Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma.

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways "BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation" and "AMAN pathway". In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Carvedilol ameliorates experimental atherosclerosis by inhibiting the NLRP3 inflammasome.

BACKGROUND: To investigate the protective effect of carvedilol against atherosclerosis by inhibiting the NLRP3 inflammasome. METHODS: In-vitro experiments, human umbilical vein endothelial cells (HUVEC) were divided into the control group, ox-LDL group, carvedilol 5 µM group, carvedilol 10 µM group, and carvedilol 20 µM group. The optimal concentration of carvedilol was determined using the CCK-8 method to assess cell proliferation levels and oil red O staining to observe intracellular lipid droplet formation. Subsequently, the cells were further divided into the control group, ox-LDL group, carvedilol 5 µM (optimal concentration) group, and MCC950 (inhibitor of NLRP3 Inflammasome) group. The expression levels of intracellular proteins NLRP3, pro-Caspase-1, Caspase1, pro-IL-1ß, IL-1ß, p65, GSDMD, and N-GSDMD were detected by ELISA, or Western Blotting. RESULTS: Compared to the control group, the ox-LDL group exhibited a significant reduction in cell proliferation level (P<0.05), accompanied by an increase in lipid droplet formation upon induction. In contrast, pretreatment with carvedilol at concentrations of 5 µM, 10 µM, and 20 µM effectively promoted cell proliferation (P<0.05) and inhibited intracellular lipid droplet formation. Notably, the most pronounced effect was observed with carvedilol pretreatment at a concentration of 5µM. Furthermore, compared to the control group, HUVEC cells in the ox-LDL group demonstrated substantial upregulation of NLRP3, pro-Caspase-1, Caspase1, pro-IL-1ß, IL-1ß, p65 GSDMD and N-GSDMD; however, these markers were downregulated following treatment with carvedilol and MCC950 administration-particularly evident in the carvedilol group. CONCLUSIONS: Carvedilol effectively inhibits the progression of atherosclerosis by targeting the NLRP3 inflammasome, thereby providing valuable mechanistic insights into its beneficial effects on atherosclerotic cardiovascular disease.

[Research Progress of Ferroptosis in Ulcerative Colitis].

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous inflammation and ulcer formation in the intestinal mucosa.Its pathogenesis involves immune dysfunction,dysbiosis of gut microbiota,and mucosal damage caused by inflammation.Ferroptosis is an iron-dependent form of cell death regulated by disturbances in iron metabolism,lipid peroxidation,and depletion of glutathione (GSH).Studies have indicated that ferroptosis plays a crucial role in the pathogenesis of UC,particularly in regulating inflammatory responses and damaging intestinal epithelial cells.This article reviews the regulatory mechanisms and roles of ferroptosis in UC and discusses the potential therapeutic strategies to alleviate UC symptoms by modulating iron metabolism,reducing lipid peroxidation,and maintaining GSH levels,providing new targets and directions for the diagnosis and treatment of UC.

Integrated Thermal Proteome Profiling and Affinity Ultrafiltration Mass Spectrometry (iTPAUMS): A Novel Paradigm for Elucidating the Mechanism of Action of Natural Products.

Natural products (NPs) are foundational to drug discovery, offering a rich repertoire of molecular diversity with multifaceted modes of action against a broad array of targets. Despite their potential, deconvoluting the intricate mechanism of action (MoA) of NPs, characterized by their multicomponent, multitarget, and multilevel interactions, remains a formidable challenge. Here, we introduce an innovative pipeline called integrated thermal proteome profiling and affinity ultrafiltration mass spectrometry (iTPAUMS). This approach combines the high-throughput capacity of thermal proteome profiling (TPP) with the specificity of affinity ultrafiltration mass spectrometry (AUMS), creating a powerful toolkit for elucidating complex MoAs of NPs. Significantly, our investigation represents a pioneering application of TPP to delineate the target group of NPs mixtures and overcome the long-standing obstacle of mapping specific component-target interactions through AUMS. Our findings demonstrate the utility of iTPAUMS in constructing a comprehensive component-target atlas, providing a robust analytical foundation for unraveling the intricate pharmacological landscapes of NPs and advancing drug discovery.

Effect of APOE gene on cerebral oxygen saturation, cerebral electrical activity and prognosis after intracerebral hemorrhage.

Cerebral hemorrhage represents a severe neurological disorder with significant implications for patient health. Numerous factors play a crucial role in determining the prognosis of this condition. In recent years, research has highlighted the polymorphism of the apolipoprotein E (APOE) gene as being closely associated with cerebrovascular diseases and the recovery of neurological functions. This study aims to explore the influence of APOE gene polymorphism on cerebral oxygen saturation, cerebral electrical activity, and the clinical prognosis of patients experiencing cerebral hemorrhage. The goal is to identify potential new biomarkers that could enhance the management and treatment of individuals who have suffered from this type of bleed in the brain.To investigate this relationship, the study analyzed the ε2, ε3, and ε4 alleles of the APOE gene through gene sequencing techniques. Measurements of cerebral oxygen saturation and electrical brain activity were conducted using specialized equipment including brain oxygen monitors and electroencephalography (EEG) devices. Additionally, detailed clinical data were gathered, encompassing neurological function assessments and the duration of recovery for each patient.A comparative analysis was performed to assess the cerebral oxygen saturation levels, EEG characteristics, and overall prognosis associated with the different APOE genotypes. The findings indicated that patients carrying the APOE ε4 allele exhibited significantly impaired cerebral oxygen metabolism and diminished electrical activity in the initial stages of intracerebral hemorrhage. This impairment potentially results in a worse prognostic outlook when compared to individuals who are non-carriers of the APOE ε4 allele. Furthermore, the relationship between the pulsatility index (PR) and regional cerebral oxygen saturation (rScO2) was found to be negatively correlated. Specifically, patients with intracerebral hemorrhage who exhibited elevated PR levels alongside reduced rScO2 demonstrated poorer clinical outcomes.

Pestiorosins A-F, New Papulacandins Isolated from the Fungus Pestalotiopsis rosea YNJ21.

Six previously unreported papulacandins, namely pestiorosins A-F (1-6), were isolated from the fermentation products of the fungus Pestalotiopsis rosea YNJ21 isolated from the fruitbody of Amanita exitialis. The structures of these compounds, along with a known compound called pestiocandin (7), were determined using MS, NMR data, and modified Mosher's method. All compounds exhibited significant antifungal activity against Candida albicans, with MIC values ranging from 0.06 to 2.00 µg/mL. In terms of cytotoxicity assays, compounds 3 and 6 demonstrated moderate inhibitory activity against human breast cancer MCF-7 cells with IC50 values of 24.50 and 16.83 µM, respectively. On the other hand, compound 7 displayed similar levels of inhibitory activity against mice microglial BV2 cells with an IC50 value of 24.51 µM.

Transcriptome analysis of lipid biosynthesis during kernel development in two walnut (Juglans regia L.) varieties of 'Xilin 3' and 'Xiangling'.

BACKGROUND: Walnut is an oilseed tree species and an ecologically important woody tree species that is rich in oil and nutrients. In light of differences in the lipid content, fatty acid composition and key genes expression patterns in different walnut varieties, the key gene regulatory networks for lipid biosynthesis in different varieties of walnuts were intensively investigated. RESULTS: The kernels of two walnut varieties, 'Xilin 3' (X3) and 'Xiangling' (XL) were sampled at 60, 90, and 120 days post-anthesis (DPA) to construct 18 cDNA libraries, and the candidate genes related to oil synthesis were identified via sequencing and expression analysis. A total of 106 differentially expressed genes associated with fatty acid biosynthesis, fatty acid elongation, unsaturated fatty acid biosynthesis, triglyceride assembly, and oil body storage were selected from the transcriptomes. Weighted gene co-expression network analysis (WGCNA), correlation analysis and quantitative validation confirmed the key role of the FAD3 (109002248) gene in lipid synthesis in different varieties. CONCLUSIONS: These results provide valuable resources for future investigations and new insights into genes related to oil accumulation and lipid metabolism in walnut seed kernels. The findings will also aid future molecular studies and ongoing efforts to genetically improve walnut.

Clinical features of neonatal testicular torsion: A retrospective analysis of 24 cases.

OBJECTIVES: To analyze the clinical characteristics, surgical management decisions, and outcomes of Neonatal testicular torsion (NTT) in order to offer guidance for future clinical practice. METHODS: Retrospectively analyzed the clinical data of patients with NTT who were admitted and underwent surgery from January 2008 to October 2023. RESULTS: A total of 24 neonates were enrolled in this study, all of whom were unilateral cases. Age of onset was 0 d (IQR: 0-1.8), while the median duration of symptoms was 73 h (IQR: 26-199). Clinical manifestation included enlarged scrotum (75 %), changes in scrotal color (79 %), and crying upon palpation (17 %). All patients underwent urgent bilateral exploration and performed by orchiectomy and contralateral orchiopexy. CONCLUSION: NTT primarily occurs prenatally with insidious manifestations, often leading to omission or misdiagnosis. The testicular salvage rate is extremely low. Physicians need to attach importance to neonatal testicular examination, improve the vigilance of NTT. Early bilateral exploration does not necessarily save the affected testes, but it is more important to prevent damage to the contralateral one.

Decreased dust particles amplify the cloud cooling effect by regulating cloud ice formation over the Tibetan Plateau.

Ice-nucleating particles (INPs) can initiate cloud ice formation, influencing cloud radiative effects (CRE) and climate. However, the knowledge of INP sources, concentrations, and their impact on CRE over the Tibetan Plateau (TP)-a highly climate-sensitive region-remains largely hypothetical. Here, we integrated data from multisource satellite observations and snowpack samples collected from five glaciers to demonstrate that dust particles constitute primary INP sources over the TP. The springtime dust influxes lead to seasonally elevated ice concentrations in mixed-phase clouds. Furthermore, the decadal reduction in dustiness from 2007 to 2019 results in decreased springtime dust INPs, thereby amplifying the cooling effect of clouds over the TP, with a 1.98 ± 0.39-watt per square meter reduction in surface net CRE corresponding to a 0.01 decrease in dust optical depth. Our findings elucidate previously unidentified pathways of climate feedback from an atmospheric INP perspective, especially highlighting the crucial role of dust in aerosol-cloud interactions.

Screening of serum markers in patients with resistant hypertension.

Background: This study delves into the intricacies of resistant hypertension (RH), a prevalent yet enigmatic chronic cardiovascular ailment that is linked to a myriad of complications. Although its full pathogenesis is still shrouded in mystery, the field of proteomics offers a beacon of hope, with its potential to shed light on the proteins that orchestrate the tapestry of life. Harnessing the power of proteomics is essential for demystifying the pathogenesis of RH, enabling more precise diagnostics and treatments, and ultimately improving prognostic outcomes. Methods: Our approach was to employ rigorous statistical analyses to home in on proteins with significant expression variances between our two cohorts. We complemented this with bioinformatics tools to unravel the intricate functions and pathways of these proteins. By synthesizing these insights with the clinical profiles of our patients, we were able to distill a set of definitive biomarkers with diagnostic potential. In our quest for clarity, we also embarked on a retrospective journey, amassing and scrutinizing clinical data from both RH and hypertension (HTN) patients. We crafted and rigorously assessed risk factor models to evaluate their diagnostic prowess. Results: Our exploration spanned across 30 blood samples from RH patients and 20 from those grappling with HTN. Our inquiry yielded some compelling revelations: (1) RH patients showcased 29 unique proteins, in contrast to the 59 unique proteins found in HTN patients. A deeper dive into the proteomic data unveiled molecular functions predominantly tied to lipid metabolism, protein networking, and oxidative stress, with a spotlight on pathways such as cholesterol metabolism, coagulation, and the complement cascade. (2) By charting receiver operating characteristic curves and rigorously analyzing the proteomic data, we surfaced 11 proteins with notable diagnostic potential, tightly interwoven with clinical metrics. Conclusion: Our research has pinpointed 11 proteins that stand as promising serum biomarkers, endowed with significant diagnostic value. This discovery marks a stride towards a more nuanced understanding and management of resistant hypertension.

Unveiling the contribution of tumor-associated macrophages in driving epithelial-mesenchymal transition: a review of mechanisms and therapeutic Strategies.

Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cancer cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in cancer progression. The review begins with a detailed exposition on the origins of TAMs and their functional heterogeneity, providing a foundational understanding of TAM characteristics. Next, it delves into the specific molecular mechanisms through which TAMs induce EMT, including cytokines, chemokines and stromal cross-talking. Following this, the review explores TAM-induced EMT features in select cancer types with notable EMT characteristics, highlighting recent insights and the impact of TAMs on cancer progression. Finally, the review concludes with a discussion of potential therapeutic targets and strategies aimed at mitigating TAM infiltration and disrupting the EMT signaling network, thereby underscoring the potential of emerging treatments to combat TAM-mediated EMT in cancer. This comprehensive analysis reaffirms the necessity for continued exploration into TAMs' regulatory roles within cancer biology to refine therapeutic approaches and improve patient outcomes.

LncRNA FAISL Inhibits Calpain 2-Mediated Proteolysis of FAK to Promote Progression and Metastasis of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is the most aggressive subtype in breast tumors. When re-analyzing TCGA breast cancer dataset, we found cell adhesion molecules are highly enriched in differentially expressed genes in TNBC samples, among which Focal Adhesion Kinase (FAK) is most significantly associated with poor survival of TNBC patients. FAK is precisely modulated in the focal adhesion dynamics. To investigate whether lncRNAs regulate FAK signaling, we performed RNA immunoprecipitation sequencing and found FAISL (FAK Interacting and Stabilizing LncRNA) abundantly enriched in FAK-interacting lncRNAs and frequently overexpressed in TCGA TNBC tissues. FAISL promotes TNBC cell adhesion, cytoskeleton spreading, proliferation, and anchor-independent survival. FAISL doesn't affect FAK mRNA but positively regulates FAK protein level by blocking Calpain 2-mediated proteolysis. FAISL interacts with the C-terminus domain of FAK, whereby masks the binding site of Calpain 2 and prevents FAK cleavage. High level of FAISL correlates with FAK expression in tumor tissues and poor prognosis of TNBC patients. A siRNA delivery system targeting FAISL using reduction-responsive nanoparticles effectively inhibits tumor growth and metastasis in TNBC mouse models. Together, these findings uncover a lncRNA-mediated mechanism of regulating FAK proteolysis in the TNBC progression, and highlight the potential of targeting lncRNA FAISL for TNBC treatment.

Predictive machine learning models based on VASARI features for WHO grading, isocitrate dehydrogenase mutation, and 1p19q co-deletion status: a multicenter study.

The objective of our study was to develop predictive models using Visually Accessible Rembrandt Images (VASARI) magnetic resonance imaging (MRI) features combined with machine learning techniques to predict the World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) mutation status, and 1p19q co-deletion status of high-grade gliomas. To achieve this, we retrospectively included 485 patients with high-grade glioma from the First Affiliated Hospital of Xinjiang Medical University, of which 312 patients were randomly divided into a training set (n=218) and a test set (n=94) in a 7:3 ratio. Twenty-five VASARI MRI features were selected from an initial set of 30, and three machine learning models - Multilayer Perceptron (MP), Bernoulli Naive Bayes (BNB), and Logistic Regression (LR) - were trained using the training set. The most informative features were identified using recursive feature elimination. Model performance was assessed using the test set and an independent validation set of 173 patients from Beijing Tiantan Hospital. The results indicated that the MP model exhibited the highest predictive accuracy on the training set, achieving an area under the curve (AUC) close to 1, indicating perfect discrimination. However, its performance decreased in the test and validation sets; particularly for predicting the 1p19q co-deletion status, the AUC was only 0.703, suggesting potential overfitting. On the other hand, the BNB model demonstrated robust generalization on the test and validation sets, with AUC values of 0.8292 and 0.8106, respectively, for predicting IDH mutation status and 1p19q co-deletion status, indicating high accuracy, sensitivity, and specificity. The LR model also showed good performance with AUCs of 0.7845 and 0.8674 on the test and validation sets, respectively, for predicting IDH mutation status, although it was slightly inferior to the BNB model for the 1p19q co-deletion status. In conclusion, integrating VASARI MRI features with machine learning techniques shows promise for the non-invasive prediction of glioma molecular markers, which could guide treatment strategies and improve prognosis in glioma patients. Nonetheless, further model optimization and validation are necessary to enhance its clinical utility.

The Estimation of Knee Medial Force with Substitution Parameters during Walking and Turning.

PURPOSE: Knee adduction, flexion moment, and adduction angle are often used as surrogate parameters of knee medial force. To verify whether these parameters are suitable as surrogates under different walking states, we investigated the correlation between knee medial loading with the surrogates during walking and turning. METHODS: Sixteen healthy subjects were recruited to complete straight walk (SW), step turn (ST), and crossover turn (CT). Knee joint moments were obtained using inverse dynamics, and knee medial force was computed using a previously validated musculoskeletal model, Freebody. Linear regression was used to predict the peak of knee medial force with the peaks of the surrogate parameters and walking speed. RESULTS: There was no significant difference in walking speed among these three tasks. The peak knee adduction moment (pKAM) was a significant predictor of the peak knee medial force (pKMF) for SW, ST, and CT (p < 0.001), while the peak knee flexion moment (pKFM) was only a significant predictor of the pKMF for SW (p = 0.034). The statistical analysis showed that the pKMF increased, while the pKFM and the peak knee adduction angle (pKAA) decreased significantly during CT compared to those of SW and ST (p < 0.001). The correlation analysis indicated that the knee parameters during SW and ST were quite similar. CONCLUSIONS: This study investigated the relationship between knee medial force and some surrogate parameters during walking and turning. KAM was still the best surrogate parameter for SW, ST, and CT. It is necessary to consider the type of movement when comparing the surrogate predictors of knee medial force, as the prediction equations differ significantly among movement types.

A facile colorimetric sensor for ketoprofen detection in milk: Integrating molecularly imprinted polymers with Cu-doped Fe3O4 nanozymes.

A facile and efficient detection method is required to address the potential health risks of ketoprofen (KP) in animal-derived foods. Herein, we integrated molecularly imprinted polymers (MIPs) with Cu-doped Fe3O4 nanozymes (Fe3O4-Cu) to develop a selective colorimetric sensor for KP detection. Chitosan and glutaraldehyde were used as functional monomers and cross-linkers to fabricate proposed the MIPs@Fe3O4-Cu. On KP addition, it was specifically captured by the imprinted cavities, thereby blocking the channels between chromogenic substrates and Fe3O4-Cu. Based on this rationale, a selective colorimetric sensor utilizing MIPs@Fe3O4-Cu was established, exhibiting a linear range of 0.25-100 µM and a detection limit of 0.073 µM. The developed method was validated through its application in milk samples, yielding satisfactory recoveries with low relative standard deviations. This efficient and selective colorimetric sensor holds immense significance for KP detection in complex samples.

Extended system-bath entanglement theorem with multiple baths in the presence of external fields.

The system-bath entanglement theorem (SBET) was established in terms of linear response functions [Du et al., J. Chem. Phys. 152, 034102 (2020)] and generalized to correlation functions [Su et al., J. Chem. Phys. 160, 084104 (2024)] in our previous studies. This theorem connects the entangled system-bath properties to the local system and bare-bath ones. In this work, we extend the SBET to field-dressed conditions with multiple baths at different temperatures. As in reality, the external fields may interact with not only the system but also environments. The extended SBET facilitates, for example, photo-acoustic, photo-thermal, pump-probe related studies. The theorem under the field-free condition (multiple baths) and its counterpart in the classical limit is also presented.

A Self-Driven Ga2O3 Memristor Synapse for Humanoid Robot Learning.

In recent years, the rapid development of brain-inspired neuromorphic systems has created an imperative demand for artificial photonic synapses that operate with low power consumption. In this study, a self-driven memristor synapse based on gallium oxide (Ga2O3) nanowires is proposed and demonstrated successfully. This memristor synapse is capable of emulating a range of functionalities of biological synapses when exposed to 255 nm light stimulation. These functionalities encompass peak time-dependent plasticity, pulse facilitation, and memory learning capabilities. It exhibits an ultrahigh paired-pulse facilitation index of 158, indicating exceptional learning performance. The transition from short-term memory to long-term memory can be attributed to the remarkable relearning capabilities. Furthermore, the potential applications of the memristor synapse is showcased through the successful manipulation of a humanoid intelligent robot. Upon establishing artificial intelligence (AI) systems, the control commands originating from the synaptic device can drive the humanoid robot to perform various actions. Based on the memristor synapses, the autonomous feedback system of the humanoid robot facilitates a good collaboration between robotic actions and bio-inspired light perception. Therefore, this research opens up an effective way to advance the development of neuromorphic computing technologies, AI systems, and intelligent robots that demand ultra-low energy consumption.

WTAP weakens oxaliplatin chemosensitivity of colorectal cancer by preventing PANoptosis.

As the most abundant post-transcriptional modification in eukaryotes, N6-methyladenosine (m6A) plays a crucial role in cancer cell proliferation, invasion and chemoresistance. However, its specific effects on chemosensitivity to oxaliplatin-based regimens and the impact of these drugs on m6A methylation levels in colorectal cancer (CRC) remain largely unexplored. In this study, we demonstrated that the m6A methyltransferase Wilms tumor 1-associating protein (WTAP) weakens oxaliplatin chemosensitivity in HCT116 and DLD1 cells. Mechanistically, oxaliplatin treatment upregulated WTAP expression, preventing multiple forms of cell death simultaneously, a process known as PANoptosis, by decreasing intracellular oxidative stress through maintaining the expression of nuclear factor erythroid-2-related factor 2 (NRF2), a major antioxidant response element, in an m6A-dependent manner. In addition, high WTAP expression in CRC patients is associated with a poor prognosis and reduced benefit from standard chemotherapy by clinical data analysis of The Cancer Genome Atlas (TCGA) database and patient cohort study. These findings suggest that targeting WTAP-NRF2-PANoptosis axis could enhance the antitumor efficacy of oxaliplatin-based chemotherapy in CRC treatment.