Gut microbiota and sepsis: bidirectional Mendelian study and mediation analysis

BackgroundThere is a growing body of evidence that suggests a connection between the composition of gut microbiota and sepsis. However, more research is needed to better understand the causal relationship between the two. To gain a deeper insight into the association between gut microbiota, C-reactive protein (CRP), and sepsis, we conducted several Mendelian randomization (MR) analyses.MethodsIn this study, publicly available genome-wide association study (GWAS) summary statistics were examined to determine the correlation between gut microbiota and sepsis, including various sepsis subgroups (such as under 75, 28-day death, Critical Care Units (ICU), 28-day death in ICU). Initially, two-sample and reverse Mendelian randomization (MR) analyses were conducted to identify causality between gut microbiota and sepsis. Subsequently, multivariable and two-step MR analyses revealed that the relationship between microbiota and sepsis was mediated by CRP. The robustness of the findings was confirmed through several sensitivity analyses.FindingsIn our study, we revealed positive correlations between 24 taxa and different sepsis outcomes, while 30 taxa demonstrated negative correlations with sepsis outcomes. Following the correction for multiple testing, we found that the Phylum Lentisphaerae (OR: 0.932, p = 2.64E-03), class Lentisphaeria, and order Victivallales (OR: 0.927, p = 1.42E-03) displayed a negative relationship with sepsis risk. In contrast, Phylum Tenericutes and class Mollicutes (OR: 1.274, p = 2.89E-03) were positively related to sepsis risk and death within 28 days. It is notable that Phylum Tenericutes and class Mollicutes (OR: 1.108, p = 1.72E-03) also indicated a positive relationship with sepsis risk in individuals under 75. From our analysis, it was shown that C-reactive protein (CRP) mediated 32.16% of the causal pathway from Phylum Tenericutes and class Mollicutes to sepsis for individuals under 75. Additionally, CRP was found to mediate 31.53% of the effect of the genus Gordonibacter on sepsis. Despite these findings, our reverse analysis did not indicate any influence of sepsis on the gut microbiota and CRP levels.ConclusionThe study showcased the connection between gut microbiota, CRP, and sepsis, which sheds new light on the potential role of CRP as a mediator in facilitating the impact of gut microbiota on sepsis

Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice

<p>Abstract</p> <p>Background</p> <p>Our previous study demonstrated that nitric oxide (NO) contributes to long-term potentiation (LTP) of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord <it>in vivo</it>. Ryanodine receptor (RyR) is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway.</p> <p>Results</p> <p>By means of field potential recordings in the adult male rat <it>in vivo</it>, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT) stably induced LTP of field excitatory postsynaptic potentials (fEPSPs). Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5)P3 receptor (IP₃R) antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs). Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG) neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca²⁺]_iin small DRG neurons.</p> <p>Conclusions</p> <p>These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.</p

Planar Antennas

This article reviews the state of the art in broadband antennas for emerging UWB applications and addresses the important issues of the broadband antenna design for UWB applications. First, a variety of planar monopoles with finite ground planes are reviewed. Next, the roll antennas with enhanced radiation performance are outlined. After that, the planar antennas printed on PCBs are described. A directional antipodal Vivaldi antenna is also presented for UWB applications. Last, a UWB antenna for wearable applications is exemplifie

Investigation on Microstructure and Optical Property of Nanocrystalline Silicon Thin Film

Nanocrystalline silicon (nc-Si:H) thin films were deposited by capacitive coupled radio-frequency plasma enhanced chemical vapor deposition (RF-PECVD) system with direct current (DC) bias applied. Raman, XRD and ultraviolet-visible transmission spectra were employed to investigate their microstructure and optical properties, respectively. Both the crystalline volume fraction and the average crystalline size increase with the substrate temperature. With the increase of silane concentration, the crystalline volume fraction increases, while the average crystalline size decreases. With the increase of the radio frequency (RF) power or the DC negative bias voltage, the crystalline volume fraction and the average crystalline size increase firstly, then decreases. Finally, the optical band gaps were discussed in detail

Allele frequency analysis of Chinese chestnut (Castanea mollissima) populations using fluorescent simple sequence repeats (SSR) analysis

The aim of this study was to establish a method for allele frequency detection in bulk samples. The abundance of polymerase chain reaction (PCR) products in bulk leaf samples was detected using fluorescent labeled Simple sequence repeat (SSR) primers and an Applied biosystems (AB) automatic DNA analyzer. Compared with the conventional SSR technique based on polyacrylamide gel electrophoresis (PAGE) and silver staining, fluorescent SSR was much more sensitive. A total of 78 alleles, an average of 4.6 alleles per locus, were detected among 17 chestnut populations with the primer CmTCR10 (NED) and a total of 41 alleles, an average of 2.4 alleles per locus, were detected with the primer CmTCR24 (6-FAM). Multiplexing the PCR reaction by combining the primer pairs of CmTCR10 and CmTCR24, using different fluorescent dyes for different primers, showed that the alleles could be discriminated and the sizes of the amplified segments were similar. Furthermore, the exact sizes of the amplified fragments and the abundance of the PCR products were determined by fluorescent SSR. After data analysis with GeneScan software and allele calling and output with Genotyper software, allele frequencies were calculated for equal pooled samples in each population using the FREQS-R module in the R statistical computing language. The results indicate that it is feasible to determine allele frequencies in bulked samples based on the detection of SSR-PCR products. The advantages and additional applications of this method are also discussed. The abundance of the PCR products can be used to determine the allele frequencies in bulk samples of chestnut populations.Keywords: Fluorescent simple sequence repeats (SSR), chestnut population, bulk sampling, allele frequencie

The role of EGFR mutation as a prognostic factor in survival after diagnosis of brain metastasis in non-small cell lung cancer: A systematic review and meta-analysis

Abstract Background The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. Methods Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017. Results 4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method. Conclusions This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases

HCV-induced miR146a Controls SOCS1/STAT3 and Cytokine Expression in Monocytes to Promote Regulatory T-cell Development

Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up‐regulated in monocytes from hepatitis C virus (HCV )‐infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll‐like receptor (TLR ) stimulation. This miR146a induction by HCV infection and differential response to TLR stimulation were recapitulated in vitro in monocytes co‐cultured with hepatocytes with or without HCV infection. Importantly, inhibition of miR146a in monocytes from HCV ‐infected patients led to a decrease in IL ‐23, IL ‐10 and TGF ‐β expressions through the induction of suppressor of cytokine signalling 1 (SOCS 1) and the inhibition of signal transducer and activator transcription 3 (STAT 3), and this subsequently resulted in a decrease in regulatory T cells (Tregs) accumulated during HCV infection. These results suggest that miR146a may regulate SOCS 1/STAT 3 and cytokine signalling in monocytes, directing T‐cell differentiation and balancing immune clearance and immune injury during chronic viral infection