Advances in targeted delivery of mRNA into immune cells for enhanced cancer therapy.

Messenger RNA (mRNA) therapy has been applied to the treatment of various human diseases including malignant tumors. Increasing evidences have shown that mRNA can enhance the efficacy of cancer immunotherapy by modulating the functions of immune cells and stimulating their activity. However, mRNA is a type of negatively charged biomacromolecules that are susceptible to serum nucleases and cannot readily cross the cell membrane. In the past few decades, various nanoparticles (NPs)-based delivery systems have been rationally designed and developed to facilitate the intracellular uptake and cytosolic delivery of mRNA. More importantly, by means of the specific recognition between the targeting ligands decorated on NP surface and receptors specifically expressed on immune cells, these mRNA delivery systems could be functionalized to target immune cells to further enhance the mRNA-based cancer immunotherapy. In this review, we briefly introduced the advancements of mRNA in cancer therapy, discussed the challenges faced by mRNA delivery, and systematically summarized the recent development in NPs-based mRNA delivery systems targeting various types of immune cells for cancer immunotherapy. The future development of NPs-mediated targeted mRNA delivery and their challenges in clinical translation are also discussed.

Predatory protists impact plant performance by promoting plant growth-promoting rhizobacterial consortia.

Plant performance is impacted by rhizosphere bacteria. These bacteria are subjected to both bottom-up control by root exudates as well as top-down control by predators, particularly protists. Protists stimulate plant growth-promoting microbes resulting in improved plant performance. However, knowledge of the mechanisms that determine the interconnections within such tripartite protist-bacteria-plant interactions remains limited. We conducted experiments examining the effects of different densities of the predatory protist Cercomonas lenta on rhizosphere bacterial communities, specifically zooming on interactions between Cercomonas lenta and key bacterial taxa, as well as interactions among key bacterial taxa. We tracked rhizosphere bacterial community composition, potential microbial interactions, and plant performance. We found that Cercomonas lenta inoculation led to an average increase in plant biomass of 92.0%. This effect was linked to an increase in plant growth-promoting rhizobacteria (Pseudomonas and Sphingomonas) and a decrease in bacteria (Chitinophaga) that negatively impact on plant growth-promoting rhizobacteria. We also found evidence for cooperative enhancements in biofilm formation within the plant growth-promoting rhizobacterial consortium. Cercomonas lenta enhanced a plant growth-promoting rhizobacterial consortium colonization by promoting its cooperative biofilm formation in the rhizosphere, leading to a 14.5% increase in phosphate solubilization that benefits plant growth. Taken together, we provide mechanistic insights into how the predatory protist Cercomonas lenta impacts plant growth, namely by stimulating plant beneficial microbes and enhancing their interactive activities such as biofilm formation. Predatory protists may therefore represent promising biological agents that can contribute to sustainable agricultural practices by promoting interactions between the plant and its microbiome.

SNAI2 as a Prognostic Biomarker Based on Cancer-Associated Fibroblasts in Patients With Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a common type of malignant tumor with therapeutic challenges. Cancer-associated fibroblasts (CAFs) promote LUAD growth and metastasis, regulate the tumor immune response, and influence tumor treatment responses and drug resistance. However, the molecular mechanisms through which CAFs control LUAD progression are largely unknown. In this study, we aimed to determine the correlations between CAF-related genes and overall survival (OS) in patients with LUAD. Methods: We acquired the gene expression data and clinical information of 522 patients with LUAD patients from The Cancer Genome Atlas (TCGA) and 442 patients with LUAD from the Gene Expression Omnibus (GEO) databases. CAF infiltration levels were assessed using the Microenvironment Cell Population (MCP) counter, the Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm, and Tumor Immune Dysfunction and Exclusion (TIDE) scores. A CAF-related gene network was constructed using the Weighted gene co-expression network analysis (WGCNA). Based on the CAF-related genes, univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to identify prognostic genes. Gene expression levels within the prognostic model were validated using the Cancer Cell Line Encyclopedia (CCLE) databases and Western blotting. Results: Our results demonstrated that high CAF scores were associated with lower survival rates in patients with LUAD. Gene modules that were highly correlated with high CAF scores were closely associated with tissue characteristics and extracellular matrix structures in LUAD. In addition, correlations between CAF scores and responses to immunotherapy and chemotherapy were observed. Finally, we found that SNAI2 expression was higher in lung cancer tissues than in normal tissues. Conclusion: Deepening our understanding of the influence of CAFs on tumor progression and treatment response at the molecular level can aid the development of more effective therapeutic strategies. This study provides important insights into the functional mechanisms of action of CAFs in LUAD and highlights their clinical implications.

Phosphorus availability influences disease-suppressive soil microbiome through plant-microbe interactions.

BACKGROUND: Soil nutrient status and soil-borne diseases are pivotal factors impacting modern intensive agricultural production. The interplay among plants, soil microbiome, and nutrient regimes in agroecosystems is essential for developing effective disease management. However, the influence of nutrient availability on soil-borne disease suppression and associated plant-microbe interactions remains to be fully explored. T his study aims to elucidate the mechanistic understanding of nutrient impacts on disease suppression, using phosphorous as a target nutrient. RESULTS: A 6-year field trial involving monocropping of tomatoes with varied fertilizer manipulations demonstrated that phosphorus availability is a key factor driving the control of bacterial wilt disease caused by Ralstonia solanacearum. Subsequent greenhouse experiments were then conducted to delve into the underlying mechanisms of this phenomenon by varying phosphorus availability for tomatoes challenged with the pathogen. Results showed that the alleviation of phosphorus stress promoted the disease-suppressive capacity of the rhizosphere microbiome, but not that of the bulk soil microbiome. This appears to be an extension of the plant trade-off between investment in disease defense mechanisms versus phosphorus acquisition. Adequate phosphorus levels were associated with elevated secretion of root metabolites such as L-tryptophan, methoxyindoleacetic acid, O-phosphorylethanolamine, or mangiferin, increasing the relative density of microbial biocontrol populations such as Chryseobacterium in the rhizosphere. On the other hand, phosphorus deficiency triggered an alternate defense strategy, via root metabolites like blumenol A or quercetin to form symbiosis with arbuscular mycorrhizal fungi, which facilitated phosphorus acquisition as well. CONCLUSION: Overall, our study shows how phosphorus availability can influence the disease suppression capability of the soil microbiome through plant-microbial interactions. These findings highlight the importance of optimizing nutrient regimes to enhance disease suppression, facilitating targeted crop management and boosting agricultural productivity. Video Abstract.

Evaluation of Cardiac Function Recovery in Patients with Paroxysmal Atrial Fibrillation after Catheter Radiofrequency Ablation Using Two-Dimensional Speckle Tracking Imaging and Real-Time Three-Dimensional Echocardiography.

INTRODUCTION: The aim of this study was to evaluate the utility of 2D-STI and real-time three-dimensional echocardiography (RT-3DE) in assessing changes in left atrial (LA) structure and function in patients with paroxysmal atrial fibrillation (PAF) post-radiofrequency catheter ablation (RFCA). METHODS: A retrospective analysis was conducted on 44 PAF patients who underwent RFCA at BA Hospital from March 2022 to March 2023. An age- and gender-matched control group of 32 healthy individuals was also included. Comprehensive echocardiographic parameters including LA dimensions (LAAPD, LALRD), volumes (LAVmin, LAVmax), ejection fraction (LAEF), and tissue velocities (a', Ar) were compared between groups. Post-RFCA changes in these parameters were also assessed at 1, 3, and 6 months. RESULTS: Pre-RFCA, PAF patients demonstrated larger LA dimensions and volumes with reduced LAEF and tissue velocities compared to controls. Post-RFCA, there was a significant improvement in LAEF and left ventricular ejection fraction at 1, 3, and 6 months, with the most pronounced changes observed at 6 months. LA dimensions increased initially but then decreased from 1 to 6 months post-RFCA. Notably, strain rate (SRS, SRE, SRA) measurements in various LA segments improved progressively, with the most significant enhancements at 6 months, suggesting improved atrial mechanics. CONCLUSION: The application of 2D-STI and RT-3DE provides a quantitative means to evaluate the structural and functional changes in the LA of PAF patients following RFCA. The progressive improvements in LA dimensions, volumes, and strain measurements up to 6-month post-RFCA indicate the potential of these techniques in monitoring treatment efficacy and patient recovery.

The occurrence of banana Fusarium wilt aggravates antibiotic resistance genes dissemination in soil.

The spread of antibiotic resistance genes (ARGs) and subsequent soil-borne disease outbreaks are major threats to soil health and sustainable crop production. However, the relationship between occurrences of soil-borne diseases and the transmission of soil ARGs remains unclear. Here, soil ARGs, mobile genetic elements and microbial communities from co-located disease suppressive and conducive banana orchards were deciphered using metagenomics and metatranscriptomics approaches. In total, 23 ARG types, with 399 subtypes, were detected using a metagenomics approach, whereas 23 ARG types, with 452 subtypes, were discovered using a metatranscriptomics method. Furthermore, the metagenomics analysis revealed that the ARG total abundance levels were greater in rhizospheres (0.45 ARGs/16S rRNA on average) compared with bulk (0.32 ARGs/16S rRNA on average) soils. Interestingly, metatranscriptomics revealed that the total ARG abundances were greater in disease-conducive (8.85 ARGs/16S rRNA on average) soils than disease suppressive (1.45 ARGs/16S rRNA on average) soils. Mobile genetic elements showed the same trends as ARGs. Network and binning analyses indicated that Mycobacterium, Streptomyces, and Blastomonas are the main potential hosts of ARGs. Furthermore, Bacillus was significantly and negatively correlated with Fusarium (P < 0.05, r = -0.84) and hosts of ARGs (i.e., Mycobacterium, Streptomyces, and Blastomonas). By comparing metagenomic and metatranscriptomic analyses，this study demonstrated that metatranscriptomics may be more sensitive in indicating ARGs activities in soil. Our findings enable the more accurate assessment of the transmission risk of ARGs. The data provide a new perspective for recognizing soil health, in which soil-borne disease outbreaks appear to be associated with ARG spread, whereas beneficial microbe enrichment may mitigate wilt disease and ARG transmission.

Treatment outcomes of infertile women with endometrial hyperplasia undergoing their first IVF/ICSI cycle: A matched-pair study.

OBJECTIVE: The aim was to analyze the clinical characteristics, controlled ovarian stimulation status, pregnancy outcomes, and major factors influencing live births in patients with endometrial hyperplasia (EH) undergoing IVF/ICSI for assisted reproduction, so as to identify potential intervention measures. STUDY DESIGN: Patients with EH who achieved complete remission (CR) after conservative treatment and who were undergoing their first IVF/ICSI cycle were included in this matched-pair study. Patients with normal endometriums were matched at a 1:2 ratio with the control group for the first cycle of controlled ovarian stimulation. Matching was based on age, and reproductive outcomes were analyzed. RESULTS: Among the 263 patients (including 51 cases with atypical endometrial hyperplasia) in the study group, the pregnancy rate after the first controlled ovarian stimulation cycle was 48.67 % (128/263), and the live birth rate was 34.98 % (92/263). Multiple logistic regression analysis revealed that maternal age, body mass index (BMI), and endometrial thickness were significantly associated with live births (P<0.001). Specifically, being aged ≥ 35 years (OR 0.450, 95 % CI 0.223-0.907) and having a BMI≥28 kg/m2 (OR 0.358, 95 % CI 0.161-0.798) were identified as unfavorable factors for a clinical live birth, while an endometrial thickness ≥ 10 mm was found to be a favorable factor. CONCLUSION(S): ART is effective in patients with EH who have achieved CR after conservative treatment. Avoiding unnecessary intrauterine procedures, controlling body weight appropriately, and choosing suitable ART methods as soon as possible may be beneficial for clinical outcomes.

Rice Varieties Intercropping Induced Soil Metabolic and Microbial Recruiting to Enhance the Rice Blast (Magnaporthe Oryzae) Resistance.

[Background] Intercropping is considered an effective approach to defending rice disease. [Objectives/Methods] This study aimed to explore the resistance mechanism of rice intraspecific intercropping by investigating soil metabolites and their regulation on the rhizosphere soil microbial community using metabolomic and microbiome analyses. [Results] The results showed that the panicle blast disease occurrence of the resistant variety Shanyou63 (SY63) and the susceptible variety Huangkenuo (HKN) were both decreased in the intercropping compared to monoculture. Notably, HKN in the intercropping system exhibited significantly decreased disease incidence and increased disease resistance-related enzyme protease activity. KEGG annotation from soil metabolomics analysis revealed that phenylalanine metabolic pathway, phenylalanine, tyrosine, and tryptophan biosynthesis pathway, and fructose and mannose metabolic pathway were the key pathways related to rice disease resistance. Soil microbiome analysis indicated that the bacterial genera Nocardioides, Marmoricola, Luedemannella, and Desulfomonile were significantly enriched in HKN after intercropping, while SY63 experienced a substantial accumulation of Ruminiclostridium and Cellulomonas. Omics-based correlation analysis highlighted that the community assembly of Cellulomonas and Desulfomonile significantly affected the content of the metabolites D-sorbitol, D-mannitol, quinic acid, which further proved that quinic acid had a significantly inhibitory effect on the mycelium growth of Magnaporthe oryzae, and these three metabolites had a significant blast control effect. The optimal rice blast-control efficiency on HKN was 51.72%, and Lijiangxintuanheigu (LTH) was 64.57%. [Conclusions] These findings provide a theoretical basis for rice varieties intercropping and sustainable rice production, emphasizing the novelty of the study in elucidating the underlying mechanisms of intercropping-mediated disease resistance.

Case report: Bullous pemphigoid combined with Sjögren's syndrome complicated by central nervous system infection.

Background: Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease in humans, characterized by tense blisters, erosions, urticarial lesions, and itching on normal or erythematous skin. Many autoimmune diseases are considered comorbidities of BP, but clinical case reports of BP complicated by Sjögren's syndrome are very scarce. Furthermore, cases of central nervous system infection secondary to both autoimmune diseases are even rarer. Case presentation: We report a 74-year-old woman diagnosed with bullous pemphigoid, who showed relief of active lesions after treatment with methylprednisolone and dupilumab injections. However, she was admitted for pulmonary infection during which she was diagnosed with Sjögren's syndrome (SS). Subsequently, the patient developed altered consciousness, indicating a central nervous system infection. Adjustment of steroid dosage and aggressive antimicrobial therapy led to alleviation of symptoms. Conclusion: The coexistence of autoimmune subepidermal blistering diseases and SS is rare. The role of SS in the pathogenesis of skin lesions is unclear, and the relationship between these blistering diseases and SS remains elusive. Further research is needed to determine whether there are common pathological mechanisms between the two conditions.

Analysis and identification of mRNAsi­related expression signatures via RNA sequencing in lung cancer.

High stemness index scores are associated with poor survival in patients with lung cancer. Studies on the mRNA expression-based stemness index (mRNAsi) are typically conducted using tumor tissues; however, mRNAsi-related expression signatures based on cell-free RNA (cfRNA) are yet to be comprehensively investigated. The present study aimed to elucidate the gene expression profiles of tumor stemness in lung cancer tissues and corresponding cfRNAs in blood, and to assess their links with immune infiltration. Tumor tissue, paracancerous tissue, peripheral blood and lymph node samples were collected from patients with stage I-III non-small cell lung cancer and RNA sequencing was performed. The TCGAbiolinks package was used to calculate the mRNAsi for each of these four types of sample. Weighted gene co-expression network analysis and differentially expressed gene analyses were performed to investigate mRNAsi-related genes, and pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology-based annotation system. In addition, the STAR-Fusion tool was used to detect fusion variants, and CIBERSORT was used to analyze the correlations of stemness signatures in tissues and blood with immune cell infiltration. The mRNAsi values in peripheral blood and lymph nodes were found to be higher than those in cancer tissues. 'Hematopoietic cell lineage' was the only KEGG pathway enriched in mRNAsi-related genes in both lung cancer tissues and peripheral blood. In addition, the protein tyrosine phosphatase receptor type C associated protein gene was the only gene commonly associated with the mRNAsi in these two types of sample. The expression of mRNAsi-related genes was increased in the dendritic and Treg cells in tumor tissues, but was elevated in Treg and CD8 cells in the blood. In conclusion, cfRNAs in the blood exhibit unique stemness signatures that have potential for use in the diagnosis of lung cancer.

Anti-infective properties of mung bean (Vigna radiata (L.)R. Wilczek) coat extract on Pseudomonas aeruginosa-infected Caenorhabditis elegans: Transcriptomics and pathway analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Mung bean coat has long been known for its wide-ranging health benefits, including antibacterial, anti-inflammatory, and immune-modulatory properties. For many years in China, mung beans have been employed in the therapeutic management of inflammation induced by pathogenic bacteria infection, yet the precise underlying protective mechanisms remain to be comprehensively elucidated. AIM OF THE STUDY: Given the growing concern over antibiotic resistance, there is a necessity to explore new anti-infective agents. Here, the anti-infective properties of Mung bean coat extract (MBCE) were investigated using a model of Pseudomonas aeruginosa-infected nematodes. MATERIALS AND METHODS: The protective effects of MBCE on Pseudomonas aeruginosa (PA14) infected nematodes were assessed by lifespan assay, reactive oxygen species (ROS) levels, transcriptomics, and Quantitative real-time PCR (qRT-PCR). RESULTS: MBCE significantly improved the survival rates and reduced ROS levels in infected worms. Transcriptomic profiling disclosed predominant KEGG pathway enrichments in immune responses, energy metabolism processes such as oxidative phosphorylation and the tricarboxylic acid cycle, alongside aging-related neurodegenerative diseases and longevity regulatory pathways like PI3K-AKT, MAPK, mTOR, and FOXO. qRT-PCR validation showed that MBCE upregulated antimicrobial peptides (spp-3, lys-1, lys-7, abf-2, cnc-2, nlp-33, clec-85), gram-negative responses (irg-3, src-2, grd-3, col-179), and mitochondrial function (mev-1) gene expressions, while downregulated insulin signaling-related (age-1, akt-1, akt-2, daf-15) gene expressions. Mutant strains lifespan analysis indicated that the nsy-1, sek-1, pmk-1, daf-2, aak-2, sir-2.1, and skn-1 were necessary for lifespan extension mediated by MBCE under PA14 infection, but not clk-1, isp-1, mev-1, or daf-16. CONCLUSION: Collectively, our findings suggested that MBCE increased the survival rates of PA14-infected worms by activating downstream antimicrobial and antioxidant gene expressions through modulation of MAPK, daf-2, aak-2, sir-2.1, and skn-1 pathways. The research underscored the potential of natural plant compounds to strengthen the body's defenses against infections, potentially mitigating harmful ROS levels and improving survival. Additionally, these findings elucidated the mechanisms by which these plant-derived compounds enhance the immune system, implying their potential utility as dietary supplements or as an alternative to conventional antibiotics.

[Synergistic removal of malachite green and Cr(â ¥) using ethylenediamine disuccinic acid functionalized silica gel].

As common industrial raw materials, malachite green (MG) and Cr(Ⅵ) generally coexist in waste liquids discharged from the paper printing, leather, and textile industries, causing serious harm to humans and the environment. Therefore, developing an effective method for the synergistic removal of MG and Cr(Ⅵ) from aquatic environments is of great research value. In this work, the non-homogeneous Fenton-like catalysts, namely, EDDS-Silica and EDDS-Co2+-Silica were successfully prepared using ethylenediamine disuccinic acid (EDDS) and silica gel (Silica) as raw materials, and a non-homogeneous Fenton-like catalytic method was developed for the efficient and synergistic removal of MG and Cr(Ⅵ) from wastewater. EDDS-Silica and EDDS-Co2+-Silica were analyzed using Fourier infrared spectroscopy and X-ray photoelectron spectroscopy to determine their structural composition and elemental contents. The catalytic degradation and removal effects of these materials in an MG single-waste system were also investigated. The results demonstrated that the incorporation of both materials can overcome the limitation of the conventional Fenton reaction, which is its applicability to acidic environments only. Moreover, EDDS-Co2+-Silica showed better degradation effects on MG than EDDS-Silica. Quantitative calculations based on density functional theory were used to predict the optimal coordination forms between Co2+and EDDS-Silica as well as the MG structure. The lowest unoccupied and highest occupied molecular orbitals of the catalysts were then used to predict the active sites on which MG tends to capture or release electrons during the degradation reaction. The optimal conditions for the synergistic removal of MG and Cr(Ⅵ) from a binary system using EDDS-Co2+-Silica were further investigated under different influencing factors. The results showed that EDDS-Co2+-Silica still had excellent catalytic effect on the degradation rate of MG in the range of pH 3-7, and the optimal conditions were as follows: solution pH, 7; degradation time, 1 h; temperature, 25 ℃; H2O2 concentration, 20 mmol/L; and the initial mass concentration of Cr(Ⅵ), 25 mg/L. Under the above conditions, the degradation rate was increased from 87.25% to 96.67% compared with that in the MG monosystem. Obvious enhancements in degradation effect and efficiency confirmed that the incorporation of EDDS-Co2+-Silica was favorable for the synergistic removal of MG and Cr(Ⅵ) in the binary system. Strongly oxidizing Cr(Ⅵ) can participate in the Fenton reaction, thus promoting MG degradation over a wide pH range. Thus, a positive synergistic effect exists between MG and Cr(Ⅵ). Considering that a large number of metal ions remained in the solution after the degradation reaction, EDDS-Silica was added to the degradation solution, and adsorption experiments were performed for 4 h at 30 ℃to adsorb and remove Cr and Fe via the strong chelating property of EDDS. The total residual mass concentrations of Cr and Fe were 4.96 and 1.02 mg/L, respectively, which meet national emission standards. These findings indicate that EDDS-Silica has good effects on the removal of residual metal ions after the nonhomogeneous Fenton reaction. As heterogeneous Fenton-like catalysts, the aminopolycarboxylic acid-modified materials proposed in this study can simultaneously promote the Fenton reaction and remove residual metal ions, thereby effectively removing MG and Cr(Ⅵ) from the binary system while ensuring that the content of residual metal ions in the system meets environmental emission standards. This study has broad application prospects in dye degradation and heavy-metal-ion wastewater treatment, and provides a reference value and theoretical basis for the development of other similar ligand-modified materials.

[Effect of Meteorological Elements and Air Pollutants on Ozone in Yinchuan City Park].

To examine the underlying determinants of ozone （O3） in Yinchuan's urban park during varying seasons and to ascertain the role played by meteorological events and air contaminants in influencing O3 concentrations at high altitudes, data on O3, meteorological factors, and air pollutants were collected through prolonged positional observations carried out at the Ningxia Yinchuan National Urban Ecosystem Research Station. Pearson correlation analysis and a structural equation model were utilized to investigate the spatio-temporal distribution patterns, trends, and the primary factors influencing O3. The findings demonstrated a notable seasonal variability in O3 levels in Yinchuan's urban park, displaying an "unimodal type" with the O3 concentration peaking in summer （131.18 µg·m-3） and bottoming out in winter （71.45 µg·m-3）. Among the meteorological factors, the highest impact on O3 was attributed to temperature and wind speed （temperature mainly through direct effects and wind speed mainly through indirect effects）. Conversely, air pollutants such as NOx and SO2 greatly affected O3 primarily through direct effects. Wind speed was identified as the primary influencing factor on O3 during spring and summer, potentially contributing 29% and 24.7%, respectively. Conversely, NO2 was implicated as the primary factor during autumn and winter, with an estimated contribution of 26.6% and 29.7%, respectively. Thus, a structural equation model can efficiently reveal the primary determinants behind O3 variations throughout various seasons, which could furnish a scientifically rigorous foundation and technical aid for mitigating and managing O3 levels in high-altitude regions.

Exosomal miR-502-5p suppresses the progression of gastric cancer by repressing angiogenesis through the Wnt/ß-catenin pathway.

BACKGROUND: Gastric cancer (GC) is a significant global health concern, ranking as the fifth most common cancer and the third leading cause of cancer-related deaths. The role of miR-502-5p in various cancers has been studied, but its specific impact on gastric cancer through exosomes is not well understood. This study aimed to investigate the role and mechanism of exosome-derived miR-502-5p in gastric cancer. METHODS: Differential expression of miR-502-5p in tissues or serum of GC patients was determined using qRT-PCR. The impact of miR-502-5p on cell proliferation, migration, and invasion was assessed through in vitro and in vivo experiments. The potential of exosome-miR-502-5p to inhibit metastatic ability was also explored by using vivo and vitro assay. Furthermore, the underlying mechanism of miR-502-5p in gastric cancer was investigated using western blotting. RESULTS: It was found that miR-502-5p suppressed the proliferation, migration, and invasion of gastric cancer cells. Exosome-miR-502-5p expression was negatively linked to metastatic ability and demonstrated inhibition of metastasis in vitro and in vivo. Additionally, miR-502-5p appeared to inhibit angiogenesis through the Wnt/ß-catenin pathway in gastric cancer. CONCLUSIONS: Exosomal miR-502-5p acts as a suppressor in the development and progression of gastric cancer, suggesting its potential as a target for anti-cancer therapy or as a diagnostic biomarker.

Evaluation and Application of Population Pharmacokinetic Models for Optimising Linezolid Treatment in Non-Adherence Multidrug-Resistant Tuberculosis Patients.

BACKGROUND: Population pharmacokinetic (popPK) models can optimise linezolid dosage regimens in patients with multidrug-resistant tuberculosis (MDR-TB); however, unknown cross-centre precision and poor adherence remain problematic. This study aimed to assess the predictive ability of published models and use the most suitable model to optimise dosage regimens and manage compliance. METHODS: One hundred fifty-eight linezolid plasma concentrations from 27 patients with MDR-TB were used to assess the predictive performance of published models. Prediction-based metrics and simulation-based visual predictive checks were conducted to evaluate predictive ability. Individualised remedial dosing regimens for various delayed scenarios were optimised using the most suitable model and Monte Carlo simulations. The influence of covariates, scheduled dosing intervals, and patient compliance were assessed. RESULTS: Seven popPK models were identified. Body weight and creatinine clearance were the most frequently identified covariates influencing linezolid clearance. The model with the best performance had a median prediction error (PE%) of -1.62%, median absolute PE of 29.50%, and percentages of PE within 20% (F20, 36.97%) and 30% (F30, 51.26%). Monte Carlo simulations indicated that a twice-daily 300 mg linezolid dose may be more efficient than 600 mg once daily. For the 'typical' patient treated with 300 mg twice daily, half the dosage should be taken after a delay of ≥ 3 hours. CONCLUSIONS: Monte Carlo simulations based on popPK models can propose remedial regimens for delayed doses of linezolid in patients with MDR-TB. Model-based compliance management patterns are useful for balancing efficacy, adverse reactions, and resistance suppression.

Spatial and temporal dynamics of microbes and genes in drinking water reservoirs: Distribution and potential for taste and odor generation.

Numerous reservoirs encounter challenges related to taste and odor issues, often attributed to odorous compounds such as geosmin (GSM) and 2-methylisoborneol (2-MIB). In this study, two large reservoirs located in northern and southern China were investigated. The Jinpen (JP) reservoir had 45.99 % Actinomycetes and 14.82 % Cyanobacteria, while the Xikeng (XK) reservoir contained 37.55 % Actinomycetes and 48.27 % Cyanobacteria. Most of the 2-MIB produced in surface layers of the two reservoirs in summer originated from Cyanobacteria, most of the 2-MIB produced in winter and in the bottom water originated from Actinomycetes. Mic gene abundance in the XK reservoir reached 5.42 × 104 copies/L in winter. The abundance of GSM synthase was notably high in the bottom layer and sediment of both reservoirs, while 2-MIB synthase was abundant in the surface layer of the XK reservoir, echoing the patterns observed in mic gene abundance. The abundance of odor-producing enzymes in the two reservoirs was inhibited by total nitrogen, temperature significantly influenced Actinomycetes abundance in the JP reservoir, whereas dissolved oxygen had a greater impact in the XK reservoir. Overall, this study elucidates the molecular mechanisms underlying odor compounding, providing essential guidance for water quality management strategies and the improvement of urban water reservoir quality.

Prevalence and disparities in sexual and reproductive health of women of reproductive age (20-49 years) in China: A national cross-sectional study.

Background: Ensuring women's sexual and reproductive health (SRH) is a fundamental human right and key to 2030 agenda of the UN Sustainable Development Goals (SDGs), yet limited evidence exists on SRH in China, including national estimates and disparities of women's SRH experiences, gynaecological diseases, and sexually transmitted diseases (STDs). Methods: A national cross-sectional survey based on a multistage stratified sampling from 15 provinces of China was performed from May 2019 to April 2021. A total of 12 815 reproductive-aged (20-49 years) women were involved. The SRH experiences (including age at menarche, age at first sexual activity, history of abortion, miscarriage, recurrent miscarriage, stillbirth, age at first delivery, types of delivery), the history of gynaecological diseases and STDs, as well as the environmental factors of participants were investigated. Human development index (HDI) was utilised to categorise and describe the socioeconomic status of the regions. The prevalence rates of diseases were compared among different HDI regions. Results: We observed a decrease in the mean age at menarche, an increase in the proportion of women who became sexually active before 20, and a modest rise in mean age at first childbirth across generations. Age-standardised prevalence estimates of miscarriage, recurrent miscarriage, artificial abortion, ectopic pregnancy, and stillbirth were 9.3, 1.4, 55.7, 3.3, and 2.1%, respectively. Approximately 50% of participants reported a history of gynaecological diseases, with vulvovaginitis, cervicitis, and pelvic infection diseases being the most prevalent. The overall prevalence of STDs was estimated at 22.2‰, with mycoplasma genitalium infection having the highest reported prevalence. Disease prevalence varies across HDI regions. Conclusions: Women's SRH behaviours and experiences have evolved, along with shifts in the spectrums of gynaecological diseases and STDs in China. Urgent recalibration of health care policies and disease control strategies is necessary, aligning them with women's changing SRH needs, ultimately ensuring their reproductive health and rights.

LINC00618 facilitates growth and metastasis of hepatocellular carcinoma via elevating cholesterol synthesis by promoting NSUN2-mediated SREBP2 m5C modification.

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1-101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

A Novel Asymmetric Diffusion Path for Superior Ion Dynamic in High-Voltage Mg-Based Hybrid Batteries.

Magnesium-based batteries have garnered significant attention due to their high energy density, excellent intrinsic safety, and low cost. However, the application process has been hindered by the high Mg2+ ions diffusion barrier in solid-state structures and solid-liquid interphase. To address this issue, a hybrid battery technology based on Mg anode and Fe-based Prussian Blue Analogue cathode doped with functional transition metal ions and N═O bonds is proposed. Combined multiscale experimental characterizations with theoretical calculations, the subtle lattice distortion can create an asymmetric diffusion path for the active ions, which enables reversible extraction with significantly reduced diffusion barriers achieved by synergistic doping. The optimized cathode exhibits a working potential of 2.3 V and an initial discharge capacity of 152 mAh g-1 at 50 mA g-1. With the preferred electrolyte combined with equivalent concentration [Mg2(µ-Cl)2(DME)4][AlCl4]2 and NaTFSI salt solution, the hybrid system demonstrates superior cycling performance over 200 cycles at a high current density of 200 mA g-1, maintaining ≈100% coulombic efficiency with superior ion dynamic. The findings are expected to be marked an important step in the further application of high-voltage cathodes for Mg-based hybrid batteries.

Sesquiterpenoids from the roots and rhizomes of Valeriana officinalis var. latifolia.

The genus Valeriana is used in traditional Chinese medicine to treat nervous disorders, sleep disorders, epilepsy and skin diseases. A large number of sesquiterpenoids from this genus have been found to exhibit anti-inflammatory, antiproliferative, anti-influenza virus and neuroprotective activities. In order to discover more sesquiterpenoids with structural diversity and bioactivity from Valeriana plants, fifteen sesquiterpenoids, including ten undescribed ones, valernaenes A-J (1, 5-7, 9-11 and 13-15), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated by extensive spectroscopic techniques (1D, 2D NMR and HRESIMS) and electronic circular dichroism (ECD) calculation. Structurally, valernaenes C (6) and D (7) were two caryophyllane-type norsesquiterpenoids. In addition, valernaenes A (1) and F (10) exhibited anti-influenza virus activity with EC50 values of 38.76 ± 1.44 and 23.01 ± 4.89 µM, respectively. Furthermore, caryophyllenol A (2) showed promoting effect on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells with differentiation rate of 12.26% at a concentration of 10 µM. This study not only enriched the structural diversity of sesquiterpenoids in the genus Valeriana, but also provided theoretical basis for the discovery of anti-influenza virus and neuroprotective agents from this genus.