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Abstract This study aimed to investigate the beneficial effects of probiotic yogurt on lipid metabolism and gut microbiota in metabolic‐related fatty liver disease (MAFLD) golden hamsters fed on a high‐fat diet (HFD). The results demonstrated that probiotic yogurt significantly reversed the adverse effects caused by HFD, such as body and liver weight gain, liver steatosis and damage, sterol deposition, and oxidative stress after 8 weeks of intervention. qRT‐PCR analysis showed that golden hamsters fed HFD had upregulated genes related to adipogenesis, increased free fatty acid infiltration, and downregulated genes related to lipolysis and very low‐density lipoprotein secretion. Probiotic yogurt supplements significantly inhibited HFD‐induced changes in the expression of lipid metabolism‐related genes. Furthermore, 16S rRNA gene sequencing of the intestinal content microbiota suggested that probiotic yogurt changed the diversity and composition of the gut microbiota in HFD‐fed hamsters. Probiotic yogurt decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS‐producing genus Desulfovibrio, and bacteria involved in lipid metabolism, whereas it increased the relative abundance of short‐chain fatty acids producing bacteria in HFD‐fed hamsters. Predictive functional analysis of the microbial community showed that probiotic yogurt‐modified genes involved in LPS biosynthesis and lipid metabolism. In summary, these findings support the possibility that probiotic yogurt significantly improves HFD‐induced metabolic disorders through modulating intestinal microflora and lipid metabolism and effectively regulating the occurrence and development of MAFLD. Therefore, probiotic yogurt supplementation may serve as an effective nutrition strategy for the treatment of patients with MAFLD clinically.

Abstract Background and aims Epidemiological evidence suggests that the phenotype of glutathione S-transferase mu 1 (GSTM1), a hepatic high-expressed phase II detoxification enzyme, is closely associated with the incidence of alcohol-related liver disease (ALD). However, whether and how hepatic GSTM1 determines the development of ALD is largely unclear. This study was designed to elucidate the role and potential mechanism(s) of hepatic GSTM1 in the pathological process of ALD. Methods GSTM1 was detected in the liver of various ALD mice models and cultured hepatocytes. Liver-specific GSTM1 or/and micro (miR)-743a-3p deficiency mice were generated by adenoassociated virus-8 delivered shRNA, respectively. The potential signal pathways involving in alcohol-regulated GSTM1 and GSTM1-associated ALD were explored via both genetic manipulation and pharmacological approaches. Results GSTM1 was significantly upregulated in both chronic alcohol-induced mice liver and ethanol-exposed murine primary hepatocytes. Alcohol-reduced miR-743a-3p directly contributed to the upregulation of GSTM1, since liver specific silencing miR-743a-3p enhanced GSTM1 and miR-743a-3p loss protected alcohol-induced liver dysfunctions, which was significantly blocked by GSTM1 knockdown. GSTM1 loss robustly aggravated alcohol-induced hepatic steatosis, oxidative stress, inflammation, and early fibrotic-like changes, which was associated with the activation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), and p38. GSTM1 antagonized ASK1 phosphorylation and its downstream JNK/p38 signaling pathway upon chronic alcohol consumption via binding with ASK1. ASK1 blockage significantly rescued hepatic GSTM1 loss-enhanced disorders in alcohol-fed mice liver. Conclusions Chronic alcohol consumption-induced upregulation of GSTM1 in the liver provides a feedback protection against hepatic steatosis and liver injury by counteracting ASK1 activation. Down-regulation of miR-743a-3p improves alcohol intake-induced hepatic steatosis and liver injury via direct targeting on GSTM1. The miR-743a-3p–GSTM1 axis functions as an innate protective pathway to defend the early stage of ALD. Graphical Abstract

Penthorum chinense Pursh (P. chinense), a functional food, has been applied to protect the liver against alcohol-related fatty liver disease (ALD) for a long history in China. This study was designed to evaluate the ameliorative activity of the polyphenolic fraction in P. chinense (PGF) depending on the relief of ALD. The ALD mouse model was established by exposing the mice to a Lieber-DeCarli alcohol liquid diet. We found that PGF administration significantly ameliorated alcohol-induced liver injury, steatosis, oxidative stress, and inflammation in mice. Furthermore, alcohol-increased levels of the critical hepatic lipid synthesis proteins sterol regulatory element binding transcription factor (SREBP-1) and diacylglycerol o-acyltransferase 2 (DGAT2) were attenuated by PGF. Similarly, PGF inhibited the expression of the lipid transport protein very low-density lipoprotein receptor (VLDLR). Interestingly, PGF restored alcohol-inhibited expression of carnitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-activated receptor alpha (PPARα), essential fatty acid β-oxidation proteins. Mechanistic studies revealed that PGF protects against alcohol-induced hepatocyte injury and lipid deposition via the SIRT1/AMPK signaling pathway. In sum, this research clearly demonstrated the protective effects of PGF against ALD, which was mediated by activating SIRT1/AMPK pathways in hepatocytes. We provide a new theoretical basis for using P. chinense as a functional food in ALD.

This study aimed to evaluate the protective role and potential mechanisms of Xie Zhuo Tiao Zhi decoction (XZTZ) on alcohol-associated liver disease (ALD). XZTZ significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration. Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by XZTZ, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by XZTZ. In conclusion, XZTZ demonstrates potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease.

BackgroundHigh intake of ultra-processed food (UPF) has been associated with increased risk of chronic kidney disease(CKD), but the results remain inconsistent. We therefore performed this systematic review and dose–response meta-analysis of observational studies that shed light on the association between UPF consumption and the risk of CKD.MethodsA systematic literature search of PubMed, Embase, Web of Science, Scopus and China National Knowledge Infrastructure (CNKI) databases was carried out to find the eligible articles published up to October 31, 2023. Random-effects or fixed-effects models were used to pool the relative risks(RRs) and their 95% confidence intervals (CIs).The potential sources of heterogeneity across studies were examined using the Cochran’s Q test and I-square(I2). Publication bias was examined using the visual inspection of asymmetry in funnel plots and quantified by Begg’s and Egger’s tests.ResultsEight studies (six cohort and two cross-sectional studies) exploring the association between UPF consumption and risk of CKD, were included in the final analysis. The pooled analyses revealed that high consumption of UPF was associated with an increased risk of CKD (RR = 1.25; 95%CI: 1.09–1.42, p

ABSTRACT: The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007‐2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (β = ‐0.209 (95% CI: ‐0.310, ‐0.114)), and caused an increased Tg concentration (β = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and β =‐0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and β =‐0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.

Mineralization characterized by Au, Hg, and Tl enrichment is rare, and research on Au, Hg, and Tl mineralization is limited. The Lanmuchang Au–Hg–Tl deposit is located in the “Golden Triangle” of Yunnan, Guizhou, and Guangxi Provinces in China. In this study, we used scanning electron microscopy (SEM), electron microprobe analysis (EPMA), and a Tescan integrated mineral analyzer (TIMA) to analyze the mineral composition and distribution of the different types of ores and identify the occurrence state and enrichment mechanism of ore-forming elements in the Lanmuchang deposit. The results show that the primary ore minerals in the Lanmuchang deposit are pyrite, cinnabar, and lorandite. Cinnabar is the primary carrier of Hg (>90%), and pyrite is the primary carrier of Tl (>60%). Gold, Hg, and Tl primarily occur as solid solutions in hydrothermal pyrite, whereas they primarily occur as nano-scale particles in diagenetic pyrite. The substitution of As for S in hydrothermal pyrite promotes Au enrichment. The coupled substitution of 2Fe2+ ⇔ Tl+ + As3+ may be a significant Tl incorporation mechanism and promotes the occurrence of Hg in pyrite. The As and Se contents and Cu/Au and Co/Ni ratios of the hydrothermal pyrite demonstrate that the ore-forming fluid was mostly in a low-temperature, low-salinity, almost-neutral pH, and nearly reducing environment. The results show that the mineralization of the Lanmuchang deposit is associated with the cooling, oxidation, water–rock interaction, and boiling processes of the ore-forming fluid(s).

ABSTRACTBackground Acute lung injury (ALI) is a severe and often fatal pulmonary disease. Current treatments for ALI and acute respiratory distress syndrome (ARDS) are limited. Natural product metabolites have shown promise as therapeutic alternatives. However, the effects of Licochalcone B (LCB) on ALI are largely unknown.Methods We investigated the effects of LCB on lipopolysaccharide-challenged mice and human pulmonary microvascular endothelial cells. Cell viability, apoptosis, and ROS production were assessed. Lung tissue histopathology and oxidative stress and inflammation markers were evaluated. Protein expression levels were measured.Results LCB had no cytotoxic effects on cells and increased cell viability. It reduced apoptosis and ROS levels in cells. In mice with ALI, LCB decreased lung tissue weight and improved oxidative stress and inflammation markers. It also enhanced expression levels of Nrf2, HO-1, and NQO1 while reducing Keap1.Conclusion LCB protects against LPS-induced acute lung injury in cells and mice. The Keap1/Nrf2 pathway may be involved in its protective effects. LCB shows potential as a strategy to alleviate ALI caused by LPS.

BackgroundMycoplasma pneumoniae pneumonia (MPP) is common among children, but the impact of atopy on MPP severity in children is unknown. This study investigated whether atopic vs. nonatopic children had greater MPP severity.MethodsRetrospective analysis was conducted on 539 (ages 3–14 years) patients who were hospitalized in the First Affiliated Hospital of Anhui Medical University for MPP between January 2018 and December 2021, 195 were atopic and 344 were nonatopic. Of them, 204 had refractory MPP, and 335 had general MPP. And of atopic children, 94 had refractory MPP, and 101 had general MPP. Data on demographic and clinical characteristics, laboratory findings, clinical treatments were analyzed.ResultsSignificantly more boys with MPP were atopic than nonatopic (P

Southwest Guizhou mining area is a typical karst development mining area in China. Under the influence of mining, the height of karst roof water conducting cracks is abnormally developed. During the rainy season, atmospheric precipitation is extremely easy to enter the underground working face through ultra-high water conducting channels, causing water inrush disasters at the working face, seriously affecting the normal production of the mine. Therefore, based on the analysis of the occurrence characteristics of karst caves in Xintian Coal Mine, the development rules of karst roof water conducting fracture zones during mining were studied by means of on-site measurement, indoor simulation, and theoretical analysis. The development mechanism of ultra-high water conducting fractures was revealed. The results show that: ①The roof karst caves in the study area have obvious zonation phenomenon from top to bottom in the layers such as the surface, the Yulongshan section, and the Changxing Formation. The surface water holes develop along the gullies, and the karst caves in the upper and middle parts of the strong aquifer in the Yulongshan section develop, presenting different forms of beads. The Changxing Formation only locally hosts karst caves with smaller diameters; ② Karst caves in karst aquifers have an important impact on water conducting fractures. Without karst caves, the development height of water conducting fractures is 43.1 m, and the fracture mining ratio is 14.4. Under karst caves, the development of water conducting fractures is abnormal, with a height of 173.1 m, and a fracture mining ratio of 57.7, which communicates with the strong limestone aquifer in the Yulong Mountain section; ③ Karst roof water conducting fissures consist of two parts: mining upward fissures and karst cave instability downward fissures. Under the influence of mining, karst caves become unstable under the combined action of concentrated stress and mining additional stress, and are prone to form downward fissures, which communicate with mining upward fissures, ultimately forming a special ultra-high water conducting fissure in southwestern Guizhou mining area.

Abstract Traditional Chinese medicine (TCM) has been used for centuries to prevent and treat a variety of illnesses, and its popularity is increasing worldwide. However, the clinical applications of natural active components in TCM are hindered by the poor solubility and low bioavailability of these compounds. To address these issues, Chinese medicine self-assembly nanostrategy (CSAN) is being developed. Many active components of TCM possess self-assembly properties, allowing them to form nanoparticles (NPs) through various noncovalent forces. Self-assembled NPs (SANs) are also present in TCM decoctions, and they are closely linked to the therapeutic effects of these remedies. SAN is gaining popularity in the nano research field due to its simplicity, eco-friendliness, and enhanced biodegradability and biocompatibility compared to traditional nano preparation methods. The self-assembly of active ingredients from TCM that exhibit antitumour effects or are combined with other antitumour drugs has generated considerable interest in the field of cancer therapeutics. This paper provides a review of the principles and forms of CSAN, as well as an overview of recent reports on TCM that can be used for self-assembly. Additionally, the application of CSAN in various cancer diseases is summarized, and finally, a concluding summary and thoughts are proposed. We strongly believe that CSAN has the potential to offer fresh strategies and perspectives for the modernization of TCM.

Abstract A lightweight and portable spectrometer is desirable for miniaturization and integration. The unprecedented capability of optical metasurfaces has shown much promise to perform such a task. We propose and experimentally demonstrate a compact high-resolution spectrometer with a multi-foci metalens. The novel metalens is designed based on wavelength and phase multiplexing, which can accurately map the wavelength information into its focal points located on the same plane. The measured wavelengths in the light spectra agree with simulation results upon the illumination of various incident light spectra. The uniqueness of this technique lies in the novel metalens that can simultaneously realize wavelength splitting and light focusing. The compactness and ultrathin nature of the metalens spectrometer render this technology have potential applications in on-chip integrated photonics where spectral analysis and information processing can be performed in a compact platform.

Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug doxorubicin (DOX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. However, peptide ligands composed of natural L-configuration amino acids have the defects of easy enzymatic degradation and insufficient biological stability. In this study, two new PDCs (LT7-SS-DOX and DT7-SS-DOX) were designed and synthesized by conjugating a transferrin receptor (TfR) peptide ligand LT7 (HAIYPRH) and its retro-inverso analog DT7 (hrpyiah), respectively, with DOX via a disulfide bond linker. Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX. In conclusion, the coupling of antitumor drugs with the DT7 peptide ligand can be used as a promising strategy for the further development of stable and efficient PDCs with the potential to facilitate TfR-targeted drug delivery.

Pro-inflammatory factor-associated vascular cell adhesion molecule 1 (VCAM1) activation initiates cardiovascular events. This study aimed to explore the protective role of nuciferine on TNFα-induced VCAM1 activation. Nuciferine was administrated to both high-fat diet (HFD)-fed mice and the TNFα-exposed human vascular endothelial cell line. VCAM1 expression and further potential mechanism(s) were explored. Our data revealed that nuciferine intervention alleviated VCAM1 activation in response to both high-fat diet and TNFα exposure, and this protective effect was closely associated with autophagy activation since inhibiting autophagy by either genetic or pharmaceutical approaches blocked the beneficial role of nuciferine. Mechanistical studies revealed that Akt/mTOR inhibition, rather than AMPK, SIRT1, and p38 signal pathways, contributed to nuciferine-activated autophagy, which further ameliorated TNFα-induced VCAM1 via repressing AP1 activation, independent of transcriptional regulation by IRF1, p65, SP1, and GATA6. Collectively, our data uncovered a novel biological function for nuciferine in protecting VCAM1 activation, implying its potential application in improving cardiovascular events.

Tenghuang Jiangu Capsule (THJGC) is a Chinese herbal formula used for the treatment of osteoporosis and osteoarthritis in China, but its mechanism for treating osteoporosis is not clear. The aim of this study was to investigate the therapeutic effect of THJGC on osteoporosis and its intrinsic mechanism through network pharmacology and experimental validation. Drugs and potential targets were obtained from several reliable databases through network pharmacology, and these targets were integrated and analyzed using bioinformatics and molecular docking strategies. Quercetin, lignans and kaempferol were identified as key components, and the key targets included Akt1, MAPKs, and CASP3. Subsequently, UPLC-MS/MS analysis confirmed the presence of components in THJGC for the treatment of osteoporosis. In addition, using ex vivo and in vivo models, it was confirmed that THJGC inhibited H2O2-induced ROS generation and apoptosis, and reduced OVX-induced bone loss in a mouse model of osteoporosis. Our data suggest that THJGC has antioxidant, bone formation-promoting, bone resorption-inhibiting, and MC3T3-E1 apoptosis-reducing effects, and thus has anti-osteoporotic properties. In conclusion, it may be a promising pharmacologic adjuvant treatment for osteoporosis.

Based on the phase change properties of vanadium dioxide (VO2), we propose a terahertz metamaterial absorber that can be switched flexibly between ultra-broadband and dual bands. The absorber consists of a resonator array above a conductive ground layer separated with a dielectric spacer, which includes four square-loop VO2 resonators and a crossed gold resonator in each unit cell. By changing the conductivity of VO2 through thermal control, the absorber can achieve the switching between ultra-broadband absorption and dual-band absorption. Simulation results show that at high temperature, the absorber realizes more than 90% absorption bandwidth in the range of 3.98 to 9.06 THz, which can be elucidated by the wave-interference theory and impedance matching theory. At low temperature, up to 95% of the dual-band absorption occurs at 5.95 and 6.95 THz, which originates the dipole mode and nonlocal surface-Bloch mode of metal resonators. In addition, the absorber has the advantages of polarization-independence and wide-angle absorption. Compared with previous studies, our design can switch between two absorption modes and its absorption performance is greatly improved. The proposed absorber design scheme is expected to expand terahertz devices and enable a variety of applications in the terahertz range, such as modulation, sensing, stealth, and switching devices.

The distribution pattern of species is determined by the environment and their adaptability to the environment. Qinghai-Tibet Plateau has become a natural laboratory for studying adaptive evolution due to its extreme environmental characteristics such as low temperature, low oxygen, high salinity and high ultraviolet radiation (UVR). Fish are sensitive to the environmental stress, so they are ideal materials for studying high-altitude adaptation of animals. Previous studies have mainly focused on the adaptability of plateau species, but the reasons why plain species cannot spread to the plateau have been ignored. In this study, stress experiments and histological experiments were used to compare the tolerance of six Barbini fishes (family: Cyprinidae) distributed at different altitudes and regions to low temperature, low oxygen, salinity and UVR. Results showed that the tolerance of fishes to high-altitude environmental stress factors was closely related to the environmental stress of their main habitats. The high-altitude fish Gymnocypris eckloni had strong tolerance to all stress factors, while the other five fishes from middle and low altitudes could not adapt to single or multiple stress factors, with significant interspecific differences. Among these factors, middle- and low-altitude fishes showed common low tolerance to UVR, suggesting that high UVR, the factor lacking at low altitude areas, plays an important role. Moreover, during the uplift of the Qinghai-Tibet Plateau, Schizothorax fish disappeared from the middle of the plateau. We speculate that this was caused by its intolerance to the increasingly extreme plateau environment, especially salinity.

Abstract Background Alcoholic liver disease (ALD) is one of the most prevalent chronic liver disease worldwide. Alcohol-induced alterations in hepatic lipids play an important role in ALD develpoment and progression. The present study aimed to thoroughly describe the changes of lipid profiling in liver of mice with early-stage alcoholic liver disease. Methods C57BL/6J male mice aged 7-week were randomized into alcohol-fed (AF) group and pair-fed control group (PF) (n = 10 per group). The early stage of ALD was induced with Lieber-DeCarli liquid diet. The lipids profiling was analyzed by absolute quantitative lipidomics with UHPLC-QTRAP-MS/MS. Results Alcohol intake significantly increased the levels of alanine aminotransferase (ALT) in plasma, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and triacylglycerols (TAG) levels in liver. Lipidomis analyses showed that 41 TAGs were up-regulated and 8 TAGs were down-regulated in response to alcohol intake. The 8 decreased TAGs were with more double bond, longer carbon chain length and mostly contained docosahexaenoic acid (C22:6n-3) and eicosapentaenoic acid (C20:5n-3), compared with the up-regulated TAGs. Furthermore, the down-regulated TAG(56:9)_FA20:5 was inversely associated with ALT and IL-6 levels. In addition, several altered lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE) and hexosylceramides (HCER) were all significantly decreased in response to alcohol consumption, especially HCer(18:1/22:0), with the top reduction among all the down-regulated lipids. Conclusions These findings suggest that not only the up-regulated lipids, alcohol-induced reduction in some specific lipids might also contribute to the ALD development, especially TAG(56:9)_FA20:5 and HCer(18:1/22:0). Their physiological functions and effects on ALD development warrants further investigation.

The corona virus disease 2019 (COVID-19) global pandemic has had an unprecedented and persistent impact on oncological practice, especially for patients with lung cancer, who are more vulnerable to the virus than the normal population. Indeed, the onset, progression, and prognosis of the two diseases may in some cases influence each other, and inflammation is an important link between them. The original chronic inflammatory environment of lung cancer patients may increase the risk of infection with COVID-19 and exacerbate secondary damage. Meanwhile, the acute inflammation caused by COVID-19 may induce tumour progression or cause immune activation. In this article, from the perspective of the immune microenvironment, the pathophysiological changes in the lungs and whole body of these special patients will be summarised and analysed to explore the possible immunological storm, immunosuppression, and immune escape phenomenon caused by chronic inflammation complicated by acute inflammation. The effects of COVID-19 on immune cells, inflammatory factors, chemokines, and related target proteins in the immune microenvironment of tumours are also discussed, as well as the potential role of the COVID-19 vaccine and immune checkpoint inhibitors in this setting. Finally, we provide recommendations for the treatment of lung cancer combined with COVID-19 in this special group.

Background:. Adipose tissue thermogenic activities use fatty acids from lipolysis for heat generation. Therefore, a tight coupling between lipolysis and thermogenesis is physiologically imperative in maintaining not only body temperature but also lipids homeostasis. Adipose tissue dysfunction contributes to alcoholic liver disease (ALD). Here, studies were conducted to examine how alcohol intake affects adipose tissue thermogenic activities and whether altered adipose tissue thermogenesis contributes to ALD. Methods:. Both the Lieber-DeCarli and the NIAAA mouse models of ALD were used. Denervation surgery in epididymal fat pads was performed. CL316,243, a selective β3-adrenoceptor agonist, SR59230A, a selective β3 adrenoceptor (ADRB3) antagonist, and rapamycin, a selective mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, were administrated through i.p. injection. Adipocyte-specific Prdm16 knockout mice were subjected to alcohol-containing diet chronically. Results:. Chronic alcohol consumption, which enhances adipose tissue lipolysis, inhibits thermogenic activities of beige adipocytes in inguinal white adipose tissue (WAT), leading to an uncoupling status between lipolysis and thermogenesis in WAT at both basal and ADRB3 stimulation states. CL316,243 administration exacerbates liver pathologies of ALD. Alcohol intake inhibits mTORC1 activities in WAT. In mice, mTORC1 inhibition by rapamycin inhibits the thermogenesis of iWAT, whereas enhancing WAT lipolysis. Further investigations using adipocyte-specific Prdm16 knockout mice revealed that functional deficiency of beige adipocytes aggravates liver pathologies of ALD, suggesting that the inhibitory effect of alcohol on WAT browning/thermogenesis contributes to ALD pathogenesis. Conclusion:. Chronic alcohol consumption induces an “uncoupling status” between lipolysis and browning/thermogenesis in WAT by inhibiting mTORC1 activation. Diminished WAT browning/thermogenesis, concomitant with enhanced lipolysis, contributes to ALD pathogenesis.

BackgroundStudies have shown that young maternal age at childbirth can increase the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring, but a study of the U.S. population has not been reported. Moreover, there is no reported research on young and advanced maternal age at childbirth and whether it can contribute to the risk of learning disability (LD) in offspring.MethodsThis study evaluated the association between young and advanced maternal age at childbirth and offspring risk of ADHD and LD in the U.S. population. Using data from 8,098 participants included in the National Health and Nutrition Examination Survey (NHANES) conducted in 1999–2004, we analyzed the association between maternal age at childbirth and ADHD and LD risk in offspring. Odds ratios (ORs) and 95% confidence intervals (CIs) for maternal age at childbirth in association with ADHD and LD risk in offspring were estimated using multivariate logistic regression models after adjustment for age, sex, race, body mass index (BMI), poverty income ratio, smoking status during pregnancy, and NHANES cycle. Restricted cubic spline (RCS) models were used to evaluate potential non-linear relationships. Sensitivity analyses were performed to ensure the reliability of the results.ResultsAmong all participants, the offspring of subjects with a maternal age at childbirth of 18–24 years had an increased risk of ADHD (OR = 1.34, 95% CI: 1.01, 1.79) and LD (OR = 1.36, 95% CI: 1.06, 1.79) or either ADHD or LD (OR = 1.48, 95% CI: 1.20, 1.81). Additionally, compared with subjects with a maternal age at childbirth of 25–29 years, subjects with a maternal age at childbirth of 35–39 years had lower odds of having offspring with ADHD (OR = 0.60, 95% CI: 0.36, 1.00) and higher odds of having offspring with LD (OR = 1.34, 95% CI: 1.01, 1.78). The relationship between maternal age at childbirth and LD risk presented a U-shaped curve.ConclusionsThese results provide epidemiological evidence showing that young and advanced maternal age at childbirth are associated with ADHD and LD risk.

Pyroptosis is a type of regulated cell death that relies on caspases, vesicles, and the cleavage of gasdermin proteins (which create pores in the cell membrane). The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, which is involved in this process, is the most widely studied inflammasome. Caspase-1 activates pro-inflammatory cytokines, such as IL-1β and IL-18. Gasdermin D (GSDMD) is the most important executive protein. GSDMD, a substrate rather than an upstream protease, determines the occurrence of pyroptosis. Pyroptosis is essential for maintaining body homeostasis, but excessive or poorly regulated cell death can aggravate the inflammatory response. Undoubtedly, this will be an important direction for future research on Alzheimer’s disease (AD). Here, we review recent research progress on the morphological characteristics, molecular mechanisms, and role of pyroptosis in the context of AD, thereby providing new directions for identifying potential disease biomarkers and treatment strategies for AD.

In order to study the seepage process of rainwater on granite residual soil cut slopes, a numerical model for seepage analysis of granite residual soil cut slopes was established. Then, by applying the rainfall boundary condition, the seepage path of rainwater on the slope was analyzed under the condition of rainfall infiltration. Finally, during rainwater seepage, the volumetric water content and pore-water pressure change characteristics inside the slope were analyzed, and the seepage mechanism of rainwater in the granite residual soil slope was revealed. The results show that, under the condition of rainfall infiltration, the surface area of the slope gradually forms a saturated area in a temporary stable state. As the saturated area in the temporary stable state gradually extends to the inside of the slope, the area gradually increases and a groundwater level recharge area is gradually formed at the foot of the slope. Rainwater infiltration changes the original stable state of the slope, causing the granite residual soil slope to change from the two original distribution states of the unsaturated area and saturated area to the three distribution states of the temporarily stable saturated area, unsaturated area, and saturated area from top to bottom. The volumetric moisture content of slope-monitoring points increased gradually with an increase in the duration, and the overall distribution showed an “S” shape. The infiltration of rainwater causes the pore-water pressure of the granite residual soil to increase gradually, and matric suction gradually disappears. In particular, the disappearance of the matric suction at the foot of the slope will lead to the gradual weakening of the shear strength of the slope soil, thus affecting the slope stability.

This present study was designed to explore the protective role of Lactobacillus plantarum ZJUIDS14 against Non-alcoholic Fatty Liver Disease (NAFLD) in a high-fat-diet (HFD)-induced C57BL/6 mice model. The probiotic (109 CFU/every other day) was administered by oral gavage for 12 weeks. We found that L. plantarum ZJUIDS14 intervention significantly alleviated HFD related hepatic steatosis, liver damage, insulin resistance, and increased hepatic expression of peroxisome proliferator activated receptor α (PPAR-α) while stimulating the activation of AMP-activated protein kinase (AMPK). Furthermore, L. plantarum ZJUIDS14 improved mitochondrial function as reflected by an increase in dynamin related protein 1 (DRP1) and a decrease of proteins associated with oxidative phosphorylation (OXPHOS) after the treatment. Additionally, mice from the L. plantarum ZJUIDS14 group had a restored intestinal flora and homeostasis involving Coprostanoligenes group, Ruminococcaceae UCG-014, Allobaculum, Ruminiclostridium 1, and Roseburia. Meanwhile, these five genera exhibited a significant (negative or positive) association with ileum inflammation mRNA levels and SCFA contents, by Spearman’s correlation analysis. In general, our data demonstrated that L. plantarum ZJUIDS14 mitigates hepatic steatosis and liver damage induced by HFD. Specifically, they strengthened the integrity of the intestinal barrier, regulated gut microbiota, and improved mitochondrial function. Our data provide an experimental basis for L. plantarum ZJUIDS14 as a promising candidate to prevent NAFLD.

Ultraviolet radiation (UVR) is a ubiquitous environmental factor and with complex and diverse effects on organisms, and the UVR tolerance of species varies due to selection, adaptation and evolution. This study aimed to improve our understanding of the interspecific differences in UVR tolerance of fishes. First, we compared skin histology between high-altitude fishes and their low-altitude relatives. Second, we assessed the skin histological changes of 22 fish species after UVR exposure and quantified their damage levels. Finally, the factors affecting the difference in UVR tolerance among fishes were studied. Thin or absent scales was a common characteristic of high-altitude fishes in different taxonomic groups, but other skin structure parameters (the thickness of the dermis and epidermis, the size and number of mucous and club cells) did not show convergence. After UVR exposure, the size and number of mucous cells and club cells in the experimental fishes were generally reduced, but the changes in epidermal and dermal thickness varied among species. The change rata of melanin area was strong negatively correlated with the level of damage, indicating that increased melanin was helpful to reduce UVR damage. On the whole, the skin histological changes of high-altitude fishes after UVR exposure did not differ from those of low-altitude fishes. However, the epidermis and dermis of Gymnocypris eckloni and Oncorhynchus mykiss, which had the highest UVR tolerance, were nonpathologically thickened, indicating that they may contribute to UVR tolerance. There were significant interspecific differences in UVR tolerance among the experimental fishes, with high-altitude and cold water fishes showing stronger UVR tolerance. Interestingly, some low-altitude cold water fish (e.g., O. mykiss) also showed high UVR tolerance, suggesting that besides high-altitude adaptation, low-temperature adaptation also may play an important role in organismal adaptation to UVR.

This work proposes a novel unsupervised deep non-negative matrix factorization (NMF) model called AGDNMF by deep exploration of the structure of the original data. Compared with the existing NMF research results, the model explores the deep association of data and constructs accurate spatial structure from a new perspective. Specifically, for the purpose of effectively learning low-dimensional representations of data. This work constructs a deep NMF method to approximate the coding structure of the original data, which enables AGDNMF to learn the hierarchical mapping relationship between the categories of the original data, and learn the hidden association information of the data from low-to-high in the middle layer. Moreover, the model gives an adversarial graph regularization representation for the manifoldization of data structures to push away the spatial distances between different sample clusters. Finally, based on the mathematical model of the proposed algorithm, the optimization strategy and convergence proof are given. Extensive experiments and data analysis demonstrate that the proposed model outperforms state-of-the-art unsupervised NMF methods.

Abstract Background Few studies have reported the prevalence of metabolic syndrome (MS) and examined relationships between socioeconomic status and MS in rural China. This study aimed to evaluate the prevalence of MS and MS components as well as their associations with socioeconomic status among rural Chinese adults. Methods A cross-sectional study of 26,836 participants aged 20 years and older was conducted from June to December 2012 in Yuhuan City, Zhejiang Province, China, which is located on Yuhuan Island. A multivariable logistic regression model was used to identify risk factors for MS and their possible interactions. Results Among 26,836 subjects with an average age of 53.4 ± 14.0 years, 59% were female. The overall prevalence of MS was 20.5%, and there was a significant sex difference in the prevalence (15.1% for males vs. 24.2% for females, P

The Paleo-Asian Ocean controlled the tectonic evolution of Northeast Asia and formed the Karamaili Orogenic Belt in the eastern Junggar basin. However, the chronological constrain of the evolution of the paleo-Karamaili Ocean remains unclear. In this study, we focused on the sandstones of the Lower Jurassic Badaowan and Sangonghe Formations in the Dongdaohaizi Depression, Junggar basin near the Karamaili orogenic belt. After detailed observations and descriptions of the macroscopic features of the sandstone, we obtained information on petrology and geochronology. The Dickinson diagrams indicate that the provenance area had the characteristics of a transitional and recycling provenance, which is a collisional orogenic belt with a background of oceanic-continental subduction. The detrital zircon ages of the Lower Jurassic sediments in the Dongdaohaizi Depression can be divided into three peaks: ~300 Ma, ~420 Ma, and ~510 Ma for Badaowan Formation and ~310 Ma, ~410 Ma, and ~500 Ma for Sangonghe Formation. The youngest detrital zircon age is 241 ± 2 Ma, representing an Early Permian depositional age. Combined with previous studies, the sediments in the study area represent a provenance from the Karamaili Ocean. During the Early Jurassic, the consistent subduction of the residual East Junggar Ocean induced continuous uplift in the Karamaili region, resulting in an increasing exposure of deep-seated rocks to provide sedimentary material. According to the tectonic background of the Junggar region, the results indicate that the Karamaili Ocean, as part of the Paleo-Asian Ocean, experienced three evolutionary stages: Cambrian-Early Silurian (460–540 Ma), Late Silurian-Early Carboniferous (360–440 Ma), and Late Carboniferous–Triassic (240–340 Ma).

Dietary fat composition is closely associated with the pathological development of alcoholic liver disease (ALD). Fat enriched with saturated fatty acids protects whereas with polyunsaturated fatty acids aggravates alcohol-induced liver injury. However, limited study has addressed how monounsaturated fatty acids (MUFAs) determines the pathological process of ALD. Our study was conducted to evaluate the effect of MUFAs-enriched-camellia seed oil (CSO) on alcohol-induced liver injury. The ALD model was established by feeding C57BL/6 mice with Lieber-DeCarli diet, and with either CSO or polyunsaturated fatty acids (PUFAs)-enriched-corn oil (CO) as fat source. After 4-week-intervention, CSO-feed rescued alcohol-induced liver injury compared to CO-feed, evidenced by measurements of plasma ALT activity, H&E stain, and hepatic cleaved-Caspase-3 expression. Besides, CSO-feed alleviated alcohol-induced oxidative stress, associated with NRF2 and Hif-1α expressions improvement. The reduction of F4/80 immunostaining and the decreased expressions of hepatic TNF-α and IL-6 suggested CSO-feed improved alcohol-induced inflammation. The mechanistic analysis showed that the inhibition of ASK1 and MAPKs might contribute to CSO-protected liver injury. Notably, we observed CSO-feed relieved the gut microbiota disturbance with the decreased Firmicutes and Turicibater, and the increased Bacteroidota, Alloprevotella, and Bacteroides, and reduced circulatory endotoxin level and lipolysis of adipose tissue, which are the known pathogenic factors in alcohol-induced liver injury. Unexpectedly, CSO induced more hepatic steatosis than CO-feed. In conclusion, CSO attenuated chronic alcohol consumption-induced liver injury but enhanced hepatic steatosis. CSO could be a potential dietary choice for alcoholic individuals with liver injury.

Carboxycellulose nanofibers (CNFs) promise to be a sustainable and inexpensive alternative material for polymer electrolyte membranes compared to the expensive commercial Nafion membrane. However, its practical applications have been limited by its relatively low performance and reduced mechanical properties under typical operating conditions. In this study, carboxycellulose nanofibers were derived from wood pulp by TEMPO oxidation of the hydroxyl group present on the C6 position of the cellulose chain. Then, citric acid cross-linked CNF membranes were prepared by a solvent casting method to enhance performance. Results from FT-IR spectroscopy, 13C NMR spectroscopy, and XRD reveal a chemical cross-link between the citric acid and CNF, and the optimal fuel cell performance was obtained by cross-linking 70 mL of 0.20 wt % CNF suspension with 300 µL of 1.0 M citric acid solution. The membrane electrode assemblies (MEAs), operated in an oxygen atmosphere, exhibited the maximum power density of 27.7 mW cm−2 and the maximum current density of 111.8 mA cm−2 at 80 °C and 100% relative humidity (RH) for the citric acid cross-linked CNF membrane with 0.1 mg cm−2 Pt loading on the anode and cathode, which is approximately 30 times and 22 times better, respectively, than the uncross-linked CNF film. A minimum activation energy of 0.27 eV is achieved with the best-performing citric acid cross-linked CNF membrane, and a proton conductivity of 9.4 mS cm−1 is obtained at 80 °C. The surface morphology of carboxycellulose nanofibers and corresponding membranes were characterized by FIB/SEM, SEM/EDX, TEM, and AFM techniques. The effect of citric acid on the mechanical properties of the membrane was assessed by tensile strength DMA.

In order to solve the problem that building engineering construction needs to consume a lot of energy and cause environmental pollution, which will pose a great pressure on urban resources and environment, this paper proposes that, in building engineering construction, appropriate green construction technology must be selected in combination with the actual situation, so as to effectively reduce the energy consumption of building engineering and improve the use efficiency of building engineering. Firstly, good thermal insulation nanomaterials are selected, which are cost-effective, safe, and nontoxic and has small thermal conductivity, large heat storage coefficient, stable chemical performance, and good construction performance. Secondly, it also needs to be selected according to the actual service life of the building. Because the current evaluation system is mostly aimed at the planning and design stage, and the structure occupies a large part in the building, for example, the impact on the construction period accounts for more than 50% and the impact on the cost accounts for 35%. Therefore, Duan Xiaorong and others established the grey cluster evaluation model of green building structure design based on the triangular whitening weight function. Finally, according to the relevant national regulations, this paper optimizes the design of green buildings based on the basic principles of energy conservation and emission reduction, high quality, and high efficiency.

Background: Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), induces hepatocyte necrosis, and leads to acute liver failure. Atractylenolide I (AO-I), a phytochemical found in Atractylodes macrocephala Koidz, is known to exhibit antioxidant activity. However, its clinical benefits against drug-induced liver injury remain largely unclear.Purpose: This study aimed at evaluating the protective effects of AO-I against APAP-induced acute liver injury.Methods: C57BL/6 mice were administered 500 mg/kg APAP to induce hepatotoxicity. AO-Ⅰ (60 and 120 mg/kg) was intragastrically administered 2 h before APAP dosing. Liver histopathological changes, oxidative stress and hepatic inflammation markers from each group were observed.Results: We observed that AO-I treatment significantly reversed APAP-induced liver injury, as evidenced by improved plasma alanine transaminase (ALT) level, aspartate aminotransferase (AST) and liver H&E stain. APAP treatment increased liver malondialdehyde (MDA) content and reduced catalase (CAT) and glutathione (GSH) level; however, these effects were alleviated by AO-I intervention. Moreover, AO-I treatment significantly inhibited APAP-induced activation of pro-inflammatory factors, such as IL-1β, IL-6, and TNF-α, at both the mRNA and protein levels. Mechanistic studies revealed that AO-I attenuated APAP-induced activation of TLR4, NF-κB and MAPKs (including JNK and p38).Conclusion: AO-I mediates protective effects against APAP-induced hepatotoxicity via the TLR4/MAPKs/NF-κB pathways. Thus, AO-I is a candidate therapeutic compound for APAP-induced hepatotoxicity.

There are a large number of karst caves in the limestone rock strata in the karst mining area, and the karst water in rock strata seriously restricts the safe and efficient recovery of coal resources. In order to reveal the influence law of karst caves of rock strata on the evolution of water-conducting fissures in coal seam mining, the numerical simulation method in UDEC software is employed to analyze the development characteristics of water-conducting fissures in coal seam mining under the conditions of karst caves of different sizes. By comparing and analyzing the development characteristics of overlying fissures in rock strata and the displacement fields in coal seam mining under the conditions of different karst caves, the evolution law of water-conducting fissures in coal seam mining is obtained. The research results show that the size of karst cave directly affects the maximum height of the water-conducting fissures in the overlying rock strata in coal seam mining; when the thickness of the coal seam is 3.0 m, the larger the radius of karst cave is, the higher the development height of water-conducting fissures in the overlying rock strata is, and the greater the overall sinking displacement in the Yulongshan limestone is. When the radius of karst cave is between 10 m and 15 m, a through-type water-conducting channel is formed between the working face and the karst cave after the coal seam is mined, and the numerical simulation results are consistent with the field monitoring results. The research results provide an important reference for the prevention and treatment for water inrush disaster in karst mining areas.

Introduction. There is a common concern about the pain and rehabilitation of the knee after femoral retrograde intramedullary nailing. It is essential for early postoperative knee function required for physical self-maintenance in daily life. And a favorable rehabilitation of the knee usually promotes the quality of life. However, early rehabilitation is absent or insufficient for many patients in postoperative management. This retrospective study aims to evaluate the effect of early knee function improvement in comparison to postoperative fascia iliaca blocking (FIB) and multimodal drug injection (MDI). Patients and Methods. A retrospective analysis of 41 patients receiving femoral fracture treatment with retrograde intramedullary nailing, was performed during 2018–2020. 19 patients were treated with MDI as postoperative analgesia, and 22 patients were treated with FIB. Rehabilitation started on the first postoperative day and lasted for 3 months. Visual analog scale (VAS), the range of motion (ROM) of the knee, and single assessment numeric evaluation (SANE) were assessed. Results. There was no significant difference shown in any of the demographic, fracture types, and operative time. All patients performed regular and voluntary knee rehabilitation and weight-bearing at home following the instruction from the orthopedic staff. Pain in the FIB group at postoperative 1-day was milder (1.7 ± 1.1), compared with that in the MDI group (2.8 ± 1.3, p=0.038). There was a significant difference in VAS between two groups at postoperative 1-month (p=0.031), with a peak score in the FIB group (3.3 ± 0.9). At postoperative 3-month, both groups had pain relief with similar VAS (p=0.465). The ROM of the knee in both groups was continuously improved during the first three months. The SANE in the MDI group was significantly different compared with FIB at 1-month (p=0.026). However, scores of SANE were similar in both groups at 3 months (p=0.541). All patients were identified as fractures union at 9-month or 12-month follow-up. Conclusion. The knee pain was commonly experienced in this series of retrograde femoral nailings. Both MDI and FIB provided immediate and effective pain control after femoral fracture surgery. MDI was more beneficial to continuous pain control and knee rehabilitation in the early follow-up. The extent of pain relief and knee function improvement reached the same level at postoperative 3-month.

IntroductionCisplatin, a chemotherapeutic drug, is widely used for the treatment of various malignant tumors with good effects. However, cisplatin-induced nephrotoxicity is a major dose-limiting factor and a significant adverse event. Mannitol is used to reduce cisplatin-induced nephrotoxicity, which is controversial. This study aimed to evaluate the efficacy and safety of a hydration regimen containing mannitol against cisplatin-induced nephrotoxicity through a meta-analysis.MethodsPotential records from PubMed, EMBASE, Cochrane Library, and ClinicalTrials that met the inclusion criteria were included from inception to May 2021. Cochrane Collaboration tools were used to assess the risk of bias in the included studies. Jadad’s and NOS scores were applied to assess the quality of randomized controlled trials (RCTs) and case-control studies. A random-effects model or fixed-effects model was used depending on the heterogeneity. Subgroup analyses were performed to evaluate the potential study characteristics. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated.ResultsFour RCTs and seven case-control studies involving 4168 patients were included. Pooled results showed that mannitol use could reduce the incidence of cisplatin-induced nephrotoxicity (OR = 0.66, 95% CI [0.45–0.97], p = 0.03), especially reducing grade 3 nephrotoxicity events according to CTCAE 4.0 (OR = 0.37,95% CI [0.16–0.84]). Moreover, mannitol use was not significantly associated with creatinine clearance, serum creatine, and electrolyte disturbance (p > 0.05). Gastrointestinal cancer (OR = 0.36, 95% CI [0.15–0.83], p = 0.02) and urinary tract cancer (OR = 0.32,95% CI [0.14–0.73], p = 0.007) may be more sensitive to mannitol, although the test for overall effect was significantly different (OR = 0.66, 95% CI [0.49–0.89], p = 0.007). For patients with diabetes and hypertension, mannitol may worsen renal function (OR = 1.80, 95% CI [1.18–2.72], p = 0.006; OR = 2.19, 95% CI [1.50, 3.19], p < 0.0001, respectively). Mannitol may have a better protective effect when doses of mannitol were ≥ 25 g (OR = 0.58, 95% CI [0.39–0.88], p = 0.01) and doses of cisplatin < 75 mg/m2 (OR = 0.59, 95% CI [0.36–0.94], p = 0.03). It revealed that mannitol use was likely to cause nausea or vomiting (OR = 1.86, 95% CI [1.20–2.89], p = 0.006).ConclusionCurrent evidence revealed that mannitol was an effective and safe drug to reduce cisplatin-induced nephrotoxicity events, especially Grade 3 events. However, it may cause more nausea/vomiting events and deteriorate renal function in patients with diabetes or hypertension. We also found that mannitol had the best effect when mannitol was ≥ 25 g in total or cisplatin was < 75 mg/m2. Meanwhile, mannitol may have a better effect on gastrointestinal and urinary tract cancers.Systematic Review Registrationcrd. york. ac. uk/PROSPERO, CRD 42021253990

Background: Alcoholic liver disease (ALD) caused by chronic ethanol overconsumption is a common type of liver disease with a severe mortality burden throughout the world. The pathogenesis of ALD is complex, and no effective clinical treatment for the disease has advanced so far. Prolonged alcohol abstinence is the most effective therapy to attenuate the clinical course of ALD and even reverse liver damage. However, the molecular mechanisms involved in alcohol abstinence-improved recovery from alcoholic fatty liver remain unclear. This study aims to systematically evaluate the beneficial effect of alcohol abstinence on pathological changes in ALD.Methods: Using the Lieber-DeCarli mouse model of ALD, we analysed whether 1-week alcohol withdrawal reversed alcohol-induced detrimental alterations, including oxidative stress, liver injury, lipids metabolism, and hepatic inflammation, by detecting biomarkers and potential targets.Results: Alcohol withdrawal ameliorated alcohol-induced hepatic steatosis by improving liver lipid metabolism reprogramming via upregulating phosphorylated 5′-AMP -activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor-α (PPAR-α), and carnitine palmitoyltransferase-1 (CPT-1), and downregulating fatty acid synthase (FAS) and diacylglycerol acyltransferase-2 (DGAT-2). The activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), were significantly enhanced by alcohol withdrawal. Importantly, the abstinence recovered alcohol-fed induced liver injury, as evidenced by the improvements in haematoxylin and eosin (H&E) staining, plasma alanine aminotransferase (ALT) levels, and liver weight/body weight ratio. Alcohol-stimulated toll-like receptor 4/mitogen-activated protein kinases (TLR4/MAPKs) were significantly reversed by alcohol withdrawal, which might mechanistically contribute to the amelioration of liver injury. Accordingly, the hepatic inflammatory factor represented by tumour necrosis factor-alpha (TNF-α) was improved by alcohol abstinence.Conclusion: In summary, we reported that alcohol withdrawal effectively restored hepatic lipid metabolism and reversed liver injury and inflammation by improving metabolism reprogramming. These findings enhanced our understanding of the biological mechanisms involved in the beneficial role of alcohol abstinence as an effective treatment for ALD.

Receptor activator of nuclear factor-κB ligand (RANKL) has been found to induce osteoclastogenesis and bone resorption. However, the underlying molecular mechanisms remain unclear. Via conducting a series of biochemical experiments with in vitro cell lines, this study investigated the role and mechanism of NADPH oxidase 4 (Nox4) in RANKL-induced autophagy and osteoclastogenesis. In the current study, we found that RANKL dramatically induced autophagy and osteoclastogenesis, inhibition of autophagy with chloroquine (CQ) markedly attenuates RANKL-induced osteoclastogenesis. Interestingly, we found that the protein level of Nox4 was remarkably upregulated by RANKL treatment. Inhibition of Nox4 by 5-O-methyl quercetin or knockdown of Nox4 with specific shRNA markedly attenuated RANKL-induced autophagy and osteoclastogenesis. Furthermore, we found that Nox4 stimulated the production of nonmitochondrial reactive oxygen species (ROS), activating the critical unfolded protein response (UPR)-related signaling pathway PERK/eIF-2α/ATF4, leading to RANKL-induced autophagy and osteoclastogenesis. Blocking the activation of PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS scavenger (NAC) or PERK inhibitor (GSK2606414) significantly inhibited autophagy during RANKL-induced osteoclastogenesis. Collectively, this study reveals that Nox4 promotes RANKL-induced autophagy and osteoclastogenesis via activating ROS/PERK/eIF-2α/ATF4 pathway, suggesting that the pathway may be a novel potential therapeutic target for osteoclastogenesis-related disease.

Background and Aim: The worldwide prevalence of alcoholic liver disease (ALD) due to escalating alcohol consumption has presented an unprecedented pressure on human health. A few studies have determined long non-coding RNAs (lncRNAs) involved in the pathogenesis of liver diseases. However, the roles of lncRNAs in ALD development is still poorly understood.Methods: An ALD mouse model was established and confirmed. Expression profiles of lncRNAs were obtained by whole transcriptome sequencing. The altered lncRNAs in ALD mice were further verified by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions of these lncRNAs. In combination with miRNA and mRNA profiles, we constructed concise endogenous RNA (ceRNA) networks. The function of the most up/downregulated lnRNA was further verified and investigated in both ALD model and AML-12 cells.Results: Totally, five downregulated lncRNAs were obtained and verified in ALD mice. The GO term and KEGG pathway analyses revealed that the identified lncRNAs were associated with alcohol-induced hepatic oxidative damage, cellular inflammation, and lipid metabolism. Combination the differentially modulated miRNAs and mRNAs with ceRNA network analysis, we constructed five ceRNA networks and obtained 30 miRNAs and 25 mRNAs that may participate in ALD. Further, we verified and investigate the function of the most downregulated lnc_1700023H06Rik. Depletion lnc_1700023H06Rik reduced genes encoding for lipid metabolism, especially mRNA Acat2 (ENSMUST00000159697) and Pgrmc2 (ENSMUST00000058578) both in vivo and in vitro. Knocking down lnc_1700023H06Rik induced triglyceride accumulation and lactate dehydrogenase leakage in AML12 cells, consisting with that in alcohol-treated cells.Conclusion: The five remarkably downregulated lncRNAs in ALD mouse model were identified as novel biomarkers, highlighting the key role of lncRNAs in the development of ALD. The effect of lnc_1700023H06Rik plays a pivotal role in lipid deposition and its pathological pathway in ALD needs further investigation.

The outstanding ability of optical metasurfaces to tailor light's amplitude, phase, and polarization with a subwavelength resolution has attracted big interest. A multifunctional metasurface device is reported and experimentally demonstrated that integrates an arbitrary polarization profile for image concealment and a computer‐generated hybrid hologram. Herein, a high‐resolution image is hidden in the polarization profile of the light beam, while the holographic images are encoded in its phase profile for the reconstruction of two different types of holographic images. The designed polarization profile is realized based on the superposition of two different phase profiles for circular polarization states with opposite handedness. This method can further extend the design degree of freedom in optical metasurfaces, which may open an alternative avenue for anticounterfeiting, optical image encoding, and optical information security.

In this work, we studied the effects of different reinforcements on a metal matrix composite (MMC) using molecular dynamics (MD) simulations, where graphene was chosen as the two-dimensional (2D) material and diamond was selected as the three-dimensional (3D) material. Sintering and tensile processes were conducted on the MMC models containing reinforcements of various sizes, and the effects of reinforcements with the same surface area were compared. The results indicated that the 2D material was more beneficial for sintering at the heating stage, producing a higher-density structure. The volume of Al atoms fell from 752 to 736 nm3 as the graphene size in the composite system increased. However, a slight increase from 749 to 755 nm3 was observed when the diamond radius was small. Converted to relevant metrics in the experiments, the density of the composite reached 2.84 g/cc with a 3.3 wt.% addition of single-layer graphene (SLG) and 2.87 g/cc with a 15.4 wt.% addition of diamond, and the results were slightly higher than the experimental reports. Both SLG and diamond could reduce the number of arranged Al atoms from 43,550 to approximately 35,000, and bilayer graphene (BLG) with the largest size could further decrease the number of arranged atoms to nearly 30,000, implying that grain refinement could be obtained by increasing the surface area of reinforcements. Considering the scale of these models, the reinforcement size and pore location in the initial structures were deemed to have an impact on the mechanical properties. The composite with the largest proportion of SLG showed an increase of more than 1.6 GPa in tensile strength; however, BLG showed a significant drop of 1.9 GPa when stretched in the normal direction, as the large interlayer space acted as a large hole in tension. The diamond size did not appear to affect the strengthening effects. Nevertheless, the elongation values of composites with graphene were generally 35% higher than the Al-diamond composites.

Schizothorax dulongensis Huang (1985) is an endemic species in China, which is mainly distributed in the Irrawaddy River and its tributaries. In this study, the complete mitochondrial genome was sequenced. Its length is 16,579 bp, containing 22 tRNAs, two rRNAs, and 13 PCGs. The phylogenetic results showed that S. dulongensis and these species from Brahmaputra River clustered a clade, and supported the Brahmaputra River and the Irrawaddy River have been reorganized of drainage.

Recently, wearable sensor technology has drawn attention to many health-related appliances due to its varied existing optical, electrical, and mechanical applications. Similarly, we have designed a simple and cheap lift-off fabrication technique for the realization of large-area biocompatible random lasers to customize wearable sensors. A large-area random microcavity comprises a matrix element polymethyl methacrylate (PMMA) in which rhodamine B (RhB, which acts as a gain medium) and gold nanorods (Au NRs, which offer plasmonic feedback) are incorporated via a spin-coating technique. In regards to the respective random lasing device residing on a heterogenous film (area > 100 cm2), upon optical excitation, coherent random lasing with a narrow linewidth (~0.4 nm) at a low threshold (~23 μJ/cm2 per pulse) was successfully attained. Here, we maneuvered the mechanical flexibility of the device to modify the spacing between the feedback agents (Au NRs), which tuned the average wavelength from 612.6 to 624 nm under bending while being a recoverable process. Moreover, the flexible film can potentially be used on human skin such as the finger to serve as a motion and relative-humidity sensor. This work demonstrates a designable and simple method to fabricate a large-area biocompatible random laser for wearable sensing.