Overall water splitting (OWS) to produce hydrogen has attracted large attention in recent years due to its ecological‐friendliness and sustainability. However, the efficiency of OWS has been forced by the sluggish kinetics of the four‐electron oxygen evolution reaction (OER). The replacement of OER by alternative electrooxidation of small molecules with more thermodynamically favorable potentials may fundamentally break the limitation and achieve hydrogen production with low energy consumption, which may also be accompanied by the production of more value‐added chemicals than oxygen or by electrochemical degradation of pollutants. This review critically assesses the latest discoveries in the coupled electrooxidation of various small molecules with OWS, including alcohols, aldehydes, amides, urea, hydrazine, etc. Emphasis is placed on the corresponding electrocatalyst design and related reaction mechanisms (e.g., dual hydrogenation and N–N bond breaking of hydrazine and C═N bond regulation in urea splitting to inhibit hazardous NCO⁻ and NO⁻ productions, etc.), along with emerging alternative electrooxidation reactions (electrooxidation of tetrazoles, furazans, iodide, quinolines, ascorbic acid, sterol, trimethylamine, etc.). Some new decoupled electrolysis and self‐powered systems are also discussed in detail. Finally, the potential challenges and prospects of coupled water electrolysis systems are highlighted to aid future research directions.

Pancreatic ductal adenocarcinoma (PDAC) represents a major clinical challenge due to its dense fibrotic stroma, hypovascular characteristics, and immunosuppressive tumor microenvironment (TME), which collectively hinder effective drug delivery and contribute to recurrence and metastasis. The TME not only restricts therapeutic penetration but also compromises antitumor immune responses through multiple immunosuppressive mechanisms, thereby constituting a central obstacle in PDAC treatment. Nanoparticles (NPs)-mediated sonodynamic therapy (SDT) offers several advantages, including enhanced tissue penetration, improved biosafety profiles, and reactive oxygen species (ROS)-independent tumor-killing mechanisms. Nevertheless, the limitation to tumor inhibition instead of shrinkage and the incapability of eliminating metastatic tumors hinder the clinical potential for SDT. Fortunately, immune checkpoint blockade (ICB) can revive immunological function and induce a long-term immune memory against tumor rechallenges. Therefore, the synergistic combination of NP-based SDT with ICB presents a promising strategy for improving therapeutic outcomes in PDAC. This review provides an overview of the fundamental principles underlying ultrasonic cavitation, sonodynamic effects, sonosensitizer classification, and ICB mechanisms. This review highlighted the synergistic anti-tumor mechanisms and summarized the representative preclinical trials on SDT-assisted immunotherapy. Furthermore, this work explores the molecular basis of SDT-ICB synergy from the perspective of TME complexity. In addition, current nanomedicine engineering approaches aimed at overcoming stromal barriers in pancreatic tumors are critically evaluated. Finally, key challenges and future directions for the development of this combinatorial therapeutic strategy are discussed, offering novel perspectives on the application of biomaterials in advanced cancer therapy.

During the inflammatory phase, the persistent macrophage-mediated inflammatory response, followed by excessive fibroblast activation in the proliferative phase, impairs the repair of deep partial-thickness burn wounds and contributes to scar formation. Hence, precise spatiotemporal regulation of both macrophages and fibroblasts is of paramount importance. In this study, we developed a structurally biomimetic bilayer hydrogel system designed to promote scar-minimizing burn wound healing by sequentially targeting macrophages in the inflammatory phase and modulating fibroblast behavior in the proliferative phase. This biomimetic bilayer hydrogel (designated BHM@VP@PPs) consists of a lower layer (LHM) loaded with PBA-PEI@siRNA (TNF-α) nanocomplexes (LHM@PPs) and an upper layer (HHM) encapsulating the small-molecule YAP inhibitor verteporfin (HHM@VP). By varying the HM polymer concentration and crosslinking density, the bilayer hydrogel was designed to provide degradation-dependent, stage-matched release of siRNA and VP. During the inflammatory phase, released siRNA silenced TNF-α via blockade of its mRNA expression, thereby attenuating local inflammation and accelerating the transition to the proliferative phase. Upon degradation of the lower layer, the upper layer subsequently released VP, which suppressed excessive fibroblast activation through YAP-related signaling pathways during the proliferative phase, thus favoring scar-minimizing healing. Moreover, VP-mediated photodynamic therapy (PDT) generated abundant reactive oxygen species (ROS), effectively eradicating bacteria and preventing infection. Collectively, this bilayer hydrogel system synergistically facilitates scar-minimizing repair of deep second-degree burn wounds, offering a promising therapeutic strategy for clinical translation.