Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

Background/AimsBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).MethodsSerum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.ResultsA marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.ConclusionsFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.     

rTMS及CBT-I对慢性失眠障碍患者治疗效果的随机对照研究

背景 目前,药物疗法是失眠障碍的一线治疗手段,但仍然存在着一定的不良反应。与药物治疗相比,重复经颅磁刺激（rTMS）和失眠的认知行为治疗（CBT-I）的不良反应较少、患者耐受性较好。目的 探讨rTMS与CBT-I治疗慢性失眠障碍的效果,以期为慢性失眠障碍患者提供更优的治疗方案。方法 选取2020年9月21日—2021年12月16日在内蒙古自治区精神卫生中心门诊或社区医院就诊的、符合《国际睡眠障碍分类第三版》（ICSD-3）诊断标准的慢性失眠障碍患者（n=50）,同期在社区招募与患者组年龄和性别相匹配的健康人作为对照组（n=16）。采用随机数字表法将慢性失眠障碍患者分为rTMS组与CBT-I组各25例,分别接受为期6周的rTMS或CBT-I干预。于干预前和干预后,慢性失眠障碍患者接受多导睡眠监测（PSG）以及匹兹堡睡眠质量指数量表（PSQI）、失眠严重程度指数量表（ISI）、重复性成套神经心理状态测验（RBANS）评定。对患者组和对照组进行静息态磁共振成像（rs-fMRI）扫描,并进行静息态低频振幅（ALFF）分析。将患者组和对照组ALFF值差异有统计学意义的脑区作为感兴趣区域（ROI）,将其作为种子点与患者全脑进行功能连接分析。结果 rTMS组和CBT-I组的PSQI评分、ISI评分以及RBANS中的即刻记忆、言语功能、延时记忆维度评分的时间效应均有统计学意义（F=41.160、69.615、47.923、12.090、28.193,P均<0.05）;两组总睡眠时间的时间效应、睡眠效率的时间效应和组别效应以及N1%的时间效应均有统计学意义（F=8.995、12.414、4.342、7.806,P均<0.05）。干预后,CBT-I组睡眠效率高于干预前（t=-2.785,P<0.05）。rTMS组眶部额上回与左侧豆状壳核（t=4.991,P<0.05）、右内侧和旁扣带回（t=4.471,P<0.05）和右侧中央后回（t=4.922,P<0.05）之间的功能连接增强,CBT-I组眶部额上回与左侧额中回之间的功能连接增强（t=6.586,P<0.05）。结论 rTMS及CBT-I可能有助于改善慢性失眠障碍患者的失眠情况和认知功能。     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

Association between Excessive Dietary Branched-Chain Amino Acids Intake and Hypertension Risk in Chinese Population

The dietary intake of branched-chain amino acids (BCAAs) has been reported to be associated with both elevated blood pressure (BP) and hypertension risk, while published findings were inconsistent, and the causality has never been well disclosed. We performed this prospective study aiming to find out the relationship between dietary BCAAs intake and hypertension risk in the Chinese population. A total of 8491 participants (40,285 person-years) were selected. The levels of dietary BCAAs intake were estimated using the 24-h Food Frequency Questionnaire. Associations of both BP values and hypertension risk with per standard deviation increase of BCAAs were estimated using linear and COX regression analysis, respectively. The hazard ratios and 95% confidence interval were given. Restricted cubic spline analysis (RCS) was used to estimate the nonlinearity. Both systolic and diastolic BP values at the end points of follow-up were positively associated with dietary BCAAs intake. Positive associations between BCAAs intake and hypertension risk were shown in both men and women. By performing a RCS analysis, the nonlinear relationship between BCAAs intake and hypertension was shown. As the intake levels of Ile, Leu, and Val, respectively, exceeded 2.49 g/day, 4.91 g/day, and 2.88 g/day in men (2.16 g/day, 3.84 g/day, and 2.56 g/day in women), the hypertension risk increased. Our findings could provide some concrete evidence in the primary prevention of hypertension based on dietary interventions.     

强心冲剂对充血性心力哀竭家兔模型心钠素、血管紧张素Ⅱ的影响

目的观察强心冲剂干预后充血性心力衰竭(CHF)家兔模型心钠素(ANP)、血管紧张素Ⅱ(AngⅡ)的变化,探讨强心冲剂对神经内分泌活性的影响.方法将40只家兔随机分为4组,假手术组、模型组、地高辛组、强心冲剂组,每组10只.采用腹主动脉缩窄术建立家兔CHF模型,予强心冲剂和地高辛灌胃,检测并比较ANP、AngⅡ的活性.结果CHF家兔模型ANP、AngⅡ活性显著升高,神经内分泌激素释放失衡,强心冲剂干预后,可以纠正其失衡状态,明显降低ANP、AngⅡ水平.结论强心冲剂能显著纠正神经内分泌激素释放失衡状态,改善神经内分泌激素的激活,可以防止CHF的进一步恶化.     

Analysis of Carbonation Behavior of Cracked Concrete

The crack and carbonation of concrete pose a great challenge to its durability. Therefore, this paper studies the effect of cracks on the carbonation depth of cement paste under different factors. The relationship between carbonation and cracks was determined, and the carbonation mechanism of cement paste with cracks was clarified. The results show that a small water–binder ratio can effectively inhibit the carbonation process. The bidirectional carbonation enlarged the carbonation area around the crack. Within 21 days of the carbonation, the carbonation depth increased with carbonation time, and the Ca(OH)₂ on the surface of the specimen was sufficient, allowing for a convenient chemical reaction with CO₂. The influence of crack width on the carbonation process at the crack was greater than the influence of the crack depth. Carbonation influenced the hydration of cement-based materials, altering the types and quantities of hydration products. In conclusion, accurately predicting the regularity of carbonation in cracked structures is critical for improving the durability of concrete.     

Numerical Simulation and Process Optimization on Hot Twist-Stretch Straightening of Ti-6Al-4V Alloy Profile

Ti-6Al-4V profiles prepared by hot extrusion are usually accompanied by bending and twisting. The hot twist-stretch straightening is an effective strategy such that the bending deflection and twisting angle can be simultaneously decreased by a single straightening process. In addition, utilizing stress relaxation effect, the residual stress and springback can be greatly reduced by holding the straightening temperature and strain constant for a period after twist-stretch straightening. In this study, the hot deformation behaviors of the Ti-6Al-4V profile were revealed by experiments. The tensile model was obtained by uniaxial tensile tests within ranges of temperatures (500–700 °C) and strain rates (5 × 10⁻⁵–1 × 10⁻³ s⁻¹). The creep constitutive model was acquired with stress relaxation experiments in ranges of temperatures (500–700 °C) and pre-strain of 1.5%. Then, the coupled thermo-mechanical model of hot twist-stretch straightening was established. Based on orthogonal experiment strategy, the effects of straightening temperature, stretch strain, and holding time on the bending deflection and torsion angle of profile were investigated systematically and the process was optimized. The straightening accuracy is significantly affected by straightening temperature and holding time. By using optimized process parameters in practical straightening experiments, the deflection/length and angle/length after straightening does not exceed 2‰ and 2.5‰°/mm, respectively, which is basically consistent with the numerical simulation result.     

A Novel Preparation of Special-Shaped Phosphors-in-Glass by Gel Casting with Isobam for High-Power WLEDs Lighting

Phosphors-in-glass (PiGs) regarded as a promising phosphor-converter for white light emitting diodes (WLEDs) is being researched widely. However, there are few reports on the effect of changing the shape of PiGs on the color rendering index (CRI) and heat dissipation of WLEDs. In this paper, gel casting with Isobam was first attempted in preparing special-shaped PiGs successfully. It exhibited that 76 wt.% was the optimum solid content based on the rheological properties of slurry and the shrinkage of green bodies. The sintering rate should be kept at a low speed and glass transition temperature (Tg) of glass powders must be higher than sublimation temperatures (Ts) of APS and Isobam. The CRI of PiGs was increased by about 27% after changing the shape of PiGs from cylinder to dome. Most importantly, operating temperature also reduced effectively the increase of the surface area of PiGs. Therefore, changing the shape of PiGs by gel casting with Isobam is a creative way for high-power WLEDs lighting.     

Microstructure and Friction Properties of CoCrFeMnNiTix High-Entropy Alloy Coating by Laser Cladding

To enhance the friction and wear properties of 40Cr steel’s surface, CoCrFeMnNi high-entropy alloy (HEA) coatings with various Ti contents were prepared using laser cladding. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) were used to characterize the phase composition, microstructure, and chemical composition of the samples. The findings demonstrated that the CoCrFeMnNiTi_x HEA coatings formed a single FCC phase. Fe₂Ti, Ni₃Ti, and Co₂Ti intermetallic compounds were discovered in the coatings when the molar ratio of Ti content was greater than 0.5. The EDS findings indicated that Cr and Co/Ni/Ti were primarily enriched in the dendrite and interdendrite, respectively. Ti addition can effectively enhance the coating’s mechanical properties. The hardness test findings showed that when the molar ratio of Ti was 0.75, the coating’s microhardness was 511 HV0.5, which was 1.9 times the hardness of the 40Cr (256 HV0.5) substrate and 1.46 times the hardness of the CrCrFeMnNi HEA coating (348 HV0.5). The friction and wear findings demonstrated that the addition of Ti can substantially reduce the coating’s friction coefficient and wear rate. The coating’s wear resistance was the best when the molar ratio of Ti was 0.75, the friction coefficient was 0.296, and the wear amount was 0.001 g. SEM and 3D morphology test results demonstrated that the coating’s wear mechanism changed from adhesive wear and abrasive wear to fatigue wear and abrasive wear with the increase in Ti content.