In recent years, magnetic hyperthermia therapy (MHT), recognized as a clinically promising anticancer treatment, has focused on enhancing therapeutic outcomes in tumor management, such as optimizing magnetic nanoparticle accumulation within tumor microenvironments and developing synergistic combination approaches with other therapies. Herein, we developed nanoengineered neutrophils (NE) by loading magnetic nanoparticles (FPP) onto healthy-derived NE, designated as FPPN. The combination of FPP's pronounced T₂-weighted magnetic resonance imaging (MRI) and superior magnetothermal efficiency with the high tumor-targeting and cancer-killing activity of NE successfully achieved the synergistic implementation of MHT and NE. Under the guidance of T₂-weighted MRI, the accumulation of FPPN within the tumor site demonstrated a significant enhancement compared with free FPP. Under exposure to alternating magnetic fields, the thermal energy produced by FPP and FPPN could ablate tumor cells directly. Intriguingly, mitochondria within NE exhibit significant reactive oxygen species (ROS) under magnetothermal activation, thereby enhancing therapeutic efficacy and enabling synergistic tumor treatment through the combination of MHT and NE-mediated ROS. This therapeutic strategy not only highlighted the significant potential of nanoengineered NE for highly efficient MHT but also established a novel therapeutic platform for precision-targeted treatment of deep-seated tumors.

Bacillus Calmette-Guérin (BCG) immunotherapy is limited by resistance in ∼50% of patients, linked to tumor microenvironment (TME) angiogenesis. The work explored if BCG-activated tumor-associated macrophages (TAMs) drive angiogenesis via hypoxia-inducible factor-1α (HIF-1α) to impair BCG efficacy. Results demonstrated that macrophages stimulated with BCG significantly enhanced the proliferation, migration, and tube formation of endothelial cells. Further mechanistic studies revealed that this pro-angiogenic effect was mediated through the activation of the NF-_κB, PI3K/AKT and p38/MAPK signaling pathways. Activation of these pathways subsequently led to the upregulated expression of HIF-1α and vascular endothelial growth factor A (VEGFA). Critically, HIF-1α deficiency in macrophages effectively inhibited BCG-induced angiogenesis without exerting a significant impact on the infiltration of CD8⁺ T cells or B cells. Additionally, BCG stimulation enhanced the secretion of VEGF encapsulated in exosomes in an HIF-1α-dependent manner, and these VEGF-enriched exosomes further facilitated the activation of endothelial cell functions. In conclusion, the present study confirms that BCG can promote tumor angiogenesis by activating macrophages to induce the release of exosome-derived VEGF through an HIF-1α-dependent pathway. Targeting the HIF–1α-exosome-derived VEGF (HIF-1α–exoVEGF) axis holds promise as a potential strategy to overcome BCG resistance and improve its therapeutic efficacy.

The escalating threat of antibacterial resistance demands innovative approaches for the discovery of novel antibiotics. Identifying hit and lead compounds with unique scaffolds during the early phases of drug development remains a significant challenge. Although various generative models have been proposed to create drug-like molecules, their capacity to design wet-lab-validated target-specific compounds with novel scaffolds has been scarcely validated. Herein, we propose TargetGen-recurrent neural network (RNN), a state-of-the-art deep generative learning model designed to explore chemical space and generate novel tailor-made virtual compound libraries for specific biological targets. By leveraging a combination of transfer learning, temperature-modulated sampling, and stringent chemical validation, TargetGen-RNN was trained on 5.7 million drug-like compounds from the ZINC database and fine-tuned with 82 known Staphylococcus aureus DHFR inhibitors, yielding 28,708 structurally diverse and chemically viable novel, tailor-made molecules. Virtual screening, including QSAR analysis, pharmacophore mapping, molecular docking, molecular dynamic simulations, and multi-criteria decision analysis against the generated tailor-made compound library, led to the discovery of a potent antibiotic compound (SAK-2970) with a novel scaffold with high predicted antibiotic activity, binding affinity, and favorable ADMET profiles. SAK-2970 demonstrated remarkable in vitro bactericidal activity against S. aureus, strong biofilm inhibition and eradication capabilities, and exceptional efficacy against ciprofloxacin resistant S. aureus. In a mouse model of drug-resistant bacteremia, SAK-2970 significantly reduced bacterial load and improved survival rates with minimal systemic toxicity, underscoring its biocompatibility and therapeutic potential. These findings validate SAK-2970 as a promising candidate for developing antibiotic treatments targeting resistant bacterial infections and highlight TargetGen-RNN's powerful capability to generate hit compounds with novel scaffolds, advancing the frontier of antibiotic discovery.

Rapid, sensitive, and accurate detection of ingredients in body fluids is crucial for monitoring health status and diagnosing diseases. Fluorescent biosensors have emerged as a user-friendly tool for biomarker detection, because of their high sensitivity, rapid response, and adaptability. Among the various signal probes used in fluorescent biosensors, aggregation-induced emission (AIE) luminogens (AIEgens) stand out as a highly promising candidate owing to their unique property of enhanced emission in the aggregated or solid state. This review outlines the sensing mechanisms and design strategies of AIE probes for constructing AIE-based fluorescent biosensors. It provides a comprehensive overview of recent advancements in AIE probes for detecting various ingredients in body fluids, including blood, urine, saliva, throat swabs, and sweat. The efficacy of AIEgen-based fluorescent biosensors in these applications is highlighted, focusing on the design of probes, response mechanisms, and luminescence principles. Finally, the current challenges of AIEgen-based biosensors and future research perspectives are discussed, aiming to inspire the development of AIE probes and improve the sensitivity and accessibility of AIEgen-based fluorescent biosensors.

Single-cell spatial transcriptomics enables comprehensive gene expression profiling with precise cellular localization within tissue architecture. To systematically evaluate the compatibility and performance of alternative sequencing platforms for this application, we directly compared Illumina NovaSeq 6000 and GeneMind SURFSeq 5000 using SeekSpace single-cell spatial transcriptomics on mouse brain and lung tissues. Identical cDNA libraries were sequenced on both platforms and processed with a unified bioinformatics pipeline to ensure direct comparability. Across all key sequencing quality metrics—including unique molecular identifier and spatial barcode detection, gene identification, and mapping rates—SURFSeq 5000 demonstrated performance highly similar to NovaSeq 6000, with nearly equivalent quality control metrics and data yields. Integrated downstream analyses—including dimensionality reduction, cell type annotation, spatial mapping, differential gene expression, cell–cell interaction, and spatial hotspot module detection—revealed highly concordant spatial patterns and cellular compositions across both brain and lung tissues. The overlap of differentially expressed genes between platforms reached approximately 65%, and cross-platform cell type assignments showed high reproducibility (Area Under the Receiver Operation Characteristic curve > 0.92). No significant batch effects were observed. These results demonstrate that GeneMind SURFSeq 5000 is a reliable and cost-effective alternative to Illumina NovaSeq 6000 for single-cell spatial transcriptomics, providing comparable data quality and analytical robustness in murine tissue studies. The robust performance of SURFSeq 5000 supports the broader adoption of alternative and affordable sequencing technologies in spatial omics research.

The microstructure of scaffolds is essential for enhancing cell-extracellular matrix interactions, which are critical for osteochondral regeneration. This study investigates the innovative use of 3D printing to mimic DOUGONG brackets to achieve this goal. Composite scaffolds of β-tricalcium phosphate, akermanite (AKer), and strontium silicate (SrSiO₃) at 1%, 5%, and 10% concentrations were fabricated via 3D printing. The osteogenic differentiation effects on bone marrow mesenchymal stromal cells and chondrogenic promotion effects on chondrocytes of different scaffolds were analyzed in vitro. An osteochondral defect model was created in SD rat knee joints, and various scaffold materials were implanted to evaluate their repair and anti-inflammatory effects. Characterization showed that SrSiO₃ composite scaffolds had uniform pore structures and high porosity with improved mechanical properties and sustained strontium ion release capacities. The Aker/Sr5% scaffold significantly enhanced cell viability and proliferation, inhibited apoptosis, and upregulated osteogenic markers (RUNX2, COL1A1, OCN, OPN) while downregulating inflammatory factors (IL-6 and TNF-α). This scaffold also improved the chondrocyte phenotype as indicated by increased chondrogenic markers (COL2A1 and SOX9). Additionally, it excelled in bone volume, bone mineral density, and tissue repair scores. The DOUGONG-inspired AKer/SrSiO₃ composite scaffold promotes osteochondral regeneration by enhancing osteogenesis via the PI3K/Akt signaling pathway and cytokine-cytokine receptor interaction, while simultaneously facilitating cartilage repair by promoting chondral phenotypes. This work provides a theoretical basis and new strategies for the clinical transformation of osteochondral repair.

Gut microbiota, a complex microbial community in the human intestine, are vital for digestion, nutrient absorption, and immune regulation, maintaining gut micro-ecological balance. Accurate detection of its composition, structure, and function is crucial for understanding the relationship between health and disease, early disease diagnosis, personalized treatment, and exploring disease mechanisms. Traditional detection methods such as culture and conventional polymerase chain reaction (PCR) have limitations. Culture methods, which rely on specific media, struggle with anaerobic and fastidious microbes and thus have long detection times. Conventional PCR is complex, has low throughput, and is prone to contamination, not meeting the need for efficient, accurate, and high-throughput analysis. Microfluidic technology, manipulating small fluid volumes through microscale channels, offers new opportunities with advantages such as simple operation, low reagent consumption, and fast analysis. This review encompasses the microfluidic-based detection methods of gut microbiota in recent years. It expounds on the principles of these methods and analyzes their achievements, advantages, and limitations in practical applications. The aim is to provide multi-dimensional technical references for relevant research, thereby promoting the application of this technology in the research of gut microbiota and the management of gut diseases.

Infections are a leading contributor to delayed mortality in patients with combat-related trauma. Thus, the real-time, accurate, and rapid detection of invasive pathogens is essential for optimizing wound management and accelerating recovery. Recent innovations in point-of-care testing (POCT) biosensors, which are characterized by enhanced portability and multifunctionality, offer promising solutions for onsite diagnostics without relying on centralized laboratories. These technologies are particularly effective for the minimally invasive monitoring of real-time biophysical or biochemical signals at wound sites. This review explores the species and distribution of bacteria associated with combat-related injuries. Thereafter, we summarize recent advancements in optical and other biosensors (electrochemical, piezoelectric, and thermal) used in bacterial POCT. Key integration strategies are highlighted, including biosensor coupling with microdevices (e.g., microfluidics and microarrays), smart systems (e.g., smartphone readouts and artificial intelligence-based interpretation), and the Internet of Things. We also address the current challenges in biosensor fabrication and outline the expected future directions for biosensing. This review aims to provide a useful reference for the development of POCT biosensors for bacterial detection in combat and trauma care settings.

Dengue fever, an acute Aedes-borne infectious disease caused by the dengue virus (DENV), is a substantial global health challenge, necessitating the development of swift and effective surveillance methodologies. We have developed a Recombinase Aided Amplification (RAA)–Cas12a assay that exhibits superior analytical sensitivity compared with real-time PCR while maintaining comparable specificity. In clinical specimen testing, the assay demonstrated a sensitivity of 92.3% and a specificity of 100%, using a signal-to-noise ratio of ≥2.0 as the positivity threshold. Furthermore, the RAA–Cas12a assay displayed remarkable sensitivity in detecting DENV in both adult and larval mosquitoes, with field data from mosquito surveillance aligning closely with the emergence of local dengue cases. Characterized by its simplicity, rapidity, and precision, the RAA–Cas12a approach emerges as a highly promising technology for monitoring virus carriage in field-collected mosquitoes, thereby functioning as both an early warning system and a crucial indicator for effective dengue outbreak management. The practicality and cost-effectiveness of this methodology provide a robust foundation for the establishment of an efficient global collaborative surveillance and risk assessment platform to mitigate the rapid spread of dengue.

For colorectal cancer (CRC), treatment outcomes and prognosis remain poor even when using first-line chemotherapeutics and immunotherapeutics. The main reasons include (i) lack of tumor specificity, severe off-target cytotoxicity leading to adverse side effects, and occurrence of chemoresistance, and (ii) the immunosuppressive “cold” tumor microenvironment (TME). Herein, we demonstrate an example of highly efficient targeted CRC chemoimmunotherapy with cisplatin (CDDP)-containing nanomedicine (CDDP@MSN-Anti-CD47) in a patient-derived organoids xenograft model. The CDDP@MSN-Anti-CD47 is composed of CDDP-loaded mesoporous silica nanoparticles with superficially functionalized anti-CD47 antibodies to target cluster of differentiation CD47, a transmembrane integrin-associated protein that is over-expressed in CRC cells and can bind with signal regulatory protein α on tumor-associated macrophages (TAMs) to maintain the immunosuppressive TME. Our results demonstrated that CDDP@MSN-Anti-CD47 achieved targeted delivery of CDDP to CRC cells with extended release, and induced reactive oxygen species overproduction to inhibit CRC cells and CRC patient-derived organoids growth via activating caspase-3-related apoptosis and immunogenic cell death. DAMPs released following CDDP@MSN-Anti-CD47 treatment promoted the polarization of TAMs from immunosuppressive M2 to pro-inflammatory M1 phenotype and also synergized with the functionalized anti-CD47 antibodies to restore macrophage phagocytic activity against CRC cells. In both CRC cell and patient-derived organoid xenograft models, CDDP@MSN-Anti-CD47 could specifically target the tumor, showing strong anti-tumor effects, prolonged survival rate, and low systemic cytotoxicity. Overall, CDDP@MSN-Anti augments combination chemotherapy and immunotherapy, and can be developed as a novel and promising strategy for the clinical treatment of CRC.

Tissue engineering holds immense promise for repairing damaged tissues and organs, yet current approaches often fall short due to poor host integration, limited drug delivery precision, and scalability challenges. Recent developments in electrostimulation-responsive biomaterials incorporating drug or growth factor-loaded nanoparticles offer a novel path forward. However, a comprehensive review integrating these emerging strategies within a unified framework is lacking. This review uniquely synthesizes current advances in electroactive materials such as conductive polymers, hydrogels, and piezoelectric scaffolds, and their dynamic interactions with electrostimulation at the cellular and molecular levels. It highlights how the incorporation of nanoparticles such as iron oxide, silver, and carbon-based enhances localized therapeutic delivery and regenerative outcomes. Unlike existing literature, this work provides a cross-tissue perspective, covering applications in cardiac, bone, cartilage, skin, neural, and cancer tissue regeneration. It also critically analyses fabrication techniques, biocompatibility issues, and design strategies for clinical scalability. By integrating diverse findings, the review identifies key knowledge gaps and emerging trends including smart, responsive scaffolds and interdisciplinary approaches that are shaping the future of regenerative medicine. This comprehensive and forward-looking review serves as a novel resource for researchers and clinicians aiming to translate electrostimulation-responsive platforms into effective next-generation therapeutic solutions.

Vat photopolymerization (VP)-based bioprinting is rapidly emerging as a transformative platform for fabricating complex, cell-laden tissue constructs with unparalleled spatial resolution and geometric precision. This review presents a comprehensive overview of recent advances in VP-based bioprinting, organized around core themes of photopolymerization chemistry, printing modalities, bio-ink design, and biomedical applications. We first describe the underlying crosslinking mechanisms including chain-growth, step-growth, redox-mediated, and initiator-free systems that enable spatiotemporal control over polymerization. The discussion then moves to key VP-based bioprinting techniques such as stereolithography apparatus (SLA), digital light processing, two-photon polymerization, and volumetric additive manufacturing, emphasizing their printing principles and suitability for bioprinting applications. A central focus is placed on the rational design of photo-crosslinkable bio-inks, comprising functional monomers, photo-initiators (PIs), and photo-absorbers (PAs). We critically examine design criteria such as cytocompatibility, rheological and optical behavior, mechanical performance, degradation profiles, and scalability, highlighting the complex trade-offs between print fidelity and biological function. The utility of VP-based bioprinting is further illustrated through its application in constructing advanced tissues, including bone, cardiac, cartilage, corneal, and hepatic models. Finally, we explore emerging frontiers such as multi-material and multi-modal bioprinting, machine learning-guided optimization, and regulatory pathways toward clinical translation. Collectively, these insights outline a roadmap for advancing VP-based bioprinting into a clinically viable, high-throughput tissue engineering technology.

Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis and arises from the convergence of genetic susceptibility, environmental exposures, immune dysregulation, and gut microbiome perturbations. Metabolic reprogramming has emerged as a central feature of IBD pathogenesis. Immune and epithelial cells in IBD show coordinated disturbances in glycolysis, fatty-acid metabolism, and oxidative phosphorylation, which shape macrophage and T-cell polarization and weaken epithelial barrier integrity. Microbiota-derived metabolites, including short-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives, act as key immunometabolic signals, with SCFAs promoting regulatory programs and barrier repair, whereas disordered bile-acid pools and dysregulated receptor signaling can drive inflammation and disrupt the barrier. These insights motivate metabolic interventions that complement immunotherapy, including modulation of the microbiota, supplementation or engineered delivery of specific metabolites, and targeting of metabolic pathways (AMPK, mTOR) and receptors (FXR, TGR5, AhR). Early clinical studies indicate potential benefit in selected patient subsets, although effect sizes are variable, and translation remains limited by disease heterogeneity, context-dependent metabolite effects, suboptimal delivery to inflamed segments, and the absence of predictive biomarkers. This review synthesizes recent advances in IBD immunometabolism, integrates evidence across cells, pathways, and microbial metabolites, and outlines actionable opportunities for development, including patient stratification, target-engagement readouts, and rigorously designed trials with endpoints such as mucosal healing, corticosteroid-free remission, and relapse reduction.

In recent years, cancer immunotherapy has gained substantial momentum, particularly in the field of vaccines and immunotherapeutics. Among these advancements, extracellular vesicles (EVs) have emerged as a promising cell-free vaccine system due to their unique capacity to display diverse antigens and immune-stimulatory molecules. Additionally, their excellent biocompatibility, ability to permeate across biological barriers, and targeting properties make EVs a promising platform for delivery of various therapeutics for cancer immunotherapy, such as RNAs, proteins, lipids, and chemotherapeutic agents. To date, EV-based vaccines and immunotherapeutics have demonstrated remarkable efficacy in combating various types of cancers. Herein, we endeavor to give a comprehensive summary of EV-based vaccines and immunotherapeutics for the treatment of cancers, delving into their advantages and challenges. Furthermore, emphasis was given on offering insight into the design rationale of each platform. Lastly, we recapitulate the recent preclinical and clinical application progress of EV-based vaccines and immunotherapeutics, highlighting their pivotal role in cancer immunotherapy.