[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Green synthesis of carbon-supported ultrafine ZnS nanoparticles for superior lithium-ion batteries.

Zinc sulfide (ZnS) is a promising anode material for lithium-ion batteries (LIBs) because of its high theoretical capacity, abundance, cost-effectiveness, and environmental friendliness. Herein, a hydrangea-like ZnS-carbon composite (ZnS-NC) is synthesized through the hydrothermal method and subsequent pyrolysis of a supramolecular precursor guanosine. The resulting composite comprises ultrafine ZnS nanoparticles firmly stabilized on a nitrogen-doped carbon matrix, featuring mesoporous channels and high surface areas. When utilized as an anode material for LIBs, the initial discharge specific capacity of the ZnS-NC electrode reaches an impressive value of 944 mA h g-1 at 1.0 A g-1, and even after 450 cycles, it maintains a reversible capacity of 597 mA h g-1. Compared with pure ZnS, the ZnS-NC composite exhibits significantly improved rate performance and cycling stability. This enhancement in Li-storage performance can be attributed to a synergistic effect within the ZnS-NC composite, which arises from the large exposed active site area, efficient ion/electron transfer, and strong interaction between the ZnS nanoparticles and the carbon framework. Overall, this work presents an eco-friendly approach for developing metal sulfide-carbon composites with exceptional potential for energy storage applications.

Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.

Sphingolipids, a type of bioactive lipid, play crucial roles within cells, serving as integral components of membranes and exhibiting strong signaling properties that have potential therapeutic implications in anti-cancer treatments. However, due to the diverse group of lipids and intricate mechanisms, sphingolipids still face challenges in enhancing the efficacy of different therapy approaches. In recent decades, mass spectrometry has made significant advancements in uncovering sphingolipid biomarkers and elucidating their impact on cancer development, progression, and resistance. Primary sphingolipids, such as ceramide and sphingosine-1-phosphate, exhibit contrasting roles in regulating cancer cell death and survival. The evasion of cell death is a characteristic hallmark of cancer cells, leading to treatment failure and a poor prognosis. The escape initiates with long-established apoptosis and extends to other programmed cell death (PCD) forms when patients experience chemotherapy, radiotherapy, and/or immunotherapy. Gradually, supportive evidence has uncovered the fundamental molecular mechanisms underlying various forms of PCD leading to the development of innovative molecular, genetic, and pharmacological tools that specifically target sphingolipid signaling nodes. In this study, we provide a comprehensive overview of the sphingolipid biomarkers revealed through mass spectrometry in recent decades, as well as an in-depth analysis of the six main forms of PCD (apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis) in aspects of tumorigenesis, metastasis, and tumor response to treatments. We review the corresponding small-molecule compounds associated with these processes and their potential implications in cancer therapy.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

An miRNA-mRNA integrative analysis in human placentas and mice: role of the Smad2/miR-155-5p axis in the development of fetal growth restriction.

Introduction: Functional disorder of the placenta is the principal cause of fetal growth restriction (FGR), usually cured with suitable clinical treatment and good nursing. However, some FGR mothers still give birth to small for gestational age (SGA) babies after treatment. The ineffectiveness of treatment in such a group of patients confused physicians of obstetrics and gynecology. Methods: In this study, we performed a microRNA-messenger RNA integrative analysis of gene expression profiles obtained from Gene Expression Omnibus. Differentially expressed genes were screened and checked using quantitative polymerase chain reaction. Target genes of significantly changed microRNA were screened and enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Function of the obtained microRNA-messenger RNA was evaluated using HTR-8/SVneo trophoblast cells, human umbilical vein endothelial cells, and heterozygote male mice. Result: MiR-155-5p was upregulated (p = 0.001, fold-change = 2.275) in fetal-side placentals. Among the hub genes identified as key targets for miR-155-5p in fetal reprogramming, Smad2 was downregulated (p = 0.002, fold change = 0.426) and negatively correlated with miR-155-5p expression levels (r = -0.471, p < 1.0 E - 04) in fetal-side placental tissues. The miR-155-5p mimic blocks Smad2 expression and suppresses villous trophoblast cell and endothelial cell function (proliferation, migration, and invasion), indicating a close relationship with placental development. Luciferase assays further confirmed the targeting of miR-155-5p to Smad2. Furthermore, Smad2+/- heterozygote male mice were born small with low body weight (p = 0.0281) and fat composition (p = 0.013) in the fourth week post-natal. Discussion: We provide the first evidence of the role of the Smad2/miR-155-5p axis in the placental pathologies of FGR. Our findings elucidate the pathogenesis of FGR and provide new therapeutic targets.

Rational Engineering of p-n Heterogeneous ZnS/SnO2 Quantum Dots with Fast Ion Kinetics for Superior Li/Na-Ion Battery.

Constructing heterogeneous nanostructures is an efficient strategy to improve the electrical and ionic conductivity of metal chalcogenide-based anodes. Herein, ZnS/SnO2 quantum dots (QDs) as p-n heterojunctions that are uniformly anchored to reduced graphene oxides (ZnS-SnO2 @rGO) are designed and engineered. Combining the merits of fast electron transport via the internal electric field and a greatly shortened Li/Na ion diffusion pathway in the ZnS/SnO2 QDs (3-5 nm), along with the excellent electrical conductivity and good structural stability provided by the rGO matrix, the ZnS-SnO2 @rGO anode exhibits enhanced electronic and ionic conductivity, which can be proved by both experiments and theoretical calculations. Consequently, the ZnS-SnO2 @rGO anode shows a significantly improved rate performance that simple counterpart composite anodes cannot achieve. Specifically, high reversible specific capacities are achieved for both lithium-ion battery (551 mA h g-1 at 5.0 A g-1 , 670 mA h g-1 at 3.0 A g-1 after 1400 cycles) and sodium-ion battery (334 mA h g-1 at 5.0 A g-1 , 313 mA h g-1 at 1.0 A g-1 after 400 cycles). Thus, this strategy to build semiconductor metal sulfides/metal oxide heterostructures at the atomic scale may inspire the rational design of metal compounds for high-performance battery applications.

A case of West syndrome and global developmental delay in a child with a heterozygous mutation in the TBL1XR1 gene: A case report.

BACKGROUND: TBL1XR1, also known as IRA1 or TBLR1, encodes a protein that is localized in the nucleus and is expressed in most tissues. TBL1XR1 binds to histones H2B and H4 in vitro and functions in nuclear receptor-mediated transcription. TBL1XR1 is also involved in the regulation of the Wnt-ß-catenin signaling pathway. Mutations in the TBL1XR1 gene impair the Wnt-ß-catenin signaling pathway's ability to recruit Wnt-responsive element chromatin, affecting brain development. Mutations in this gene cause various clinical phenotypes, including Pierpont syndrome, autism spectrum disorder, speech and motor delays, mental retardation, facial dysmorphism, hypotonia, microcephaly, and hearing impairment. CASE SUMMARY: A 5-month-old female child was admitted with "episodic limb tremors for more than 1 month." At the time of admission, the child had recurrent episodes of limb tremors with motor retardation and a partially atypical and hypsarrhythmic video electroencephalogram. It was determined that a heterozygous mutation in the TBL1XR1 gene caused West syndrome and global developmental delay. Recurrent episodes persisted for 6 months following oral treatment with topiramate; the addition of oral treatment with vigabatrin did not show any significant improvement, and the disease continued to recur. The child continued to have recurrent episodes of limb tremors at follow-up until 1 year and 3 months of age. Additionally, she developed poor eye contact and a poor response to name-calling. CONCLUSION: We report the case of a child with West syndrome and a global developmental delay caused by a heterozygous mutation in the TBL1XR1 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.

A Liquid-Liquid Phase Separation-Related Index Associate with Biochemical Recurrence and Tumor Immune Environment of Prostate Cancer Patients.

To identify liquid-liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS, which was the potential biomarker related to PCa liquid-liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.

Head-to-head comparisons of [68Ga]Ga-PSMA-11 PET/CT, multiparametric MRI, and prostate-specific antigen for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer patients: a prospective study.

PURPOSE: The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [68Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([68Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa. METHODS: This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [68Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa index. Logistic regression analysis was used to determine the independent predictive value of [68Ga]Ga-PSMA-11 PET/CT-derived parameters. RESULTS: All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [68Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson's R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [68Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [68Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool.

Semantic Computed Tomography Features for Predicting BRCA1-associated Protein 1 and/or Tumor Protein p53 Gene Mutation Status in Clear Cell Renal Cell Carcinoma.

PURPOSE: The purpose of this study was to explore the semantic computed tomography (CT) features associated with BRCA1-associated protein 1 (BAP1) and/or tumor protein p53 (TP53) mutation in clear cell renal cell carcinoma (ccRCC). METHODS AND MATERIALS: Clinical characteristics and gene mutation information of 336 ccRCC patients were retrieved from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma database (TCGA-KIRC). Kaplan-Meier analysis was performed to examine prognosis by gene mutation. The CT imaging data and gene mutation information of 156 ccRCC patients treated between January 2019 and January 2021 (the training cohort) were retrospectively analyzed. The CT imaging information and gene mutation data of 123 patients with ccRCC were downloaded from The Cancer Imaging Archive and The Cancer Genome Atlas database (the external validation cohort). Univariate Chi-square test and multivariate binary logistic regression analysis were performed to determine predictors of gene mutation; a nomogram was developed using these predictors. Receiver operating characteristic curve analysis and the Hosmer-Lemeshow test were performed to evaluate the performance of the nomogram. RESULTS: Kaplan-Meier analysis showed that BAP1 and/or TP53 mutation was significantly correlated with worse survival outcome. Multivariate binary logistic regression analysis indicated ill-defined margin (P = .001), spiculated margin (P = .018), renal vein invasion (P = .002), and renal pelvis invasion (P = .001) were independent predictors of BAP1 and/or TP53 mutation. A nomogram containing these 4 semantic CT features was constructed; the area under the receiver operating characteristic curves was 0.872 (95% CI, 0.809-0.920). The Hosmer-Lemeshow test showed acceptable goodness-of-fit for the nomogram (X2 = 1.194, P = .742). The nomogram was validated in the validation cohort; it showed good accuracy (area under the receiving operating characteristic curve = 0.819, 95% CI, 0.740-0.883) and was well calibrated (X2 = 3.934, P = .559). CONCLUSIONS: Semantic CT features are a potential and promising method for predicting BAP1 and/or TP53 mutation status in ccRCC patients.

A Novel Tumor Mutation Burden Related lncRNA Signature Identified Prognosis and Tumor Immune Microenvironment Features in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Emerging evidence indicates that long noncoding RNA (lncRNA) plays an important biological role in clear cell renal cell carcinoma (ccRCC); however, the clinical value of tumor mutation burden-related lncRNA in ccRCC patients is unknown yet. METHODS: Somatic mutation profiles and lncRNA expression data of ccRCC were downloaded from the TCGA database. We retrospectively analyzed lncRNA expression data and survival information from 116 patients with ccRCC fromJanuary 2013 to January 2014. Univariate and multivariate Cox regression analyses were performed to construct lncRNA signature, and the prognosis value was determined by Kaplan-Mayer and receiver operating characteristic curve (ROC) analysis. RESULTS: Based on 160 differentially expressed TMB-related lncRNAs, two TMB-related molecular clusters with distinct immune checkpoints expression and immune cells infiltration were established for ccRCC patients. Moreover, a novel TMB-related lncRNA signature was constructed based on five lncRNAs for individualized prognosis assessment. High-risk group represents significantly worse overall survival in all cohorts. The area under the ROC curve was 0.716, 0.775 and 0.744 in the training cohort, testing cohort and TCGA cohort, respectively. Results of qRT-PCR successfully validated the expression levels of AP002360.3, LINC00460, AL590094.1, LINC00944 and LINC01843 in HK-2, 786-O, 769-P and ACHN cells. More importantly, the predictive performance of TMB-related lncRNA signature was successfully validated in an independent cohort of 116 ccRCC patients at our institution. CONCLUSION: This study successfully developed and validated a novel TMB-related lncRNA signature for individualized prognosis assessment of ccRCC patients.

VARS2 gene mutation leading to overall developmental delay in a child with epilepsy: A case report.

BACKGROUND: The mitochondrial respiratory chain defects have become the most common cause of neurometabolic disorders in children and adults, which can occur at any time in life, often associated with neurological dysfunction, and lead to chronic disability and premature death. Approximately one-third of patients with mitochondrial disease have biochemical defects involving multiple respiratory chain complexes, suggesting defects in protein synthesis within the mitochondria. We here report a child with VARS2 gene mutations causing mitochondrial disease. CASE SUMMARY: A girl, aged 3 years and 4 mo, had been unable to sit and crawl alone since birth, with obvious seizures and microcephaly. Brain magnetic resonance imaging showed symmetrical, flaky, long T1-weighted and low T2-weighted signals in the posterior part of the bilateral putamen with a high signal shadow. T2 fluid-attenuated inversion recovery imaging showed a slightly high signal and diffusion-weighted imaging showed an obvious high signal. Whole-exome gene sequencing revealed a compound heterozygous mutation in the VARS2 gene, c.1163(exon11)C>T and c.1940(exon20)C>T, which was derived from the parents. The child was diagnosed with combined oxidative phosphorylation deficiency type 20. CONCLUSION: In this patient, mitochondrial disorders including Leigh syndrome and MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) were ruled out, and combined oxidative phosphorylation deficiency type 20 was diagnosed, expanding the phenotypic spectrum of the disease.

Lithium Storage Performance Boosted via Delocalizing Charge in Znx Co1- x PS3 /CoS2 of 2D/3D Heterostructure.

A promising anode material consisting of bimetallic thiophosphate Znx Co1- x PS3 and CoS2 with 2D/3D heterostructure is designed and prepared by an effective chemical transformation. Density functional theory calculations illustrate that the Zn2+ can effectively modulate the electrical ordering of Znx Co1- x PS3 on the nanoscale: the reduced charge distribution emerging around the Zn ions can enhance the local built-in electric field, which will accelerate the ions migration rate by Coulomb forces and provide tempting opportunities for manipulating Li+ storage behavior. Moreover, the merits of the large planar size enable Znx Co1- x PS3 to provide abundant anchoring sites for metallic CoS2 nanocubes, generating a 2D/3D heterostructure with a strong electric field. The resultant Znx Co1- x PS3 /CoS2 can offer the combined advantages of bimetallic alloying and heterostructure in lithium storage applications, leading to outstanding performance as an anode material for lithium-ion batteries. Consequently, a high capacity of 794 mA h g-1 can be retained after 100 cycles at 0.2 A g-1 . Even at 3.0 A g-1 , a satisfactory capacity of 465 mA h g-1 can be delivered. The appealing alloying-heterostructure and electrochemical performance of this bimetallic thiophosphate demonstrate its great promise for applications in practical rechargeable batteries.

Relationship between seaweeds consumption and hyperuricaemia in general adults: a Population-based study from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study.

Seaweeds have numerous biologically active ingredients, such as polysaccharides, polyphenols and carotenoids, that are beneficial to human health. Although these benefits might be related to the synthesis, secretion or reabsorption of uric acid, no studies have explored the relationship between seaweeds consumption and hyperuricaemia (HUA) in the general population. The aim of this study was to investigate whether seaweeds consumption is related to HUA in a large-scale adult population. A cross-sectional study was conducted with 32 365 adults (17 328 men and 15 037 women) in Tianjin, People's Republic of China. Frequency of seaweeds consumption was assessed by a validated self-administered FFQ. HUA was defined as serum uric acid levels >420 µmol/L in men and >350 µmol/L in women. The association between seaweeds consumption and HUA was assessed by multiple logistic regression analysis. Restricted cubic spline functions were used for non-linearity tests. The prevalence of HUA in men and women was 21·17 % and 5·93 %, respectively. After adjustments for potential confounding factors, the OR (95 % CI) for HUA across seaweed consumption (g/1000 kcal per d) were 1·00 (reference) for level 1, 0·91 (95 % CI 0·81, 1·02) for level 2; 0·90 (95 % CI 0·81, 1·01) for level 3; 0·86 (95 % CI 0·78, 0·97) for level 4 in men and 0·90 (95 % CI 0·73, 1·10) for level 2; 0·82 (95 % CI 0·67, 1·00) for level 3; 0·84 (95 % CI 0·68, 1·03) for level 4 in women, respectively. A negative correlation between seaweeds consumption and HUA in males but not in females was observed. Further studies are needed to explore the causal relationship.

The association between daily yogurt consumption and serum lipid profiles in the general adult population: the TCLSIH cohort study.

The purpose of this cross-sectional study is to determine the association between yogurt consumption and lipid profiles in the general Chinese population. In this cross-sectional study, a total of 26,824 participants were included from Tianjin, China. Lipid profiles were determined by automated biochemical analyser. Yogurt consumption frequency was assessed by a validated food frequency questionnaire. Analysis of covariance was used to determine the association between daily yogurt consumption and lipid profiles. In the final multivariate model, daily yogurt consumption was negatively associated with triglyceride (TG) (p for trend <0.001) and positively associated with high density lipoprotein cholesterol (HDL-C) (p for trend = 0.02). There were no significant differences (p for trend >0.05) between daily yogurt consumption and total cholesterol (TC) or low density lipoprotein cholesterol (LDL-C). Results suggested that higher daily yogurt consumption was negatively correlated with TG and positively correlated with HDL-C in the general Chinese population.

Overweight/obesity-related transcriptomic signature as a correlate of clinical outcome, immune microenvironment, and treatment response in hepatocellular carcinoma.

Backgrounds: The pandemic of overweight and obesity (quantified by body mass index (BMI) ≥ 25) has rapidly raised the patient number of non-alcoholic fatty hepatocellular carcinoma (HCC), and several clinical trials have shown that BMI is associated with the prognosis of HCC. However, whether overweight/obesity is an independent prognostic factor is arguable, and the role of overweight/obesity-related metabolisms in the progression of HCC is scarcely known. Materials and methods: In the present study, clinical information, mRNA expression profile, and genomic data were downloaded from The Cancer Genome Atlas (TCGA) as a training cohort (TCGA-HCC) for the identification of overweight/obesity-related transcriptome. Machine learning and the Cox regression analysis were conducted for the construction of the overweight/obesity-associated gene (OAG) signature. The Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and the Cox regression analysis were performed to assess the prognostic value of the OAG signature, which was further validated in two independent retrospective cohorts from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). Subsequently, functional enrichment, genomic profiling, and tumor microenvironment (TME) evaluation were utilized to characterize biological activities associated with the OAG signature. GSE109211 and GSE104580 were retrieved to evaluate the underlying response of sorafenib and transcatheter arterial chemoembolization (TACE) treatment, respectively. The Genomics of Drug Sensitivity in Cancer (GDSC) database was employed for the evaluation of chemotherapeutic response. Results: Overweight/obesity-associated transcriptome was mainly involved in metabolic processes and noticeably and markedly correlated with prognosis and TME of HCC. Afterward, a novel established OAG signature (including 17 genes, namely, GAGE2D, PDE6A, GABRR1, DCAF8L1, DPYSL4, SLC6A3, MMP3, RIBC2, KCNH2, HTRA3, PDX1, ATHL1, PRTG, SHC4, C21orf29, SMIM32, and C1orf133) divided patients into high and low OAG score groups with distinct prognosis (median overall survival (OS): 24.87 vs. 83.51 months, p < 0.0001), and the values of area under ROC curve (AUC) in predicting 1-, 2-, 3-, and 4-year OS were 0.81, 0.80, 0.83, and 0.85, respectively. Moreover, the OAG score was independent of clinical features and also exhibited a good ability for prognosis prediction in the ICGC-LIHC-JP cohort and GSE54236 dataset. Expectedly, the OAG score was also highly correlated with metabolic processes, especially oxidative-related signaling pathways. Furthermore, abundant enrichment of chemokines, receptors, MHC molecules, and other immunomodulators as well as PD-L1/PD-1 expression among patients with high OAG scores indicated that they might have better responses to immunotherapy. However, probably exclusion of T cells from infiltrating tumors resulting in lower infiltration of effective T cells would restrict immunotherapeutic effects. In addition, the OAG score was significantly associated with the response of sorafenib and TACE treatment. Conclusions: Overall, this study comprehensively disclosed the relationship between BMI-guided transcriptome and HCC. Moreover, the OAG signature had the potential clinical applications in the future to promote clinical management and precision medicine of HCC.

Mechanically Induced Switching between Two Discrete Conductance States: A Potential Single-Molecule Variable Resistor.

The fabrication of solid-state single-molecule switches with high on-off conductance ratios has been proposed to advance conventional technology in areas such as molecular electronics. Herein, we employed the scanning tunneling microscope break junction (STM-BJ) technique to modulate conductance in single-molecule junctions using mechanically induced stretching. Compound 1a possesses two dihydrobenzothiophene (DHBT) anchoring groups at the opposite ends linked with rigid alkyne side arms to form a gold-molecule-gold junction, while 1b contains 4-pyridine-anchoring groups. The incorporation of ferrocene into the backbone of each compound allows rotational freedom to the cyclopentadienyl (Cp) rings to give two distinct conductance states (high and low) for each. Various control experiments and suspended junction compression/retraction measurements indicate that these high- and low-conductance plateaus are the results of conformational changes within the junctions (extended and folded states) brought about by mechanically induced stretching. A high-low switching factor of 42 was achieved for 1a, whereas an exceptional conductance ratio in excess of 2 orders of magnitude (205) was observed for 1b. To the best of our knowledge, this is the highest experimental on-off conductance switching ratio for a single-molecule junction exploiting the mechanically induced STM-BJ method. Computational studies indicated that the two disparate conductance states observed for 1a and 1b result from mechanically induced conformational changes due to an interplay between conductance and the dihedral angles associated with the electrode-molecule interfaces. Our study reveals the structure-function relationship that determines conductance in such flexible and dynamic systems and promotes the development of a single-molecule variable resistor with high on-off switching factors.

Soil Bacteria to Regulate Phoebe bournei Seedling Growth and Sustainable Soil Utilization under NPK Fertilization.

Soil bacteria play a key role in the plant-soil system and can regulate the growth of Phoebe bournei seedlings under fertilization. However, there are few reports on how soil bacteria respond to fertilization and regulate seedling growth. This study adopted the "3414" field fertilization experiment, combined with soil microbial sequencing, nutrient contents, and biomass measurement, to explore the changes of soil chemical properties and bacterial structure under different NPK fertilization conditions and to establish the coupling relationship between soil bacteria, soil nutrients, and plant growth. The results showed that NPK fertilization decreased soil pH; increased soil N, P, and K content; reduced bacterial diversity and abundance; promoted the growth of dominant bacterial species; and enhanced Phoebe bournei seedlings' soil N, P, and K elements. NPK fertilization promoted Proteobacteria growth, especially of three genera (Methylobacterium, Sphingobium, and Acinetobacter) and Actinobacteria, while it decreased Acidobacteria and Chloroflexi. By reducing the ratio of N to K and increasing P, NPK fertilization can slow soil acidification, promote bacterial reproduction, maintain P. bournei seedlings' soil ecological stability, and balance the seedlings' growth and sustainable soil utilization. AD3, Pseudomonas, and Rhodanobacter can be used as the marker species for N, P, and K fertilization, respectively, while Methylobacterium, Brevundimonas, Acinetobacter, and Sphingobium can be used as indicator species for soil pH and soil N, P, and K content changes, respectively. These results provided a theoretical basis and technical guidance for the effective fertilization and cultivation of robust P. bournei seedlings.

Se4P4nanoparticles confined within porous carbon as a lithium-ion battery anode with superior electrochemical performance.

The exploration of advanced anode materials through rational structure/phase design is the key to developing high-performance rechargeable batteries. Herein, tetraphosphorus tetraselenide (Se4P4) nanoparticles confined within porous carbon (named SeP@C) are developed for lithium-ion batteries. The designed SeP@C shows a set of structural/compositional advantages as lithium-ion battery anodes including high electrical conductivity, low ion diffusion barrier, and relieved lithiation stress. Consequently, the SeP@C electrode displays superior comprehensive lithium storage performance, e.g., high reversible capacity (640.8 mA h g-1at 0.1 A g-1), excellent cycling stability (500 cycles with respective capacity retention of over or nearly 100%), and good rate capability, representing a comparable lithium storage performance in reported phosphide-based anodes. More significantly, it shows excellent energy storage properties in lithium-ion full cells which can light up 85 red LEDs for over 3.2 h. This work offers an advanced electrode construction guidance of phosphorous-based anodes for the development of high-performance energy storage devices.