Diabetes, a common metabolic condition, poses a substantial health burden worldwide. To revolutionize diabetes management, enhance glycemic control, and decrease the risk of complications, recent research has revealed innovative targets and therapeutic options. A thorough examination of modern drugs that target particular receptors and metabolic pathways for glucose and fat metabolism is presented. Recent research has revealed innovative targets and therapeutic options. Liraglutide, a GLP-1 receptor agonist, has been shown to effectively lower glucagon levels and promote weight loss. Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor with substantial promise in decreasing blood glucose levels, and providing cardiovascular and renal advantages. Pegbelfermin (BMS-986036), a fibroblast growth factor 21 (FGF21) analogue, is being investigated for its ability to regulate glucose and lipid metabolism, and potentially enhance glycemic control and lipid profiles. Additionally, G-protein-coupled receptor (GPCR) agonists and adenosine monophosphate-activated protein kinase (AMPK) activators are emerging as potential medicines to improve insulin sensitivity, glucose uptake, and insulin signaling pathways. Despite being in early research stages, bile acid receptor agonists and mitochondrial uncouplers have promising potential for modifying lipid and glucose metabolism. The long-acting insulin analogue insulin glargine, which replaces basal insulin, continues to be a cornerstone of advanced diabetes management. In the future, these medications are expected to be improved through the use of combination therapy and personalized, precision medicine. Gene therapies show promise as novel strategies to address genetic defects and provide potential treatments. Additionally, patient monitoring, adherence, and self-management will be greatly aided by the integration of digital health technology, telemedicine, and artificial intelligence (AI), thus leading to better treatment outcomes and patient quality of life. Healthcare professionals, researchers, politicians, and patients working together will pave the way to substantial improvements in the management of metabolic disorders including diabetes. In conclusion, hope for more efficient, individualized, and secure therapies may come from continuing research and breakthroughs in novel diabetes treatment targets. These developments are at the forefront of offering people with diabetes and related metabolic disorders a better and healthier future, by revolutionizing diabetes management.

As the altitude increases, the partial pressure of oxygen will decrease and cause hypobaric hypoxia conditions. During hypoxia, the anaerobic glycolysis will be activated, which is facilitated by the lactate dehydrogenase (LDH) enzyme. This study aimed to analyze the LDH-specific activity in rat muscle and liver tissue, as well as lactate and glucose levels in blood plasma after intermittent hypobaric hypoxia exposure. Twenty-five Wistar rats were divided into five groups: one control group and four hypobaric hypoxia (HH) exposure groups consisting of group 1 (1× HH), group 2 (2× HH), group 3 (3× HH), and group 4 (4× HH) with a range of 7 days between exposure. This study found that LDH-specific activity increased in muscle tissues in group 1, but then decreased in the intermittent group (groups 2–4). The change in LDH-specific activity in muscle tissues was similar to the change in lactate plasma levels. Interestingly, in liver tissues, there was a slight increase in the LDH-specific activity in group 1, and it started to increase significantly in group 2 and kept increasing in groups 3 and 4. The change in LDH-specific activity in liver tissues was similar to the change in glucose plasma level. We conclude that the LDH activity in muscle tissue contributes to lactate plasma levels, but the LDH activity in liver tissue contributes to maintaining glucose plasma after intermittent hypobaric hypoxia exposures. This finding could be implemented in individuals who experience intermittent hypoxia exposures or in various diseases with hypoxic conditions as their pathogenesis

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in China in December 2019, rapidly spread worldwide, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Understanding the structural and functional interactions between the virus and host cells is critical for developing therapeutic strategies.

Methods: In this study, we employed in silico docking models to investigate the molecular interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, derived from the Brazilian genome sequence, and seven clinically approved drugs: umifenovir, darunavir, lopinavir, ritonavir, remdesivir, pirfenidone, and oseltamivir. The three-dimensional structure of the Omicron RBD model was generated through homology modeling, and potential active site cavities were predicted within the RBD structure.

Results: Among the seven drugs tested, only lopinavir and ritonavir demonstrated significant binding affinities to the RBD. Lopinavir exhibited a binding affinity of −9.8 kcal/mol, forming interactions with residues PHE168, GLY167, SER176, GLN175, GLU166, LEU134, LEU137, TYR171, PHE138, LEU174, and PHE172. Ritonavir showed a binding affinity of −8.9 kcal/mol, interacting with residues ARG148, ASN130, VAL23, SER81, ASN33, PHE29, TYR33, SER31, ASN132, ALA26, ALA30, ALA34, and TYR133. Molecular dynamics simulations confirmed the stability of the complexes formed between lopinavir and ritonavir and the RBD active site.

Conclusion: These findings underscore the potential of these protease inhibitors as therapeutic agents targeting the SARS-CoV-2 spike protein.

Neurologic disorders currently affect approximately 100 million people worldwide. Neurologic disorders most often occur due to inherent genetic mutations, which lead to numerous types of functional disruptions in nervous system development. Neurologic disease-related events, such as genetic and epigenetic changes, cause inflammatory processes in the area which may enhance the disease cycle. Gene therapy has progressed to a compelling therapeutic approach for various neurodegenerative disorders. Several efforts to enhance gene therapy rely on discovering novel vectors, recent curative targets, and the dependability of transgenic delivery paths. These viral and non-viral vectors techniques are carefully screened through preclinical and clinical levels and eventually render patients with effective therapies. This review addresses gene therapy developments and obstacles for neurodegenerative diseases and discusses emerging strategies, goals, and prospects.

Lipid-based Nanoparticles (LBNPs) have emerged as a transformative approach in cancer treatment, offering innovative drug delivery solutions that enhance therapeutic efficacy while minimizing adverse effects. By exploring the characterization, classification, synthesis, targeting strategies, and advantages of LBNPs, this study highlights how LBNPs have been used to overcome the limitations of traditional chemotherapy and improve patient outcomes. As nanotechnology revolutionizes cancer therapy, the emergence of LBNPs as a promising strategy for targeted drug delivery has led to optimism regarding the future of cancer treatment. This review extensively assesses the structure, categories, production methods, targeting strategies, benefits, and recent advancements in LBNPs for treating cancer. It also highlights current challenges and possible future directions. This review is aimed at providing a comprehensive understanding of LBNPs’ potential in cancer therapy. Liposomes, nanostructured lipid carriers, solid lipid nanoparticles, and lipid-polymer hybrid nanoparticles are all types of LBNPs, each with unique features of interest for cancer therapy. These particles can be synthesized through various procedures, such as bulk nanoprecipitation, solvent-based emulsification, or microfluidics. Passive targeting systems, active targeting systems, and responsive delivery platforms direct LBNPs to tumors. Consequently, LBNPs provide an improved drug release pattern that minimizes side effects while enhancing therapeutic efficacy. With the potential for combination therapy, LBNPs offer a hopeful future for cancer treatment. Continued research is expected to improve patient outcomes and overall quality of life in cancer care.

Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by excessive extracellular matrix deposition and tissue scarring, and leading to impaired lung function and respiratory failure. Although current treatments, such as pirfenidone and nintedanib, slow disease progression, they fail to completely halt or reverse fibrosis. Therefore, innovative therapeutic strategies are needed. Targeted drug delivery systems (TDDSs) are emerging as promising solutions. Biomaterials play critical roles in these systems by enhancing drug specificity, availability, and efficacy, while minimizing systemic toxicity. The most notable biomaterials include nanotechnology-based systems, including liposomes and polymeric nanoparticles, which facilitate drug penetration and slow release in fibrotic tissues. Hydrogels have three-dimensional structures providing controlled and sustained drug release at inflammation sites, and therefore are particularly valuable in PF treatment. Furthermore, biological carriers such as stem cells and extracellular vesicles have biocompatibility and anti-inflammatory effects that improve therapeutic outcomes. Despite the promising potential of these systems, clinical translation is hindered by several challenges, including immune clearance, stability of delivery platforms, and optimization of drug retention within diseased tissues. Interdisciplinary approaches integrating precision medicine with advancements in biomaterials may provide solutions opening new avenues for PF treatment. This review discusses current developments in targeted drug delivery for PF, emphasizing the importance of biomaterials, the mechanisms and barriers involved in pulmonary drug delivery, and future perspectives for overcoming current limitations. The ultimate goal is to improve patient outcomes by revolutionizing the approach to PF treatment through advanced drug delivery technologies.

Background: Bladder cancer (BLCA) is one of the most common malignancies and the second most frequent urogenital tract tumor. Cell and gene therapy, which offer many advantages in treating BLCA, are urgently needed. However, there is an important limitation of the currently reported single chain antibody used as a chimeric antigen receptor (CAR) targeting domain. Specifically, CAR aggregation leads to CAR-T depletion, which may originate from the linker peptide and folding stability between the variable domains (VH and VL) of the single chain antibody of the CAR. Humanized, small size, strong affinity single domain antibodies (variable domain of heavy chain of heavy-chain antibody [VHH]) derived from camelids are promising alternatives.

Methods: Second-generation Nectin4-targeted VHH-CAR-T cells were constructed and the specific killing efficacy was determined against BLCA cells in vitro. VHH Nectin4-CAR lentivirus was transduced into human T cells and CAR-T cell phenotypes were analyzed by flow cytometry. Cell killing efficacy was assessed using Nectin4-positive BLCA cells (SW780 and RT4) and Nectin4-negative U87-MG cells as controls using the xCELLigence Real Time Cell Analysis system. Cytokine secretion expression (IFN-γ and IL-2) were measured by an enzyme-linked immunosorbent assay.

Results: VHH^Nectin4-CAR lentivirus treatment increased the proportion of CD4+ T and memory T cells. VHH^Nectin4-CAR-T cells had increased specific killing ability compared to the control using VH-VL-based CAR-T cells, specifically recognized Nectin4⁺ BLCA cells, secreted cytokines, and mediated cell apoptosis. Furthermore, VHH^Nectin4-CAR-T had no effect on Nectin4^- U87-MG cell growth.

Conclusions: VHH^Nectin4-CAR-T cells were established with potent killing ability that specifically recognized Nectin4⁺ BLCA cells in vitro. Statement of Significance: Second-generation targeted Nectin4 VHH-CAR-T cells were established. VHH^Nectin4-CAR-T cells with strong killing ability specifically recognized Nectin4⁺ BLCA cells in vitro.

Diabetes mellitus (DM) is a widespread metabolic disorder with profound effects on vital organs. Often referred to as a “systemic” or “multi-organ” disorder due to the impact on key organs, such as the kidneys, pancreas, eyes, and heart, DM is characterized by elevated blood glucose levels due to insufficient insulin production. DM consists of three subtypes (type 1 DM, type 2 DM, and gestational DM). Approximately 537 million adults are living with DM, a number predicted to increase to 643 million by 2030, according to the International Diabetes Federation (IDF) data. With the rising prevalence of DM, the Pan American Health Organization and World Health Organization estimate an age-standardized mortality rate of 20.9 deaths per 100,000 people. Therefore, it is important to study the prevention and cure of DM and determine the underlying mechanism and regulation. Numerous receptors and pathways help to regulate DM. This article delves into the intricate regulatory mechanisms underlying DM involving receptors and pathways, such as K_ATP (sulfonylurea), 5′AMP-activated protein kinase enzyme (biguanides), PPAR gamma, alpha-glucosidase, Glucose transporters (GLUT4), dipeptide peptidase-4 (DPP-4), and sodium-glucose co-transporters type 2 (SGLT2). The article highlights recent advances from 2020–2024 in synthesizing compounds targeting specific receptors for diabetes management. In so doing, insights into newly synthesized compounds, marketed drugs, phytoconstituents, and drugs currently in clinical trials will be provided. The role of each receptor in maintaining glucose homeostasis is reviewed in detail and various compounds with potential as effective antidiabetic agents are evaluated. This comprehensive review presents the pharmacologic mechanisms underlying these receptors and an in-depth analysis of promising new drug candidates.

Vitamin C (vitC), an essential nutrient for human health, has critical roles in numerous biological processes. VitC’s potential in disease prevention and treatment is a focus of ongoing research. Recent clinical studies have highlighted its promising effects in combating various tumor diseases, thus spurring further exploration of its anti-tumor mechanisms. Historically, the known anti-tumor mechanisms of vitC have included redox regulation and epigenetic modifications. He et al. have now uncovered a novel pathway in which covalent modification directly targets immune signaling proteins (Cell, 2025, 188, 1858–1877. DOI: 10.1016/j.cell.2025.01.043). These findings, particularly lysine vitcylation, substantially change the understanding of vitC’s mechanistic landscape. This Commentary comprehensively analyzes He’s study elucidating the key mechanisms underlying vitC’s anti-tumor efficacy. Furthermore, it thoroughly examines the newly proposed mechanism and discusses potential implications for clinical applications as well as future challenges.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M.tb) complex (MTBC), which includes M.tb as one of the causative bacteria. In contrast, non-tuberculous mycobacteria (NTM) refers to Mycobacterium spp. that do not cause TB or leprosy (MTBC spp., M. leprae, and M. lepromatosis). Mycobacterium spp. are responsible for the deadliest infections and remain a significant challenge in diagnosis and treatment. Mycobacterium spp. have developed multiple complementary mechanisms to defend against antibiotics. Specifically, the mechanisms include modifying the drug target sites, enzymatically inactivating the drugs, and lowering intracellular antibiotic concentrations by overexpressing efflux pumps. These adaptations contribute to the emergence of multi-drug resistant pathogens. This review provides an overview of antibiotic resistance inMycobacterium spp. with a focus on several key factors, such as enzyme-mediated antibiotic deactivation, gene expression, biofilm formation, and the role of efflux pumps. A critical objective of this review includes Mycobacterium efflux pumps, the significant role in antibiotic resistance, and compounds that act against these efflux pumps.

Liver fibrosis is caused by excessive extracellular matrix accumulation, which in turn is driven by activation of hepatic stellate cells. MicroRNAs (miRNAs), a class of small non-coding RNAs, are increasingly recognized as crucial regulators of gene expression in liver pathology, including fibrosis, by influencing intercellular crosstalk. Among these miRNAs, microRNA-223 (miR-223) has emerged as a key regulator of fibrosis, beyond its originally recognized role in innate immunity. By traveling between liver cell types via exosomes, miR-223 modulates inflammation and fibrosis via Hedgehog, platelet-derived growth factor (PDGF), and transforming growth factor-β signaling, and additionally dampens hepatic stellate cell activation by repressing glioma-associated oncogene homolog 2, PDGF receptor β, α-smooth muscle actin, and autophagy related 7, thereby influencing mechanotransduction and autophagy. However, numerous studies have reported opposite results, in which miR-223 promotes fibrosis under certain conditions, thus underscoring the roles of cellular environments, expression levels, and competing RNA networks. This Commentary synthesizes the current, sometimes contradictory, evidence; outlines how context shapes miR-223’s dual actions; and surveys the development of therapeutic strategies, including miRNA mimics, nanoparticle formulations, and extracellular-vesicle delivery, including major challenges in tissue targeting, cargo stability, and long-term safety. These insights together highlight miR-223 as a complex but intriguing target for antifibrotic treatment.

This article provides a systematic review of music therapy research progress and clinical applications in stroke rehabilitation. Music therapy, through techniques such as Melodic Intonation Therapy (MIT) and Rhythmic Auditory Stimulation (RAS), offers distinct advantages by activating alternative neural pathways and promoting neuroplasticity, which significantly improves emotional regulation, cognitive function, language expression, and motor function in stroke patients. According to clinical evidence, music therapy notably decreases depression and anxiety; promotes neuroplasticity; activates brain regions associated with language and motor function; and improves gait stability and limb coordination. However, current research faces challenges such as insufficient sample sizes, unclear long-term effects, and a lack of standardized protocols. Future studies should incorporate technologies such as artificial intelligence and virtual reality to explore personalized music therapy interventions and establish multi-center collaborative clinical research systems, thereby promoting standardized application of music therapy in stroke rehabilitation.

Asymmetric cell division (ACD) has a crucial role in normal cellular differentiation and tissue homeostasis. The mechanisms underlying ACD are highly intricate and involve coordinated molecular and cellular processes. Dysregulation of ACD has been implicated in various human cancers by contributing to malignant tumor initiation, progression, metastasis, and treatment resistance. Although numerous studies have explored the relationship between ACD and cancer, many questions remain unanswered. This literature review aims to evaluate the potential biological significance of ACD in cancer with a focus on the diagnostic and prognostic relevance to glioblastoma. A comprehensive PubMed search was conducted from 2008 to the present using keywords, such as “asymmetric cell division”, “cancer”, “glioblastoma”, and “tumorigenesis”. The selected articles were analyzed to assess ACD-related data and the clinical correlations. Special emphasis was placed on glioblastomas, an aggressive brain tumor with limited improvement in patient survival over recent years. The review underscores the crucial role of ACD in normal tissue homeostasis and ACD dysregulation in cancer initiation, progression, therapeutic resistance, and metastatic potential. Understanding how ACD contributes to cancer heterogeneity may provide insights into innovative strategies for tumor detection, monitoring, and treatment. Future research into the molecular mechanisms governing ACD could facilitate the development of novel glioblastoma therapies aimed at restoring or modulating ACD processes to improve patient outcomes.

The pyrimidine analog 5-flurouracil (5-FU) is effective against solid tumors. However, the half-life of intravenously administered 5-FU is less than 20 min, and the compound is quickly eliminated and shows systemic toxicity. This study was aimed at developing a nanohydrogel of 5-FU to improve anticancer drug delivery for skin cancer treatment. We prepared 5-FU Chitin nanoparticles (5-FCHNPs) through the ionic gelation technique, and used a 3²-factorial design approach to optimize the 5-FCHNPs and nanohydrogel formulations. Subsequently, 5-FCHNP particle size, zeta potential, and entrapment efficiency were evaluated. The optimized nanohydrogel formulation was assessed for pH, spreadability, consistency, morphology, and transmission electron microscopy (TEM), scanning electron microscopy (SEM), and in vitro cytotoxicity analyses were conducted. The developed nanohydrogel formulation (5-FNH9) showed 68.40% entrapment efficiency, 72.88% drug release, and 1.418% skin penetration. The IC₅₀ value of 5-FU was greater than that of 5-FNH9. The developed 5-FNH exhibited enhanced skin penetration and pH-responsive controlled drug release, and therefore has potential in skin cancer treatment.

Background: Imbalances in the intestinal microbiome are closely associated with the occurrence and development of cancer, and can affect tumorigenesis by influencing the inflammatory response, regulating the immune system, producing specific metabolites, and participating in tumor signaling pathways. Methods: This study investigated the relationships among intestinal microbial dynamics, metabolite profiles, and neoadjuvant chemotherapy (NAC) outcomes in patients with breast cancer. Patients were stratified by Miller-Payne (MP) grade into good (MP 4–5) or poor (MP 1–3) responders. Fecal samples from patients (pre- and post-NAC) were analyzed via 16S rRNA sequencing and untargeted metabolic analysis. Results: After neoadjuvant chemotherapy, the species diversity and abundance of the intestinal microbiome significantly decreased, and these trends were not correlated with neoadjuvant chemotherapy efficacy. Fusobacterium abundance remained significantly higher in poor responders than good responders post-NAC, thus suggesting its association with chemoresistance. The Firmicutes/Bacteroidetes ratio was lower in patients with breast cancer than healthy controls, and was correlated with the therapeutic response: this ratio rose post-NAC but remained suboptimal in poor responders. Untargeted metabolomics identified upregulated amino acids (Thr-Thr and histidine) in poor responders and elevated lipids (C17-sphinganine) in good responders. ROC (receiver operating characteristic curve) analysis validated these metabolites (AUC >0.7) as predictive biomarkers. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis highlighted enrichment in mTOR signaling, endocrine resistance, and estrogen signaling pathways. Conclusions: These findings underscore the intestinal microbiome’s potential as a predictor of NAC efficacy and a therapeutic target. Modulating Fusobacterium or metabolite pathways may enhance chemotherapy response.

Natural killer cell adoptive therapy is a novel immunotherapy strategy for the treatment of multiple refractory tumors, including ovarian cancer. However, natural killer cells’ anti-tumor effectiveness is limited by their viability and cytotoxicity. Our preliminary study suggested that ultrasound irradiation improves the therapeutic effects of natural killer cells on ovarian cancer through an unclear mechanism. The Wnt/β-catenin signaling pathway is a complex protein network system associated with the maturation and function of natural killer cells. Therefore, herein, to reveal the precise mechanism underlying the effects of ultrasound on natural killer cells, we measured the expression of Wnt/β-catenin signaling pathway proteins before and after ultrasound irradiation. The expression of therapeutic factors secreted by natural killer cells increased after ultrasound irradiation. Therefore, this study provides an additional strategy for optimizing the therapeutic efficiency of natural killer cells.

Background: Extended tight-binding (xTB) methods offer a computationally efficient alternative to classical force fields and ab initio quantum methods in modeling molecular systems. In the context of end-point free energy calculations, integrating xTB with implicit solvation models provides a promising route for enhanced accuracy. However, systematic benchmarking of xTB-based protocols remains limited, particularly in diverse host-guest systems.

Methods: We investigated the integration of xTB Hamiltonians (GFN0, GFN1, and GFN2) with post-simulation implicit-solvent models [Poisson−Boltzmann (PB), generalized Born (GB), and the most recent CPCM-X] for end-point free energy calculations. A total of over 250 host-guest complexes were used, covering cucurbiturils, octa acids, and pillararenes. Both single-trajectory and three-trajectory sampling protocols were applied. Entropic contributions were estimated via MM-based normal mode analysis and xTB-based statistical approximations. We evaluated predictive performance using Kendall τ, Pearson r, and predictive index.

Results: The three-trajectory protocol consistently outperformed the single-trajectory counterpart across Hamiltonians and solvent models. Among all configurations, the GFN2-xTB/PB combination showed the best predictive accuracy, although it fell short of the top-performing MM/GBOBCSA ΔG method. Notably, in challenging systems like sulfur-substituted pillararenes, xTB methods exhibited superior performance, whereas MM/GBSA failed due to inadequate error cancellation. The use of CPCM-X did not further enhance accuracy, possibly due to unsuccessful error cancellation.

Conclusions: While MM/GBSA remains the most robust protocol for general use, the GFN2-xTB/PB ΔH method emerges as a viable alternative for cases where MM-based methods perform poorly. These findings highlight the value of xTB-based multiscale approaches for receptor-ligand binding, especially in complex or chemically diverse systems.

As a mechanical wave capable of transmitting thermal and mechanical energy, ultrasound has emerged as a pivotal tool in regenerative medicine due to its non-invasive nature. Low-intensity pulsed ultrasound (LIPUS), a mechanoregulatory technique independent of thermal effects, delivers controlled mechanical stimuli to activate endogenous mechanotransduction pathways, such as ion channels, transmembrane proteins, and cytoskeleton-mediated signaling cascades. These pathways regulate critical cellular processes, such as proliferation, differentiation, and apoptosis, positioning LIPUS as a promising modality for targeted modulation of cell fate. Preclinical and clinical studies have demonstrated the therapeutic efficacy of LIPUS across diverse applications, including bone repair, neural regeneration, and soft tissue rehabilitation. However, optimizing stimulation parameters and advancing clinical translation remain key challenges. This review summarizes the central role of LIPUS in promoting tissue regeneration through non-thermal regulation of cellular homeostasis and explores strategies to accelerate clinical adoption of LIPUS. By integrating mechanistic insights with translational perspectives, this review provides a roadmap for advancing LIPUS-driven regenerative medicine in the era of precision bioengineering.

Osteochondral damage is primarily caused by degeneration of articular cartilage due to trauma, degenerative injury. Current approaches to treating cartilage damage typically involve medications, physical therapy, interventional therapy, and surgery. Drug delivery to the cartilage has shown promise in cartilage regeneration and slowing the progression of cartilage degeneration. However, the unique physiologic composition of articular cartilage poses challenges for effective drug delivery. Systemic administration of drugs may lead to inadequate drug distribution within the cartilage. Direct intra-articular injection of drugs can result in rapid clearance and limited retention time of the drug in the joint cavity. In summary, the limited duration of drug efficacy within the joint due to a short half-life and restricted diffusion through cartilage poses challenges for long-term drug therapy. Surgical intervention becomes necessary in cases of severe joint degeneration or ineffectiveness of alternative treatments. Various clinical studies have demonstrated the effectiveness of surgical approaches, such as an osteochondral autograft transplantation system (OATS), autologous chondrocyte implantation (ACI), and microfracture. Unfortunately, these interventions are also associated with potential adverse effects. The ongoing advances in biomaterials for osteochondral tissue regeneration and replacement have led to a growing interest in the utilization of biomaterial-based drug delivery systems for tissue regeneration. The integration of bioactive molecules, drugs, and genes with biomaterials presents a novel strategy for advancing osteochondral regeneration. A desirable drug delivery system should be able to penetrate cartilage tissue before the drug is cleared by synovial capillaries and lymphatic vessels, and bind to components of the cartilage extracellular matrix to reduce the physical deformation of cartilage during locomotion, resulting in a cartilage-specific drug pool. This paper was motivated by the great potential of biomaterials for osteochondral tissue regeneration and reviews recent progress in biomaterial-based drug delivery systems for osteochondral regeneration.

Quercetin, a bioactive flavonoid abundant in diverse plant species, has been extensively investigated for its neuroprotective properties against neurodegenerative diseases (NDDs), such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. This review systematically explored the multifaceted therapeutic potential of quercetin, emphasizing the mechanisms of action, pharmacologic efficacy, and translational significance in modern neurotherapeutics. Quercetin demonstrated potent antioxidant effects by scavenging reactive oxygen species and modulating the Nrf2-ARE pathway, thereby mitigating oxidative stress, a hallmark of NDDs associated with mitochondrial dysfunction, protein aggregation, and neuronal apoptosis. Furthermore, the ability of quercetin to regulate the PI3K/Akt pathway promoted mitochondrial biogenesis and preserved neuronal integrity by stabilizing membrane potential. Anti-inflammatory effects were evident vis-a-vis inhibition of the NF-κB and MAPK pathways, suppression of microglial activation, and cytokine release. In addition, quercetin disrupted tau hyperphosphorylation via GSK3β inhibition and attenuated amyloid-beta toxicity, offering cognitive protection. Preclinical studies highlighted the ability of quercetin to modulate excitotoxicity and enhance neuroplasticity, while emerging evidence support synergy of quercetin with existing pharmacologic agents. Genetic variations influencing key pathways, including Nrf2 and PI3K, underscore the necessity for personalized therapeutic approaches. Advances in drug delivery systems, scaffold modelling, and CRISPR-mediated interventions revealed the potential for optimizing the bioavailability and specificity of quercetin. This review bridges critical knowledge gaps by integrating mechanistic insights with clinical perspectives, advocating for translating quercetin-based therapies into precision medicine. By addressing challenges in bioavailability and exploring innovative strategies, this article underscores the promise of quercetin as a cornerstone for neuroprotective interventions in NDDs.

Objective: This study examined the complex interactions among differential gene expression, immune responses, therapy-associated genes in Alzheimer’s disease (AD), and cognitive impairment, with a distinct focus on the integration of music therapy. Our objective was to delineate the landscape of differentially expressed genes (DEGs), particularly the interconnections between gene expression changes and therapeutic interventions, including exercise and music therapy, to discover immune-associated therapeutic targets.

Methods: Through evaluation of the gene expression datasets GSE140831 and GSE48624, we identified DEGs and investigated their interactions with genes whose expression is induced by exercise and music therapy. Through protein-protein interaction analysis, gene set variation analysis, immune infiltration studies, and correlation analyses, we revealed the regulatory interactions and pathway enrichments. An mRNA-miRNA interaction network was constructed to elucidate regulatory mechanisms, and a drug-target interaction analysis was performed to discover potential therapeutic avenues.

Results: Our study revealed the complex organization of DEGs. In addition to identifying IL2RB and TUBA1B, we propose these genes as critical modulators in the context of exercise, music therapy, and AD. Our results indicated a substantial upregulation of pathways, such as glycolysis and TGF-beta signaling, in response to exercise, music therapy, and AD. These pathways revealed significant changes in gene expression compared to baseline conditions, highlighting their involvement in immune response modulation. The network of mRNA-miRNA interactions revealed key regulators of immune response and cognition. Our examination of drug and target interactions provided insights into potential mechanisms of action for disease modulation.

Conclusions: This research provided a comprehensive overview of DEGs in AD and cognitive impairment, and uniquely incorporated evaluation of music therapy. Our findings underscore the importance of IL2RB and TUBA1B as potential therapeutic targets; provide initial insights into the mechanisms of immune response; and suggest new pathways for targeted treatment development.

Solid tumors are characterized by extensive extracellular matrix (ECM) remodeling prominently featuring massive collagen deposition. This dense collagen network does not act as inert scaffolding but actively orchestrates critical aspects of tumor progression and therapy resistance, thereby shaping the fate of cancer cells. Collagen influences cellular behavior through multiple mechanisms, including providing structural rigidity, modulating mechanotransduction signaling pathways, creating physical barriers to immune cell infiltration and drug penetration, and serving as a reservoir for signaling molecules. Here, we discuss recent findings regarding the critical roles of collagen in tumors and potential therapies for armored and cold tumors, a refractory subset demonstrating high collagen deposition and low immune infiltration.

Ultraviolet (UV) photofunctionalization is a promising surface activation strategy for orthopedic implants that offers a safe, coating-free, and intraoperatively applicable approach to enhance bone implant integration. This commentary evaluates the translational potential of UV photofuntionalization and outlines key mechanisms and applications. By removing hydrocarbons and increasing hydrophilicity and protein adsorption, UV treatment transforms titanium into a biologically active interface that accelerates osteoblast attachment, proliferation, and differentiation. Evidence from in vitro and in vivo models, including diabetic and osteoporotic conditions, demonstrates consistently improved osseointegration, while early clinical data indicate reduced healing time and enhanced implant stability, especially in spinal fusion and large bone defect reconstruction. Moreover, UV photofunctionalization synergizes with advanced implant technologies, such as 3D-printed porous scaffolds, ion-doped alloys, and polymer–metal composites, enhancing biological performance without altering geometry or introducing chemical agents. Despite challenges in standardization and workflow integration, the intraoperative applicability and favorable safety profile of UV photofunctionalization support readiness for clinical adoption. Given the demand for effective strategies in complex or biologically compromised bone reconstructions, UV photofunctionalization represents a novel, additive-free, deployable method that significantly improves osseointegration across implant materials, even under high-risk conditions, ultimately enhancing outcomes and reducing implant failure.

Extracellular vesicles (EVs) are nanoscale, membrane-bound carriers that are naturally secreted by cells and capable of transporting proteins, lipids, and nucleic acids across biological barriers. As key mediators of intercellular communication, EVs participate in immune regulation, tissue repair, and disease progression. The structural integrity of EVs, which is conferred by a lipid bilayer, protects cargo from degradation, while surface molecules facilitate targeted cell interactions. With increasing interest in their therapeutic utility, EVs have emerged as promising candidates in diagnostics, drug delivery, and regenerative medicine. EVs derived from milk, plants, and microbes exhibit distinct bioactivities, broadening the applicability in translational research. The intrinsic biocompatibility and low immunogenicity of EVs further enhance their clinical relevance. This review highlights recent advances in the understanding and biomedical utilization of exogenous EVs. The structural features, mechanisms of cellular uptake, and functional roles in modulating disease pathways are discussed. Furthermore, the unique advantages and challenges of leveraging exogenous EVs for clinical translation are explored, including standardization, loading efficiency, and targeting specificity. With continuous innovation at the interface of nanotechnology, synthetic biology, and biomedicine, exogenous EVs are poised to become next-generation platforms for precision therapy and regenerative strategies.

Cell membrane-derived nanovesicles (CMNVs) are natural nanocarriers efficiently encapsulating bioactive molecules and imaging probes. Conventional nanoprobes face challenges, like rapid immune clearance, off-target accumulation, and long-term toxicity. CMNVs overcome these challenges by leveraging inherent biofunctionalization. CMNVs enhance encapsulated nanoprobe targeting, prolong circulation, boost specific tissue accumulation, and improve imaging precision through inherited membrane proteins or minimally disruptive exogenous modifications. CMNVs show significant promise across multiple imaging modalities, including fluorescence, bioluminescence, photoacoustic, and MRI. This review systematically evaluates the limitations of traditional nanoprobes, highlights the unique advantages of CMNVs in enhancing diverse probe performance, discusses current challenges in harnessing CMNVs for imaging, and provides insights for developing future high-precision imaging strategies.

In recent years, substantial advancements have been made in the field of wearable flexible sensors. These sensors possess elasticity and conformability, coupled with enhanced data collection and processing capabilities, which lead to increases in hardware performance and significant enhancements in software data processing capabilities. These sensors can precisely measure a wide range of human physiological parameters, including heart rate, respiration, temperature, blood glucose levels, muscle activity, and ion concentrations in sweat. Beyond their fundamental functions, these sensors can transmit data in real time through wireless transmission modules. Therefore, these sensors are highly valuable for sports monitoring, and have considerable potential for personal healthcare and medical systems. This review comprehensively summarizes recent advancements in material innovation, stretchable structural designs, and energy integration technology breakthroughs in wearable flexible sensors. The applications in motion monitoring are systematically categorized by signal type into physical, chemical, and electrophysiological sensors. Finally, challenges in wearable flexible sensors for motion monitoring are discussed, and feasible strategies are proposed to guide future research.

Transdermal drug delivery (TDD) offers a non-invasive alternative to conventional administration routes, yet the efficacy of TDD is constrained by the impermeable stratum corneum (SC) of the skin, particularly for macromolecules exceeding 500 Da. While microneedle technology addresses this barrier by creating micro-scale channels, the limited penetration depth of microneedles restricts drug delivery to superficial epidermal layers. This review highlights the transformative potential of combining ultrasound and microneedles for enhanced TDD, which synergistically integrate physical disruption and energy-driven permeation enhancement. Unlike material-based or charge/magnetism-dependent strategies, ultrasound leverages multifactorial mechanisms (mechanical stress, cavitation, and thermal effects) to propel drugs through microneedle-generated pathways into deeper tissues. The ultrasound-microneedle (US-MN) system enables spatiotemporally controlled drug release with sonochemical/piezoelectric effects expanding applications in precision medicine. The underlying mechanisms, technological innovations, and clinical translation challenges of the US-MN have been critically evaluated herein, emphasizing the versatility for macromolecules and precision medicine. By bridging mechanisms with translational gaps, this work provides a roadmap for optimizing the US-MN platform, offering researchers actionable strategies to advance TDD for chronic diseases, vaccines, and targeted therapies.

The emerging application of artificial intelligence (AI) in pediatric ultrasound has shown significant potential to improve diagnostic accuracy and efficiency, particularly in addressing the challenges of conventional ultrasound in operator dependence, inconsistent image quality, and limited quantitative analysis capabilities. These limitations arise from the inherent complexity of pediatric ultrasound image interpretation, such as organ immaturity, motion artifacts, and intestinal gas interference. AI can enhance structural recognition, offering automated, standardized measurements. AI applications can also assist non-expert physicians in enhancing diagnostic accuracy. This review summarizes recent advances in AI applications for pediatric ultrasound across different systems, including preliminary diagnosis, screening, detailed analysis, and decision support, while providing a detailed discussion of technical advances, unmet challenges, and future directions. Future research can focus on intelligent cross-system feature analysis frameworks, translational application of AI-driven pediatric ultrasound in multi-disease diagnosis, and fine-tuned models for personalized treatment based on large-scale randomized controlled trials. This review provides an up-to-date reference for clinicians, ultrasound technicians, researchers, and biomedical engineers.

Radiation therapy (RT) has a critical role in cancer treatment, yet the efficacy is often limited by tumor resistance mechanisms, such as cellular DNA repair activation, heterogeneous cell cycle, hypoxia, and an immunosuppressive microenvironment. Conventional radiosensitization strategies face significant challenges, which are caused by insufficient efficiency, a short treatment window, and off-target toxicities. In contrast, living cells offer a novel strategy to overcome these limitations by leveraging innate characteristics, including tumor chemotaxis and radiosensitization factor secretion. Living cells have recently been applied in radiotherapy to amplify tumor cell killing effects and avoid healthy tissue damage. This review systematically summarizes recent advances in living cell-based radiosensitization strategies, emphasizing the dual roles as tumor targeting carriers and dynamic microenvironment modulators. The radiosensitization mechanisms underlying diverse cell types are analyzed. For example, stem cells enhance radiotherapy via STAT3-mediated DNA repair inhibition, while immune cells and bacteria use immunogenic cell death synergy to induce immune activation. Finally, the challenges and prospects of living cells in achieving radiosensitization are highlighted.

Artificial intelligence (AI) is rapidly reshaping research across disciplines. In tasks as diverse as automating literature reviews and decoding complex datasets, AI has become central to modern inquiry. However, its rise has also prompted critical questions regarding human judgment, ethics, and dependence on machine outputs. Although AI increases efficiency, it cannot replace the creativity, intuition, and moral responsibility that underpin credible research. The challenge is therefore not to surrender human intellect to algorithms but to cultivate a partnership between them.

Background: Indigo naturalis (IN), a traditional Chinese herbal medicine, shows promising potential for treating autoimmune inflammatory diseases. However, its clinical translation and application are being limited by concerns regarding vascular toxicity.

Methods: Mendelian randomization (MR) and colocalization analyses were conducted to systematically investigate the target-specific vascular risks associated with IN.

Results: Causal associations were identified between four targets of IN and multiple vascular disorders, including deep vein thrombosis (DVT) (OR = 1.001, 95% CI = 1.003–1.000, P = 0.008), among others. Notably, urate was identified as a mediator between IN and DVT, exhibiting a mild mediation effect (7.3%, P = 0.048).

Conclusion: For the first time, the causal effects of IN on vascular toxicity were demonstrated using MR. This study provides insights into the safety implications of IN for anti-inflammatory applications, which would facilitate evidence-based research on IN and its clinical translation.

Objective: The purpose of this work was to establish and assess deep learning (DL) models based on ultrasound images for discriminating between benign and malignant adnexal lesions in postmenopausal women.

Materials and methods: In this retrospective multicenter study, a total of 662 adnexal lesions from 662 postmenopausal women between January 2020 and December 2024 were included. Five DL models (model_Resnet50, model_{swin_transformer}, model_vit, model_{Convnext_tiny}, and model_{Regnet_y_8gf}) were trained and validated. Model performance was assessed with area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. The Assessment of Different NEoplasias in the adneXa (ADNEX) model without CA-125 was applied for comparison. The diagnostic performance of junior radiologists was assessed without or with DL model assistance. In addition, subgroup analysis was performed to assess the robustness of the DL models.

Results: Model_{swin_transformer} yielded the highest AUC (0.964) among DL models in the external validation cohort (n = 93), with high sensitivity (0.952) and specificity (0.903). No statistical difference was observed between the AUCs of model_{swin_transformer} and the ADNEX model (AUC: 0.968;P = 0.819). Junior radiologists assisted by the DL model exhibited improved diagnostic performance, with higher AUCs (0.938 vs. 0.819; 0.944 vs. 0.838) and sensitivity (0.905 vs. 0.667; 1.000 vs. 0.857), while maintaining comparable specificity. However, model_{swin_transformer} did not significantly improve the diagnostic performance of attending radiologists and senior radiologists. Subgroup analyses revealed that model_{swin_transformer} presented superior diagnostic accuracy in purely cystic lesions, solid lesions, and lesions with a maximum diameter < 100 mm.

Conclusion: The proposed DL model has potential to assist radiologists in classifying adnexal lesions in postmenopausal women by effectively enhancing the diagnostic performance of junior radiologists in resource-limited healthcare settings.