Identification of a novel Scn3b mutation in a Chinese Brugada syndrome pedigree: implications for Nav1.5 electrophysiological properties and intracellular distribution of Nav1.5 and Navß3.

Background: The Scn3b gene encodes for Navß3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined. Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55 mv and peaked at -25 mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (INa) at -25 mv. The parameters for half-maximal activation voltages (V1/2) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups (P = 0.98 and P = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V1/2 and k (with P-values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ (P = 0.59) and late sodium current density (P = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization. Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak INa activation current coupled with decreased cell surface expression of Nav1.5 and Navß3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS.

[Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1ß signaling pathway].

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1ß(IL-1ß). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1ß signaling pathway-mediated microglia p38/IL-1ß inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.

Anti-inflammatory therapeutic biomarkers identified of human bone marrow mesenchymal stem cell therapy on aging mice by serum proteomics and peptidomics study.

Aging is accompanied by deterioration in physical condition, and creates high risks of diseases. Stem cell therapy exhibited promising potential in delaying aging. However, the unelucidated therapeutic mechanism limits future clinical application. Herein, to systematically understand the response to stem cell transfusion at the molecular level, we performed quantitative serum proteomic and peptidomics analyses in the 24-month-old aging mice model with or without mesenchymal stem cell (MSC) treatment. As a result, a total of 560 proteins and 2131 endogenous peptides were identified, among which, 6 proteins and 9 endogenous peptides derived from 6 precursor proteins were finally identified as therapeutic biomarkers after MSC transfusion on aging mice both by untargeted label-free quantification and targeted parallel reaction monitoring (PRM) quantification. Amazingly, the biological function of these differential proteins was mainly related to inflammation, which is not only the important hallmark of aging, but also the main cause of inducing aging. The reduction of these inflammatory protein content after MSC treatment further suggests the anti-inflammatory effect of MSC therapy reported elsewhere. Therefore, our study provides new evidence for the anti-inflammatory effect of MSC therapy for anti-aging and offers abundant data to support deeper investigations of the therapeutic mechanism of MSC in delaying aging.

Comparison of the Nerve Regeneration Capacity and Characteristics between Sciatic Nerve Crush and Transection Injury Models in Rats.

Objective: To provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies, and to compare nerve regeneration capacity and characteristics between them. Methods: Sixty adult SD rats were randomly divided into two groups and underwent crush injury alone (group A, n = 30) or transection injury followed by surgical repair (group B, n = 30) of the right hind paw. Each group was subjected to the CatWalk test, gastrocnemius muscle evaluation, pain threshold measurement, electrophysiological examination, retrograde neuronal labeling, and quantification of nerve regeneration before and 7, 14, 21, and 28 days after injury. Results: Gait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days. At 21 days, the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B, and the number of labeled motor neurons in group B was lower than that in group A. The number of new myelin sheaths and the g-ratio were higher in group A than in group B. There was a 7-day time difference in the regeneration rate between the two injury groups. Conclusion: The regeneration of nerve fibers was rapid after crush nerve injury, whereas the transection injury was relatively slow, which provides some ideas for the selection of clinical research models.

The Effect of Female Sex on Short-Term Outcomes of Patients Undergoing Off-Pump Versus On-Pump Coronary Artery Bypass Grafting

ABSTRACT Introduction: According to the American Heart Association guideline for coronary artery bypass grafting (CABG), female patients undergoing on-pump CABG (ONCAB) are at higher risk of short-term adverse outcomes than male patients. However, whether off-pump CABG (OPCAB) can improve the short-term outcome of female patients compared to ONCAB remains unclear. Methods: We conducted a meta-analysis to study the effect of the female sex on short-term outcomes of OPCAB vs. ONCAB. A total of 31,115 patients were enrolled in 12 studies, including 20,245 females who underwent ONCAB and 10,910 females who underwent OPCAB. Results: The in-hospital mortality in female patients who underwent OPCAB was significantly lower than in those in the ONCAB group with (2.7% vs. 3.4%; odds ratio [OR] 0.76; 95% confidence interval [CI] 0.65-0.89) and without (OR 0.68; 95% CI 0.52-0.89) adjustment for cardiovascular risk factor. The incidence of postoperative stroke in female patients who underwent OPCAB was lower than in those in the ONCAB group (1.2% vs. 2.1%; OR 0.59; 95% CI 0.48-0.73) before cardiovascular risk factor adjustment but was not significant (OR 0.87; 95% CI 0,66-1.16) after adjustment. There was no significant difference in the incidence of postoperative myocardial infarction between women who underwent OPCAB and those in the ONCAB group (1.3% vs. 2.3%; OR 0.88; 95% CI 0.54-1.43). Conclusion: In contrast to the American Heart Association CABG guideline, female patients who had OPCAB don't have unfavorable outcomes compared with the ONCAB group.

Partial replacement of soybean meal by yellow mealworm (Tenebrio molitor) meal influences the flesh quality of Nile tilapia (Oreochromis niloticus).

This study investigated the effects of yellow mealworm meal (YM) replacing soybean meal (SBM) at different proportions (0%, 15%, 30% and 45%, referred as YM0, YM15, YM30 and YM45, respectively) on the flesh quality of Nile tilapia. A total of 360 fish (70.0 ± 0.12 g) were randomly divided into 4 groups (3 tanks per group). Fish were fed the experimental diet twice daily for 10 wk. The results showed that muscle protein content significantly decreased in YM30 and YM45, while the lipid content significantly decreased in YM45 (P < 0.05). The essential amino acids and flavor amino acids of the muscle were not affected by the YM substitution, while saturated fatty acid content decreased in YM30 and YM45 compared with YM0 (P < 0.05). Fillets in YM45 had higher hardness, gumminess, and a higher proportion of thin myofibers (≤100 µm, P < 0.05) than those in other groups. Further analysis revealed that apoptosis and atrophy related genes were up-regulated, while the muscle antioxidant capacity decreased significantly in YM45 (P < 0.05), which may be related to the high acid value in YM45 diet. Our findings indicated that YM could replace up to 30% SBM without substantially altering the flesh quality. When the replacement ratio increased to 45%, the flesh quality would change. Special attention should be paid to avoid feed rancidity which may affect the flesh quality of fish.

The Effect of Female Sex on Short-Term Outcomes of Patients Undergoing Off-Pump Versus On-Pump Coronary Artery Bypass Grafting.

INTRODUCTION: According to the American Heart Association guideline for coronary artery bypass grafting (CABG), female patients undergoing on-pump CABG (ONCAB) are at higher risk of short-term adverse outcomes than male patients. However, whether off-pump CABG (OPCAB) can improve the short-term outcome of female patients compared to ONCAB remains unclear. METHODS: We conducted a meta-analysis to study the effect of the female sex on short-term outcomes of OPCAB vs. ONCAB. A total of 31,115 patients were enrolled in 12 studies, including 20,245 females who underwent ONCAB and 10,910 females who underwent OPCAB. RESULTS: The in-hospital mortality in female patients who underwent OPCAB was significantly lower than in those in the ONCAB group with (2.7% vs. 3.4%; odds ratio [OR] 0.76; 95% confidence interval [CI] 0.65-0.89) and without (OR 0.68; 95% CI 0.52-0.89) adjustment for cardiovascular risk factor. The incidence of postoperative stroke in female patients who underwent OPCAB was lower than in those in the ONCAB group (1.2% vs. 2.1%; OR 0.59; 95% CI 0.48-0.73) before cardiovascular risk factor adjustment but was not significant (OR 0.87; 95% CI 0,66-1.16) after adjustment. There was no significant difference in the incidence of postoperative myocardial infarction between women who underwent OPCAB and those in the ONCAB group (1.3% vs. 2.3%; OR 0.88; 95% CI 0.54-1.43). CONCLUSION: In contrast to the American Heart Association CABG guideline, female patients who had OPCAB don't have unfavorable outcomes compared with the ONCAB group.

Gate-tunable bolometer based on strongly coupled graphene mechanical resonators.

Bolometers based on graphene have demonstrated outstanding performance with high sensitivity and short response time. In situ adjustment of bolometers is very important in various applications, but it is still difficult to implement in many systems. Here we propose a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. Both resonators are exposed to the same light field, and we can measure the properties of one bolometer by directly tracking the resonance frequency shifts, and indirectly measure the other bolometer through mechanical coupling. We find that the sensitivity and the response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. Moreover, the properties of the indirectly measured bolometer show a dependence on the coupling between the two resonators, with other parameters being fixed. Our method has the potential to optimize the design of large-scale bolometer arrays, and open new horizons in infrared/terahertz astronomy and communication systems.

[Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway].

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Ab initio determination on diffusion coefficient and viscosity of FeNi fluid under Earth's core condition.

The Earth's outer core is mainly composed of Fe and Ni. The geodynamo of the Earth's core are closely correlated with the transport properties of the fluid in the Earth's core. We selected the typical FeNi fluid, and systemically calculated its diffusion coefficient and viscosity under Earth's core condition by quantum molecular dynamics simulation. The diffusion coefficients are almost constant along the core adiabatic curve. The self-diffusion coefficients of Ni along the core adiabatic curve range from 2.47 × 10-9 to 3.37 × 10-9 m2s-1. The diffusion coefficient increases with temperature increase, while viscosity decrease with temperature increase. The calculations on the transport properties suggest that the Ni impurities have a negligible effect on the diffusion coefficient and viscosity of Earth's core.

Availability and Affordability of Therapeutic Monoclonal Antibodies After the New Medical Reform in Hubei Province, China.

OBJECTIVE: In 2017, China launched a new round of medical reform (NMR) to address the inaccessibility of high-priced drugs for patients with serious diseases. This study explored the impact of the NMR on the accessibility and affordability of high-priced monoclonal antibodies (mAbs), and the effective promotion policies after the NMR. METHODS: We used a standard method developed by the World Health Organization to conduct two surveys on the availability of mAbs and their prices before and after the NMR in the public hospitals in Hubei province, China. By interviewing hospital pharmacy experts, we identified the potential value of the current NMR in improving the access to therapeutic mAbs. RESULTS: The average availability of 13 mAbs increased by 8.1% in the surveyed hospitals of Hubei province after the NMR. The median unit price of 10 mAbs dropped by 34.3%. The average affordability of a treatment cycle of 10 mAbs dropped from 680 days to 298 days of the disposable daily income for a middle-income resident (56.2% reduction). The drug price negotiation of medical insurance inclusion and the promotion of consistent evaluation of generic and original drugs could effectively promote the accessibility of mAbs. However, the zero markup of drug pricing and the limit on the proportion of drug revenues in public hospitals showed certain negative effects on the availability of mAbs. CONCLUSION: Not all current NMR policies play a positive role in promoting the accessibility of mAbs. To further improve the accessibility of mAbs in the future in China, it is therefore critical to increase the investment in independent research and development of high-quality mAbs, establish localized guidelines for the rational use of mAbs in clinical practice, and have a cost-sharing mechanism for high-priced drugs with multiple stakeholders.

Effects of dietary mannan oligosaccharides (MOS) supplementation on metabolism, inflammatory response and gut microbiota of juvenile Nile tilapia (Oreochromis niloticus) fed with high carbohydrate diet.

High-carbohydrate diet could achieve cost-sparing effect in aquafeed, but it may cause adverse effects on the growth condition or health status of fish. In order to reduce the adverse effects caused by high carbohydrate diet, mannan oligosaccharides (MOS), a commonly used prebiotics, was used as the feed additive to feed juvenile Nile tilapia (Oreochromis niloticus) (1.19 ± 0.01g) for ten weeks. Three treatments including CON (35% carbohydrate diet), HC (45% carbohydrate diet) and HM (45% carbohydrate supplemented diet with 5 g/kg MOS) were involved. The results showed that MOS supplementation increased the weight gain and body length of juvenile Nile tilapia compared with the HC group. Addition of MOS decreased serum glucose and liver glycogen by increasing enzymes activity related to glycolysis. Furthermore, supplementation of MOS decreased the high carbohydrate diet induced triglycerides accumulation in liver by reducing the expression level of genes related to TG synthesis. Dietary MOS also down-regulated the gene expression level of inflammation factors in liver. Intestinal bacterial composition analyses showed that supplementation of MOS in high carbohydrate diet altered the gut microbial composition and enriched pathways related to the glucose metabolism based on KEGG analyses. In general, our results demonstrated that MOS supplementation in high carbohydrate diet could regulate glucose and lipid homeostasis which may be related to the alteration of gut microbiota. These findings shed light on the application of prebiotics to increase the growth performance, alleviate the metabolic disorders and regulate inflammatory response in aquaculture.

Nationwide Termite Pest Survey Conducted in Taiwan as a Citizen Science Project.

Information regarding the species composition and dispersal flight season of termites is crucial for termite management. The major obstacles to collecting such information are a lack of access to private buildings and shortage of workers to monitor and report on termite swarming. To overcome these difficulties, we launched a citizen science project in which members of the public and pest management professionals were invited to collect termite samples. We created the website, Taiwan Termite Identification Service, on which populace could log the collection information, and ship termite samples to our laboratory for identification. We also established a Facebook group, called the "Termite Forum," to publicize this project. A total of 3024 samples were collected from 2015 to 2020, and we identified the species of >93% of the samples. Based on 1499 samples collected from buildings, five structural termite pests were identified, and species composition in each county of Taiwan is available. According to 844 dispersal flight events, termite dispersal flight timing peak and degree of centralization were estimated using a Gaussian model. The collected data demonstrated that the invasive termite species, Coptotermes gestroi (Wasmann) (Blattodea: Rhinotermitidae), continued northward expansion. The first intercepted alate of Schedorhinotermes sp. (Blattodea: Rhinotermitidae) indicated that it may be a new invasive pest from Southeast Asia. This study reports on a successful case of a citizen science project where urban pest data were collected on a national scale.

Single-tube Multiplex Nested PCR System for Efficient Detection of Pathogenic Microorganisms in SPF Rodents.

PCR testing is increasingly important for microbial control in SPF facilities. However, most current PCR methods are timeconsuming and require compromise between high sensitivity and high multiplexing. We developed a one-tube multiplex nested PCR strategy (MN-PCR) for simultaneous direct (that is, without culturing) detection of multiple pathogens. We first aligned sequences for the 16S rDNA genes of selected target bacteria and a panel of closely related organisms. From these data, we designed a pair of universal primers and multiple sets of species-specific PCR primers to amplify the target sequences; the universal primers were modified to include various degenerate bases and locked nucleic acids. In a single tube, 16S rDNA sequences were amplified by using the nested PCR primers under high temperature (that is, above 65°C) during the first stage of the MN-PCR procedure, when the target-species-specific PCR primers do not support amplification due to their short length. In addition, the concentration of the nested PCR primers during the first stage was adjusted to ensure that they were consumed and did not yield visible bands themselves. During the second stage, the enriched 16S rDNA sequences then served as templates for amplification of the species-specific fragments by using the multiple PCR primers at low annealing temperatures (that is, below 60°C). The results showed that our MN-PCR method detected as little as 1 fg of target bacterial DNA in a 20-µL reaction volume, whereas conventional multiplex PCR detected a minimum of 1 pg only. Compared with traditional multiplex PCR assays, our MN-PCR system is an effective and efficient culture-free process.

Tuning the nonlinearity of graphene mechanical resonators by Joule heating.

As an inherent property of the device itself, nonlinearity in micro-/nano- electromechanical resonators is difficult to eliminate, and it has shown a wide range of applications in basic research, sensing and other fields. While many application scenarios require tunability of the nonlinearity, inherent nonlinearity of a mechanical resonator is difficult to be changed. Here, we report the experimental observation of a Joule heating induced tuning effect on the nonlinearity of graphene mechanical resonators. We fabricated multiple graphene mechanical resonators and detected their resonant properties by an optical interference method. The mechanical vibration of the resonators will enter from the linear to the nonlinear intervals if we enhance the external driving power to a certain value. We found that at a fixed drive power, the nonlinearity of a mechanical resonator can be tuned by applying a dc bias current on the resonator itself. The tuning mechanism could be explained by the nonlinear amplitude-frequency dependence theory. Our results may provide a research platform for the study of mechanical nonlinearity by using atomic-thin layer materials.

Microbiota derived butyrate affected the muscle texture of Nile tilapia (Oreochromis niloticus) fed with different protein sources.

Flesh quality is influenced by diet components, but the underlying mechanism remains unclear. This study aimed to investigate the effect of replacing soybean meal (SBM) protein with cottonseed protein concentrate (CPC) at different levels (0%, CK; 15%, CPC15; 30%, CPC30 and 45%, CPC45) on the flesh quality of Nile tilapia. The results indicated that different protein sources influenced muscle amino acid composition instead of fatty acid composition. Lower muscle lipid content was found in CPC45, which in turn significantly altered the muscle texture. The hepatic lipid metabolism-related genes were detected and we found that CPC45 significantly suppressed the lipogenesis and promoted lipolysis. Higher content of microbiota-derived butyrate was found in the intestinal content of CPC45 and butyrate could decrease the lipid accumulation in vitro. Replacing SBM with CPC increased the intestinal butyrate to suppress the lipogenesis in the liver which may account for the increased muscle hardness.

Antagonism of G protein-coupled receptor 55 prevents lipopolysaccharide-induced damages in human dental pulp cells.

Pulpitis is a common oral inflammatory disease in dental pulp commonly associated with bacterial infection. G protein-coupled receptor 55 (GPR55) is a member of the G protein-coupled receptors family that has been found to regulate inflammatory response. However, its roles in dental pulp inflammation have not been investigated. In this study, we used lipopolysaccharide (LPS) to induce inflammation in human dental pulp cells (hDPCs) to simulate an in vitro model of pulpitis. We found that LPS markedly induced the GPR55 expression in hDPCs. Treatment with the GPR55 antagonist ML-193 ameliorated the LPS-caused decrease in cell viability and increase in lactate dehydrogenase release. The upregulated inflammatory cytokines, interleukin-6 (IL-6) and tumour necrosis factor α, in LPS-challenged hDPCs were also attenuated by ML-193. Treatment with ML-193 ameliorated LPS-induced production of the inflammatory mediators cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2), and inducible nitric oxide synthase/nitric oxide (iNOS/NO) in hDPCs. ML-193 also inhibited the activation of Toll-like receptor 4-myeloid differentiation primary response 88-nuclear factor-κB (TLR4-Myd88-NF-κB) signaling in LPS-induced hDPCs via decreased expressions of TLR4, Myd88, and p-NF-κB 65. Our study provides evidence that the GPR55 antagonist ML-193 exhibited anti-inflammatory activity in LPS-stimulated hDPCs through inhibiting TLR4-Myd88-NF-κB signaling. The results imply that ML-193 might be a novel agent for pulpitis.

Intestinal Microbiota Mediates Gossypol-Induced Intestinal Inflammation, Oxidative Stress, and Apoptosis in Fish.

Gossypol, the main antinutritional factor in cottonseed protein concentrate (CPC), could affect the growth conditions of fish, but the underlying mechanism remains unclear. In this study, an 8-week feeding trial was carried out to investigate the effects of gossypol on Nile tilapia (Oreochromis niloticus). Three experimental diets were designed, including control diet (CON), control diet supplemented with 150 mg/kg gossypol (ML), and 300 mg/kg gossypol (MH). 16S rRNA gene sequencing showed that gossypol significantly reduced the richness and diversity of the gut microbiota. Untargeted metabolite analysis revealed that most metabolites were down-regulated by gossypol, and riboflavin was the key metabolite with significant difference between CON-treated and gossypol-treated groups. Gossypol caused intestinal inflammation, oxidative stress, and apoptosis. Through fecal bacteria transplantation experiments, we demonstrated that intestinal microbiota mediated gossypol-induced negative effects, suggesting that intestinal microbiota and its metabolite may account for the harmful effects of gossypol.

Architecting Braided Porous Carbon Fibers Based on High-Density Catalytic Crystal Planes to Achieve Highly Reversible Sodium-Ion Storage.

Carbonaceous materials are considered strong candidates as anode materials for sodium-ion batteries (SIBs), which are expected to play an indispensable role in the carbon-neutral era. Herein, novel braided porous carbon fibres (BPCFs) are prepared using the chemical vapour deposition (CVD) method. The BPCFs possess interwoven porous structures and abundant vacancies. The growth mechanism of the BPCFs can be attributed to the polycrystalline transformation of the nanoporous copper catalyst in the early stage of CVD process. Density functional theory calculations suggest that the Na+ adsorption energies of the mono-vacancy edges of the BPCFs (-1.22 and -1.09 eV) are lower than that of an ideal graphene layer (-0.68 eV), clarifying in detail the adsorption-dominated sodium storage mechanism. Hence, the BPCFs as an anode material present an outstanding discharge capacity of 401 mAh g-1 at 0.1 A g-1 after 500 cycles. Remarkably, this BPCFs anode, under high-mass-loading of 5 mg cm-2, shows excellent long-term cycling ability with a reversible capacity of 201 mAh g-1 at 10 A g-1 over 1000 cycles. This study provided a novel strategy for the development of high-performance carbonaceous materials for SIBs.

A Spontaneous H2-Aa Point Mutation Impairs MHC II Synthesis and CD4+ T-Cell Development in Mice.

Major histocompatibility complex class II (MHC II) is an essential immune regulatory molecule that plays an important role in antigen presentation and T-cell development. Abnormal MHC II expression can lead to immunodeficiency, clinically termed as type II bare lymphocyte syndrome (BLS), which usually results from mutations in the MHC II transactivator (CIITA) and other coactivators. Here, we present a new paradigm for MHC II deficiency in mice that involves a spontaneous point mutation on H2-Aa. A significantly reduced population of CD4+ T cells was observed in mice obtained from the long-term homozygous breeding of autophagy-related gene microtubule-associated protein 1 light chain 3 ß (Map1lc3b, Lc3b) knockout mice; this phenotype was not attributed to the original knocked-out gene. MHC II expression was generally reduced, together with a marked deficiency of H2-Aa in the immune cells of these mice. Using cDNA and DNA sequencing, a spontaneous H2-Aa point mutation that led to false pre-mRNA splicing, deletion of eight bases in the mRNA, and protein frameshift was identified in these mice. These findings led to the discovery of a new type of spontaneous MHC II deficiency and provided a new paradigm to explain type II BLS in mice.