Organelle-targeted photodynamic therapy (PDT) shows substantial promise for precision tumor treatment. However, the clinical translation of oxygen-independent photosensitizers (PSs) designed for mitochondrial localization remains challenging. Herein, we propose a "dual-boosting" strategy to enhance the type-I PDT efficacy of mitochondria-targeted PSs. The first boost leverages multi-branched donor/π-bridge engineering to develop a series of mitochondria-targeted pyrido cyanines. Among them, McL3 displays broad visible-light absorption and a reduced singlet-triplet energy gap (ΔE S1-T3 = 0.24 eV), which collectively lead to a 4.2-fold increase in superoxide anion radical (•O2 -) generation compared to McL1. The second boost is achieved through the self-assembly of McL3 with human serum albumin (HSA) into McL3@HSA nanoparticles (~40 nm). This confinement further narrows ΔE S1-T2 to 0.08 eV, amplifying •O2 - production by 20.3-fold. Mechanistic studies indicate that HSA confinement modulates molecular conformation and promotes ISC efficiency from 33% to 52%, enabling efficient •O2 - generation. Upon white-light irradiation, McL3@HSA selectively accumulates in mitochondria, inducing apoptosis and effectively inhibiting tumor growth even under hypoxic conditions. This work establishes a "dual-boosting" paradigm for the rational design of mitochondria-targeted, hypoxia-tolerant PSs, offering a promising avenue for clinical phototheranostics.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is a major and unavoidable environmental contaminant that poses serious risks to intestinal health. Lycopene (LYC), a natural carotenoid with potent antioxidant properties, has been reported to exert protective effects against oxidative stress. Phosphoglycerate mutase family member 5 (PGAM5) acts as a key signaling hub to control mitochondrial dynamics and mitophagy. This study aimed to elucidate the potential role of LYC in DON-induced intestinal damage and clarify the contribution of PGAM5. We established intestinal porcine epithelial cell models to explore the effects of DON and LYC on intestinal barrier integrity, mitochondrial function, mitophagy, and ferroptosis through assessments of cell viability, oxidative stress, iron accumulation, and autophagic activity. Mechanistic insights were validated using RNA sequencing, molecular docking, Western blotting, and immunofluorescence analyses. PGAM5 expression was modulated via plasmids and small interfering RNA. Our results demonstrated that DON disrupted barrier integrity, reduced cell motility, and induced cytoskeletal disorganization, accompanied by excessive mitophagy, lipid peroxidation, and ferrous iron accumulation, ultimately leading to ferroptosis. Notably, LYC alleviated DON-induced intestinal damage by inhibiting mitophagy and ferroptosis. Importantly, PGAM5 overexpression abolished the protective effects of LYC, indicating that PGAM5-mediated mitophagy-dependent ferroptosis plays a critical role in DON-induced intestinal damage. These findings suggest that LYC may serve as a potential therapeutic strategy for treating mycotoxin-induced intestinal disorders.

Electroactive microbes are uniquely capable of aggressively corroding metals like stainless steel that were once thought immune to microbial attack. This activity has been attributed to microbial destruction of the protective chromium oxide passive film on the stainless steel surface that protects the underlying Fe0 from corrosive agents, allowing the microbes to establish direct electrical contact with the Fe0 and extract electrons to support anaerobic respiration. We show here that the electroactive microbe Geobacter sulfurreducens, despite its high corrosive activity, is unable to physically breach the passive film. Instead, it enables biologically mediated electron transfer across an intact chromium oxide-rich layer that remains sufficiently insulating to block abiotic proton reduction. These findings challenge the prevailing assumption that electroactive microbes must directly contact Fe0 for corrosion and provide new guidance for the design of corrosion-resistant metals.

The persistent hyperglycemic microenvironment in diabetic wounds causes dysfunction of repair cells, resulting in impaired angiogenesis and disorganized extracellular matrix (ECM) deposition. Small extracellular vesicles (sEVs) derived from hypoxia-challenged chorionic plate mesenchymal stem cells (CP-MSC-sEVsHypo) have been explored as novel acellular therapeutics. However, the effects of oxygen tension during culturing parent cells on the pro-regenerative efficacy and mechanisms of CP-MSC-sEVs have not been systematically investigated. In addition, their rapid clearance and limited interaction with target cells at wound sites constrained therapeutic efficacy. In this study, oxygen tension was first optimized systematically during the precondition of CP-MSCs to improve the pro-regenerative properties of the derived sEVsHypo. Then, sEVsHypo-engineered nanofiber scaffolds were fabricated to achieve the sustained release of sEVsHypo at wound sites by polydopamine (PDA)-mediated interfacial adhesion. Invitro experiments revealed that sEVs obtained under 5% oxygen tension (sEVsHypo-5%) exhibited the most pronounced angiogenic and collagen-regenerative performance. Furthermore, small RNA sequencing and bioinformatic analyses revealed that miR-21-5p was the most abundant miRNA in sEVsHypo-5%, and functional rescue assays validated that miR-21-5p was the key mediator of endothelial activation and ECM remodeling. To improve the bioavailability of sEVsHypo-5%, PDA was leveraged to immobilize sEVsHypo-5% onto a biocompatible, ECM-mimicking poly(ε-caprolactone) nanofiber scaffold to achieve high loading efficacy and sustained release. In a full-thickness diabetic wound model, the sEVsHypo-5%-loaded nanoscaffold accelerated wound closure and achieved superior pro-healing effects on D14 via enhancing neovascularization and ECM deposition, as confirmed by histological and immunofluorescence analyses. Collectively, this sEVsHypo-5%-loaded nanoscaffold achieved efficient immobilization and sustained delivery of sEVsHypo-5% to promote angiogenesis and matrix repair by endogenously delivering miR-21-5p at diabetic wound sites, with strong potential for clinical translation.

Locomotion in animals such as fish, snakes, inchworms, and octopuses exhibits a remarkable diversity, with each species utilizing distinct body morphologies and movement strategies. Currently, no existing kinematic model is capable of describing the full range of locomotion exhibited by these animals. Addressing this challenge holds important implications for both the study of biomechanics of animals and the development of bioinspired robots. In this work, we propose a general kinematic model that integrates the curvature equation with a nonlinear oscillator. Through parameter adjustments, its morphology can transition between the motions of various animals. It is the most versatile kinematic model to date for describing multimodal locomotion of animals so far as we know. By translating the general kinematic model into a motion control algorithm and combining it with virtual simulation, we create a motion optimization framework that substantially simplifies the complexity of multimodal control for bionic robots with diverse actuation mechanisms, thereby enhancing their maneuverability. Using fish locomotion as an example, we validate the methodology on an untethered multijoint robotic fish, successfully enabling the robotic fish to perform cruising and various fast turn motions, thereby demonstrating its effectiveness in guiding motion control. This work is believed to have laid the foundation for the study of bionic motion and bioinspired robots.

T7 RNA polymerase (T7 RNAP) is the most widely used enzyme for synthesizing therapeutic mRNA. However, RNA transcribed by T7 RNAP often contains double-stranded RNA (dsRNA) by-products that trigger innate immune responses and complicate purification. Here, we report an engineered T7 RNAP variant, M30, which exhibits higher catalytic efficiency and reduced dsRNA by-product formation. M30 was developed through 4 rounds of directed evolution using an ultrahigh-throughput aptamer-based fluorescence-activated droplet sorting system. M30 displays a 10-fold increase in catalytic efficiency over wild-type T7 RNAP at 37 °C, along with markedly enhanced thermostability and approximately 10-fold lower production of dsRNA by-products. mRNAs synthesized with M30 achieve efficient protein expression in human cells and in mice, while eliciting reduced immunogenicity compared with mRNAs produced by wild-type T7 RNAP. Biophysical assays and structural analyses suggest that these improvements result from increased DNA template binding affinity and decreased RNA binding affinity. Together, these features make M30 a promising catalyst for high-quality therapeutic mRNA production.

Liver fibrosis shows limited treatment efficacy, driven by metabolic reprogramming and epigenetics, while the role of lactate-mediated lactylation in hepatic microenvironment remains unclear. Here, through integrative analysis of public databases and human cirrhotic liver tissues, we identified a pathogenic FSP1+ (fibroblast specific protein 1) macrophage subset as a key therapeutic target. We uncovered a novel FSP1-glycolysis-lactylation axis that drives fibrotic progression through metabolic-immune crosstalk. Expanded FSP1+ macrophage infiltration was observed in human cirrhotic liver tissues and myeloid-specific Fsp1 knockout markedly attenuates inflammation and fibrosis. Mechanistic investigations reveal that FSP1 physically interacts with pyruvate kinase M2 (PKM2) in macrophages, inhibiting its ubiquitin-proteasome degradation to stabilize the enzyme. This FSP1-PKM2 interaction enhances glycolytic flux and lactate production, which in turn promotes KAT2B-dependent lactylation of phosphoglycerate kinase 1 (PGK1) at lysine 353 (K353). The posttranslational modification creates a positive feedback loop by concurrently activating PGK1 and pyruvate dehydrogenase kinase 1, which blocks mitochondrial pyruvate metabolism, thereby amplifying glycolysis and PGK1 lactylation. Notably, we developed a cell-penetrating peptide targeting PGK1-K353 lactylation that effectively attenuates the progression of liver fibrosis. Our findings establish lactate-mediated lactylation of PGK1 as a critical node in fibrotic metabolism and reveal a previously unrecognized FSP1-glycolysis axis that sustains the pro-fibrotic microenvironment. Targeting PGK1-K353 lactylation represents a promising therapeutic strategy for chronic liver diseases.

The development of fast-charging anode materials is crucial for overcoming the sluggish reaction kinetics of conventional graphite electrodes in lithium-ion batteries. This work presents a kilogram-scale producible hard carbon/graphene flake (HC-GF) composite anode engineered based on an "electron Velcro" conductive network design. In this architecture, highly conductive GFs are intimately integrated with the HC matrix, creating multidimensional electron/ion transport channels while effectively minimizing interfacial resistance. The resulting HC-GF anode exhibits exceptional electrochemical performance, delivering a reversible capacity of 506.4 mAh g-1 and maintaining 223.8 mAh g-1 at a 10 C rate (corresponding to 6-min fast charging). Remarkably, when blended with graphite at a 20% ratio in a 5 Ah LFP//graphite + 20% (HC-GF) pouch cell, this minimal doping level substantially enhances multiple performance metrics, particularly fast-charging capability and cycling stability. The pouch cell retains 3.39 Ah after 600 cycles at 3 C, corresponding to an impressive capacity retention of 94.6%. This study provides a valuable material strategy for advancing fast-charging lithium-ion battery technologies.

4-Chromanone is a biologically important heterocyclic scaffold found in natural products and pharmaceuticals. Traditional syntheses of 2-substituted 4-chromanones often rely on high-temperature peroxide initiation, transition-metal catalysis, or complex photocatalytic systems, limiting functional-group tolerance and sustainability. Herein, we report a Giese-type strategy for direct C-H functionalization of chromone derivatives, where chromones act as both substrates and hydrogen atom transfer (HAT) reagents to active inert C(sp3)-H bonds and P-H bonds under mild, metal-free conditions. Upon light irradiation, chromones form triplet states that mediate HAT for diverse substrates, including ethers, esters, alcohols, alkanes, sulfides, and arylphosphines. The resulting radicals are captured by ground-state chromones, efficiently affording 2-substituted 4-chromanones. Mechanistic studies and density functional theory calculations support the radical-mediated pathway, and the method avoids the use of metal catalysts, external redox mediators, or photocatalysts, highlighting its scalability and sustainable potential.

Foxtail millet (Setaria italica L.), a C4 cereal crop domesticated in China, exhibits exceptional nitrogen use efficiency (NUtE) with marked genotypic variation; however, the molecular basis remains underexplored. Here, we identified candidate genes through a sequential filtering strategy from genetic linkage (bulked segregant analysis sequencing) to transcriptional response (RNA sequencing) within defined quantitative trait locus intervals to dissect NUtE mechanisms in contrasting genotypes: the low-nitrogen-tolerant variety Yugu28 and the low-nitrogen-sensitive variety Qiyehuang, to identify the genetic regulatory mechanisms. Several candidate genes were screened, such as glutamine synthetase (GS2, Seita.3G024100), glutathione S-transferase (GLUS, Seita.3G386000) and nitrogen regulatory protein P-II (Seita.3G051900). Seita.3G051900 was identified as LOW-NITROGEN REGULATORY GENE (SiLNR1), which is highly expressed in different organs. The functional characterization revealed that SiLNR1 overexpression results in strikingly low-N resilience: Compared with the wild-type controls, the transgenic lines presented 106% longer primary roots, 91.3% greater plant height, and 18.9% greater root nitrogen accumulation under low-nitrogen (LN) conditions and boosted grain yield and NUtE by 29.5% and 24.3%, respectively. By contrast, the silnr1 mutant presented markedly shorter primary roots and plant height and lower shoot N accumulation under LN conditions. Field validation of the SiLNR1 allele in the recombinant inbred line population demonstrated that the SiLNR1 allele from Yugu28 confers a substantial and measurable yield gain under LN field conditions. The functions of SiLNR1 associated with enhanced nitrogen uptake and utilization have been revealed, indicating that SiLNR1 contributes to nitrogen metabolism and NUtE positively, thus providing a theoretical basis and application prospect for resource conservation, environmental protection, and sustainable agricultural development.