Identification of genome-wide copy number variation-driven subtypes for the treatment and prognostic prediction of esophageal carcinoma.

Background: Esophageal carcinoma (ESCA) is a frequently detected gastrointestinal cancer. Copy number variants (CNVs) have a dramatic impact on the screening, diagnosis and prognostic prediction of cancers. However, the mechanism of action of CNVs on ESCA occurrence and progression remains unclear. Methods: ESCA samples from The Cancer Genome Atlas (TCGA) were typed by consensus clustering using CNV-associated genes. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to section gene modules closely related to the two clusters, and sub-networks were constructed as hub genes. In addition, seven prognosis-correlated genes were further screened and retained by multivariate Cox regression analysis to develop a prognostic assessment model. The ssGSEA algorithm assessed energy metabolism levels in patients from different clusters and risk groups. Finally, quantitative real-time PCR (qRT-PCR) and live-dead cell staining verified the expression of genes associated with CNV risk scores. Results: ESCA was classified into two subtypes based on CNV values. Compared with cluster 1, cluster 2 had significantly higher level of immune score and tumor-associated immune cell infiltration as well as a noticeably better overall survival. The three modules most associated with the two clusters were identified by WGCNA, and a prognostic model with a strong prediction performance was constructed with their genes. Glycolysis, lactate metabolism, fatty acid synthesis, glutathione, methionine, and tryptophan metabolic pathway enrichment scores were remarkably higher in patients in cluster 1 and the high-risk group than in cluster 2 and the low-risk group. Knockdown PIK3C2A promoted ESCA cells apoptosis and inhibited cell vibiality. Conclusion: The current research maybe provides new understanding for the pathogenesis of ESCA based on CNV, providing an effective guidance for its clinical diagnosis and prognostic evaluation.

Multiple measures for self-identification improve matching donors with patients in unrelated hematopoietic stem cell transplant.

BACKGROUND: Questions persist around whether and how to use race or geographic ancestry in biomedical research and medicine, but these forms of self-identification serve as a critical tool to inform matching algorithms for human leukocyte antigen (HLA) of varying levels of resolution for unrelated hematopoietic stem cell transplant in large donor registries. METHODS: Here, we examined multiple self-reported measures of race and ancestry from a survey of a cohort of over 100,000 U.S. volunteer bone marrow donors alongside their high-resolution HLA genotype data. RESULTS: We find that these self-report measures are often non-overlapping, and that no single self-reported measure alone provides a better fit to HLA genetic ancestry than a combination including both race and geographic ancestry. We also found that patterns of reporting for race and ancestry appear to be influenced by participation in direct-to-consumer genetic ancestry testing. CONCLUSIONS: While these data are not used directly in matching for transplant, our results demonstrate that there is a place for the language of both race and geographic ancestry in the critical process of facilitating accurate prediction of HLA in the donor registry context.

Self-identification with respect to race and ancestry is an important component in the process of finding a matching unrelated bone marrow donor for a patient in large donor registries. Here, we considered whether terms specific to either race or the geographic ancestry of donors would be more useful in the matching process. We found that rather than using either of these terms alone, collecting responses for both race and geographic ancestry from potential donors is most likely to provide the information necessary to find a genetic match among millions of donors for a patient in need of a transplant.

Target-inhibited MCOF-Apt-AuNPs self-assembly for multicolor colorimetric detection of Salmonella Typhimurium.

Pathogens detection is a crucial measure in the prevention of foodborne diseases. This study developed a novel multicolor colorimetric assay to visually detect Salmonella Typhimurium (S. Typhimurium), by utilizing the etching process of gold nanorods (AuNRs) with TMB2+. The strategy involved the construction of nanozyme by assembling magnetic covalent organic framework (MCOF) with aptamer-conjugated AuNPs (Apt-AuNPs), exhibiting remarkable peroxidase-like activity to catalyze the oxidation of TMB/H2O2 and inducing the etching of AuNRs. The presence of S. Typhimurium could inhibit this process, resulting in the generation of vivid colors. The multicolor colorimetric assay could specifically determine S. Typhimurium from 102 to 108 CFU mL-1 in 60 min with visual detection limit of 102 CFU mL-1, and instrumental detection limit of 2.3 CFU mL-1. Moreover, detecting S. Typhimurium in chicken, milk, pork and lettuce samples has shown promise in practical applications.

Porous starch microspheres loaded with luteolin exhibit hypoglycemic activities and alter gut microbial communities in type 2 diabetes mellitus mice.

Luteolin (LUT), a natural flavonoid known for its hypoglycemic properties, is primarily sourced from vegetables such as celery and broccoli. However, its poor stability and low bioavailability in the upper digestive tract hinder its application in the functional food industry. To address these challenges, this study employed porous starch (PS) as a carrier to develop PS microspheres loaded with luteolin (PSLUT), simulating its release in vitro. The research assessed the hypoglycemic effects of LUT in type 2 diabetes mellitus (T2DM) mice both before and after PS treatment. In vitro findings demonstrated that PS improved LUT's stability in simulated gastric fluids and enhanced its in vivo bioavailability, aligning with experimental outcomes. PSLUT administration significantly improved body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), pancreatic islet function, and other relevant indicators in T2DM mice. Moreover, PSLUT alleviated abnormal liver biochemical indicators and liver tissue injury caused by T2DM. The underlying hypoglycemic mechanism of PSLUT is thought to involve the regulation of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2). After four weeks of intervention, various PSLUT doses significantly reduced the Firmicutes to Bacteroidetes ratio at the phylum level and decreased the relative abundance of harmful bacteria at the genus level, including Acetatifactor, Candidatus-Arthromitus, and Turicibacter. This microbial shift was associated with improvements in hyperglycemia-related indicators such as FBG, the area under the curve (AUC) of OGTT, and homeostasis model assessment of insulin resistance (HOMA-IR), which are closely linked to these bacterial genera. Additionally, Lachnoclostridium, Parasutterella, Turicibacter, and Papillibacter were identified as key intestinal marker genera involved in T2DM progression through Spearman correlation analysis. In conclusion, PS enhanced LUT's hypoglycemic efficacy by modulating the transcription and protein expression levels of AKT-1 and GLUT-2, as well as the relative abundance of potential gut pathogens in T2DM mice. These results provide a theoretical foundation for advancing luteolin's application in the functional food industry and further investigating its hypoglycemic potential.

Association of circulating cytokine levels and tissue-infiltrating myeloid cells with achalasia: results from Mendelian randomization and validation through clinical characteristics and single-cell RNA sequencing.

BACKGROUND: Achalasia is a rare motility disorder of the esophagus often accompanied by immune dysregulation, yet specific underlying mechanisms remain poorly understood. METHODS: We utilized Mendelian randomization (MR) to explore the causal effects of cytokine levels on achalasia, with cis-expression/protein quantitative trait loci (cis-eQTLs/pQTLs) for 47 cytokines selected from a genome-wide association study (GWAS) meta-analysis and GWAS data for achalasia obtained from FinnGen. For cytokines significantly linked to achalasia, we analyzed their plasma concentrations and expression differences in the lower esophageal sphincter (LES) using enzyme-linked immunosorbent assay and single-cell RNA sequencing (scRNA-seq) profiling, respectively. We further employed bioinformatics approaches to investigate underlying mechanisms. RESULTS: We revealed positive associations of circulating Eotaxin, macrophage inflammatory protein-1b (MIP1b), soluble E-selectin (SeSelectin) and TNF-related apoptosis-inducing ligand (TRAIL) with achalasia. When combining MR findings with scRNA-seq data, we observed upregulation of TRAIL (OR = 2.70, 95% CI, 1.20-6.07), encoded by TNFSF10, in monocytes and downregulation of interleukin-1 receptor antagonist (IL-1ra) (OR = 0.70, 95% CI 0.59-0.84), encoded by IL1RN, in FOS_macrophages in achalasia. TNFSF10high monocytes in achalasia displayed activated type I interferon signaling, and IL1RNlow FOS_macrophages exhibited increased intercellular communications with various lymphocytes, together shaping the proinflammatory microenvironment of achalasia. CONCLUSIONS: We identified circulating Eotaxin, MIP1b, SeSelectin and TRAIL as potential drug targets for achalasia. TNFSF10high monocytes and IL1RNlow macrophages may play a role in the pathogenesis of achalasia.

Tumor-derived IL-6 promotes chordoma invasion by stimulating tumor-associated macrophages M2 polarization and TNFα secretion.

AIMS: Chordoma is a rare and aggressive bone tumor with high-recurrence and lack of effective treatment methods. Tumor associated macrophages (TAMs) are abundant in tumor microenvironment (TME) and polarize toward M2 in chordoma. It has been observed that the high proportion of M2 cells is associated with chordoma rapid progression. However, the mechanism of TAMs polarization and promotion to tumor progression in chordoma is still unclear. The is an urgent need for further research. MATERIALS AND METHODS: Flow cytometry and immunohistochemical staining was used to detect the degree of macrophages infiltration in chordoma. A co-culture model of chordoma cells and macrophages was established in vitro to investigate the effects of their interaction on cell function, cytokine secretion, and RNA transcriptome expression. KEY FINDINGS: In this study, we found M2 macrophage was predominantly abundant immune cell population in chordoma, and its proportion was associated with the degree of bone destruction. We demonstrated that interleukin 6 (IL-6) derived from chordoma cells could induce TAMs polarization by activating STAT3 phosphorylation, and TAMs could enhance chordoma cells migration and invasion through TNFα/NF-κB pathway. The interaction of chordoma cells and TAMs could promote the bone destruction-related factor Cathepsin B (CTSB) and inhibitory immune checkpoints expression. We also confirmed blocking IL-6/STAT3 pathway could significantly attenuate the M2 polarization of TAMs and decrease the secretion of TNFα. SIGNIFICANCE: This study illustrates the dynamics between chordoma cells and TAMs in promoting chordoma invasion and suggests that IL-6/STAT3 pathway is a potential therapeutic target to reduce TAM-induced chordoma invasion.

Isotropically Polarized Bipiezoelectric Polyacrylonitrile-Poly(vinylidene Fluoride) Advanced Triboelectric Nanogenerator for Operation in High-Humidity Environments.

Conventional hybrid piezo-triboelectric nanogenerators (PTNGs) have potential applications as energy supply devices for microelectronic devices, but their low power density and unstable performance under high-humidity conditions are challenges that need to be solved. Here, we report a novel flexible hybrid bifiezo-triboelectric nanogenerator (Bi-PTNG) based on isotropic polarization design of piezoelectric PVDF and PAN nanofiber membranes, which greatly improves power density of devices and performances in high-humidity conditions. The performance enhancement mechanism of the Bi-PTNG was investigated by model analysis, experimental measurements, and simulations. The results showed that the power density output of Bi-PTNG increased by approximately 88% compared to that of a depolarized PAN/PVDF-based triboelectric nanogenerator (TENG). The application studies demonstrated that a 2 × 2 cm2 Bi-PTNG can be directly used to run more than 120 commercial LEDs, and this highly flexible and breathable all-fiber device can be integrated into clothing or insoles to monitor human movement in high-humidity conditions. This work not only provides an effective strategy for enhancing the power output of TENGs and advancing their practical applications but also offers robust guidance for the material selection and optimization of the polarization direction in such nanogenerators.

Vinegar - a beneficial food additive: production, safety, possibilities, and applications from ancient to modern times.

Vinegar is a natural product derived from fruits or grains after being subjected to food fermentation processes. Vinegar is a beneficial food additive, preservative, and condiment. It is appreciated across the Islamic world following the Prophetic teaching where Prophet Muhammad (peace be upon him) recommended its utility, saying: "The best of condiments is vinegar". Modern medicine recognizes the health benefits, especially upon metabolism and circulation, mediated by the bioactive constituents of vinegar, including acetic acid, caffeic acid, ferulic acid, chlorogenic acid, gallic acid, p-coumaric acid, catechin, and epicatechin. Using a variety of search engines, including Google Scholar, Sci-Finder, Wiley publications, Springer Link, Scopus, MDPI, Web of Science, and PubMed, a thorough survey of the literature was carried out. To compile a comprehensive data on the various varieties of vinegar, this review highlights and updates the existing information of different vinegar-related topics including production methods, quality assessment using different quantitative analysis tools, preclinical and clinical studies, structure-activity relationship, consumption, and applications from antiquity to the present.

Confocal image of three oxoaporphine alkaloids in cancer cell lines and their interaction with DNA by multispectroscopic and molecular docking techniques.

Dicentrinone (Di), liriodenine (Li) and lysicamine (Ly) are three natural oxoaporphine alkaloids (OAs), which revealed significant biological activity such as anticancer, anti-inflammatory and antimicrobial activities and were considered as potential lead compounds for the development of new clinical chemicals. In the present study, confocal laser scanning fluorescence microscopy observation demonstrated these three natural OAs could traverse inside of the nucleus and get an opportunity to interact with DNA. Their interaction properties with DNA were then investigated simultaneously by two spectral fluorescent probes of ethidium bromide (EB) and methyl green (MG), as well as UV-vis absorption and cyclic voltammetry measurements, and further verified by the molecular docking analysis. Results indicated Di and Li were distinctly classified as the intercalative molecules to DNA, however, Ly was confirmed with a mixed-mode binding of partial intercalation and groove affinity. Their binding ability was revealed as the follows: Di ≥ Li > Ly, which was correlated with their structural changes. Thermodynamic studies revealed the binding process of Li and Ly with ctDNA was all spontaneous, the hydrophobic interaction was the major binding force for Li-ctDNA complex, however, the interaction between Ly and ctDNA relied on both hydrophobic and hydrogen binding force. Molecular docking provided detailed computational interaction of Di, Li and Ly with DNA, which proved the intercalation binding of Li-DNA complex and Di-DNA complex stabilizing mainly by the π-π binding force, however, apart from a small quantity of π-π interaction, another binding force in the Ly-DNA complex mainly was supplied from the weaker Pi-Alkyl, hydrogen bond and Pi-Anion interactions.

Prospects of phycoerythrin: Structural features, antioxidation and applications in food.

Phycoerythrin (PE) is a naturally occurring plant protein of algal origin. The colour, bioactivity and stability of PE are inextricably linked to its structure. PE has powerful antioxidant properties that effectively prevent oxidative stress and cellular damage, for which the chromophore structure plays a key role. However, the relationship between the chromophore and thermal stability is unclear in PE. The environmental factors affecting the thermal stability of PE are mainly light, high temperature and extreme pH. PE stability can be enhanced through various techniques, including the incorporation of additives, cross-linking processes, and the formation of complexes. Improving the stability of PE is of significant importance for its applications within the food industry. This paper outlines the structural characteristics of PE, discusses the relationship between its structure and antioxidant activity, and focuses on the application of PE in the food industry, as well as the factors affecting its stability and strategies for its improvement.

An enhanced SPR optical fiber biosensor using Ti3C2Tx MXene/AuNPs for label-free and sensitive detection of human IgG.

Abnormal human immunoglobulin G (IgG) may induce the risk of immune system disorder, infectious diseases, tumors and so on. However, the current detection methods exhibit low sensitivity, which limits their practical application. In this work, an SPR optical fiber sensor (SPR-OFS) with high sensitivity is designed for label-free detection of human IgG. It is fabricated using a heterostructure optical fiber coated with Au film/AuNPs and the Ti3C2Tx MXene biofunctionalized with goat anti-human IgG by polydopamine (PDA). In the experiment, the optimal thickness of the Ti3C2Tx MXene was explored and determined to be about 93 nm by comprehensively considering the refractive index (RI) sensitivity and spectral bandwidth of the SPR sensor. When the largest figure of merit (FOM) is calculated to be 17.8279 RIU-1, its RI sensitivity was ultimately found to be 2804.5 nm per RIU. The SPR-OFS was employed to detect human IgG within the concentration range of 0-30 µg mL-1 and its sensitivity is demonstrated to be 1.7046 nm (µg mL-1)-1. The SPR-OFS was also proved to have excellent linearity, specificity and stability. The proposed sensor offers outstanding performance with simple fabrication, providing a cutting-edge bioanalytical platform with potential applications in clinical diagnosis.

The complete chloroplast genome of Pilea notata C. H. Wright, 1899 (Urticaceae).

Pilea notata (Pilea notata C. H. Wright_C. H. Wright, 1899) is Pilea Lindl. of Urticaceae, which is a commonly used Miao medicine in Guizhou province. The P. notata chloroplast genome is 150,979 bp, contains a pair of inverted repeats (IRs 25,743bp), and is separated by a large single-copy region (81,446bp) and a small single-copy region (18,047bp). A total of 131 genes, including 86 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that P. notata, P. verrucosa and P. monilifera united as a single branch, while Pilea cadierei was defined as a sister group of this branch.

Combining systems pharmacology, metabolomics, and transcriptomics to reveal the mechanism of Salvia miltiorrhiza-Cortex moutan herb pair for the treatment of ischemic stroke.

Ischemic stroke (IS), predominantly triggered by blockages in cerebral blood flow, is increasingly recognized as a critical public health issue. The combination of Salvia miltiorrhiza (SM) and Cortex moutan (CM), traditional herbs in Eastern medicine, are frequently used for managing heart and brain vascular conditions. However, the exact mechanisms by which this herb pair (SC) combats IS remain largely unexplored. This investigation focuses on pinpointing the active constituents in SC that contribute to its protective role and deciphering the mechanisms countering cerebral ischemia, particularly in a middle cerebral artery occlusion (MCAO) rat model. We employed UPLC-Q-TOF-MS/MS alongside network pharmacology for predicting SC's target actions against IS. Key ingredients were examined for their interaction with principal targets using molecular docking. The therapeutic impact was gauged through H&E, TUNEL, and Nissl staining, complemented by transcriptomic and metabolomic integration for mechanistic insights, with vital genes confirmed via western blot. UPLC-Q-TOF-MS/MS analysis revealed that the main components of SC included benzoylpaeoniflorin, salvianolic acid B, oxypaeoniflora, salvianolic acid A, and others. Network pharmacology analysis indicated that SC's mechanism in treating IS primarily involves inflammation, angiogenesis, and cell apoptosis-related pathways, potentially through targets such as AKT1, TNF, PTGS2, MMP9, PIK3CA, and VEGFA. Molecular docking underscored strong affinities between these constituents and their targets. Our empirical studies indicated SC's significant role in enhancing neuroprotection in IS, with transcriptomics suggesting the involvement of the VEGFA/PI3K/AKT pathway and metabolomics revealing improvements in various metabolic processes, including amino acids, glycerophospholipids, sphingomyelin, and fatty acids metabolisms.

Study of Mesoporous Zr-TiO2 Catalyst with Rich Oxygen Vacancies for N-Methylmorpholine Oxidation to N-Methylmorpholine-N-oxide.

A series of Zr-TiO2 catalysts were prepared using a facile sol-gel method and were used for N-methylmorpholine (NMM) oxidation to N-methylmorpholine-N-oxide (NMMO). The structure features of Zr-TiO2 catalysts were studied in detail through a variety of characterization methods, such as XRD, SEM, N2 adsorption-desorption isotherms, XPS, EPR, and O2-TPD. As-obtained 5%Zr-TiO2 catalysts had superior catalytic performance and stability with a 97.6% NMMO yield at 40 °C, which related to Zr doping, a higher surface area, more oxygen vacancies, and oxygen chemisorption on the catalytic surface. This work provides an efficient preparation strategy of TiO2-based catalysts for selective oxidation reactions by a facile method.

Mutation pressure mediates a pattern of substitution rates with latitude and climate in carnivores.

The evolutionary patterns of the mitochondrial genome are influenced by both adaptive and nonadaptive forces, with their contributions varying among taxa. There appears to be a correlation linking mutagenesis and latitude, which could be due to differences in metabolic rates. These discrepancies in metabolic rates exhibit a positive connection with mutation pressure. On this basis, we hypothesise that nonadaptive forces play a role in the differences in mutation rates observed along latitudinal gradients. In this study, we selected widely distributed carnivores as representatives of mammals to test our hypothesis. We examined the correlations between the dN/dS ratio (ω), as well as the substitution rates (dS and dN), of 13 PCGs in the mtDNA of 122 carnivores, and the latitude and climatic factors. We found that taxa distributed in higher latitudes tend to have higher substitution rates, but not ω values indicating selective pressure. Notably, dN shows a strong positive correlation with dS, although dS is primarily influenced by mutation pressure, while dN is also influenced by effective population size (N e ). Phylogenetic generalised least squares (PGLS) regression analyses showed that both substitution rates were correlated with climatic factors representing the temperature, precipitation and variability of climate. Based on our findings, we propose that the mutations are primarily influenced by nonadaptive forces (mutation pressure). This forms the fundamental premise for natural selection and speciation. Moreover, the correlation between substitution rates and latitudinal distribution and climate, which are outcomes of nonadaptive factors, can aid in comprehending the global distribution of species diversity.

Exploring the antimicrobial activity of rare ginsenosides and the progress of their related pharmacological effects.

BACKGROUND: Panax ginseng C. A. Mey is a precious medicinal resource that could be used to treat a variety of diseases. Saponins are the most important bioactive components of, and rare ginsenosides (Rg3, Rh2, Rk1 and Rg5, etc.) refer to the chemical structure changes of primary ginsenosides through dehydration and desugarization reactions, to obtain triterpenoids that are easier to be absorbed by the human body and have higher activity. PURPOSE: At present, the research of P. ginseng. is widely focused on anticancer related aspects, and there are few studies on the antibacterial and skin protection effects of rare ginsenosides. This review summarizes the rare ginsenosides related to bacterial inhibition and skin protection and provides a new direction for P. ginseng research. METHODS: PubMed and Web of Science were searched for English-language studies on P. ginseng published between January 2002 and March 2024. Selected manuscripts were evaluated manually for additional relevant references. This review includes basic scientific articles and related studies such as prospective and retrospective cohort studies. CONCLUSION: This paper summarizes the latest research progress of several rare ginsenosides, discusses the antibacterial effect of rare ginsenosides, and finds that ginsenosides can effectively protect the skin and promote wound healing during use, so as to play an efficient antibacterial effect, and further explore the other medicinal value of ginseng. It is expected that this review will provide a wider understanding and new ideas for further research and development of P. ginseng drugs.

Self-assembled superstructure alleviates air-water interface effect in cryo-EM.

Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (<100 kDa) at near-atomic resolution. This study expands the understanding of SAMs and provides a key to better control the interaction of protein with air-water interface.