The screening of α-glucosidase inhibitory peptides from ß-conglycinin and hypoglycemic mechanism in HepG2 cells and zebrafish larvae.

Inhibition of carbohydrate digestive enzymes is a key focus across diverse fields, given the prominence of α-glucosidase inhibitors as preferred oral hypoglycaemic drugs for diabetes treatment. ß-conglycinin is the most abundant functional protein in soy; however, it is unclear whether the peptides produced after its gastrointestinal digestion exhibit α-glucosidase inhibitory properties. Therefore, we examined the α-glucosidase inhibitory potential of soy peptides. Specifically, ß-conglycinin was subjected to simulated gastrointestinal digestion by enzymatically cleaving it into 95 peptides with gastric, pancreatic and chymotrypsin enzymes. Eight soybean peptides were selected based on their predicted activity; absorption, distribution, metabolism, excretion and toxicity score; and molecular docking analysis. The results indicated that hydrogen bonding and electrostatic interactions play important roles in inhibiting α-glucosidase, with the tripeptide SGR exhibiting the greatest inhibitory effect (IC50 = 10.57 µg/mL). In vitro studies revealed that SGR markedly improved glucose metabolism disorders in insulin-resistant HepG2 cells without affecting cell viability. Animal experiments revealed that SGR significantly improved blood glucose and decreased maltase activity in type 2 diabetic zebrafish larvae, but it did not result in the death of zebrafish larvae. Transcriptomic analysis revealed that SGR exerts its anti-diabetic and hypoglycaemic effects by attenuating the expression of several genes, including Slc2a1, Hsp70, Cpt2, Serpinf1, Sfrp2 and Ggt1a. These results suggest that SGR is a potential food-borne bioactive peptide for managing diabetes.

Vibronics of multi-material nanopillared membranes and impact on the thermal conductivity.

Atomic motion in nanopillars standing on the surface of a silicon membrane generates vibrons, which are wavenumber-independent phonons that act as local resonances. These vibrons couple with the vast majority of the phonon population, including heat-carrying phonons, traveling along the base membrane causing a reduction in the in-plane lattice thermal conductivity. In this work, we examine isolated silicon and gallium nitride nanopillars and for each compare the vibrons density of states (DOS) to those of phonons in an isolated version of the silicon membrane. We show that while the conformity of the phonon-vibron DOS distribution between the two components across the full spectrum is a key factor in reducing the thermal conductivity of the assembled nanostructure, the presence of an intense vibron population at more dominant low frequencies plays a competing role. We report predictions from molecular dynamics simulations showing lower thermal conductivities for a silicon membrane with gallium-nitride nanopillars compared to a silicon membrane with silicon nanopillars.

The effects of BMP2 and the mechanisms involved in the invasion and angiogenesis of IDH1 mutant glioma cells.

PURPOSE: This study investigated the effect of an isocitrate dehydrogenase 1 (IDH1) mutation (mutIDH1) on the invasion and angiogenesis of human glioma cells. METHODS: Doxycycline was used to induce the expression of mutIDH1 in glioma cells. Transwell and wound healing assays were conducted to assess glioma cell migration and invasion. Western blotting and cell immunofluorescence were used to measure the expression levels of various proteins. The influence of bone morphogenetic protein 2 (BMP2) on invasion, angiogenesis-related factors, BMP2-related receptor expression, and changes in Smad signaling pathway-related proteins were evaluated after treatment with BMP2. Differential gene expression and reference transcription analysis were performed. RESULTS: Successful infection with recombinant lentivirus expressing mutIDH1 was demonstrated. The IDH1 mutation promoted glioma cell migration and invasion while positively regulating the expression of vascularization-related factors and BMP2-related receptors. BMP2 exhibited a positive regulatory effect on the migration, invasion, and angiogenesis of mutIDH1-glioma cells, possibly mediated by BMP2-induced alterations in Smad signaling pathway-related factors.After BMP2 treatment, the differential genes of MutIDH1-glioma cells are closely related to the regulation of cell migration and cell adhesion, especially the regulation of Smad-related proteins. KEGG analysis confirmed that it was related to BMP signaling pathway and TGF-ß signaling pathway and cell adhesion. Enrichment analysis of gene ontology and genome encyclopedia further confirmed the correlation of these pathways. CONCLUSION: Mutation of isocitrate dehydrogenase 1 promotes the migration, invasion, and angiogenesis of glioma cells, through its effects on the BMP2-driven Smad signaling pathway. In addition, BMP2 altered the transcriptional patterns of mutIDH1 glioma cells, enriching different gene loci in pathways associated with invasion, migration, and angiogenesis.

Analysis of mechanism, therapeutic strategies, and potential natural compounds against atherosclerosis by targeting iron overload-induced oxidative stress.

Ferroptosis is a novel form of cell demise characterized primarily by the reduction of trivalent iron to divalent iron, leading to the release of reactive oxygen species (ROS) and consequent induction of intense oxidative stress. In atherosclerosis (AS), highly accumulated lipids are modified by ROS to promote the formation of lipid peroxides, further amplifying cellular oxidative stress damage to influence all stages of atherosclerotic development. Macrophages are regarded as pivotal executors in the progression of AS and the handling of iron, thus targeting macrophage iron metabolism holds significant guiding implications for exploring potential therapeutic strategies against AS. In this comprehensive review, we elucidate the potential interplay among iron overload, inflammation, and lipid dysregulation, summarizing the potential mechanisms underlying the suppression of AS by alleviating iron overload. Furthermore, the application of Traditional Chinese Medicine (TCM) is increasingly widespread. Based on extant research and the pharmacological foundations of active compounds of TCM, we propose alternative therapeutic agents for AS in the context of iron overload, aiming to diversify the therapeutic avenues.

USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway.

The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.

Ferroptosis and secondary nephrosis. / é“æ­»äº¡ä¸Žç»§å‘æ€§è‚¾è„ç— .

Secondary nephrosis is a series of chronic kidney diseases secondary to other underlying diseases, mainly manifesting as structural and functional abnormalities of the kidneys and metabolic disorders. It is one of the important causes of end-stage renal disease, with high morbidity and significant harm. Iron is an essential metal element in human cells, and ferroptosis is a non-traditional form of iron-dependent cell death, and its main mechanisms include iron accumulation, lipid metabolism disorders, abnormal amino acid metabolism, and damage to the antioxidant system. Recently studies have found that ferroptosis is involved in the occurrence and progression of secondary nephrosis, and the mechanism of ferroptosis in different secondary nephrosis vary. Therefore, an in-depth and systematic understanding of the association between ferroptosis and secondary nephrosis, as well as their specific regulatory mechanisms, can provide a theoretical basis for the diagnosis, prevention, treatment, and prognosis assessment of secondary nephrosis, laying the foundation for exploring new clinical therapeutic targets for secondary nephrosis.

Genome-Wide Characterization of Fructose 1,6-Bisphosphate Aldolase Genes and Expression Profile Reveals Their Regulatory Role in Abiotic Stress in Cucumber.

The fructose-1,6-bisphosphate aldolase (FBA) gene family exists in higher plants, with the genes of this family playing significant roles in plant growth and development, as well as response to abiotic stresses. However, systematic reports on the FBA gene family and its functions in cucumber are lacking. In this study, we identified five cucumber FBA genes, named CsFBA1-5, that are distributed randomly across chromosomes. Phylogenetic analyses involving these cucumber FBAs, alongside eight Arabidopsis FBA proteins and eight tomato FBA proteins, were conducted to assess their homology. The CsFBAs were grouped into two clades. We also analyzed the physicochemical properties, motif composition, and gene structure of the cucumber FBAs. This analysis highlighted differences in the physicochemical properties and revealed highly conserved domains within the CsFBA family. Additionally, to explore the evolutionary relationships of the CsFBA family further, we constructed comparative syntenic maps with Arabidopsis and tomato, which showed high homology but only one segmental duplication event within the cucumber genome. Expression profiles indicated that the CsFBA gene family is responsive to various abiotic stresses, including low temperature, heat, and salt. Taken together, the results of this study provide a theoretical foundation for understanding the evolution of and future research into the functional characterization of cucumber FBA genes during plant growth and development.

Kinetically Controlled Self-Assembly of Ag Nanoclusters with Enhanced Luminescence.

Constructing self-assembly with definite assembly structure-property correlation is of great significance for expanding the property richness and functional diversity of metal nanoclusters (NCs). Herein, a well-designed liquid reaction strategy was developed through which a highly ordered nanofiber superstructure with enhanced green photoluminescence (PL) was obtained via self-assembly of the individual silver nanoclusters (Ag NCs). By visual monitoring of the kinetic reaction process using time-dependent and in situ spectroscopy measurements, the assembling structure growth and the structure-determined luminescence mechanisms were revealed. The as-prepared nanofibers featured a series of advantages involving a high emission efficiency, large Stokes shift, homogeneous chromophore, excellent photostability, high temperature, and pH sensibility. By virtue of these merits, they were successfully employed in various fields of luminescent inks, encryption and anticounterfeiting platforms, and optoelectronic light-emitting diode (LED) devices.

An investigation of a strengthening polysaccharide interfacial membrane strategy utilizing an anionic polysaccharide-alkaline ligand interfacial assembly for all-liquid printing.

The applications of polysaccharides as emulsifiers are limited due to the lack of hydrophobicity. However, traditional hydrophobic modification methods used for polysaccharides are complicated and involve significant mechanical and thermal losses. In this study, soy hull polysaccharide (SHP) and terminally aminopropylated polydimethylsiloxane (NPN) were selected to investigate the feasibility of a simple and green interfacial membrane strengthening strategy based on the interfacial polymerization of anionic polysaccharides and fat-soluble alkaline ligands. Our results show that deprotonated SHP and protonated NPN can be complexed at the water/oil (W/O) interface, reduce interfacial tension, and form a strong membrane structure. Moreover, they can quickly form a membrane at the W/O interface upon the moment of contact to produce stable all-liquid printing products with complex patterns. However, the molecular weight of NPN affects the complexation reaction. Consequently, this study has long-term implications to expanding the areas of application for anionic polysaccharides.

Strong, tough, conductive and transparent nanocellulose hydrogel based on Ca2+-induced cross-linked double-networks and its adsorption of methylene blue dye.

A novel multi-performance SHNC/SA/CaCl2 hydrogel with multi-performance was prepared via ultra-low-temperature freeze-thaw cycling and Ca2+ cross-linking for the removal of methylene blue (MB) from industrial wastewater. Various methods were used to characterize the structure and properties of hydrogel, and the internal structure of hydrogel showed a three-dimensional network with hydrogen and ester bonds. The SHNC/SA/CaCl2-15 hydrogel exhibited the highest tensile properties (elongation = 800 %), viscoelasticity (90 kPa), compressive strength (0.45 MPa), tensile strength (0.47 MPa) and ionic conductivity (4.34 S/cm). The maximum adsorption capacity of 2 g SHNC/SA/CaCl2-15 hydrogel was 608.49 mg/g at 40 °C, pH = 8 and adsorption 24 h. The adsorption process of hydrogel toward MB was more consistent with the second-order kinetic model and Langmuir isothermal adsorption model. According to the Langmuir isotherm model, the maximum monolayer adsorption capacity of SHNC/SA/CaCl2-15 hydrogel toward MB can reach 613.88 mg/g. Finally, it was found that the removal rate of SHNC/SA/CaCl2-15 hydrogel for MB was still as high as 90 % after five cycles of the adsorption-desorption test, and it could be reused. The hydrogel can be used as cheap and reusable adsorption material for cationic dyes. Our study provides a new perspective for the development of multifunctional cellulose hydrogel adsorbent materials.

Recent trends in the incidence of early-onset prostate cancer.

Early-onset prostate cancer (EOPC) is relatively uncommon. It is unclear if the incidence of EOPC is evolving. Utilizing data from the SEER database from 2000 to 2020, the study identified prostate cancer cases in men under 55 years, focusing on trends in annual age-adjusted incidence rates (AAIR), stage at presentation, race/ethnicity, and local treatment patterns. The study encompassed 93 071 cases of EOPC, with the median age at diagnosis being 51 years. From 2000 to 2007, the AAIR of EOPC experienced a wave-like increase from 6.9 to 8.3 per 100 000 people. It then sharply declined to 5.4 by 2014, followed by 6 years of stability, and by 2020 it had dropped to its lowest point of 4.5. The trend observed across different racial groups was consistent with the overall pattern, where non-Hispanic Black patients consistently exhibited the highest incidence and the least reduction rate (annual percent change, -1.0; 95% confidence interval, -1.8 to -0.2; P < 0.05). Stage II was the most commonly diagnosed, although its AAIR declined from 4.9 to 1.2 per 100 000 people. From 2010 through 2020, the proportion of receiving prostatectomy decreased from 63.0 to 43.6%. The declining rates of EOPC across diverse racial groups emphasize the critical need for focused research and interventions. Specifically, there is an urgent call to establish a tailored screening protocol for prostate cancer targeting Black youth.

Exploration of chemical components and metabolite synthesis pathways in eight Ephedra species based on HS-GC-MS and UPLC-Q-TOF-MS.

Objective: Ephedra, widely used in clinical practice as a medicinal herb, belongs to the genus Ephedra in the family Ephedraceae. However, the presence of numerous Ephedra varieties and variants requires differentiation for accurate identification. Methods: In this study, we employed headspace gas chromatography mass spectrometry (HS-GC-MS), ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and global natural products social molecular networking (GNPS) for chemical component identification. Chemometric analysis was used to analyze the differential components. Metabolic analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment were utilized to explore the synthesis pathways of different components. Result: A total of 83 volatile and 79 non-volatile components were identified in Ephedra species. Differential analysis revealed that among the eight Ephedra stems, 18 volatile and 19 non-volatile differential compounds were discovered, whereas Ephedra roots exhibited 21 volatile and 17 non-volatile markers. Volatile compounds were enriched in four synthetic pathways, while non-volatile components were enriched in five pathways among the differentiated components. Conclusion: This study is the first to conduct a comparative analysis of chemical components in different Ephedra species and parts. It provides a foundational reference for authenticating Ephedra herbs, evaluating medicinal resources, and comparing quality in future studies.

Dissecting heritability, environmental risk, and air pollution causal effects using > 50 million individuals in MarketScan.

Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype information and approximate pedigree structures. Here we use the approximate geographical locations of patients as a proxy for spatially correlated community-level environmental risk factors. We develop a spatial mixed linear effect (SMILE) model that incorporates both genetics and environmental contribution. We extract EHR and geographical locations from 257,620 nuclear families and compile 1083 disease outcome measurements from the MarketScan dataset. We augment the EHR with publicly available environmental data, including levels of particulate matter 2.5 (PM2.5), nitrogen dioxide (NO2), climate, and sociodemographic data. We refine the estimates of genetic heritability and quantify community-level environmental contributions. We also use wind speed and direction as instrumental variables to assess the causal effects of air pollution. In total, we find PM2.5 or NO2 have statistically significant causal effects on 135 diseases, including respiratory, musculoskeletal, digestive, metabolic, and sleep disorders, where PM2.5 and NO2 tend to affect biologically distinct disease categories. These analyses showcase several robust strategies for jointly modeling genetic and environmental effects on disease risk using large EHR datasets and will benefit upcoming biobank studies in the era of precision medicine.

The Effect of Microbiome-Modulating Agents (MMAs) on Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the microbiome from dysbiosis. The objective of this systematic review and meta-analysis was to assess the impact of MMAs on hemoglobin A1c (HbA1c) and biomarkers associated with (T1D). A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, National Knowledge Infrastructure, WeiPu, and WanFang Data up to 30 November 2023. Ten randomized controlled trials (n = 630) were included, with study quality evaluated using the Cochrane risk-of-bias tool. Random-effect models with standardized mean differences (SMDs) were utilized. MMA supplementation was associated with improvements in HbA1c (SMD = -0.52, 95% CI [-0.83, -0.20]), daily insulin usage (SMD = -0.41, 95% confidence interval (CI) [-0.76, -0.07]), and fasting C-peptide (SMD = 0.99, 95% CI [0.17, 1.81]) but had no effects on FBG, CRP, TNF-α, IL-10, LDL, HDL, and the Shannon index. Subgroup analysis of HbA1c indicated that a long-term intervention (>3 months) might exert a more substantial effect. These findings suggest an association between MMAs and glycemic control in T1D. Further large-scale clinical trials are necessary to confirm these findings with investigations on inflammation and gut microbiota composition while adjusting confounding factors such as diet, physical activity, and the dose and form of MMA intervention.

Remodeling of tumor microenvironment by extracellular matrix protein 1a differentially regulates ovarian cancer metastasis.

We previously reported that extracellular matrix protein 1 isoform a (ECM1a) promotes epithelial ovarian cancer (EOC) through autocrine signaling by binding to cell surface receptors αXß2. However, the role of ECM1a as a secretory molecule in the tumor microenvironment is rarely reported. In this study, we constructed murine Ecm1-knockout mice and human ECM1a-knockin mice and further generated orthotopic or peritoneal xenograft tumor models to mimic the different metastatic stages of EOC. We show that ECM1a induces oncogenic metastasis of orthotopic xenograft tumors, but inhibits early-metastasis of peritoneal xenograft tumors. ECM1a remodels extracellular matrices (ECM) and promotes remote metastases by recruiting and transforming bone marrow mesenchymal stem cells (BMSCs) into platelet-derived growth factor receptor beta (PDGFRß+) cancer-associated fibroblasts (CAFs) and facilitating the secretion of angiopoietin-like protein 2 (ANGPTL2). Competing with ECM1a, ANGPTL2 also binds to integrin αX through the P1/P2 peptides, resulting in negative effects on BMSC differentiation. Collectively, this study reveals the dual functions of ECM1a in remodeling of TME during tumor progression, emphasizing the complexity of EOC phenotypic heterogeneity and metastasis.

Punicalagin Ameliorates Diabetic Liver Injury by Inhibiting Pyroptosis and Promoting Autophagy via Modulation of the FoxO1/TXNIP Signaling Pathway.

Diabetic liver injury (DLI) is one of the complications of diabetes mellitus, which seriously jeopardizes human health. Punicalagin (PU), a polyphenolic compound mainly found in pomegranate peel, has been shown to ameliorate metabolic diseases such as DLI, and the mechanism needs to be further explored. In this study, a HFD/STZ-induced diabetic mouse model is established to investigate the effect and mechanism of PU on DLI. The results show that PU intervention significantly improves liver histology and serum biochemical abnormalities in diabetic mice, significantly inhibits the expression of pyroptosis-related proteins such as NLRP3, Caspase1, IL-1ß, and GSDMD in the liver of diabetic mice, and up-regulated the expression of autophagy-related proteins. Meanwhile, PU treatment significantly increases FoxO1 protein expression and inhibits TXNIP protein expression in the liver of diabetic mice. The above results are further verified in the HepG2 cell injury model induced by high glucose. AS1842856 is a FoxO1 specific inhibitor. The intervention of AS1842856 combined with PU reverses the regulatory effects of PU on pyroptosis and autophagy in HepG2 cells. In conclusion, this study demonstrates that PU may inhibit pyroptosis and upregulate autophagy by regulating FoxO1/TXNIP signaling, thereby alleviating DLI.

A novel pathogenic mitochondrial DNA variant m.4344T>C in tRNAGln causes developmental delay.

Mitochondrial diseases are a group of genetic diseases caused by mutations in mitochondrial DNA and nuclear DNA. However, the genetic spectrum of this disease is not yet complete. In this study, we identified a novel variant m.4344T>C in mitochondrial tRNAGln from a patient with developmental delay. The mutant loads of m.4344T>C were 95% and 89% in the patient's blood and oral epithelial cells, respectively. Multialignment analysis showed high evolutionary conservation of this nucleotide. TrRosettaRNA predicted that m.4344T>C variant would introduce an additional hydrogen bond and alter the conformation of the T-loop. The transmitochondrial cybrid-based study demonstrated that m.4344T>C variant impaired the steady-state level of mitochondrial tRNAGln and decreased the contents of mitochondrial OXPHOS complexes I, III, and IV, resulting in defective mitochondrial respiration, elevated mitochondrial ROS production, reduced mitochondrial membrane potential and decreased mitochondrial ATP levels. Altogether, this is the first report in patient carrying the m.4344T>C variant. Our data uncover the pathogenesis of the m.4344T>C variant and expand the genetic mutation spectrum of mitochondrial diseases, thus contributing to the clinical diagnosis of mitochondrial tRNAGln gene variants-associated mitochondrial diseases.

DAPK1 mediates cognitive dysfunction and neuronal apoptosis in PSD rats through the ERK/CREB/BDNF signaling pathway.

Post-stroke depression (PSD) is one of the most common mental sequelae after a stroke and can damage the brain. Although PSD has garnered increasing attention in recent years, the precise mechanism remains unclear. Studies have indicated that the expression of DAPK1 is elevated in various neurodegenerative conditions, including depression, ischemic stroke, and Alzheimer's disease. However, the specific molecular mechanism of DAPK1-mediated cognitive dysfunction and neuronal apoptosis in PSD rats is unclear. In this study, we established a rat model of PSD, and then assessed depression-like behaviors and cognitive dysfunction in rats using behavioral tests. In addition, we detected neuronal apoptosis and analyzed the expression of DAPK1 protein and proteins related to the ERK/CREB/BDNF signaling pathway. The findings revealed that MCAO combined with CUMS can induce more severe depression-like behaviors and cognitive dysfunction in rats, while overexpression of DAPK1 may hinder the downstream ERK/CREB/BDNF signaling pathways, resulting in neuronal loss and exacerbation of brain tissue damage. In this study, we will focus on DAPK1 and explore its role in PSD.