Interfacial design of pyrene-based covalent organic framework for overall photocatalytic H2O2 synthesis in water.

Covalent organic frameworks (COFs) have shown great potential in the photocatalytic production of hydrogen peroxide (H2O2) due to their precisely designed and customized ability. Nevertheless, the quest for efficient overall photosynthesis of H2O2 in pure water without sacrificial agents using COF photocatalysts remains a formidable challenge. Herein, three pyrene-based covalent organic frameworks are synthesized using an advanced interfacial design strategy. By incorporating functional groups of F, H, and OH into a COF skeleton, their wettability and charge-separation properties are fine-tuned. These COFs show great performances as photocatalysts for H2O2 production from water and air by utilizing both the oxygen reduction reaction and water oxidation reaction pathways. Compared to PyCOF-F and PyCOF-H, PyCOF-OH demonstrates superior H2O2 production efficiency due to its improved hydrophilicity and enhanced carrier separation, achieving a remarkable rate of 2961 µmol g-1 h-1 from 25 mL pure water and air. Further, the mechanism of H2O2 production over PyCOF-OH is clarified by combining a series of control experiments, in situ characterizations, and theoretical calculations. This study offers valuable insights into the interfacial design of high-performance photocatalysts for H2O2 synthesis.

Unleashing the Potential: High Responsivity at Room Temperature of Halide Perovskite-Based Short-Wave Infrared Detectors with Ultrabroad Bandwidth.

Short-wave infrared (SWIR) imaging systems offer remarkable advantages, such as enhanced resolution and contrast, compared to their optical counterparts. However, broader applications demand improvements in performance, notably the elimination of cryogenic temperature requirements and cost reduction in manufacturing processes. In this manuscript, we present a new development in SWIR photodetection, exploiting the potential of metal halide perovskite materials. Our work introduces a cost-effective and easily fabricated SWIR photodetector with an ultrabroad detection range from 900 to 2500 nm, a room-temperature responsivity of 1.57 × 102 A/W, and a specific detectivity of 4.18 × 1010 Jones at 1310 nm. We then performed comprehensive static and time-resolved optical and electrical measurements under ambient conditions, complemented by extensive density functional theory simulations, validating the formation of heterojunctions within the intrinsic n-type and extrinsic p-type perovskite structures. The potential of our perovskite-based SWIR materials extends from photodetectors to photovoltaic cells and introduces a possibility for high SWIR responsivity at room temperature and atmospheric pressure, which promotes its economic efficiency.

AVM: A Manually Curated Database of Aerosol-transmitted Virus Mutations, Human Diseases, and Drugs.

Aerosol-transmitted viruses possess strong infectivity and can spread over long distances, earning the difficult-to-control title. They cause various human diseases and pose serious threats to human health. Mutations can increase the transmissibility and virulence of the strains, reducing the protection provided by vaccines and weakening the efficacy of antiviral drugs. In this study, we established a manually curated database (termed AVM) to store information on aerosol-transmitted viral mutations (VMs). The current version of the AVM contains 42,041 VMs (including 2613 immune escape mutations), 45 clinical information datasets, and 407 drugs/antibodies/vaccines. Additionally, we recorded 88 human diseases associated with viruses and found that the same virus can target multiple organs in the body, leading to diverse diseases. Furthermore, the AVM database offers a straightforward user interface for browsing, retrieving, and downloading information. This database is a comprehensive resource that can provide timely and valuable information on the transmission, treatment, and diseases caused by aerosol-transmitted viruses (http://www.bio-bigdata.center/AVM).

Integrating genomic profiling to clinical data: assessing the impact of CD147 expression on plaque stability.

Background: Acute Coronary Syndrome (ACS) continues to be a leading cause of death and illness worldwide. Differentiating stable from unstable coronary plaques is essential for enhancing patient outcomes. This research investigates the role of CD147 as a biomarker for plaque stability among coronary artery disease patients. Methods: The study began with high-throughput sequencing of blood samples from six patients, divided equally between those with Stable Angina (SA) and Unstable Angina (UA), followed by bioinformatics analysis. Expanding upon these findings, the study included 31 SA patients and 30 patients with ACS, using flow cytometry to examine CD147 expression on platelets and monocytes. Additionally, logistic regression was utilized to integrate traditional risk factors and evaluate the predictive value of CD147 expression for plaque stability. Results: Initial sequencing displayed a notable difference in CD147 expression between SA and UA groups, with a significant increase in UA patients. Further analysis confirmed that elevated platelet CD147 expression was strongly associated with unstable plaques (OR = 277.81, P < .001), after adjusting for conventional risk factors, whereas monocyte CD147 levels did not show a significant difference. Conclusion: Elevated CD147 expression on platelets is a crucial biomarker for identifying unstable coronary artery plaques, offering insights into patient risk stratification and the development of targeted treatment strategies. This underscores the pivotal role of molecular research in understanding and managing coronary artery disease, paving the way for improved clinical outcomes.

Dual-energy computed tomography for predicting histological grading and survival in patients with pancreatic ductal adenocarcinoma.

OBJECTIVES: We evaluated the value of dual-energy computed tomography (DECT) parameters derived from pancreatic ductal adenocarcinoma (PDAC) to discriminate between high- and low-grade tumors and predict overall survival (OS) in patients. METHODS: Data were retrospectively collected from 169 consecutive patients with pathologically confirmed PDAC who underwent third-generation dual-source DECT enhanced dual-phase scanning before surgery between January 2017 and March 2023. Patients with prior treatments, other malignancies, small tumors, or poor-quality scans were excluded. Two radiologists evaluated three clinical and seven radiological features and measured sixteen DECT-derived parameters. Univariate and multivariate analyses were applied to select independent predictors. A prediction model and a corresponding nomogram were developed, and the area under the curve (AUC), calibration, and clinical applicability were assessed. The correlations between factors and OS were evaluated using Kaplan-Meier survival and Cox regression analyses. RESULTS: One hundred sixty-nine patients were randomly divided into training (n = 118) and validation (n = 51) cohorts, among which 43 (36.4%) and 19 (37.3%) had high-grade PDAC confirmed by pathology, respectively. The vascular invasion, normalized iodine concentration in the venous phase, and effective atomic number in the venous phase were independent predictors for histological grading. A nomogram was constructed to predict the risk of high-grade tumors in PDAC, with AUCs of 0.887 and 0.844 in the training and validation cohorts, respectively. The nomogram exhibited good calibration and was more beneficial than a single parameter in both cohorts. Pathological- and nomoscore-predicted high-grade PDACs were associated with poor OS (all p < 0.05). CONCLUSIONS: The nomogram, which combines DECT parameters and radiological features, can predict the histological grade and OS in patients with PDAC before surgery. KEY POINTS: Question Preoperative determination of histological grade in PDAC is crucial for guiding treatment, yet current methods are invasive and limited. Findings A DECT-based nomogram combining vascular invasion, normalized iodine concentration, and effective atomic number accurately predicts histological grade and OS in PDAC patients. Clinical relevance The DECT-based nomogram is a reliable, non-invasive tool for predicting histological grade and OS in PDAC. It provides essential information to guide personalized treatment strategies, potentially improving patient management and outcomes.

Tumor-Selective Nano-Dispatcher Enforced Cancer Immunotherapeutic Effects via Regulating Lactate Metabolism and Activating Toll-Like Receptors.

The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed. By using the tumor-targeting properties of c-RGD, the system can effectively deliver monocarboxylate transporters 4 (MCT4) inhibitor (Syro) to inhibit lactate efflux in tumor cells, leading to decreased lactate levels in the tumor microenvironment (TME) and increased accumulation within tumor cells. The reduction of lactate in TME will reduce the nutritional support for regulatory T cells (Tregs) and promote the effector function of T cells. The accumulation of lactate in tumor cells will lead to tumor death due to cellular acidosis. In addition, it will also reduce the uptake of glucose by tumor cells, reduce nutrient plunder, and further weaken the inhibition of T cell function. Furthermore, the pH-responsive release of Toll-like receptors (TLR) 7/8 agonist IMDQ within the TME activates dendritic cells (DCs) and promotes the infiltration of T cells. These findings offer a promising approach for enhancing tumor immune response through targeted metabolic interventions.

Expert Consensus on Big Data Collection of Skin and Appendage Disease Phenotypes in Chinese.

The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.

Effect of leucine on mitochondria and oxidative stress to reduce virulence and pathogenicity of Acinetobacter baumannii.

Elucidating the virulence mechanisms of A. baumannii is essential for developing strategies to mitigate pathogenicity. Although high-virulent strains are associated with increased mortality rate in severely infected patients, the underlying mechanisms remains not well understood. Our analysis revealed leucine as a pivotal biomarker, with the 11dP and paaK being significant contributors to virulence. The ATP-dependent activity and antioxidant activity were identified as the most important pathways in distinguishing the virulence of A. baumannii. Exogenous leucine was found to modulate mitochondria dysfunction and oxidative stress, thereby diminishing the pathogenicity of A. baumannii towards Beas 2B cells. Moreover, leucine reduced the virulence of A. baumannii to Galleria mellonella (G. mellonella) and alleviated pathological damage to lung tissues in mice. Our study offers a novel treatment strategy based on metabolomics, which may assist in the exploration and management of infections caused by highly virulent pathogens. It sets a new course for reducing the impact of highly virulent A. baumannii infections and has significant implications for the development of future therapeutic interventions.

Rational design of adjuvants boosts cancer vaccines.

Cancer vaccines are expected to be next breakthrough in cancer immunotherapy. In cancer vaccines, adjuvants play an important role by enhancing and reshaping tumor antigen-specific immune responses. Failures in previous cancer vaccine clinical trials can be attributed to inappropriate selection and design of tumor antigens and adjuvants. Using basic theories of tumor immunology, the development of sequencing technology and nanotechnology enables the creation of cancer vaccines through appropriate selection of tumor antigens and adjuvants and their nanoscale assembly based on the specific characteristics of each tumor. In this chapter, we begin by discussing the various types of cancer vaccines and categories of tumor antigens. Then, we summarize the classification of adjuvants for cancer vaccines, including immunostimulatory molecules and delivery systems, and clarify the various factors that influence the properties of adjuvants, such as chemical composition, structure, and surface modification. Finally, we provide perspectives and insights on rational design of adjuvants in cancer vaccines to enhance their efficacy.

Image Copy-Move Forgery Detection via Deep PatchMatch and Pairwise Ranking Learning.

Recent advances in deep learning algorithms have shown impressive progress in image copy-move forgery detection (CMFD). However, these algorithms lack generalizability in practical scenarios where the copied regions are not present in the training images, or the cloned regions are part of the background. Additionally, these algorithms utilize convolution operations to distinguish source and target regions, leading to unsatisfactory results when the target regions blend well with the background. To address these limitations, this study proposes a novel end-to-end CMFD framework that integrates the strengths of conventional and deep learning methods. Specifically, the study develops a deep cross-scale PatchMatch (PM) method that is customized for CMFD to locate copy-move regions. Unlike existing deep models, our approach utilizes features extracted from high-resolution scales to seek explicit and reliable point-to-point matching between source and target regions. Furthermore, we propose a novel pairwise rank learning framework to separate source and target regions. By leveraging the strong prior of point-to-point matches, the framework can identify subtle differences and effectively discriminate between source and target regions, even when the target regions blend well with the background. Our framework is fully differentiable and can be trained end-to-end. Comprehensive experimental results highlight the remarkable generalizability of our scheme across various copy-move scenarios, significantly outperforming existing methods.

CaARP1/CaSGT1 Module Regulates Vegetative Growth and Defense Response of Pepper Plants against Phytophthora capsici.

Pepper (Capsicum annuum L.) suffers severe quality and yield loss from oomycete diseases caused by Phytophthora capsici. CaSGT1 was previously determined to positively regulate the immune response of pepper plants against P. capsici, but by which mechanism remains elusive. In the present study, the potential interacting proteins of CaSGT1 were isolated from pepper using a yeast two-hybrid system, among which CaARP1 was determined to interact with CaSGT1 via bimolecular fluorescence complementation (BiFC) and microscale thermophoresis (MST) assays. CaARP1 belongs to the auxin-repressed protein family, which is well-known to function in modulating plant growth. The transcriptional and protein levels of CaARP1 were both significantly induced by infection with P. capsici. Silencing of CaARP1 promotes the vegetative growth of pepper plants and attenuates its disease resistance to P. capsici, as well as compromising the hypersensitive response-like cell death in pepper leaves induced by PcINF1, a well-characterized typical PAMP from P. capsici. Chitin-induced transient expression of CaARP1 in pepper leaves enhanced its disease resistance to P. capsici, which is amplified by CaSGT1 co-expression as a positive regulator. Taken together, our result revealed that CaARP1 plays a dual role in the pepper, negatively regulating the vegetative growth and positively regulating plant immunity against P. capsici in a manner associated with CaSGT1.

Cultural translation of the ethical dimension: a study on the reliability and validity of the Chinese nurses' professional ethical dilemma scale.

BACKGROUND: Quantifying the professional ethical challenges that nurses encounter is crucial for both theoretical insights and practical outcomes. The objective of this research is to assess the psychometric properties of the Chinese adaptation of the Moral Distress Scale for Healthcare Professionals (MD-APPS). METHODS: In 2024, a survey approach was utilized to engage with several tertiary-level healthcare institutions throughout China. A cohort of 448 nursing professionals who satisfied the specified selection benchmarks was consequently incorporated into the study. To evaluate the scale's reliability and validity, methods including the Content Validity Index (CVI), Factor Analysis-both Exploratory (EFA) and Confirmatory (CFA)-alongside assessments of internal consistency and test-retest reliability were employed. RESULTS: Expert evaluations yielded an I-CVI of 0.90, suggesting good content validity for the MD-APPS's Chinese adaptation. Exploratory Factor Analysis (EFA) revealed a bi-dimensional framework with 7 components, explaining 56.34% of the cumulative variance. Confirmatory Factor Analysis (CFA) outcomes displayed a χ-square/df ratio of 1.542. The estimate for Robust RMSEA was 0.054, and the SRMR was ascertained to be 0.041. Indices for both Robust TLI and Robust CFI surpassed the 0.9 threshold, indicating an acceptable fit; this aspect was supported by a P-value (Chi-square) of 0.094. The internal consistency, measured by Cronbach's α, was found to be 0.74, while the test-retest reliability over a two-week period reached 0.964. These findings provide initial evidence for the psychometric properties of the Chinese MD-APPS. CONCLUSION: The Chinese adaptation of the MD-APPS demonstrates promising initial psychometric properties, suggesting its potential suitability for exploring nurses' professional ethical challenges within the Chinese cultural context. This scale may facilitate the identification of diverse elements influencing nurses' professional ethics and the assessment of the ethical climate in nursing practices. However, further validation studies are needed to fully establish its psychometric robustness across various healthcare settings in China.

MIR937 amplification potentiates ovarian cancer progression by attenuating FBXO16 inhibition on ULK1-mediated autophagy.

High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological cancer. Genetic studies have revealed gene copy number alterations (CNAs) frequently occurred in HGSOC pathogenesis, however the function and mechanism of CNAs for microRNAs are still not fully understood. Here, we show the dependence on gene copy number amplification of MIR937 that enhances cell autophagy and dictates HGSOC proliferative activity. Data mining of TCGA database revealed MIR937 amplification is correlated with increased MIR937 expression and cell proliferation of HGSOC. Deletion of MIR937 in HGSOC cells led to impaired autophagy and retarded cell proliferation, and the extent for its inhibitory effects scaled with the degree of MIR937 copy loss. Rescue assay confirmed miR-937-5p, a mature product of MIR937, was sufficient to restore its oncogenic function. Mechanistically, MIR937 amplification raised the expression of miR-937-5p, enhanced its binding to 3' UTR of FBXO16 transcript, and thereby restricting FBXO16 degradative effects on ULK1. Our results demonstrate that MIR937 amplification augments cell autophagy and proliferation, and suggest an alternative strategy of MIR937/FBXO16/ULK1 targeting for HGSOC treatment.

MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB.

Clinical evidence supports the notion that T cell exhaustion and terminal differentiation pose challenges to the persistence and effectiveness of chimeric antigen receptor-T (CAR-T) cells. MEK1/2 inhibitors (MEKIs), widely used in cancer treatment due to their ability to inhibit aberrant MAPK signaling, have shown potential synergistic effects when combined with immunotherapy. However, the impact and mechanisms of MEKIs on CAR-T cells remain uncertain and controversial. To address this, we conducted a comprehensive investigation to determine whether MEKIs enhance or impair the efficacy of CAR-T cells. Our findings revealed that MEKIs attenuated CAR-T cell exhaustion and terminal differentiation induced by tonic signaling and antigen stimulation, thereby improving CAR-T cell efficacy against hematological and solid tumors. Remarkably, these effects were independent of the specific scFvs and costimulatory domains utilized in CARs. Mechanistically, analysis of bulk and single-cell transcriptional profiles demonstrates that the effect of MEK inhibition was related to diminish anabolic metabolism and downregulation of c-Fos and JunB. Additionally, the overexpression of c-Fos or JunB in CAR-T cells counteracted the effects of MEK inhibition. Furthermore, our Cut-and-Tag assay revealed that MEK inhibition downregulated the JunB-driven gene profiles associated with exhaustion, differentiation, anergy, glycolysis, and apoptosis. In summary, our research unveil the critical role of the MAPK-c-Fos-JunB axis in driving CAR-T cell exhaustion and terminal differentiation. These mechanistic insights significantly broaden the potential application of MEKIs to enhance the effectiveness of CAR-T therapy.

The Impact of Multidisciplinary Educational Team-Based Clinical Nursing Pathway on the Psychological Resilience, Treatment Adherence, Pain Management and Quality of Life in Cancer Patients.

Background: We aimed to investigate the impact of multidisciplinary educational team-based clinical nursing pathway on the psychological resilience, treatment adherence, pain management and quality of life in cancer patients. Methods: From 2019 to 2020, eighty two cancer patients were selected and randomly divided into the control group and the observational group. Both groups were treated with routine oncology nursing and the multidisciplinary educational team-based clinical nursing pathway, respectively. Psychological resilience, pain management and qualify of life were assessed by the Chinese version of the Connor-Davidson resilience scale, revised American Pain Society Patient Outcome Questionnaire and the Nottingham health profile, respectively. Treatment adherence was semi-quantitatively classified as "good", "fair" and "bad". Results: Patient's psychological resilience, compliance, pain outcome and quality of life were similar between the control group and the observational group on admission. Patient's psychological resilience, compliance and pain outcome in the observational group were significantly superior to those in the control group one day prior to discharge and 2 months post-discharge (all P<0.05). The scores of energy, emotions, sleep and mobility were significantly different between the observational group and the control group one day prior to discharge and 2 months post-discharge (all P<0.05). Significant improvements were observed with regard to the scores of energy, sleep and mobility in the control group 2 months post-discharge, whereas the scores of energy, emotions, sleep and mobility improved dramatically in the observational group (all P<0.05). Conclusion: Compared with routine oncology nursing, multidisciplinary educational team-based clinical nursing pathway could improve patient's psychological resilience, treatment adherence, pain management and quality of life.

Vitamin D levels and risk of ocular disorders: insights from bidirectional and multivariable Mendelian randomization analysis.

Purpose: This study aimed to assess the causal relationships between vitamin D levels and ocular disorders. Methods: Independent genetic variables were obtained from genome-wide association studies (GWAS) and publicly available databases. The summary statistics for 25-hydroxyvitamin D (25(OH)D) were obtained from two large-scale GWAS studies, with sample sizes of 324,105 and 417,580 European individuals. The genetic variants of myopia, primary open angle glaucoma (POAG), anterior iridocyclitis, senile cataract, diabetic retinopathy (DR), retinal vein occlusion (RVO), wet age-related macular degeneration (WAMD) and optic neuritis were extracted from the latest release of FinnGen consortium, which contains genome data from Finnish participants. Subsequently, Mendelian randomization (MR) analyses were conducted to obtain effect estimates. Additionally, we performed multivariable MR analysis and mediation analysis to validate the results. Results: In the discovery dataset, genetically predicted vitamin D concentration was found to be causally associated with an increased risk of WAMD, (odd ratio (OR) = 1.35, 95% confidence interval (CI) = 1.09-1.67, P IVW = 0.005). However, no causal effects of genetically predisposed vitamin D levels on the risk of most types of ocular disorders were observed. Reverse MR revealed no causal relationships between the ocular diseases and vitamin D concentrations. The MR analyses of the validation dataset yielded consistent results. Additionally, the causal effect of vitamin D levels on the risk of WAMD remained significant after adjusting for potential confounders in the multivariable MR analysis (OR = 1.86, 95% CI = 1.26-2.73, P IVW = 0.002). Conclusion: Our MR analysis results provide robust evidence of a causal relationship between genetically predicted 25(OH)D levels and an increased risk of WAMD in European population. These findings offer important insights into the management and control of ocular disorders.

The potential adverse effects of hypodermic glucagon-like peptide -1 receptor agonist on patients with type 2 diabetes: A population-based study.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long-term safety of GLP-1 RAs remains insufficiently studied. This study aimed to provide real-world evidence on potential adverse outcomes associated with GLP-1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. METHODS: We conducted a retrospective cohort study involving 7746 T2D patients on GLP-1 RAs in Shenzhen, China. They were compared with 124 371 metformin-only users and 36 146 insulin-only users, forming two therapy control groups. GLP-1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP-1 RAs use. RESULTS: Compared with metformin-only users, GLP-1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24-3.24), acute nephritis (3.20, 2.17-4.70), kidney failure (3.73, 2.74-5.08), thyroid cancer (2.25, 1.23-4.10), and thyroid dysfunction (1.27, 1.00-1.63), respectively; Similar results were also found when compared with insulin-only users. Importantly, long-term (≥12 months) GLP-1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. CONCLUSION: Compared with traditional T2D treatments, GLP-1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP-1 RAs. Further validation is crucial across diverse populations.

Wuzi Yanzong Decoction Ameliorates Oligoasthenozoospermia by Up-Regulating Methyltransferase and Increasing Spata, Bcl, and Pik3 Series Genes Methylation Level.

Wuzi Yanzong decoction (WZYZD) belongs to the traditional formula for treating male infertility caused by oligoasthenozoospermia (OLI). This research aims to elucidate the therapeutic substance basis and potential pharmacological mechanisms of WZYZD in treating OLI. A total of 52 chemical ingredients were identified from WZYZD. HE and TUNEL staining demonstrated that WZYZD can markedly alleviate OLI. Immunofluorescence analysis showed that WZYZD can significantly increase the expression levels of DNMT3A, PIWIL1, SETDB1, and PRMT5. Methyl capture sequencing proved that WZYZD can markedly upregulate the methylated level of Spata, Bcl, and Pik3 series genes. Network pharmacology analysis proved that WZYZD can ameliorate OLI through BCL-2 and PI3K-AKT signaling pathways. The immunofluorescence assay of BCL-2 and SPATA18 proved the aforementioned results. The potential mechanism of WZYZD in treating OLI mainly involved recruiting methyltransferase DNMT3A, PIWIL1, PRMT5, and SETDB1 and increasing the methylation degree of Spata, Bcl, and Pik3 series genes.

Knockout of neutrophil cytosolic factor 1 ameliorates neuroinflammation and motor deficit after traumatic brain injury.

Traumatic brain injury (TBI) is a predominant cause of long-term disability in adults, yet the molecular mechanisms underpinning the neuropathological processes associated with it remain inadequately understood. Neutrophil cytosolic factor 1 (NCF1, also known as p47phox) is one of the cytosolic components of NADPH oxidase NOX2. In this study, we observed a reduction in the volume of TBI-induced brain lesions in NCF1-knockout mice compared to controls. Correspondingly, the neuronal loss induced by TBI was mitigated in the NCF1-knockout mice. Behavioral analysis also demonstrated that the motor coordination deficit following TBI was mitigated by the depletion of NCF1. Mechanistically, our findings revealed that NCF1 deficiency attenuated TBI-induced inflammatory responses by inhibiting the release of proinflammatory factors and reducing neutrophil infiltration into the brain parenchyma. Additionally, our results indicated that NCF1 deficiency significantly decreased the levels of reactive oxygen species in neutrophils. Taken together, our findings indicate that NCF1 plays a crucial role in the regulation of brain injury and secondary inflammation post-TBI.