Chromosome-level genome assembly of ridgetail white shrimp Exopalaemon carinicauda.

Exopalaemon carinicauda, a eurythermal and euryhaline shrimp, contributes one third of the total biomass production of polyculture ponds in eastern China and is considered as a potential ideal experimental animal for research on crustaceans. We conducted a high-quality chromosome-level genome assembly of E. carinicauda combining PacBio HiFi and Hi-C sequencing data. The total assembly size was 5.86 Gb, with a contig N50 of 235.52 kb and a scaffold N50 of 138.24 Mb. Approximately 95.29% of the assembled sequences were anchored onto 45 pseudochromosomes. BUSCO analysis revealed that 92.89% of 1,013 single-copy genes were highly conserved orthologs. A total of 44, 288 protein-coding genes were predicted, of which 70.53% were functionally annotated. Given its high heterozygosity (2.62%) and large proportion of repeat sequences (71.49%), it is one of the most complex genome assemblies. This chromosome-scale genome will be a valuable resource for future molecular breeding and functional genomics research on E. carinicauda.

A Biodegradable Fiber Calcium Ion Sensor by Covalently Bonding Ionophores on Bioinert Nanoparticles.

Implantable sensors, especially ion sensors, facilitate the progress of scientific research and personalized healthcare. However, the permanent retention of implants induces health risks after sensors fulfill their mission of chronic sensing. Biodegradation is highly anticipated while biodegradable chemical sensors are rare due to concerns about the leakage of harmful active molecules after degradation, such as ionophores. Here, we introduce a novel biodegradable fiber calcium ion sensor, wherein ionophores are covalently bonded with bioinert nanoparticles to replace the classical ion-selective membrane. The fiber sensor demonstrates comparable sensing performance to classical ion sensors and good flexibility. It can monitor the fluctuations of Ca2+ in a four-day lifespan in vivo, and biodegrade in four weeks. Benefiting from the stable bonding between ionophores and nanoparticles, the biodegradable sensor exhibited a good biocompatibility after degradation. Moreover, our approach of bonding active molecules on bioinert nanoparticles can serve as an effective methodology for minimizing health concerns about biodegradable chemical sensors. This article is protected by copyright. All rights reserved.

Integrin αVß1-activated PYK2 promotes the progression of non-small-cell lung cancer via the STAT3-VGF axis.

BACKGROUND: Non-small-cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer and is the leading cause of cancer-related deaths globally. Although various treatment strategies have been introduced, the 5-year survival rate of patients with NSCLC is only 20-30%. Thus, it remains necessary to study the pathogenesis of NSCLC and develop new therapeutic drugs. Notably, PYK2 has been implicated in the progression of many tumors, including NSCLC, but its detailed mechanism remains unclear. In this study, we aimed to elucidate the mechanisms through which PYK2 promotes NSCLC progression. METHODS: The mRNA and protein levels of various molecules were measured using qRT-PCR, western blot (WB), and immunohistochemistry (IHC), respectively. We established stable PYK2 knockdown and overexpression cell lines, and CCK-8, EdU, and clonogenic assays; wound healing, transwell migration, and Matrigel invasion assays; and flow cytometry were employed to assess the phenotypes of tumor cells. Protein interactions were evaluated with co-immunoprecipitation (co-IP), immunofluorescence (IF)-based colocalization, and nucleocytoplasmic separation assays. RNA sequencing was performed to explore the transcriptional regulation mediated by PYK2. Secreted VGF levels were examined using ELISA. Dual-luciferase reporter system was used to detect transcriptional regulation site. PF4618433 (PYK2 inhibitor) and Stattic (STAT3 inhibitor) were used for rescue experiments. A public database was mined to analyze the effect of these molecules on NSCLC prognosis. To investigate the role of PYK2 in vivo, mouse xenograft models of lung carcinoma were established and examined. RESULTS: The protein level of PYK2 was higher in human NSCLC tumors than in the adjacent normal tissue, and higher PYK2 expression was associated with poorer prognosis. PYK2 knockdown inhibited the proliferation and motility of tumor cells and caused G1-S arrest and cyclinD1 downregulation in A549 and H460 cells. Meanwhile, PYK2 overexpression had the opposite effect in H1299 cells. The siRNA-induced inhibition of integrins alpha V and beta 1 led to the downregulation of p-PYK2(Tyr402). Activated PYK2 could bind to STAT3 and enhance its phosphorylation at Tyr705, regulating the nuclear accumulation of p-STAT3(Tyr705). This further promoted the expression of VGF, as confirmed by RNA sequencing in a PYK2-overexpressing H1299 cell line and validated by rescue experiments. Two sites in promoter region of VGF gene were confirmed as binding sites of STAT3 by Dual-luciferase assay. Data from the TGCA database showed that VGF was related to the poor prognosis of NSCLC. IHC revealed higher p-PYK2(Tyr402) and VGF expression in lung tumors than in adjacent normal tissues. Moreover, both proteins showed higher levels in advanced TNM stages than earlier ones. A positive linear correlation existed between the IHC score of p-PYK2(Tyr402) and VGF. Knockdown of VGF inhibited tumor progression and reversed the tumor promoting effect of PYK2 overexpression in NSCLC cells. Finally, the mouse model exhibited enhanced tumor growth when PYK2 was overexpressed, while the inhibitors PF4618433 and Stattic could attenuate this effect. CONCLUSIONS: The Integrin αVß1-PYK2-STAT3-VGF axis promotes NSCLC development, and the PYK2 inhibitor PF4618433 and STAT3 inhibitor Stattic can reverse the pro-tumorigenic effect of high PYK2 expression in mouse models. Our findings provide insights into NSCLC progression and could guide potential therapeutic strategies against NSCLC with high PYK2 expression levels.

A nomogram combining prognostic nutritional index and platelet lymphocyte ratio predicts postoperative pulmonary infection following D2 radical gastrectomy for gastric cancer.

INTRODUCTION: the prognostic nutritional index (PNI) and platelet-lymphocyte ratio (PLR) have been found to correlate with outcomes following radical gastrectomy for gastric cancer (GC). OBJECTIVES: to construct a nomogram combining PNI and PLR for individually forecasting the risk of postoperative pulmonary infection (POI) following D2 radical gastrectomy for GC. METHODS: retrospectively, clinical data was gathered from 404 patients treated with D2 radical gastrectomy for GC. The study used multivariate logistic regression analysis to screen independent risk factors for POI after surgery. Subsequently, a nomogram was developed based on the above factors to forecast the POI probability accurately. RESULTS: the multivariate logistic regression analysis identified age, PNI, PLR, CA199 level, ASA score, and ICU treatment as independent risk variables for POI following D2 radical gastrectomy (p < 0.001 or 0.05). The nomogram's area under the receiver operating characteristic curve (AUC) for predicting the risk of POI was 0.736 (95 % confidence interval (CI) = 0.678-0.794). The nomogram was internally validated using the bootstrap approach, involving repeated sampling 1000 times. The result yielded a concordance index (c-index) of 0.707 (95 % CI = 0.705-0.709). The calibration curves demonstrated an excellent concordance between the predicted values of the nomogram and the observed values. The nomogram's clinical value was shown to be high using decision analysis curves. CONCLUSIONS: a nomogram combining PNI and PLR is a dependable tool for forecasting the probability of POI following D2 radical gastrectomy for GC.

Suppression of lysosome metabolism-meditated GARP/TGF-ß1 complexes specifically depletes regulatory T cells to inhibit breast cancer metastasis.

Regulatory T cells (Tregs) prevent autoimmunity and contribute to cancer progression. They exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-ß1 (TGF-ß1). However, the absence of a specific surface marker makes inhibiting the production of active TGF-ß1 to specifically deplete human Tregs but not other cell types a challenge. TGF-ß1 in an inactive form binds to Tregs membrane protein Glycoprotein A Repetitions Predominant (GARP) and then activates it via an unknown mechanism. Here, we demonstrated that tumour necrosis factor receptor-associated factor 3 interacting protein 3 (TRAF3IP3) in the Treg lysosome is involved in this activation mechanism. Using a novel naphthalenelactam-platinum-based anticancer drug (NPt), we developed a new synergistic effect by suppressing ATP-binding cassette subfamily B member 9 (ABCB9) and TRAF3IP3-mediated divergent lysosomal metabolic programs in tumors and human Tregs to block the production of active GARP/TGF-ß1 for remodeling the tumor microenvironment. Mechanistically, NPt is stored in Treg lysosome to inhibit TRAF3IP3-meditated GARP/TGF-ß1 complex activation to specifically deplete Tregs. In addition, by promoting the expression of ABCB9 in lysosome membrane, NPt inhibits SARA/p-SMAD2/3 through CHRD-induced TGF-ß1 signaling pathway. In addition to expose a previously undefined divergent lysosomal metabolic program-meditated GARP/TGF-ß1 complex blockade by exploring the inherent metabolic plasticity, NPt may serve as a therapeutic tool to boost unrecognized Treg-based immune responses to infection or cancer via a mechanism distinct from traditional platinum drugs and currently available immune-modulatory antibodies.

A quinoline derivative-based supramolecular gel for fluorescence 'turn-off' detection of Fe3+and Cu2.

In this research, we synthesized and constructed a novel gelator (namedQN) combining quinoline and naphthalene that self-assembled in N, N-dimethylformamide (DMF) to form a stable supramolecular gel (namedOQN). Under UV light, gelOQNexhibited extremely bright yellow fluorescence. The gelOQNshowed excellent sensing performance for both Fe3+and Cu2+, with a fluorescence 'turn-off' detection mechanism and the lowest detection limit of 7.58 × 10-8M and 1.51 × 10-8M, respectively. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectra, x-ray powder diffraction (XRD), rheological measurements, x-ray photoelectron spectroscopy (XPS), and fluorescence spectroscopy were used to characterize the gelOQN. TheOQNion-responsive membrane created is an excellent fluorescent writing material.

Complete mitochondrial genome data and phylogenetic analysis of Papilio macilentus Janson, 1877 (Lepidoptera: Papilionoidea: Papilionidae).

In the present study, the complete mitochondrial genome (mitogenome) of the Papilio macilentus (Lepidoptera: Papilionoidea: Papilionidae) was sequenced by next-generation sequencing method. The mitochondrial genome is a circular DNA molecule of 15,264 bp in size with 80.7% AT content, including 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and a long non-coding region (Control region). All protein-coding genes are initiated by ATN codons, and terminated with TAA, TAG, or single T. All tRNAs can be folded into common clover leaf secondary structure, except trn-S1. Phylogenetic analyses based on 13 protein-coding genes and 2 rRNA genes using maximum likelihood and Bayesian inference confirmed that P. macilentus and Papilio memnon are clustered into a clade, and revealed the relationships between Papilionini, Troidini, Teinopaippini and Leptocircini.

Discovery of Novel Azaindoles as Potent and Selective PI3Kδ Inhibitors for Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system and the unmet need for MS treatment demands new therapeutic development. Particularly, PI3Kδ is a high-value target for autoimmune disease, while the investigation of PI3Kδ inhibitors for MS therapy is relatively scarce. Herein, we report a novel class of azaindoles as PI3Kδ inhibitors for MS treatment. Compound 31, designed via nitrogen bioisosterism, displayed excellent PI3Kδ inhibitory activity and selectivity. In vitro assay showed that 31 exhibited superior activity on T lymphocytes to inhibit the proliferation of CD4+, CD8+, and CD3+ T cells. In the experimental autoimmune encephalomyelitis (EAE) model, 31 showed a comparable therapeutical efficacy with Dexamethasone to significantly ameliorate EAE symptoms. Mechanistic studies showed that compound 31 could significantly inhibit the PI3K/AKT/mTOR signaling pathway and inhibited T-cell proliferation and differentiation. Overall, this work provides a new structural PI3Kδ inhibitor and a new vision for MS therapy.

The cell cycle regulator p16 promotes tumor infiltrated CD8+ T cell exhaustion and apoptosis.

The therapeutic efficacy of adoptive T cell therapy is largely restricted by reduced viability and dysfunction of CD8+ T cells. Continuous antigen stimulation disrupts the expansion, effector function, and metabolic fitness of CD8+ T cells, leading to their differentiation into an exhausted state within the tumor microenvironment (TME). While the function of the cell cycle negative regulator p16 in senescent cells is well understood, its role in T cell exhaustion remains unclear. In this study, we demonstrated that TCR stimulation of CD8+ T cells rapidly upregulates p16 expression, with its levels positively correlating with TCR affinity. Chronic TCR stimulation further increased p16 expression, leading to CD8+ T cell apoptosis and exhaustion differentiation, without inducing DNA damage or cell senescence. Mechanistic investigations revealed that p16 downregulates mTOR, glycolysis, and oxidative phosphorylation (OXPHOS) associated gene expression, resulting in impaired mitochondrial fitness, reduced T cell viability, and diminished effector function. Furthermore, the deletion of p16 significantly enhances the persistence of CD8+ T cells within tumors and suppresses the terminal exhaustion of tumor-infiltrating T cells. Overall, our findings elucidate how increased p16 expression reshapes T cell intracellular metabolism, drives T cell apoptosis and exhaustion differentiation, and ultimately impairs T cell anti-tumor function.

Research progress of inland river water quality monitoring technology based on unmanned aerial vehicle hyperspectral imaging technology.

In recent years, increasing demand for inland river water quality precision management has heightened the necessity for real-time, rapid, and continuous monitoring of water conditions. By analyzing the optical properties of water bodies remotely, unmanned aerial vehicle (UAV) hyperspectral imaging technology can assess water quality without direct contact, presenting a novel method for monitoring river conditions. However, there are currently some challenges to this technology that limit the promotion application of this technology, such as underdeveloped sensor calibration, atmospheric correction algorithms, and limitations in modeling non-water color parameters. This article evaluates the advantages and disadvantages of traditional sensor calibration methods and considers factors like sensor aging and adverse weather conditions that impact calibration accuracy. It suggests that future improvements should target hardware enhancements, refining models, and mitigating external interferences to ensure precise spectral data acquisition. Furthermore, the article summarizes the limitations of various traditional atmospheric correction methods, such as complex computational requirements and the need for multiple atmospheric parameters. It discusses the evolving trends in this technology and proposes streamlining atmospheric correction processes by simplifying input parameters and establishing adaptable correction algorithms. Simplifying these processes could significantly enhance the accuracy and feasibility of atmospheric correction. To address issues with the transferability of water quality inversion models regarding non-water color parameters and varying hydrological conditions, the article recommends exploring the physical relationships between spectral irradiance, solar zenith angle, and interactions with water constituents. By understanding these relationships, more accurate and transferable inversion models can be developed, improving the overall effectiveness of water quality assessment. By leveraging the sensitivity and versatility of hyperspectral sensors and integrating interdisciplinary approaches, a comprehensive database for water quality assessment can be established. This database enables rapid, real-time monitoring of non-water color parameters which offers valuable insights for the precision management of inland river water quality.

Electrochemistry-assisted in-situ regeneration of oxygen vacancies and Ti(III) active sites for persistent uranium recovery at a low potential.

Electrochemical uranium extraction (EUE) from seawater is a very promising strategy, but its practical application is hindered by the high potential for electrochemical system, as well as the low selectivity, efficiency, and poor stability of electrode. Herein, we developed creatively a low potential strategy for persistent uranium recovery by electrochemistry-assisted in-situ regeneration of oxygen vacancies and Ti(III) active sites coupled with indirect reduction of uranium, finally achieving high selectivity, efficient and persistent uranium recovery. As-designed titanium dioxide rich in oxygen vacancies (TiO2-VO) electrode displayed an EUE efficiency of ∼99.9 % within 180 min at a low potential of 0.09 V in simulated seawater with uranium of 5∼20 ppm. Moreover, the TiO2-VO electrode also showed high selectivity (89.9 %) to uranium, long-term cycling stability and antifouling activity in natural seawater. The excellent EUE property was attributed to the fact that electrochemistry-assisted in-situ regeneration of oxygen vacancies and Ti(III) active sites enhanced EUE cycling process and achieved persistent uranium recovery. The continuous regeneration of oxygen vacancies not only reduced the adsorption energy of U(VI)O22+ but also serve as a storage and transportation channel for electrons, accelerating electron transfer from Ti(III) to U(VI) at solid-liquid interface and promoting EUE kinetic rate.

Effect of hydrogel drug delivery system for treating ulcerative colitis: A preclinical meta-analysis.

Hydrogel drug delivery systems (DDSs) for treating ulcerative colitis (UC) have garnered attention. However, there is a lack of meta-analysis summarizing their effectiveness. Therefore, this study aimed to conduct a meta-analysis of pre-clinical evidence comparing hydrogel DDSs with free drug administration. Subgroup analyses were performed based on hydrogel materials (polysaccharide versus non-polysaccharide) and administration routes of the hydrogel DDSs (rectal versus oral). The outcome indicators included colon length, histological scores, tumor necrosis factor-α (TNF-α), zonula occludens protein 1(ZO-1), and area under the curve (AUC). The results confirmed the therapeutic enhancement of the hydrogel DDSs for UC compared with the free drug group. Notably, no significant differences were found between polysaccharide and non-polysaccharide materials, however, oral administration was found superior regarding TNF-α and AUC. In conclusion, oral hydrogel DDSs can serve as potential excellent dosage forms in oral colon -targeting DDSs, and in the design of colon hydrogel delivery systems, polysaccharides do not show advantages compared with other materials.

Genome-Wide Identification and Characterization of the CCT Gene Family in Rapeseed (Brassica napus L.).

The CCT gene family is present in plants and is involved in biological processes such as flowering, circadian rhythm regulation, plant growth and development, and stress resistance. We identified 87, 62, 46, and 40 CCTs at the whole-genome level in B. napus, B. rapa, B. oleracea, and A. thaliana, respectively. The CCTs can be classified into five groups based on evolutionary relationships, and each of these groups can be further subdivided into three subfamilies (COL, CMF, and PRR) based on function. Our analysis of chromosome localization, gene structure, collinearity, cis-acting elements, and expression patterns in B. napus revealed that the distribution of the 87 BnaCCTs on the chromosomes of B. napus was uneven. Analysis of gene structure and conserved motifs revealed that, with the exception of a few genes that may have lost structural domains, the majority of genes within the same group exhibited similar structures and conserved domains. The gene collinearity analysis identified 72 orthologous genes, indicating gene duplication and expansion during the evolution of BnaCCTs. Analysis of cis-acting elements identified several elements related to abiotic and biotic stress, plant hormone response, and plant growth and development in the promoter regions of BnaCCTs. Expression pattern and protein interaction network analysis showed that BnaCCTs are differentially expressed in various tissues and under stress conditions. The PRR subfamily genes have the highest number of interacting proteins, indicating their significant role in the growth, development, and response to abiotic stress of B. napus.

Tumor-Targeted Oxaliplatin(IV) Prodrug Delivery Based on ROS-Regulated Cancer-Selective Glycan Labeling.

Platinum-drug-based chemotherapy in clinics has achieved great success in clinical malignancy therapy. However, unpredictable off-target toxicity and the resulting severe side effects in the treatment are still unsolved problems. Although metabolic glycan labeling-mediated tumor-targeted therapy has been widely reported, less selective metabolic labeling in vivo limited its wide application. Herein, a novel probe of B-Ac3ManNAz that is regulated by reactive oxygen species in tumor cells is introduced to enhance the recognition and cytotoxicity of DBCO-modified oxaliplatin(IV) via bioorthogonal chemistry. B-Ac3ManNAz was synthesized from Ac4ManNAz by incorporation with 4-(hydroxymethyl) benzeneboronic acid pinacol ester (HBAPE) at the anomeric position, which is confirmed to be regulated by ROS and could robustly label glycans on the cell surface. Moreover, N3-treated tumor cells could enhance the tumor accumulation of DBCO-modified oxaliplatin(IV) via click chemistry meanwhile reduce the off-target distribution in normal tissue. Our strategy provides an effective metabolic precursor for tumor-specific labeling and targeted cancer therapies.

Self-assembly formation of Co quantum dot loaded N-doped porous carbon cathode for quinoline degradation in the electro-Fenton system.

Quinoline is high toxicity and difficult biodegradation in oil washing wastewater. Therefore, efficient removal of quinoline contaminant from water bodies poses a major challenge. Hence, Co quantum dot loaded N-doped porous carbon (CoNC) nanosheets grown in situ on carbon cloth were fabricated as cathode for the degradation of quinoline in electro-Fenton system. Under optimal conditions (c(Fe2+) = 0.5 mM, U = -0.3 V, pH = 3), quinoline was completely degraded within 15 min with superior apparent rate constant of 0.385 min-1, which was 19.6 times higher than that of the ZIF-L precursor, due to the abundance of Co QDs active sites and hydrophilicity and electrical conductivity of N-doped porous carbon. In addition, three reaction pathways for quinoline were deduced by combining Density Functional Theory (DFT) calculation and Liquid Chromatography-Mass Spectrometry (LC-MS). More importantly, in situ FTIR and free energy calculations were analyzed to reveal that pathway Ⅰ as spontaneous reaction was the main reaction pathway. Finally, the toxicity of the intermediates was assessed with ECOSAR software and E. coli experiments, and the overall toxicity decreased during the degradation reactions. This work provides novel perspectives on environmental protection by designing in-situ grown cathodes through self-assembly method, thereby effectively purifying pollutants from wastewater.

Longer fatty acid-protected GalNAz enables efficient labeling of proteins in living cells with minimized S-glyco modification.

Metabolic glycoengineering provides a powerful tool to label proteins with chemical tags for cell imaging and protein enrichment. The structures of per-O-acetylation on unnatural sugars facilitate membrane permeability and increase cellular uptake and are widely used for metabolic glycan labeling. However, unexpected S-glyco modification was discovered via a non-enzymatic reaction with protein cysteines, which was initially conducted with the hydrolysis of anomeric acetate by esterase. Herein, we synthesized a series of GalNAz derivatives that were protected with various lengths of short-chain fatty acid, including acetate, propionate, butyrate, valerate and pivalate, to detect differences in labeling efficiencies and occurrence of S-glyco modification. Our results demonstrate that all the GalNAz derivatives could effectively label proteins in HeLa cells, except the pivalate group. Of note, But4GalNAz exhibited excellent labeling abilities compared with Ac4GalNAz from the results for western blot, flow cytometry and confocal laser scanning microscopy. Moreover, the results for the S-glyco-modification assay by western blot and chemoproteomic analysis indicated that But4GalNAz generated negligible unexpected labeling signals compared to Ac4GalNAz. Our study uncovers the distinct labeling efficiency of different protected groups on unnatural sugars, which provides an alternative strategy to explore novel glycan probes.

Osteocyte ferroptosis induced by ATF3/TFR1 contributes to cortical bone loss during ageing.

Cortical bone loss is intricately associated with ageing and coincides with iron accumulation. The precise role of ferroptosis, characterized by iron overload and lipid peroxidation, in senescent osteocytes remains elusive. We found that ferroptosis was a crucial mode of osteocyte death in cortical bone during ageing. Using a single-cell transcriptome analysis, we identified activating transcription factor 3 (ATF3) as a critical driver of osteocyte ferroptosis. Elevated ATF3 expression in senescent osteocytes promotes iron uptake by upregulating transferrin receptor 1 while simultaneously inhibiting solute carrier family 7-member 11-mediated cystine import. This process leads to an iron overload and lipid peroxidation, culminating in ferroptosis. Importantly, ATF3 inhibition in aged mice effectively alleviated ferroptosis in the cortical bone and mitigated cortical bone mass loss. Taken together, our findings establish a pivotal role of ferroptosis in cortical bone loss in older adults, providing promising prevention and treatment strategies for osteoporosis and fractures.

NET-related gene signature for predicting AML prognosis.

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan-Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs-CFTR, ENO1, PARVB, DDIT4, MPO, LDLR-were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p < 0.001), which was validated in two external datasets (GSE71014 and GSE106291). The 6-NRG signature and corresponding nomograms exhibit superior predictive accuracy, offering insights for pre-immune response evaluation and guiding future immuno-oncology treatments and drug selection for AML patients.

In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice.

Despite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.