CDK1 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Pan-Cancer, Especially in Gastrointestinal Tumors.

OBJECTIVE: Cyclin-dependent kinase 1 (CDK1) regulates the cell cycle and is highly expressed in most tumors. CDK1 expression has been associated with poor disease prognosis. This study aimed to identify the prognostic value of CDK1 in pan-cancer and investigate the association between CDK1 expression and immune cell infiltration. METHODS: CDK1 expression and its correlation with prognosis in pan-cancer were analyzed using online databases. Immune infiltration was assessed by ESTIMATE and CIBERSORT algorithms. We then evaluated the relationship between CDK1 expression and tumor mutational burden (TMB), microsatellite instability (MSI), or tumor-infiltrating immune cells. In addition, we performed the co-expression analysis of immune-related genes and GO analysis with CDK1 expression in pan-cancer. Finally, we compared the CDK1 expression profile with the immune-related genes in 30 pairs of clinical gastrointestinal tumor samples. RESULTS: Our analysis demonstrated overexpression of CDK1 in most tumor tissues, especially in gastrointestinal tumors. The high expression of CDK1 was associated with poor overall survival, disease-specific survival, disease-free interval, and progression-free interval in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), and sarcoma (SARC). Besides, CDK1 expression was significantly associated with TMB in 22 cancer types and MSI in 8 cancer types as well as greater frequencies of MSI-high (MSI-H) status and high tumor mutational burden (TMB-H) in uterine corpus endometrial carcinoma (UCEC), stomach adenocarcinoma (STAD), sarcoma (SARC), rectum adenocarcinoma (READ), mesothelioma (MESO), head and neck squamous cell carcinoma (HNSC), and colon adenocarcinoma (COAD). In addition, CDK1 expression correlated with immune cell infiltrating levels, such as M0, M1, or M2 macrophages, memory CD4 T cells, T follicular helper cells, and naive B cells. Our data showed that CDK1 was remarkably correlated with 47 immune-related and immune checkpoint genes in many cancer types. Furthermore, CDK1 was up-regulated in gastrointestinal tumor samples, especially in gastric cancer and intestinal cancer. CDK1 was positively correlated with IDO1 in gastric cancer and PD-1 in intestinal cancer. CONCLUSION: Taken together, our data demonstrated the roles of CDK1 in oncogenesis and metastasis in pan-cancer. Thus, CDK1 is a potential prognostic biomarker and a target for tumor immunotherapy.

Network pharmacology combined with experimental validation reveals the mechanism of action of Erpixing granules on functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Functional dyspepsia (FD) is a prevalent gastrointestinal disorder characterised by high incidence and recurrence rates, posing significant health risks. Erpixing Granules (EPX), approved by the National Food and Drug Administration in 2002, are known for their spleen and stomach invigorating properties, effectively treating FD. However, its mechanism of action remains unclear. AIM OF THE STUDY: This study aims to elucidate EPX's mechanism of treating FD through network pharmacology, and experimental validation using FD animal models. METHODS: In this study, the chemical composition of EPX in positive and negative ion modes was analyzed by UHPLC-Q-TOF MS. The mass spectral data were processed and analyzed using MS-DIAL software to automatically match compound fragment information and identify the known components with the compound database to obtain the active components of EPX. SwissTargetPrediction was used to obtain EPX targets, while FD-related targets were sourced from GeneCards, OMIM and DisGeNET databases. A protein-protein interaction (PPI) network was constructed using the STRING platform, and potential signalling pathways of EPX were determined through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, an FD model was established in rates by administering a 0.1% iodoacetamide sucrose solution, followed by tail clamp stimulation to experimentally validate the network pharmacology findings. RESULTS: Our results revealed 139 effective ingredients in EPX, targeting 60 core FD-related genes. PPI network analysis identified EGFR, CTNNB1 and NFκB1 as core target genes. The KEGG pathway analysis indicated that EPX can modulate FD progression through the PI3K/AKT signalling pathway. Animal experiments demonstrated EPX's capacity to increase body mass, food intake and food utilisation efficiency in FD rats, alongside increased gastric juice secretion, pepsin activity, trypsin activity, cholesterol, bile acid and bilirubin activity. HE examination revealed that EPX improved the inflammatory infiltration of gastric mucosal cells in rats. Furthermore, EPX also promoted gastric emptying and intestinal propulsion in mice. These results suggest that EPX improves spleen and stomach function, enhances the protective effect on the spleen and stomach and promotes food digestion and absorption. Immunofluorescence studies revealed upregulated expression of PI3K, AKT and ANO1 proteins in gastric tissue following EPX administration, while Western blotting indicated increased expression of SCF and C-kit proteins. CONCLUSION: Suggesting EPX's anti-FD effect may involve the regulation of the SCF/C-kit signalling pathway and activation of downstream PI3K/AKT signalling pathway, thereby promoting gastrointestinal motility and improving FD symptoms.

Impact of BSA and Au3+ concentration on the formation and fluorescence properties of Au nanoclusters.

Bovine serum albumin-stabilized Au nanoclusters (BSA-Au NCs) have emerged as promising contenders for imaging agents and highly sensitive fluorescence sensors due to their biocompatibility and strong photoluminescence. Optimizing the synthesis conditions of BSA-Au NCs is crucial for enhancing fluorescence imaging and other nanocluster applications. In this study, for the first time, we systematically investigated the effects of BSA concentration and Au3+ on both particle size and optical characteristics of BSA-Au NCs. When the two components achieved a suitable concentration ratio, it was beneficial to form BSA-Au NCs with a high quantum yield (QY = 74.30%) and good fluorescence stability. In contrast, an inappropriate concentration ratio would lead to the formation of gold nanoparticles (Au NPs), and their internal filtration effect (IFE) would attenuate the fluorescence emission of BSA-Au NCs. The BSA-Au NCs were then employed as efficient fluorescence sensors for detecting Hg2+. Furthermore, the growth mechanism of BSA-Au NCs was elucidated by monitoring fluorescence changes during different incubation times. The BSA-Au NCs with a high quantum yield introduce a novel synthetic concept for sensitive fluorescent probes and expanding versatile applications of BSA-Au NCs in catalysis, chemical sensing and biomedicine.

Polymer Fiber Rigid Network with High Glass Transition Temperature Reinforces Stability of Organic Photovoltaics.

Organic photovoltaics (OPVs) need to overcome limitations such as insufficient thermal stability to be commercialized. The reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology, however, exhibiting limited applicability. Therefore, it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor-acceptor compatibilizers, or by introducing another third component. Herein, a unique approach is presented, based on constructing a polymer fiber rigid network with a high glass transition temperature (Tg) to impede the movement of acceptor and donor molecules, to immobilize the active layer morphology, and thereby to improve thermal stability. A high-Tg one-dimensional aramid nanofiber (ANF) is utilized for network construction. Inverted OPVs with ANF network yield superior thermal stability compared to the ANF-free counterpart. The ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart, thereby leaving fundamental processes such as charge separation, transport, and collection, determining the device efficiency, largely unaltered. This strategy is also successfully applied to other photovoltaic systems. The strategy of incorporating a polymer fiber rigid network with high Tg offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

Insights Into Preaggregation Control of Y-Series Nonfullerene Acceptors in Liquid State for Highly Efficient Binary Organic Solar Cells.

Leveraging breakthroughs in Y-series nonfullerene acceptors (NFAs), organic solar cells (OSCs) have achieved impressive power conversion efficiencies (PCEs) exceeding 19%. However, progress in advancing OSCs has decelerated due to constraints in realizing the full potential of the Y-series NFAs. Herein, a simple yet effective solid additive-induced preaggregation control method employing 2-chloro-5-iodopyridine (PDCI) is reported to unlock the full potential of the Y-series NFAs. Specifically, PDCI interacts predominantly with Y-series NFAs enabling enhanced and ordered phase-aggregation in solution. This method leads to a notable improvement and a redshifted absorption of the acceptor phase during film formation, along with improved crystallinity. Moreover, the PDCI-induced preaggregation of NFAs in the solution enables ordered molecule packing during the film-formation process through delicate intermediate states transition. Consequently, the PDCI-induced preaggregated significantly improves the PCE of PM6:Y6 OSCs from 16.12% to 18.12%, among the best values reported for PM6:Y6 OSCs. Importantly, this approach is universally applicable to other Y-series NFA-based OSCs, achieving a champion PCE of 19.02% for the PM6:BTP-eC9 system. Thus, the preaggregation control strategy further unlocks the potential of Y-series NFAs, offering a promising avenue for enhancing the photovoltaic performance of Y-series NFA-based OSCs.

Proteome-wide association study using cis and trans variants and applied to blood cell and lipid-related traits in the Women's Health Initiative study.

In most Proteome-Wide Association Studies (PWAS), variants near the protein-coding gene (±1 Mb), also known as cis single nucleotide polymorphisms (SNPs), are used to predict protein levels, which are then tested for association with phenotypes. However, proteins can be regulated through variants outside of the cis region. An intermediate GWAS step to identify protein quantitative trait loci (pQTL) allows for the inclusion of trans SNPs outside the cis region in protein-level prediction models. Here, we assess the prediction of 540 proteins in 1002 individuals from the Women's Health Initiative (WHI), split equally into a GWAS set, an elastic net training set, and a testing set. We compared the testing r2 between measured and predicted protein levels using this proposed approach, to the testing r2 using only cis SNPs. The two methods usually resulted in similar testing r2, but some proteins showed a significant increase in testing r2 with our method. For example, for cartilage acidic protein 1, the testing r2 increased from 0.101 to 0.351. We also demonstrate reproducible findings for predicted protein association with lipid and blood cell traits in WHI participants without proteomics data and in UK Biobank utilizing our PWAS weights.

Self-Assembled Pure Covalent Tubes Exhibiting Circularly Polarized Luminescence.

Here, we successfully synthesized four structurally analogous, self-assembled chiral molecular tubes with relatively high yields. This achievement involved the condensation of six equivalents of enantiomerically pure trans-cyclohexane-1,2-diamine (trans-CHDA) and three equivalents of the corresponding tetraformyl precursor. Each precursor was equipped with a luminescent linker terminated by two m-phthalaldehyde units. Even though these tetraformyl precursors are barely soluble in almost all organic solvents, the molecular tubes are highly soluble in nonpolar solvents such as chloroform, allowing us to fully characterize them in solution. The stereo-chirality of the chiral bisamino building blocks endows the frameworks of molecular tubes with planar chirality. As a consequence, all of these molecular tubes exhibit circularly polarized luminescence (CPL) with relatively large dissymmetry values |glum| up to 7×10-3, providing an efficient method for synthesizing CPL-active materials.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

Comparison of screening indicators for different types of thalassemia carriers in Hunan Province.

Background: Carrier screening is the most effective method to block the occurrence of thalassemia. However, due to differences in race and genotype, MCV, MCH, HbA2 and other indicators are far from each other. The purpose of this study is to evaluate the common screening indicators of a, b and ab-compound thalassemia carriers in Hunan Province, and try to use the relevant formulas in the existing literature to predict and distinguish different types of thalassemia carriers. Methods: Receiver operating characteristic curve (ROC curve) combined with Youden index was utilized to analyze results of blood routine examination, hemoglobin electrophoresis, and literature-related formulas for 1111 a-thalassemia carriers, 464 b-thalassemia carriers and 24 ab-thalassemia carriers.

A preliminary study of modified inflatable mediastinoscopic and single-incision plus one-port laparoscopic esophagectomy.

Background: Esophageal malignancies have a high morbidity rate worldwide, and minimally invasive surgery has emerged as the primary approach for treating esophageal cancer. In recent years, there has been increasing discussion about the potential of employing inflatable mediastinoscopic and laparoscopic approaches as an option for esophagectomy. Building on the primary modification of the inflatable mediastinoscopic technique, we introduced a secondary modification to further minimize surgical trauma. Methods: We conducted a retrospective analysis of patients who underwent inflatable mediastinoscopy combined with laparoscopic esophagectomy at the Second Affiliated Hospital of Naval Medical University from March 2020 to March 2023. The patients were allocated to the following two groups: the traditional (primary modification) group, and the secondary modification group. Operation times, intraoperative bleeding, and postoperative complications were compared between the groups. Results: The procedure was successfully performed in all patients, and conversion to open surgery was not required in any case. There were no statistically significant differences in the surgical operation time, intraoperative bleeding, number of dissected lymph nodes, and rate of postoperative anastomotic leakage between the two groups. However, a statistically significant difference was observed in the length of the mobilized esophagus between the two groups. The mobilization of esophagus to the level of diaphragmatic hiatus via the cervical incision was successfully achieved in more patients in the secondary modification group than the primary modification group. Conclusions: Inflatable mediastinoscopy combined with single-incision plus one-port laparoscopic esophagectomy is a safe and effective surgical procedure. The use of a 5-mm flexible endoscope, ultra-long five-leaf forceps, and LigaSure Maryland forceps facilitates esophageal mobilization and lymph node dissection through a single cervical incision.

Light Supplementation in Pitaya Orchards Induces Pitaya Flowering in Winter by Promoting Phytohormone Biosynthesis.

The interaction between light and phytohormones is crucial for plant growth and development. The practice of supplementing light at night during winter to promote pitaya flowering and thereby enhance yield has been shown to be crucial and widely used. However, it remains unclear how supplemental winter light regulates phytohormone levels to promote flowering in pitaya. In this study, through analyzing the transcriptome data of pitaya at four different stages (NL, L0, L1, L2), we observed that differentially expressed genes (DEGs) were mainly enriched in the phytohormone biosynthesis pathway. We further analyzed the data and found that cytokinin (CK) content first increased at the L0 stage and then decreased at the L1 and L2 stages after supplemental light treatment compared to the control (NL). Gibberellin (GA), auxin (IAA), salicylic acid (SA), and jasmonic acid (JA) content increased during the formation of flower buds (L1, L2 stages). In addition, the levels of GA, ethylene (ETH), IAA, and abscisic acid (ABA) increased in flower buds after one week of development (L2f). Our results suggest that winter nighttime supplemental light can interact with endogenous hormone signaling in pitaya, particularly CK, to regulate flower bud formation. These results contribute to a better understanding of the mechanism of phytohormone interactions during the induction of flowering in pitaya under supplemental light in winter.

Ventral frontostriatal circuitry mediates the computation of reinforcement from symbolic gains and losses.

Reinforcement learning (RL), particularly in primates, is often driven by symbolic outcomes. However, it is usually studied with primary reinforcers. To examine the neural mechanisms underlying learning from symbolic outcomes, we trained monkeys on a task in which they learned to choose options that led to gains of tokens and avoid choosing options that led to losses of tokens. We then recorded simultaneously from the orbitofrontal cortex (OFC), ventral striatum (VS), amygdala (AMY), and the mediodorsal thalamus (MDt). We found that the OFC played a dominant role in coding token outcomes and token prediction errors. The other areas contributed complementary functions with the VS coding appetitive outcomes and the AMY coding the salience of outcomes. The MDt coded actions and relayed information about tokens between the OFC and VS. Thus, OFC leads the process of symbolic reinforcement learning in the ventral frontostriatal circuitry.

Computational Mechanisms Underlying Motivation to Earn Symbolic Reinforcers.

Reinforcement learning is a theoretical framework that describes how agents learn to select options that maximize rewards and minimize punishments over time. We often make choices, however, to obtain symbolic reinforcers (e.g., money, points) that are later exchanged for primary reinforcers (e.g., food, drink). Although symbolic reinforcers are ubiquitous in our daily lives, widely used in laboratory tasks because they can be motivating, mechanisms by which they become motivating are less understood. In the present study, we examined how monkeys learn to make choices that maximize fluid rewards through reinforcement with tokens. The question addressed here is how the value of a state, which is a function of multiple task features (e.g., the current number of accumulated tokens, choice options, task epoch, trials since the last delivery of primary reinforcer, etc.), drives value and affects motivation. We constructed a Markov decision process model that computes the value of task states given task features to then correlate with the motivational state of the animal. Fixation times, choice reaction times, and abort frequency were all significantly related to values of task states during the tokens task (n = 5 monkeys, three males and two females). Furthermore, the model makes predictions for how neural responses could change on a moment-by-moment basis relative to changes in the state value. Together, this task and model allow us to capture learning and behavior related to symbolic reinforcement.

ODF3B affects the proliferation and apoptosis of glioma via the JAK/STAT pathway.

The pathogenesis of glioma has remained unclear. In this study, it was found that high expression of the outer dense fibers of sperm tail 3B (ODF3B) in gliomas was positively correlated with the grade of glioma. The higher the grade, the worse the prognosis. ODF3B is closely related to the growth and apoptosis of glioma. In terms of mechanism, ODF3B was found to affect the proliferation and apoptosis of glioma through the JAK1 and JAK2/STAT3 pathways. ODF3B was also found to affect the growth and apoptosis of glioma in vivo. We conclude that ODF3B affects glioma proliferation and apoptosis via the JAK/STAT pathway and is a potential therapeutic target.

Engineering Large-Scale Self-Mineralizing Bone Organoids with Bone Matrix-Inspired Hydroxyapatite Hybrid Bioinks.

Addressing large bone defects remains a significant challenge owing to the inherent limitations in self-healing capabilities, resulting in prolonged recovery and suboptimal regeneration. Although current clinical solutions are available, they have notable shortcomings, necessitating more efficacious approaches to bone regeneration. Organoids derived from stem cells show great potential in this field; however, the development of bone organoids has been hindered by specific demands, including the need for robust mechanical support provided by scaffolds and hybrid extracellular matrices (ECM). In this context, bioprinting technologies have emerged as powerful means of replicating the complex architecture of bone tissue. The research focused on the fabrication of a highly intricate bone ECM analog using a novel bioink composed of gelatin methacrylate/alginate methacrylate/hydroxyapatite (GelMA/AlgMA/HAP). Bioprinted scaffolds facilitate the long-term cultivation and progressive maturation of extensive bioprinted bone organoids, foster multicellular differentiation, and offer valuable insights into the initial stages of bone formation. The intrinsic self-mineralizing quality of the bioink closely emulates the properties of natural bone, empowering organoids with enhanced bone repair for both in vitro and in vivo applications. This trailblazing investigation propels the field of bone tissue engineering and holds significant promise for its translation into practical applications.

Overexpression of HSP27 accelerates stress-induced gastric ulcer healing via the CXCL12/CXCR4 axis.

Chronic stress often triggers gastrointestinal complications, including gastric injury and ulcers. Understanding the role of heat shock protein 27 (HSP27) in stress-induced gastric ulcers could unveil novel therapeutic targets. Here, we established a stress-induced gastric ulcer rat model using water immersion restraint stress and administered adenovirus-packaged HSP27 overexpression vector. Gastric ulcer severity was scored, and mucosal changes were assessed. Gastric epithelial and endothelial cells were treated with lipopolysaccharide and transfected with HSP27 overexpression vectors to evaluate cell viability, migration and angiogenesis. Expression levels of HSP27, C-X-C motif chemokine ligand 12 (CXCL12) and C-X-C motif chemokine receptor 4 (CXCR4) were measured in tissues and cells. HSP27 expression was initially low during stress-induced gastric ulceration but increased during ulcer healing. HSP27 overexpression accelerated ulcer healing in rats, promoting gastric epithelial cell proliferation and migration and gastric endothelial cell angiogenesis through the CXCL12/CXCR4 axis. Inhibitor IT1t reversed the effects of HSP27 overexpression on cell proliferation, migration and angiogenesis. In summary, HSP27 overexpression facilitated ulcer healing, which was partially mediated by the CXCL12/CXCR4 axis.

Investigating aluminum toxicity effects on callose deposition, oxidative stress, and nutrient homeostasis in banana genotypes.

Aluminum (Al) toxicity poses a significant challenge to agricultural productivity, particularly in acidic soils. The banana crop, predominantly cultivated in tropical and subtropical climates, often grapples with low pH and Al toxicity. This study seeks to explore the differential responses of two banana genotypes with varying Al tolerance (Baodao and Baxi) to Al exposure (100 and 500 µM) for 24 h. Microscopic analysis uncovered distinctive structural modifications in root cells, with Baodao displaying more severe alterations in response to Al stress. There was higher superoxide (O2-.) and hydrogen peroxide (H2O2) production and lipid peroxidation in Baodao indicating enhanced oxidative stress and membrane damage. Al accumulation in root tips was higher in Baxi than Baodao, while the roots of Baodao had a higher accumulation of callose. Nutrient content analysis revealed alterations in ion levels, highlighting the impact of Al exposure on nutrient uptake and homeostasis. In summary, Al differentially affects callose deposition, which, in turn, leads to Al uptake and nutrient homeostasis alteration in two contrasting banana genotypes. This intricate interplay is a key factor in understanding plant responses to aluminum toxicity and can inform strategies for crop improvement and soil management in aluminum-stressed environments.

Runx3 Regulates CD8+ T Cell Local Expansion and CD43 Glycosylation in Mice by H1N1 Influenza A Virus Infection.

We have recently reported that transcription factor Runx3 is required for pulmonary generation of CD8+ cytotoxic T lymphocytes (CTLs) that play a crucial role in the clearance of influenza A virus (IAV). To understand the underlying mechanisms, we determined the effects of Runx3 knockout (KO) on CD8+ T cell local expansion and phenotypes using an inducible general Runx3 KO mouse model. We found that in contrast to the lungs, Runx3 general KO promoted enlargement of lung-draining mediastinal lymph node (mLN) and enhanced CD8+ and CD4+ T cell expansion during H1N1 IAV infection. We further found that Runx3 deficiency greatly inhibited core 2 O-glycosylation of selectin ligand CD43 on activated CD8+ T cells but minimally affected the cell surface expression of CD43, activation markers (CD44 and CD69) and cell adhesion molecules (CD11a and CD54). Runx3 KO had a minor effect on lung effector CD8+ T cell death by IAV infection. Our findings indicate that Runx3 differently regulates CD8+ T cell expansion in mLNs and lungs by H1N1 IAV infection. Runx3 is required for CD43 core 2 O-glycosylation on activated CD8+ T cells, and the involved Runx3 signal pathway may mediate CD8+ T cell phenotype for pulmonary generation of CTLs.

Beyond guilty by association at scale: searching for causal variants on the basis of genome-wide summary statistics.

Understanding the causal genetic architecture of complex phenotypes is essential for future research into disease mechanisms and potential therapies. Here, we present a novel framework for genome-wide detection of sets of variants that carry non-redundant information on the phenotypes and are therefore more likely to be causal in a biological sense. Crucially, our framework requires only summary statistics obtained from standard genome-wide marginal association testing. The described approach, implemented in open-source software, is also computationally efficient, requiring less than 15 minutes on a single CPU to perform genome-wide analysis. Through extensive genome-wide simulation studies, we show that the method can substantially outperform usual two-stage marginal association testing and fine-mapping procedures in precision and recall. In applications to a meta-analysis of ten large-scale genetic studies of Alzheimer's disease (AD), we identified 82 loci associated with AD, including 37 additional loci missed by conventional GWAS pipeline. The identified putative causal variants achieve state-of-the-art agreement with massively parallel reporter assays and CRISPR-Cas9 experiments. Additionally, we applied the method to a retrospective analysis of 67 large-scale GWAS summary statistics since 2013 for a variety of phenotypes. Results reveal the method's capacity to robustly discover additional loci for polygenic traits and pinpoint potential causal variants underpinning each locus beyond conventional GWAS pipeline, contributing to a deeper understanding of complex genetic architectures in post-GWAS analyses.

Ecosystem service valuation and multi-scenario simulation in the Ebinur Lake Basin using a coupled GMOP-PLUS model.

The Ebinur Lake Basin is an ecologically sensitive area in an arid region. Investigating its land use and land cover (LULC) change and assessing and predicting its ecosystem service value (ESV) are of great importance for the stability of the basin's socioeconomic development and sustainable development of its ecological environment. Based on LULC data from 1990, 2000, 2010, and 2020, we assessed the ESV of the Ebinur Lake Basin and coupled the grey multi-objective optimization model with the patch generation land use simulation model to predict ESV changes in 2035 under four scenarios: business-as-usual (BAU) development, rapid economic development (RED), ecological protection (ELP), and ecological-economic balance (EEB). The results show that from 1990 to 2020, the basin was dominated by grassland (51.23%) and unused land (27.6%), with a continuous decrease in unused land and an increase in cultivated land. In thirty years, the total ESV of the study area increased from 18.62 billion to 67.28 billion yuan, with regulation and support services being the dominant functions. By 2035, cultivated land increased while unused land decreased in all four scenarios compared with that in 2020. The total ESV in 2035 under the BAU, RED, ELP, and EEB scenarios was 68.83 billion, 64.47 billion, 67.99 billion, and 66.79 billion yuan, respectively. In the RED and EEB scenarios, ESV decreased by 2.81 billion and 0.49 billion yuan, respectively. In the BAU scenario, provisioning and regulation services increased by 6.05% and 2.93%, respectively. The ELP scenario, focusing on ecological and environmental protection, saw an increase in ESV for all services. This paper can assist policymakers in optimizing land use allocation and provide scientific support for the formulation of land use strategies and sustainable ecological and environmental development in the inland river basins of arid regions.