Dermatophytosis, or tinea, is a common superficial fungal infection affecting people of all ages worldwide. It is caused by keratinophilic dermatophytes that invade the skin barrier, colonize keratinized tissues, and activate host immune responses, leading to inflammation and tissue damage. Understanding the molecular pathogenesis is critical for standardizing treatment and developing targeted therapies. Key aspects include fungal invasion mechanisms, adhesion and proliferation on skin, secreted molecules, virulence factors, colonization patterns, and host-pathogen interactions. As new dermatophyte species emerge, advanced techniques are needed to study gene expression regulation during infection, disease progression, and how fungal factors modulate the host immune response, particularly in keratinocytes. Functional annotation of dermatophyte genes and their human counterparts is essential to map these interactions. This review summarizes the most common clinical forms of dermatophytosis, discusses selected host-dermatophyte interactions and evolutionary adaptations, and highlights current strategies for diagnosis and therapy. A deeper comprehension of these mechanisms will help in designing precise antifungal drugs and improving disease management.

Alstonia boonei (Apocynaceae) is a medicinal plant widely used in West and Central Africa to manage malaria, fever, intestinal worms, rheumatism, and hypertension. This review compiles evidence on its traditional uses, phytoconstituents, pharmacological activities, and formulations, to encourage future research into its therapeutic potential for modern health challenges. Literature review confirms notable anti-inflammatory, antimalarial, and ulcer-protective activities, while additional studies highlight its potential in antioxidant, anti-diabetic, neuroprotective, antiobesity, cytochrome P450 (CYP) enzyme inhibitory, anti-cataract, anticancer, and antibacterial effects. Phytochemical analysis reveals the presence of diverse bioactive compounds, including alkaloids, saponins, tannins, terpenes, phenolic compounds, and glycosides, which may act individually or synergistically to yield broad pharmacological actions. Recent experimental data reinforce its therapeutic relevance, positioning Alstonia boonei as a promising source of natural products. The wide spectrum of biological activities, coupled with the structural diversity of its phytoconstituents, underscores its importance as a valuable medicinal resource. In conclusion, Alstonia boonei shows significant potential for the development of anti-inflammatory, antimalarial, and ulcerprotective bioactive agents, justifying further scientific exploration and drug discovery efforts.

Justicidins are naturally occurring arylnaphthalene lignans, mainly from Justicia, Phyllanthus, and Linum species. Justicidin and its derivatives have gained scientific attention for their structural adaptability and wide-ranging pharmacological activities. Their rigid arylnaphthalene core, featuring hydroxyl, methoxy, dioxymethylene groups, and a five-membered lactone ring, offers chemical stability and scope for modification, enabling targeted drug design. Preclinical studies show that justicidin has potent cytotoxicity against breast, lung, leukemia, colorectal, and bladder cancer cells through mechanisms such as apoptosis induction via mitochondrial pathways, topoisomerase inhibition, cell cycle modulation, angiogenesis suppression, and interference with metastasis-related signaling. Beyond oncology, it demonstrates anti-inflammatory, antiviral, neuroprotective, antibacterial, antiplatelet, and antiangiogenic effects. Its multi-target activity involves modulation of NF-κB, MAPK, and PI3K/Akt pathways, as well as DNA damage induction, mitochondrial membrane potential disruption, and regulation of caspases. Low toxicity in normal cells and favorable pharmacokinetics in experimental models strengthen its therapeutic promise. Advances in total synthesis and biotechnological production further enhance its research value. This review compiles current insights into the chemistry, biosynthesis, biotechnological production, pharmacology, and molecular mechanisms of justicidin, underscoring its dual potential as an anticancer lead and a versatile agent for chronic diseases. Understanding structure-activity relationships and optimizing drug-like properties may enable the development of novel, multi-target therapeutics inspired by this natural product.

Glioblastoma (GBM) is an exceptionally aggressive brain malignancy with a dismal prognosis, characterized by a median survival of roughly 15 months despite standard radiotherapy and Temozolomide treatment. A primary driver of this therapeutic resistance is autophagy. While initially tumor-suppressive, autophagy transitions into a cytoprotective mechanism in established GBM, acting as a molecular survival switch that enables cells to withstand metabolic stress, hypoxia, and therapy-induced DNA damage. Crucially, this complex intracellular degradation process has emerged as a powerful tool for GBM diagnosis and prognosis. Autophagy-related genes (ARGs) are now established as highly sensitive diagnostic and prognostic biomarkers. Utilizing advanced bioinformatics, researchers have constructed robust prognostic risk models, such as 4-gene, 7-gene, and 10-lncRNA-mRNA signatures, that can accurately stratify patient risk, forecast tumor progression, and estimate overall survival. These molecular signatures provide vital diagnostic utility by distinguishing aggressive GBM phenotypes from lower-grade gliomas. Furthermore, these prognostic models strongly correlate with tumor microenvironment dynamics and immune infiltration, providing deep insights into immunosuppressive macrophage polarization. By profiling these autophagy-driven markers, clinicians can reliably anticipate chemoresistance and tailor personalized immunotherapy regimens. This review explores the signaling pathways regulating autophagy, the mechanisms driving radioresistance and chemoresistance, and the profound diagnostic and prognostic value of ARG signatures, highlighting emerging translational strategies to therapeutically target autophagy, overcome resistance, and improve clinical outcomes.

The fat mass and obesity-associated protein (FTO), the first identified N6-methyladenosine (m6A) RNA demethylase, has become both a leading candidate target in oncology and one of its most contested, behaving as an oncogene in some malignancies and as a tumor suppressor in others. Multiple inhibitor classes, FB23 derivatives, proteolysis-targeting chimera (PROTAC) degraders, repurposed entacapone, and tumor-targeted nanomedicines, have entered preclinical development, yet the clinical proposition remains unresolved because no framework currently predicts directionality or matches strategy to patient. We argue that this impasse reflects a missing conceptual frame, not missing molecules. Reading the field through a three-layer regulatory code offers a way to organize this paradox: an input code, in which K88 acetylation, USP7/USP30-mediated deubiquitination, oncometabolite 2-hydroxyglutarate, microbial CagA, lineage-specific transcription factors, and non-coding RNA scaffolds set FTO state; a processing code, in which subcellular localization, including localization to membraneless compartments, the YTHDF2 versus IGF2BP reader dichotomy, and a proposed non-catalytic scaffolding role select substrate fate; and an output code that maps onto metabolic rewiring, ferroptotic and pyroptotic decisions, immune sculpting, therapy resistance, and exosomal microenvironmental reach. The framework reorganizes therapeutic logic, direct inhibition, indirect modulation, rational combinations, or pharmacological activation, and reframes FTO from a contested target to a context-aware one whose translation depends on direction-aware precision oncology. Because the input, processing, and output layers are frequently drawn from different experimental systems, we present this code as an interpretive and hypothesis-generating scaffold rather than a validated predictive tool: it clarifies why FTO directionality varies and defines what must be measured to anticipate it, while prospective, within-model testing is still required before directionality can be assigned, or therapy matched, in an individual tumor.

The extensive array of Natural Products (NPs), ranging from plants to microbes, is wellknown for their varied chemical characteristics and significant biological activity. Historically significant in drug discovery, natural products provide distinctive stereochemistry and complexity generated by diverse biosynthetic pathways. Structural alterations improve effectiveness and diminish adverse effects, driven by advancements in screening, chemistry, and bioinformatics. Natural products have been approved as drug candidates despite the laborious process involved in their isolation and elucidation, demonstrating their relevance. Cinnamaldehyde (CA), derived from Cinnamomum tree bark, exhibits antibacterial, anti-inflammatory, anticancer, antioxidant, neuroprotective, antifungal, and anti-diabetic properties by affecting cellular processes and signaling pathways like PI3K/AKT/mTOR, TGF-β/Smad, NF-κB, TLR4/MyD88/NF-κB, MAPKs, JAK/STAT, and Nrf2/HO-1. Small molecular entities, along with the presence of α,β-unsaturated carbonyl functionality, offer intriguing possibilities within the research framework of synthetic chemistry. Synthetic analogues of CA have been produced; nonetheless, their biological actions remain largely unexamined. The review highlights the pharmacological significance of cinnamoyl functionality, indicating its potential for creating multi-targeted drugs through unexamined structural changes. This review adopts a comprehensive study design, featuring an extensive search of databases like PubMed, Science Direct and Scopus using keywords such as "cinnamoyl compounds," "synthetic derivatives," "therapeutic flexibility," and "pharmacological pathways." Studies were selected based on their relevance to the pharmacological activities of cinnamoyl compounds' synthetic derivatives and their effects on multiple signaling pathways in therapeutic contexts, including experimental data. This article aims to provide theoretical support for the promising development of cinnamoyl compounds as potential candidates for new discoveries and therapeutic advancements.

Hepatocellular carcinoma (HCC) develops within a chronically inflamed and immunologically dysregulated hepatic microenvironment that contributes to therapeutic resistance and disease progression. Gasdermin-mediated pyroptosis has emerged as a context-dependent inflammatory cell-death program capable of reshaping antitumor immunity, stromal remodeling, and immune checkpoint responsiveness. Acute and localized activation of GSDMD or GSDME may enhance immune-cell recruitment and tumor antigen exposure, whereas persistent pyroptotic signaling promotes fibrosis, angiogenesis, and immunosuppressive remodeling. This review examines the molecular circuitry linking pyroptosis with inflammasomes, metabolic stress, mitochondrial dysfunction, hypoxia, and epigenetic regulation in HCC. We further discuss how single-cell and spatial transcriptomic approaches reveal distinct pyroptotic immune niches associated with macrophage polarization, T-cell infiltration, and therapeutic response. Emerging therapeutic strategies including inflammasome modulation, gasdermin-targeted interventions, metabolic sensitization, and combination immunotherapy are also evaluated. Collectively, regulated pyroptosis may represent a promising immunomodulatory framework for improving precision therapy in HCC.

Type 2 diabetes mellitus (T2DM) affects over 537 million adults worldwide; conventional insulin therapy suffers from poor oral bioavailability, enzymatic degradation, and hypoglycemia risk. We developed a dual pH- and glucose-responsive PEG-GOx@ZIF-8-Ins nanoplatform for oral insulin delivery via biomimetic co-precipitation. The optimized nanoplatform (178 ± 7.0 nm; zeta potential -26.5 ± 1.8 mV; surface area 891 m2/g) achieved 79.8 ± 2.7% encapsulation efficiency and 87.4% GOx retention. Release was minimal under gastric conditions (<10%) but reached 97.2% at 25 mM glucose, with high glucose selectivity. Cytotoxicity assays confirmed biocompatibility (IC50 > 200 μg/mL). In diabetic rats, oral bioavailability reached 7.2%, 5.5-fold higher than free insulin, with prolonged half-life, higher area under the curve (AUC), and 10-h normoglycemia without hypoglycemia. PEG-GOx@ZIF-8-Ins is a promising oral insulin delivery strategy for T2DM.

Purpurogallin is a naturally occurring benzotropolone derivative, first isolated from oak nutgalls, and has emerged as a molecule of significant biomedical interest due to its broad spectrum of bioactivities. It exhibits anticancer, antioxidant, anti-inflammatory, anti-platelet, anti-thrombotic, antibacterial, antimalarial, diabetic nephropathy, and neuroprotective properties. Mechanistically, purpurogallin modulates several key signaling pathways, including NF-κB, MAPK, c-Fos, NFATc1, and TNNT2, which are central to inflammation, apoptosis, and cellular proliferation. Its anticancer potential is underscored by its ability to inhibit crucial oncogenic targets such as Pololike kinases (PLKs), xanthine oxidase, and catechol-O-methyltransferase (COMT). These interactions disrupt cancer cell growth, induce apoptosis, and maintain cellular redox homeostasis. Additionally, its structural resemblance to tropolone-based pharmacophores enhances its utility as a scaffold in anticancer drug development, allowing for strategic chemical modifications to improve efficacy and selectivity. Recent research highlights its promise in the treatment of oxidative stressrelated disorders, including diabetic nephropathy and neurodegenerative diseases, through its potent redox-modulating capabilities. This multifaceted bioactivity profile positions purpurogallin as a compelling candidate for therapeutic advancement. This review delves into the current body of evidence on purpurogallin's biological effects, molecular mechanisms, and synthesis, emphasizing its dual functionality in targeting cancer-related signaling and oxidative stress. Such findings support further investigation into its pharmacological optimization and development as a lead compound in future drug discovery efforts.

Astrocyte-elevated gene-1 (AEG-1), also known as metadherin (MTDH), is a pleiotropic oncogene critically involved in the onset and development of glioblastoma (GBM), other malignant gliomas, and neuroblastoma. Its expression is upregulated under hypoxic conditions and during glucose deprivation, enabling tumor cells to survive severe metabolic stress while sustaining glycolysis. AEG-1 also has emerged as a reliable prognostic and diagnostic biomarker in gliomas, astrocytomas, oligodendrogliomas, and neuroblastomas. High AEG-1 expression correlates with advanced tumor grade, rapid disease progression, metastasis, and poor overall survival, independent of conventional clinical variables. Co-expression of AEG-1 with MDM2 further predicts higher recurrence and reduced survival, highlighting its value in patient stratification and clinical decision-making. Beyond its prognostic relevance, AEG-1 is a promising therapeutic target. Importantly, gene silencing studies demonstrate that AEG-1 knockdown reduces proliferation, promotes apoptosis, and enhances sensitivity to chemotherapeutic agents such as cisplatin, doxorubicin, and temozolomide. Mechanistically, inhibition of AEG-1 disrupts survival pathways including PI3K/Akt, impairs DNA repair, and attenuates immunosuppressive tumor microenvironments. Small-molecule inhibitors, such as DYT-40, synergistically target AEG-1 and NF-κB, reducing tumor growth and invasion in glioblastoma models. Moreover, AEG-1 suppression sensitizes cancer cells to radiotherapy by impairing homologous recombination repair and enhancing DNA damage-induced apoptosis. Collectively, these findings underscore AEG-1 as a central regulator of tumor progression, chemoresistance, and radioresistance, and support its potential as a target for combinatorial therapeutic strategies to improve outcomes in aggressive brain and pediatric tumors.

Gliomas are molecularly heterogeneous central nervous system tumors with variable treatment responsiveness and survival outcomes. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is an important biomarker because it is associated with reduced DNA repair capacity and increased sensitivity to alkylating agents, particularly temozolomide (TMZ). However, its clinical meaning is not uniform across glioma subtypes and should not be interpreted as a universal prognostic marker. In IDH-wildtype glioblastoma, MGMT promoter methylation has the strongest evidence as a predictive biomarker for benefit from TMZ-containing therapy, although survival advantages in treated cohorts should be interpreted mainly as treatment-associated effects unless treatment-independent prognostic value is demonstrated. In IDH-mutant astrocytoma, MGMT methylation may partly reflect IDH-associated global hypermethylation and appears to have limited independent clinical value. In IDH-mutant, 1p/19q-codeleted oligodendroglioma, MGMT methylation may provide supportive, treatment-context-dependent information, particularly in patients receiving alkylating chemotherapy. In pediatric-type and rare molecularly defined gliomas, including histone-altered tumors, MGMT status remains exploratory and should be interpreted alongside methylation class, lineage-defining alterations, tumor location, and treatment history. Technical factors, including assay platform, CpG-site selection, cutoff definition, tissue quality, tumor-cell content, and intratumoral heterogeneity, further complicate interpretation. Because MGMT methylation is biologically continuous, this review further argues that borderline results should be reported as gray-zone or intermediate categories when validated, and that quantitative methylation values should be integrated into subtype-aware multivariable models rather than being reduced exclusively to binary calls. This review summarizes the biological and clinical relevance of MGMT promoter methylation across glioma subtypes and proposes a subtype-aware, treatment-conditional, and assay-aware framework for interpreting its predictive and survival-related significance.

ABSTRACT Rapid and ultrasensitive viral diagnostics remain a global priority for effective outbreak control and timely clinical intervention. MXene quantum dots (MQDs) have recently emerged as a powerful class of nanomaterials for electrochemical biosensing due to their exceptional electrical conductivity, tunable surface chemistry, high surface‐to‐volume ratio, and quantum confinement effects. These features collectively enable efficient biomolecule immobilization, accelerated electron transfer, and amplified analytical signals, making MQDs highly attractive for next‐generation rapid viral detection platforms. This review systematically examines the structural, electronic, and interfacial properties of MQDs that underpin their biosensing performance, with particular emphasis on electrochemical transduction mechanisms. Recent advances in MQD‐enabled immunosensors, nucleic acid assays, and hybrid photoelectrochemical (PEC) and photothermal systems are critically analyzed to highlight emerging design principles for high‐sensitivity viral detection. Furthermore, key barriers to clinical implementation—including material reproducibility, biointerface stability, device integration, and regulatory considerations—are discussed in depth. By bridging nanoscale engineering with translational diagnostic requirements, this work outlines a strategic roadmap for advancing MQD‐based electrochemical platforms toward robust, point‐of‐care viral diagnostics.

The estrobolome, the community of gut microbial genes involved in estrogen metabolism, may influence hormone bioavailability and cancer risk, although human evidence remains largely associative. This review summarizes evidence that bacterial β-glucuronidases, sulfatases, and hydroxysteroid dehydrogenases regulate enterohepatic estrogen recycling, while microbial metabolism also shapes receptor signaling, genotoxic estrogen metabolites, inflammation, and immune responses. Observational studies link gut microbial composition and function with breast and endometrial cancer, but causality remains unproven. Early dietary, probiotic, antibiotic, and fecal microbiota transplantation studies show biological effects, yet they are not sufficient for clinical application. We propose a functional framework that prioritizes microbial enzymatic activity over taxonomy and highlight multiparametric biomarkers and selective β-glucuronidase inhibition as promising research directions for prevention and adjunct therapy in hormone-driven cancers.

Neuroinflammation is the body's immune reaction that occurs inside the central nervous system to keep brain cells balanced and healthy. Uncontrolled and chronic neuroinflammation can start damaging neuronal cells and lead to neurodegenerative diseases. Glial cells, especially microglia and astrocytes, play an important role in this process. Microglia act as immune guards of the brain, shifting between protective and harmful states depending on certain signals such as NADPH oxidase 2, histone deacetylases, and transforming growth factor. Astrocytes support neurons and maintain the blood-brain barrier. During injury or stress, they become overactive and release numerous chemicals that make inflammation worse. Further, neuroinflammation is controlled by several signalling pathways, including NF-κB, PI3K/Akt, and MAPK. When these systems lose their balance, they cause ongoing inflammation and oxidative stress, which eventually harm brain cells. During the progression of neurodegenerative disorders, especially Alzheimer's Disease (AD) and Parkinson's Disease (PD), overactive microglia and astrocytes release large amounts of cytokines, reactive oxygen species, and inflammasome components that speed up neuron loss. The constant interaction between NF-κB, NLRP3, and oxidative stress worsens this damage, linking faulty molecular signals with the progression of these disorders. Ferulic acid, a natural antioxidant found in grains, fruits, and vegetables, has shown remarkable protective effects on the brain. It is biologically synthesized from aromatic amino acids L-phenylalanine and L-tyrosine through the shikimate pathway. By clearing free radicals and stopping lipid damage, ferulic acid protects neurons from degeneration. Experimental studies have shown that ferulic acid offers significant antioxidant and anti-neuroinflammatory effects and prevents the accumulation of harmful proteins, such as Aβ and α-synuclein, in the brain. Furthermore, ferulic acid has a strong capacity to modulate several cellular and molecular signaling pathways, including Nrf2/HO-1, NF-κB, and MAPK, which are closely linked to the development and progression of neurodegenerative disorders such as AD and PD. Interestingly, ferulic acid inhibits the generation of pro-inflammatory mediators, ameliorates mitochondrial dysfunction, prevents apoptosis, and consequently protects cholinergic and dopaminergic neurons in the brain, thereby exhibiting remarkable neuroprotective effects. Thus, the current review addressed that ferulic acid is considered a promising natural compound that could be an alternative natural phytoconstituent for the prevention and management of neuroinflammationassociated neurodegenerative disorders like AD and PD.

Gastrointestinal (GI) cancers, more broadly, colorectal, gastric, pancreatic, and esophageal malignancies, remain major contributors to global cancer mortality, driven by late diagnosis, metastasis, and resistance to therapy. Increasing evidence highlights the enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), as a central epigenetic driver of GI tumorigenesis through deposition of H3K27me3 and silencing of tumour-suppressor genes. However, the oncogenic functions of EZH2 are not autonomous; long non-coding RNAs (lncRNAs) critically shape its locus specificity, chromatin recruitment, stability, and integration into broader transcriptional programs. Numerous lncRNAs in GI cancers, such as LINC00337, LINC00673, ZFAS1, MSTO2P, and HOXA-AS2, recruit EZH2 to repress key regulators of the cell cycle and differentiation. Other lncRNAs act through ceRNA mechanisms to de-repress EZH2 expression, or engage EZH2 within oncogenic signalling pathways including AKT, STAT3, Notch, and Wnt/β-catenin. These interactions contribute to malignant proliferation, invasion, metastasis, cancer stemness, and therapeutic resistance. Despite intense investigation, mechanistic ambiguity remains due to limitations in distinguishing direct EZH2 recruitment from correlative chromatin association, and in validating ceRNA activity within physiologic stoichiometric constraints. Nevertheless, the lncRNA-EZH2 axis presents a promising therapeutic avenue, with RNA-based strategies offering the potential to disrupt pathological lncRNA-EZH2 assemblies with greater precision than catalytic EZH2 inhibitors alone. This review synthesizes current mechanistic and functional insights into lncRNA-EZH2 regulation in GI cancers, organizing these interactions into key biological modules and highlighting emerging opportunities for diagnostic and therapeutic development.

As food and environmental contaminants become increasingly complex, there is a growing need for analytical sensing platforms that offer high sensitivity, rapid response, and robust adaptability to a wide range of targets. Detection methods based on boronic acid-cis-diol interactions have attracted significant attention because they provide strong binding affinity, customizable selectivity, fast kinetics, and compatibility with various transduction techniques. This makes them a promising foundation for developing high-performance sensing systems. As a result, extensive research has focused on designing and synthesizing boronic acid-functionalized materials (BAFMs) for detecting food and environmental contaminants. This review summarizes recent advancements in the conceptual design and fabrication of BAFMs with different compositions and morphologies, explaining how these structural features influence their properties. Additionally, we examine the development of BAFM-based sensors targeting major contaminant categories, including pathogenic microorganisms, pesticide residues, heavy metals, antibiotics, mycotoxins, and organic pollutants, utilizing fluorescence, electrochemical, and surface-enhanced Raman scattering (SERS) platforms. Lastly, we outline recent challenges and future perspectives to guide the development of BAFMs with optimized performance and the engineering of sensing systems with enhanced analytical capabilities. Overall, this work aims to support ongoing advances in sensitive and reliable contaminant detection, while also facilitating the transition of these technologies toward real-world and commercial applications.

Pharmaceutical cocrystals have emerged as an effective strategy for enhancing the solubility and bioavailability of poorly water-soluble drugs. The successful design of cocrystals largely depends on the selection of suitable coformers, which requires an understanding of the molecular interactions governing cocrystal formation during the process. The objective of this study was to develop robust machine learning models for predicting Hansen solubility parameters of pharmaceutical cocrystal using molecular descriptors generated from COSMO-RS and group contribution methods. A dataset consisting of 181 samples and 86 input features was utilized, incorporating molecular descriptors related to hydrogen-bonding capability, van der Waals interactions, and structural functional groups. Data preprocessing included outlier detection using the Isolation Forest algorithm and feature selection through Sequential Floating Forward Selection (SFFS). Three tree-based ensemble learning models, namely Random Forest (RF), Extra Trees (ET), and Gradient Boosting Regression Trees (GBRT), were developed and optimized using the Dragonfly algorithm for hyperparameter tuning. The obtained results demonstrated that the Extra Trees model consistently outperformed the RF and GBRT models in predicting all three Hansen solubility parameters. For the three target outputs, the ET model achieved test-set R2 values of 0.9175, 0.8661, and 0.9815, respectively, while also exhibiting the lowest RMSE and MAE values. Feature importance analysis revealed that both group contribution descriptors and COSMO-RS-derived molecular properties play significant roles in determining the Hansen solubility parameters of coformers. Overall, the proposed machine learning framework provides an efficient and accurate approach for predicting Hansen solubility parameters and screening pharmaceutical cocrystals. The findings highlight the superior predictive capability of the Extra Trees model and demonstrate the potential of combining molecular thermodynamic descriptors with advanced machine learning techniques for pharmaceutical cocrystal design.

The increasing threat of antibiotic-resistant bacteria (ARB) necessitates rapid and accurate diagnostic tools to guide effective treatment strategies. Traditional culture-based methods are time-consuming, delaying crucial interventions and potentially contributing to the spread of resistance. Electrochemical biosensors offer a promising alternative, providing high sensitivity, specificity, and rapid detection capabilities suitable for pointof-care applications. These platforms leverage biorecognition elements, advanced electrode materials, and the electrochemical detection of microbial products or genetic material to identify ARB. Recent advancements include the integration of microfluidics and lab-on-a-chip systems for high-throughput antimicrobial susceptibility testing, significantly improving diagnostic speed and precision. This review critically examines the latest developments in electrochemical biosensing for ARB detection, highlighting key strategies such as DNA probebased sensors and the use of nanomaterials to increase performance. It also addresses persistent challenges, including sensor reproducibility and cost-effectiveness, and explores future directions aimed at improving the clinical applicability and accessibility of these vital diagnostic technologies in the fight against antimicrobial resistance worldwide.

Natural killer (NK) cells are critical components of the innate immune system, renowned for their ability to recognize and eliminate malignant and infected cells without prior sensitization. NK cell immunotherapy encompasses various approaches, including adoptive transfer of ex vivo expanded NK cells, cytokine stimulation to enhance their activity, and genetic modifications to improve persistence and specificity. CREM is a cAMP-responsive transcription factor that modulates gene expression in response to receptor- and cytokine-driven signaling. Recent evidence now shows that IL-15 and CAR stimulation rapidly induce CREM in activated NK cells. Rafei (Nature 643:1076–1086, 2025) further demonstrated in CAR-NK models that CREM functions as a regulatory checkpoint limiting NK cell cytotoxicity and cytokine production, while its relevance in resting/native NK cells remains to be established. The CREM–IL-15 signaling axis has emerged as a pivotal regulator of NK cell biology, influencing their development, activation, and longevity. IL-15 is a critical cytokine for NK cell survival, proliferation, and functional maturation. Understanding this axis is vital, as it offers insights into mechanisms that sustain NK cell activity and those that lead to functional exhaustion, thereby informing strategies to enhance therapeutic efficacy. A central challenge in NK cell immunotherapy is balancing cellular persistence with functional exhaustion. Persistent NK cell activity is desirable for sustained tumor control; however, prolonged activation often results in cellular exhaustion characterized by diminished cytotoxicity and cytokine production. This paradox hampers the long-term success of NK cell-based treatments. The CREM–IL-15 axis plays a complex role in this dynamic, potentially promoting NK cell survival and persistence while also contributing to exhaustion under certain conditions. Deciphering the molecular underpinnings of this paradox is essential for developing interventions that maintain NK cell functionality over time, thereby improving therapeutic outcomes in cancer patients.

Natural products (NPs) have long served as a rich inspirational source for drug discovery and development, offering diverse chemical structures and biological activities. Among these, topsentin, a marine alkaloid derived from marine sponges, has emerged as a promising scaffold due to its remarkable pharmacological properties and structural versatility. This review explores the significance of topsentin and its derivatives in drug discovery efforts. It discusses the diverse biological activities of topsentin and its analogs, including anticancer, antimicrobial, anti-inflammatory, and antiviral properties, highlighting their potential therapeutic applications. Moreover, it also focuses on the structural features of topsentin that contribute to its pharmacological profile, emphasizing its importance in the design and development of novel therapeutic agents. Structural modifications and synthetic strategies employed to enhance the pharmacological properties of topsentin derivatives are also discussed. Overall, this review underscores the significance of topsentin as a promising scaffold in drug discovery.