Comparative Study of the Antibacterial Effects of S-Nitroso-N-acetylcysteine and Sodium Nitrite against Escherichia coli and Their Application in Beef Sausages.

This study investigated the antibacterial effects of S-nitroso-N-acetylcysteine (SNAC) and sodium nitrite (NaNO2) against Escherichia coli and their application in beef sausages. Both SNAC and NaNO2 demonstrated pH-responsive antibacterial activity, with SNAC showing greater efficacy than NaNO2 (p < 0.05) at the same pH (3, 5, and 7). The reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced in E. coli by SNAC were significantly higher than those induced by NaNO2 (p < 0.05), and both ROS and RNS values increased as the pH decreased. In addition, a lower pH led to more pores on the E. coli cell surface and increased membrane permeability, resulting in a more pronounced inhibitory effect. When applied to a beef sausage, SNAC-treated sausages had significantly lower total colony counts and carbonyl content compared to NaNO2-treated ones (p < 0.05). Consequently, SNAC shows great potential as a replacement for NaNO2 in meat products.

Gui Qi Zhuang Jin Decoction ameliorates mitochondrial dysfunction in sarcopenia mice via AMPK/PGC-1α/Nrf2 axis revealed by a metabolomics approach.

OBJECTIVE: Sarcopenia, as a condition of muscle mass loss and functional decline typically diagnosed in elderly individuals, severely affects human physical activity, metabolic homeostasis, and quality of life. Gui Qi Zhuang Jin Decoction (GQZJD), an approved hospital-based prescription with years of clinical application, has been demonstrated to have a notable therapeutic effect on sarcopenia. However, its potential mechanism of action in the treatment of sarcopenia remains uncertain. METHODS: Ultra-performance liquid chromatography paired with Q Exactive™ HF-X mass spectrometry (UPLC-QE-MS) was used to identify the ingredients of GQZJD. Subsequently, GQZJD observed the basic growth and muscles of the sarcopenia mouse, while the behavioral indicators were also tested. Muscle histopathology and serum oxidative stress biochemicals were also detected, and mitochondrial function and energy metabolism-related indicators in the gastrocnemius muscle were examined. Then, a metabolomics strategy was applied to predict possible pathways involving mitochondria by which GQZJD could improve sarcopenia. Finally, quantitative real-time polymerase chain reaction and western blot analyses were carried out to validate the effects of GQZJD on sarcopenia-induced mitochondrial dysfunction, together with uncovering the associated mechanisms. RESULTS: Twenty-seven ingredients absorbed into the blood (IAIBs) of GQZJD were identified using UPLC-QE-MS, which were regarded as the main active ingredients behind its sarcopenia treatment effects. GQZJD administration increased the body weight, gastrocnemius muscle mass, and autonomic activity, mitigated muscle tissue morphology and pathology; and alleviated the oxidative stress levels in sarcopenia mice. Treatment with GQZJD also decreased the mitochondrial reactive oxygen species level and serum lipid peroxide Malonaldehyde concentration. and increased the mitochondrial membrane potential, adenosine triphosphate level, 8­hydroxy-2-deoxyguanosine content, mitochondrial DNA copy number, and the mitochondrial fission factor dynamin-related protein 1. Non-targeted metabolomics suggested that the sarcopenia therapeutic effect of GQZJD on sarcopenia may occur through the glycerophospholipid metabolism, choline metabolism in cancer, phenylalanine metabolism and tyrosine metabolism pathways, implying an association with AMP-activated protein kinase (AMPK) and related signals. Further, the molecular docking results hinted that AMPK performed well in terms of binding energy with the 27 IAIBs of GQZJD (average binding energy, -7.5 kcal/mol). Finally, we determined that GQZJD significantly activated the key targets of the AMPK/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis.. CONCLUSIONS: Our results demonstrated that GQZJD ameliorated d-galactose-induced sarcopenia by promoting the animal behaviours, facilitating mitochondrial function and restoring mitochondrial energy metabolism. with its effects mediated by the AMPK/PGC-1α/Nrf2 axis. Over all, GQZJD represents a promising therapeutic candidate that ameliorated sarcopenia in aging mice.

Structure and Diversity of Endophytic Bacteria in Maize Seeds and Germinating Roots.

Seed endophytes in maize, which facilitate the transmission of microorganisms from one plant generation to the next, may play a crucial role in plant protection and growth promotion. This study aimed to investigate the effects of various maize varieties on the communities of endophytic bacteria in seeds and germinating roots. This study utilized Illumina high-throughput sequencing technology to examine the structural and diversity differences of endophytic bacterial communities within seed maize (BY1507), silage maize (QQ446), and wild maize (Teosinte) in both seeds and germinating roots. The results showed that 416 bacterial genera were detected, with Pantoea, Lachnospiraceae, Pararhizobium, Enterobacteriaceae, Stenotrophomonas, and Pseudonocardia being the most prevalent (relative abundance > 10%) at the genus level. No significant difference was observed in diversity indices (Chao1, ACE, Shannon, and Simpson) of seed endophytes among BY1507, QQ446, and Teosinte. The Shannon and Simpson indices for the germinating root endophyte from the wild variety (Teosinte) were significantly higher than the domesticated varieties (BY1507 and QQ446). PCoA revealed a notable overlap in the endophytic bacterial communities from the seeds of BY1507, QQ446, and Teosinte. Yet, clustering patterns were found. Co-occurrence network analysis showed that BY1507, QQ446, and Teosinte share a notable proportion of shared endophytic bacteria (>30%) between the seeds and germinating roots. This investigation elucidates the characteristics of endophytic microbial communities of seeds and germinating roots with seed maize, silage maize, and wild maize, offering data for future research on the physiological ecological adaptation of these endophytic microbial communities.

Trends and Directions in Oats Research under Drought and Salt Stresses: A Bibliometric Analysis (1993-2023).

With global climate change leading to increasing intensity and frequency of droughts, as well as the growing problem of soil salinization, these factors significantly affect crop growth, yield, and resilience to adversity. Oats are a cereal widely grown in temperate regions and are rich in nutritive value; however, the scientific literature on the response of oat to drought and salt stress has not yet been analyzed in detail. This study comprehensively analyzed the response of oat to drought stress and salt stress using data from the Web of Science core database and bibliometric methods with R (version4.3.1), VOSviewer (version 1.6.19), and Citespace (version6.3.1.0) software. The number of publications shows an increasing trend in drought stress and salt stress in oat over the past 30 years. In the field of drought-stress research, China, the United States, and Canada lead in terms of literature publication, with the most academic achievements being from China Agricultural University and Canadian Agricultural Food University. The journal with the highest number of published papers is Field Crops Research. Oat research primarily focuses on growth, yield, physiological and biochemical responses, and strategies for improving drought resistance. Screening of drought-tolerant genotypes and transformation of drought-tolerant genes may be key directions for future oat drought research. In the field of salt-stress research, contributions from China, the United States, and India stand out, with the Chinese Academy of Agricultural Sciences and Inner Mongolia Agricultural University producing the most significant research results. The largest number of published articles has been found in the Physiologia Plantarum journal. Current oat salt-stress research primarily covers growth, physiological and biochemical responses, and salt-tolerance mechanisms. It is expected that future oat salt research will focus more on physiological and biochemical responses, as well as gene-editing techniques. Despite achievements under single-stress conditions, combined drought and salt-stress effects on oat remain understudied, necessitating future research on their interaction at various biological levels. The purpose of this study is to provide potential theoretical directions for oat research on drought and salt stress.

Identification of atrial fibrillation-related genes through transcriptome data analysis and Mendelian randomization.

Background: Atrial fibrillation (AF) is a common persistent arrhythmia characterized by rapid and chaotic atrial electrical activity, potentially leading to severe complications such as thromboembolism, heart failure, and stroke, significantly affecting patient quality of life and safety. As the global population ages, the prevalence of AF is on the rise, placing considerable strains on individuals and healthcare systems. This study utilizes bioinformatics and Mendelian Randomization (MR) to analyze transcriptome data and genome-wide association study (GWAS) summary statistics, aiming to identify biomarkers causally associated with AF and explore their potential pathogenic pathways. Methods: We obtained AF microarray datasets GSE41177 and GSE79768 from the Gene Expression Omnibus (GEO) database, merged them, and corrected for batch effects to pinpoint differentially expressed genes (DEGs). We gathered exposure data from expression quantitative trait loci (eQTL) and outcome data from AF GWAS through the IEU Open GWAS database. We employed inverse variance weighting (IVW), MR-Egger, weighted median, and weighted model approaches for MR analysis to assess exposure-outcome causality. IVW was the primary method, supplemented by other techniques. The robustness of our results was evaluated using Cochran's Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out sensitivity analysis. A "Veen" diagram visualized the overlap of DEGs with significant eQTL genes from MR analysis, referred to as common genes (CGs). Additional analyses, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and immune cell infiltration studies, were conducted on these intersecting genes to reveal their roles in AF pathogenesis. Results: The combined dataset revealed 355 differentially expressed genes (DEGs), with 228 showing significant upregulation and 127 downregulated. Mendelian randomization (MR) analysis identified that the autocrine motility factor receptor (AMFR) [IVW: OR = 0.977; 95% CI, 0.956-0.998; P = 0.030], leucine aminopeptidase 3 (LAP3) [IVW: OR = 0.967; 95% CI, 0.934-0.997; P = 0.048], Rab acceptor 1 (RABAC1) [IVW: OR = 0.928; 95% CI, 0.875-0.985; P = 0.015], and tryptase beta 2 (TPSB2) [IVW: OR = 0.971; 95% CI, 0.943-0.999; P = 0.049] are associated with a reduced risk of atrial fibrillation (AF). Conversely, GTPase-activating SH3 domain-binding protein 2 (G3BP2) [IVW: OR = 1.030; 95% CI, 1.004-1.056; P = 0.024], integrin subunit beta 2 (ITGB2) [IVW: OR = 1.050; 95% CI, 1.017-1.084; P = 0.003], glutaminyl-peptide cyclotransferase (QPCT) [IVW: OR = 1.080; 95% CI, 1.010-0.997; P = 1.154], and tripartite motif containing 22 (TRIM22) [IVW: OR = 1.048; 95% CI, 1.003-1.095; P = 0.035] are positively associated with AF risk. Sensitivity analyses indicated a lack of heterogeneity or horizontal pleiotropy (P > 0.05), and leave-one-out analysis did not reveal any single nucleotide polymorphisms (SNPs) impacting the MR results significantly. GO and KEGG analyses showed that CG is involved in processes such as protein polyubiquitination, neutrophil degranulation, specific and tertiary granule formation, protein-macromolecule adaptor activity, molecular adaptor activity, and the SREBP signaling pathway, all significantly enriched. The analysis of immune cell infiltration demonstrated associations of CG with various immune cells, including plasma cells, CD8T cells, resting memory CD4T cells, regulatory T cells (Tregs), gamma delta T cells, activated NK cells, activated mast cells, and neutrophils. Conclusion: By integrating bioinformatics and MR approaches, genes such as AMFR, G3BP2, ITGB2, LAP3, QPCT, RABAC1, TPSB2, and TRIM22 are identified as causally linked to AF, enhancing our understanding of its molecular foundations. This strategy may facilitate the development of more precise biomarkers and therapeutic targets for AF diagnosis and treatment.

Quantitative regulation of electron-phonon coupling.

Electron-phonon (e-p) coupling plays a crucial role in various physical phenomena, and regulation of e-p coupling is vital for the exploration and design of high-performance materials. However, the current research on this topic lacks accurate quantification, hindering further understanding of the underlying physical processes and its applications. In this work, we demonstrate quantitative regulation of e-p coupling, by pressure engineering andin-situspectroscopy. We successfully observe both a distinct vibrational mode and a strong Stokes shift in layered CrBr3, which are clear signatures of e-p coupling. This allows us to achieve precise quantification of the Huang-Rhys factorSat the actual sample temperature, thus accurately determining the e-p coupling strength. We further reveal that pressure efficiently regulates the e-p coupling in CrBr3, evidenced by a remarkable 40% increase inSvalue. Our results offer an approach for quantifying and modulating e-p coupling, which can be leveraged for exploring and designing functional materials with targeted e-p coupling strengths.

Bifunctional black phosphorus quantum dots platform: Delivery and remarkable immunotherapy enhancement of STING agonist.

Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-ß. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.

Parabacteroides distasonis regulates the infectivity and pathogenicity of SVCV at different water temperatures.

BACKGROUND: Spring viremia of carp virus (SVCV) infects a wide range of fish species and causes high mortality rates in aquaculture. This viral infection is characterized by seasonal outbreaks that are temperature-dependent. However, the specific mechanism behind temperature-dependent SVCV infectivity and pathogenicity remains unclear. Given the high sensitivity of the composition of intestinal microbiota to temperature changes, it would be interesting to investigate if the intestinal microbiota of fish could play a role in modulating the infectivity of SVCV at different temperatures. RESULTS: Our study found that significantly higher infectivity and pathogenicity of SVCV infection in zebrafish occurred at relatively lower temperature. Comparative analysis of the intestinal microbiota in zebrafish exposed to high- and low-temperature conditions revealed that temperature influenced the abundance and diversity of the intestinal microbiota in zebrafish. A significantly higher abundance of Parabacteroides distasonis and its metabolite secondary bile acid (deoxycholic acid, DCA) was detected in the intestine of zebrafish exposed to high temperature. Both colonization of Parabacteroides distasonis and feeding of DCA to zebrafish at low temperature significantly reduced the mortality caused by SVCV. An in vitro assay demonstrated that DCA could inhibit the assembly and release of SVCV. Notably, DCA also showed an inhibitory effect on the infectious hematopoietic necrosis virus, another Rhabdoviridae member known to be more infectious at low temperature. CONCLUSIONS: This study provides evidence that temperature can be an important factor to influence the composition of intestinal microbiota in zebrafish, consequently impacting the infectivity and pathogenicity of SVCV. The findings highlight the enrichment of Parabacteroides distasonis and its derivative, DCA, in the intestines of zebrafish raised at high temperature, and they possess an important role in preventing the infection of SVCV and other Rhabdoviridae members in host fish. Video Abstract.

Higher Magnesium Depletion Score Increases the Risk of All-cause and Cardiovascular Mortality in Hypertension Participants.

The magnesium depletion score (MDS) is a novel index utilized for evaluating body magnesium status. The present study intended to explore the association of MDS with mortality among hypertension (HTN) participants. In this cohort study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2003 to 2018. MDS levels were categorized into three groups (lower: MDS = 0-1; middle: MDS = 2; higher: MDS = 3-5). Kaplan-Meier curves were employed to illustrate survival differences between groups with varying MDS levels. The relationship between MDS and mortality was assessed through weighted multivariate Cox regression models. Subgroup analyses, along with sensitivity analyses, were also conducted to further explore and validate the findings. This study encompassed 12,485 participants, recording 2537 all-cause deaths and 707 cardiovascular deaths. The Kaplan-Meier curves revealed that the higher MDS group had the highest rates of all-cause and cardiovascular death. (P < 0.001). Controlling for all confounding variables, participants belonging to the higher MDS group demonstrated a substantially elevated risk of mortality in comparison to the lower MDS group (all-cause mortality: hazard ratio (HR) = 1.31, 95% confidence interval (CI) 1.10-1.54; cardiovascular mortality: HR = 1.63, 95% CI 1.19-2.22). There were no interaction factors found in subgroup analyses that affected the relationship between MDS and mortality, except for cardiovascular disease. The findings were confirmed to be robust through further sensitivity analyses. Higher MDS levels independently predict an elevated risk of mortality among US adults with HTN. Therefore, MDS may serve as a cost-effective and widely available prognostic marker for HTN.

Association between body roundness index and overactive bladder: results from the NHANES 2005-2018.

BACKGROUND AND AIM: An increasing amount of research has indicated obesity greatly affects individuals with overactive bladder (OAB). However, traditional anthropometric methods present challenges in accurately assessing the likelihood of OAB. Hence, this study's objective was to identify the correlation between the body roundness index (BRI) and OAB. METHODS: The research included 12,401 individuals who participated in the National Health and Nutrition Examination Survey spanning 2005-2018. The correlation between BRI and OAB was explored by using weighted multiple logistic regression and weighted restricted cubic spline (RCS). Subgroup analyses showed the associations based on different population types. The study also analyzed the predictive capability of various anthropometric indices, including BRI, body mass index, waist circumference, and weight, in assessing the likelihood of OAB through Receiver-operating characteristic (ROC) curves. RESULTS: An independent positive correlation between OAB and BRI was identified after adjusting for potential confounders in weighted multivariate logistic models[odds ratio (OR) = 1.15, 95% confidence interval (CI), 1.12-1.17]. Weighted RCS analysis found a positive dose-response correlation between OAB and BRI. The effect size of BRI on OAB remained stable across all prespecified subgroups (all P for interactions > 0.05). In ROC analysis, BRI showed better discriminatory ability for OAB compared with other anthropometric measures for both genders (all P < 0.01). The best BRI cutoff for predicting OAB was lower for men (5.151) than for women (5.383), suggesting that men were more susceptible to changes in BRI than women. CONCLUSIONS: This study demonstrated that a raised BRI is correlated with a higher likelihood of OAB. Due to the effectiveness and non-invasiveness of BRI in predicting OAB, it is expected to become the preferred method for early detection and management strategies.

Prevalence of anemia in patients with rheumatoid arthritis and its association with dietary inflammatory index: A population-based study from NHANES 1999 to 2018.

Anemia is common in patients with rheumatoid arthritis (RA), and it is unknown whether the dietary inflammatory index (DII) is linked to anemia. This study aimed to clarify the prevalence of anemia in RA patients and its association with the DII. The data utilized in this study were collected from the National Health and Nutrition Examination Survey database from 1999 to 2018. The prevalence of anemia in RA patients was estimated by ethnicity, sex, and age. Weighted multivariate logistic regression was utilized to explore the correlation between anemia risk and DII. The most crucial dietary factors related to the risk of anemia in RA patients were screened by stepwise regression. A nomogram model was established according to key dietary factors. A total of 10.25% (confidence interval, 8.58-11.92%) of RA patients will develop anemia, with the lowest prevalence around the age of 60. In addition, higher DII levels were discovered in anemic patients than in nonanemic patients. In multivariate regression models, an important positive association was revealed between anemia and growing quartiles of DII (Q4 vs Q1: odds ratio = 1.98; confidence interval, 1.25-3.15). In the subgroup analysis, the adjusted relation of DII with anemia in females, Mexicans, smokers, nondrinkers, and age groups ≥ 60 years was statistically significant. The same association was observed in the sensitivity analysis. A nomogram model based on stepwise regression screening of key dietary factors showed good discriminatory power to identify anemic risk in RA patients (area under the curve: 0.707). In patients with RA, high DII levels were associated with the risk of anemia. More attention should be given to controlling dietary inflammation to better prevent and treat anemia.

ESG guidance and artificial intelligence support for power systems analytics in the energy industry.

In order to increase the precision and effectiveness of power system analysis and fault diagnosis, this study aims to assess the power systems in the energy sector while utilizing artificial intelligence (AI) and environmental social governance (ESG). First, the ESG framework is presented in this study to fully account for the effects of the power system on the environment, society, and governance. Second, to coordinate the operation of various components and guarantee the balance and security of the power system, the CNN-BiLSTM power load demand forecasting model is built by merging convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM). Lastly, the particle swarm optimization (PSO) algorithm is used to introduce and optimize the deep belief network (DBN), and a power grid fault diagnostic model is implemented using the PSO technique and DBN. The model's performance is assessed through experimentation. The outcomes demonstrate how the CNN-BiLSTM algorithm significantly increases forecasting accuracy while overcoming the drawback of just having one dimension of power load data. The values of 0.054, 0.076, and 0.102, respectively, are the root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE). Effective processing of large-scale nonlinear data is achieved in the area of power grid fault diagnosis, resulting in prediction accuracy of 96.22% and prediction time of only 129.94 s. This is clearly better than other algorithms and increases fault prediction efficiency and accuracy. Consequently, the model presented in this study not only produces impressive results in fault diagnosis and load demand forecasting, but also advances the field of power system analysis in the energy industry and offers a significant amount of support for the sustainable and intelligent growth of the energy industry.

A natural hydrogel complex improves intervertebral disc degeneration by correcting fatty acid metabolism and inhibiting nucleus pulposus cell pyroptosis.

The degeneration of intervertebral discs is strongly associated with the occurrence of pyroptosis in nucleus pulposus (NP) cells. This pyroptosis is characterized by abnormal metabolism of fatty acids in the degenerative pathological state, which is further exacerbated by the inflammatory microenvironment and degradation of the extracellular matrix. In order to address this issue, we have developed a fibrin hydrogel complex (FG@PEV). This intricate formulation amalgamates the beneficial attributes of platelet extravasation vesicles, contributing to tissue repair and regeneration. Furthermore, this complex showcases exceptional stability, gradual-release capabilities, and a high degree of biocompatibility. In order to substantiate the biological significance of FG@PEV in intervertebral disc degeneration (IVDD), we conducted a comprehensive investigation into its potential mechanism of action through the integration of RNA-seq sequencing and metabolomics analysis. Furthermore, these findings were subsequently validated through experimentation in both in vivo and in vitro models. The experimental results revealed that the FG@PEV intervention possesses the capability to reshape the inflammatory microenvironment within the disc. It also addresses the irregularities in fatty acid metabolism of nucleus pulposus cells, consequently hindering cellular pyroptosis and slowing down disc degeneration through the regulation of extracellular matrix synthesis and degradation. As a result, this injectable gel system represents a promising and innovative therapeutic approach for mitigating disc degeneration.

PSMA2 promotes glioma proliferation and migration via EMT.

BACKGROUND: Gliomas advance rapidly and are associated with a poor prognosis. Epithelial-mesenchymal transition (EMT) accelerates the progression of gliomas, exerting a pivotal role in glioma development. Proteasome subunit alpha type-2 (PSMA2) exhibits high expression levels in gliomas. however, its specific involvement in glioma progression and its correlation with EMT remain elusive. This study aims to elucidate the role of PSMA2 in glioma progression and its potential association with EMT. METHODS: Online tools were employed to analyze the expression patterns and survival curves of PSMA2 in gliomas. The relationship between PSMA2 and various characteristics of glioma patients was investigated using data from the TCGA and CGGA databases. In vitro, cell proliferation and migration were assessed through CCK-8, colony formation, and transwell assays. Furthermore, a tumor xenograft model in nude mice was established to evaluate in vivo tumorigenesis. Protein binding to PSMA2 was scrutinized using co-immunoprecipitation MS (co-IP MS). The potential biological functions and molecular pathways associated with PSMA2 were explored through GO analysis and KEGG analysis, and the correlation between PSMA2 and EMT was validated through correlation analysis and Western blot experiments. RESULTS: Bioinformatics analysis revealed a significant upregulation of PSMA2 across various cancers, with particularly heightened expression in gliomas. Moreover, elevated PSMA2 levels were correlated with advanced tumor stages and diminished survival rates among glioma patients. Inhibition of PSMA2 demonstrated a pronounced suppressive effect on glioma cell proliferation, both in vitro and in vivo. Knockdown of PSMA2 also impeded the migratory capacity of glioma cells. GO and KEGG enrichment analyses indicated that PSMA2-binding proteins (identified through Co-IP-MS) were associated with cell adhesion molecule binding and cadherin binding. Western blot results further confirmed the role of PSMA2 in promoting epithelial-mesenchymal transition (EMT) in glioma cells. CONCLUSION: Our study provides evidence supporting the role of PSMA2 as a regulatory factor in EMT and suggests its potential as a prognostic biomarker for glioma progression.

The dawn of a new Era: mRNA vaccines in colorectal cancer immunotherapy.

Colorectal cancer (CRC) is a typical cancer that accounts for 10% of all new cancer cases annually and nearly 10% of all cancer deaths. Despite significant progress in current classical interventions for CRC, these traditional strategies could be invasive and with numerous adverse effects. The poor prognosis of CRC patients highlights the evident and pressing need for more efficient and targeted treatment. Novel strategies regarding mRNA vaccines for anti-tumor therapy have also been well-developed since the successful application for the prevention of COVID-19. mRNA vaccine technology won the 2023 Nobel Prize in Physiology or Medicine, signaling a new direction in human anti-cancer treatment: mRNA medicine. As a promising new immunotherapy in CRC and other multiple cancer treatments, the mRNA vaccine has higher specificity, better efficacy, and fewer side effects than traditional strategies. The present review outlines the basics of mRNA vaccines and their advantages over other vaccines and informs an available strategy for developing efficient mRNA vaccines for CRC precise treatment. In the future, more exploration of mRNA vaccines for CRC shall be attached, fostering innovation to address existing limitations.

Injectable hydrogel harnessing foreskin mesenchymal stem cell-derived extracellular vesicles for treatment of chronic diabetic skin wounds.

Chronic skin wounds are a serious complication of diabetes with a high incidence rate, which can lead to disability or even death. Previous studies have shown that mesenchymal stem cells derived extracellular vesicles (EVs) have beneficial effects on wound healing. However, the human foreskin mesenchymal stem cell (FSMSCs)-derived extracellular vesicle (FM-EV) has not yet been isolated and characterized. Furthermore, the limited supply and short lifespan of EVs also hinder their practical use. In this study, we developed an injectable dual-physical cross-linking hydrogel (PSiW) with self-healing, adhesive, and antibacterial properties, using polyvinylpyrrolidone and silicotungstic acid to load FM-EV. The EVs were evenly distributed in the hydrogel and continuously released. In vivo and vitro tests demonstrated that the synergistic effect of EVs and hydrogel could significantly promote the repair of diabetic wounds by regulating macrophage polarization, promoting angiogenesis, and improving the microenvironment. Overall, the obtained EVs-loaded hydrogels developed in this work exhibited promising applicability for the repair of chronic skin wounds in diabetes patients.

Recent progress in lactate oxidase-based drug delivery systems for enhanced cancer therapy.

Lactate oxidase (LOX) is a natural enzyme that efficiently consumes lactate. In the presence of oxygen, LOX can catalyse the formation of pyruvate and hydrogen peroxide (H2O2) from lactate. This process led to acidity alleviation, hypoxia, and a further increase in oxidative stress, alleviating the immunosuppressive state of the tumour microenvironment (TME). However, the high cost of LOX preparation and purification, poor stability, and systemic toxicity limited its application in tumour therapy. Therefore, the rational application of drug delivery systems can protect LOX from the organism's environment and maintain its catalytic activity. This paper reviews various LOX-based drug-carrying systems, including inorganic nanocarriers, organic nanocarriers, and inorganic-organic hybrid nanocarriers, as well as other non-nanocarriers, which have been used for tumour therapy in recent years. In addition, this area's challenges and potential for the future are highlighted.

IRF1 governs the expression of SMARCC1 via the GCN5-SETD2 axis and actively engages in the advancement of osteoarthritis.

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA. Objective: This study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development. Methods: A single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1ß-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis. Results: IRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant role in the development of osteoarthritis (OA). The knockdown of either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1ß in chondrocytes, leading to a mitigation of OA-like symptoms, including inflammatory infiltration, cartilage degradation, and tissue injury, in rat models. Additionally, this intervention resulted in a reduction in the predominance of M1 macrophages both in vitro and in vivo. Significant epigenetic modifications, such as abundant H3K27ac and H3K4me3 marks, were observed near the SMARCC1 promoter and 10 kb upstream region. These modifications were attributed to the recruitment of GCN5 and SETD2, which are functional enzymes responsible for these modifications. Remarkably, the overexpression of either GCN5 or SETD2 restored SMARCC1 expression in rat cartilages or chondrocytes, consequently exacerbating the OA-like symptoms. Conclusion: This research postulates that the transcriptional activity of SMARCC1 can be influenced by IRF1 through the recruitment of GCN5 and SETD2, consequently regulating the H3K27ac and H3K4me3 modifications in close proximity to the SMARCC1 promoter and 10 kb upstream region. These modifications, in turn, facilitate the M1 skewing of macrophages and contribute to the progression of osteoarthritis (OA). The Translational Potential of this Article: The study demonstrated that the regulation of SMARCC1 by IRF1 plays a crucial role in the development of OA. Knocking down either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1ß in chondrocytes, leading to a mitigation of OA-like symptoms in rat models. These symptoms included inflammatory infiltration, cartilage degradation, and tissue injury. These findings suggest that targeting the IRF1-SMARCC1 regulatory axis, as well as the associated epigenetic modifications, could potentially be a novel approach in the development of OA therapies, offering new opportunities for disease management and improved patient outcomes.

Size control of ropivacaine nano/micro-particles by soft-coating with peptide nanosheets for long-acting analgesia.

Rationale: To meet the need of long-acting analgesia in postoperative pain management, slow-releasing formulations of local anesthetics (LAs) have been extensively investigated. However, challenges still remain in obtaining such formulations in a facile and cost-effective way, and a mechanism for controlling the release rate to achieve an optimal duration is still missing. Methods: In this study, nanosheets formed by a self-assembling peptide were used to encapsulate ropivacaine in a soft-coating manner. By adjusting the ratio between the peptide and ropivacaine, ropivacaine particles with different size were prepared. Releasing profile of particles with different size were studied in vitro and in vivo. The influence of particle size and ropivacaine concentration on effective duration and toxicity were evaluated in rat models. Results: Our results showed that drug release rate became slower as the particle size increased, with particles of medium size (2.96 ± 0.04 µm) exhibiting a moderate release rate and generating an optimal anesthetic duration. Based on this size, formulations at different ropivacaine concentrations generated anesthetic effect with different durations in rat sciatic nerve block model, with the 6% formulation generated anesthetic duration of over 35 h. Long-acting analgesia up to 48 h of this formulation was also confirmed in a rat total knee arthroplasty model. Conclusion: This study provided a facile strategy to prepare LA particles of different size and revealed the relationship between particle size, release rate and anesthetic duration, which provided both technical and theoretical supports for developing long-acting LA formulations with promising clinical application.

Fixed-time command filtered output feedback control for twin-roll inclined casting system with prescribed performance.

The article investigates the issue of fixed-time control with adaptive output feedback for a twin-roll inclined casting system (TRICS) with disturbance. First, by using the mean value theorem, the nonaffine functions are decoupled to simplify the system. Second, radial basis function neural networks (RBFNNs) are introduced to approximate an unknown term, and a nonlinear neural state observer is created to handle the effects of unmeasured states. Then, the backstepping design framework is combined with prescribed performance and command filtering techniques to demonstrate that the scheme proposed in this article guarantees system performance within a fixed-time. The control design parameters determine the upper bound of settling time, regardless of the initial state of the system. Meanwhile, it ensures that all signals in the closed-loop system (CLS) remain bounded, and it can also maintain the tracking error within a predefined range within a fixed time. Finally, simulation results assert the effectiveness of the method.