Heterometallic [2]Catenane-Crosslinked Supramolecular Networks with Improved Antibacterial Activity.

The construction of supramolecular networks with novel crosslinks is of great significance in expanding their chemical structures and exploring their advanced functions. Herein, we prepare a type of [2]catenane-cored supramolecular networks based on the crosslinking of polyethylene glycol (PEG) using a heterometallic [2]catenane unit. By adjusting the molecular weight of PEG, the solubility of the networks can be tuned and gels are formed using low molecular weight PEG. The introduction of heterometallic [2]catenane offers the networks good antibacterial properties owing to the synergistic antimicrobial activity of Pt(II) and Cu(I) ions in the [2]catenane. This study provides a simple and efficient strategy for constructing supramolecular networks with topological crosslinks as antibacterial materials, which will promote the structural design and biological applications of supramolecular networks.

Z/E configuration controlled by a Taxus sesquiterpene synthase facilitating the biosynthesis of (3Z,6E)-α-farnesene.

Plant enzymes often present advantages in the synthesis of natural products with specific configurations. Farnesene is a pharmacologically active sesquiterpene with three natural Z/E configurations, among which the enzyme selectively responsible for the biosynthesis of (3Z,6E)-α-farnesene remains elusive. Herein, a sesquiterpene synthase TwSTPS1 biosynthesizing (3Z,6E)-α-farnesene as the major product was identified from Taxus wallichiana through genome mining. Utilizing molecular dynamics simulations and mutation analysis, the catalytic mechanism of TwSTPS1, especially Z/E configuration control, was explored. Moreover, the crucial residues associated with the specific catalytic activity of TwSTPS1 was elucidated through mutagenesis experiments. The findings contribute to our understanding of the Z/E configuration control by plant terpene synthases and also provide an alternative tool for manipulating (3Z,6E)-α-farnesene production using synthetic biology.

Unlocking the potential: machine learning applications in electrocatalyst design for electrochemical hydrogen energy transformation.

Machine learning (ML) is rapidly emerging as a pivotal tool in the hydrogen energy industry for the creation and optimization of electrocatalysts, which enhance key electrochemical reactions like the hydrogen evolution reaction (HER), the oxygen evolution reaction (OER), the hydrogen oxidation reaction (HOR), and the oxygen reduction reaction (ORR). This comprehensive review demonstrates how cutting-edge ML techniques are being leveraged in electrocatalyst design to overcome the time-consuming limitations of traditional approaches. ML methods, using experimental data from high-throughput experiments and computational data from simulations such as density functional theory (DFT), readily identify complex correlations between electrocatalyst performance and key material descriptors. Leveraging its unparalleled speed and accuracy, ML has facilitated the discovery of novel candidates and the improvement of known products through its pattern recognition capabilities. This review aims to provide a tailored breakdown of ML applications in a format that is readily accessible to materials scientists. Hence, we comprehensively organize ML-driven research by commonly studied material types for different electrochemical reactions to illustrate how ML adeptly navigates the complex landscape of descriptors for these scenarios. We further highlight ML's critical role in the future discovery and development of electrocatalysts for hydrogen energy transformation. Potential challenges and gaps to fill within this focused domain are also discussed. As a practical guide, we hope this work will bridge the gap between communities and encourage novel paradigms in electrocatalysis research, aiming for more effective and sustainable energy solutions.

Recovering chromium from electroplating sludge using an integrated technology of bipolar membrane electrodialysis and H2O2 oxidation.

Chromium electroplating produces Cr(III)-containing electroplating sludge (EPS) in large volumes, which is easily oxidised to Cr(Ⅵ) and is harmful to the environment and human health. This study recovered Cr(III) as Na2CrO4 from EPS using an integrated bipolar membrane electrodialysis (BMED)-H2O2 oxidation technology. During the treatment process, Cr(III) was oxidised to Cr(VI) using H2O2 in an alkaline environment, BMED was used to separate and recover Cr(VI). Experimental results showed that H2O2 dosage and pH affected Cr(III) oxidation-the highest Cr(III) oxidation ratio of 68.4% was observed when H2O2 dosage and pH were 5.5 mL and 12.0, respectively. The current density, solid/liquid ratio and sludge particle size affected Cr(III) recovery, energy consumption and current efficiency. Under a current density of 20.0 mA/cm2, solid/liquid ratio of 1.0:45 and sludge particle size of 100 mesh, 58.2% of Cr(III) was recovered. When the number of the equipped EPS compartments was increased from one to two and three, the specific energy consumption decreased from 1.04 to 0.87 and 0.81 kW·h/g, respectively, but the current efficiency remained almost constant. After EPS treatment, the Cr(III) remaining in the sludge was mainly in the residual state, which is less environmentally harmful. The obtained Na2CrO4 had similar properties according to X-ray diffraction analysis. Thus, the proposed integrated technology effectively recovers Cr(III) from EPS and other chromium-containing solid wastes.

Role of glucose metabolic reprogramming in colorectal cancer progression and drug resistance.

Colorectal cancer (CRC), with the incidence and mortality rising on a yearly basis, greatly threatens people's health. It is considered an important hallmark of tumorigenesis that aberrant glucose metabolism in cancer cells, particularly the Warburg effect. In CRC, the Warburg effect predominantly influences cancer development and progression via its involvement in the glycolytic pathway regarding cell metabolism. The critical mechanisms underlying this process include key glycolytic enzymes, transport proteins, regulatory molecules, and signaling pathways. Furthermore, targeting the reprogrammed glucose metabolism in cancer cells can be potentially used for CRC treatment. However, the mechanisms driving CRC onset and progression, especially in relation to glucose metabolism reprogramming, are not fully understood and represent an emerging field of research. The review aims at providing new insights into the role that glucose metabolism reprogramming plays in the progression of CRC progression together with its resistance to treatment. Ultimately, these insights strive to diminish the risks of CRC metastasis and recurrence.

Predictive model for identification of gangrenous or perforated appendicitis in adults: a multicenter retrospective study.

BACKGROUND: Gangrene and perforation are severe complications of acute appendicitis, associated with a higher mortality rate compared to uncomplicated appendicitis. Accurate preoperative identification of Gangrenous or perforated appendicitis (GPA) is crucial for timely surgical intervention. METHODS: This retrospective multicenter study includes 796 patients who underwent appendectomy. Univariate and multivariate logistic regression analyses are used to develop a nomogram model for predicting GPA based on laboratory tests and computed tomography (CT) findings. The model is validated using an external dataset. RESULTS: Seven independent predictors were included in the nomogram: white blood cell count, lymphocyte count, D-dimer, serum glucose, albumin, maximum outer diameter of the appendix, and presence of appendiceal fecalith. The nomogram achieved good discrimination and calibration in both the training and testing sets. In the training set, the AUC was 0.806 (95%CI: 0.763-0.849), and the sensitivity and specificity were 82.1% and 66.9%, respectively. The Hosmer-Lemeshow test showed good calibration (P = 0.7378). In the testing set, the AUC was 0.799 (95%CI: 0.741-0.856), and the sensitivity and specificity were 70.5% and 75.3%, respectively. Decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSION: The laboratory test-CT nomogram model can effectively identify GPA patients, aiding in surgical decision-making and improving patient outcomes.

LTF ameliorates cartilage endplate degeneration by suppressing calcification, senescence and matrix degradation through the JAK2/STAT3 pathway.

Intervertebral disc degeneration (IDD)-induced cervical and lumbar herniations are debilitating diseases. The function of intervertebral disc (IVD) mainly depends on the cartilage endplate (CEP), which provides support and waste removal. Therefore, IDD stems from the degeneration of CEP. Our study shows that the expression of lactotransferrin (LTF), an iron-binding protein, is significantly decreased in degenerated human and rat CEP tissues. In addition, we found that LTF knockdown promoted calcification, senescence, and extracellular matrix (ECM) degradation in human endplate chondrocytes. Furthermore, the in vivo experiment results confirmed that the JAK2/STAT3 pathway inhibitor AG490 significantly reversed these effects. In addition to investigating the role and mechanism of LTF in CEP degeneration, this study provides a theoretical basis and experimental evidence to improve IDD treatment.

SnRNA-seq reveals differential functional transcriptional pathway alterations in three mutant types of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure, characterized by ventricular dilation, thinning of the ventricular walls, and systolic dysfunction in either the left or both ventricles, often accompanied by fibrosis. Human cardiac tissue is composed of various cell types, including cardiomyocytes (CMs), fibroblasts (FBs), endothelial cells (ECs), macrophages, lymphocytes and so on. In DCM patients, these cells frequently undergo functional and phenotypic changes, contributing to contractile dysfunction, inflammation, fibrosis, and cell death, thereby increasing the risk of heart failure. This study focuses on DCM patients with mutations (LMNA, RBM20, and TTN) and analyzes functional changes in subpopulations of four cardiac cell types. The study involves functional annotation of subpopulations within each cell type and explores the association between gene mutations and specific functions and pathways. Additionally, the SCENIC method is employed of a particular cell subpopulation with significant functional importance, aiming to identify key transcriptional regulators in specific cell states. By analyzing the expression levels of ligand-receptor pairs in vCM4, vFB2, EC5.0, T cells, and NK cells across the DCM mutant genotypes, we predicted their signaling pathways and communications. This research provides insights into the molecular mechanisms of DCM and potential therapeutic targets.

Metabolome and transcriptome integration reveals cerebral cortical metabolic profiles in rats with subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe subtype of hemorrhagic stroke. The molecular mechanisms of its secondary brain damage remain obscure. To investigate the alterations in gene and metabolite levels following SAH, we construct the transcriptome and metabolome profiles of the rat cerebral cortex post-SAH using whole transcriptome sequencing and untargeted metabolomics assays. Transcriptomic analysis indicated that there were 982 differentially expressed genes (DEGs) and 540 differentially expressed metabolites (DEMs) between the sham group and SAH 1d, and 292 DEGs and 254 DEMs between SAH 1d and SAH 7d. Most notably, DEGs were predominantly involved in the activation of immune and inflammatory pathways, particularly the Complement and coagulation cascades, TNF signaling pathway, and NOD-like receptor signaling pathway. Metabolic analysis revealed that the metabolic pathways of Arginine and proline, Arachidonic acid, Folate biosynthesis, Pyrimidine, and Cysteine and methionine were remarkably affected after SAH. Metabolites of the above pathways are closely associated not only with immune inflammation but also with oxidative stress, endothelial cell damage, and blood-brain barrier disruption. This study provides new insights into the underlying pathologic mechanisms of secondary brain injury after SAH and further characterization of these aberrant signals could enable their application as potential therapeutic targets for SAH.

Prevalence and associated risk factors for depression symptoms in adolescent girls with polycystic ovary syndrome: a hospital-based cross-sectional study.

Background: Depression symptoms are a growing concern for adolescent girls with PCOS around the world. However, relatively small samples have given varying reports of its prevalence and risk factors in previous studies. Therefore, there is an urgent need for further research on the prevalence and associated factors of depression among adolescent girls with PCOS. Methods: A cross-sectional study was performed from October 2021 to May 2022 using a questionnaire and examination of the medical records of a convenience sample of 335 adolescent girls with PCOS. The Chinese version of the Children's Depression Scale (CDI) was used to investigate depression symptoms. A multivariate logistic regression model was used to determine factors that were significantly associated with depression symptoms. Results: The prevalence of depression symptoms was 36.12% among adolescent girls with PCOS. A multivariate logistic regression model identified significant factors as perceived social support (95% CI: 0.921 ~ 0.965%, p = 0.000), sleep quality (95% CI: 1.134 ~ 1.324%, p = 0.000), belief illness (95% CI, 1.040 ~ 1.102%, p = 0.000), hirsutism (95% CI, 1.292 ~ 4.392%, p = 0.005), and LH/FSH ≥ 2 (95% CI, 1.939 ~ 6.369%, p = 0.000). Conclusion: Depression symptoms are an important problem among adolescent girls with PCOS in China. A comprehensive approach that encompasses social support, structured health education for the disease, and evaluation of the psychological status of PCOS girls with hirsutism (and) or LH/FSH ≥ 2 in time is important to minimize depression symptoms and improve psychological health among adolescent girls with PCOS.

Tangzu granule alleviate neuroinflammation in diabetic peripheral neuropathy by suppressing pyroptosis through P2X7R /NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus, mainly manifested as paresthesia. Tangzu granule (TZG) is derived from famous traditional Chinese medicine decoctions and optimized by long-term temporary practice. TZG has good efficacy in improving numbness, pain and pruritus of the lower extremities of DPN patients. However, the overall regulatory mechanisms underlying its effects on DPN remain unclear. AIM OF THE STUDY: This study aims to explore the potential mechanism of TZG for treating DPN. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were used to establish an in vivo model of DPN with streptozotocin (STZ) injection and high-fat diet (HFD) feeding. Additionally, sciatic glial RSC96 cells were induced with high glucose in vitro. SD rats in intervention group received TZG treatment for 12 weeks. After 12 weeks of treatment, sciatic nerve function was evaluated by intelligent hot plate meter and neuro electrophysiology detector. The morphological changes of sciatic nerve cells were observed by hematoxylin-eosin staining and transmission electron microscope. IL-1ß, IL-18 inflammatory cytokines, pyroptosis and P2X7R/NLRP3 signaling pathway were observed by Western blotting, immunofluorescence staining and ELISA. RESULTS: TZG improved nerve conduction velocity and sciatic neuropathy rational structural changes in DPN rats. It also inhibited RSC96 inflammatory response and cell death that induced by high glucose. This may be related to TZG inhibiting P2X7R, decreasing the activation of NLRP3 inflammasomes, down-regulating the levels of pyroptosis proteins such as caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N, and inhibiting the release of interleuki (IL)-18 and IL-1ß inflammatory cytokines. CONCLUSIONS: TZG inhibited pyroptosis through P2X7R/NLRP3 signaling pathway, alleviated neuroinflammation, and showed protective effect in the treatment of DPN.

Pt@WS2 -an Extrinsic 2D Dilute Ferromagnetic Semiconductor Beyond Room Temperature.

Extrinsic dilute magnetic semiconductors achieve magnetic functionality through tailored interaction between a semiconducting matrix and a non-magnetic dopant. The absence of intrinsic magnetic impurities makes this approach promising to investigate the newly emerging field of 2D dilute magnetic semiconductors. Here the first realization of an extrinsic 2D DMS in Pt-doped WS2 is demonstrated. A bottom-up synthesis approach yields a uniform and highly crystalline monolayer where platinum selectively occupies the tungsten sub-lattice. The orbital overlap between W 4d and Pt 5d results in spin-selective hybrid states that produce a strong valley-Zeeman splitting. Combined experimental and theoretical results show that this interaction yields a sizable ferromagnetic response with a Curie temperature ≈375 K. These results open up a new route toward 2D magnetic properties through tailoring of atomic interactions for future applications in spintronics and magnetic nanoactuation.

Transcriptome analysis of the coexpression network of genes related to antioxidant characteristics after grain filling in purple rice.

Antioxidant capacity is an important indicator for evaluating the growth and developmental quality of rice. This study has guiding significance for the cultivation of high-nutrient-value varieties. To investigate the molecular mechanisms underlying the antioxidant characteristics of rice grains after the filling stage, Yangzinuo 1 (YZN1) was used as the experimental material, and grains collected at five different time points (7 days apart) after the filling stage were used for transcriptome sequencing. Through weighted gene coexpression network analysis (WGCNA), a coexpression network of gene weights related to antioxidant characteristics was constructed. LOC_Os10g39140, LOC_Os10g38276, and LOC_Os05g45740 were identified from the 2 modules showing the highest correlations with the target traits. GO functional annotation showed that target modules were enriched in pathways related to phenylalanine, flavonoids, and other related pathways, such as GO:0006558, GO:0006559, GO:0009812, and GO:0009813. Correlation analysis with metabolites revealed that differentially expressed genes were significantly enriched in pathways related to antioxidant characteristics and energy metabolism processes, such as glycolysis/gluconeogenesis and flavonoid biosynthesis. The core genes identified in this study were found to be highly correlated with antioxidant characteristics and enriched in pathways related to metabolic and energy pathways and molecular activities. These results provide an effective dataset supporting breeding targeting functional rice characteristics.

Urban synergistic carbon emissions reduction research: A perspective on spatial complexity and link prediction.

Reducing urban carbon emissions (UCEs) holds paramount importance for global sustainable development. However, the complexity of interactions among urban spatial units has impeded further research on UCEs. This study investigates synergistic emission reduction between cities by analyzing the spatial complexity within the UCEs network. The future potential for synergistic carbon emissions reduction is predicted by the link prediction algorithm. A case study conducted in the Pearl River Basin of China demonstrates that the UCEs network has a complex spatial structure, and the synergistic capacity of emission reduction among cities is enhanced. The core cities in the UCEs network, including Dongguan, Shenzhen, and Guangzhou, have spillover effects that contribute to synergistic emission reduction. Community detection reveals that the common characteristics associated with UCEs become concentrated, thereby enhancing the synergy of joint efforts between cities. The link prediction algorithm indicates a high probability of strengthened carbon emission connections in the Pearl River Delta, alongside those between upstream cities, which shows potential in forecasting synergistic emission reductions. Our research framework offers a comprehensive analysis for synergistic emission reduction from the spatial complexity of UCEs network and link prediction. It acts as a worthwhile reference for developing differentiated policies on synergistic emission reduction.

[Mechanism of Linggui Zhugan Decoction in inhibiting myocardial fibrosis by regulating Wnt/ß-catenin pathway].

This study aimed to investigate the regulatory mechanism of Linggui Zhugan Decoction(LGZGD)-medicated serum on the fibrosis of cardiac fibroblasts(CFs) and the protein expression of the Wnt/ß-catenin signaling pathway. Blank serum and LGZGD-medicated serum were prepared, and primary CFs were isolated and cultured using trypsin-collagenase digestion and differential adhesion method. Immunofluorescence labeling was used to identify primary CFs. Cells were divided into normal control group, model group, 20% blank serum group, and 5%, 10%, and 20% LGZGD-medicated serum groups. Except for the normal control group, all other groups were stimulated with hydrogen peroxide(H_2O_2) after pretreatment with 20% blank serum or 5%, 10%, 20% LGZGD-medicated serum for 12 hours to establish a model of fibrosis in primary CFs. Scratch healing assay was used to observe cell migration ability. ELISA was used to detect the content of collagen type Ⅰ(Col Ⅰ) and type Ⅲ(Col Ⅲ). Western blot was used to detect the protein expression of α-smooth muscle actin(α-SMA), Wnt1, glycogen synthase kinase 3ß(GSK-3ß), phosphorylated GSK-3ß(p-GSK-3ß), ß-catenin, and nuclear ß-catenin. RT-qPCR was used to detect the gene expression of ß-catenin and matrix metalloproteinase 9(MMP9), and immunofluorescence technique was used to detect the expression and localization of key proteins α-SMA and ß-catenin. CFs with Wnt1 overexpression were prepared and treated with H_2O_2. The following groups were set up: normal control group, model group, 20% LGZGD-medicated serum group, empty plasmid+20% LGZGD-medicated serum group, and Wnt1 overexpression+20% LGZGD-medicated serum group. ELISA was used to detect the content and ratio of Col Ⅰ and Col Ⅲ. Western blot was used to detect the protein expression of α-SMA, Wnt1, GSK-3ß, p-GSK-3ß, ß-catenin, and nuclear ß-catenin. RT-qPCR was used to detect the gene expression of ß-catenin and MMP9. Immunofluorescence staining showed that CFs expressed Vimentin positively, appearing green, with blue nuclei and purity greater than 90%, which were identified as primary CFs. RESULTS:: showed that compared with the normal control group, CFs in the model group had enhanced healing rate, increased content of Col Ⅰ and Col Ⅲ, increased ratio of Col Ⅰ/Col Ⅲ, upregulated protein expression of α-SMA, Wnt1, p-GSK-3ß, ß-catenin, nuclear ß-catenin, decreased GSK-3ß expression, elevated mRNA expression of ß-catenin and MMP9, and enhanced fluorescence intensity and expression of ß-catenin and α-SMA. Compared with the model group, 5%, 10%, 20% LGZGD-medicated serum significantly inhibited cell migration ability, reduced the content of Col Ⅰ and Col Ⅲ, decreased ratio of Col Ⅰ/Col Ⅲ, downregulated protein expression of α-SMA, Wnt1, p-GSK-3ß, ß-catenin, nuclear ß-catenin, increased GSK-3ß expression, decreased mRNA expression of ß-catenin and MMP9, and reduced fluorescence intensity and expression of ß-catenin and α-SMA. Compared with the empty plasmid+20% LGZGD-medicated serum group, the effect of LGZGD-medicated serum was significantly reversed after overexpression of Wnt1. LGZGD can reduce excessive deposition of collagen fibers, inhibit excessive proliferation of fibroblasts, and improve the process of myocardial fibrosis. The improvement of myocardial fibrosis by LGZGD is related to the regulation of the Wnt/ß-catenin pathway, reduction of collagen deposition, and protection of myocardial cells.

Bioorthogonal conjugation and responsive nanocoating of probiotics for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is closely associated with dysregulated immune response, gut mucosal barrier, and microbiota. Conventional treatments suffer from inferior bioavailability and inadequate efficiency. Herein, we present a synergistic therapeutic strategy based on multifunctionalized probiotics to mitigate IBD through single oral administration. The probiotic (Escherichia coli Nissle 1917) is bioorthogonally conjugated with immunomodulators and subsequently encapsulated by an enteric coating. The viability and bioactivity of probiotics are not affected by the modifications. And the armored probiotics are able to resist the harsh environment of the stomach and shed their enteric coating in the intestinal tract, exposing immunomodulators to polarize pro-inflammatory M1-type macrophages into anti-inflammatory M2-type. In a mouse colitis model, orally administered multifunctionalized probiotics cooperatively alleviate IBD with increased body weight to 1.13 folds and decreased disease activity index to 0.43 folds, through downregulating the pro-inflammatory cytokines expression, upregulating the epithelial tight junction-associated proteins levels to restore the intestinal barrier, and increasing the microbiota richness and abundance. This work exhibits a feasible approach to construct functionalized orally administered probiotics for enhanced synergistic therapy of IBD.

Unveiling the charge storage mechanisms of Co-based perovskite fluoride in a mild aqueous electrolyte.

This study is an in-depth exploration of the charge storage mechanisms of KCoF3 in 1 M Na2SO4 mild aqueous electrolytes via an array of ex situ/in situ physicochemical/electrochemical methods, especially the electrochemical quartz crystal microbalance (EQCM) technique, showing a combination of conversion, insertion/extraction and adsorption mechanisms. Specifically, during the first charge phase, Co(OH)2 is formed/oxidized into amorphous CoOOH and Co3O4, and then CoOOH undergoes partial proton extraction to yield CoO2, which is simultaneously accompanied by the transformation of Co3O4 into CoOOH and (hydrated) CoO2. During the first discharge process, the partial insertion of H+ into (hydrated) CoO2 leads to the formation of CoOOH and Co3O4, with the conversion of Co3O4 into CoOOH and both Co3O4 and CoOOH undergoing further transformations into (hydrated) Co(OH)2via the insertion of H+. This work offers valuable references for the development of aqueous energy storage.

Triterpenoid saponins from the roots of Panax notoginseng with protective effects against APAP-induced liver injury.

Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (1-5), together with eighteen known triterpenoid saponins (6-23) were isolated from the roots of Panax notoginseng. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy-ß-d-glucose moiety from Panax species. Compounds 1-4, 7, 10, 12, 21-22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (12), ginsenoside Rg1 (21), and ginsenoside Re (22) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.

A disulfidptosis-associated long noncoding RNA signature to predict low-grade glioma classification, prognosis, tumor microenvironment, and therapy regimens: Observational study.

This study aimed to investigate the function of disulfidptosis-associated long noncoding RNAs (DAlncRNAs) in low-grade gliomas (LGG) through bioinformatics analysis and construct a signature to predict the classification, prognosis, tumor microenvironment, and selection of immunotherapy and chemotherapy in LGG. Genomic, clinical, and mutational information of 526 patients with LGG was retrieved from The Cancer Genome Atlas repository. A nonnegative matrix factorization algorithm was applied to classify patients with LGG. Univariate, LASSO regression, and multivariate Cox regression analyses were performed to determine prognostic DAlncRNAs. Following the median risk score, we defined the sample as a high-risk (HR) or low-risk group. Finally, survival, receiver operating characteristic curve, risk curve, principal component, independent prognosis, risk difference, functional enrichment, tumor microenvironment, immune cell infiltration, mutation, and drug sensitivity analyses were performed. Patients were classified into C1 and C2 subtypes associated with disulfidptosis. Eight prognostic DAlncRNAs (AC003035.2, AC010157.2, AC010273.3, AC011444.3, AC092667.1, AL450270.1, AL645608.2, and LINC01571) were identified, and a prognostic signature of LGG was developed. The DAlncRNA-based signature was found to be an independent prognostic factor in patients with LGG, thereby constructing a nomogram. In addition, in the HR group, immune function was more active and the tumor mutation burden was higher. The patients were mainly composed of subtype C2, and their prognosis was worse. Immunotherapy and chemotherapy were predicted in the HR and low-risk groups, respectively. Our study, based on DAlncRNAs, highlights 2 disulfidptosis-associated LGG subtypes with different prognostic and immune characteristics and creates a novel disulfidptosis-associated prognostic signature, which may inform the classification, prognosis, molecular pathogenesis, and therapeutic strategies for patients with LGG.

Molecular traits of MAPK kinases and the regulatory mechanism of GhMAPKK5 alleviating drought/salt stress in cotton.

Mitogen-activated protein kinase kinases (MAPKKs) play a critical role in the mitogen-activated protein kinase (MAPK) signaling pathway, transducing external stimuli into intracellular responses and enabling plant adaptation to environmental challenges. Most research has focused on the model plant Arabidopsis (Arabidopsis thaliana). The systematic analysis and characterization of MAPKK genes across different plant species, particularly in cotton (Gossypium hirsutum), are somewhat limited. Here, we identified MAPKK family members from 66 different species, which clustered into 5 different sub-groups, and MAPKKs from four cotton species clustered together. Through further bioinformatic and expression analysis, GhMAPKK5 was identified as the most responsive MAPKK member to salt and drought stress among the 23 MAPKKs identified in Gossypium hirsutum. Silencing GhMAPKK5 in cotton through virus-induced gene silencing (VIGS) led to quicker wilting under salt and drought conditions, while overexpressing GhMAPKK5 in Arabidopsis enhanced root growth and seed germination under these stresses, demonstrating GhMAPKK5's positive role in stress tolerance. Transcriptomics and Yeast-Two-Hybrid assays revealed a MAPK cascade signal module comprising GhMEKK (Mitogen-activated protein kinase kinase kinases)3/8/31-GhMAPKK5-GhMAPK11/23. This signaling cascade may play a role in managing drought and salt stress by regulating transcription factor genes, such as WRKYs, which are involved in the biosynthesis and transport pathways of ABA, proline, and RALF. This study is highly important for further understanding the regulatory mechanism of MAPKK in cotton, contributing to its stress tolerance and offering potential in targets for genetic enhancement.