Identifying specific TLS-associated genes as potential biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in soft tissue sarcoma.

Background: The tertiary lymphatic structure (TLS) is an important component of the tumor immune microenvironment and has important significance in patient prognosis and response to immune therapy. However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear. Methods: A total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and "MCPcounter" algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes. Results: In this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells. Conclusion: This study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.

Active Oxygenated Structure-Intensified CO2 Capture Enables Efficient Electrochemical Ethylene Production Over Carbon Nanofibers.

The pursuit of high efficacy C-C coupling during the electrochemical CO2 reduction reaction remains a tremendous challenge owing to the high energy barrier of CO2 activation and insufficient coverage of the desired intermediates on catalytic sites. Inspired by the concept of capture-coupled CO2 activation, we fabricated quinone-grafted carbon nanofibers via an in situ oxidative carbonylation strategy. The quinone functionality of carbon nanofibers promotes the capture of CO2 followed by activation. At a current density of 400 mA cm-2, the Faradaic efficiency of ethylene reached 62.9%, and a partial current density of 295 mA cm-2 was achieved on the quinone-rich carbon nanofibers. The results of in situ spectroscopy and theoretical calculations indicated that the remarkable selectivity enhancement in ethylene originates from the quinone structure, rather than the electronic properties of Cu particles. The interaction of quinone with CO2 increases the local *CO coverage and simultaneously hinders the co-adsorption of *H on Cu sites, which greatly reduces the energy barrier for C-C coupling and restrains subsequent *CO protonation. The modulation strategy involving specific oxygenated structure, as an independent degree of freedom, guides the design of functionalized carbon materials for tailoring the selectivity of desired products during the CO2 capture and reduction.

Predicting TCR sequences for unseen antigen epitopes using structural and sequence features.

T-cell receptor (TCR) recognition of antigens is fundamental to the adaptive immune response. With the expansion of experimental techniques, a substantial database of matched TCR-antigen pairs has emerged, presenting opportunities for computational prediction models. However, accurately forecasting the binding affinities of unseen antigen-TCR pairs remains a major challenge. Here, we present convolutional-self-attention TCR (CATCR), a novel framework tailored to enhance the prediction of epitope and TCR interactions. Our approach utilizes convolutional neural networks to extract peptide features from residue contact matrices, as generated by OpenFold, and a transformer to encode segment-based coded sequences. We introduce CATCR-D, a discriminator that can assess binding by analyzing the structural and sequence features of epitopes and CDR3-ß regions. Additionally, the framework comprises CATCR-G, a generative module designed for CDR3-ß sequences, which applies the pretrained encoder to deduce epitope characteristics and a transformer decoder for predicting matching CDR3-ß sequences. CATCR-D achieved an AUROC of 0.89 on previously unseen epitope-TCR pairs and outperformed four benchmark models by a margin of 17.4%. CATCR-G has demonstrated high precision, recall and F1 scores, surpassing 95% in bidirectional encoder representations from transformers score assessments. Our results indicate that CATCR is an effective tool for predicting unseen epitope-TCR interactions. Incorporating structural insights enhances our understanding of the general rules governing TCR-epitope recognition significantly. The ability to predict TCRs for novel epitopes using structural and sequence information is promising, and broadening the repository of experimental TCR-epitope data could further improve the precision of epitope-TCR binding predictions.

Mesoporous Electrocatalysts with p-n Heterojunctions for Efficient Electroreduction of CO2 and N2 to Urea.

The electrocatalytic synthesis of high-value-added urea by activating N2 and CO2 is a green synthesis technology that has achieved carbon neutrality. However, the chemical adsorption and C-N coupling ability of N2 and CO2 on the surface of the catalyst are generally poor, greatly limiting the improvement of electrocatalytic activity and selectivity in electrocatalytic urea synthesis. Herein, novel hierarchical mesoporous CeO2/Co3O4 heterostructures are fabricated, and at an ultralow applied voltage of -0.2 V, the urea yield rate reaches 5.81 mmol g-1 h-1, with a corresponding Faraday efficiency of 30.05%. The hierarchical mesoporous material effectively reduces the mass transfer resistance of reactants and intermediates, making it easier for them to access active centers. The emerging space-charge regions at the heterointerface generate local electrophilic and nucleophilic regions, facilitating CO2 targeted adsorption in the electrophilic region and activation to produce *CO intermediates and N2 targeted adsorption in the nucleophilic region and activation to generate *N ═ N* intermediates. Then, the electrons in the σ orbitals of *N ═ N* intermediates can be easily accepted by the empty eg orbitals of Co3+ in CeO2/Co3O4, which presents a low-spin state (LS: t2g6eg0). Subsequently, *CO couples with *N ═ N* to produce the key intermediate *NCON*. Interestingly, it was discovered through in situ Raman spectroscopy that the CeO2/Co3O4 catalyst has a reversible spinel structure before and after the electrocatalytic reaction, which is due to the surface reconstruction of the catalyst during the electrocatalytic reaction process, producing amorphous active cobalt oxides, which is beneficial for improving electrocatalytic activity.

CD36-mediated podocyte lipotoxicity promotes foot process effacement.

Background: Lipid metabolism disorders lead to lipotoxicity. The hyperlipidemia-induced early stage of renal injury mainly manifests as podocyte damage. CD36 mediates fatty acid uptake and the subsequent accumulation of toxic lipid metabolites, resulting in podocyte lipotoxicity. Methods: Male Sprague-Dawley rats were divided into two groups: the normal control group and the high-fat diet group (HFD). Podocytes were cultured and treated with palmitic acid (PA) and sulfo-N-succinimidyl oleate (SSO). Protein expression was measured by immunofluorescence and western blot analysis. Boron-dipyrromethene staining and Oil Red O staining was used to analyze fatty acid accumulation. Results: Podocyte foot process (FP) effacement and marked proteinuria occurred in the HFD group. CD36 protein expression was upregulated in the HFD group and in PA-treated podocytes. PA-treated podocytes showed increased fatty acid accumulation, reactive oxygen species (ROS) production, and actin cytoskeleton rearrangement. However, pretreatment with the CD36 inhibitor SSO decreased lipid accumulation and ROS production and alleviated actin cytoskeleton rearrangement in podocytes. The antioxidant N-acetylcysteine suppressed PA-induced podocyte FP effacement and ROS generation. Conclusions: CD36 participated in fatty acid-induced FP effacement in podocytes via oxidative stress, and CD36 inhibitors may be helpful for early treatment of kidney injury.

[Identification and expression analysis of the HSP70 gene family under abiotic stresses in Litchi chinensis].

HSP70 protein, as an important member of the heat shock protein (HSP) family, plays an important role in plant growth, development, and response to biotic and abiotic stresses. In order to explore the role of HSP70 gene family members in Litchi chinensis under low temperature, high temperature, drought, and salt stress, bioinformatics methods were used to identify the HSP70 gene family members within the entire L. chinensis genome. The expression of these genes under various abiotic stresses was then detected using quantitative real-time PCR (qRT-PCR). The results showed that the LcHSP70 gene family consisted of 18 members, which were unevenly distributed across ten L. chinensis chromosomes. The LcHSP70 protein contained 479-851 amino acids, with isoelectric points ranging from 5.07 to 6.95, and molecular weights from 52.44 kDa to 94.07 kDa. The predicted subcellular localization showed that LcHSP70 protein was present in the nucleus, cytoplasm, endoplasmic reticulum, mitochondria, and chloroplast. Phylogenetic analysis divided the LcHSP70 proteins into five subgroups, namely Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅵ. The promoter regions of the LcHSP70 genes contained various cis-acting elements related to plant growth, development, hormone response, and stress response. Moreover, the expression of LcHSP70 genes displayed distint tissue-specific expression level, categorized into universal expression and specific expression. From the selected 6 LcHSP70 genes (i.e., LcHSP70-1, LcHSP70-5, LcHSP70-10, LcHSP70-14, LcHSP70-16, and LcHSP70-18), their relative expression levels were assessed under different abiotic stresses using qRT-PCR. The results indicated that the gene family members exhibited diverse responses to low temperature, high temperature, drought, and salt stress, with significant variations in their expression levels across different time periods. These results provide a foundation for further exploration of the function of the LcHSP70 gene family.

Boosting the Carrier Lifetime and Optical Activity of CsPbX3 Nanocrystals through Aromatic Ligand Passivation.

Ligand engineering is crucial for tuning the structural and optoelectronic properties of perovskite nanocrystals (NCs), which also improves their stability. In contrast to the typically used long-chain alkylamine ligands, we successfully introduced an aromatic 1-(p-tolyl)ethylamine (PTEA) ligand to synthesize the CsPbX3 (X = Br or I) NCs. The CsPbI3 and CsPbBr3 NCs demonstrated long carrier lifetimes of ∼877 and 49 ns, respectively, as well as high photoluminescence quantum yields (PLQYs) of ∼99% and 95%, respectively. Furthermore, such NCs realized excellent long-term stability in an ambient atmosphere without obvious degradation over one month. All of these properties were better than the properties of NCs coated with the conventional alkylamine ligands. The high performance of these NCs was discussed with the effective surface passivation by PTEA. Our finding suggests a facile and effective ligand (PTEA) for modulating perovskites, achieving enhancement of both the carrier lifetime and the PLQY.

Spatiotemporal characterization of PM2.5, O3, and trace gases associated with East Asian continental outflows via drone sounding.

East Asian continental outflows with PM2.5, O3, and other species may determine the baseline conditions and affect the air quality in downwind areas via long-range transport (LRT). To gain insight into the impact and spatiotemporal characteristics of airborne pollutants in East Asian continental outflows, a versatile multicopter drone sounding platform was used to simultaneously observe PM2.5, O3, CO2, and meteorological variables (temperature, specific humidity, pressure, and wind vector) above the northern tip of Taiwan, Cape Fuiguei, which often encounters continental outflows during winter monsoon periods. By coordinating hourly high-spatial-resolution profiles provided by drone soundings, WRF/CMAQ model air quality predictions, HYSPLIT-simulated backward trajectories, and MERRA-2 reanalysis data, we analyzed two prominent phenomena of airborne pollutants in continental outflows to better understand their physical/chemical characteristics. First, we found that pollutants were well mixed within a sounding height of 500 m when continental outflows passed through and completely enveloped Cape Fuiguei. Eddies induced by significant fluctuations in wind speeds coupled with minimal temperature inversion and LRT facilitated vertical mixing, possibly resulting in high homogeneity of pollutants within the outflow layer. Second, the drone soundings indicated exceptionally high O3 concentrations (70-100 ppbv) but relatively low concentrations of PM2.5 (10-20 µg/m3), CO2 (420-425 ppmv), and VOCs in some air masses. The low levels of PM2.5, CO2, and VOCs ruled out photochemistry as the cause of the formation of high-level O3. Further coordination of spatiotemporal data with air mass trajectories and O3 cross sections provided by MERRA-2 suggested that the high O3 concentrations could be attributed to stratospheric intrusion and advection via continental outflows. High-level O3 concentrations persisted in the lower troposphere, even reaching the surface, suggesting that stratospheric intrusion O3 may be involved in the rising trend in O3 concentrations in parts of East Asia in recent years in addition to surface photochemical factors.

The efficacy and safety of PD-1 inhibitor combined with TACE in the first-line treatment of unresectable hepatocellular carcinoma.

The application of immune checkpoint inhibitors (ICIs) has changed the treatment of advanced hepatocellular carcinoma. Transcatheter arterial chemoembolization (TACE) is a first-line treatment for intermediate hepatocellular carcinoma. Serving as a local treatment modality that can induce immunogenic cell death, the efficacy and safety of combined use with ICI have not been evaluated. Although there have been prospective studies aimed at evaluating the efficacy and safety of ICI combined with TACE in BCLC stage B HCC patients, there are few reports on the evaluation of BCLC stage C patients with distant metastasis or portal vein cancer thrombus. Data of unresectable hepatocellular carcinoma patients received PD-1 inhibitor and TACE were collected in Xijing Hospital from June 2019 to December 2022. The tumor response was evaluated according to the Solid Tumor Modified Response Evaluation Standard (mRECIST), including complete response (CR), partial response (PR), disease stability (SD), disease progression (PD), objective response rate (ORR), and disease control rate (DCR). The progression-free survival (PFS) and overall survival (OS) were used to estimate therapy efficacy. The treatment-related adverse events were evaluated based on National Cancer Institute Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. A total of 42 patients with unresectable hepatocellular carcinoma were included in this study, including 34 males (80.5%) and 8 females (19.5%). The average age is 54.5 years, ranging from 34 to 72. The median follow-up time was 12.3 months, with an ORR of 42.9% and a DCR of 90.5% as of the follow-up time. The median PFS is 7.5 months (95% CI: 5.76-9.23), and the median OS has not yet been reached; 6-month PFS was 62.2%. Safety analysis showed that 41 (97.6%) patients experienced treatment-related adverse reactions, mainly including elevated AST and ALT, fever, elevated bilirubin, hypothyroidism, nausea, abdominal pain, and rash. 40 patients had grade 1/2 adverse reactions, and only one patient had grade 3 adverse reactions, manifested as intolerable rash, nausea, and vomiting. Treatment is terminated when symptomatic treatment and drug suspension cannot be alleviated. In this study, thre patients with unresectable hepatocellular carcinoma were treated with PD-1 inhibitor combined with TACE to achieve good tumor reduction effect and underwent liver cancer resection surgery. For patients with unresectable hepatocellular carcinoma, whether in BCLC stage B or stage C, effective systemic therapy (PD-1 inhibitor) combined with local therapy (TACE) can achieve a high rate of tumor regression and objective response. Some patients may even pursue surgical treatment opportunities, and the treatment-related adverse reactions are controllable, which is expected to provide new options for extending the survival of unresectable hepatocellular carcinoma patients.

Repair of hydrogel wearable devices through topological adhesion and cross-shaped sectional enhancement strategy.

Hydrogels, recognized for their biocompatibility, are extensively employed in the realm of wearable devices. Nevertheless, their application is often constrained by their low mechanical robustness, rendering them susceptible to damage during operation. The restoration of their load-bearing and sensory functionalities post-damage represents a captivating yet underexplored domain. Conventional repair techniques, reliant on hydrogen bonding or van der Waals forces, falter in the face of hydrogels' high water content. In this study, a novel composite adhesive gel (SGG), integrating sodium alginate, guar gum, and graphene oxide, was engineered to mend impaired hydrogels. Furthermore, an optimized repair approach, utilizing a cross-shaped sectional (CSS) enhancement strategy, was devised to reinstate the hydrogels' load and sensory capabilities. Investigations revealed that the SGG adhesive infiltrated the hydrogel, establishing an intermediary gel stratum, subsequently solidifying to mend the material through topological adhesion. This process reestablished the continuity of the polymer network and the aqueous phase within the hydrogel. Following the application of the CSS augmentation method, the peak tensile strain of the remediated hydrogel exceeded 200 %, with the uppermost observable adhesive energy touching 2526 J/m2. In addition, the ability to respond to strain was significantly rejuvenated, suggesting an effective methodology for the rehabilitation of wearable technology.

Genome-Wide Characterization and Phylogenetic and Stress Response Expression Analysis of the MADS-Box Gene Family in Litchi (Litchi chinensis Sonn.).

The MADS-box protein is an important transcription factor in plants and plays an important role in regulating the plant abiotic stress response. In this study, a total of 94 MADS-box genes were predicted in the litchi genome, and these genes were widely distributed on all the chromosomes. The LcMADS-box gene family was divided into six subgroups (Mα, Mß, Mγ, Mδ, MIKC, and UN) based on their phylogenetical relationships with Arabidopsis, and the closely linked subgroups exhibited more similarity in terms of motif distribution and intron/exon numbers. Transcriptome analysis indicated that LcMADS-box gene expression varied in different tissues, which can be divided into universal expression and specific expression. Furthermore, we further validated that LcMADS-box genes can exhibit different responses to various stresses using quantitative real-time PCR (qRT-PCR). Moreover, physicochemical properties, subcellular localization, collinearity, and cis-acting elements were also analyzed. The findings of this study provide valuable insights into the MADS-box gene family in litchi, specifically in relation to stress response. The identification of hormone-related and stress-responsive cis-acting elements in the MADS-box gene promoters suggests their involvement in stress signaling pathways. This study contributes to the understanding of stress tolerance mechanisms in litchi and highlights potential regulatory mechanisms underlying stress responses.

Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy in melanoma.

BACKGROUND: Tumor cells frequently suffer from endoplasmic reticulum (ER) stress. Previous studies have extensively elucidated the role of tumorous unfolded protein response in melanoma cells, whereas the effect on tumor immunology and the underlying mechanism remain elusive. METHODS: Bioinformatics, biochemical assays and pre-clinical mice model were employed to demonstrate the role of tumorous inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in anti-tumor immunity and the underlying mechanism. RESULTS: We firstly found that IRE1α signaling activation was positively associated with the feature of tumor-infiltrating lymphocytes. Then, pharmacological ER stress induction by HA15 exerted prominent anti-tumor effect in immunocompetent mice and was highly dependent on CD8+T cells, paralleled with the reshape of immune cells in tumor microenvironment via tumorous IRE1α-XBP1 signal. Subsequently, tumorous IRE1α facilitated the expression and secretion of multiple chemokines and cytokines via XBP1-NF-κB axis, leading to increased infiltration and anti-tumor capacity of CD8+T cells. Ultimately, pharmacological induction of tumorous ER stress by HA15 brought potentiated therapeutic effect along with anti-PD-1 antibody on melanoma in vivo. CONCLUSIONS: Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy by regulating chemokines and cytokines via XBP1-NF-κB axis. The combination of ER stress inducer and anti-PD-1 antibody could be promising for increasing the efficacy of melanoma immunotherapy.

The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells / 中华创伤杂志(英文版)

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Genome-Wide Development of Polymorphic SNP Markers and Evaluation of Genetic Diversity of Litchi (Litchi chinensis Sonn.).

Litchi (Litchi chinensis Sonn.) is a highly valuable fruit crop that is widely grown in tropical and subtropical areas of the world. Studying its genetic diversity and population structure is critical for effective conservation and breeding programs. In this study, we developed 150 single-nucleotide polymorphism (SNP) markers that were evenly spaced across litchi genome and applied them to the evaluation of the genetic diversity of 84 litchi accessions, including old cultivars, modern cultivars, hybrids from known parents and wild accessions. Ninety-one SNP markers, showing high levels of polymorphism and high genotyping success rates, were used for further analysis. The newly developed SNP markers captured a relatively higher level of genetic diversity (He = 0.364) in litchi cultivars and could be successfully applied for the identification of synonymous cultivars and hybrids with close genetic backgrounds. Cluster analysis grouped all genotypes into three clusters that showed perfect association with their fruit maturation period, among which wild accessions clustered with their corresponding domesticated cultivars, and hybrids from different parent combinations showed different inheritance tendencies. Our study not only provided a set of efficient SNP markers for future genetic research, but also laid an important foundation for the conservation and genetic breeding of litchi.

An LcMYB111-LcHY5 Module Differentially Activates an LcFLS Promoter in Different Litchi Cultivars.

Flavonol synthase (FLS) is the crucial enzyme of the flavonol biosynthetic pathways, and its expression is tightly regulated in plants. In our previous study, two alleles of LcFLS,LcFLS-A and LcFLS-B, have been identified in litchi, with extremely early-maturing (EEM) cultivars only harboring LcFLS-A, while middle-to-late-maturing (MLM) cultivars only harbor LcFLS-B. Here, we overexpressed both LcFLS alleles in tobacco, and transgenic tobacco produced lighter-pink flowers and showed increased flavonol levels while it decreased anthocyanin levels compared to WT. Two allelic promoters of LcFLS were identified, with EEM cultivars only harboring proLcFLS-A, while MLM cultivars only harbor proLcFLS-B. One positive and three negative R2R3-MYB transcription regulators of LcFLS expression were identified, among which only positive regulator LcMYB111 showed a consistent expression pattern with LcFLS, which both have higher expression in EEM than that of MLM cultivars. LcMYB111 were further confirmed to specifically activate proLcFLS-A with MYB-binding element (MBE) while being unable to activate proLcFLS-B with mutated MBE (MBEm). LcHY5 were also identified and can interact with LcMYB111 to promote LcFLS expression. Our study elucidates the function of LcFLS and its differential regulation in different litchi cultivars for the first time.

Machine learning applications for the prediction of extended length of stay in geriatric hip fracture patients.

BACKGROUND: Geriatric hip fractures are one of the most common fractures in elderly individuals, and prolonged hospital stays increase the risk of death and complications. Machine learning (ML) has become prevalent in clinical data processing and predictive models. This study aims to develop ML models for predicting extended length of stay (eLOS) among geriatric patients with hip fractures and to identify the associated risk factors. AIM: To develop ML models for predicting the eLOS among geriatric patients with hip fractures, identify associated risk factors, and compare the performance of each model. METHODS: A retrospective study was conducted at a single orthopaedic trauma centre, enrolling all patients who underwent hip fracture surgery between January 2018 and December 2022. The study collected various patient characteristics, encompassing demographic data, general health status, injury-related data, laboratory examinations, surgery-related data, and length of stay. Features that exhibited significant differences in univariate analysis were integrated into the ML model establishment and subsequently cross-verified. The study compared the performance of the ML models and determined the risk factors for eLOS. RESULTS: The study included 763 patients, with 380 experiencing eLOS. Among the models, the decision tree, random forest, and extreme Gradient Boosting models demonstrated the most robust performance. Notably, the artificial neural network model also exhibited impressive results. After cross-validation, the support vector machine and logistic regression models demonstrated superior performance. Predictors for eLOS included delayed surgery, D-dimer level, American Society of Anaesthesiologists (ASA) classification, type of surgery, and sex. CONCLUSION: ML proved to be highly accurate in predicting the eLOS for geriatric patients with hip fractures. The identified key risk factors were delayed surgery, D-dimer level, ASA classification, type of surgery, and sex. This valuable information can aid clinicians in allocating resources more efficiently to meet patient demand effectively.

Relationships among body weight, lipids and bone mass in elderly individuals with fractures: A case-control study.

BACKGROUND: The prevalence of osteoporosis and low bone mass is steadily rising each year. Low body weight is commonly linked to diminished bone mass and serves as a robust predictor of osteoporosis. Nonetheless, the connection between body mass index (BMI), bone mineral density, and lipid profiles among the elderly remains elusive. AIM: To examine the association between BMI and bone mass, explore the correlation between lipid profiles and bone mass, and delve into the interplay between lipid metabolism and bone health. METHODS: The study included 520 patients aged ≥ 65 years (178 men and 342 women). Age, sex, weight, and height were recorded. Femoral neck bone mineral density and T scores were determined using a dual-energy X-ray absorptiometry scanner. Blood calcium (Ca), phosphorus (P), albumin (ALB), alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured. Patients were classified by sex (male and female), age (65-79 years and ≥ 80 years), and T score (normal bone mineral density, osteopenia and osteoporosis). RESULTS: Age, sex, BMI, and ALP and TG levels were independent risk factors for osteoporosis. For the 65-79- and ≥ 80-year-old groups, females presented lower T scores than males. Ca, P, ALB, ALP, TC, HDL and LDL levels were significantly different between men and women in the 65-79-year-old group. In addition, BMI and TG levels were significantly decreased in osteoporotic patients compared with patients with normal bone mass. TC levels declined in 65- to 79-year-old male and female osteoporosis patients. In the group of women aged ≥ 80 years, osteoporotic patients showed significantly increased ALP levels. Furthermore, we found positive correlations between BMI and TG levels in the male and female patient groups. However, we found no significant differences in ALB, Ca, P, HDL and LDL levels in osteoporotic patients compared to patients with normal bone mass. CONCLUSION: Osteoporotic patients showed significantly decreased BMI and TG levels compared with those with normal bone mass. BMI showed positive correlations with TG levels in male and female patients. These results indicate correlations between BMI and bone mass and between lipid profiles and bone mass.

The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis.

Purpose: Hepatocellular carcinoma(HCC) is the most common type of liver cancer and the sixth largest common cancer worldwide. Although surgical resection, hepatic arterial chemoembolization, targeted drugs and immunotherapy are currently available, the mortality of advanced patients remains high. Therefore, new therapeutic targets are urgently needed. In recent years, many studies have found that The long non-coding RNA(lncRNA) has multiple functions in human tumors, including participating in epigenetic, transcriptional, post-transcriptional and translational regulation, and is closely related to the progression of HCC. The purpose of this study was to investigate the role of AC006329.1 in HCC progression and provide theoretical guidance for finding new targets. Patients and Methods: AC006329.1 was screened out by transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Then a series of functional tests in vivo and in vitro were conducted to investigate the effects of AC006329.1 on HCC progression and metastasis. Epithelial-mesenchymal transformation (EMT) of HCC was detected by Western blot and immunofluorescence staining. The targeted miRNA and downstream gene of AC006329.1 were predicted by databases and the pathway regulation axis eventually validated by dual luciferase reporter assays, qRT-PCR and WB. Results: AC006329.1 was found high expressed in HCC tissues and cell lines by qRT-PCR. The prognosis of HCC patients with high expressed AC006329.1 was poor. In vitro and in vivo, overexpression of AC006329.1 can promote the progression, metastasis and EMT of HCC by acting as a sponge of miR-127-5p to increase the expression of SHC3. In addition, up-regulation of miR-127-5p or knockdown of SHC3 can both reverse the promoting effects of AC006329.1 on progression, metastasis and EMT of HCC. Finally, WB and qRT-PCR analysis was discovered that AC006329.1 can facilitate HCC progression, EMT and metastasis by competitively inhibiting miR-127-5p to activate SHC3/ERK signaling pathway. Conclusion: These above experimental results confirmed that AC006329.1 can facilitate HCC progression, EMT and metastasis by acting as a competing endogenous RNA (ceRNA) to inhibit miR-127-5p and activate SHC3/ERK signaling pathway.

HIV-1 molecular transmission network and drug resistance in Chongqing, China, among men who have sex with men (2018-2021).

BACKGROUND: Over the past few years, HIV transmission among men who have sex with men (MSM) in China has increased significantly. Chongqing, located in the southwest of China, has the highest prevalence of HIV among MSM in the country. METHODS: Blood samples were taken from 894 MSM in Chongqing who had recently been diagnosed with HIV-1 infection and had not yet started getting treatment. In order to determine the distribution of HIV-1 subtypes, transmitted drug resistance, and assessments of molecularly transmitted clusters, we sequenced the Pol genes and employed them in phylogenetic analysis. The genetic distance between molecular clusters was 1.5%. To find potential contributing factors, logistic regression analyses were performed. RESULTS: Of the 894 HIV-1 pol sequences acquired from study participants, we discovered that CRF07_BC (73.6%) and CRF01_AE (19.6%) were the two most prevalent HIV-1 genotypes in Chongqing among MSM, accounting for 93.2% of all infections. In addition, CRF08_BC (1.1%), B subtype (1.0%), CRF55_01B (3.4%), and URF/Other subtypes (1.3%) were less frequently observed. Among MSM in Chongqing, transmitted drug resistance (TDR) was reported to be present at a rate of 5.6%. 48 clusters with 600 (67.1%, 600/894) sequences were found by analysis of the molecular transmission network. The distributions of people by age, sexual orientation, syphilis, and genotype were significantly differentially related to being in clusters, according to the multivariable logistic regression model. CONCLUSION: Despite the low overall prevalence of TDR, the significance of genotypic drug resistance monitoring needs to be emphasized. CRF07_BC and CRF01_AE were the two main genotypes that created intricate molecular transmission networks. In order to prevent the expansion of molecular networks and stop the virus's spread among MSM in Chongqing, more effective HIV intervention plans should be introduced.

HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis.

BACKGROUND: Accumulating data indicate that N6-methyladenosine (m6A) RNA methylation and lncRNA deregulation act crucial roles in cancer progression. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as an m6A "reader" has been reported to be an oncogene in multiple malignancies. We herein aimed to elucidate the role and underlying mechanism by which HNRNPA2B1-mediated m6A modification of lncRNAs contributes to non-small cell lung cancer (NSCLC). METHODS: The expression levels of HNRNPA2B1 and their association with the clinicopathological characteristics and prognosis in NSCLC were determined by RT-qPCR, Western blot, immunohistochemistry and TCGA dataset. Then, the role of HNRNPA2B1 in NSCLC cells was assessed by in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. HNRNPA2B1-mediated m6A modification of lncRNAs was screened by m6A-lncRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (Me-RIP). The lncRNA MEG3-specific binding with miR-21-5p was evaluated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses. RESULTS: We found that upregulation of HNRNPA2B1 was associated with distant metastasis and poor survival, representing an independent prognostic factor in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis in vitro and in vivo, whereas ectopic expression of HNRNPA2B1 possessed the opposite effects. Mechanical investigations revealed that lncRNA MEG3 was an m6A target of HNRNPA2B1 and inhibition of HNRNPA2B1 decreased MEG3 m6A levels but increased its mRNA levels. Furthermore, lncRNA MEG3 could act as a sponge of miR-21-5p to upregulate PTEN and inactivate PI3K/AKT signaling, leading to the suppression of cell proliferation and invasion. Low expression of lncRNA MEG3 or elevated expression of miR-21-5p indicated poor survival in patients with NSCLC. CONCLUSIONS: Our findings uncover that HNRNPA2B1-mediated m6A modification of lncRNA MEG3 promotes tumorigenesis and metastasis of NSCLC cells by regulating miR-21-5p/PTEN axis and may provide a therapeutic target for NSCLC.