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Objective: We aimed to estimate the spatiotemporal patterns of the encephalitis burden along with its attributable risk factors at the national, regional, and global levels, which may be helpful in guiding targeted prevention and treatment programs.Methods: Based on available data sources, the incidence, mortality, and disability-adjusted life years (DALYs) of encephalitis in 204 countries and regions from 1990 to 2019 were reconstructed by the Global Burden of Disease Study 2019 using the Cause of Death Ensemble model, spatiotemporal Gaussian process regression, and DisMod-MR 2.1. We conducted a systematic analysis on the epidemiological characteristics of encephalitis in detail by gender, region, and age over the past three decades.Results: Globally, 1,444,720 incident cases, 89,900 deaths, and 4.80 million DALYs related to encephalitis were estimated in 2019. The age-standardized incidence rate and age-standardized mortality rate (ASMR) decreased from 23.17 and 2.18 to 19.33 and 1.19 per 100,000 person-years over the past 30 years, respectively. However, beginning in 2011-2013, the burden of encephalitis has shown an inflection point, with a further decline of the ASRs ceasing. Lower socio-demographic index (SDI) regions in South Asia, Western and Eastern Sub-Saharan Africa had the highest burden of encephalitis in 2019. During the past three decades, most countries of South Asia achieved significant control of the burden. In contrast, developed countries with a higher SDI have shown a notable increase in ASMR and age-standardized DALYs rate. Children and older adults have always been high-risk groups for encephalitis.Conclusion: Although the global burden of encephalitis has decreased in the past 30 years, a further decline stopped from 2011 to 2013. The diverse burden in different regions calls for differentiated management, and the persistent high burden in some low-SDI regions and the increased burden in developed countries with higher SDIs deserve more attention. [ABSTRACT FROM AUTHOR]

• Multi-channel feature fusion based on CSES-NET neural network for AD diagnosis. • Deep neural network based on attention mechanism extracts deep voxel features. • Fully connected network and LightGBM focuses on multi-channel feature fusion. • Single Model extracts more heterogeneous information. • GWAS is used to analyze risk genes for structural changes in the brain. Alzheimer's disease (AD) is an irreversible brain disease. The structural Magnetic Resonance Imaging (sMRI) has been widely used in the diagnosis of AD. However, the characteristic information from a single-mode is not comprehensive. In this paper, we proposed a Convolutional- Squeeze-Excitation-Softmax-NET (CSES-NET) deep neural network combined with multi-channel feature fusion for the diagnosis of AD. First, three kinds of features were extracted including patches based on voxel morphology, cortical features based on surface morphology, and radiomics features. Next, the residual network CSES-NET was proposed to extract the deep features from the patch images in which the features were re-scaled in the residual structure in order to fit the correlation between channels. Then, the fused features of the three channels were applied to classify AD/EMCI/LMCI/NC with the fully connected neural network. Finally, radiomics and cortical features were combined with genetic data for genome-wide association study to assess genetic variants. We performed experiments with 1539 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results verified that the proposed method improved the effectiveness of the model by extracting nonlinear deep features and fusing the multi-channel features. In addition, the genome-wide association study identified multiple risk SNPs loci which were associated with the pathological of AD and contributed to the early prevention and control of AD. [ABSTRACT FROM AUTHOR]

According to the statistics, large public building’s total area is less than 4% of the total construction area of town; But the total energy consumption of large public buildings accounts for 22% of the town’s total power consumption; So large public buildings is the focus of energy efficiency with great energy saving space. However, in the energy-saving renovation project of office buildings which is an important part in large public buildings, people often focus on unit product upgrades and technical improvement of energy-using equipment in building, and ignore the user equipment for energy saving space.This research aims at indoor terminal controlling end system of energy-controlling electrical equipment; With the real-time monitoring of environmental parameters and working-status control of electric equipment, it is proposed to complete the premise function of building use, reduce the power consumption cost of office buildings’ operation, improve the buildings’ electrical energy to efficiency ratio and promoting the development of green building’s construction process. It has high social and economic benefits, and has good prospects for development. [ABSTRACT FROM AUTHOR]

Objective The aim of this review is to evaluate the roles of myeloid-derived suppressor cells (MDSC) in autoimmune arthritis. Methods The terms “myeloid-derived suppressor cells,” “regulatory T cell,” “Th17 cell” and “autoimmune arthritis” were used for literature search from the PubMed. The publications about the characteristics of MDSC, the immunosuppression of MDSC, the role of MDSC in the regulation of Tregs and Th17 cells, and the potential clinical applications of MDSC against rheumatoid arthritis (RA) were identified, retrieved and reviewed. Results MDSC are defined as a heterogeneous population of pathologically activated immature and mature myeloid cells consisting of granulocytic and monocytic subsets. Published data showed that the role of MDSC in Tregs and Th17 cells expansion were inconsistent. Given their role in suppressing T-cell responses, MDSC have been tested for their capability of preventing RA. Conclusions Although MDSC hold promise in the treatment of RA, their exact role in the expansion of Tregs and Th17 cells is unclear during RA. The definite effect of MDSC in RA therapy needs to be studied further. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. Autophagy is a process in which cytoplasmic components such as organelles and proteins are delivered to the lysosomal compartment for degradation, and plays an essential role in the maintenance of cellular homeostasis. The activity of autophagy is enhanced during oxidative stress. The objectives of this work were first to study the inhibitory action of antioxidant ascorbic acid on behavioral changes and brain damage induced by high doses of pilocarpine, then to study the effect of ascorbic acid on oxidative stress (MDA and SOD were used to estimate oxidative stress) and activated autophagy (beclin 1 was used to estimate autophagy) induced by seizures, aiming to further clarify the mechanism of action of this antioxidant compound. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (500mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (340mg/kg, i.p., P340 model) in rats. Ascorbic acid injections prior to pilocarpine suppressed behavioral seizure episodes by increasing the latency to the first myoclonic, clonic and tonic seizure and decreasing the percentage of incidence of clonic and tonic seizures as well as the mortality rate. These findings suggested that oxidative stress can be produced and autophagy is increased during brain damage induced by seizures. In the P340 model, ascorbic acid significantly decreased cerebral damage, reduced oxidative stress and inhibited autophagy by reducing de novo synthesis of beclin 1. Antioxidant compound can exert neuroprotective effects associated with inhibition of free radical production and autophagy. These results highlighted the promising therapeutic potential of ascorbic acid in treatment for seizures. [Copyright &y& Elsevier]

Abstract: Intense poly(ADP-ribose) polymerase-1 (PARP-1) activation was implicated as a major cause of caspase-independent cell death in the hippocampal neuronal culture (HNC) model of acute acquired epilepsy (AE). The molecular mechanisms are quite complicated. The linkage among neuronal death, cellular nicotinamide adenine dinucleotide (NAD) levels, apoptosis-inducing factor (AIF) translocation, SIRT1 expression and activity were investigated here. The results showed that PARP-1 over-activation caused by Mg2+-free stimuli led to cellular NAD depletion which could block AIF translocation from mitochondria to nucleus and attenuate neuronal death. Also, SIRT1 deacetylase activity was reduced by Mg2+-free treatment, accompanied by elevated ratio of neuronal death, which could be rescued by NAD repletion. These data demonstrated that cellular NAD depletion and decline of SIRT1 activity play critical roles in PARP-1-mediated epileptic neuronal death in the HNC model of acute AE. [Copyright &y& Elsevier]

Abstract: In many cases, it is desirable to maintain the native status of the target glycoproteins when they are deglycosylated. However, most conventional deglycosylation process often causes the irreversible denaturation of the target glycoproteins. In the present study, we developed a deglycosylation method that could obtain the native deglycosylated proteins employing Png1p-ΔH1, which was confirmed to tolerate high concentration of dithiothreitol (DTT). To prove this process, ribonuclease B (RNase B) and Yeast carboxypeptidase (CPY) were employed as the targeting glycoproteins. Our results confirmed that both of them could be completely deglycosylated in the presence of high concentration DTT and could be refolded when DTT was removed. The circular dichroism spectroscopy (CD) measurement of refolded CPY and RNase B indicated that the structure of deglycosylated proteins had recovered their native status. This method offers the possibility of efficiently releasing N-linked glycans from glycoproteins and obtaining the native target proteins. [Copyright &y& Elsevier]

Abstract: Glucocorticoid-induced tumor necrosis factor receptor and its ligand (GITRL) are critically involved in the regulation of immune response. In this study, we aimed to generate bone marrow-derived dendritic cells (BMDCs) transfected with recombinant adenovirus expressing GITRL (pAd-GITRL-BMDCs) and explore their therapeutic efficacy in murine Lewis lung carcinoma. In vitro, pAd-GITRL-BMDCs greatly enhanced effector T cells proliferation but markedly abrogate the suppression of Treg cells. Moreover, vaccination with pAd-GITRL-BMDCs significantly retarded tumor growth, which was accompanied with increased IFN-γ-producing CD8+ T cells and markedly decreased Treg cells in vivo. These findings suggest GITRL could enhance the immune stimulation of DC and might facilitate the potential development of DCs-based anti-tumor therapies. [ABSTRACT FROM AUTHOR]

Abstract: Calcineurin (CaN) is a neuronally enriched, calcium-dependent phosphatase, which plays an important role in a number of neuronal processes including development of learning and memory, and modulation of receptor''s function and neuronal excitability as well as induction of apoptosis. It has been established in kindling model that the status epilepticus (SE)-induced increase in CaN activity is involved in the development of seizures through down-regulation of γ-aminobutyric acid A receptor (GABAAR) activation. However, the mechanism by which CaN mediates GABAA receptor dephosphorylation in SE is not fully understood. Here, using a model of kainic acid (KA)-induced SE and CaN inhibitor FK506, we observed the behaviors induced by KA and levels of CaN activity and CaN expression in hippocampus by immunobloting. The results showed that the SE-induced CaN activity was time-dependent, with a peak at 2h and a return to basal level at 24h, whereas a significant increase in CaN expression was seen at 24h after SE. It is proposed that the rapid elevation in CaN activity after KA-induced SE is not likely due to an increase in CaN expression but rather an increase in CaN activation state or kinetics. In addition, we also demonstrated that pre-treatment with FK506 remarkably suppressed the SE-induced CaN activity and its expression, and reversed the SE-induced dephosphorylation of GABAAR 2/3 subunits. Taken together, our data suggest that down-regulation in inhibition of GABAAR 2/3 by CaN activity contributes to an elevation in neuronal excitability of hippocampus, which may be involved in development of chronic processes of seizures. [Copyright &y& Elsevier]

Abstract: Status epilepticus (SE) is a severe clinical manifestation of epilepsy which causes brain damage. The pathological process and underlying mechanisms involved in the programmed cell death (PCD) are still not fully clear. In the current study, rats were induced SE by lithium–pilocarpine administration. Our data showed hippocampal neurons death appeared at 6h after SE and sustained for 7 days. By blotting the activation of μ-calpain and its specific cleavage of nonerythroid α-spectrin (αSpII) (145kDa) was evident at 1 and 3 days after SE, which coincided with Bid activation, apoptosis inducing factor (AIF) translocation and cytochrome c release from mitochondria, whereas, activated caspase-3 and caspase-3-specific fragments of αSpII (120kDa) predominantly appeared at 5 and 7 days after SE. Moreover, MDL-28170, a calpain inhibitor, partially rescued the neuron death and attenuated the expression of activated μ-calpain, cleavage of Bid (15kDa), AIF translocation and cytochrome c release. Taken together, our study indicated that μ-calpain mediated hippocampal neuron PCD is prior to caspase-3 activation. It functioned via translocation of Bid, AIF and cytochrome c release. [Copyright &y& Elsevier]

Several recent epidemiological investigations raise serious questions about the health effects of high-dose supplements of Vitamin E (VE) in cigarette smokers. To examine these findings, a total of 96 C57BL/6 mice were randomly assigned to eight groups in a 2×4 factorial design (smoke vs. sham smoke and normal diet vs. 3 VE supplements). The mice were exposed to sidestream cigarette smoke (SSCS), at 0.4 mg total particulate matter/m3 air, from standard research cigarettes (1R4)/day or filtered room air at 30 min/day, 5 days/week, for 9 weeks through a nose-only exposure chamber. The American Institute of Nutrition 93G purified rodent diet was modulated with 75 (regular diet, 1-fold), 1050 (15-fold), 5550 (75-fold), and 11 175 (150-fold) IU dl-α-tocopherol acetate (α-TA)/kg as VE supplementation and provided ad libitum at an average intake rate of 4.11 g diet/mouse/day. This result demonstrated that SSCS exposure results in lung dysfunction, as indicated by a decrease of pulmonary dynamic compliance (Cdyn) and increase of lung resistance (RL), and body weight loss in mice fed with regular diet. These changes accompanied with increases of bronchoalveolar lavage (BAL) concentrations of cytokines interleukin (IL)-1β, IL-4 and IFN-γ, as well as hepatic lipid peroxidation. However, supplemental α-TA at the doses of ⩾1050 IU/kg diet prevented the SSCS-induced body weight loss and lung dysfunction. α-TA at ⩾5550 IU/kg significantly increased BAL levels of IL-2 and IL-4 in both the sham SSCS and the SSCS groups. Given at 5550 IU α-TA/kg, but not higher, mice elevated BAL IL-1β level if they were exposed to SSCS. Hepatic lipid peroxidation was decreased in a dose-dependent fashion with different α-TA supplements in both the sham SSCS and SSCS groups. Neither SSCS nor α-TA had an effect on lung permeability, BAL IL-6, splenic T and B lymphocyte proliferation and their T helper (Th)1 and Th2 cytokines measured among all groups. Data suggest that supplemental α-TA may be needed to counteract SSCS-induced oxidative stress, but that potential side effects introduced by high dosage of this synthetic compound should be considered. [Copyright &y& Elsevier]

Alveolar type II epithelial cells (AIIE) and pulmonary alveolar macrophages (PAM) are involved in pulmonary toxicity of JP-8 jet fuel exposure. To further elucidate their inflammatory mechanisms, the effect(s) of JP-8 jet fuel on cytokine secretion were examined in a transformed rat AIIE cell line (RLE-6TN) culture alone, primary PAM (from Fischer 344 rats) culture alone, and the co-culture of AIIE and primary PAM. A series of JP-8 jet fuel concentrations (0–0.8 μg/ml), which may actually be encountered in alveolar space of lungs exposed in vivo, were placed in cell culture for 24 h. Cultured AIIE alone secreted spontaneously interleukin (IL)-1β and -6 [below detectable limits for IL-10 and tumor necrosis factor-α (TNF-α)], whereas cultured PAM alone secreted IL-1β, -10, and TNF-α, in a concentration-dependent manner. These data suggest that the release of cytokines, not only from PAM but also from AIIE cells, may contribute to JP-8 jet fuel-induced inflammatory response in the alveolar space. However, the co-cultures of AIIE and PAM showed no significant changes in IL-1β, -6, and TNF-α at any JP-8 jet fuel concentration compared to control values. These cytokine levels in co-cultures of AIIE and PAM were inversely related to these of cultured AIIE or PAM alone. Interestingly, IL-10 levels in the co-culture system were concentration-dependently increased up to 1058% at JP-8 concentrations of 0.8 μg/ml, although under detectable limits in cultured AIIE alone and no significant concentration change in cultured PAM alone. It appears that PAM may possibly act via paracrine and/or autocrine pathways to signal AIIE cells to regulate cytokine release. [Copyright &y& Elsevier]

Abstract: Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play an essential role in tumor-associated immunosuppression, which hampers effective immunotherapeutic approaches. MicroRNAs (miRNAs) are short noncoding RNAs that negatively regulate target gene expression at the posttranscriptional level. miRNAs are involved in regulating cell proliferation, differentiation and maturation, and abnormal expression and function of miRNAs are recognized in various human diseases. Accumulating evidence shows that various miRNAs modulate the development and differentiation of myeloid cells, which implies their possible role in the differentiation of MDSCs into mature myeloid cells. Our recent studies have found that the classical myeloid differentiation related gene runt-related transcription factor 1 (Runx1) and target nuclear factor 1/A (NFI-A) are modulated during the differentiation and maturation of MDSCs while six miRNAs are found to possibly regulate these two targets by miRNA array analysis. Thus, we hypothesize that the predicted miRNAs may modulate the target genes to regulate the differentiation and maturation of MDSCs. Further studies will provide a novel potential approach for tumor immunotherapy. [Copyright &y& Elsevier]

Netrin-1 is a member of the laminin-like protein family and was initially identified as a potent chemotactic molecule involved in axonal guidance and cell migration during embryonic development. Many studies have focused on the non-neural effects of netrin-1, and the results revealed that netrin-1 may be extensively involved in the regulation of angiogenesis, inflammation, tissue remodeling, and cancer. The pathogenic or protective effect of netrin-1 suggests that it may be a potential therapeutic target in multiple diseases. Netrin-1 plays different roles by interacting with its receptors, such as deleted in colorectal cancer (DCC)/neogenin and the uncoordinated-5 homolog family members (UNC5). Interestingly, contradictory actions in certain physiological pathways serve to highlight its manifold and often opposite effects on numerous physiological and pathophysiological processes. Netrin-1 regulates inflammation and leukocyte infiltration, suggesting roles for netrin-1 in the immune response. In this study, we review recent advances in the understanding of netrin-1 and its receptors in many inflammatory diseases and look forward to the bioavailability of netrin-1 for the future. [Display omitted] • Netrin-1 contains a highly conserved N-terminal LN domain, domain V and a small positively charged C-terminal domain. • The netrin-1-receptor axis is usually dynamically fine-tuned at specific locations and times. • Netrin-1 engages several different receptors to activate chemotropic responses and adhesive mechanisms in non-neural systems. • Netrin-1 involved in angiogenesis, leukocyte migration, and macrophage phenotype switching. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are important components of the tumor microenvironment (TME), which drive the tumor immune escape by inducing immunosuppression. The expansion and function of MDSCs are tightly associated with signaling pathways induced by molecules from tumor cells, stromal cells, and activated immune cells in the TME. Although these pathways have been well-characterized, the understanding of the epigenetic regulators involved is incomplete. Since histone modifications are the most studied epigenetic changes in MDSCs, we summarize current knowledge on the role of histone modifications in MDSCs within this review. We first discuss the influence of the TME on histone modifications in MDSCs, with an emphasis on histone modifications and modifiers that direct MDSC differentiation and function. Furthermore, we highlight current epigenetic interventions that can reverse MDSC-induced immunosuppression by modulating histone modifications and discuss future research directions to fully appreciate the role of histone modifications in MDSCs. [Display omitted] • MDSCs induce immunosuppression and drive tumor immune escape in the TME. • Signaling pathways in the TME impact histone modifications that regulate MDSC differentiation and function. • Epigenetic interventions targeting histone modifications hold potential for reversing MDSC-induced immunosuppression. [ABSTRACT FROM AUTHOR]

• A novel coaxial parallel five-link mechanism classification method is proposed. • The leg linkage design problem is combined with motion planning of robot's body. • An alternating optimization approach for jumping robot leg design is proposed. • The experiments on biped robot show a jumping performance comparable to human. Jumping, as widely observed amongst agile terrestrial creatures, is regarded as an indispensable ability for legged robots with high-performance in dealing with complex environments. This study presents a novel leg design methodology for jumping robot using the alternating iteration approach that optimizes the leg linkage and the specified jumping motion to completely leverage the capability of the actuator. First, a coaxial parallel five-link mechanism (CPFM) classification method was proposed to extract feasible candidates of leg configuration to alleviate the intensely searching complexity due to multi-link singularity. An alternating optimization paradigm was developed by elaborately combining the motion planning (MP) and the linkage design (LD) to generate a favorable leg with a CPFM morphology. The MP task was constructed to maximize the jumping distance of the robot while the LD task was proposed to minimize the peak demand of the actuators. Finally, a sagittal jumping robot prototype was developed based on the optimal results from the proposed paradigm. We obtained a horizontal jumping performance of 1.8 times the maximum leg length, which is comparable to the natural performance of a human. [ABSTRACT FROM AUTHOR]

In recent years, there has been a significant increase in the incidence of metabolic-associated fatty liver disease (MAFLD), which has been attributed to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. MAFLD affects more than one-third of adults worldwide, making it the most prevalent liver disease globally. Moreover, MAFLD is considered a significant risk factor for hepatocellular carcinoma (HCC), with MAFLD-related HCC cases increasing. Approximately 1 in 6 HCC patients are believed to have MAFLD, and nearly 40 % of these HCC patients do not progress to cirrhosis, indicating direct transformation from MAFLD to HCC. N6-methyladenosine (m6A) is commonly distributed in eukaryotic mRNA and plays a crucial role in normal development and disease progression, particularly in tumors. Numerous studies have highlighted the close association between abnormal m6A modification and cellular metabolic alterations, underscoring its importance in the onset and progression of MAFLD. However, the specific impact of m6A modification on the progression of MAFLD to HCC remains unclear. Can targeting m6A effectively halt the progression of MAFLD-related HCC? In this review, we investigated the pivotal role of abnormal m6A modification in the transition from MAFLD to HCC, explored the potential of m6A modification as a therapeutic target for MAFLD-related HCC, and proposed possible directions for future investigations. [Display omitted] • It analyzes how aberrant m6A modifications contribute to the progression of MAFLD to HCC. • It explores the potential of m6A modification as a therapeutic target and biomarker for MAFLD-HCC. • It elucidates paradoxical m6A regulation and proposes a new model for future research. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy, such as PD-1/PD-L1 blockade, has shown promising clinical efficacy in patients with various types of tumors. However, the response to PD-1/PD-L1 blockade in a majority of malignancies is limited, indicating an urgent need for a deeper understanding of the mechanisms of PD-1/PD-L1 axis-mediated tumor tolerance. As the most abundant immune cells in the tumor stroma, macrophages display multiple phenotypes and functions in response to the stimuli of the tumor microenvironment. PD-1/PD-L1 has been demonstrated to be highly expressed in tumor-associated macrophages (TAMs), and TAM polarization has been shown to be important during tumor progression. In this review, we outline the relationship between TAM PD-1/PD-L1 expression and polarizations, summarize the involvement of M2 TAMs in PD-1/PD-L1-mediated T-cell exhaustion, and discuss improved approaches for overcoming PD-1/PD-L1 blockade resistance by inducing M2/M1 switching of TAMs. [Display omitted] • TAMs express both the receptor PD-1 and PD-L1 highly within tumor tissues. • PD-1/PD-L1 axis induces TAMs to polarize toward an M2 phenotype. • M2 TAMs contribute to PD-1/PD-L1 blockade resistance by inducing T-cell exclusion. • M2 TAMs contribute to PD-1/PD-L1 blockade resistance by inhibiting T-cell functions. • M2/M1 switching of TAMs is a promising strategy for improving tumor immunotherapy. [ABSTRACT FROM AUTHOR]

The regulation of T cell response depends on co-inhibitory pathways that serve to control immune-mediated tissue damage and resolve inflammation by modulating the magnitude and duration of immune response. In this process, the axis of T-cell-expressed programmed death-1 (PD-1) and its ligands (PD-L1 and PD-L2) play a key role. While the PD-1/PD-L pathway has received considerable attention for its role in the maintenance of T cell exhaustion in cancer and chronic infection, the PD-1/PD-L pathway also plays diverse roles in regulating host immunity beyond T cell exhaustion. In this review, we will discuss emerging concepts in co-stimulatory functions of PD-1/PD-L pathway on T cell- and B cell response and explore the potential underlying mechanisms. In addition, based on the elevated expression of PD-1 and its ligands in local inflamed tissues, we further discussed the role of PD-1/PD-L pathway in autoimmune diseases. [Display omitted] • The inhibitory or co-stimulatory function of PD-1/PD-L pathway is influenced by many factors. • PD-1/PD-L pathway also contributes to T cell and B cell development and activation. • The role of PD-1/PD-L pathway is involved in autoimmune diseases. [ABSTRACT FROM AUTHOR]

RNA N6-methyladenosine (m6A) modification is abundant in eukaryotes, bacteria and archaea. It is an RNA modification mainly existing in messenger RNA (mRNAs) and has a significant effect on the metabolism and function of mRNAs. m6A modification is controlled by three types of proteins, namely methyltransferase as the "writers", demethylase as the "erasers", and specific m6A recognized protein (YTHDF1–3) as the "readers". Recent studies have shown that m6A modification plays an important role in cancer, viral infection and autoimmune diseases. In this review, we will elaborate on the m6A modifications in the homeostasis and differentiation of T cells. Then we will further summarize the effects of m6A modification on the T cell responses and T cell-mediated autoimmune diseases. This will advance T cell epigenetics research and provide potential biomarkers and therapeutic targets for autoimmune diseases. [Display omitted] • RNA m6A modification is an important regulator of T cells homeostasis and differentiation. • Regulation of m6A modification in antigen presenting cells may control T cell differentiation and function. • m6A modification involved in T cell mediated autoimmune diseases. [ABSTRACT FROM AUTHOR]

B cells play a pivotal role in the pathogenesis of autoimmune disease (AD) by the production of autoantibodies, secretion of cytokines and presentation of autoantigens. As a pro-survival factor mainly produced by myeloid cells, B cell-activating factor (BAFF) maintains B cell maturation and homeostasis at various B cell differentiation stages. Under autoimmune conditions, BAFF acts on autoreactive B cells that have escaped checkpoint apoptosis from negative selection. Numerous studies have shown increased levels of BAFF in patients with ADs and in mouse models with ADs wherein the production of autoantibodies is a prominent feature of immunopathology. Compelling evidence has indicated a key function of BAFF in driving autoreactive B cell response during autoimmune progression. Recent clinical studies have demonstrated BAFF as a therapeutic target in various ADs. Here, we review recent findings on BAFF expression and its effector mechanisms in autoimmune pathogenesis as well as newly developed therapeutic targeting of BAFF in the treatment of ADs. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Rectorite is a kind of new clay raw materials. To study properties of the gradient pores porous ceramics on the basis of rectorite clay raw materials is of great significance. Gradient pores porous ceramics having cordierite crystalline phases were made from rectorite, talc and α-alumina by adjusting grade of particle and pore-forming agents at 1200 °C for 1 h. The physical/chemical properties and microstructures of products were tested. The results show that the samples exhibit relatively high strength, low coefficient of thermal expansion and well-distributed gradient pores due to the excellent properties of rectorite clay material (i.e., good binder, great plasticity index, low drying and firing shrinkage, high refractoriness and good thermal shock resistance, combination and distribution). [Copyright &y& Elsevier]

Head-down tilt models have been used as ground-based simulations of microgravity. Our previous animal research has demonstrated that there are significant changes in fluid distribution within 2 h after placement in a 45° head-down tilt (45HDT) position and these changes in fluid distribution were still present after 14 days of 45HDT. Consequently, we investigated changes in fluid distribution during recovery from 16 days of 45HDT. Changes in radioactive tracer distribution and organ/body weight ratio were examined in rats randomly assigned to a 45HDT or prone control group. The 45HDT rats were suspended for 16 days and then allowed to recover at the prone position 0, 77, 101, or 125 h post-suspension. Animals were injected with technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, MW=492 amu, physical half-life of 6.02 h) and then killed 30 min post-injection. Lungs, heart, liver, spleen, kidneys, and brain were harvested, weighed, and measured for radioactive counts. Statistical analyses included two-way analysis of variance (ANOVA) that compared 45HDT versus controls at the four experimental time points. The organ weight divided by the body weight ratio for the brain, heart, kidneys and liver in the 45HDT rats was significantly different than the control rats, regardless of time (treatment). There was no difference between the different time points (time). The average 99mTcDTPA count divided by the organ weight ratio values for the heart, liver, and spleen were significantly higher in the 45HDT group than the control group. The average counts for the heart and spleen were significantly higher at 77, 101, and 125 h than at time zero. We conclude that the major organs have different recovery patterns after 45HDT for 16 days in the rat. [Copyright &y& Elsevier]

Group 2 innate lymphoid cells (ILC2s), characterized by secretion of type 2 cytokines, regulate multiple immune responses. ILC2s are found in different tumor tissues, and ILC2-derived interleukin (IL)-4, IL-5, and IL-13 act on the cells in tumor microenvironment to participate in tumor progression. ILC2s are abundant in colorectal cancer (CRC) tissue, but the role of ILC2s in CRC remains unclear. In this study, we found that the percentage of ILC2s was higher in CRC tissue than in the adjacent normal tissue and that these ILC2s were the dominant IL-9-secreting cell-subsets in CRC tissue, as shown by flow cytometry analysis. ILC2s-derived IL-9 could activate CD8+ T cells to inhibit tumor growth, while anti-IL-9 reversed this effect. In vivo experiments showed that neutralizing ILC2s promoted tumor growth, while tumor inhibition occurred by intravenous injection of IL-9. In conclusion, our results demonstrated that ILC2-derived IL-9 could activate CD8+ T cells to promote anti-tumor effects in CRC. [ABSTRACT FROM AUTHOR]

• IRF8 is composed of the N-terminal region which is a helix-turn-helix DNA binding domain, and C-terminal IRF association domain. • IRF8 controls the lineage specification of dendritic cells and monocyte/macrophage development. • IRF8 is a negative regulator of MDSCs and involved in neoplasia deterioration. • Using or developing specific targeted therapies for IRF8 may contribute to the treatment and prognosis of immune disorders. Interferon regulatory factors (IRFs) are a family of central transcriptional regulators that produce type I interferon and regulate innate and adaptive immune responses. Interferon regulatory factor 8 (IRF8) exists mainly in hematopoietic cells and is essential for the development of several myeloid lineages, including monocytes/macrophages and dendritic cells. In recent years, an increasing number of studies have focused on the roles of IRF8 in the differentiation of myeloid pedigree and MDSC aggregation in diseases such as tumors. In this review, we provide a comprehensive overview of the roles of IRF8 in the regulation of myeloid cell development, with particular reference to multiple disease conditions. Clarifying the various functions of IRF8 may suggest targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

The immunomodulatory effects of maca polysaccharides (MCPs) on macrophages have been demonstrated in many studies. However, the effects of MCPs on CD4+ T cells have not been studied. Four water-soluble MCPs, labeled MCP1 (weight-average molecular weights [Mws] of 896.1 and 276.6 kDa), MCP2 (Mws of 337.8 and 219.0 kDa), MCP3 (Mws of 110.6, 58.1, and 38.9 kDa), and MCP4 (Mws of 15.7, 12.6, and 12.1 kDa), were obtained from maca by graded ethanol precipitation. The immunoregulatory effects of MCPs on CD4+ T cells were evaluated for the first time. The experimental results indicated that all MCPs had immunoregulatory effects on CD4+ T cells. However, the effects of MCP2 were stronger compared to the other three components, not only in promoting the proliferation of CD4+ T cells but also in terms of secretion of interferon-γ (IFN-γ). The molecular weight and monosaccharide compositions of MCPs were analyzed to explore the structure–activity relationship. The results suggested that the molecular weight and the galactosamine (GalN) of MCPs might be determining factors for its bioactivity. These findings suggest that the MCP2 isolated in our study have immune potentiation effects on CD4+ T cells. Unlabelled Image [ABSTRACT FROM AUTHOR]

• Pseudorabies virus (PRV) can cause illnesses in humans. • A case series of five patients with PRV encephalitis is reported. • PRV should be considered in patients with a central nervous system infection. Pseudorabies virus (PRV) has been thought to cause diseases only in animals. However, recent studies have shown that PRV can also cause illnesses in humans. This was a case series study. The cases of five patients with clinical symptoms of acute encephalitis, which were confirmed to be caused by PRV infections, were reviewed. The five patients all had jobs involving the handling of pigs. They had acute onset and rapid progression of clinical presentations, which were consistent with central nervous system infections. Four of them had respiratory failure, which required ventilator support. Brain magnetic resonance imaging showed abnormal signals in the bilateral temporal lobes and insular cortex in all five patients, bilateral frontal lobes in one patient, and caudate nucleus in one patient. Cerebrospinal fluid analysis results were consistent with a viral infection. Next-generation sequencing of the cerebrospinal fluid confirmed the presence of PRV. All patients received human immunoglobulin, glucocorticoids, antiviral agents, and symptomatic supportive treatments. All patients survived until discharge, but suffered from various sequelae. Pneumonia was the most common complication during the disease course. PRV encephalitis should be included in the differential diagnosis of patients with a clinical presentation of central nervous system infection, especially for those who have had recent contact with pigs. [ABSTRACT FROM AUTHOR]