Single-Cell RNA Sequencing Resolves Spatiotemporal Development of Pre-thymic Lymphoid Progenitors and Thymus Organogenesis in Human Embryos.

Generation of the first T lymphocytes in the human embryo involves the emergence, migration, and thymus seeding of lymphoid progenitors together with concomitant thymus organogenesis, which is the initial step to establish the entire adaptive immune system. However, the cellular and molecular programs regulating this process remain unclear. We constructed a single-cell transcriptional landscape of human early T lymphopoiesis by using cells from multiple hemogenic and hematopoietic sites spanning embryonic and fetal stages. Among heterogenous early thymic progenitors, one subtype shared common features with a subset of lymphoid progenitors in fetal liver that are known as thymus-seeding progenitors. Unbiased bioinformatics analysis identified a distinct type of pre-thymic lymphoid progenitors in the aorta-gonad-mesonephros (AGM) region. In parallel, we investigated thymic epithelial cell development and potential cell-cell interactions during thymus organogenesis. Together, our data provide insights into human early T lymphopoiesis that prospectively direct T lymphocyte regeneration, which might lead to development of clinical applications.

Cyclic stretch promotes vascular homing of endothelial progenitor cells via Acsl1 regulation of mitochondrial fatty acid oxidation.

Endothelial progenitor cells (EPCs) play an important role in vascular repair and re-endothelialization after vessel injury. EPCs in blood vessels are subjected to cyclic stretch (CS) due to the pulsatile pressure, but the role of CS in metabolic reprogramming of EPC, particularly its vascular homing and repair, is largely unknown. In the current study, physiological CS applied to EPCs at a magnitude of 10% and a frequency of 1 Hz significantly promoted their vascular adhesion and endothelial differentiation. CS enhanced mitochondrial elongation and oxidative phosphorylation (OXPHOS), as well as adenosine triphosphate production. Metabolomic study and Ultra-high performance liquid chromatography-mass spectrometry assay revealed that CS significantly decreased the content of long-chain fatty acids (LCFAs) and markedly induced long-chain fatty acyl-CoA synthetase 1 (Acsl1), which in turn facilitated the catabolism of LCFAs in mitochondria via fatty acid ß-oxidation and OXPHOS. In a rat carotid artery injury model, transplantation of EPCs overexpressing Acsl1 enhanced the adhesion and re-endothelialization of EPCs in vivo. MRI and vascular morphology staining showed that Acsl1 overexpression in EPCs improved vascular repair and inhibited vascular stenosis. This study reveals a mechanotransduction mechanism by which physiological CS enhances endothelial repair via EPC patency.

Effect of aberrant fructose metabolism following SARS-CoV-2 infection on colorectal cancer patients' poor prognosis.

Most COVID-19 patients have a positive prognosis, but patients with additional underlying diseases are more likely to have severe illness and increased fatality rates. Numerous studies indicate that cancer patients are more prone to contract SARS-CoV-2 and develop severe COVID-19 or even dying. In the recent transcriptome investigations, it is demonstrated that the fructose metabolism is altered in patients with SARS-CoV-2 infection. However, cancer cells can use fructose as an extra source of energy for growth and metastasis. Furthermore, enhanced living conditions have resulted in a notable rise in fructose consumption in individuals' daily dietary habits. We therefore hypothesize that the poor prognosis of cancer patients caused by SARS-CoV-2 may therefore be mediated through fructose metabolism. Using CRC cases from four distinct cohorts, we built and validated a predictive model based on SARS-CoV-2 producing fructose metabolic anomalies by coupling Cox univariate regression and lasso regression feature selection algorithms to identify hallmark genes in colorectal cancer. We also developed a composite prognostic nomogram to improve clinical practice by integrating the characteristics of aberrant fructose metabolism produced by this novel coronavirus with age and tumor stage. To obtain the genes with the greatest potential prognostic values, LASSO regression analysis was performed, In the TCGA training cohort, patients were randomly separated into training and validation sets in the ratio of 4: 1, and the best risk score value for each sample was acquired by lasso regression analysis for further analysis, and the fifteen genes CLEC4A, FDFT1, CTNNB1, GPI, PMM2, PTPRD, IL7, ALDH3B1, AASS, AOC3, SEPINE1, PFKFB1, FTCD, TIMP1 and GATM were finally selected. In order to validate the model's accuracy, ROC curve analysis was performed on an external dataset, and the results indicated that the model had a high predictive power for the prognosis prediction of patients. Our study provides a theoretical foundation for the future targeted regulation of fructose metabolism in colorectal cancer patients, while simultaneously optimizing dietary guidance and therapeutic care for colorectal cancer patients in the context of the COVID-19 pandemic.

VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites.

Mature neurons have stable dendritic architecture, which is essential for the nervous system to operate correctly. The ability to undergo structural plasticity, required to support adaptive processes like memory formation, is still present in mature neurons. It is unclear what molecular and cellular processes control this delicate balance between dendritic structural plasticity and stabilization. Failures in the preservation of optimal dendrite structure due to atrophy or maladaptive plasticity result in abnormal connectivity and are associated with various neurological diseases. Vascular endothelial growth factor D (VEGFD) is critical for the maintenance of mature dendritic trees. Here, we describe how VEGFD affects the neuronal cytoskeleton and demonstrate that VEGFD exerts its effects on dendrite stabilization by influencing the actin cortex and reducing microtubule dynamics. Further, we found that during synaptic activity-induced structural plasticity VEGFD is downregulated. Our findings revealed that VEGFD, acting on its cognate receptor VEGFR3, opposes structural changes by negatively regulating dendrite growth in cultured hippocampal neurons and in vivo in the adult mouse hippocampus with consequences on memory formation. A phosphoproteomic screening identified several regulatory proteins of the cytoskeleton modulated by VEGFD. Among the actin cortex-associated proteins, we found that VEGFD induces dephosphorylation of ezrin at tyrosine 478 via activation of the striatal-enriched protein tyrosine phosphatase (STEP). Activity-triggered structural plasticity of dendrites was impaired by expression of a phospho-deficient mutant ezrin in vitro and in vivo. Thus, VEGFD governs the equilibrium between stabilization and plasticity of dendrites by acting as a molecular brake of structural remodeling.

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

Social evolution of shared biofilm matrix components.

Biofilm formation is an important and ubiquitous mode of growth among bacteria. Central to the evolutionary advantage of biofilm formation is cell-cell and cell-surface adhesion achieved by a variety of factors, some of which are diffusible compounds that may operate as classical public goods-factors that are costly to produce but may benefit other cells. An outstanding question is how diffusible matrix production, in general, can be stable over evolutionary timescales. In this work, using Vibrio cholerae as a model, we show that shared diffusible biofilm matrix proteins are indeed susceptible to cheater exploitation and that the evolutionary stability of producing these matrix components fundamentally depends on biofilm spatial structure, intrinsic sharing mechanisms of these components, and flow conditions in the environment. We further show that exploitation of diffusible adhesion proteins is localized within a well-defined spatial range around cell clusters that produce them. Based on this exploitation range and the spatial distribution of cell clusters, we constructed a model of costly diffusible matrix production and related these length scales to the relatedness coefficient in social evolution theory. Our results show that production of diffusible biofilm matrix components is evolutionarily stable under conditions consistent with natural biofilm habitats and host environments. We expect the mechanisms revealed in this study to be relevant to other secreted factors that operate as cooperative public goods in bacterial communities and the concept of exploitation range and the associated analysis tools to be generally applicable.

RankCompV3: a differential expression analysis algorithm based on relative expression orderings and applications in single-cell RNA transcriptomics.

BACKGROUND: Effective identification of differentially expressed genes (DEGs) has been challenging for single-cell RNA sequencing (scRNA-seq) profiles. Many existing algorithms have high false positive rates (FPRs) and often fail to identify weak biological signals. RESULTS: We present a novel method for identifying DEGs in scRNA-seq data called RankCompV3. It is based on the comparison of relative expression orderings (REOs) of gene pairs which are determined by comparing the expression levels of a pair of genes in a set of single-cell profiles. The numbers of genes with consistently higher or lower expression levels than the gene of interest are counted in two groups in comparison, respectively, and the result is tabulated in a 3 × 3 contingency table which is tested by McCullagh's method to determine if the gene is dysregulated. In both simulated and real scRNA-seq data, RankCompV3 tightly controlled the FPR and demonstrated high accuracy, outperforming 11 other common single-cell DEG detection algorithms. Analysis with either regular single-cell or synthetic pseudo-bulk profiles produced highly concordant DEGs with the ground-truth. In addition, RankCompV3 demonstrates higher sensitivity to weak biological signals than other methods. The algorithm was implemented using Julia and can be called in R. The source code is available at https://github.com/pathint/RankCompV3.jl . CONCLUSIONS: The REOs-based algorithm is a valuable tool for analyzing single-cell RNA profiles and identifying DEGs with high accuracy and sensitivity.

E3 ligase Cul2 mediates Drosophila early germ cell differentiation through targeting Bam.

Drosophila ovary has been one of the most mature and excellent systems for studying the in vivo regulatory mechanisms of stem cell fate determination. It has been well-known that the bone morphogenetic protein (BMP) signaling released by the niche cells promotes the maintenance of germline stem cells (GSCs) through inhibiting the transcription of the bag-of-marbles (bam) gene, which encodes a key factor for GSC differentiation. However, whether Bam is regulated at the post-translational level remains largely unknown. Here we show that the E3 ligase Cullin-2 (Cul2) is involved in modulating Bam ubiquitination, which occurs probably at multiple lysine residues of Bam's C-terminal region. Genetic evidence further supports the notion that Cul2-mediated Bam ubiquitination and turnover are essential for GSC maintenance and proper germline development. Collectively, our data not only uncovers a novel regulatory mechanism by which Bam is controlled at the post-translational level, but also provides new insights into how Cullin family protein determines the differentiation fate of early germ cells.

Molecular mechanisms and therapeutic significance of Tryptophan Metabolism and signaling in cancer.

Tryptophan (Trp) metabolism involves three primary pathways: the kynurenine (Kyn) pathway (KP), the 5-hydroxytryptamine (serotonin, 5-HT) pathway, and the indole pathway. Under normal physiological conditions, Trp metabolism plays crucial roles in regulating inflammation, immunity, and neuronal function. Key rate-limiting enzymes such as indoleamine-2,3-dioxygenase (IDO), Trp-2,3-dioxygenase (TDO), and kynurenine monooxygenase (KMO) drive these metabolic processes. Imbalances in Trp metabolism are linked to various cancers and often correlate with poor prognosis and adverse clinical characteristics. Dysregulated Trp metabolism fosters tumor growth and immune evasion primarily by creating an immunosuppressive tumor microenvironment (TME). Activation of the KP results in the production of immunosuppressive metabolites like Kyn, which modulate immune responses and promote oncogenesis mainly through interaction with the aryl hydrocarbon receptor (AHR). Targeting Trp metabolism therapeutically has shown significant potential, especially with the development of small-molecule inhibitors for IDO1, TDO, and other key enzymes. These inhibitors disrupt the immunosuppressive signals within the TME, potentially restoring effective anti-tumor immune responses. Recently, IDO1 inhibitors have been tested in clinical trials, showing the potential to enhance the effects of existing cancer therapies. However, mixed results in later-stage trials underscore the need for a deeper understanding of Trp metabolism and its complex role in cancer. Recent advancements have also explored combining Trp metabolism inhibitors with other treatments, such as immune checkpoint inhibitors, chemotherapy, and radiotherapy, to enhance therapeutic efficacy and overcome resistance mechanisms. This review summarizes the current understanding of Trp metabolism and signaling in cancer, detailing the oncogenic mechanisms and clinical significance of dysregulated Trp metabolism. Additionally, it provides insights into the challenges in developing Trp-targeted therapies and future research directions aimed at optimizing these therapeutic strategies and improving patient outcomes.

Radiomic profiling for insular diffuse glioma stratification with distinct biologic pathway activities.

Current literature emphasizes surgical complexities and customized resection for managing insular gliomas; however, radiogenomic investigations into prognostic radiomic traits remain limited. We aimed to develop and validate a radiomic model using multiparametric magnetic resonance imaging (MRI) for prognostic prediction and to reveal the underlying biological mechanisms. Radiomic features from preoperative MRI were utilized to develop and validate a radiomic risk signature (RRS) for insular gliomas, validated through paired MRI and RNA-seq data (N = 39), to identify core pathways underlying the RRS and individual prognostic radiomic features. An 18-feature-based RRS was established for overall survival (OS) prediction. Gene set enrichment analysis (GSEA) and weighted gene coexpression network analysis (WGCNA) were used to identify intersectional pathways. In total, 364 patients with insular gliomas (training set, N = 295; validation set, N = 69) were enrolled. RRS was significantly associated with insular glioma OS (log-rank p = 0.00058; HR = 3.595, 95% CI:1.636-7.898) in the validation set. The radiomic-pathological-clinical model (R-P-CM) displayed enhanced reliability and accuracy in prognostic prediction. The radiogenomic analysis revealed 322 intersectional pathways through GSEA and WGCNA fusion; 13 prognostic radiomic features were significantly correlated with these intersectional pathways. The RRS demonstrated independent predictive value for insular glioma prognosis compared with established clinical and pathological profiles. The biological basis for prognostic radiomic indicators includes immune, proliferative, migratory, metabolic, and cellular biological function-related pathways.

Platelet-derived microvesicles regulate vascular smooth muscle cell energy metabolism via PRKAA after intimal injury.

Vascular intimal injury initiates various cardiovascular disease processes. Exposure to subendothelial collagen can cause platelet activation, leading to collagen-activated platelet-derived microvesicles (aPMVs) secretion. In addition, vascular smooth muscle cells (VSMCs) exposed to large amounts of aPMVs undergo abnormal energy metabolism; they proliferate excessively and migrate after the loss of endothelium, eventually contributing to neointimal hyperplasia. However, the roles of aPMVs in VSMC energy metabolism are still unknown. Our carotid artery intimal injury model indicated that platelets adhered to injured blood vessels. In vitro, phosphorylated Pka (cAMP-dependent protein kinase) content was increased in aPMVs. We also found that aPMVs significantly reduced VSMC glycolysis and increased oxidative phosphorylation, and promoted VSMC migration and proliferation by upregulating phosphorylated PRKAA (α catalytic subunit of AMP-activated protein kinase) and phosphorylated FoxO1. Compound C, an inhibitor of PRKAA, effectively reversed the enhancement of cellular function and energy metabolism triggered by aPMVs in vitro and neointimal formation in vivo. We show that aPMVs can affect VSMC energy metabolism through the Pka-PRKAA-FoxO1 signaling pathway and this ultimately affects VSMC function, indicating that the shift in VSMC metabolic phenotype by aPMVs can be considered a potential target for the inhibition of hyperplasia. This provides a new perspective for regulating the abnormal activity of VSMCs after injury.

Advanced paternal age exacerbates neuroinflammation in offspring via m6A modification-mediated intergenerational inheritance.

BACKGROUND: The trend of postponing childbearing age is prevalent worldwide. Advanced paternal age (APA) is associated with adverse pregnancy outcomes and offspring health. However, the underlying mechanism by which paternal aging affects the risk of offspring neuropsychiatric disorders is unclear. Our study aims to explore the behavioral phenotypes and the pathologic epigenetic alterations of APA offspring inherited from aging sperm. METHODS: Behavioral tests, ELISA assay, immunofluorescence and western blotting were performed on offspring mice. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA immunoprecipitation sequencing (RIP-seq) were used to investigate the modified N6-methyladenosine (m6A) profiles of paternal sperm and offspring hippocampus. Intervention of gene expression by lentivirus and adeno-associated virus in both vivo and vitro examined the potential therapeutic targets of intergenerational inherited neuroinflammation. RESULTS: In our study, APA offspring exhibit cognitive impairment and autism-like behavior. An increase in neuroinflammation in APA offspring is associated with microglial overactivation, which manifests as abnormal morphology and augmented engulfment. MeRIP-seq of F0 sperm and F1 hippocampus reveal that Nr4a2 is hypermethylated with decreased expression in APA offspring involving in synaptic plasticity and microglial function. In addition, Ythdc1, an m6A reader protein, is markedly elevated in aging sperm and remains elevated in adult hippocampus of APA group. Enhanced Ythdc1 recognizes and suppresses the hypermethylated Nr4a2, thereby contributing to the abnormal phenotype in offspring. The overexpression of Ythdc1 triggers microglial activation in vitro and its suppression in the hippocampus of APA progeny alleviates behavioral aberrations and attenuates neuroinflammation. CONCLUSION: Our study provides additional evidence of the abnormal behavioral phenotypes of APA offspring and reveals potential epigenetic inheritance signatures and targeted genes for future research.

Broad-spectrum resistance gene RPW8.1 balances immunity and growth via feedback regulation of WRKYs.

Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.

Circ_0002395 promotes aerobic glycolysis and proliferation in pancreatic adenocarcinoma cells via miR-548c-3p/PDK1 axis.

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.

Dual-function DEFENSIN 8 mediates phloem cadmium unloading and accumulation in rice grains.

Grain cadmium (Cd) is translocated from source to sink tissues exclusively via phloem, though the phloem Cd unloading transporter has not been identified yet. Here, we isolated and functionally characterized a defensin-like gene DEFENSIN 8 (DEF8) highly expressed in rice (Oryza sativa) grains and induced by Cd exposure in seedling roots. Histochemical analysis and subcellular localization detected DEF8 expression preferentially in pericycle cells and phloem of seedling roots, as well as in phloem of grain vasculatures. Further analysis demonstrated that DEF8 is secreted into extracellular spaces possibly by vesicle trafficking. DEF8 bound to Cd in vitro, and Cd efflux from protoplasts as well as loading into xylem vessels decreased in the def8 mutant seedlings compared with the wild type. At maturity, significantly less Cd accumulation was observed in the mutant grains. These results suggest that DEF8 is a dual function protein that facilitates Cd loading into xylem and unloading from phloem, thus mediating Cd translocation from roots to shoots and further allocation to grains, representing a phloem Cd unloading regulator. Moreover, essential mineral nutrient accumulation as well as important agronomic traits were not affected in the def8 mutants, suggesting DEF8 is an ideal target for breeding low grain Cd rice.

PHR1 involved in the regulation of low phosphate-induced leaf senescence by modulating phosphorus homeostasis in Arabidopsis.

Phosphorus (P) is a crucial macronutrient for plant growth, development, and reproduction. The effects of low P (LP) stress on leaf senescence and the role of PHR1 in LP-induced leaf senescence are still unknown. Here, we report that PHR1 plays a crucial role in LP-induced leaf senescence, showing delayed leaf senescence in phr1 mutant and accelerated leaf senescence in 35S:PHR1 transgenic Arabidopsis under LP stress. The transcriptional profiles indicate that 763 differentially expressed SAGs (DE-SAGs) were upregulated and 134 DE-SAGs were downregulated by LP stress. Of the 405 DE-SAGs regulated by PHR1, 27 DE-SAGs were involved in P metabolism and transport. PHR1 could bind to the promoters of six DE-SAGs (RNS1, PAP17, SAG113, NPC5, PLDζ2, and Pht1;5), and modulate them in LP-induced senescing leaves. The analysis of RNA content, phospholipase activity, acid phosphatase activity, total P and phosphate content also revealed that PHR1 promotes P liberation from senescing leaves and transport to young tissues under LP stress. Our results indicated that PHR1 is one of the crucial modulators for P recycling and redistribution under LP stress, and the drastic decline of P level is at least one of the causes of early senescence in P-deficient leaves.

Noninvasive prediction of BRAF V600E mutation status of pleomorphic xanthoastrocytomas with MRI morphologic features and diffusion-weighted imaging.

OBJECTIVES: Seeking a noninvasive predictor for BRAF V600E mutation status of pleomorphic xanthoastrocytomas (PXAs) is essential for their prognoses and therapeutic use of BRAF inhibitors. We aimed to noninvasively diagnose BRAF V600E-mutated PXAs using MRI morphologic, DWI and clinical parameters. METHODS: The clinical findings, anatomical MRI characteristics, and diffusion parameters of 36 pathologically confirmed PXAs were retrospectively analyzed, and BRAF V600E-mutated (n = 16) and wild-type (n = 20) groups were compared. A binary logistic-regression analysis was performed, and a ROC curve was calculated to determine the independent predictors of BRAF V600E mutation status, diagnostic accuracy, and optimal cut-off value. RESULTS: A comparison of findings between groups showed that BRAF V600E-mutated PXAs were more frequent in children and young adults (≤ 35 years; P = 0.042) who often had histories of seizures (P = 0.004). Furthermore, BRAF V600E-mutated PXAs generally presented as solitary masses (P = 0.024), superficial locations with meningeal attachment (P < 0.001), predominantly cystic with mural nodules (P = 0.005), and had greater minimal ADC ratio (ADCratio) values of the tumor and peritumoral edema (P < 0.001). Binary logistic regression showed that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and a greater minimal ADCratio of the tumor were independent predictors of BRAF V600E-mutated PXAs. The combination of all four independent predictors resulted in the highest sensitivity (100%) and specificity (90%), with AUC = 0.984. CONCLUSION: The BRAF V600E mutation status of PXAs could be noninvasively predicted using clinical and MRI characteristics. CRITICAL RELEVANCE STATEMENT: The noninvasive diagnostic criteria for BRAF V600E-mutated PXAs could offer guidance for the administration of BRAF V600E mutation inhibitors in the future.

N, S-Codoped Carbon Quantum Dots with High Inhibition Efficiency: Implications for Corrosion Mitigation of Carbon Steel in Acidic Environments.

The environmental friendliness, economic feasibility, and high efficiency of carbon quantum dots (CQDs) render them as highly promising candidates for corrosion inhibitors. The present study proposed the fabrication of nitrogen- and sulfur-codoped CQDs via an one-step hydrothermal method using l-cysteine and 4-aminosalicylic acid as precursors. The structure, particle size, and surface ligands of the prepared CQDs were determined through spectroscopy and transmission electron microscopy characterization. Subsequently, the inhibition performance of the CQDs on carbon steel in a 0.5 M sulfuric acid solution was evaluated through weight loss measurement, electrochemical methods, and surface analysis. The CQDs exhibited remarkable inhibition efficiencies of 97.9% at 293 K and 98.9% at 313 K, with a concentration of 150 ppm. In addition, the obtained CQDs demonstrated a combined physisorption and chemisorption adsorption behavior, which complied with the Langmuir adsorption isotherm. These findings provide insight into the inhibition mechanism and highlight the potential of codoped CQDs for corrosion mitigation applications in acidic environments.

Glycine-Ti3C2Tx Hybrid Material Improves the Electrochemical Corrosion Resistance of a Water-Borne Epoxy Coating.

Improving the dispersibility and compatibility of nanomaterials in water-borne epoxy resins is an important means to improve the protection ability and corrosion resistance of coatings. In this study, glycine-functionalized Ti3C2Tx (GT) was used to prepare an epoxy composite coating. The results of Fourier transform infrared spectroscopy and X-ray diffraction showed that glycine was successfully modified. The scanning electron microscopy and transmission electron microscopy results showed that the aggregation of Ti3C2Tx was alleviated. Electrochemical impedance spectroscopy test results show that, after 60 days of immersion, GT coating still shows the best protection performance, and the composite coating |Z|f = 0.01 Hz is 3 orders of magnitude higher than that of the pure epoxy coating. This is mainly because, after adding glycine, the -COOH group on the surface of glycine binds to the -OH group on the surface of Ti3C2Tx, improving the aggregation of Ti3C2Tx itself. At the same time, the -NH group of glycine can also participate in the curing reaction of epoxy resin to strengthen the bonding strength between the coating and the metal. The good dispersion of GT in epoxy resin makes it fill the pores and holes left by epoxy resin curing and strengthen the corrosion resistance. The easy availability and green properties of glycine provide a simple and environmentally friendly method for the modification of Ti3C2Tx.

Novel hypothalamic pathways for metabolic effects of spexin.

One of the main underlying etiologies of type 2 diabetes (T2DM) is insulin resistance, which is most frequently caused by obesity. Notably, the deregulation of adipokine secretion from visceral adiposity has been identified as a crucial characteristic of type 2 diabetes and obesity. Spexin is an adipokine that is released by many different tissues, including white adipocytes and the glandular stomach, and is negatively connected with the state of energy storage. This peptide acts through GALR2/3 receptors to control a wide range of metabolic processes, including inflammation, browning, lipolysis, energy expenditure, and eating behavior. Specifically, spexin can enter the hypothalamus and regulate the hypothalamic melanocortin system, which in turn balances energy expenditure and food intake. This review examines recent advances and the underlying mechanisms of spexin in obesity and T2DM. In particular, we address a range of topics from basic research to clinical findings, such as an analysis of the possible function of spexin in the hypothalamic melanocortin response, which involves reducing energy intake and increasing energy expenditure while also enhancing insulin sensitivity and glucose tolerance. Gaining more insight into the mechanisms that underlie the spexin system's control over energy metabolism and homeostasis may facilitate the development of innovative treatment approaches that focus on combating obesity and diabetes.