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Multiple sclerosis is an inflammatory disorder characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Although current first-line therapies can help manage symptoms and slow down disease progression, there is no cure for multiple sclerosis. The gut-brain axis refers to complex communications between the gut flora and the immune, nervous, and endocrine systems, which bridges the functions of the gut and the brain. Disruptions in the gut flora, termed dysbiosis, can lead to systemic inflammation, leaky gut syndrome, and increased susceptibility to infections. The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors, and gut flora may play a pivotal role in regulating immune responses related to multiple sclerosis. To develop more effective therapies for multiple sclerosis, we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis. This review provides an overview of the role of the gut flora in multiple sclerosis.

Background: Respiratory failure requiring mechanical ventilation (MV) is a common and severe complication of Guillain-Barré syndrome (GBS) with a reported incidence ranging from 20 % to 30 %. Thus, we aim to develop a nomogram to evaluate the risk of MV in patients with GBS at admission and tailor individualized care and treatment. Methods: A total of 633 patients with GBS (434 in the training set, and 199 in the validation set) admitted to the First Hospital of Jilin University, Changchun, China from January 2010 to January 2021 were retrospectively enrolled. Subjects (n = 71) from the same institution from January 2021 to May 2022 were prospectively collected and allocated to the testing set. Multivariable logistic regression analysis was applied to build a predictive model incorporating the optimal features selected in the least absolute shrinkage and selection operator (LASSO) in the training set. The predictive model was validated using internal bootstrap resampling, an external validation set, and a prospective testing set, and the model's performance was assessed by using the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Finally, we established a multivariable logistic model by using variables of the Erasmus GBS Respiratory Insufficiency Score (EGRIS) and did the same analysis to compare the performance of our predictive model with the EGRIS model. Results: Variables in the final model selected by LASSO included time from onset to admission, facial and/or bulbar weakness, Medical Research Council sum score at admission, neutrophil-to-lymphocyte ratio, and platelet-lymphocyte ratio. The model presented as a nomogram displaying favorable discriminative ability with a C-index of 0.914 in the training set, 0.903 in the internal validation set, 0.953 in the external validation set, and 0.929 in the testing set. The model was well-calibrated and clinically useful as assessed by the calibration curve and DCA. As compared with the EGRIS model, our predictive model displayed satisfactory performance. Conclusions: We constructed a nomogram for early prediction of the risk of MV in patients with GBS. This model had satisfactory performance and appeared more efficient than the EGRIS model in Chinese patients with GBS.

In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.

Abstract Background Pseudorabies (PR) (also called Aujeszky’s disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections. Methods The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines. Results Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90–100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits. Conclusions The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.

Background Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses.Methods A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted via RevMan 5.3 software using a random-effects model. Stata (version 15.0) was used to analyze the publication bias.Results Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety.Conclusions HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

ABSTRACTIn recent years, an increasing number of emerging and remerging virus outbreaks have occurred and the rapid development of vaccines against these viruses has been crucial. Controlling the replication of premature termination codon (PTC)-containing viruses is a promising approach to generate live but replication-defective viruses that can be used for potent vaccines. Here, we used anticodon-engineered transfer RNAs (ACE-tRNAs) as powerful precision switches to control the replication of PTC-containing viruses. We showed that ACE-tRNAs display higher potency of reading through PTCs than genetic code expansion (GCE) technology. Interestingly, ACE-tRNA has a site preference that may influence its read-through efficacy. We further attempted to use ACE-tRNAs as a novel viral vaccine platform. Using a human immunodeficiency virus type 1 (HIV-1) pseudotyped virus as an RNA virus model, we found that ACE-tRNAs display high potency for read-through viral PTCs and precisely control their production. Pseudorabies virus (PRV), a herpesvirus, was used as a DNA virus model. We found that ACE-tRNAs display high potency for reading through viral PTCs and precisely controlling PTC-containing virus replication. In addition, PTC-engineered PRV completely attenuated and lost virulence in mice in vivo, and immunization with PRV containing a PTC elicited a robust immune response and provided complete protection against wild-type PRV challenge. Overall, replication-controllable PTC-containing viruses based on ACE-tRNAs provide a new strategy to rapidly attenuate virus infection and prime robust immune responses. This technology can be used as a platform for rapidly developing viral vaccines in the future.

Peritoneal dialysis is an efficient renal replacement therapy for patients with end-stage kidney disease. However, continuous exposure of the peritoneal membrane to dialysate frequently leads to peritoneal fibrosis, which alters the function of the peritoneal membrane and results in withdrawal from peritoneal dialysis in patients. Among others, high glucose dialysate is considered as a predisposing factor for peritoneal fibrosis in patients on peritoneal dialysis. Glucose-induced inflammation, metabolism disturbance, activation of the renin–angiotensin–aldosterone system, angiogenesis and noninflammation-induced reactive oxygen species are implicated in the pathogenesis of high glucose dialysate-induced peritoneal fibrosis. Specifically, high glucose causes chronic inflammation and recurrent peritonitis, which could cause migration and polarization of inflammatory cells, as well as release of cytokines and fibrosis. High glucose also interferes with lipid metabolism and glycolysis by activating the sterol-regulatory element-binding protein-2/cleavage-activating protein pathway and increasing hypoxia inducible factor-1α expression, leading to angiogenesis and peritoneal fibrosis. Activation of the renin–angiotensin-aldosterone system and Ras-mitogen activated protein kinase signaling pathway is another contributing factor in high glucose dialysate-induced fibrosis. Ultimately, activation of the transforming growth factor-β1/Smad pathway is involved in mesothelial-mesenchymal transition or epithelial-mesenchymal transition, which leads to the development of fibrosis. Although possible intervention strategies for peritoneal dialysate-induced fibrosis by targeting the transforming growth factor-β1/Smad pathway have occasionally been proposed, lack of laboratory evidence renders clinical decision-making difficult. We therefore aim to revisit the upstream pathways of transforming growth factor-beta1/Smad and propose potential therapeutic targets for high glucose-induced peritoneal fibrosis.

ObjectiveCognitive impairment is a common complication of chronic kidney disease (CKD). Caffeine intake has been reported to improve cognitive performance in several studies. However, whether the benefits of caffeine intake on cognitive function apply to patients with CKD remains unknown.MethodsWe performed a retrospective cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). The data of CKD subjects and non-CKD subjects from NHANES 2011−2014 were analyzed. Propensity score matching (PSM) was performed based on age, sex, diabetes, cancer, educational level, energy intake and protein intake to select subjects. The Consortium to Establish a Registry for Alzheimer’s Disease Word Learning Test (CERAD-WL), the CERAD Word List Recall Test (CERAD-DR), the Animal Fluency Test (AF) and the Digit Symbol Substitution Test (DSST) were used, whereby the occurrence of cognitive impairment was identified. Logistic regression models were performed to evaluate the association between caffeine intake and cognitive performance in CKD and non-CKD participants. Stratified analyses according to the stage of CKD and the urinary albumin/creatinine ratio levels were performed. Plot curves were then generalized to present a non-linear relationship, and the inflection point for each non-linear model was obtained by using a recursive algorithm.ResultsCognitive impairment was more prevalent in CKD patients than in non-CKD subjects. For CKD patients, caffeine intake was associated with higher CERAD-WL, CERAD-DR, AF and DSST scores. For non-CKD subjects, caffeine intake was associated with higher DSST scores only. Subgroup analysis revealed that caffeine only benefited the cognitive function of patients with CKD stages 2 and 3. The analysis showed non-linear relationships of caffeine intake and cognitive function for both CKD and non-CKD subjects. The inflection point of caffeine intake for CKD patients was 279 mg/day.ConclusionThe recommended dose of caffeine intake to improve the cognitive function of CKD patients is ≤279 mg/day.

Abstract Background Oxidative stress is an important pathogenic factor in influenza A virus infection. It has been found that reactive oxygen species induced by the H9N2 influenza virus is associated with viral replication. However, the mechanisms involved remain to be elucidated. Methods In this study, the role of autophagy was investigated in H9N2 influenza virus-induced oxidative stress and viral replication in A549 cells. Autophagy induced by H9N2 was inhibited by an autophagy inhibitor or RNA interference, the autophagy level, viral replication and the presence of oxidative stress were detected by western blot, TCID50 assay, and Real-time PCR. Then autophagy and oxidative stress were regulated, and viral replication was determined. At last, the Akt/TSC2/mTOR signaling pathways was detected by western blot. Results Autophagy was induced by the H9N2 influenza virus and the inhibition of autophagy reduced the viral titer and the expression of nucleoprotein and matrix protein. The blockage of autophagy suppressed the H9N2 virus-induced increase in the presence of oxidative stress, as evidenced by decreased reactive oxygen species production and malonaldehyde generation, and increased superoxide dismutase 1 levels. The changes in the viral titer and NP mRNA level caused by the antioxidant, N-acetyl-cysteine (NAC), and the oxidizing agent, H2O2, confirmed the involvement of oxidative stress in the control of viral replication. NAC plus transfection with Atg5 siRNA significantly reduced the viral titer and oxidative stress compared with NAC treatment alone, which confirmed that autophagy was involved in the replication of H9N2 influenza virus by regulating oxidative stress. Our data also revealed that autophagy was induced by the H9N2 influenza virus through the Akt/TSC2/mTOR pathway. The activation of Akt or the inhibition of TSC2 suppressed the H9N2 virus-induced increase in the level of LC3-II, restored the decrease in the expression of phospho-pAkt, phospho-mTOR and phospho-pS6 caused by H9N2 infection, suppressed the H9N2-induced increase in the presence of oxidative stress, and resulted in a decrease in the viral titer. Conclusion Autophagy is involved in H9N2 virus replication by regulating oxidative stress via the Akt/TSC2/mTOR signaling pathway. Thus, autophagy maybe a target which may be used to improve antiviral therapeutics.

The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P < 0.05). Group B patients had the lowest clinical pregnancy, implantation, and live birth rates of all groups (P < 0.05). No differences were found in the miscarriage rate or birth defects among the groups (P > 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

Introduction Endothelial dysfunction appears in many smoking-related diseases, it is also an important pathophysiological feature. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and have a crucial effect on the repair and maintenance of endothelial integrity. Sca-1 is not only common in bone marrow-derived hematopoietic stem cells (HSCs), but it is also expressed in nonhematopoietic organs by tissue-resident stem and progenitor cells. The aim of this study is to investigate the impact of cigarette smoke extract (CSE) on the function of bone marrow-derived EPCs and the expression level of Sca-1 in EPCs, and also whether the methylation of Sca-1 is involved in EPC dysfunction. Methods We measured EPC capacities including adhesion, secretion and proliferation, the concentration of endothelial nitric oxide synthase (eNOS) and apoptosis-inducing factor (AIF) in cell culture supernatant, and also Sca-1 expression and promoter methylation in EPCs induced by CSE. Decitabine (Dec) was applied to test whether it could alter the impact caused by CSE. Results The adhesion, proliferation and secretion ability of EPCs can be induced to be decreased by CSE in vitro, accompanied by decreased concentrations of AIF and eNOS in cell culture supernatant and decreased Sca-1 expression in EPCs. In addition, Dec could partly attenuate the impact described above. There were no significant differences in the quantitative analysis of Sca-1 promoter methylation among different groups. Conclusions The decreased Sca-1 expression was related to EPC dysfunction induced by CSE. EPC dysfunction resulting from CSE may be related to methylation mechanism, but not the methylation of Sca-1 promoter.

Introduction: Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study’s primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients. Methods: The study enrolled retrospectively and prospectively patients diagnosed with severe AR who eventually underwent TAVR procedure from January 2019 to September 2022 at Fuwai cardiovascular Hospital, Beijing. Baseline information, MDCT measurements, anatomical classification, perioperative, and 1-year follow-up outcomes were collected and analyzed. Based on a novel anatomical categorization and dual anchoring theory, patients were divided into four categories according to the level of anchoring area. Type 1, 2, and 3 patients (with at least two anchoring regions) will receive TAVR with a transcatheter heart valve (THV), but Type 4 patients (with zero or one anchoring location) will be deemed unsuitable for TAVR and will instead receive medical care (retrospectively enrolled patients who already underwent TAVR are an exception). Results: The mean age of the 37 patients with severe chronic AR was 73.1 ± 8.7 years, and 23 patients (62.2%) were male. The American Association of Thoracic Surgeons’ score was 8.6 ± 2.1%. The MDCT anatomical classification included 17 cases of type 1 (45.9%), 3 cases of type 2 (8.1%), 13 cases of type 3 (35.1%), and 4 cases of Type 4 (10.8%). The VitaFlow valve (MicroPort, Shanghai, China) was implanted in 19 patients (51.3%), while the Venus A valve (Venus MedTech, Hangzhou, China) was implanted in 18 patients (48.6%). Immediate TAVR procedural and device success rates were 86.5% and 67.6%, respectively, while eight cases (21.6%) required THV-in-THV implantation, and nine cases (24.3%) required permanent pacemaker implantation. Univariate regression analysis revealed that the major factors affecting TAVR device failure were sinotubular junction diameter, THV type, and MDCT anatomical classification (p < 0.05). Compared with the baseline, the left ventricular ejection fraction gradually increased, while the left ventricular end-diastolic diameter remained small, and the N-terminal-pro hormone B-type natriuretic peptide level significantly decreased within one year. Conclusion: According to the results of our study, TAVR with a self-expanding THV is safe and feasible for patients with chronic severe AR, particularly for those who meet the criteria for the appropriate MDCT anatomical classification with intact dual aortic anchors, and it has a significant clinical effect for at least a year.

Heading date is a crucial agronomic trait. However, rice usually delays heading due to the photoperiod, temperature, hormones or age. The present research was conducted to analyze the mechanism controlling heading date in F1 hybrid rice. We constructed two test-crossing populations using two introgression lines (ILs), P20 and P21 coming from SH527/FH838 as the male parent, respectively, and male sterile line Jin23A as the female parent. Meanwhile, the F1 hybrids of H20, obtained by mating P20 with Jin23A and having no heading, and H21, from the crossing between P21 and Jin23A having normal heading, were both observed under long days. Here, we analyzed the photoperiodic response of F1 hybrids by transcriptome and metabolome profiling. The greater differences displayed in the transcriptome and the metabolome were caused by photoperiod (exogenous) instead of genes (endogenous). The coping mechanism resulted from long days (LD) in H20, leading to differences in the circadian rhythm and glutathione metabolism relative to other samples. The circadian oscillator and GSH/GSSG cycle typically regulate ROS homeostasis, and both of them are responsible for modulating ROS in H20 under LD condition. Both circadian rhythm genes and the reported genes related to heading date function via the DHD1/OsMFT1-Ehd1-RFT1-OsMADS14/OsMADS18 pathway and the glutathione metabolism pathway by regulating oxidative reduction processes. Both pathways are involved in the heading process and they interacted through the oxidative reduction process which was induced by photoperiod regulation, and all of them collectively modulated the heading process. The results of this study will be helpful for unraveling the mechanism of F1 hybrid responses to unheading under LD condition.

Introduction The aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN). Material and methods We selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 µg P0 peptide 180–199 emulsion in 25 µl of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 µl of Freund’s incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit. Results We found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-γ, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts. Conclusions Based on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.

Innate immunity is the front line for antiviral immune responses and bridges adaptive immunity against viral infections. However, various viruses have evolved many strategies to evade host innate immunity. A typical virus is the porcine reproductive and respiratory syndrome virus (PRRSV), one of the most globally devastating viruses threatening the swine industry worldwide. PRRSV engages several strategies to evade the porcine innate immune responses. This review focus on the underlying mechanisms employed by PRRSV to evade pattern recognition receptors signaling pathways, type I interferon (IFN-α/β) receptor (IFNAR)-JAK-STAT signaling pathway, and interferon-stimulated genes. Deciphering the antiviral immune evasion mechanisms by PRRSV will enhance our understanding of PRRSV’s pathogenesis and help us to develop more effective methods to control and eliminate PRRSV.

Guillain–Barré syndrome (GBS) is an acute polyneuropathy mostly characterized by acute flaccid paralysis with or without sensory/autonomous nerve dysfunction. Current immuno therapies including intravenous immunoglobulin (IVIg), plasma exchange (PE), and newly developed biological drugs benefit patients by alleviating hyperreactive immune responses. Up to 30% of patients develop respiratory failure during hospitalization and require mechanical ventilation and intensive care. Immunotherapies, mechanical ventilation, supportive care, and complication management during the intensive care unit (ICU) stay are equally emphasized. The most important aspect of intensive care and treatment of severe GBS, that is, mechanical ventilation, has been extensively reviewed elsewhere. In contrast to immunotherapies, care and treatment of GBS in the ICU setting are largely empirical. In this review, we intend to stress the importance of intensive care and treatment, other than mechanical ventilation in patients with severe GBS. We summarize the up-to-date knowledge of pharmacological therapies and ICU management of patients with severe GBS. We aim to answer some key clinical questions related to the management of severe GBS patients including but not limited to: Is IVIg better than PE or vice versa? Whether combinations of immune therapies benefit more? How about the emerging therapies promising for GBS? When to perform tracheal intubation or tracheostomy? How to provide multidisciplinary supportive care for severe cases? How to avert life-threatening complications in severe cases?

ABSTRACTAs one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.

Mounting evidence suggests that neuroinflammation is not just a consequence but a vital contributor to the development and progression of Parkinson’s disease (PD). Microglia in particular, may contribute to the induction and modulation of inflammation in PD. Upon stimulation, microglia convert into activated phenotypes, which exist along a dynamic continuum and bear different immune properties depending on the disease stage and severity. Activated microglia release various factors involved in neuroinflammation, such as cytokines, chemokines, growth factors, reactive oxygen species (ROS), reactive nitrogen species (RNS), and prostaglandins (PGs). Further, activated microglia interact with other cell types (e.g., neurons, astrocytes and mast cells) and are closely associated with α-synuclein (α-syn) pathophysiology and iron homeostasis disturbance. Taken together, microglial activation and microglia-mediated inflammatory responses play essential roles in the pathogenesis of PD and elucidation of the complexity and imbalance of microglial activation may shed light on novel therapeutic approaches for PD.

Background: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. Methods: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i.p.) on the first day of the study. The MCT + simvastatin group received simvastatin (2 mg/kg) daily for 4 weeks, after which pulmonary arterial pressure was measured by right heart catheterization. The protein and mRNA levels of Rho and ROCK1 were measured by immunohistochemistry, Western blot, and PCR. For in vitro experiments, human pulmonary endothelial cells were divided into seven groups: control, simvastatin, monocrotaline pyrrole (MCTP), MCTP + simvastatin, MCTP + simvastatin + mevalonate, MCTP + simvastatin + farnesyl pyrophosphate (FPP), and MCTP + simvastatin + FPP + geranylgeranyl pyrophosphate (GGPP). After 72 h exposed to the drugs, the protein and mRNA levels of RhoA and ROCK1 were measured by Western blot and PCR. Results: The MCT group showed increased mean pulmonary arterial pressure, marked vascular remodeling, and increased protein and mRNA levels of RhoA and ROCK1 compared to the other groups (P < 0.05). In vitro, the MCTP group showed a marked proliferation of vascular endothelial cells, as well as increased protein and mRNA levels of RhoA and ROCK1 compared to the MCTP + simvastatin group. The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Conclusions: Simvastatin improved vascular remodeling and inhibited the development of PAH. The effects of simvastatin were mediated by inhibition of RhoA/ROCK1. Simvastatin decreased RhoA/ROCK1 overexpression by inhibition of mevalonate, FPP, and GGPP synthesis.

Abstract Background It remains an urgent need for early recognition of disease severity, treatment option and outcome of Guillain-Barré syndrome (GBS). The chief complaint may be quickly obtained in clinic and is one of the candidates for early predictors. However, studies on the chief complaint are still lacking in GBS. The aim of the study is to describe the components of chief complaints of GBS patients, and to explore association between chief complaints and disease severity/treatment option/outcome of GBS, so as to aid the early prediction of the disease course and to assist the clinicians to prescribe an optimal early treatment. Methods A total of 523 GBS patients admitted to the First Hospital of Jilin University from 2003 to 2013 were enrolled for retrospective analysis. The data of chief complaints, clinical manifestations, and treatment options, etc. were collected. The clinical severity was evaluated by the Medical Research Council sum score and the Hughes Functional Grading Scale. The prognosis at 6 month after discharge was described by modified Erasmus GBS outcome score. The clinic GBS severity evaluation scale (CGSES), a newly established model in our study, was used to explore the role of chief complaints to predict intravenous immunoglobulin (IVIg). Results The major components of the chief complaints of GBS patients were weakness, numbness, pain, cranial nerve involvement, dyspnea, ataxia and autonomic dysfunction. Chief complaint of weakness was a predictor of severe disease course and poor short-term outcome, while chief complaint of numbness and cranial nerve involvement were promising predictors. Cranial nerve involvement was the predictor of ventilator dependence. The percentages of 366 GBS patients, who need IVIg treatment at nadir with CGSES ranging from 1 to 4, were 50.00, 67.34, 80.61, and 90.67%, respectively. Conclusions Chief complaints are clinic predictors of disease severity, ventilator dependence and short-term outcome. IVIg treatment during hospitalisation could be predicted in clinic using CGSES score.

Objective: To present our treatment experiences and the follow-up data of patients with paradoxical embolism (PDE). Methods: The clinical characteristics, management, and follow-up data of all included patients who were diagnosed with PDE at Fuwai Hospital from January 1994 to October 2015 were recorded. Results: Twelve patients were included; all had a pulmonary embolism, and 8 had deep venous thrombosis. The artery embolisms involved the cerebral artery (7 patients), renal artery (2 patients), mesentery artery (2 patients), popliteal artery (1 patient), descending aorta thrombus (1 patient), and thrombus-straddled patent foramen ovale (PFO) (1 patient). PFO was found in 3 cases. One patient underwent thrombectomy and PFO closure; Six patients received thrombolysis; and 3 patients were implanted with a vena cava filter. Long-term anticoagulation with warfarin was recommended for each patient. One patient died from ventricular fibrillation despite cardiopulmonary resuscitation. Eleven patients were discharged with improvements. No late mortality occurred in 8 patients with a complete follow-up of 10.6â17.7 years. One had a recurrent deep venous thrombosis. No patient had a recurrent pulmonary or arterial embolism. Two patients changed their treatment from warfarin to aspirin; others remained on warfarin. Only 1 case had an occasional gum bleeding. Conclusions: PDE treatment including thrombolysis, anticoagulation, and embolectomy should be individualized. We recommend long-term anticoagulation therapy to prevent the recurrence of PDE, especially to those with an intracardiac communication or persistent risk factors for re-thrombosis. Keywords: Paradoxical embolism, Pulmonary embolism, Deep venous thrombosis, Patent foramen ovale

This article contains the clinical characteristics of the paradoxical embolized patients and the following up results. Data included are related to the article “Paradoxical embolism: Experiences from a single center” (Zhang Hong-liang, Liu Zhi-hong, Luo Qin, Wang Yong, Zhao Zhi-hui, Xiong Chang-ming, in press) [1]. The data are obtained from the hospital records and telephone interview.

The lower seed setting is one of the major hindrances which face grain yield in rice. One of the main reasons to cause low spikelet fertility (seed setting) is male sterility or pollen abortion. Notably, pollen abortion has been frequently observed in advanced progenies of rice. In the present study, 149 BC2F6 individuals with significant segregation in spikelet fertility were generated from the cross between N040212 (indica) and Nipponbare (japonica) and used for primary gene mapping. Three QTLs, qSS-1, qSS-7 and qSS-9 at chromosomes 1, 7 and 9, respectively, were found to be associated with seed setting. The recombinant analysis and the physical mapping information from publicly available resources exhibited that the qSS-, qSS-7 and qSS-9 loci were mapped to an interval of 188, 701 and 3 741 kb, respectively. The seed setting responsible for QTL qSS-1 was further fine mapped to 93.5 kb by using BC2F7 population of 1 849 individuals. There are 16 possible putative genes in this 93.5 kb region. Pollen vitality tests and artificial pollination indicated that the male gamete has abnormal pollen while the female gamete was normal. These data showed that low seed setting rate relative to qSS-1 may be caused by abnormal pollen grains. These results will be useful for cloning, functional analysis of the target gene governing spikelet fertility (seed setting) and understanding the genetic bases of pollen sterility.

Background: Blood-brain barrier (BBB) pathology exists in neuromyelitis optica spectrum disorders (NMOSD). However, the clinical use of BBB permeability, such as predicting disease severity of NMOSD, has rarely been studied in a large cohort of patients.Objectives: The current study explored the association between BBB permeability and clinical parameters in order to assess if BBB permeability could be a biomarker to predict disease severity and clinical characteristics of NMOSD.Methods: Among 69 enrolled NMOSD patients, 47 with albumin index over 5 × 10−3 were assigned to the increased BBB permeability group, and the remaining 22 were to the normal BBB permeability group. Disease severity was assessed using the Expanded Disability Status Scale (EDSS).Results: Patients in the increased BBB permeability group had significantly higher EDSS scores, anti-aquporin-4 immunoglobulin G titers, more dense cerebrospinal fluid protein concentrations, white blood cell counts, myelin basic protein levels and more dense complement 3 concentrations than found in the comparative normal BBB permeability group. The albumin index was positively correlated to the length of lesions in spinal cord.Conclusions: BBB permeability was associated with clinical features, laboratory results and radiological data of NMOSD patients, and may be a potential biomarker to predict disease severity and clinical characteristics of NMOSD.

Glial cells are the most abundant cell type in the central nervous system (CNS) and play essential roles in maintaining brain homeostasis, forming myelin, and providing support and protection for neurons, etc. Over the past decade, significant progress has been made in the reprogramming field. Given the limited accessibility of human glial cells, in vitro differentiation of human induced pluripotent stem cells (hiPSCs) into glia may provide not only a valuable research tool for a better understanding of the functions of glia in the CNS but also a potential cellular source for clinical therapeutic purposes. In this review, we will summarize up-to-date novel strategies for the committed differentiation into the three major glial cell types, i.e., astrocyte, oligodendrocyte, and microglia, from hiPSCs, focusing on the non-neuronal cell effects on the pathology of some representative neurological diseases. Furthermore, the application of hiPSC-derived glial cells in neurological disease modeling will be discussed, so as to gain further insights into the development of new therapeutic targets for treatment of neurological disorders.

Astrocytes, which are five-fold more numerous than neurons in the central nervous system (CNS), are traditionally viewed to provide simple structural and nutritional supports for neurons and to participate in the composition of the blood brain barrier (BBB). In recent years, the active roles of astrocytes in regulating cerebral blood flow (CBF) and in maintaining the homeostasis of the tripartite synapse have attracted increasing attention. More importantly, astrocytes have been associated with the pathogenesis of Alzheimer’s disease (AD), a major cause of dementia in the elderly. Although microglia-induced inflammation is considered important in the development and progression of AD, inflammation attributable to astrogliosis may also play crucial roles. A1 reactive astrocytes induced by inflammatory stimuli might be harmful by up-regulating several classical complement cascade genes thereby leading to chronic inflammation, while A2 induced by ischemia might be protective by up-regulating several neurotrophic factors. Here we provide a concise review of the emerging roles of astrocytes in the homeostasis maintenance of the neuro-vascular unit (NVU) and the tripartite synapse with emphasis on reactive astrogliosis in the context of AD, so as to pave the way for further research in this area, and to search for potential therapeutic targets of AD.

This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs showed that the microspheres were nearly spherical in shape. The mean size of CTS microspheres was 4.07 μm (varying from 1.50 to 7.21 μm) and of WSC microspheres was 2.00 μm (varying from 0.85 to 3.58 μm). The rats were classified into eight groups (n = 8) and were fed with high-fat diets for two weeks to establish the hyperlipidemic condition and were then treated with CTS microspheres and WSC microspheres, CTS and WSC for four weeks. The results showed that CTS and WSC microspheres reduced blood lipids and plasma viscosity and increased the serum superoxide dismutase (SOD) levels significantly. This study is the first report of the lipid-lowering effects of CTS and WSC microspheres. CTS and WSC microspheres were found to be more effective in improving hyperlipidemia in rats than common CTS and WSC.

China is one of the largest centers of genetic diversity of Oryza sativa L. and is the original centers of Oryza sativa L. subspecies japonica. Using a genetically representative core collection of 1 442 rice landraces of japonica in China, the genetic structure, differentiation, and geographic diversity were analyzed. The model-based structure analysis on varieties within three ecotypes revealed 16 eco-geographical types, which are partially accorded with some of the ecological zones in China. The differentiation of eco-geographical types contributed to the local ecological adaption and physical isolation, and maybe could be used to develop the heterotic groups of japonica. To facilitate the identification of different ecotypes and eco-geographical types, we provided the SSR character alleles of each ecotype or geographical eco-group and a rapid discriminated method based on these character alleles. Lastly, investigation on genetic diversity, genetic differentiation indicated that southwest region of China, including south of Yunnan Province, northwest of Guangxi Zhuang Autonomous Region, and southwest of Guizhou Province, possessed the highest genetic diversity and all the necessary conditions as a center of genetic diversity and should be the center of genetic diversity of rice landraces of japonica in China.

OBJECTIVE:Clinical characteristics of pediatric Guillain-Barré syndrome (GBS) have been extensively studied whereas scarcely been compared with those of adult GBS. Herein we compared the clinical features of GBS between pediatric and adult patients. METHODS:We retrospectively collected the clinical data of 750 patients with GBS (541 adults and 209 children), and compared the clinical characteristics between children and adults. RESULTS:Pain was a more frequent complaint in children (17.2% vs 9.6%, p < 0.01), who were also found with shorter interval from disease onset to nadir (6.3d vs 7.3d, p < 0.01) and higher incidence of bulbar dysfunction (22.0% vs 14.8%, p < 0.05). The disease severity in children was comparable with adults. In addition, a higher incidence of pediatric GBS was found in summer, especially in July and August (both p < 0.01). However, the incidence of antecedent infections of different seasons in adult and pediatric patients was comparable (p > 0.05). The clinical features of acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) in children were overall comparable with adult ones (p > 0.05). Similar to adults, bulbar dysfunction (odds ratio [OR]: 4.621, 95% confidence interval [CI]: 1.240-17.218, p < 0.05) and lower nadir Medical Research Council (MRC) sum score (OR: 0.897, 95% CI: 0.855-0.941, p < 0.01) were also risk factors for mechanical ventilation in children. However, distinct from adult ones, autonomic dysfunction was significantly higher in mechanically ventilated childhood GBS (39.1% vs 8.8%, p < 0.01), which also served as a predictor for mechanical ventilation in pediatric GBS (OR: 70.415, 95% CI: 9.265-535.158, p < 0.01). As to the efficacy of intravenous immunoglobulin, insignificant difference was identified between children and adults. CONCLUSION:The clinical features of pediatric GBS differ from those of adults. Autonomic dysfunction is an independent risk factor for mechanical ventilation in pediatric patients.

The QTL qTGW3-1 was located on chromosome 3 of rice (Oryza sativa L.) and associated with the 1000-grain weight (TGW) according to the result of our earlier study. With the objective of fine mapping of this locus, we developed a F2 population consisting of 3 428 plants derived from the cross between TGW-related near isogenic line DL017 (BC3F4 generation of GSL156×Nipponbare) and the recurrent parent Nipponbare. Using six microsatellites, this QTL was delimited between RM5477 and RM6417. Markers MM1455 and MM1456 within this region were used for further mapping of this QTL. Finally, qTGW3-1 was fine-mapped into a 89-kb interval between RM5477 and MM1456, which locates in the BAC clone AC107226 harboring five putative candidate genes.

Background Emphysema is the main pathological feature of COPD and also is the focus of the related research. Although several emphysema animal models have been established, exact comparison of findings is seldom. The present study aimed to compare cigarette smoke (CS) exposure-induced emphysema model and intraperitoneal injection of cigarette smoke extract (CSE)-induced emphysema model to evaluate the effectiveness of the two different modeling methods. Methods Six-week-old male C57BL/6 J mice were used and randomly divided into two groups: CS exposure and intraperitoneal injection of CSE. Each group was subdivided into two subgroups: control and CS or CSE. Lung function, mean linear intercept (MLI), destructive index (DI), apoptotic index (AI), total and differential cells count in broncholavolar lavage fluid (BALF), SOD and IL-6 concentration in serum were measured. Results Compared with their respective controls, lung function was significantly decreased in CS and CSE groups (P

Guillain-Barré syndrome (GBS), the axonal subtype of which is mainly triggered by C. jejuni with ganglioside-mimicking lipooligosaccharides (LOS), is an immune-mediated disorder in the peripheral nervous system (PNS) accompanied by the disruption of the blood-nerve barrier (BNB) and the blood-cerebrospinal fluid barrier (B-CSF-B). Biomarkers of GBS have been extensively explored and some of them are proved to assist in the clinical diagnosis and in monitoring disease progression as well as in assessing the efficacy of immunotherapy. Herein, we systemically review the literature on biomarkers of GBS, including infection-/immune-/BNB, B-CSF-B, and PNS damage-associated biomarkers, aiming at providing an overview of GBS biomarkers and guiding further investigations. Furthermore, we point out further directions for studies on GBS biomarkers.

Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.

A potential association between diabetes and Guillain-Barré syndrome (GBS) has been indicated by a few case studies. We retrospectively analyzed the clinical features of a large cohort of GBS patients to explore the relationship between the level of fasting plasma glucose (FPG) obtained in the acute phase at admission and the severity of GBS.Three hundred and four GBS patients were divided into two groups, one with normal FPG and the other with high FPG levels according to the international standards of FPG.The GBS disability scale score was positively, the Medical Research Council (MRC) sum score was negatively correlated to the level of FPG, but not to blood HBA1c or CSF glucose concentrations. A relatively higher FPG level was observed in older and younger GBS patients, and more often in those with cranial nerve involvement, autonomic deficit, dyspnea and ventilator dependence than in patients without these clinical characteristics. Importantly, higher levels of FPG at admission were associated with poorer short-term prognosis measured by the MRC sum score and the GBS disability scale at discharge.Our data demonstrates that FPG in the acute phase of GBS correlates with the severity of GBS and may predict the short-term prognosis of GBS.

Multiple sclerosis (MS) is an immune-mediated disorder in the central nervous system (CNS) characterized by inflammation and demyelination as well as axonal and neuronal degeneration. So far effective therapies to reverse the disease are still lacking; most therapeutic drugs can only ameliorate the symptoms or reduce the frequency of relapse. Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are key players in both mediating immune responses and inducing immune tolerance. Increasing evidence indicates that DCs contribute to the pathogenesis of MS and might provide an avenue for therapeutic intervention. Here, we summarize the immunogenic and tolerogenic roles of DCs in MS and review medicinal drugs that may affect functions of DCs and have been applied in clinic for MS treatment. We also describe potential therapeutic molecules that can target DCs by inducing anti-inflammatory cytokines and inhibiting proinflammatory cytokines in MS.

Ganglioside as a neurotrophic drug has been hitherto widely used in China, although Guillain-Barré syndrome (GBS) following intravenous ganglioside treatment was reported in Europe several decades ago. We identified 7 patients who developed GBS after intravenous use of gangliosides (ganglioside+ group) and compared their clinical data with those of 77 non-ganglioside-associated GBS patients (ganglioside- group) in 2013, aiming at gaining the distinct features of ganglioside-associated GBS. Although the mean age, protein levels in cerebrospinal fluid (CSF) and frequency of cranial nerve involvement were similar between the two groups, the Hughes Functional Grading Scale (HFGS) score and the Medical Research Council (MRC) sum score at nadir significantly differed (4.9 ± 0.4 vs 3.6 ± 1.0; 7.7 ± 5.5 vs 36.9 ± 14.5, both p

The Guillain-Barré syndrome (GBS) is considered a T helper 1 (Th1) cells-mediated acute inflammatory peripheral neuropathy. However, some changes in GBS could not be explained completely by Th1 cells pathogenic role. Recently, Th17 cells have been identified and can mediate tissue inflammation and autoimmune response. Therefore, a study on the role of Th17 and Th22 cells and their cytokines in GBS is necessary for exploring the pathogenesis of GBS. Here, we detected the frequency of Th1, Th17, and Th22 cells by using 4-color flow cytometry and we detected the plasma levels of IL-17 and IL-22 by ELISA in GBS patients, relapsing-remitting multiple sclerosis patients at the acute phase of relapse, viral encephalitis or meningitis patients and healthy controls. Our data showed that the frequency of circulating Th1, Th17, and Th22 cells was significantly increased in GBS patients. The plasma levels of IL-17 and IL-22 in GBS and relapsing-remitting multiple sclerosis at the acute phase of relapse were also markedly elevated. Enhanced circulating Th22 cells were correlated with GBS severity. Intravenous immunoglobulin therapy downregulated Th17, and Th22 cells and the plasma levels of IL-17 and IL-22 in GBS patients. Th17 and Th22 cells may be involved in the pathogenesis of GBS, and intravenous immunoglobulin mediates therapeutic effects by downregulating these cells and their cytokines.

The role of tumor necrosis factor (TNF)-α and its receptors in neuroautoimmune and neuroinflammatory diseases has been controversial. On the basis of our previous studies, we hereby aimed to further clarify TNF-α's mechanism of action and to explore the potential role of TNF-α receptor (TNFR)1 as a therapeutic target in experimental autoimmune neuritis (EAN). EAN was induced by immunization with P0 peptide 180-199 in TNF-α knockout (KO) mice and anti-TNFR1 antibodies were used to treat EAN. Particularly, the effects of TNF-α deficiency and TNFR1 blockade on macrophage functions were investigated. The onset of EAN in TNF-α KO mice was markedly later than that in wild type (WT) mice. From day 14 post immunization, the clinical signs of TNF-α KO mice were significantly milder than those of their WT counterparts. Further, we showed that the clinical severity of WT mice treated with anti-TNFR1 antibodies was less severe than that of the control WT mice receiving PBS. Nevertheless, no difference with regard to the clinical signs of EAN or inflammatory infiltration in cauda equina was seen between TNF-α KO and WT mice with EAN after blockade of TNFR1. Although TNF-α deficiency did not alter the proliferation of lymphocytes in response to either antigenic or mitogenic stimuli, it down-regulated the production of interleukin (IL)-12 and nitric oxide (NO), and enhanced the production of IL-10 in macrophages. Increased ratio of regulatory T cells (Tregs) and reduced production of interferon (IFN)-γ in cauda equina infiltrating cells, and elevated levels of IgG2b antibodies against P0 peptide 180-199 in sera were found in TNF-α KO mice with EAN. In conclusion, TNF-α deficiency attenuates EAN via altering the M1/M2 balance of macrophages.

Apolipoprotein E (apoE) is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT) cells, and so forth. Increasing studies have revealed that APOE ε allele might be associated with multiple sclerosis (MS), although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOE ε allele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE).

Electric-double-layer oxide-based thin-film transistors gated by nanogranular SiO2 solid electrolyte have been fabricated at room temperature. The effects of humidity on performances are investigated. At the relative humidity of 65 %, the measured capacitance is 10 μF/cm2, and the device shows Ion/off ratio of 8.93 × 107, field-effect mobility of 5.9 cm2/Vs. As relative humidity declines, the measured capacitance decreases, which gives rise to the degradation in performance. Especially, at the relative humidity of 0 %, the capacitance of 0.01 μF/cm2 is measured, so the device cannot be turned off. The reason may be that humidity can promote H2O molecules to permeate into solid electrolyte, which can cause charges accumulation.

Byline: Pang. Hui-Mei, Huang. Guang-Ming, Qin. Xiao-Ling, Zhang. Hong-Liang, Wei. Si-Jun To investigate the regularity and characteristics of adverse drug reaction (ADR) of reactive cutaneous capillary endothelial proliferation caused by [...]

Light-absorbing carbonaceous aerosols are important contributors to both air pollution and radiative forcing. However, their abundances and sources are still subject to non-negligible uncertainties, which are highly responsible for the frequently-identified discrepancies between the observed and modeled results. In this study, we focused on elemental carbon (EC) and light-absorbing organic carbon (i.e., BrC) in Northeast China, a new targeted region of the latest clean air actions in China. Three campaigns were conducted during 2018-2021 in Harbin, covering distinct meteorological conditions and emission features. Various analytical methods were first evaluated, and the mass concentrations of both BrC and EC were validated. The validated BrC and EC measurement results were then used for source apportionment, together with other species including tracers (e.g., levoglucosan). The observation-based results suggested that despite the frigid winter in Harbin, the formation of secondary organic aerosol (SOA) was enhanced at high levels of relative humidity (RH). This enhancement could also be captured by an air quality model incorporating heterogeneous chemistry. However, the model failed to reproduce the 27 observed abundances of SOA, with significant underestimations regardless of RH levels. In addition, agricultural fires effectively increased the observation-based primary organic carbon (POC) concentrations and POC to EC ratios. Such roles of agricultural fires were not captured by the model, pointing to substantial underestimation of open burning emissions by the inventory. This problem merits particular attention for Northeast China, given its massive agricultural sector. [ABSTRACT FROM AUTHOR]