ABSTRACTCancer is a complex disease characterized by systemic dysfunction, necessitating a balance between therapeutic efficacy and safety. Immunotherapy is a core treatment approach for activating the antitumor immune response in the human body. The development of intelligent hydrogels has provided an innovative platform for tumor immunotherapy, owing to their adjustable properties for controlled drug delivery and immune modulation. Tumor immunotherapy has achieved remarkable success in recent years. However, it continues to face critical challenges such as targeting and delivery barriers, suppression by the TME, and immune evasion and drug resistance. In response, as injectable or implantable biomaterials, hydrogels are emerging as a promising platform to address these limitations by enabling localized, controllable drug delivery and immunomodulation. This review systematically categorizes contemporary hydrogel construction strategies tailored for immunotherapy, highlighting the distinct advantages of specific architectures in diverse clinical contexts. By classifying hydrogel applications according to immune‐based strategies, the work underscores their multifunctional utility as precision delivery platforms and modulators of the immune microenvironment. This comprehensive overview elucidates the progress and design principles of hydrogel‐based immunotherapeutic platforms, providing valuable insights to guide future research and development in this evolving field.

ABSTRACTInflammatory diseases, encompassing conditions like inflammatory bowel disease and rheumatoid arthritis, present a significant clinical challenge with substantial treatment‐refractory patient populations despite biologic therapy advances. Stem cell therapeutics have emerged as a transformative approach, leveraging multifaceted regenerative mechanisms to address the complex pathophysiology of these conditions, which involves genetic, microbial, immunological, and epithelial dysregulation. This review focuses on comparing the clinical efficacy of contemporary stem cell strategies. We analyze outcomes across diverse cell sources, with a detailed examination of delivery methodologies. Our systematic analysis demonstrates superior efficacy with targeted delivery systems, particularly in managing localized inflammatory lesions (e.g., fistulas) and tissue restoration. Notably, minimally processed cellular interventions, such as autologous fat grafting and stromal vascular fraction therapy, show unexpected therapeutic promise. Critical translational barriers include suboptimal cell homing, limited engraftment persistence, and uncharacterized long‐term safety profiles. We propose strategic solutions through induced pluripotent stem cell platforms, precision genetic modifications, and advanced delivery technologies. By integrating mechanistic insights with robust clinical evidence, this review establishes an evidence‐based framework for optimizing stem cell therapeutics in inflammatory disease management. The analysis addresses fundamental scalability and safety considerations while identifying promising avenues for personalized regenerative medicine approaches in treatment‐refractory inflammatory conditions.

Hydrogels, with excellent hydrophilicity and high-water content, have emerged as highly versatile biomaterials for tissue engineering and regenerative medicine. On account of the natural mimicry of extracellular matrix (ECM), moisture retention, porosity, biocompatibility, biodegradability, and tunable functionality, they provide crucial structural and biochemical support for tissue repair. As chronic wounds, aging, and degenerative diseases continue to increase, hydrogels offer great potential to overcome the limitations of traditional therapies. Despite these developments, there remains a crucial need for hydrogels that can effectively address the complex, multiphase nature of tissue repair while being cost-effective and easily applicable in various clinical settings. This review begins by taking wound healing as a representative example, particularly elaborating on the process of wound healing and therapeutic strategies to illustrate the importance of hydrogel design by tissue engineering technology. We then comprehensively evaluate the emerging hydrogel systems that integrate multiple therapeutic functions, including drug delivery, infection prevention, stimulus responsiveness, and clinical translation for wound dressings. Additionally, this review further extends to the application scope and incorporates the latest research advancements of multifunctional hydrogels in other biomedical applications. Finally, we summarize the shortcomings of existing studies and propose future research directions, with a view to providing a valuable reference basis for the development of multifunctional hydrogels within the realm of tissue engineering and regenerative medicine.

Although the physiological level of reactive oxygen species (ROS) is crucial for governing life processes through redox signaling, the excessive accumulation of ROS can contribute to biomolecular damage and pathological state, namely, oxidative stress. This review systematically summarizes the molecular mechanisms underlying the dynamic equilibrium of cellular redox state, including the intracellular sources of ROS and the multilayered antioxidant defense network. When ROS production exceeds the regulatory limits of the antioxidant system, excessive ROS will act on a series of molecular targets and participate in the pathogenesis of diseases. Therapeutic targeting of the redox balance is regarded as an effective strategy for treating oxidative stress-related diseases, such as supplementation of direct antioxidants and enhancement of endogenous antioxidant defense network. Nevertheless, clinical trials that attempt to delay the onset or progression of such diseases are mostly negative. This review discusses the challenges encountered in the clinical application of antioxidant therapy and highlights the opportunities brought by novel technologies such as intelligent drug delivery system and personalized medicine. By adopting these new technologies, it is expected to overcome the limitations of traditional antioxidant therapy.

The 2022 global mpox outbreak caused by the monkeypox virus (MPXV) has underscored the urgent need for improved vaccine development. To address this need, we developed four candidate vaccine antigens based on conserved sequences of the MPXV A35R and M1R proteins utilizing a lipid nanoparticle (LNP) delivery system. All four vaccine candidates elicited varying degrees of humoral and cellular immune responses and conferred differential protection against MPXV and vaccinia virus (VACV) in BALB/c mice; notably, the dual-antigen vaccines MV1 and MV2 induced more potent immunogenicity, including higher neutralizing antibody titers and cytokine secretion levels. However, among the four candidates, only the dual-antigen vaccines MV1 and MV2 conferred protective efficacy in AGB6 mice and reduced infection-induced pox lesion formation, indicating that antigens containing both intracellular mature virus (IMV) and extracellular enveloped virus (EEV) targets may be key to exerting robust protection. Notably, MV2-which was designed via structural truncation and recombination based on poxvirus-broad-spectrum antibodies using the AlphaFold3 prediction platform and adopts a single-chain "dimer-like" configuration-exhibited not only optimal protective efficacy but also sustained durable immune responses and protection. These findings indicate that MV2 induces favorable immunogenicity and has potential for preventing MPXV and VACV infections, supporting its promise as a clinical vaccine candidate for MPXV.

ABSTRACT Traditional Chinese medicine (TCM), consisting of a complete TCM diagnosis and treatment system, is a valuable treasure in the long river of Chinese clinical history. However, the subjective diagnosis, ambiguous mechanisms, and complex formulas make it slightly lag behind the development of modern medicine. With the emergence of novel technologies such as artificial intelligence (AI) and nanotechnology, TCM modernization has regained its promise of hope. In this review, we provide an overview of applications of AI and nanotechnology to assist TCM modernization. Firstly, we summarize the auxiliary TCM diagnosis approaches based on machine learning and deep learning, which facilitate “four diagnostic methods” (inspection, auscultation–olfaction, inquiry, and pulse palpation) with standard and quantifiable data collection, and objective syndrome differentiation and diagnostic decisions. Secondly, a comprehensive overview of the nanotechnology used to enhance the therapeutic effects of TCM is provided, including optimizing TCM formulas and enhancing active targeting. Finally, we summarize the current challenges, clinical translation, and future perspectives of AI, TCM diagnosis, and nanotechnology. Our review and insights aim to provide valuable guidance for the continued advancement of TCM modernization.

Mycoplasma pneumoniae infections resurged globally in 2023-2024 following a significant decline during the coronavirus disease 2019 (COVID-19) pandemic. To understand the genomic epidemiology of this resurgence in China, a nationwide 1-year genomic surveillance identified 9907 patients infected with M. pneumoniae, resulting in an overall positive rate of 10.05%. We developed a hybrid capture-based targeted next-generation sequencing (hc-tNGS) assay, obtaining 271 high-quality genomes directly from clinical samples. Phylogenetic analysis of a global collection of 562M. pneumoniae genomes identified six distinct lineages, including three newly emerged main Chinese clades (MCCs) that co-circulated across various regions of China. Among these MCCs, one clade, comprising P1-1, ST17, and L4, was localized in Taiwan, while two others-P1-1, ST3, and L6 clade, and P1-2, ST14 and L2 clade-co-circulated in different regions of China during the 2023-2024 epidemic season. Notably, 96.31% of the isolates identified in this study exhibited a point mutation, primarily A2063G (95.94%). This study offers a comprehensive genomic characterization of the post-pandemic M. pneumoniae resurgence in China, highlighting the emergence and spread of resistant clades. These findings emphasize the importance of adopting a One Health approach to address the potential global public health threats posed by this resurgent pathogen.

Polycystic ovary syndrome (PCOS) is a well-documented endocrine disorder associated with metabolic abnormalities. Research has indicated potential links between PCOS and the gut microbiome, and the presence of microbial communities in follicular fluid (FF) has been demonstrated; however, their functional interplay with metabolites has not been elucidated. This case-control study involved 40 patients with PCOS and 40 controls matched for age. A comprehensive analysis of FF metabolites and microbial communities by means of metabolomics analysis and 16S rDNA sequencing was performed. Twelve metabolites and 15 microbial communities were significantly different between the PCOS and control groups. AMH and AFC were significantly associated with the majority of the differentially abundant metabolites and bacteria, suggesting a potential association between FF components and ovarian function. In this study, we found that D-glucose and Alicyclobacillus were the most important variables in the metabolite model and microbial model, respectively. Mechanistically, Alicyclobacillus acidoterrestris, Terrimonas ferruginea, or Terrimonas pekingense can efficiently utilize glucose thereby reducing FF glucose levels, which provides insights into the microbiome-metabolite connection. These findings suggest a potential link among bacteria-metabolite-ovarian function, which could have implications for understanding the pathophysiology of PCOS and developing novel diagnostic and therapeutic strategies targeting metabolic and microbial aspects.

ABSTRACTEstrogen receptor (ER) α is a central regulator of osteoclasts in osteoporosis induced by estrogen deficiency. ERα is regulated through interactions with various coactivators; however, the precise mechanisms of these interactions are not yet fully understood. We screened for proteins that bind to ERα using LC–MS/MS and identified a physical interaction between HSD17B7 and ERα, specifically ERα binding to the 119–172 domain of HSD17B7. This interaction blocked ubiquitin–proteasomal degradation of ERα and increased ERE activity. Estrogen‐deficient mice lacking HSD17B7 in their preosteoclasts showed more severe bone loss than control mice. This was attributed to increased mitochondrial biogenesis through the activation of PLD1–mTOR signaling. Additionally, in preosteoclasts derived from patients with severe osteoporosis, the expression of HSD17B7 and ERα was significantly reduced compared to the control subjects. Finally, raloxifene, which boosts ERα, did not inhibit bone loss without HSD17B7, confirming the modulation of ERα through HSD17B7. Therefore, HSD17B7 regulation is a novel therapeutic approach for alleviating estrogen‐deficient osteoporosis.