International Journal of Biology and Life Sciences
type: channel
description: International Journal of Biology and Life Sciences (IJBLS) is a peer-reviewed journal published by Darcy & Roy Press. The mission of the journal is to provide an academic forum for discussing the issues of biology, medicine, health, life sciences across the world. All articles published are rigorously and fast reviewed meeting the Journal Quality standards.
publisher: Darcy & Roy Press
language: en
publication name: International Journal of Biology and Life Sciences
issn: 2957-9511
items: Methodological and Application Progress of EEG for Early Screening and Digital Intervention in Alzheimer's Disease
items: The mechanism of action of alpha-lipoic acid in the treatment of type 2 diabetes and its complications
items: Targeted Therapy and Immunotherapy are Novel Treatment Plans of Hepatocellular Carcinoma that is not Amenable to Surgical Resection: Emerging Trends in Combined Treatment Strategies
items: From “Anti-inflammatory Medicine” to Public Resource: Antibiotic Culture, Intergenerational Memory, and the Ethics of AMR Governance in China
items: Advances in Dual-Crosslinking Strategies for Hydrogels: From Physical-Chemical Synergy to Stimuli-Responsive Control
items: Research Progress on the Gut–Brain Axis in the Pathogenesis and Progression of Alzheimer’s Disease
items: Analysis of P-wave Morphology Changes and Related Influencing Factors during PICC Catheterization in Tumor Patients Using Intracavitary Electrocardiographic Monitoring Localization Technology
items: Research Progress on Perioperative Thirst Management in Patients Undergoing Gastrointestinal Tumor Surgery
items: Research Progress on the Mechanism of Action of Modern Anesthetic Drugs
items: Applications of Artificial Intelligence in Traditional Chinese Medicine
items: Exploration of Remote Nutrition Intervention for Metabolic Diseases Supported by Multimodal Dietary Data
items: The effection of gene variation in Familial
items: Neuroimaging Evidence of Acupuncture Treatment for Depression Over the Past Decade: A Systematic Review
items: The Application of Anti-inflammatory Diet Patterns in Weight Control of Obese Population: Mechanism and Clinical Manifestations
items: Engineering Probiotics for Serotonin Production as a Potential Adjunctive Therapy for Depression
items: Economic Feasibility and Ecological Effects of Alternative Protein Feeds: Input Evidence and Subsequent Environmental Impacts of Fish and Other Farmed Animals
items: Replacing Fetal Bovine Serum with Food Processing Byproducts in Culture Media for Cultured Meat – a Sustainable Development Path
items: Progress on Molecular Mechanism of Disulfide Death in Gastric Cancer and its Clinical Targeted Treatment Strategy
items: Fragility and Plasticity of CCR8+Tregs: Providing New Directions for Cancer Treatment
items: Role of Epidemic Tumor Vaccine in Cold Tumors to Hot Tumors
items: The Metabolic Reprogramming of Immune Cells in the Tumor Microenvironment and the Mechanism of Immune Therapy Resistance
items: CRISPR/Cas9-Mediated PD-1 Engineered T Cells: New Strategy to Block Tumor Immune Escape
items: Protein Phase Separation and Regulatory Mechanisms of Transcriptional Programming in Tumor Microenvironment in Stress Response
items: Research on the Regulation of RNA by Traditional Chinese Medicine to Alleviate Chemotherapy Side Effects
items: Bortezomib and autoimmune hemolytic anemia: a systematic review and meta-analysis
items: Screening of Key Biomarkers and Molecular Mechanisms of Major Depressive Disorder Based on Multi-Cohort Transcriptomic Data
items: The Application of Gut Microbiota in the Diagnosis, Prognosis and Treatment of Colorectal Cancer
items: Research on Foot Function Adaptation and Injury Prevention from the Perspective of Sports Biomechanics
items: Feature Selection for Autism Spectrum Disorder via a Multi-Pack Cooperative Grey Wolf Optimization Framework
items: The CD155-TIGIT Signaling Axis in NK Cell Immune Evasion in Tumors: Mechanisms, Synergy with TGF-β, and Combined Intervention Strategies

Methodological and Application Progress of EEG for Early Screening and Digital Intervention in Alzheimer's Disease
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description: Alzheimer's disease (AD), which has a slow, insidious onset and minimal success in treatment, stresses the significance of early screening and intervention. The paper discusses the latest developments on how electroencephalography (EEG) can be used at an early stage to screen AD and digital intervention solutions. It provides an overview of some fundamental approaches like spectral analysis, functional connectivity analysis, and topographical analysis of a network of the brain. Moreover, it analyses the translational uses created by the application of those approaches in combination with multimodal features and machine learning, especially in the categorisation of risks and digital therapeutics. To summarise, EEG has many benefits, including being non-invasive, cheap, and capable of repeated measurements. Its general acceptance will, however, depend upon creating standard methods, validating using big samples, and integrating multimodal methods, including integrating EEG data with other imaging modalities and clinical evaluations to improve the accuracy of diagnosis. In the future, given that digital health care and intelligent analytics technology are still developing, it is expected that EEG will also be playing a more crucial part in the initial screening, intervention and long-term care of AD.
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creator: Mengyan Xia
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 170
ending page: 175
doi: 10.54097/mqbe0j16

The mechanism of action of alpha-lipoic acid in the treatment of type 2 diabetes and its complications
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description: Type 2 diabetes mellitus is now one of the metabolic disorders in the world, Oxidative stress and chronic inflammation are the reasons for serious diseases such as insulin resistance and peripheral neuropathy, and the existing drugs are unable to prevent these diseases at the level of pathology. Alpha-lipoic acid is a very effective multi-functional antioxidant and has shown some good results in diabetes research, First, we will introduce the main mechanisms by which alpha-lipoic acid has antioxidant and anti-stress effects; there are many reasons for its good antioxidant and anti-aging properties, such as directly scavenging free radicals and reactive oxygen species (ROS), chelating metal ions, repairing oxidative damage, regenerating endogenous antioxidants, modulating signaling pathways, etc, It is non-inflammatory and may lower the amount of pro-inflammatory cytokines in the body by suppressing inflammation. It also reveals that there are some neuroprotective and symptomatic-reducing effects on diabetic peripheral neuropathy, By comparing the old way of treating diseases, this paper finds that alpha-lipoic acid has two advantages in targeted treatment and blocking the course of disease, However, its clinical dosage and safety over long periods have not been confirmed yet. In order to learn how to use α-lipoic acid for preventing and treating complications of type 2 diabetes better, this paper will explore related research at the molecular level and provide a reference for the development of new drugs.
subject: Articles
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creator: Yuli Wang
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 201
ending page: 208
doi: 10.54097/hpe9zh52

Targeted Therapy and Immunotherapy are Novel Treatment Plans of Hepatocellular Carcinoma that is not Amenable to Surgical Resection: Emerging Trends in Combined Treatment Strategies
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description: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with advanced unresectable disease presenting a significant therapeutic challenge. The treatment paradigm has undergone a fundamental transformation, shifting from tyrosine kinase inhibitor (TKI) monotherapy to combination strategies integrating targeted therapy with immunotherapy. Atezolizumab plus bevacizumab, combining programmed cell death ligand 1 (PD-L1) blockade with anti-vascular endothelial growth factor (VEGF) therapy, established itself as the standard first-line regimen following the landmark IMbrave150 trial, with median overall survival of approximately 19.7 months. Durvalumab plus tremelimumab (STRIDE), a dual immune checkpoint inhibitor regimen, has emerged as an alternative first-line option with unprecedented long-term survival data. Emerging combination strategies include PD-1 inhibitors paired with multitargeted TKIs, bispecific antibodies, and novel therapeutic approaches. Network meta-analyses and real-world evidence suggest comparable efficacy among these regimens, with differential safety profiles facilitating individualized treatment selection. However, significant challenges persist, including the lack of reliable predictive biomarkers for patient stratification, with only approximately one-third of patients responding to current regimens. Emerging biomarkers such as circulating tumor DNA dynamics, interferon-γ signaling signatures, imaging-based radiomic features, and machine learning-based prognostic models show promise in predicting treatment response. The optimal integration of combination immunotherapy with locoregional therapies such as transarterial chemoembolization and radiotherapy remains an area of active investigation. This review synthesizes current evidence on targeted therapy combined with immunotherapy for advanced unresectable HCC, emphasizing combination treatment strategies, comparative efficacy, predictive biomarkers, and future…
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creator: Gaoxiong Tan
creator: Wenyong Feng
creator: Deren Yang
creator: Jian Pu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 83
ending page: 91
doi: 10.54097/kk0j7n02

From “Anti-inflammatory Medicine” to Public Resource: Antibiotic Culture, Intergenerational Memory, and the Ethics of AMR Governance in China
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description: The abuse of antibiotics in China cannot be considered solely a consequence of the scientific illiteracy of the population. On the contrary, one needs to look at this phenomenon in the context of historically developed “antibiotic culture” which can be seen through history. From penicillin as a symbol of modern medicine and national salvation to the role of barefoot doctors and primary health care in the distribution of antibiotics in rural China to the liberalization of health care following Reform and Opening-up, antibiotics have increasingly become for many people “effective anti-inflammatory medicines.” Due to the cultural memory, different generations perceive disease, infection, doctors, and pharmacies differently. However, in the wake of the growing antimicrobial resistance crisis that poses a threat to the public health globally, antibiotics have been re-conceptualized as resources requiring collective effort in its preservation. This creates ethical dilemmas both in terms of misuse reduction and providing access to reliable and affordable treatment for those who still need antibiotics. The essay will discuss possible solutions to these dilemmas.
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creator: Jingyi Yang
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 346
ending page: 356
doi: 10.54097/skrqgp45

Advances in Dual-Crosslinking Strategies for Hydrogels: From Physical-Chemical Synergy to Stimuli-Responsive Control
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description: Population aging and the rising burden of trauma and chronic disease have increased the demands placed on biomedical hydrogels. In addition to biocompatibility, these materials are expected to provide mechanical support, processability, and environmental responsiveness. A single crosslinked network rarely balances all of these requirements. Dual-crosslinked networks, which combine reversible physical interactions with stable chemical bonds, have therefore received increasing attention. This review examines the network-forming mechanisms of dual-crosslinked hydrogels, with emphasis on how crosslinking density, degree of oxidation, and energy-dissipation structures affect mechanical behavior. Strategies for pH-, temperature-, light-, and redox-responsive functions and the corresponding characterization methods are also summarized. Available studies indicate that a suitable combination of two crosslinking mechanisms can improve strength, toughness, and tissue adhesion while retaining injectability, self-healing, and stimulus responsiveness to varying degrees. We further discuss translational barriers, including degradation-rate matching, coupling among performance parameters, and scale-up. This review is intended to support the structural design of hydrogels for tissue regeneration, drug delivery, and flexible bioelectronics.
subject: Articles
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creator: Xunwei Gan
creator: Lianyong Wang
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 334
ending page: 345
doi: 10.54097/8z2zv618

Research Progress on the Gut–Brain Axis in the Pathogenesis and Progression of Alzheimer’s Disease
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description: Memory impairment and broader cognitive decline emerge gradually in Alzheimer’s disease (AD), although amyloid-β deposition, tau abnormalities, and neuroinflammatory changes often develop well before the clinical picture is fully established. Drug therapy can lessen selected symptoms, but it does not prevent continuing neuronal loss, and its long-term value is further limited by adverse effects and inadequate delivery across the blood–brain barrier. These shortcomings have increased interest in the microbiota–gut–brain axis (MGBA) as a framework for studying how intestinal biology may influence the brain. In this framework, microbial products and host responses are transmitted through vagal, endocrine, immune, and metabolic routes, while central nervous system activity can in turn alter intestinal conditions. This review evaluates those reciprocal pathways and discusses the roles of the hypothalamic–pituitary–adrenal axis, inflammatory signaling, short-chain fatty acids, tryptophan-derived metabolites, and trimethylamine N-oxide. It then examines microbial diversity and composition in AD and considers evidence for probiotics, fecal microbiota transplantation, and lifestyle-based intervention. Reports of dysbiosis before overt cognitive decline suggest that microbial change may participate in early disease development rather than simply accompany advanced pathology. That possibility remains unproven because most mechanistic evidence comes from animal models and much of the human literature is cross-sectional. Differences in cohort selection, sampling, and control of confounding variables further weaken causal interpretation. Longitudinal cohorts, integrated multi-omics analysis, and clinically meaningful patient stratification will therefore be essential for determining whether the MGBA can be used in AD prevention or treatment.
subject: Articles
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creator: Yujie Gao
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 323
ending page: 333
doi: 10.54097/8yaq6q43

Analysis of P-wave Morphology Changes and Related Influencing Factors during PICC Catheterization in Tumor Patients Using Intracavitary Electrocardiographic Monitoring Localization Technology
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description: Objective To explore the changes in P-wave morphology during peripherally inserted central catheter (PICC) placement under intracavitary electrocardiographic (ECG) monitoring and analyze the related influencing factors. Methods A total of 180 patients who underwent PICC procedures at a tertiary cancer hospital in Shandong Province from December 2025 to May 2026 were selected as the study subjects. All patients underwent catheterization guided by intracavitary ECG monitoring, and their ECG monitor's lead II was observed to record characteristic high-spike P-waves, double-peaked P-waves, and the extraction rate and positioning accuracy of bidirectional P-waves. Univariate analysis of variance (ANOVA) and multivariate linear regression analysis were used to investigate the influencing factors of intracavitary ECG P-waves. Results All 180 patients completed PICC placement, and intracavitary ECG monitoring was performed after catheterization. The results indicated that the top two factors affecting intracavitary ECG P-wave changes were characteristic high-spike P-waves and bidirectional P-waves in lead II, accounting for 93.87% and 85% respectively. Univariate ANOVA revealed that patient height, gender, baseline P-wave amplitude, and catheterization site were associated with changes in intracavitary ECG P-waves (P < 0.05); multivariate linear regression analysis showed that patient baseline P-wave amplitude and catheterization site had significant effects on intracavitary ECG P-waves (P < 0.05). Conclusion The application of intracavitary ECG monitoring for PICC placement can reduce radiation hazards, is safe, low-cost, and holds positive significance and broad application prospects.
subject: Articles
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creator: Jie Liu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 79
ending page: 82
doi: 10.54097/he124x80

Research Progress on Perioperative Thirst Management in Patients Undergoing Gastrointestinal Tumor Surgery
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description: This article provides an overview of the thirst issue faced by patients undergoing gastrointestinal tumor surgery during the perioperative period and its management strategies. Gastrointestinal tumors are one of the most common types of cancer globally, with surgical resection being the preferred treatment method. Postoperative thirst is a commonly overlooked issue in perioperative management, yet it significantly impacts patient recovery and satisfaction. By optimizing preoperative fluid intake, adopting combined anesthesia techniques, and implementing real-time fluid replenishment strategies, patients' thirst can be effectively alleviated. Furthermore, early postoperative oral fluid intake and multimodal pain control strategies are equally crucial for improving patients' quality of life and accelerating the recovery process. This article presents a series of evidence-based recommendations aimed at improving perioperative management for patients undergoing gastrointestinal tumor surgery.
subject: Articles
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creator: Jie Liu
creator: Mingzhe Li
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 75
ending page: 78
doi: 10.54097/g7bv1g24

Research Progress on the Mechanism of Action of Modern Anesthetic Drugs
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description: Anesthesiology, as an important part of the modern surgical system, is widely applied in surgical operations, first aid, cardiopulmonary resuscitation, as well as the research and treatment of pain and many other fields. This article is mainly divided into the following sections; Objective: By summarizing the action mechanisms of diverse anesthetics, this article explores the functional mechanisms and existing limitations of contemporary anesthetics, alongside current improvement strategies and research directions proposed to tackle these drawbacks. Methods: Systematically elaborate from the perspective of mechanism of action. Result: Every drug has its own target receptors. Conclusion: The Necessity of Combining Intravenous Anesthesia with Inhalation Anesthesia and the demand for the development of new anesthetics.
subject: Articles
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creator: Hanting Wang
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 70
ending page: 74
doi: 10.54097/vr65x147

Applications of Artificial Intelligence in Traditional Chinese Medicine
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description: Traditional Chinese medicine (TCM) represents a valuable part of Chinese cultural heritage. It is characterized by complex compositions and multiple therapeutic targets, which pose significant challenges to its modernization research. In recent years, the rapid advancement of artificial intelligence (AI) has enabled flexible, data-driven approaches that are now widely applied in TCM studies, including active ingredient analysis, quality control, and safety evaluation. This article reviews recent applications of AI in the TCM field, focusing on several key aspects: the advantages of graph neural network-based network pharmacology in analyzing multi-target interactions; computer vision and hyperspectral imaging for automatic medicinal material identification and quality grading; multimodal fusion techniques for component content detection and production process quality control; and graph attention networks and heterogeneous network representation learning for predicting TCM toxicity and assessing potential risks associated with combined use of Chinese and Western medicines. Based on a narrative review of the latest literature, this paper identifies current challenges such as data standardization and the lack of interpretability in model computation processes. Finally, it offers perspectives on how AI can support the standardization, precision, and global promotion of TCM.
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creator: Xinyi Zhao
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-28
publication date: 2026-08-28
starting page: 60
ending page: 69
doi: 10.54097/hew4m638

Exploration of Remote Nutrition Intervention for Metabolic Diseases Supported by Multimodal Dietary Data
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description: The prevalence rate of metabolic syndrome, type 2 diabetes and dyslipidemia in adults in China continues to rise, and the affected population is becoming younger. Nutritional intervention is a key measure for the control of metabolic chronic diseases. Traditional offline guidance is constrained by time and space, and dietary data relies on subjective recollection, which has shortcomings such as large errors and insufficient personalization. This article aims to explore new intervention pathways that are suitable for long-term management of chronic diseases. This study integrates multi-dimensional data on diet, physiology, metabolism, and behavior, relying on image recognition, wearable devices, and cloud technology, to build a remote nutrition intervention system that integrates data collection, intelligent analysis, individualized intervention plans, and online follow-up and guidance. Combining authoritative monitoring data and scientific research achievements, the architecture and application path are sorted out. The results confirm that multimodal data can overcome the inherent limits of traditional nutritional interventions and effectively improve the level of dietary management and the effectiveness of chronic disease control. This model is suitable for the development needs of primary healthcare and can provide theoretical and practical support for digital remote nutrition management of metabolic diseases.
subject: Articles
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creator: Yue Wang
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 316
ending page: 322
doi: 10.54097/31wjja40

The effection of gene variation in Familial
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description: Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated levels of low-density lipoprotein cholesterol (LDL-C) in the blood, which increases the risk of atherosclerotic cardiovascular diseases (ASCVD). It is usually accompanied by tendinitis xanthomatosis and a family history of early-onset coronary heart disease. Mutations in LDLR, PCSK9, and APOB are the main pathogenic basis of FH. Although there have been many studies on FH in recent years, there has been no clear summary of the mutation types in the population, thus making it impossible to conduct targeted screening and medication for different FH patients. This review conducts an in-depth analysis of the distribution of mutations in the LDLR, PCSK9, and APOB genes, the impact of LDLR, PCSK9, and APOB mutations on FH, and summarizes the main mutation types of these three genes in different populations. This can further summarize the genetic basis of FH and provide a strong basis for the subsequent development of treatment strategies targeting specific mutation types.
subject: Articles
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creator: Ziwen Zhao
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 311
ending page: 315
doi: 10.54097/pq337c45

Neuroimaging Evidence of Acupuncture Treatment for Depression Over the Past Decade: A Systematic Review
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description: This systematic review aims to synthesise evidence from neuroimaging studies to illustrate that acupuncture does have measurable multi-target central actions for major depressive disorder (MDD) treatment. The key mechanisms identified in studies over the past decade, using fMRI, PET and EEG, are: Acupuncture reduces hyperconnectivity of the default mode network (DMN) and increases its anti-correlation with the salience network. In task-based imaging, there is observed reduction in hyperactivity in the amygdala in conjunction with an increase in activity in the dorsolateral prefrontal cortex. Morphometric analyses showed that sustained EAc caused an increase in gray matter in the hippocampus and prefrontal cortex. PET studies have been reported to show alterations in serotonin transporter (SERT) binding and opioid receptor (OR) availability in the limbic system following treatment. So far, although there have been a lot of clinical evidence showing the antidepressant effects of acupuncture, the neurobiological understanding of acupuncture’s effects remained unclear. Existing studies suggest that there are potential neural modulation targets to consider for the pathophysiology of MDD, such as dysregulated neurotransmission, and corticolimbic connectivity; however, there have been some limitations in the studies, with small sample sizes, heterogeneous protocols, and relatively short follow-up. Further multicenter randomized controlled trials involving longitudinal imaging will be required to determine definite mechanistic and clinical standards.
subject: Articles
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creator: Jia Sun
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 303
ending page: 310
doi: 10.54097/660g1733

The Application of Anti-inflammatory Diet Patterns in Weight Control of Obese Population: Mechanism and Clinical Manifestations
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description: Obesity is now a serious public health problem worldwide, which is closely related to chronic low-degree inflammation and metabolic disorders. Over recent decades, people have been paying increasing attention to the anti-inflammatory diet in obesity management. This review summarizes the potential mechanism and clinical effect of anti-inflammatory diet in weight control of obese people. The relevant research on the anti-inflammatory diet pattern, mainly the Mediterranean diet (Med) and Dietary Approaches to Stop Hypertension (DASH) were analyzed. Current studies show that anti-inflammatory dietary patterns are very useful to improve obesity by reducing the level of inflammatory factors, enhancing insulin sensitivity, improving adipose tissue function, regulating intestinal microbiota and promoting energy metabolism. In addition, some clinical studies suggest that long-term adherence to an anti-inflammatory diet is linked to lower body mass index (BMI), and it can reduce visceral adipose tissue (VAT) accumulation and improve metabolic health. These findings show that an anti-inflammatory diet may help control weight and prevent obesity-related complications. Overall, an anti-inflammatory diet provides a practical and sustainable way to prevent and manage obesity. However, the optimal components of anti-inflammatory diets and their effects in different populations remain unclear. Research needs to be further carefully designed, with larger populations and longer-term follow-up periods to provide stronger evidence for its clinical application.
subject: Articles
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creator: Jingyi Dong
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 297
ending page: 302
doi: 10.54097/8rgmhv87

Engineering Probiotics for Serotonin Production as a Potential Adjunctive Therapy for Depression
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description: Depression remains the main cause affecting global mental health, but current drug treatments are often limited by slow onset and significant side effects. As a potential alternative, we explored the possibility of programming bacterial hosts to directly synthesize serotonin (5-HT) in the gut. To this end, we constructed a synthetic operon containing tryptophan hydroxylase (TPH) and tryptophan decarboxylase (TDC) genes, which were fused by overlapping PCR and inserted under the control of the trc promoter in the pTrc99k plasmid. After transforming the plasmid into E. coli BL21 (DE3), we drove gene expression by gradient regulating IPTG concentration within the range of 0 to 10 mM. The SDS-PAGE electrophoresis results showed that both protein bands significantly increased with the increase of IPTG concentration and reached a plateau at approximately 5 mM. These results confirm that the dual enzyme 5-HT production module can operate normally in laboratory strains. However, applying this design to the field of probiotics is still a necessary next step, and we must further verify its actual production in the intestine.
subject: Articles
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creator: Qinhan Liu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 291
ending page: 296
doi: 10.54097/v0qgpb63

Economic Feasibility and Ecological Effects of Alternative Protein Feeds: Input Evidence and Subsequent Environmental Impacts of Fish and Other Farmed Animals
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description: The large-scale production of traditional fish and farmed animal feed is causing increasingly severe resource consumption and greenhouse gas emissions, and alternative protein feed is seen as a potential solution to alleviate the above environmental pressures. However, the existing technology and research are still immature in terms of environmental assessment methods and cost control systems. This paper discusses the economic feasibility and ecological effect of alternative protein feed, life cycle assessment and economic feasibility through integrated analysis. The results show that the core dilemmas faced by alternative protein feed at present include: due to the supply of raw materials and production scale, its cost competitiveness is still weaker than that of traditional feed; In terms of ecological effects, although the performance of greenhouse gas, land and water resources indicators is better than that of traditional protein, there are phenomena of environmental burden transfer such as energy consumption transfer, land occupation transfer and nutrient transfer; In addition, regulations and market access barriers also restrict its promotion. Overall, alternative proteins have shown economic potential in specific scenarios, but do not yet have the conditions to fully replace conventional feeds. Future research should focus on cost control, raw material selection, technological innovation and policy guidance to promote alternative protein feeds from experimental stage to large-scale application.
subject: Articles
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creator: Yiming Bian
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 285
ending page: 290
doi: 10.54097/8yfjdc96

Replacing Fetal Bovine Serum with Food Processing Byproducts in Culture Media for Cultured Meat – a Sustainable Development Path
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description: With increasing population and worsening environmental pollution, cultured meat is considered a promising protein source. However, current cultured meat production faces significant challenges, primarily due to the high cost of fetal bovine serum (FBS), a widely used culture medium. In recent years, widely available and abundant food processing byproducts have gained attention, considered as potential alternatives to FBS. This review summarizes three representative food processing byproducts: grain processing byproducts (okara), dairy processing byproducts (whey), and oil processing byproducts (soybean meal). The review first introduces the global annual production and current processing methods of these byproducts. It then discusses the key components in these byproducts that promote cell growth and proliferation. Based on existing experimental data, the application effects of these three food processing byproducts are described. Finally, considering environmental factors, extraction costs, and application effects, the potential of these three types of food processing byproducts as FBS substitutes is comprehensively evaluated, providing a theoretical reference for developing efficient and stable serum alternatives.
subject: Articles
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creator: Xinyu Liu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 279
ending page: 284
doi: 10.54097/p85eqy58

Progress on Molecular Mechanism of Disulfide Death in Gastric Cancer and its Clinical Targeted Treatment Strategy
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description: Disulfide death is a newly discovered regulatory cell death mode in 2023, which is driven by the high expression of SLC7A11 and glucose starvation, and is characterized by the collapse of actin skeleton. It shows great potential in the targeted treatment of gastric cancer. This paper systematically reviewed the molecular mechanism of disulfide death, summarized the research progress of disulfide death related genes (DRGs) in the prognosis evaluation, molecular typing and immune microenvironment regulation of gastric cancer, and discussed the targeted treatment strategy based on Glucose Transporter 1 (GLUT) inhibitor, SLC7A11 precise regulation and nano drug delivery system. The results showed that the DRGs related prognostic model can effectively predict the survival of gastric cancer patients, and its low-risk group often presents an "immune fever" phenotype, while the GLUT inhibitor bay-876 has been confirmed in preclinical models to induce disulfide death and inhibit tumor growth. However, the field still faces challenges such as the lack of specific detection markers, functional studies mostly stay in correlation inference and lack of causal mechanism verification. The further research need to analyze the real role of disulfide death in the tumor microenvironment with the help of single-cell and space omics technology, and accelerate the clinical transformation process by carrying out clinical trials with SLC7A11 expression level as a hierarchical marker.
subject: Articles
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creator: Yujie Liu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-27
publication date: 2026-08-27
starting page: 273
ending page: 278
doi: 10.54097/tp9knj46

Fragility and Plasticity of CCR8+Tregs: Providing New Directions for Cancer Treatment
type: item
description: Regulatory T cells (Tregs) are crucial for maintaining immune homeostasis. However, in the tumor microenvironment, tumor cells induce Tregs to exert immunosuppressive effects, leading to the failure of anti-tumor immunity. Traditional Treg clearance strategies, due to their lack of selectivity, damage peripheral normal Tregs during treatment, causing severe autoimmune side effects. This article analyzes the biological characteristics, fragility, and plasticity of CCR8+Tregs and their molecular mechanisms. The results show that CCR8+Tregs are specifically highly expressed on tumor-infiltrating Tregs, and after binding to the C-C Motif Chemokine Ligand 1 (CCL1), they maintain the stability of the Foxp3 transcriptional complex through the PI3K/AKT signaling axis. Blocking CCR8 signaling can trigger FOXO1 nuclear export and inhibit c-MAF expression, inducing IFN-γ-dependent fragility in Tregs. This fragility is the molecular basis of its functional plasticity, which can drive Tregs to reprogram to a Th1-like pro-inflammatory phenotype, thereby reshaping the TME from inhibition to activation. In summary, targeting the fragility and plasticity of CCR8+Tregs holds promise for achieving precise immune regulation, providing new insights for optimizing combined immunotherapy for tumors.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Yuhao He
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 267
ending page: 272
doi: 10.54097/1aye9c25

Role of Epidemic Tumor Vaccine in Cold Tumors to Hot Tumors
type: item
description: Small cell lung cancer (SCLC) is a type of highly aggressive, prone to early metastasis and recurrence, neuroendocrine malignant tumor. The treatment effect of second-line therapy for patients with recurrence/refractory cases is limited, and new therapeutic targets and strategies are urgently needed. Delta-like ligand 3 (DLL3) is abnormally highly expressed on the surface of most SCLC cells, while its expression is limited in normal tissues, making it a promising therapeutic target. The DLL3/CD3 bispecific antibody can redirect T cells to the vicinity of the tumor, inducing the formation of immune synapses, T cell activation, and tumor cell lysis. Tarlatamab, as the first bispecific antibody targeting DLL3/CD3 to enter clinical trials and obtain regulatory approval, has completed the transformation from preclinical validation to key clinical studies. Studies have shown that tarlatamab has durable anti-tumor activity and manageable safety in patients with recurrent/refractory SCLC. This article reviews the biological basis of DLL3, the mechanism of action of DLL3/CD3 bispecific antibodies, as well as the preclinical and clinical research progress of tarlatamab, and assesses its efficacy and safety in heavily treated SCLC. Overall, DLL3/CD3 bispecific antibodies provide a new immunotherapy pathway for recurrent/refractory SCLC, achieving significant clinical relief and survival improvement. Future research needs to further optimize toxicity management, analyze resistance mechanisms, and screen for advantageous populations to promote its precise and sustainable clinical application.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Chunqing Liu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 261
ending page: 266
doi: 10.54097/1p0ss824

The Metabolic Reprogramming of Immune Cells in the Tumor Microenvironment and the Mechanism of Immune Therapy Resistance
type: item
description: The efficacy of immune checkpoint inhibitors (ICIs) is often limited by primary and acquired resistance induced by the tumor microenvironment (TME), with the metabolic reprogramming of immune cells being the core mechanism. This review systematically analyzes the three key metabolic stresses in the TME: glucose deprivation, lactate accumulation, and adenosine accumulation. How these metabolic stresses, by reshaping the metabolic states and functions of T cells, macrophages, and dendritic cells, jointly construct an immunosuppressive ecosystem and lead to ICIs resistance. Glucose deprivation directly weakens the activation and function of effector T cells, while lactate and adenosine further inhibit effector immune cells and support the functions of immunosuppressive cells such as regulatory T cells and M2-type macrophages, ultimately forming a treatment-tolerant microenvironment. The article further explores therapeutic strategies targeting metabolic nodes such as lactate dehydrogenase A (LDHA), CD73/CD39 - adenosine axis, to reverse immunosuppression and enhance the efficacy of ICIs, and looks forward to the future direction of using "metabolism-immunity" typing to guide individualized combination therapy.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Ganyu Yi
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 256
ending page: 260
doi: 10.54097/60qcx819

CRISPR/Cas9-Mediated PD-1 Engineered T Cells: New Strategy to Block Tumor Immune Escape
type: item
description: At present, overexpression of immune-related genes is one of the key mechanisms of tumor immune evasion. As a tumor cell-mediated immune escape core checkpoint molecule, the PD-L1 (programmed death ligand 1) will recruit SHP-1/SHP-2 (Src homology phosphotyrosyl phosphatase 1/ Src homology phosphotyrosyl phosphatase 2) phosphatase by interacting with PD-1 (Programmed Death 1) on T cells' surface, dephosphorylation of key molecules of the downstream signaling pathway of T cell receptors (TCR) (such as CD3ζ, ZAP70, PI3K/Akt), thereby inhibiting T cell expansion, cytokine secretion, cytotoxic particle release, and metabolic reprogramming. Eventually, it leads to T cell failure or apoptosis and directly inhibiting the anti-tumor function of T cells. Today, existing immune checkpoint blockade still has some problems during treatment, such as some patients do not respond or lose their efficacy due to drug resistance. According to the basic principles of PD-1 immune escape and the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9) system, this paper explores the mechanism and advantages and disadvantages of the CRISPR/Cas9 technique in PD-1 expression inhibition combined with existing research, so as to provide a theoretical basis, summarize the shortcomings and future prospects for tumor immunotherapy Page layout.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Weiyang Xu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 252
ending page: 255
doi: 10.54097/edfqwy74

Protein Phase Separation and Regulatory Mechanisms of Transcriptional Programming in Tumor Microenvironment in Stress Response
type: item
description: Malignant tumor evolution is governed by its symbiotic relationship with the tumor microenvironment, which features steep oxygen and acidity gradients that drive malignant progression. Traditional biochemical frameworks fail to adequately explain the rapid, coordinated genomic alterations under such stresses. This review focuses on liquid-liquid phase separation (LLPS), which acts as a biophysical switch regulating transcriptional programming. The study demonstrates that tumor microenvironmental stress directly modulates the phase behavior of intrinsically disordered proteins, forming transcriptional condensates. These condensates partition transcriptional machinery, condense super-enhancer regions, and amplify oncogenic expression. Key factors analyzed include c-Myc and YAP, establishing a physical environment–LLPS–transcriptional program axis that mediates tumor adaptation. Additionally, condensed-state physical properties induce non-genetic heterogeneity and chemotherapy resistance. This work introduces a novel therapeutic strategy combining molecular antagonism with physical state intervention, offering new approaches for previously intractable transcriptional drivers. It also underscores the value of measuring protein aggregate dynamics in improving prognosis for advanced malignancies.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Xingjian Luo
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 246
ending page: 251
doi: 10.54097/xnpyyv51

Research on the Regulation of RNA by Traditional Chinese Medicine to Alleviate Chemotherapy Side Effects
type: item
description: Chemotherapy is the main treatment for tumors; however, its side effects, like bone marrow suppression, gastrointestinal reactions, and neurotoxicity, can seriously impact the patient's quality of life and the treatment process. Traditional Chinese medicine (TCM), which possesses the advantages of multi-component, multi-target, and overall regulation, appears quite promising in relieving the side effects brought about by chemotherapy.However, the molecular operating mechanism of it has not been fully figured out yet.In recent years, non-coding RNAs (including miRNAs, lncRNAs, and circRNAs) have been confirmed to play a key regulatory role in cell proliferation, apoptosis and damage repair and other aspects, thus providing a new perspective for us to understand the mechanism of chemotherapy-related adverse reactions. This article systematically reviews the research progress of how TCM active ingredients (such as ginsenosides, astragaloside IV and curcumin and the like) reduce chemotherapy side effects by regulating specific RNA molecules and regulating related signaling pathways, including protecting bone marrow hematopoiesis, reducing gastrointestinal toxicity and relieving neurotoxicity and the like. This article further delves into the challenges currently encountered in this domain and also envisions the future direction of precise TCM intervention combined with technologies like high-throughput sequencing and gene editing, with the purpose of offering a theoretical basis for integrating traditional Chinese and Western medicine in cancer supportive care.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Zixi Di
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 238
ending page: 245
doi: 10.54097/67z41q93

Bortezomib and autoimmune hemolytic anemia: a systematic review and meta-analysis
type: item
description: Conventional treatments for autoimmune hemolytic anemia (AIHA) are associated with drawbacks including high recurrence rates and limited therapeutic efficacy. As a proteasome inhibitor, bortezomib demonstrates potential value in relapsed/refractory AIHA, yet existing evidence mostly consists of small-sample case reports without quantitative integrated analyses. The results of this meta-analysis revealed that the pooled overall response rate (ORR) of bortezomib for AIHA was 81% (95%CI: 0.71–0.92), with extremely low inter-study heterogeneity (I²=0.0%, P=0.950). After excluding 2 conference abstracts, the pooled ORR of the remaining 4 full-text studies reached 82% (95%CI: 0.69–0.94), and leave-one-out sensitivity analysis identified no single study exerting a significant impact on the overall conclusions. Current evidence indicates that bortezomib can serve as a second-line salvage therapy for relapsed/refractory patients. However, the included studies were predominantly single-arm retrospective small-sample trials, lacking long-term safety data, failing to differentiate therapeutic effects between warm-type AIHA and cold agglutinin disease subgroups, and containing no controlled trials for direct comparisons with conventional regimens. In conclusion, bortezomib delivers stable efficacy and acceptable tolerability in relapsed/refractory AIHA. Large-sample, multicenter, prospective controlled studies are still required to clarify the optimal administration regimen, eligible patient populations and long-term safety profiles.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: YuXuan Li
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 229
ending page: 237
doi: 10.54097/j43d1z38

Screening of Key Biomarkers and Molecular Mechanisms of Major Depressive Disorder Based on Multi-Cohort Transcriptomic Data
type: item
description: Purpose: Major depressive disorder (MDD) is a highly heterogeneous psychiatric disorder with a complex etiology. Its molecular pathological mechanisms are not fully understood. To identify stable biomarkers with potential clinical value and explore their associated molecular pathways, we performed a systematic bioinformatic analysis of three publicly available transcriptomic datasets. Methods: Three expression profile datasets related to major depressive disorder (MDD)—GSE54562, GSE54572, and GSE54568—were retrieved from the Gene Expression Omnibus (GEO) database. After normalization, we performed a differential expression analysis on each dataset and visualized the results using box plots, principal component analysis (PCA), and heat maps. The first dataset underwent further analysis using GO, KEGG, and GSEA enrichment. Then, a protein-protein interaction (PPI) network was constructed using the STRING database. The second and third datasets were then used to validate the candidate features independently. Results: In the first dataset, the major depressive disorder (MDD) and control groups exhibited distinct overall expression patterns, and normalization was effective. Differential analysis identified several markedly dysregulated genes. Among them, SPP1, GLDN, and MEIS1 were upregulated in the MDD group, while MORN4, PCBP3, and SORCS1 were downregulated. Gene ontology (GO) enrichment analysis revealed that the differentially expressed genes were primarily associated with the myelin sheath, compact myelin, and gap junctions. KEGG analysis revealed significant enrichment of the phospholipase D (PLD) signaling pathway and several amino acid metabolism pathways. GSEA also indicated aberrant activation of oxidative phosphorylation, processes related to reactive oxygen species, the phagosome, antigen processing and presentation, ferroptosis, and multiple immune-inflammatory pathways. The PPI network revealed interaction modules centered on myelin structural and membrane …
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Jie Fang
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 216
ending page: 228
doi: 10.54097/y8rfr285

The Application of Gut Microbiota in the Diagnosis, Prognosis and Treatment of Colorectal Cancer
type: item
description: The gut microbiota plays a significant role in the occurrence and development of colorectal cancer (CRC), and its application value in the diagnosis and treatment of CRC has received extensive attention in recent years. The gut microbiota has shown great potential as a non-invasive biomarker and therapeutic target in CRC. However, existing reviews mostly focus on mechanism descriptions and lack systematic analysis of clinical translation barriers. This article focuses on CRC and systematically reviews the research progress of the microbiota as a diagnostic biomarker, prognostic biomarker, and therapeutic target, and emphasizes the discussion of translation barriers and solutions. In terms of diagnosis, fecal microbiota testing faces the lack of standardization and interference from confounding factors. About prognosis, the unclear causal relationship and insufficient standardization of bioinformatics limit clinical application. In terms of treatment, fecal microbiota transplantation and probiotics and other intervention strategies are limited by individual variability, regulatory barriers, and insufficient strain specificity. This article proposes three major solution paths: standardization construction, multi-omics integration, and precise intervention, providing a reference for the clinical translation of microbiota research results.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Jingyi Sun
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 209
ending page: 215
doi: 10.54097/d6f9xy38

Research on Foot Function Adaptation and Injury Prevention from the Perspective of Sports Biomechanics
type: item
description: Due to frequent exercise during the offseason, some damage has developed in the structure and function of the feet, and the risk of overuse injuries in sports has increased. Systematically explore the functional adaptation characteristics, biomechanical mechanisms, and dialectical relationship with injury risk in the three areas of the midfoot, lateral foot and heel from the perspective of sports biomechanics in this study. The three levels of the damage prevention framework in this paper are training interventions, equipment interventions and monitoring and evaluation. This paper provides a theoretical basis for the regional-specific patterns and bidirectional effects of functional adaptation, offering evidence-based support for training load planning, shoe design and scientific management of injury risk in practice.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Junxi Luo
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 195
ending page: 200
doi: 10.54097/73wvce07

Feature Selection for Autism Spectrum Disorder via a Multi-Pack Cooperative Grey Wolf Optimization Framework
type: item
description: Autism Spectrum Disorder (ASD) is a prevalent neurodevelopmental condition in childhood and adolescence. However, its heterogeneous genetic mechanisms make early diagnosis particularly challenging. Identifying robust molecular biomarkers from high-dimensional gene expression data remains a critical bottleneck. In this study, we proposed the Multi-pack cooperative grey wolf optimization (MPC-GWO) algorithm to select robust gene biomarkers for ASD using two public blood-based transcriptomic datasets (GSE25507 for training, GSE18123 for independent testing). MPC-GWO was applied to GSE25507 to identify the minimal gene subset that reliably discriminated ASD from controls. The selected biomarker genes were then evaluated on GSE18123 to test cross-dataset generalizability. After statistical preselection and MPC-GWO refinement, we identified a 24-gene signature that achieved superior classification performance on the discovery cohort (accuracy=0.808, AUC=0.823), outperforming both the all-features baseline (accuracy=0.713) and filter-based t-test selection (accuracy=0.678). Compared with LASSO (accuracy=0.732, AUC=0.756) and Random Forest (accuracy=0.678, AUC=0.737), MPC-GWO demonstrated superior classification performance. The algorithm reduced the feature set by >88% and converged within 50 iterations. On the independent cohort, the signature achieved accuracy=0.674 and AUC=0.733. Functional enrichment analysis revealed that the selected genes are strongly associated with nervous system development, Ig-like C2-type, neurodevelopmental disorders, and extracellular space, most of which have been repeatedly implicated in ASD. These results demonstrate that MPC-GWO is effective for ASD biomarker discovery. The identified gene signature showed improved classification accuracy, and its enriched biological functions provided insights into ASD-related molecular mechanisms, suggesting potential value for future ASD-related genomic research and non-invasive diagnostic exploration.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Alicia Fei
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 183
ending page: 194
doi: 10.54097/67bnyv59

The CD155-TIGIT Signaling Axis in NK Cell Immune Evasion in Tumors: Mechanisms, Synergy with TGF-β, and Combined Intervention Strategies
type: item
description: Although significant progress has been made in cancer immunotherapy, the issue of immune resistance has become an increasingly important issue. NK cell dysfunction is the key factor contributing to poor treatment response. The CD155-TIGIT signaling axis serves as the core pathway mediating tumor cell immune evasion, however, the outcome of clinical trials concerning about T cell immunoreceptor with Ig and ITIM domains (TIGIT) blockade alone in Phase III settings has failed to meet expectations. It suggests the existence of synergistic inhibitory mechanisms. This review systematically integrates and finds that TGF-β not only directly suppresses NK cell function but also upregulates cluster of differentiation 155 (CD155) expression on tumor cells through both classical and non-classical pathways. Therefore, it is able to amplify TIGIT-mediated negative signaling. More notably, a positive feedback loop may exist between CD155 and TGF-β, mutually reinforcing each other to form an immunosuppressive circuit. The clinical challenges of TIGIT inhibitors highlight the need for combination intervention strategies. At present, the precise molecular mechanisms and general relevance of this feedback loop remain to be explored. Based on these gaps, this review discusses four key parts: the inhibitory effects of the CD155-TIGIT axis on NK cells; the dual suppressive mechanisms of TGF-β and their positive feedback loop; current clinical challenges in targeting these pathways; and combined intervention strategies of TIGIT/TGF-β bispecific antibodies. The aim is to provide theoretical guidance for optimizing NK cell-based cancer immunotherapy.
subject: Articles
  topic: section
subject: Array
  topic: keywords
creator: Shuyu Liu
rights: Copyright (c) 2026 https://creativecommons.org/licenses/by-nc/4.0
date: 2026-08-24
publication date: 2026-08-24
starting page: 176
ending page: 182
doi: 10.54097/ajfrv663