Capsaicin Reduces Obesity by Reducing Chronic Low-Grade Inflammation.

Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1-/-) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1-/-) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1-/- mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin. Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of capsaicin. It has been confirmed that capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function.

Metabolomic profile of secondary hyperparathyroidism in patients with chronic kidney disease stages 3-5 not receiving dialysis.

Introduction: Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease (CKD). Elucidating the metabolic characteristics of SHPT may provide a new theoretical basis for its prevention and treatment. This study aimed to perform a metabolomic analysis of SHPT in patients with CKD stages 3-5 not receiving dialysis. Methods: A total of 76 patients with CKD, 85 patients with CKD-SHPT, and 67 healthy controls were enrolled in this study. CKD was diagnosed according to the criteria specified in the Kidney Disease Improving Global Outcomes 2012 guidelines. SHPT was diagnosed by experienced clinicians according to the Renal Disease Outcomes Quality Initiative Clinical Practice Guidelines. Serum renal function markers and the lipid profile were analyzed. Untargeted ultra performance liquid chromatography-tandem mass spectrometry was used to analyze the serum metabolites of patients with CKD and SHPT. Multivariate analysis of the data was performed using principal component analysis and partial least square discriminant analysis. Serum differential metabolites were identified and further characterized using databases. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes database. Correlations between differential metabolites and clinical parameters were determined using the Spearman correlation. Results: The serum metabolomic profiles of patients with CKD with and without SHPT differed significantly. Differential metabolites were mainly enriched in the top four Kyoto Encyclopedia of Genes and Genomes pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; sphingolipid metabolism; glycerophospholipid metabolism; and phenylalanine metabolism. In total, 31 differential metabolites were identified; of these, L-tryptophan and (R)-(+)-1-phenylethylamine were decreased, while other amino acids and their derivatives, uremia toxins, carnitine, and lipids, were increased significantly in patients with SHPT compared to those without. The 14 lipid metabolites were positively correlated with levels of Urea, serum creatinine, cystatin C, and triglycerides and negatively correlated with the estimated glomerular filtration rate and levels of total and high- and low-density lipoprotein cholesterol. Discussion: Disturbed amino acid and lipid metabolism were more apparent in patients with SHPT than in those without. This metabolomic profile of SHPT may provide a therapeutic foundation for its future clinical management.

Multisensory Fusion Training and 7, 8-Dihydroxyflavone Improve Amyloid-ß-Induced Cognitive Impairment, Anxiety, and Depression-Like Behavior in Mice Through Multiple Mechanisms.

Background: There is growing interest in the role of physical activity in patients with of Alzheimer's disease (AD), particularly regarding its impact of cognitive function, gut microbiota, metabolites, and neurotrophic factors. Objective: To investigate the impact of multisensory fusion training (MSFT) combined with 7, 8-dihydroxyflavone (DHF) on the behavioral characteristics, protein expression, microbiome, and serum metabolome using the AD model in mice induced with amyloid-ß (Aß). Methods: We assessed cognitive ability, anxiety-like and depression-like behaviors in Aß mice using behavioral measures. Western blotting was employed to detect the expression of relevant proteins. The 16S rRNA gene sequencing and metabolomics were used to analyze changes in the intestinal microbial composition and serum metabolic profile, respectively, of Aß mice. Results: The behavioral outcomes indicated that a 4-week intervention combining DHF and MSFT yielded remarkable improvements in cognitive function and reduced anxiety and depression-like behaviors in Aß mice. In the hippocampus of Aß mice, the combined intervention increased the levels of BDNF, VGF, PSD-95, Nrf2, p-GSK3ß and p-CREB proteins. Analyses of sequence and metabolomic data revealed that Bacteroides and Ruminococcaceae were remarkably more abundant following the combined intervention, influencing the expression of specific metabolites directly linked to the maintenance of neuronal and neurobehavioral functions. These metabolites play a crucial role in vital processes, such as amino acid metabolism, lipid metabolism, and neurotransmitter metabolism in mice. Conclusion: Our study highlighted that MSFT combined with DHF improves cognitive impairment, anxiety, and depression-like behavior in Aß mice through multiple mechanisms, and further validated the correlation between the gut microbiome and serum metabolome. These findings open up a promising avenue for future investigations into potential treatment strategies for AD.

Gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia.

Aims: This study aims to explore the gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia (FES). Methods: 82 patients with FES, including 50 male patients and 32 female patients, were enrolled in the present study. Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were respectively conducted to evaluate the clinical symptoms and cognitive function of patients with FES at baseline and after treatment. Repeated measure ANOVA was performed to compare gender differences in cognitive domains scores between baseline and 2-month follow-up. Stepwise liner regression model was performed to explore the effect factors of cognitive improvements in patients. Results: There was no significant difference in age of onset, education years, PANSS scores, duration of untreated psychosis and Olanzapine equivalent doses between male and female patients (all p > 0.05). In the comparisons of cognition function, male patients exhibited better performance in social cognition compared with female patients at baseline (t = 3.20, p < 0.05). After treatment, improvements of attention/vigilance and working memory were both found in male patients and female patients (attention/vigilance, F = 11.867, p < 0.05; working memory, F = 18.265, p < 0.05). In addition, improvement of speed of information processing was only found in female patients (F = 11.65, p < 0.01). Significant interaction between time and gender was found in speed information of processing (F = 4.140, p = 0.045). Stepwise liner regression model revealed that improvements of negative symptoms promote improvements of cognitive function in female patients (all p < 0.05). Conclusions: Our findings revealed gender differences of cognitive improvements in patients with FES after 2-month treatment. It provides new evidence for gender differences in cognitive symptoms of schizophrenia, and also provides preliminary clues for further individualized cognitive intervention strategies.

Upper limb motor assessment for stroke with force, muscle activation and interhemispheric balance indices based on sEMG and fNIRS.

Introduction: Upper limb rehabilitation assessment plays a pivotal role in the recovery process of stroke patients. The current clinical assessment tools often rely on subjective judgments of healthcare professionals. Some existing research studies have utilized physiological signals for quantitative assessments. However, most studies used single index to assess the motor functions of upper limb. The fusion of surface electromyography (sEMG) and functional near-infrared spectroscopy (fNIRS) presents an innovative approach, offering simultaneous insights into the central and peripheral nervous systems. Methods: We concurrently collected sEMG signals and brain hemodynamic signals during bilateral elbow flexion in 15 stroke patients with subacute and chronic stages and 15 healthy control subjects. The sEMG signals were analyzed to obtain muscle synergy based indexes including synergy stability index (SSI), closeness of individual vector (CV) and closeness of time profile (CT). The fNIRS signals were calculated to extract laterality index (LI). Results: The primary findings were that CV, SSI and LI in posterior motor cortex (PMC) and primary motor cortex (M1) on the affected hemisphere of stroke patients were significantly lower than those in the control group (p < 0.05). Moreover, CV, SSI and LI in PMC were also significantly different between affected and unaffected upper limb movements (p < 0.05). Furthermore, a linear regression model was used to predict the value of the Fugl-Meyer score of upper limb (FMul) (R2 = 0.860, p < 0.001). Discussion: This study established a linear regression model using force, CV, and LI features to predict FMul scale values, which suggests that the combination of force, sEMG and fNIRS hold promise as a novel method for assessing stroke rehabilitation.

Synthesis of ZSM-5 Zeolite Nanosheets with Tunable Silanol Nest Contents across an Ultra-wide pH Range and Their Catalytic Validation.

Zeolite synthesis under acidic conditions has always presented a challenge. In this study, we successfully prepared series of ZSM-5 zeolite nanosheets (Z-5-SCA-X) over a broad pH range (4 to 13) without the need for additional supplements. This achievement was realized through aggregation crystallization of ZSM-5 zeolite subcrystal (Z-5-SC) with highly short-range ordering and ultrasmall size extracted from the synthetic system of ZSM-5 zeolite. Furthermore, the crystallization behavior of Z-5-SC was investigated, revealing its non-classical crystallization process under mildly alkaline and acidic conditions (pH<10), and the combination of classical and non-classical processes under strongly alkaline conditions (pH≥10). What's particularly intriguing is that, the silanol nest content in the resultant Z-5-SCA-X samples appears to be dependent on the pH values during the Z-5-SC crystallization process rather than its crystallinity. Finally, the results of the furfuryl alcohol etherification reaction demonstrate that reducing the concentration of silanol nests significantly enhances the catalytic performance of the Z-5-SCA-X zeolite. The ability to synthesize zeolite in neutral and acidic environments without the additional mineralizing agents not only broadens the current view of traditional zeolite synthesis but also provides a new approach to control the silanol nest content of zeolite catalysts.

Nutrient budgets and biogeochemical dynamics in the coastal regions of northern Beibu Gulf, South China Sea: Implication for the severe impact of human disturbance.

This study examined the nutrient budgets and biogeochemical dynamics in the coastal regions of northern Beibu Gulf (CNBG). Nutrient concentrations varied spatially and seasonally among the different bays. High nutrient levels were found in the regions with high riverine inputs and intensive mariculture. Using a three end-member mixing model, nutrient biogeochemistry within the ecosystem was estimated separately from complex physical mixing effects. Nutrient consumption dominated in most bays in summer, whereas nutrient regeneration dominated in winter, likely due to phytoplankton decomposition, vertical mixing and desorption. Through the Land-Ocean Interaction Coastal Zone (LOICZ) model, the robust nutrient budgets were constructed, indicating that the CNBG behaved as a sink of dissolved inorganic nitrogen, phosphorus and silicon. River-borne nutrient inputs were the dominant nutrient source, while residual flows and water exchange flows transported nutrient off the estuaries. This study could help us better understand nutrient cycles and nutrient sources/sinks in the CNBG.

Untargeted and spatial-resolved metabolomics characterize serum and tissue-specific metabolic reprogramming in acute kidney injury.

Background: Acute kidney injury (AKI) is one of the most common clinical emergencies characterized by rapid progression, difficulty in early diagnosis, and high mortality. Currently, there are no effective AKI early diagnostic methods and treatments. Therefore, identifying new mechanisms of AKI have become urgent for development new targets for early diagnosis and treatment of AKI in the current clinical setting. Methods: In this study, systematic analysis and comparison of serum metabolic profiles of clinical AKI patients, chronic kidney disease (CKD) patients, and healthy subjects were performed using untargeted metabolomics. Moreover, the first spatial metabolomic analysis of kidney tissues in an AKI mouse model using MALDI-TOF MS technology was conducted. Differentially expressed metabolites were identified using a comprehensive, publicly available database. The metabolic data obtained were evaluated using principal component analysis, (orthogonal) partial least squares discriminant analysis, and metabolic pathway analysis to explore the unique serum metabolic profile of the patients, as well as to characterize the spatial distribution of differential metabolites in the kidneys of AKI mice. Results: Significant changes in the metabolite levels of amino acids, carnitine, and lipids were observed in the AKI and CKD groups versus the healthy population, suggesting that kidney injury may lead to abnormalities in various metabolic pathways, such as amino acids, fatty acids, and lipids. The significant difference between the AKI and CKD groups were found for the first time in these indexes including amino acid, carnitine, fatty acid, and lipid levels. Additionally, spatial metabolomics results revealed that amino acid, carnitine, organic acid, and fatty acid metabolites were more likely significantly altered in the renal cortex, while lipid metabolites were both differentially distributed in the cortex and medulla of the AKI group. Conclusion: Abnormalities in the serum metabolism of amino acids, carnitine, and lipids in patients with kidney diseases, such as AKI and CKD, are closely associated with the physiological dysfunction of kidney injury. Metabolic differences between patients with AKI and CKD were compared for the first time, showing that fatty acid oxidative inhibition was more severe in patients with AKI. Furthermore, spatial metabolomics has revealed metabolic reprogramming with tissue heterogeneity in AKI mice model. Our study provides valuable information in the molecular pathological features of AKI in the kidney tissues.

Designing a Periodic Structure with a Composition Gradient Stack Unit to Realize a Good Comprehensive Dielectric Property of Yttrium Iron Garnet Multilayer Film.

Y3Fe5O12 (YIG) thin films are highly needed in microwave devices, but the low saturation magnetization and low dielectric constant greatly limit the application of YIG thin films. It was reported that the ion substitution, for example, Pr3+, could increase the dielectric constant of Y3-xPrxFe5O12 (YPrxIG). Unfortunately, the dielectric loss would also be significantly increased. In this work, [YPr0.20IG/YPr0.15IG/YPr0.10IG]N multilayer films were fabricated via the chemical solution deposition method, by designing a periodic structure with the [YPr0.20IG/YPr0.15IG/YPr0.10IG] composition gradient stack. In comparison to the average composition of YPr0.15IG, high saturation magnetization, high dielectric constant, and low loss were successfully simultaneously achieved in the multilayer structure. The N = 6 film exhibited a higher saturation magnetization of 252.8 emu/cm3 than the value (213.1) of the YPr0.15IG (average composition) film. The dielectric constant of the N = 6 film reached 25.6 in contrast to the value of 18.3 for the YPr0.15IG film at 12.4 GHz, which was the contribution of the rapid flip of the electric dipole of a single-unit dielectric material and the accumulation of interface charge. Furthermore, the dielectric loss of the film with N = 6 decreased to 0.0036 compared with the value (0.0102) of the average composition film. This work demonstrated a strategy of designing a periodic structure with a composition gradient stack unit to realize a good comprehensive dielectric property through taking advantage of the multiple effects of "coherent growth, component matching, and interface accumulation".

Characterizing the transitory groundwater-surface water interaction and its environmental consequence of a riverside karst pool.

Exchange between groundwater (GW) and surface water (SW) is a common occurrence in karst water systems through sinking stream disappearance or groundwater emergence. However, the transitory GW-SW interaction caused by river backflowing into a spring is poorly observed and understood. In this study, we present an approach for characterizing the influence of GW-SW interaction in a karst spring by integrating high-resolution hydrology, carefully selected hydrochemistry monitoring and precise microbe measurements. The spring-fed pool water conditions can be distinguished as high, medium, and low-water level periods in a hydrological year. The high-water level accounts for <1 % in a year, while it is associated with the hydrological regimes of backflooding states. The inflow of river backflow was found to be 4.4 times that of the natural discharge of spring water during a rainfall event. The duration of river intrusion into the spring or karst conduit could be assessed by jointly interpreting hydrography and physicochemical signatures, while the lasting environmental consequences should be evaluated together with biotic factors such as Escherichia coli. The GW-SW interaction induced by river backflow has led to the retention of river water in a pool, spring, and karst conduit for 132, 94, and 56 h, respectively. Despite turbidity returning to normal levels after 56 h, E.coli continued to persist for an extended duration. Our study reveals that despite the transient nature of GW-SW induced by river backflow on the hydrograph, they present a lasting risk of contamination from heavy metals, organic matter, and microorganisms. This extended influence can persist within a karst aquifer lacking a hyporheic zone. This research contributes to the quantification of processes involved in transitory GW-SW interaction in a karst spring, and it highlights the underestimation of GW-SW interactions in karst water systems, which might negatively impact water resources management.

Neuro-inspired continual anthropomorphic grasping.

Humans can learn continuously grasping various objects dexterously. This ability is enabled partly by underlying neural mechanisms. Most current works of anthropomorphic robotic grasping learning lack the capability of continual learning (CL). They utilize large datasets to train grasp models and the trained models are difficult to improve incrementally. By incorporating several discovered neural mechanisms supporting CL, we propose a neuro-inspired continual anthropomorphic grasping (NICAG) approach. It consists of a CL framework of anthropomorphic grasping and a neuro-inspired CL algorithm. Compared with other methods, our NICAG approach achieves better CL capability with lower loss and forgetting, and gets higher grasping success rate. It indicates that our approach performs better on alleviating forgetting and preserving grasp knowledge. The proposed system offers an approach for endowing anthropomorphic robotic hands with the ability to learn grasping objects continually and has great potential to make a profound impact on robots in households and factories.

Characterization of dynamic plastisphere and their underlying effects on the aging of biodegradable and traditional plastics in freshwater ecosystems.

Recently, biodegradable plastics (BPs) are emerging as a sustainable alternative to traditional plastics. When released into an aquatic environment, the biodegradable performance of BPs is influenced by biochemical processes, especially the developed plastisphere. However, studies addressing the biodegrading capacity of BPs and traditional plastics within the plastisphere are still limited. Here, we investigated plastisphere community variations and their capacity to biodegrade polyethylene terephthalate (PET) and starch-based plastics (SBP) for four time periods (15, 30, 45, and 80 days) in three freshwaters. Unexpectedly, there is no significant difference in the microbial communities and network structure of the plastisphere between SBP and PET. Moreover, SBP tended to age rapidly at the early stage (0-15 days), while the aging degree of SBP and PET did not display an obvious difference at 80 days. Partial least squares path modeling suggested that plastic aging was mainly dominated by keystone taxa of network and aquatic environmental factors. These results suggest that the aging rate of commercial BPs may not be as fast as we imagine in freshwaters (SBP ≈ PET), and the environmental behaviors of BPs in the aquatic environment should be paid more attention to.

Spatio-temporal succession of microbial communities in plastisphere and their potentials for plastic degradation in freshwater ecosystems.

Plastics in the environment provide a new and unique habitat for microorganisms - known as the plastisphere. The microbial succession within the plastisphere and their potentials for plastic degradation in freshwater ecosystems is still not clear. Here, we investigated variation of microbial communities in plastisphere and their capacity to biodegrade non-biodegradable plastics (non-BPs), i.e., polypropylene (PP) and polyethylene (PE), and biodegradable plastics (BPs), i.e., polylactic acid+polybutylene adipate-co-terephthalate (PLA+PBAT) for four-time periods (15, 30, 45, and 80 days) in three freshwaters. Results showed that the aging degree of plastics increased with succession of plastisphere, with higher degradation rates of BP blends than those of non-BPs. High-throughput sequencing from 112 biofilm samples revealed that bacterial and fungal community structure of the plastisphere were potentially affected by plastic types and gradually converge during biofilm succession. The plastisphere of BPs reached the mature phase more quickly than those of non-BPs and increased co-exclusion to complete for resources. Furthermore, ecological networks involving plastic aging indices, environmental factors and bacterial and fungal operational taxonomic units were established. Ecological networks revealed that BPs may pose the ability to attract and retain key microorganisms (of the orders Bacillales, Myxococcales and Xanthomonadales) that significantly influence community composition such that biodegradative functions were increased in freshwaters.

Environmental exposure to perchlorate, nitrate and thiocyanate, and thyroid function in Chinese adults: A community-based cross-sectional study.

BACKGROUND: Evidence on environmental exposure to perchlorate, nitrate, and thiocyanate, three thyroidal sodium iodine symporter (NIS) inhibitors, and thyroid function in the Chinese population remains limited. OBJECTIVE: To investigate the associations of environmental exposure to perchlorate, nitrate, and thiocyanate with markers of thyroid function in Chinese adults. METHODS: A total of 2441 non-pregnant adults (mean age 50.4 years and 39.1% male) with a median urinary iodine of 180.1 µg/L from four communities in Shenzhen were included in this cross-sectional study. Urinary perchlorate, nitrate, thiocyanate, and thyroid profiles, including serum free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH), were measured. Generalized linear model was applied to investigate the single-analyte associations. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to examine the association between the co-occurrence of three anions and thyroid profile. RESULTS: The median levels of urinary perchlorate, nitrate, and thiocyanate were 5.8 µg/g, 76.4 mg/g, and 274.1 µg/g, respectively. After adjusting for confounders, higher urinary perchlorate was associated with lower serum FT4, TT4, and TT3, and higher serum FT3 and TSH (all P < 0.05). Comparing extreme tertiles, subjects in the highest nitrate tertile had marginally elevated TT3 (ß: 0.02, 95% CI: 0.00-0.04). Each 1-unit increase in log-transformed urinary thiocyanate was associated with a 0.04 (95% CI: 0.02-0.06) pmol/L decrease in serum FT3. The WQS indices were inversely associated with serum FT4, TT4, and FT3 (all P < 0.05). In the BKMR model, the mixture of three anions was inversely associated with serum FT4, TT4, and FT3. CONCLUSIONS: Our study provides evidence that individual and combined environmental exposure to perchlorate, nitrate, and thiocyanate are associated with significant changes in thyroid function markers in the Chinese population with adequate iodine intake.

Effects and mechanisms of Xiaochaihu Tang against liver fibrosis: An integration of network pharmacology, molecular docking and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a potentially harmful chronic liver disease caused by various etiologies. There is currently no specific drug for liver fibrosis. Xiaochaihu Tang (XCHT) is a traditional formula combined of seven herbs, which was first recorded in the Treatise on Febrile Diseases in Han Dynasty of ancient China. It is widely used in clinic to hepatic protection, analgesic, antipyretic and anti-inflammatory treatment. And it has been recommended for treating chronic hepatitis and chronic cholecystitis in the latest guidelines for the diagnosis and treatment of liver fibrosis with integrated traditional and western medicine. However, the underlying regulatory mechanisms remain elusive. AIM OF THE STUDY: This study aims to explore the therapeutic effects of XCHT on liver fibrosis and its underlying molecular mechanisms from the perspective of network pharmacology and experimental research. MATERIALS AND METHODS: Carbon tetrachloride (CCl4) induced and bile duct ligation (BDL) induced liver fibrosis models in mice were established to evaluate the anti-fibrosis effects of XCHT in vivo. Potential anti-fibrosis targets of XCHT were screened via network establishment. The underlying mechanisms were uncovered through GO and pathway enrichment analysis. Then, the core targets were identified from protein-protein interaction network by means of the Cytohubba plug-in of Cytoscape. Furthermore, two effective monomer components of XCHT were recognized by molecular docking. Moreover, the predicted components and pathways were verified by in vitro experiments. RESULTS: When treated with XCHT, liver fibrosis was alleviated in both mice models, showing as the improvement of liver function, the protection of hepatocytes, the inhibition of HSC activation and the reduction of hepatic collagen accumulation. 540 monomer components, 300 therapeutic targets, 109 signaling pathways, 246 GO biological processes, 77 GO cellular components, 107 GO molecular functions items and core targets were identified by network analysis. Then, 6-gingerol and baicalein were identified as the core components of anti-fibrosis effects of XCHT via leptin or Nrf2 signaling pathway. Furthermore, the experiment in vitro also validated the results. CONCLUSIONS: Our study suggests XCHT could alleviate liver fibrosis through multi-targets and multi-pathways; 6-gingerol and baicalein are its core components which may play an important role via leptin or Nrf2 signaling pathway.

Multisystem inflammatory syndrome (MIS-C) with SARS-CoV-2 omicron variant BA.2.38 in a four-year-old Chinese girl: A case report.

We report a severe COVID-19 complicated with MIS-C in a girl treated by the author in China, and discuss the current research status and progress in the diagnosis and therapy of MIS-C in children. The patient was a 4-year-old child previously healthy who was referred to the hospital with a complaint of fever, finally, Multisystem inflammatory syndrome was diagnosed with COVID-19.

Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome.

INTRODUCTION AND OBJECTIVES: Omenn syndrome (OS) is a very rare type of severe combined immunodeficiencies manifested with erythroderma, eosinophilia, hepatosplenomegaly, lymph-adenopathy, and elevated level of serum IgE. OS is inherited with an autosomal recessive mode of inheritance. Germline mutations in the human RAG1 gene cause OS. MATERIALS AND METHODS: In this study, we investigated a 2-month-old boy with cough, mild anaemia, pneumonia, immunodeficiency, repeated infection, feeding difficulties, hepatomegaly, growth retardation, and heart failure. Parents of the proband were phenotypically normal. RESULTS: Karyotype analysis and chromosomal microarray analysis found no chromosomal structural abnormalities (46, XY) and no pathogenic copy number variations (CNVs) in the proband. Whole-exome sequencing identified a novel homozygous single nucleotide deletion (c.2662delC) in exon 2 of the RAG1 gene in the proband. Sanger sequencing confirmed that both the proband parents were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters and one elder brother of the proband and in the 100 ethnically matched normal healthy individuals. This novel homozygous deletion (c.2662delC) leads to the frameshift, which finally results in the formation of the truncated protein (p.Leu888Phefs*3) V(D)J recombination-activating protein 1 with 890 amino acids compared with the wildtype V(D)J recombination-activating protein 1 of 1043 amino acids. Hence, it is a loss-of-function variant. CONCLUSIONS: Our present study expands the mutational spectrum of the RAG1 gene associated with OS. We also strongly suggested the importance of whole-exome sequencing for the genetic screening of patients with OS.

Association between meteorological factors and the epidemics of influenza (sub)types in a subtropical basin of Southwest China.

BACKGROUND: The effects of climatic conditions on the prevalence of individual influenza (sub)types are not well understood in the subtropics. This study aims to evaluate the associations between meteorological factors and seasonal epidemics of A(H3N2), A(H1N1)pdm09, and type B influenza viruses, as well as to estimate the interactions between climatic variables in a subtropical basin region. METHODS: The seasonality of influenza (sub)types during 2010-2019 were characterized in Chengdu Plain Economic Zone, a densely populated and highly humid plain area in Sichuan Basin in subtropical Southwest China. Generalized additive models were adopted to assess the independent exposure-response relationship between meteorological variables and influenza prevalence. The interactions of meteorological variables were further estimated using bivariate response surface models and strata models. RESULTS: Our analyses indicated that the temperature, relative humidity, and absolute humidity have exhibited a major influence on influenza infection in Chengdu Plain Economic Zone. Low temperature was shown to promote the prevalence of A(H1N1)pdm09 and type B in winter-spring days at all levels of relative humidity. High risk of A(H3N2) infections was observed at low temperature or high temperature, and at higher relative humidity. Moreover, absolute humidity decreased or increased influenza (sub)type infections within different ranges. CONCLUSIONS: This study found different nonlinear relationships between meteorological factors and the seasonality of influenza (sub)types, as well as significant interactive effects between climatic variables, contributing to the research on the climate drivers of influenza prevalence in warm-humid basin regions in the subtropics.

Associations of urinary perchlorate, nitrate and thiocyanate with central sensitivity to thyroid hormones: A US population-based cross-sectional study.

BACKGROUND: Perchlorate, nitrate, and thiocyanate are three well-known sodium iodine symporter inhibitors, however, associations of their individual and concurrent exposure with central thyroid hormones sensitivity remain unclear. OBJECTIVES: To investigate the associations of urinary perchlorate, nitrate, thiocyanate, and their co-occurrence with central thyroid hormones sensitivity among US general adults. METHODS: A total of 7598 non-pregnant adults (weighted mean age 45.9 years and 52.9% men) from National Health and Nutritional Examination Survey 2007-2012 were included in this cross-sectional study. Central sensitivity to thyroid hormones was estimated with the Parametric Thyroid Feedback Quantile-based Index (PTFQI). Ordinary least-squares regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were performed to examine the associations of three anions and their co-occurrence with PTFQI. RESULTS: The weighted mean values of urinary perchlorate, nitrate, thiocyanate, and perchlorate equivalent concentration (PEC) were 5.48 µg/L, 57.59 mg/L, 2.65 mg/L, and 539.8 µg/L, respectively. Compared with the lowest quartile, the least-square means difference (LSMD) of PTFQI was -0.0516 (LSMD ± SE: -0.0516 ± 0.0185, P < 0.01) in the highest perchlorate quartile. On average, PTFQI decreased by 0.0793 (LSMD ± SE: -0.0793 ± 0.0205, P < 0.001) between the highest and lowest thiocyanate quartile. Compared with those in the lowest quartile, participants in the highest PEC quartile had significantly decreased PTFQI levels (LSMD ± SE: -0.0862 ± 0.0188, P < 0.001). The WQS of three goitrogens, was inversely associated with PTFQI (ß: -0.051, 95% CI: -0.068, -0.034). In BKMR model, PTFQI significantly decreased when the levels of three anions were at or above their 60th percentiles compared to the median values. CONCLUSIONS: Higher levels of urinary perchlorate, thiocyanate, and co-occurrence of three goitrogens were associated with increased central thyroid hormones sensitivity among US general adults. Further studies are warranted to replicate our results and elucidate the underlying causative mechanistic links.

Effects of Involuntary and Voluntary Exercise in Combination with Acousto-Optic Stimulation on Adult Neurogenesis in an Alzheimer's Mouse Model.

Single-factor intervention, such as physical exercise and auditory and visual stimulation, plays a positive role on the prevention and treatment of Alzheimer's disease (AD); however, the therapeutic effects of single-factor intervention are limited. The beneficial effects of these multifactor combinations on AD and its molecular mechanism have yet to be elucidated. Here, we investigated the effect of multifactor intervention, voluntary wheel exercise, and involuntary treadmill running in combination with acousto-optic stimulation, on adult neurogenesis and behavioral phenotypes in a mouse model of AD. We found that 4 weeks of multifactor intervention can significantly increase the production of newborn cells (BrdU+ cells) and immature neurons (DCX+ cells) in the hippocampus and lateral ventricle of Aß oligomer-induced mice. Importantly, the multifactor intervention could promote BrdU+ cells to differentiate into neurons (BrdU+ DCX+ cells or BrdU+ NeuN+ cells) and astrocytes (BrdU+GFAP+ cells) in the hippocampus and ameliorate Aß oligomer-induced cognitive impairment and anxiety- and depression-like behaviors in mice evaluated by novel object recognition, Morris water maze tests, elevated zero maze, forced swimming test, and tail suspension test, respectively. Moreover, multifactor intervention could lead to an increase in the protein levels of PSD-95, SYP, DCX, NeuN, GFAP, Bcl-2, BDNF, TrkB, and pSer473-Akt and a decrease in the protein levels of BAX and caspase-9 in the hippocampal lysates of Aß oligomer-induced mice. Furthermore, sequencing analysis of serum metabolites revealed that aberrantly expressed metabolites modulated by multifactor intervention were highly enriched in the biological process associated with keeping neurons functioning and neurobehavioral function. Additionally, the intervention-mediated serum metabolites mainly participated in glutamate metabolism, glucose metabolism, and the tricarboxylic acid cycle in mice. Our findings suggest the potential of multifactor intervention as a non-invasive therapeutic strategy for AD to anti-Aß oligomer neurotoxicity.