC3(S-VC3). The total organic carbon (TOC) content of VC1, VC2 and VC3 was 38.46, 37.33 and 34.47%, the HA content was 43.50, 42.22 and 39.28 g/kg, and the HA/FA ratios was 1.47, 0.44 and 0.83, respectively. The adsorption of atrazine on the soil, on the vermicompost and on soils amended with vermicompost followed a pseudo-second-order kinetic model. The Freundlich equation better fitted the adsorption isotherm of atrazine. The vermicomposts enhanced atrazine adsorption and decreased atrazine desorption. Correlation analysis showed that the TOC and HA were significantly positively correlated with Kf, which indicated that TOC and HA of the vermicomposts contributed significantly to the adsorption and desorption of atrazine. This study demonstrated that vermicomposts have great potential in the bioremediation of atrazine pollution and that their role is related to the raw materials used to prepare them. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are essential elements of the bone marrow (BM) microenvironment, which have been widely implicated in pathways that contribute to leukemia growth and resistance. Recent reports showed genotypic and phenotypic alterations in leukemia patient‐derived MSCs, indicating that MSCs might be educated/reprogrammed. However, the results have been inconclusive, possibly due to the heterogeneity of leukemia. Here, the authors report that acute myeloid leukemia (AML) induces MSCs towards an adipogenic differentiation propensity. RNAseq analysis reveal significant upregulation of gene expression enriched in the adipocyte differentiation process and reduction in osteoblast differentiation. The alteration is accompanied by a metabolic switch from glycolysis to a more oxidative phosphorylation‐dependent manner. Mechanistic studies identify that AML cell‐derived exosomes play a vital role during the AML cell‐mediated MSCs education/reprogramming process. Pre‐administration of mice BM microenvironment with AML‐derived exosomes greatly enhance leukemia engraftment in vivo. The quantitative proteomic analysis identified a list of exosomal protein components that are differently expressed in AML‐derived exosomes, which represent an opportunity for novel therapeutic strategies based on the targeting of exosome‐based AML cells‐MSCs communication. Collectively, the data show that AML‐educated MSCs tend to differentiate into adipocytes contributing to disease progression, which suggests complex interactions of leukemia with microenvironment components. [ABSTRACT FROM AUTHOR]

Accurately estimating object numbers plays a crucial role in industrial applications. However, object counting in computer vision poses a formidable challenge, particularly when dealing with images containing tiny, similar, and stacked objects. Therefore, this paper proposes an encoder–decoder-based convolutional neural network named AMSA-CAFF Net to accurately count and regress high-quality density maps from X-ray images of highly dense microscopic components. AMSA-CAFF Net has three major components: an adaptive multi-scale feature aggregation (AMSA) module for encoding adaptive multi-scale features in the encoder, a channel-wise adaptive feature fusion (CAFF) module to ensure smooth feature fusion, and a continuous feature enhancement mechanism to promote information integration in the decoder. In addition, there is still a lack of datasets dedicated to industrial object counting tasks. To address the limitations associated with the existing datasets, we construct a novel and large-scale object counting dataset named X-ray-based industrial electronic component counting dataset (XRAY-IECCD), consisting of 1,460 X-ray images of 10 types of components, resulting in a total of 2,915,126 objects annotated with points. To the best of our knowledge, the XRAY-IECCD is the first dataset of tiny, dense, multi-class object counts with a substantial number of annotations. We evaluate the performance of AMSA-CAFF Net on three datasets: the XRAY-IECCD, crowd counting benchmark ShanghaiTech dataset, and object counting benchmark CARPK dataset. The proposed framework outperforms the state-of-the-art approaches over the proposed XRAY-IECCD and CARPK datasets, highlighting its effectiveness. Furthermore, we achieve competitive results on the ShanghaiTech dataset, which demonstrates the generalization capability of our method. [ABSTRACT FROM AUTHOR]

Background: Ambient nitrogen dioxide (NO2) is a common air pollutant in developing countries and causes skin conditions, but its effect on eczema in subtropical areas is not clear in China.Object: To measure the effect of short-term exposure of NO2 on the incidence of eczema and the change of outpatient visits.Methods: Data of daily temperature, air pollutants, and outpatient visits from 2013 to 2018 were collected in a row. The generalized additive model (GAM) and Poisson distribution were used to assess the association between short-term exposure of NO2 and the outpatient visits of patients with eczema. The cumulative exposure effect of lag 0-3 days and the displacement effect of NO2 and other pollutants were considered as well. A single pollutant model was used to examine the independent association, and a two-pollutant model was adopted to control the confounding effect.Results: The daily outpatient visits of eczema increased from 75.26 to 190.85 from 2013 to 2018 (P < 0.001). The combined influence of NO2 and the related pollutant exerted a stronger influence on the incidence of eczema. The maximum effect of NO2 appeared on the exposed day. (lag 0) and disappeared on day 4 (lag 3). The children and seniors were more vulnerable to NO2 exposure.Conclusion: Exposure to NO2 is tightly associated with eczema incidence and outpatient visits. The hospitals should react to the visit fluctuations and adjust physician duty shifts to improve outpatient service efficiency. [ABSTRACT FROM AUTHOR]

Background: The Chinese government has been strengthening the primary care system since the launch of the New Healthcare System Reform in 2009. Among all endeavors, the most obvious and significant improvement lays in maternal and child health. This study was designed to explore the association of primary care physician supply with maternal and child health outcomes in China, and provide policy suggestions to the law makers.Methods: Six-year panel dataset of 31 provinces in China from 2012 to 2017 was used to conduct the longitudinal ecological study. Linear fixed effects regression model was applied to explore the association of primary care physician supply with the metrics of maternal and child health outcomes while controlling for specialty care physician supply and socio-economic covariates. Stratified analysis was used to test whether this association varies across different regions in China.Results: The number of primary care physicians per 10,000 population increased from 15.56 (95% CI: 13.66 to 17.47) to 16.08 (95% CI: 13.86 to 18.29) from 2012 to 2017. The increase of one primary care physician per 10,000 population was associated with 5.26 reduction in maternal mortality per 100,000 live births (95% CI: - 6.745 to - 3.774), 0.106% (95% CI: - 0.189 to - 0.023) decrease in low birth weight, and 0.419 decline (95% CI: - 0.564 to - 0.273) in perinatal mortality per 1000 live births while other variables were held constant. The association was particularly prominent in the less-developed western China compared to the developed eastern and central China.Conclusion: The sufficient supply of primary care physician was associated with improved maternal and child health outcomes in China, especially in the less-developed western region. Policies on effective and proportional allocation of resources should be made and conducted to strengthen primary care system and eliminate geographical disparities. [ABSTRACT FROM AUTHOR]

Bioactive lipid mediator N-palmitoylethanolamide (PEA) is an endocannabinoid-like molecule. Based on our previous data, this study aimed to further investigate the antidepressant property of PEA via the peroxisome proliferator-activated receptor alpha (PPARα) pathway, focusing on the intervention of PEA on hippocampal neuroplasticity. Behavioral tests were performed in rats induced by unpredictable chronic mild stress (uCMS) in the last week of the experiment, and then the brain tissue samples were retained for subsequent immunohistochemical detection and Western blot analysis. In vitro, the apoptosis of HT22 cells induced by CORT and apoptosis-related proteins were detected by Hoechst staining and Western blot, respectively. The results showed that PEA ameliorated the depression-like phenotype in rats induced by uCMS, prevented the uCMS-induced reduction in the number of BrdU-positive cells, and increased BrdU/NeuN co-localization in the hippocampus, and upregulated the levels of synapse associated protein NCAM, MAP2, SYN and PSD95 in the hippocampus. Hoechst staining results showed that PEA significantly increased the CORT-induced reduction in the number of hippocampal neurons. Western blot analysis showed that PEA decreased the expression of caspase-3 and c-caspase-3, and increased the ratio of Bcl-2/Bax in CORT-induced HT22 cells. MK886, a PPARα antagonist, partially or completely reversed these effects. In conclusion, the therapeutic potential of PEA for depressive mood disorders may be through targeting the hippocampal neuroplasticity, including increasing adult neurogenesis and synaptic plasticity, as well as down-regulated neuronal apoptosis, to remodel hippocampal circuitries upon functional integration and PPARα pathway may be involved in this process. • PEA reverted uCMS-induced down-regulation of hippocampal neurogenesis. • PEA improved uCMS-induced abnormal expression of synaptic plasticity-related proteins in the hippocampus. • PEA alleviated the apoptosis of hippocampal neurons under high corticosterone conditions in vitro. [ABSTRACT FROM AUTHOR]

• We isolated and characterized a novel EV-G2 strain, CHN-SCMY2021, the first genotype 2 strain isolated in china. • Genetic characterization reveals recombination between EV-G genotype 2 strains in CHN-SCMY2021, with a whole genome similarity of 78.3%−86.4% to other EV-G genotype 2 strains. • Except for ST cells, CHN-SCMY2021 has a broad spectrum of cellular adaptations, which are susceptible to BHK-21, PK-15, IPEC-J2, LLC-PK and vero cells. • In piglets, CHN-SCMY2021 causes mild diarrhea and thinning of the intestinal wall. Enterovirus G belongs to the family Picornaviridae and are associated with a variety of animal diseases. We isolated and characterized a novel EV-G2 strain, CHN-SCMY2021, the first genotype 2 strain isolated in China. CHN-SCMY2021 is about 25 nm diameter with morphology typical of picornaviruses and its genome is 7341 nucleotides. Sequence alignment and phylogenetic analysis based on VP1 indicated that this isolate is a genotype 2 strain. The whole genome similarity between CHN-SCMY2021 and other EV-G genotype 2 strains is 78.3–86.4%, the greatest similarity is to EVG/Porcine/JPN/Iba26–506/2014/G2 (LC316792.1). Recombination analysis indicated that CHN-SCMY2021 resulted from recombination between 714,171/CaoLanh_VN (KT265894.2) and LP 54 (AF363455.1). Except for ST cells, CHN-SCMY2021 has a broad spectrum of cellular adaptations, which are susceptible to BHK-21, PK-15, IPEC-J2, LLC-PK and Vero cells. In piglets, CHN-SCMY2021 causes mild diarrhea and thinning of the intestinal wall. The virus was mainly distributed to intestinal tissue but was also found in heart, liver, spleen, lung, kidney, brain, and spinal cord. CHN-SCMY2021 is the first systematically characterized EV-G genotype 2 strain from China, our results enrich the information on the epidemiology, molecular evolution and pathogenicity associated with EV-G. [ABSTRACT FROM AUTHOR]

• The present network visualized the complex associations among multiple complications. • Our new grading approach can classify complication severity using the items. • Quantified associations among complications included cascade, cluster, and synergy. • Updating probability with new information supports prevention and clinical decision. Postoperative complications confer an increased risk of reoperation, prolonged length of hospital stay, and increased mortality. Many studies have attempted to identify the complex associations among complications to preemptively interrupt their progression, but few studies have looked at complications as a whole to reveal and quantify their possible trajectories of progression. The main objective of this study was to construct and quantify the association network among multiple postoperative complications from a comprehensive perspective to elucidate the possible evolution trajectories. In this study, a Bayesian network model was proposed to analyze the associations among 15 complications. Prior evidence and score-based hill-climbing algorithms were used to build the structure. The severity of complications was graded according to their connection to death, with the association between them quantified using conditional probabilities. The data of surgical inpatients used in this study were collected from four regionally representative academic/teaching hospitals in a prospective cohort study in China. In the network obtained, 15 nodes represented complications or death, and 35 arcs with arrows represented the directly dependent relationship between them. With three grades classified on that basis, the correlation coefficients of complications within grades increased with increased grade, ranging from −0.11 to −0.06, 0.16, and 0.21 to 0.4 in grade 1 to grade 3, respectively. Moreover, the probability of each complication in the network increased with the occurrence of any other complication, even mild complications. Most seriously, once cardiac arrest requiring cardiopulmonary resuscitation occurs, the probability of death will be up to 88.1%. The present evolving network can facilitate the identification of strong associations among specific complications and provides a basis for the development of targeted measures to prevent further deterioration in high-risk patients. [ABSTRACT FROM AUTHOR]

The fish's gradient colors symbolize the influence of the leukemia cells (in black) and hematopoietic stem cells (in red) on their respective surrounding microenvironments. B Acute Myeloid Leukemia b In article number 2105811, Yang Yang, Ye Chen, and co-workers report that acute myeloid leukemia (AML) cells educate regular mesenchymal stromal cells (MSCs) towards an adipogenic differentiation propensity with leukemia promotion capabilities. [Extracted from the article]

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) is required for EBV immortalization of primary B cells in vitro. Signal transducers and activators of transcription (STATs) play a pivotal role in the initiation and maintenance of certain cancers. STAT proteins, especially STAT-1, -3, and -5, are persistently tyrosine phosphorylated or activated in many cancers. We show here that EBV-infected type III latency cells, in which the EBV oncoprotein, LMP-1 is expressed, express high levels of four STATs (STAT-1, -2, -3, and -5A) and that LMP-1 is responsible for the induction of three (STAT-1, -2, and -3). In addition, the C-terminal activator region 1 (CTAR-1) and CTAR-2 of LMP-1 cooperatively induced the expression of STAT-1. The cooperativity was evident when CTAR-1 and CTAR-2 were present in cis, but not in trans. Furthermore, NF-κB is an essential factor involved in the induction of STAT-1. Most of the induced STATs were not phosphorylated at the critical tyrosine residue activated by many cytokines. However, the induced STATs, at least STAT-1, were functional because it could be activated by interferon (IFN) and could upregulate an IFN-inducible gene. Finally, expression of STAT-1, but not STAT-2 and -3, is associated with EBV transformation. The association of the expression of STAT-1, -2, -3, and -5A with EBV type III latency and the expression of STAT-1 in the EBV transformation process may be part of the viral programming that regulates viral latency and cellular transformation. [Copyright &y& Elsevier]

High-entropy (HE) oxides have attracted a lot of research, because it has the advantages of adjustable structure and excellent catalytic performance. However, the lack of a better understanding for the thermal stability impedes its wider application in solid oxide cells (SOCs). Here, a B site HE layered perovskite, PrBa 0.5 Sr 0.5 (Mn 0.2 Fe 0.2 Co 0.2 Ni 0.2 Cu 0.2) 2 O 5+ δ (HE-PBSC), with low Co content, exceptional resistance to thermal shock is surprisingly obtained. Additionally, the surface cation segregations on the HE-PBSC and its relationship with annealing stability are reported. The polarized impedance (Rp) of symmetrical cell with HE-PBSC electrode increases 14.77%, from 3.771 Ω cm2 to 4.328 Ω cm2, after 200 h of annealing. With respect to improving the stability, efforts need to be made in the future to mitigate cation segregations on surface. • A novel B-site high entropy layered perovskite oxygen electrode (PrBa 0.5 Sr 0.5 (Mn 0.2 Fe 0.2 Co 0.2 Ni 0.2 Cu 0.2) 2 O 5+δ). • The B-site high entropy electrode has excellent thermal shock resistance performance. • The mechanism of segregation on the surface of electrode materials is revealed. [ABSTRACT FROM AUTHOR]

• m CPBA-mediated dioxygenation of unactivated alkenes. • High selectivity for 5-imino-2-tetrahydrofuranyl methanol skeletons. • Mild reaction conditions and broad substrate scope. A m CPBA-mediated, metal-free, intramolecular dioxygenation reaction of unactivated alkenes is reported. In the presence of m -chlorobenzoic peracid, different unsaturated amide substrates could be cyclized via epoxide intermediates, producing the corresponding 5-imino-2-tetrahydrofuranyl methanol products in up to 94% yield at room temperature. [ABSTRACT FROM AUTHOR]

Rationale: The precise diagnosis and treatment of cognitive impairment remains a major challenge in the field of schizophrenia (SCZ) research. Synaptic dysfunction and loss are thought to be closely related to the occurrence and development of SCZ and may be involved in cognitive dysfunction. Objectives: The purpose of this study was to investigate whether neuronal pentraxins (NPTXs) plays a role in the etiology of SCZ and provide evidence of its possible therapeutic value a new target for drug development. Methods: We recruited 275 participants, of whom 148 were SCZ from psychiatric hospital and 127 healthy control (HC) subjects from communities. Plasma concentrations of NPTXs were measured in HC and SCZ at baseline and after 8 weeks of antipsychotic treatment. The MATRICS Cognitive Consensus Battery was used to evaluate cognitive function. Furthermore, the brain is parcellated into 246 subregions using the Brainnetome atlas, and we extracted regional white matter volumes from magnetic resonance images of the SCZ groups. Results: Plasma NPTX2 levels were significantly lower in SCZ compared with HC subjects, but were significantly raised in SCZ after 8 weeks of antipsychotic treatment compared to baseline. In addition, baseline plasma NPTX2 levels were positively correlated with cognitive performance. Conclusions: These findings indicate that NPTX2 may reveal novel aspects of disease etiology and act as a promising target for new drug development. [ABSTRACT FROM AUTHOR]

Current treatments for schizophrenia (SCZ) remain largely ineffective in one-third of patients. Recent studies using stem cell therapy show a close relationship between stem cell immunomodulatory function and neuroinflammation in SCZ. To better investigate the efficacy of stem cell therapy for SCZ, human umbilical cord blood mesenchymal stem cells (hUC-MSC) with powerful immunomodulatory effects were administered to rats via the tail vein (once a week for 5 consecutive weeks starting from the weaning period) using a maternal immune activation (MIA) rodent model. Open field, PPI, Western blotting, Q-PCR, and immunofluorescence were used to assess the biological effects of repeated tail vein injections of hUC-MSC in offspring rats following the MIA model of SCZ. The results indicated that offspring of MIA rats exhibited schizophrenia-like (SCZ-like) anxiety behavior, with observed microglial activation triggering neuroinflammation. Furthermore, levels of IBA1, HMGB1, and PSD95 were significantly up-regulated, while SYP was significantly down-regulated. It is suggested that hUCB-MSCs may act through HMGB1, Iba1, PSD95, and related pathway molecules to alleviate neuroinflammation and repair synaptic damage by regulating the activity state of microglia. Consequently, this could improve the abnormal behavior observed in MIA offspring rats. • hUCB-MSCs improve behavior of maternal immune activation(MIA) offspring. • hUCB-MSCs improve neuronal synaptic plasticity in MIA offspring. • hUCB-MSCs improve neuroinflammation in MIA offspring. • hUCB-MSCs may act by mediating HMGB1 secretion. [ABSTRACT FROM AUTHOR]

Background: Islet transplantation is an excellent method for the treatment of type I diabetes mellitus. However, due to the limited number of donors, cumbersome isolation and purification procedures, and immune rejection, the clinical application is greatly limited. The development of a simple and efficient new method to obtain islet β-cells is a key problem that urgently requires a solution for the treatment of type I diabetes mellitus. Methods: In this study, Pbx1, Rfx3, Pdx1, Ngn3, Pax4 and MafA were used to form a six-gene combination to efficiently reprogram aMSCs (adipose mesenchymal stem cells) into ra-βCs (reprogrammed aMSCs-derived islet β-cells), and the characteristics and immunogenicity of ra-βCs were detected. Feasibility of ra-βCs transplantation for the treatment of diabetes mellitus in model dogs and clinical dogs was detected. Results: In this study, aMSCs were efficiently reprogrammed into ra-βCs using a six-gene combination. The ra-βCs showed islet β-cell characteristics. The immunogenicity of ra-βCs was detected and remained low in vitro and increased after transplantation. The cotransplantation of ra-βCs and aMSCs in the treatment of a model and clinical cases of canine diabetes mellitus achieved ideal therapeutic effects. Conclusions: The aMSCs were efficiently reprogrammed into ra-βCs using a six-gene combination. The cotransplantation of ra-βCs and aMSCs as a treatment for canine diabetes is feasible, which provides a theoretical basis and therapeutic method for the treatment of canine diabetes. [ABSTRACT FROM AUTHOR]

• HSP90 inhibitors 17-AAG and VER-82576 inhibit porcine deltacoronavirus replication at the early stage of infection. • HSP90 inhibitor KW-2478 shows no significant antiviral activity at any stage of infection. • 17-AAG and VER-82576 inhibit the expressions of TNF-α, IL-6 and IL-12, which are PDCoV-induced proinflammatory cytokines. • Our findings conclude that 17-AAG and VER-82576 are promising candidates for the treatment of PDCoV infection. Porcine deltacoronavirus (PDCoV) is highly pathogenic to piglets, and no specific drugs or vaccines are available for the prevention and treatment of PDCoV infection, the need for antiviral therapies is pressing. HSP90 inhibitors have potent inhibitory effects against the replication of numerous viruses, hence we evaluated three HSP90 inhibitors, 17-AAG, VER-82576, and KW-2478, for their effects on PDCoV infection in vitro. We evaluated their effectivenesses at suppressing PDCoV by qRT-PCR, western blot, and TCID 50 assay, and found that 17-AAG and VER-82576 inhibited PDCoV at the early stage of replication, while KW-2478 showed no significant antiviral activity at any stage of infection. These results indicated that the PDCoV-inhibitory effects of 17-AAG and VER-82576 might be exerted by targeting host cell factor HSP90AB1 but not HSP90AA1. Further study showed that HSP90AB1 mRNA and protein levels were not significantly different in 17-AAG and VER-82576-treated cells versus control cells. 17-AAG and VER-82576 were also evaluated for their effects on the expressions of TNF-α, IL-6, and IL-12, which are PDCoV-induced proinflammatory cytokines. We found that both 17-AAG and VER-82576 inhibited the expressions of TNF-α, IL-6, and IL-12 to varying degrees, but in a dose dependent manner. From our data we can conclude that the HSP90 inhibitors 17-AAG and VER-82576 are promising candidates for the treatment of PDCoV infection. [ABSTRACT FROM AUTHOR]

PDCoV is an emerging enteropathogenic coronavirus that mainly causes acute diarrhea in piglets, seriously affecting pig breeding industries worldwide. To date, the molecular mechanisms of PDCoV-induced immune and inflammatory responses or host responses in LLC-PK cells in vitro are not well understood. HSP90 plays important roles in various viral infections. In this study, HSP90AB1 knockout cells (HSP90AB1KO) were constructed and a comparative transcriptomic analysis between PDCoV-infected HSP90AB1WT and HSP90AB1KO cells was conducted using RNA sequencing to explore the effect of HSP90AB1 on PDCoV infection. A total of 1295 and 3746 differentially expressed genes (DEGs) were identified in PDCoV-infected HSP90AB1WT and HSP90AB1KO cells, respectively. Moreover, most of the significantly enriched pathways were related to immune and inflammatory response-associated pathways upon PDCoV infection. The DEGs enriched in NF-κB pathways were specifically detected in HSP90AB1WT cells, and NF-κB inhibitors JSH-23, SC75741 and QNZ treatment reduced PDCoV infection. Further research revealed most cytokines associated with immune and inflammatory responses were upregulated during PDCoV infection. Knockout of HSP90AB1 altered the upregulated levels of some cytokines. Taken together, our findings provide new insights into the host response to PDCoV infection from the transcriptome perspective, which will contribute to illustrating the molecular basis of the interaction between PDCoV and HSP90AB1. [ABSTRACT FROM AUTHOR]

(1) Background: Porcine deltacoronavirus (PDCoV) is a newly emerged enteric virus affecting pig breeding industries worldwide, and its pathogenic mechanism remains unclear. (2) Methods: In this study, we preliminarily identified the endocytic pathway of PDCoV in PK-15 cells, using six chemical inhibitors (targeting clathrin-mediated endocytosis, caveolae-mediated endocytosis, macropinocytosis pathway and endosomal acidification), overexpression of dominant-negative (DN) mutants to treat PK-15 cells and proteins knockdown. (3) Results: The results revealed that PDCoV entry was not affected after treatment with chlorpromazine (CPZ), 5-(N-ethyl-N-isopropyl) amiloride (EIPA)or ammonium chloride (NH4Cl), indicating that the entry of PDCoV into PK-15 cells were clathrin-, micropinocytosis-, PH-independent endocytosis. Conversely, PDCoV infection was sensitive to nystatin, dynasore and methyl-β-cyclodextrin (MβCD) with reduced PDCoV internalization, indicating that entry of PDCoV into PK-15 cells was caveolae-mediated endocytosis that required dynamin and cholesterol; indirect immunofluorescence and shRNA interference further validated these results. (4) Conclusions: In conclusion, PDCoV entry into PK-15 cells depends on caveolae-mediated endocytosis, which requires cholesterol and dynamin. Our finding is the first initial identification of the endocytic pathway of PDCoV in PK-15 cells, providing a theoretical basis for an in-depth understanding of the pathogenic mechanism of PDCoV and the design of new antiviral targets. [ABSTRACT FROM AUTHOR]

Background: Pediatric leukemia is the most prevalent childhood cancer in China and incurs heavy economic burden to patients without sufficient insurance protection. Although all Chinese children are obliged to enroll in the national insurance scheme, "Resident Basic Medical Insurance (RBMI)", the protection may vary among patient subgroups. This study is designed to measure the disparities in economic burden for patients with leukemia under RBMI protection and explore the influencing factors.Methods: The included patients were aged ≤ 15 and diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML, with/without transplantation). They all completed treatment course consecutively in Nanfang Hospital and Zhujiang Hospital from Jan.1, 2015, to Dec.30, 2019, in Guangzhou, China. Their inpatient treatment and insurance settlement data were drawn from the Hospital Information System (HIS) and Insurance Settlement System (ISS). A total of 765 consecutive patients and 14,477 inpatient medical records were included and analyzed. Their insurance status (6 subtypes), economic burden [total cost, out-of-pocket cost (OOP), reimbursement, reimbursement rate (RR)], and cost structures (operation/procedure, blood products, drug, simple treatment) were calculated respectively. Non-normally distributed costs were reported as the median and interquartile range (IQR). Wilcoxon test was used for univariate tests and generalized linear model with log link was used to explore the influencing factors.Results: The insured patients who were treated in the location of insurance with instant reimbursement reported the highest total cost and reimbursement, while those who seek medical care cross-province with no instant reimbursement reported the lowest total cost and highest OOP payment. In terms of annual change, the total cost of children with leukemia decreased from 2015-2019 with stably increasing reimbursement rate. Blood products and drugs were the major components of total cost, but they decreased annually. Patients who received transplantation and treated across provinces were with a higher economic burden.Conclusion: The economic burden for children with leukemia decreased overtime under the protection of RBMI, but disparities exist among subtypes. The payer-provider contract on instant reimbursement and drug cost control are effective measures for insurance administrators to curb the economic burdens of pediatric leukemia treatment. [ABSTRACT FROM AUTHOR]

Background: Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored.Objectives: To study the spectrum of lymphoma subtypes prevalent within the Zambian population.Methods: Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher's exact test was used for significance testing.Results: During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin's lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin's lymphoma (CHL) was seen in 39 (16.3%). Burkitt's lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002).Conclusion: Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies. [ABSTRACT FROM AUTHOR]

Due to the expansion of human production activities, toxic ammonia (NH 3) is excessively released into the atmosphere, being a huge threat to human health and the natural environment. Therefore, it is of great significance to design an easy-synthesized gas-sensing material with both good room temperature sensitivity and selectivity for trace-level NH 3 detection. Herein, we fabricate a chemiresistive NH 3 gas sensor with enhanced performance based on Ni(OH) 2 /Ti 3 C 2 T x hybrid materials. The Ni(OH) 2 /Ti 3 C 2 T x hybrid materials are synthesized by an in-situ electrostatic self-assembly method. Attributed to the formation of interfacial heterojunctions and the modulation of carrier density, the Ni(OH) 2 /Ti 3 C 2 T x hybrid sensor exhibits high response, outstanding repeatability, good selectivity and stability in low concentrations of NH 3. Moreover, the Ni(OH) 2 /Ti 3 C 2 T x hybrid sensor has a higher response to 10 ppm NH 3 at the relative humidity of 40% and 60%, which makes it promising for applications in real complex environments with high humidity. Benefitting from the low power consumption and easy fabrication process, the Ni(OH) 2 /Ti 3 C 2 T x hybrid sensor possesses a broad application prospect in the internet of things (IoT) environmental monitoring. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is characterized by several core behavioral features, in which the gastrointestinal symptoms are frequently reported. Maternal immune activation (MIA) has been developed in a rodent model to study neurodevelopmental disorders such as schizophrenia. However, the changes in the gut environment of MIA rats remain largely unknown. Methods: 10 mg/kg of polyinosinic:polycytidylic acid (Poly I:C) on gestational day 9 was intravenously administered to rats to induce MIA in order to assess changes in behavior, the intestinal barrier and microbiota in offspring. Results: Maternal immune activation offspring shown increased anxiety as indicated by reduced exploration of central area in open field test and decreased exploration of open arms in elevated plus test. Cognitive impairment of MIA offspring was confirmed by reduced exploration of novel arm in Y maze test and deficiency of PPI. Intestinal muscle thickness became thinner and some specific microbial anomalies previously identified clinically were observed in MIA offspring. In addition, an increase of inflammatory responses was found in the gut of MIA offspring. Conclusions: Maternal immune activation alters behavior, intestinal integrity, gut microbiota and the gut inflammation in adult offspring. [ABSTRACT FROM AUTHOR]

Background multimorbidity contributes to a large portion of the disease burden in low- and middle-income countries. However, limited research has been undertaken in China. This study has investigated the prevalence of multimorbidity and the associations of multimorbidity with activities of daily living (ADL), instrumental activities of daily living (IADL) and depression in China. Methods the study participants included 10,055 adults aged 45 years and older from three rounds of the China Health and Retirement Longitudinal Study 2011–2015. Random-effects logistic regression models were used to examine the association of multimorbidity with ADL limitation, IADL limitation and mental disease. Results the prevalence of multimorbidity amongst adults in China aged 45 years and older was 62.1% in 2015. The prevalence of multimorbidity was increased with older age, among women, in a higher socio-economic group and in the most deprived regions. Multimorbidity is associated with an increased likelihood of experiencing ADL limitation (adjusted odds ratio [AOR] = 5.738, 95% confidence intervals (CI) = 5.733, 5.744) and IADL limitation (AOR = 2.590, 95% CI = 2.588, 2.592) and depression (AOR = 3.352, 95% CI = 3.350, 3.354). Rural–urban disparities in functional difficulties and depression were also found amongst patients with multimorbidity. Conclusions the burden of multimorbidity is high in China, particularly amongst the older population. Multimorbidity is associated with higher levels of functional limitations and depression. China healthcare reforms should introduce integrated care models and patient-centred healthcare delivery. The increasing need for reorientation of healthcare resources considering the distribution of multimorbidity and its adverse effect requires more attention from health policymakers in China and other developing countries. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 3 (IRF3) and IRF7 are closely related IRF members and the major factors for the induction of interferons, a key component in vertebrate innate immunity. However, there is limited knowledge regarding the evolution and adaptation of those IRFs to the environments. Two unique motifs in IRF3 and 7 were identified. One motif, GASSL, is highly conserved throughout the evolution of IRF3 and 7 and located in the signal response domain. Another motif, DPHK, is in the DNA-binding domain. The ancestral protein of IRF3 and 7 seemed to possess the DPHK motif. In the ray-finned fish lineage, while the DPHK is maintained in IRF7, the motif in IRF3 is changed to NPHK with a D → N amino acid substitution. The D → N substitution are also found in amphibian IRF3 but not in amphibian IRF7. Terrestrial animals such as reptiles and mammals predominantly use DPHK sequences in both IRF3 and 7. However, the D → N substitution in IRF3 DPHK is again found in cetaceans such as whales and dolphins as well as in marsupials. These observations suggest that the D → N substitutions in the IRF3 DPHK motif is likely to be associated with vertebrate's adaptations to aquatic environments and other environmental changes. [ABSTRACT FROM AUTHOR]

[Display omitted] • A nationwide spatial analysis on surface water pollutants and cancers integrating datasets was conducted. • Geographically weighted random forest addressed spatial heterogeneity for surface water pollutants. • Multiple pollutants of surface water spatially associated with digestive cancer incidence in China. Surface water pollution and digestive cancers are concerning environmental health issues. Multiple pollutants of surface water coexist within unique geospatial heterogeneous contexts of surface water flow, which can lead to complex patterns of impact on cancer incidence. This complexity has posed challenges to comprehensive assessment. In this study, we integrated nationwide surface water data of 21 pollutants collected from 3632 sections of nine large river basins and cancer incidence data for six digestive cancers covering 381.6 million people in China. Local Moran's I method was used to assess the patterns of spatial aggregation of each surface water pollutant separately to observe the local spatial nonstationarity and heterogeneity of the pollutant concentrations in different spatial areas. A geographically weighted random forest (GWRF) model, a spatial machine learning approach, was applied to address the spatial heterogeneity of the pollutants and assess their association with cancer incidence. Goodness-of-fit and overall performance of the GWRF model were assessed by the local statistics in the out-of-bag set, such as the mean local pseudo-R2, increase in mean squared error, and local residuals in each local model. Compared with the aspatial random forest model, the GWRF model had better performance (mean local pseudo-R2 ranged from 0.16 (gallbladder cancer) to 0.60 (pancreatic cancer)). Surface water pollution was associated with digestive cancer incidence mainly in the Songhua and Liaohe, Haihe, and Huaihe River Basins. By focusing on these areas, we identified key pollutants specific to different cancer types. Incidence of oesophageal, stomach, colorectal, gallbladder, and pancreatic cancer was associated with common pollutants such as fluoride and arsenic. Our assessment provides targets for the government and environmental health specialists to take tailored actions to control pollution and effectively prevent cancer incidence. [ABSTRACT FROM AUTHOR]

• Fourteen differential metabolites showed correlations with the PANSS scores of schizophrenia patients. • A biomarker panel composed of lipid, sulfate, and L-tryptophan can distinguish schizophrenia from healthy control. • A biomarker panel including lipid, unsaturated fatty acid, and sulfate could be used for discrimination between schizophrenia before and after medication. • Disturbances in lipid metabolism, tryptophan metabolism, anti-inflammatory and antioxidant systems were identified in schizophrenia patients. • Our findings facilitate the development of objective diagnostic tools for schizophrenia. Schizophrenia (SCZ) is a severe mental disorder. Using liquid chromatography mass spectrometry, we performed comprehensive metabolomics analyses of plasma samples from healthy controls (HC) and first episode SCZ patients before and after an acute period of medication. Ten lipid metabolites and 27 soluble small molecules were identified as potential biomarkers associated with the diagnosis and treatment of SCZ. These metabolites were significantly reduced in SCZ, and lipids and sulfate were significantly increased after treatment. Of the metabolites identified, four showed significant correlations with the Positive and Negative Syndrome Scale total scores. A biomarker panel composed of alpha-dimorphecolic, Phosphatidylcholine (PC) (16:0/18:1(11Z)), 1-methylnicotinamide, Phosphatidylethanolamine (PE) (20:2(11Z,14Z)/18:2(9Z,12Z)), sulfate, and L-tryptophan was selected to distinguish SCZ from HC; this provided the maximum classification performance with an AUC of 0.972. A biomarker panel including C16 sphinganine, gamma-linolenic acid, linoleic acid, PC(16:0/18:1(11Z)), PE(20:2(11Z,14Z)/18:2(9Z,12Z)), and sulfate, was selected for discrimination between SCZ before and after medication, and produced the optimal classification performance with an AUC of 0.905. Disturbances in lipid metabolism, sulfation modification, tryptophan metabolism, anti-inflammatory and antioxidant systems, and unsaturated fatty acids metabolism, were identified in SCZ. Our findings could facilitate the development of objective diagnostic or drug treatment monitoring tools for schizophrenia. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The disparity between government health expenditures across regions is more severe in developing countries than it is in developed countries. The capitation subsidy method has been proven effective in developed countries in reducing this disparity, but it has not been tested in China, the world's largest developing country.Methods: The convergence method of neoclassical economics was adopted to test the convergence of China's regional government health expenditure. Data were obtained from Provinces, Prefectures and Counties Fiscal Statistical Yearbook (2003-2007) edited by the Chinese Ministry of Finance, and published by the Chinese Finance & Economics Publishing House.Results: The existence of σ-convergence and long-term and short-term β-convergence indicated the effectiveness of the capitation subsidy method in the New Rural Cooperative Medical Scheme on narrowing county government health expenditure disparities. The supply-side variables contributed the most to the county government health expenditure convergence, and factors contributing to convergence of county government health expenditures per capita were different in three regions.Conclusion: The narrowing disparity between county government health expenditures across regions supports the effectiveness of the capitation subsidy method adopted by China's New Rural Cooperative Scheme. However, subsidy policy still requires further improvement. [ABSTRACT FROM AUTHOR]

Immune activation can exert multiple effects on synaptic transmission. Our study demonstrates the influence of neonatal vaccination on hippocampal synaptic plasticity in rats under normal physiological conditions. The results revealed that neonatal BCG vaccination enhanced synaptic plasticity. In contrast, HBV hampered it. Furthermore, we found that the cytokine balance shifted in favour of the T helper type 1/T helper type 2 immune response in BCG/HBV-vaccinated rats in the periphery. The peripheral IFN-γ:IL-4 ratio was positively correlated with BDNF and IGF-1 in the hippocampus. BCG raised IFN-γ, IL-4, BDNF and IGF-1 and reduced IL-1β, IL-6, and TNF-α in the hippocampus, whereas, HBV triggered the opposite effects. [ABSTRACT FROM AUTHOR]

The scope of water and land resource management has been expanded by the interregional trade beyond a single region's boundary along the trans-regional production chain, and the nexus thinking facilitate the understanding of the multi-resource interrelationships and interactions. For the investigation of the water-land nexus, besides the consideration of land use, this study first considered the soil erosion caused by agricultural activities to reveal the water-land nexus from both land cover and soil layer perspectives. The integrated nexus strength (INS) indicator combining with linkage analysis was introduced to detect the distant connections of water and land in ten counties and one city of the Heihe River Basin in Northwestern China. The results show that, from the regional perspective, Minle and Ganzhou in the middle reaches of the Heihe River Basin were essential regions for the water-land nexus, as they imported and exported products embodied with intensive water resource, land use, and soil erosion. Suzhou was the major net importer with imports from counties in middle reaches, including Gaotai, Linze, Ganzhou, and Minle. Jinta, located in the downstream of the Heihe River Basin, faced with serious water scarcity, land desertification, and soil erosion problems, still exported large amounts of agricultural products embodied with numerous resources. From sectoral perspective, the Grain Crops and Cash Crops sectors in the middle reaches had higher values of INS-net forward linkage (export direction), due to that the agricultural sector was primary resource consumers in supply chains to support the following production processes. For INS-net backward linkage (import direction), the Foods and Services sectors in the middle reaches were the dominant sectors, in the reason that food processing and service production processes required more primary products with intensive embodied resources to fulfill their production activities. • The soil erosion was incorporated into the consideration of water-land nexus. • A new metric was developed to rank the performance of water-land nexus. • The nexus strength indicator was updated by linkage analysis. [ABSTRACT FROM AUTHOR]

The cellular interferon (IFN) regulatory factor-7 (IRF7) is closely associated with the Epstein–Barr virus (EBV)-mediated transformation of B lymphocytes in vitro and in vivo. However, the exact role of IRF7 in viral transformation is not clear. We have found that knockdown of IRF7 leads to growth inhibition of EBV-transformed cells, and restoration of IRF7 by exogenous plasmid correlates with growth recovery of the viral transformed cells. In addition, IRF7-knockdown cells have a lower proliferation but a higher apoptotic rate than control cells. Moreover, reduction of IRF7 leads to reduction of major viral oncoprotein, latent membrane protein 1 (LMP1). Our data suggest that IRF7 may be a factor in EBV transformation and a useful target in the therapy of EBV-mediated neoplasia. [ABSTRACT FROM AUTHOR]

• Five LLC-PK1 cell lines, each with one of the genes of interest knocked down, were constructed using CRISPR/cas9. • STAT1 interacts with PDCoV, and plays a negative regulatory role in PDCoV infection. • The absence of STAT1 results in increased internalization of PDCoV. • PDCoV infection stimulated expression of interferon stimulated genes (ISGs) downstream of STAT1. Porcine deltacoronavirus (PDCoV) is an enteropathogen found in many pig producing countries. It can cause acute diarrhea, vomiting, dehydration, and death in newborn piglets, seriously affecting the development of pig breeding industries. To date, our knowledge of the pathogenesis of PDCoV and its interactions with host cell factors remains incomplete. Using Co-IP coupled with LC/MS-MS, we identified 67 proteins that potentially interact with PDCoV in LLC-PK1 cells; five of the identified proteins were chosen for further evaluation (IMMT, STAT1, XPO5, PIK3AP1, and TMPRSS11E). Five LLC-PK1 cell lines, each with one of the genes of interest knocked down, were constructed using CRISPR/cas9. In these knockdown cells lines, only STAT1KD resulted in a significantly greater virus yield. Knockdown of the remaining four genes resulted, to varying degrees, in a lower virus yield that wild-type LLC-PK1 cells. The absence of STAT1 did not significantly affect the attachment of PDCoV to cells, but did result in increased viral internalization. Additionally, PDCoV infection stimulated expression of interferon stimulated genes (ISGs) downstream of STAT1 (IFIT1, IFIT2, RADS2, ISG15, MX1, and OAS1) while knockdown of STAT1 resulted in a greater than 80 % decrease in the expression of all six ISGs. Our findings show that STAT1 interacts with PDCoV, and plays a negative regulatory role in PDCoV infection. [ABSTRACT FROM AUTHOR]

• Cellulose degradation is essential for vermicomposting of lignocellulosic wastes. • GH 6 cellulases play a key role in the early step of cellulose degradation. • Cellulomonas and Cellulosimicrobium were the dominant genera harboring GH 6 gene. • The abundance of GH 6 was quantified during vermicomposting process. • Succession of microbial communities led to changes in the abundance of GH 6 gene. Vermicomposting eco-friendly converts lignocellulosic wastes into bio-organic fertilizer. Cellulose is the most abundant carbohydrate in lignocellulose. Glycoside hydrolase family 6 (GH 6) plays a key role in the early step of cellulose degradation, which is essential for stabilizing lignocellulose. This study intends to quantify the abundance of GH 6 gene and to clarify the succession of GH 6 cellulase-producing microbial communities during vermicomposting. 100% of maize stover (A) and maize stover and cow dung at 60:40 ratio (B) were used. The results showed that different native genera were observed in the starting materials. Cellulomonas and Cellulosimicrobium were dominant genera harboring GH 6 gene. The peak relative abundance of Cellulomonas was 76% and 30% in B and A during vermicomposting phase, and the corresponding values of Cellulosimicrobium was 36% and 37%. Earthworms increased the abundance of GH 6 gene, which reached 1.51E + 09 from 3.46E + 08 copies/g in B. The results partially interpreted promoting effect of earthworms. [ABSTRACT FROM AUTHOR]

CD20 is a B cell surface marker that is expressed in various stages in B lymphocytes and certain lymphomas. Clinical administration of CD20 antibody, such as rituximab, is used widely to treat human B-cell lymphomas and other diseases. However, CD20 antibody failed to treat systemic lupus erythematosus (SLE or lupus). The reason for the failure is currently unknown. Type I interferons (IFN) are a major component for the host innate immunity, and a key pathogenic factor in lupus. We found that CD20 antibody potentiated human B cells for its production of IFNs in vitro. This function was specific to CD20-expressing cells and the potentiation function seems to be instant. In addition, ectopic expression of CD20 in non-B-lymphocytes increased the IFN promoter reporter activities. Because IFNs are a key pathogenic factor in lupus, our data suggest that, in the presence of virus infection, the CD20-antibody-mediated enhancement of IFN production might be related to its failure in lupus treatments. This work may provide new insights for CD20-Ab therapeutic applications. [ABSTRACT FROM AUTHOR]

Introduction: The present data on the evaluation of platelet (PLT) parameters in Chinese Han population and Tibetans are still limited. The objective of this study was to determine the differences in common PLT indices between Han population and Tibetans in China, through a large-scale investigation of healthy people. Methods: 2131 Han people from Chengdu Plain, 1099 Tibetans from Qinghai-Tibet Plateau and 956 Plateau Han migrants were included in this study. All the subjects were healthy people through the health screening. PLT indices were measured with Sysmex XE-2100 and XT-1800i blood cell automatic analyzer. Results: Compared with Han people in Chendu Plain, Tibetans had higher PLT count (P<0.01) but lower mean platelet volume (MPV), platelet distribution width (PDW) and platelet-large cell ratio (P-LCR) (P<0.01); while Plateau Han migrants had lower PLT count, MPV and P-LCR (P<0.05). When compared with Tibetans, Plateau Han migrants had lower levels of mean PLT count but higher PDW and P-LCR (P<0.05). Conclusions: There are ethnic differences in PLT indices between Chinese Han population and Tibetans. Based on this finding, it would be reasonable to conduct formal prospective studies to determine the clinical significance of these differences and to explore the effects of genetic background on these indices. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is an important environmental factor associated to the development of Burkitt lymphoma (BL) in endemic and intermediate risk regions. However, little is known about the contribution of genetic constitution to the development and clinical response of the disease. The aim of this work was to investigate the role of EBV and Interleukin 10 (IL10) single nucleotide polymorphisms (-- 1082A/G, -- 819C/T, -- 592C/A) and microsatellites (IL10.R and IL10.G) in susceptibility and clinical outcome in pediatric BL patients, in a region with intermediate EBV association frequency. The frequencies of IL10 promoter Single nucleotide polymorphisms -- 1082A/G, -- 819C/T, -- 592C/A, and IL10.R and IL10.G microsatellites were compared in 62 pediatric patients and 216 healthy donors. IL10 -- 1082GG and GCC/GCC genotypes were more frequent in patients than in controls, and associated to a higher risk of BL development (GG genotype OR 2.62, 95% CI, 1.25--5.51; P = 0.008; Pc = 0.024). EBV was detected in tumor samples by EBER-ISH in 54.1% of cases. EBV+ patients exhibited a better event free survival (EFS) (P = 0.019) than EBV -- patients. Carriers of IL10 R3-GCC had worse EFS (P = 0.028). Our results suggest a risk effect and an independent prognostic value of IL10 polymorphisms and EBV in childhood BL patients. [ABSTRACT FROM AUTHOR]

Abstract: Kaposi''s sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. RTA activates promoters by several mechanisms. RTA can bind to sequences in viral promoters and activate transcription. In addition, RTA interacts with the cellular recombination signal sequence-binding protein-J kappa (RBP-Jκ), a transcriptional repressor, converts the repressor into an activator and activates viral promoters via RBP-Jκ. Because RBP-Jκ is required for RTA to activate lytic replication, it is important to understand how RTA cooperates with RBP-Jκ protein to activate KSHV lytic replication program. Previously, we identified an RTA mutant, RTA-K152E, which has a defect in its direct DNA-binding activity. In this report, the effect of the mutant RTA on KSHV activation via RBP-Jκ protein is examined. We demonstrate that RTA-K152E interacts with RBP-Jκ physically and the mutant RTA and RBP-Jκ complex binds to target DNA properly in vivo and in vitro. However, the complex of RTA-K152E and RBP-Jκ does not activate transcription. Furthermore, the RTA mutant (RTA-K12E) inhibits cellular Notch-mediated RBP-Jκ activation. These data collectively suggest that the complex between KSHV RTA and cellular RBP-Jκ and the subsequent DNA binding by the complex are not sufficient for the activation of RBP-Jκ protein. Other factor(s) whether additional cofactor(s) in the complex or the intrinsic conformation of RTA, are predicted to be required for the activation of RBP-Jκ protein by RTA. [Copyright &y& Elsevier]

Epstein-Barr virus (EBV) infection is associated with several human cancers. Latent membrane protein 1 (LMP-1) is one of the key viral proteins required for transformation of primary B cells in vitro and establishment of EBV latency. In this report, we show that LMP-1 is able to induce the expression of several interferon (IFN)-stimulated genes (ISGs) with antiviral properties such as 2'-5' oligoadenylate synthetase (OAS), stimulated trans-acting factor of 50 kDa (STAF-50), and ISG15. LMP-1 inhibits vesicular stomatitis virus (VSV) replication at low multiplicity of infection (0.1 pfu/cell). The antiviral effect of LMP-1 is associated with the ability of LMP-1 to induce ISGs; an LMP-1 mutant that cannot induce ISGs fails to induce an antiviral state. High levels of ISGs are expressed in EBV latency cells in which LMP-1 is expressed. EBV latency cells have antiviral activity that inhibits replication of superinfecting VSV. The antiviral activity of LMP-1 is apparently not related to IFN production in our experimental systems. In addition, EBV latency is responsive to viral superinfection: LMP-1 is induced and EBV latency is disrupted by EBV lytic replication during VSV superinfection of EBV latency cells. These data suggest that LMP-1 has antiviral effect, which may be an intrinsic part of EBV latency program to assist the establishment and/or maintenance of EBV latency. [ABSTRACT FROM AUTHOR]

Background: Family doctor contract service is an important service item in China's primary care reform. This research was designed to evaluate the impact of the provision of family doctor contract services on the patient-perceived quality of primary care, and therefore give evidence-based policy suggestions. Methods: This cross-sectional study of family doctor contract service policy was conducted in three pilot cities in the Pearl River Delta, South China, using a multistage stratified sampling method. The validated Primary Care Assessment Tool-Adult Edition (PCAT-AS) was used to measure the quality of primary care services. PCAT-AS assesses each of the unique characteristics of primary care including first contact, continuity, comprehensiveness, coordination, family-centeredness, community orientation, culture orientation. Data was collected through face-to-face interviews held from July to November, 2015. Covariate analysis and multivariate Linear Regression were adopted to explore the effect of contract on the quality of primary care by controlling for the socio-demographic status and health care service utilization factors. Results: A total of 828 valid questionnaires were collected. Among the interviewees, 453 patients signed the contract (54.7%) and 375 did not (45.3%). Multivariate linear regression showed that contracted patients reported higher scores in dimensions of PCAT total score (β = − 8.98, P < 0.000), first contact-utilization(β = − 0.71,P < 0.001), first contact-accessibility(β = − 1.49, P < 0.001), continuity (β = 1.27, P < 0.001), coordination (referral) (β = − 1.42, P < 0.001), comprehensiveness (utilization) (β = − 1.70, P < 0.001), comprehensiveness (provision) (β = − 0.99, P < 0.001),family-centeredness(β = − 0.52, P < 0.01), community orientation(β = − 1.78, P < 0.001), than un- contracted after controlling socio-demographic and service utilization factors. There were no statistically significant differences in the dimensions of coordination (information system) (β = − 0.25, P = 0.137) and culture orientation (β = − 0.264, P = 0.056) between the two both groups. Conclusions: This study demonstrates that the pilot implementation of family doctor contract services has significantly improved patients' perceived primary care quality in the pilot cities, and could help solve the quality problem of primary care. It needs further promotion across the province. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been extensively explored over the past decade, including mice and humans. However, their impact on the transdifferentiation of canine bone marrow mesenchymal stem cells (cBMSCs) into insulin-producing cells (IPCs) is largely unknown. In this study, we used a three-step induction procedure to induce cBMSCs into IPCs, and samples (two biological replicates each) were obtained after each step; the samples consisted of "BMSCs" (B), "stage 1" (S1), "stage 2" (S2), "stage 3" (S3), and "islets" (I). After sequencing, 15,091 lncRNAs were identified, and we screened 110, 41, 23, and 686 differentially expressed lncRNAs (padjusted < 0.05) in B vs. S1, S1 vs. S2, S2 vs. S3, and I vs. S3 pairwise comparisons, respectively. In lncRNA target prediction, there were 166,623 colocalized targets and 2,976,362 correlated targets. Gene Ontology (GO) analysis showed that binding represented the main molecular functions of both the cis- and trans-modes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the insulin signaling pathway, Rap1 signaling pathway, tight junctions, MAPK signaling pathway, and cell cycle were enriched for these relative genes. The expression of lncRNAs was verified using qRT-PCR. This study provides a lncRNA catalog for future research concerning the mechanism of the transdifferentiation of cBMSCs into IPCs. [ABSTRACT FROM AUTHOR]

• MIA induces progressive worsening behaviors in adolescents and adults offspring. • MIA impaires ERK activation in offspring. • MIA induces age- and region-related alterations of neurofilaments in offspring. Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive deficits, but a role in this model for dynamic changes in ERK has not been established. In this study, polyinosinic:polycytidylic acid was administered to rats intravenously at a dose of 10 mg/kg on embryonic day 9.5 to produce MIA. The effect of MIA on behavior and ERK phosphorylation within the prefrontal cortex and the hippocampus of adolescent and adult offspring were explored. We also examined neurofilaments, a marker of neurogenesis, which have been reported to be modulated by ERK signaling. The results demonstrate an age- and region-specific profile of ERK expression and phosphorylation and suggest possible relationships among ERK, neurofilament expression, and cognitive performance in schizophrenia. [ABSTRACT FROM AUTHOR]

Multimorbidity (the presence of two or more chronic conditions) is a significant contributor to inequalities in health care and has become the major unaddressed challenge for the health system in China. We assessed the distribution of multimorbidity in relation to economic status and the relationships between multimorbidity, health-care use, and catastrophic health expenditure in China. We conducted a longitudinal study using three waves of data (2011, 2013, and 2015) from the China Health and Retirement Longitudinal Study (CHARLS), including 12 096 participants aged 45 years and older. Random effects logistic regression models were used to determine the sociodemographic correlates of multimorbidity, including age, sex, marital status, education, residence location, socioeconomic status quartiles (yearly per-capita household consumption expenditure), health insurance, and geographical region. Negative binomial regression models were used to assess the relationship between multimorbidity and outpatient visits, as well as days of hospitalisation. Multivariate logistic regression models were used to estimate the effect of multimorbidity on catastrophic health expenditure, defined as the point at which annual household health payments exceeded 40% of non-food household expenditure. The Biomedical Ethics Review Committee of Peking University approved the CHARLS study (approval number IRB00001052–11015), and all interviewees were required to provide informed consent. Of 12 096 participants, 5566 (46·0%) in 2011, 6069 (50·2%) in 2013, and 7399 (61·2%) in 2015 had two or more chronic diseases. The onset of multimorbidity occurred 5–10 years earlier in people in the highest economic quartile group than in the lowest group. Multimorbidity was positively associated with health service use, including outpatient visits (coefficient 0·25, 95% CI 0·24–0·27) and days of hospitalisation (0·31, 0·31–0·35). Multimorbidity was associated with an increased likelihood of experiencing catastrophic health expenditure (odds ratio 1·30, 95% CI 1·27–1·33). These associations appeared to be similar among people covered by health insurance across economic groups. By contrast, income-related disparities in the association between multimorbidity and health service use were more pronounced in the population without health insurance. Multimorbidity is associated with higher levels of health service use and a greater financial burden to individuals in China. Acceleration of progress to achieve universal health insurance coverage could improve disparities in access to health care among economic groups. Health-care reforms in China should place greater emphasis on reducing out-of-pocket spending for patients with multimorbidity. None. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have attracted increasing attention for their function in oocyte in vitro maturation (IVM). In this study, we aimed to explore the functional role and underlying mechanism of miR-375 in oocyte IVM. Cumulus-oocyte complexes (COCs) were cultured in standard cell culture conditions until they reach metaphase II (MII) stage. MiR-375 overexpression or knockdown was achieved by corresponding lentiviral transduction. Levels of miR-375, disintegrin and metalloproteinase with thrombospondin-like motifs 1 (ADAMTS1) mRNA and progesterone receptor (PGR) mRNA were detected by qRT-PCR. Western blotting was used to assess the expression of ADAMTS1 and PGR protein. The targeted interaction between miR-375 and ADAMTS1 or PGR was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Our results demonstrate that miR-375 is downregulated, and ADAMTS1 and PGR are upregulated in cumulus cells during COC maturation. MiR-375 negatively regulates COC maturation. Moreover, ADAMTS1 and PGR are two targets of miR-375 in cumulus cells. ADAMTS1 or PGR knockdown represses COC maturation and miR-375 inhibits the expression levels of ADAMTS1 and PGR in cumulus cells. Additionally, miR-375 overexpression-mediated suppressive effect on COC maturation is abated by ADAMTS1 or PGR expression restoration. In conclusion, our study suggests that miR-375 represses oocyte IVM at least partially through targeting ADAMTS1 and PGR in cumulus cells, providing a novel insight for the involvement and underlying mechanism of miR-375 in oocyte IVM. [ABSTRACT FROM AUTHOR]

Prenatal exposure to polyriboinosinic–polyribocytidylic acid (poly I:C) results in psychotic-like behavior in mature rat offspring as well as enduring modifications of glutamatergic excitatory synaptic transmission. However, little is known about the dynamic behavioral and glutamate N -methyl-D-aspartate (NMDA) receptor changes in rat offspring following poly I:C treatment of pregnant dams. In this study, poly I:C was administered to rats intravenously at a dose of 10 mg/kg on gestational day 9 in order to assess changes in behavior and NMDA receptors in offspring over time. Results demonstrate progressive worsening behaviors in adolescents and adults that manifest as increased anxiety, cognitive impairment, and pre-pulse inhibition deficits. Age-related alteration of NMDA receptors in the prefrontal cortex and hippocampus, either total number or distribution, were observed from weaning to adulthood. These results suggest that abnormalities of NMDA receptors occur prior to obvious schizophrenia-like behavioral manifestations. Hence, NMDA receptors may be potential therapeutic targets to prevent disease development during asymptomatic periods of schizophrenia, and may serve as targets for preventive and/or therapeutic strategies for schizophrenia. Further, PSD95, a scaffolding protein that is a component of the NMDA receptor signaling complex, is increased in the hippocampus of adult offspring, when serious behavioral abnormalities emerge. This result suggests that PSD95 may be involved in behavioral abnormalities of schizophrenia. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) infection is associated with many human malignancies. In vitro, EBV transforms primary B lymphocytes into continuously growing lymphoblastoid cell lines. EBV latent membrane protein 1 (LMP-1) is required for EBV transformation processes. Interferon regulatory factor 4 (IRF-4) is a transcription factor and has oncogenic potential. We find that high levels of IRF-4 are associated with EBV transformation of human primary B cells in vitro and with EBV type III latency in which LMP-1 is expressed. We show that EBV LMP-1 stimulates IRF-4 expression in B lymphocytes. The stimulation of IRF-4 by LMP-1 requires signaling from LMP-1 and involves cellular NF-κB. The growth of EBV-transformed cells is inhibited when IRF-4 is specifically down-regulated. We further demonstrate that IRF-4 knockdown cells have lower proliferation but higher apoptotic rates than control cells. Finally, IRF-4 is expressed in significant numbers of specimens of primary central nervous system (CNS) lymphomas (12/27 [44.4%]), an EBV-associated malignancy. The association between the expression levels of LMP-1 and IRF-4 is statistically significant (P = 0.011) in these CNS lymphomas. Our data suggest that IRF-4 may be a critical factor in EBV transformation and a useful target in the therapy of EBV-mediated neoplasia. [ABSTRACT FROM AUTHOR]