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The chemistry of 1,n-enynes, especially 1,4-enynes, represents a privileged scaffold in organic synthesis, constituting both the core structural units of numerous natural products and bioactive molecules and serving as a versatile substrate for diverse transition metal-catalyzed cyclization transformations. Over the past few decades, the synthesis of 1,4-enynes and their application in constructing fused and spirocyclic frameworks have attracted considerable research attention. These synthetic methods offer great promise for the assembly of diverse complex molecules, including pharmaceuticals, natural products, agrochemicals, and functional materials. In this review, recent advances in the synthesis of 1,4-enynes and their chemical transformations with diverse coupling reagents are summarized. Meanwhile, mechanistic studies, supported by experimental investigations, are discussed to illuminate the synergistic interactions governing bond formation. The practical utility of these methodologies is further demonstrated through their application in the synthesis of complex natural products and pharmaceutical intermediates, highlighting their potential for scalable and sustainable chemical manufacturing.

Microemulsion-based drug delivery systems are increasingly attracting attention in the pharmaceutical field owing to their remarkable capacity to enhance solubility, stability, and bioavailability, as well as enable targeted drug delivery. These systems comprise clear, stable, isotropic blends of oil, water, and surfactant, often accompanied by a co-surfactant. Their appeal to pharmaceutical scientists lies in their versatility as effective drug-delivery vehicles, accommodating a diverse array of drug molecules. Microemulsions have demonstrated effectiveness in protecting fragile drugs, controlling drug release, enhancing solubility, increasing bioavailability, and reducing variation in patient response. Moreover, formulations suitable for various routes of administration have been successfully devised. Since their discovery, microemulsions have gained prominence, becoming increasingly vital in both academic research and industrial settings due to their distinct characteristics, such as reduced interfacial tension, extensive interfacial area, thermodynamic stability, and the ability to solubilize otherwise immiscible substances. Transparent appearance, low viscosity, and inherent thermodynamic stability set microemulsions apart from conventional emulsions. This review aims to elucidate the potential of microemulsions as delivery vehicles and to provide insights into their formation principles. Additionally, it comprehensively explores microemulsion-based drug delivery systems, encompassing oral, topical, transdermal, ocular, and parenteral delivery methods, with a focus on recent advancements, existing challenges, and future trajectories.

Vinyl arenes are widely found in natural products, pharmaceuticals, and functional materials, and serve as important intermediates for the construction of complex molecular architectures. Among the various synthetic strategies available, transition-metal-catalyzed direct C-H olefination has emerged as a particularly concise and efficient alternative approach. Through the use of directing strategies and ligand modulation, both the regioselectivity and stereoselectivity of C-H bond cleavage can be precisely controlled. Among the available catalytic systems, palladium catalysts occupy a central position owing to their outstanding reactivity and broad applicability. In comparison, ortho-C-H functionalization has become relatively well established, whereas remote C-H functionalization remains underdeveloped due to the high-energy macrocyclic metallacyclic transition states involved, as well as factors such as conformational strain and steric hindrance. Current studies have primarily focused on directing-group design and substrate scope expansion, while other key issues have received comparatively limited attention. Building upon our group's research efforts in this area, this review systematically summarizes the recent advances, mechanistic insights, and applications of palladium-catalyzed directing-group-assisted meta-C-H olefination, with the aim of providing a useful reference for future developments in this field.

As sleep disorders and mental stress become increasingly prevalent, public demand for functional foods and health products that improve sleep quality and alleviate insomnia continue to rise. Accordingly, it is necessary to explore natural plants rich in sleep-modulating bioactive substances. Ziziphi spinosae semen (ZSS), the dried mature seed of Ziziphus jujuba Mill., is a well-known medicinal and edible material with sedative and hypnotic effects. It can be processed into various food products and serves as raw material for pharmaceuticals and cosmetics. The chemical constituents of ZSS, including fatty oils, saponins, and flavonoids, contribute to its sedative, anxiolytic, antidepressant, and anti-inflammatory activities. Therefore, ZSS boasts promising application prospects in the medicinal and food industries. Relevant literature was retrieved from Google Scholar, PubMed, and Web of Science. Data about chemical constituents, pharmacological effects, and product development of ZSS were systematically collected and analyzed. This review summarizes the chemical compositions and pharmacological activities of ZSS, and presents the latest progress in its product application. ZSS possesses abundant bioactive compounds and exerts prominent pharmacological activities. It holds great value in chronic disease prevention and treatment, and has been developed into various functional products. Further research is required to realize intensive and rational utilization of ZSS resources.

HER2 (ErbB2), a ligand-independent HER family member, regulates cell growth, differentiation, and survival. Its overexpression, gene amplification, and activating mutations are oncogenic drivers in multiple malignancies. The past two decades have witnessed transformative advances in HER2-targeted therapeutics, exemplified by tyrosine kinase inhibitors (TKIs), including first-generation reversible pan-HER (e.g., lapatinib), second-generation covalent pan-HER (neratinib, pyrotinib), and novel selective HER2 inhibitors (tucatinib, sevabertinib, zongertinib). Nonetheless, the extensive molecular heterogeneity in HER2 activation (e.g., dimerization, amplification) and mutation profiles (e.g., L755S, exon 20 insertions), combined with tumor-type-specific pathogenic mechanisms, poses significant challenges to precision oncology in clinical practice. Currently, numerous promising inhibitors in preclinical and clinical development hold potential for providing more effective treatment options. This review comprehensively summarizes recent advances in HER2-targeted TKIs and their emergent resistance mechanisms, further analyzing strategies to both mitigate off-target toxicity and overcome resistance through rational design of selective HER2 inhibitors. Collectively, these insights provide a roadmap for developing next-generation precision therapies in HER2-driven cancers.

Efficient delivery systems are essential for transporting chemotherapeutic agents to target sites, enhancing cellular uptake and reducing off-target side effects. Peptides, owing to their intrinsic biocompatibility and structural tunability, have emerged as promising carriers for delivering labile chemotherapeutics and improving pharmacokinetics and therapeutic outcomes. Along these lines, a wide variety of peptide-based delivery strategies have been developed to achieve desirable pharmaceutical properties for anticancer agents. Particularly, stimuli-responsive peptide-based nanocarriers have attracted high levels of attention due to their ability to exploit overexpressed or tumor-specific stimuli, enabling selective disassembly and controlled drug release within cancer cells. In this review, we highlight recent advances in the development of stimuli-responsive peptide nanocarriers and their applications in anticancer therapy, and discuss key challenges and future directions toward their clinical translation.

Colorectal cancer is a major global health concern, accounting for nearly 10% of all cancer deaths and causing over 900,000 deaths annually. Despite therapeutic advances, issues like poor drug bioavailability, systemic toxicity, and drug resistance persist. Chitosan, a naturally derived polysaccharide, has gained attention as a versatile nanocarrier for colorectal cancer therapy due to its pH responsiveness, mucoadhesiveness, and enzymatic biodegradability, which enable site-specific and controlled drug release. This review highlights recent progress in the design and functionalization of chitosan-based nanocomposites for targeted colon delivery. Approaches such as ligand-mediated targeting (e.g., folate, hyaluronic acid), enzyme-triggered systems, and smart hydrogels enhance tumor selectivity and therapeutic efficacy. Moreover, co-delivery systems integrating chemotherapeutics with gene modulators or immunotherapeutics offer solutions to tumor heterogeneity and drug resistance. Preclinical findings indicate improved bioavailability, tumor accumulation, and reduced systemic toxicity, while early clinical studies report favorable safety and pharmacokinetic profiles. Challenges including pH solubility and rapid clearance are being addressed through PEGylation, chemical grafting, and hybrid nanocomposites. Overall, chitosan's multifunctional nature positions it as a promising platform for next-generation, colon-targeted nanomedicine in colorectal cancer treatment.

With the rapid development of the mRNA pharmaceutical industry, Oligo(dT) chromatography, as a core step in mRNA separation and purification, has garnered increasing attention from both the industry and researchers. This article begins with the fundamental principles of mRNA affinity chromatography, analyzes the advantages and disadvantages of two typical affinity techniques, and highlights the sufficiency of Oligo(dT) chromatography as a platform technology. Aiming to the poor performance of the Oligo(dT) chromatography, the article reviews the main methods and mechanisms for enhancing its performance from three perspectives, resin structure, ligand structure, and process intensification. It also highlights the factors influencing the performance of Oligo(dT) chromatography and the challenges associated with these methods. The article provides an outlook on the future development directions of Oligo(dT) chromatography, offering insights for the advancement of next-generation Oligo(dT) chromatography resins and processes.

Nanostructured tungsten oxide (WO3) has emerged as a promising material for electrochemical sensing due to its high surface area, strong electrocatalytic activity, and efficient charge-transfer properties. This review presents recent advances in WO3-based nanocomposites, emphasizing their synthesis strategies, structural engineering, and performance in electrochemical sensing applications. The integration of WO3 with various functional nanomaterials has significantly enhanced sensitivity, selectivity, and detection limits for a wide range of chemical and biological analytes. Particular attention is given to the role of morphology, surface properties, and composite design in improving sensing efficiency. Furthermore, key challenges, including limited electrical conductivity, wide bandgap effects, and stability concerns, are critically discussed, along with comparisons to emerging sensing materials. Finally, future perspectives and research directions are outlined to support the development of robust, reliable, and high-performance WO3-based electrochemical sensors for environmental and biomedical applications.

Hypopharyngeal carcinoma (HPC) is an aggressive malignancy with poor prognosis due to difficult early diagnosis, frequent recurrence, and distant metastasis. Although surgery, radiotherapy, chemotherapy, and immunotherapy have progressed, accurate prognostic assessment and real-time monitoring remain limited. Liquid biopsy, a minimally invasive method detecting circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and microRNAs (miRNAs), shows promise in solid tumours, but its role in HPC is underexplored. A systematic search of PubMed, Embase, and Web of Science was conducted to September 2025 following PRISMA guidelines. Eligible studies evaluated ctDNA, CTCs, or miRNAs for diagnosis, treatment monitoring, or prognosis of HPC, reporting sensitivity, specificity, diagnostic odds ratio, or hazard ratio for meta-analysis. Twenty-four studies with 933 patients were included. Pooled estimates showed sensitivity 88.3% (95% CI: 84.7-91.6) and specificity 95.9% (95% CI: 93.3-97.9), with predictive intervals sensitivity 0.74-0.98 and specificity 0.85-1.00. Heterogeneity was moderate (I² sensitivity = 52.3%; specificity = 48.5%), and no publication bias was observed. Subgroup analyses indicated ctDNA was advantageous for treatment monitoring, CTCs were consistent in prognosis, and miRNAs were strong candidates due to stability and detection sensitivity. Sensitivity analyses confirmed robustness. Liquid biopsy shows strong potential for diagnosis, monitoring, and prognosis in HPC. Large-scale, multicentre studies are required to validate its clinical application and integration into patient-management pathways.

Dysregulation of the phosphatidylinositol-3-kinase (PI3K) - AKT/mTOR signaling axis is a major molecular driver of tumor initiation, progression, and therapeutic resistance across diverse cancers, underscoring the need for improved targeted therapies amid a rising global and Indian cancer burden. This comprehensive review critically summarizes advances from 2021-2025 in the design of selective PI3K inhibitors based on the 1,3,5-triazine (s-triazine) scaffold, emphasizing how its symmetric 2/4/6 substitution vectors, electron-deficient hinge-binding profile, and modular cyanuric chloride - enabled SNAr synthesis accelerate structure - activity relationship (SAR) optimization. Medicinal chemistry and biological evidence across multiple triazine chemotypes (benzoyl-hydrazide, thiophene/thiophenyl-arylurea, aminopyrimidine, dimorpholinyl, benzimidazole, phenylamino, and pyrazolyl derivatives) reveal convergent design rules: heteroaryl/aminopyrimidine hinge binders, pocket-filling hydrophobic arms, and solvent-exposed polar groups (notably morpholine/dimorpholine or sulfonyl piperazine) collectively improve potency, isoform selectivity, and cellular efficacy. Mechanistically, representative compounds induce G0/G1 arrest and apoptosis with suppression of p-PI3K/p-AKT and downstream markers, supported by docking/MD interactions frequently involving Val851 (hinge), Asp810, Lys802, and Gln859. Despite substantial progress, pharmacokinetic liabilities, resistance pathways, and isoform-associated adverse effects remain key barriers to translation. Future development should prioritize rational isoform targeting, hybrid/multitarget designs, systematic ADME refinement, and AI-driven SAR modeling to advance s-triazine PI3K inhibitors toward clinically feasible cancer therapeutics.

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Various acute and chronic disorders, such as cancer, neurological diseases, cardiovascular disorders, and arthritis, are linked to inflammation. However, the long-term utilization of the available anti-inflammatory medications is frequently restricted by side effects and inadequate selectivity, emphasizing the need for safer and more effective therapeutic agents. A thiazole scaffold emerged as a unique framework in medicinal chemistry owing to its prominent biological effectiveness and favorable pharmacokinetic characteristics. Recently, substantial interest has been gained by various thiazole-based derivatives as potential anti-inflammatory drugs. The thiazole-containing derivatives have exerted prominent anti-inflammatory effects via a variety of mechanisms, such as suppression of COX and LOX enzymes, inhibition of pro-inflammatory cytokines such as TNF-α and IL-6, as well as the impediment of the significant inflammatory signaling pathways. It has been demonstrated that the substitution patterns and hybridization of the thiazole scaffold with other bioactive pharmacophores led to the improvement of the anti-inflammatory effectiveness and selectivity. The current review highlights the thiazole-based anti-inflammatory derivatives as promising candidates, encompassing publications from 2020 to 2025 for the discovery of innovative anti-inflammatory therapies by focusing on varied synthetic routes, structure-activity relationships, and mechanistic insights, besides their binding modes within the active site of the target enzymes and cytokines.

Pre-mRNA splicing is a process of removing introns from precursor RNA and joining exons to form mature RNA for protein translation. The processes are classified into constitutive and alternative splicing, with which multiple mRNA transcripts are generated from a single coding gene to expand protein diversity. Frequent mutations or abnormal expressions of some splicing factors dysregulate splicing in a subset of transcripts, leading to aberrant gene expression patterns. Notable splicing factors, including SF3B1, U2AF1, SRSF2, and RBM39, are considered potential drug targets for various cancers. Advancement in the discovery and development of small molecules targeting specific splicing factors has become a new treatment modality for cancer therapy. Here, we review recurrent mutations and dysregulated expressions of splicing factors in cancers and provide our perspective on recent developments of small-molecule compounds targeting splicing factors and the functional assays that facilitate hit/lead discovery for development to treat cancer.

Terpenoids are valuable natural products that are widely used in medicine, agriculture, energy, and food. Traditional production by plant extraction or chemical synthesis is inefficient, costly, and polluting. Microbial fermentation via synthetic biology offers a greener alternative but faces challenges such as metabolic flux competition, cofactor imbalance, and product toxicity that limit yields. Genome-scale metabolic models (GSMMs), as essential tools in systems biology, can provide computational guidance for the rational design. This paper systematically reviews the progress of GSMMs in four typical terpenoid-producing microorganisms: the model microorganisms Escherichia coli and Saccharomyces cerevisiae, as well as the nonmodel microorganisms cyanobacteria and Yarrowia lipolytica. It focuses on their applications in fermentation process optimization and metabolic engineering strategies. Furthermore, future development directions, such as multiconstraint models and the integration of machine learning with synthetic biology, are discussed, aiming to provide a theoretical reference for the intelligent design and efficient construction of terpenoid cell factories.

Imidazoles, indoles, and pyrimidines are promising heterocyclic scaffolds for anticancer drug discovery. Based on the literature from 2020 to 2025, this review summarises that structurally diverse imidazoles, particularly ether-linked and long-chain variants, exhibit robust anticancer activity through multi-target protein inhibition and minimal off-target effects. Indoles trigger apoptosis and inhibit angiogenesis, while pyrimidines and their hybrids exhibit nanomolar potency and often outperform conventional chemotherapy. These scaffolds collectively modulate important pathways in cancer and exhibit enhanced selectivity toward tumour cells; however, clinical translation is challenging mainly due to incomplete mechanism of action and pharmacokinetics. Further rational optimisation and green synthesis methods may accelerate the development of these heterocycles into next-generation anticancer agents.

Single-atom skeletal editing has emerged as a powerful strategy for precisely modifying molecular frameworks, enabling direct access to complex structures that are difficult to achieve through traditional synthesis. Within this field, the strategic incorporation of oxygen atoms is particularly valuable, as it can significantly alter a molecule's structure, polarity, and reactivity. This review summarizes the significant progress within this burgeoning area, delineating two primary reaction classes: (1) the formal insertion of oxygen into a carbon-carbon (C─C) single bond, and (2) its insertion into a carbon-heteroatom (C─X, where X = N, B) bond. A critical evaluation of diverse strategies, including strain-driven cleavage, functional group-directed activation, photoelectrochemical methods, and hypervalent iodine-mediated rearrangements, is presented, focusing on their reaction mechanisms, substrate scopes, and applications. By providing a comprehensive overview of the progress and developments in oxygen atom insertion, this review aims to serve as a practical guide for the growing field of single-atom skeletal editing and to inspire future innovations in synthesis.

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The ever-increasing complexity of biochemical systems, alongside the rapid growth of pharmaceutical and biomedical data, underscores the urgent need for intelligent, scalable, and interpretable computational models. These models must be capable of supporting next-generation decision-support systems and driving knowledge discovery in the realm of computational science. Traditional approaches to relational biomedical modeling, however, often struggle to accurately capture intricate multi-relational dependencies and typically lack robustness in sparse or incomplete interaction domains. To address these pressing limitations, we present a novel, biologically grounded graph-based learning framework designed to overcome such challenges. Our approach comprises a two-tiered system: PHARMNet, a multi-relational graph neural network (GNN) equipped with memory-augmented attention mechanisms, and INTERACT-SCOPE, an advanced, context-aware optimization strategy that leverages structured biomedical ontologies and domain knowledge. PHARMNet employs relation-specific graph convolutions and semantic embedding alignment to effectively model latent relational dependencies in biochemical and pharmacological datasets. In parallel, INTERACT-SCOPE improves predictive generalization and stability by incorporating ontology-guided constraints, estimating epistemic uncertainty, and applying adaptive graph regularization techniques tailored to biomedical structures. Through rigorous experimental evaluations across a variety of pharmacological interaction categories, our framework consistently achieves state-of-the-art (SOTA) predictive performance, enhanced model interpretability, and notable robustness-especially in low-data or high-noise scenarios. These outcomes strongly align with the journal's mission to promote innovative and knowledge-driven advances in software engineering, artificial intelligence, and biomedical informatics. Ultimately, our article illustrates the synergistic integration of computational intelligence, domain-informed graph representation learning, and scalable modeling, contributing a powerful and interpretable solution to real-world challenges in healthcare informatics and biomedical discovery. Experimental results demonstrate that MGTNSyn outperforms existing methods, achieving an AUC of 0.873 and an F1-score of 0.831 on drug-drug interaction (DDI) benchmark datasets.