Increase in neuroexcitability of unmyelinated C-type vagal ganglion neurons during initial postnatal development of visceral afferent reflex functions

BACKGROUND: Baroreflex gain increase up closely to adult level during initial postnatal weeks, and any interruption within this period will increase the risk of cardiovascular problems in later of life span. We hypothesize that this short period after birth might be critical for postnatal development of vagal ganglion neurons (VGNs). METHODS: To evaluate neuroexcitability evidenced by discharge profiles and coordinate changes, ion currents were collected from identified A- and C-type VGNs at different developmental stages using whole-cell patch clamping. RESULTS: C-type VGNs underwent significant age-dependent transition from single action potential (AP) to repetitive discharge. The coordinate changes between TTX-S and TTX-R Na(+) currents were also confirmed and well simulated by computer modeling. Although 4-AP or iberiotoxin age dependently increased firing frequency, AP duration was prolonged in an opposite fashion, which paralleled well with postnatal changes in 4-AP- and iberiotoxin-sensitive K(+) current activity, whereas less developmental changes were verified in A-types. CONCLUSION: These data demonstrate for the first time that the neuroexcitability of C-type VGNs increases significantly compared with A-types within initial postnatal weeks evidenced by AP discharge profiles and coordinate ion channel changes, which explain, at least in part, that initial postnatal weeks may be crucial for ontogenesis in visceral afferent reflex function

Kinetics and specificity of paternal mitochondrial elimination in Caenorhabditis elegans

In most eukaryotes, mitochondria are inherited maternally. The autophagy process is critical for paternal mitochondrial elimination (PME) in Caenorhabditis elegans, but how paternal mitochondria, but not maternal mitochondria, are selectively targeted for degradation is poorly understood. Here we report that mitochondrial dynamics have a profound effect on PME. A defect in fission of paternal mitochondria delays PME, whereas a defect in fusion of paternal mitochondria accelerates PME. Surprisingly, a defect in maternal mitochondrial fusion delays PME, which is reversed by a fission defect in maternal mitochondria or by increasing maternal mitochondrial membrane potential using oligomycin. Electron microscopy and tomography analyses reveal that a proportion of maternal mitochondria are compromised when they fail to fuse normally, leading to their competition for the autophagy machinery with damaged paternal mitochondria and delayed PME. Our study indicates that mitochondrial dynamics play a critical role in regulating both the kinetics and the specificity of PME

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC

B7 family protein glycosylation: Promising novel targets in tumor treatment

Cancer immunotherapy, including the inhibition of immune checkpoints, improves the tumor immune microenvironment and is an effective tool for cancer therapy. More effective and alternative inhibitory targets are critical for successful immune checkpoint blockade therapy. The interaction of the immunomodulatory ligand B7 family with corresponding receptors induces or inhibits T cell responses by sending co-stimulatory and co-inhibitory signals respectively. Blocking the glycosylation of the B7 family members PD-L1, PD-L2, B7-H3, and B7-H4 inhibited the self-stability and receptor binding of these immune checkpoint proteins, leading to immunosuppression and rapid tumor progression. Therefore, regulation of glycosylation may be the “golden key” to relieve tumor immunosuppression. The exploration of a more precise glycosylation regulation mechanism and glycan structure of B7 family proteins is conducive to the discovery and clinical application of antibodies and small molecule inhibitors

Expressão não equilibrada do receptor de hidrocarboneto arílico nos linfócitos T CCR6+ CD4+ e CD4+ CD25+ do sangue periférico na artrite reumatoide

ResumoObjetivoAnalisar o papel do receptor de hidrocarboneto arílico (AhR) nos linfócitos T CCR6+ CD4+ e CD4+ CD25+ no sangue periférico de pacientes com artrite reumatoide (AR).MétodosFoi aplicada citometria de fluxo para determinar a proporção de células AhR positivas em linfócitos CCR6+ CD4+ e CD4+ CD25+ do sangue periférico e células mononucleares periféricas de cada indivíduo. Os níveis de expressão relativa de ácido ribonucleico mensageiro (do inglês ribonucleic acid, RNAm,) de AhR e RNAm de enzima de primeiro estágio essencial para o AhR (CYP1A1) foram testados por reação em cadeia de polimerase (do inglês polymerase chain reaction, PCR,) em tempo real.ResultadosA percentagem de células AhR positivas nas células mononucleares do sangue periférico foi maior no grupo com AR do que nos indivíduos saudáveis [(35,23±10,71)% vs. (18,83±7,32)%, (p<0,01)]. Os níveis de expressão de AhR e CYP1A1 estavam aumentados em pacientes com AR quando comparados com os controles [(3,71±1,63) vs. (2,00±1,27), p=0,002; (2,62±2,08) vs. (0,62±0,29), p<0,01, respectivamente]. Em pacientes com AR, a percentagem de células AhR positivas nos linfócitos T CD4+ CD25+ foi significativamente inferior à dos controles [17,90 (6,10±80,10)]% vs. (52,49±19,18)%, p < 0,01]; em controles saudáveis, a percentagem de células AhR positivas nos linfócitos T CD4+ CD25+ foi significativamente mais elevada do que nos linfócitos T CCR6+ CD4+ e também foi significativamente maior do que nas células mononucleares do sangue periférico (do inglês peripheral blood mononuclear cells, PBMC,) [(52,49±19,18)% vs. (23,18±5,62)% vs. (18,06±7,80)%, X 2=24,03, p < 0,01]; em pacientes com AR, a percentagem de células AHR positivas nos linfócitos T CCR6+ CD4+ era significativamente maior em comparação com os linfócitos T CD4+ CD25+ e PBMC (46,02±14,68)% vs. [17,90 (6,10±80.10)]% vs. (34,22±10,33)%, X 2=38,29, p<0,01]; no entanto, não foi encontrada correlação estatisticamente significativa entre os dados clínicos e células AhR positivas em linfócitos T CCR6+ CD4+ e CD4+ CD25+.ConclusãoO Ahr pode participar do progresso patológico da AR ao controlar a diferenciação de linfócitos Th17 e Treg no sangue periférico.AbstractObjectiveThe goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+ CD4+ and CD4+ CD25+T cells of patients with rheumatoid arthritis.MethodsFlow cytometry was applied to determine the proportion of AhR positive cells in CCR6+ CD4+T, CD4+ CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real‐time PCR.ResultsThe percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23±10.71) % vs. (18.83±7.32) %, (p<0.01)]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71±1.63) vs. (2.00±1.27), p=0.002; (2.62±2.08) vs. (0.62±0.29), p<0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90(6.10±80.10)]% vs. (52.49±19.18)%, p<0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, X2=24.03, p<0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs (46.02±14.68)% vs. [17.90 (6.10±80.10)] %vs. (34.22±10.33)%, X2=38.29, p<0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+ CD25+T cells.ConclusionAhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood

Utilisation, contents and costs of prenatal care under a rural health insurance (New Co-operative Medical System) in rural China : lessons from implementation

Peer reviewe

Improved value and carbon footprint by complete utilization of corncob lignocellulose

Lignocellulose, as the most abundant type of inedible biomass, is considered as a promising renewable feedstock for making fuels, chemicals, and materials. However, its complex structure makes most of current biorefinery processes suffer from low resource utilization rates, high energy consumption or ill-defined market orientation of the obtained products. Here, we propose and evaluate the EXA (Ethanol, Xylose, Adhesive) biorefinery strategy based on current xylose industry. This process integrates four conversion and separation stages to consecutively produce ethanol, xylose, and adhesive with total carbon utilization of 79.6%. The key innovation is the establishment of an easy-to-operate process for direct production of high-quality adhesive from a lignin-rich liquid fraction that makes the overall process significantly more sustainable. Techno-economic analysis (TEA) shows that the revenue of proposed EXA process increases more than 110 times compares with the current process and life cycle assessment (LCA) demonstrates a much lower CO2 footprint from an environmental burden per unit of revenue perspective