Current strategies for cartilage repair, including decellularized cartilage matrices and synthetic bioactive materials, often encounter challenges such as immune responses and donor morbidity. In this study, we optimized an extracellular matrix (ECM) derived from mesenchymal stem cells through preconditioning with disease-associated inflammatory factors, specifically interleukin 6, tumor necrosis factor alpha, and interferon gamma (IFN-γ). Our in vitro experiments demonstrated that the cytokine-preconditioned stem-cell-derived ECM, especially IFN-γ-ECM, supports chondrocyte homeostasis by restoring mitochondrial energy metabolism. Furthermore, bioactive molecules secreted from this preconditioned ECM boost the recruitment of endogenous stem cells and facilitate their differentiation into chondrocytes. Notably, we found that IFN-γ-ECM facilitates the chondrogenic differentiation of mesenchymal stem cells through the activation of the integrin/phosphatidylinositol 3-kinase/Akt pathway and the Smad2/3 signaling cascade. These results highlight the potential of the cytokine-stimulated ECM, especially IFN-γ-ECM, to restore chondrocyte homeostasis, optimize the mobilization of endogenous stem cells, and substantially improve the regeneration of cartilage defects, offering a promising strategy for acellular cartilage graft reconstruction.

Isovaleryl-CoA (coenzyme A) dehydrogenase (IVD) plays a pivotal role in the catabolism of leucine, converting isovaleryl-CoA to 3-methylcrotonyl-CoA. Dysfunction of IVD is linked to isovaleric acidemia (IVA), a rare metabolic disorder characterized by the accumulation of toxic metabolites. In this study, we present the cryo-electron microscopy structures of human IVD, resolved both in its apo form and in complex with its substrates, isovaleryl-CoA and butyryl-CoA. Our findings reveal a tetrameric architecture with distinct substrate-binding pockets that facilitate the enzyme's preference for short branched-chain acyl-CoAs. Key residues involved in FAD binding and substrate interaction were identified, elucidating the catalytic mechanism of IVD. Additionally, we investigated the impact of various disease-associated hotspot mutations derived from different regions, demonstrating their effects on enzyme stability and activity. Notably, mutations such as A314V, S281G/F382V, and E411K resulted in substantial loss of function, while others exhibited milder effects, which is consistent with our structural analyses. These insights enhance our understanding of IVD's enzymatic properties and provide a foundation for developing targeted therapies for IVA.

The development of clean and efficient renewable energy is of great strategic importance to realize green energy conversion and low-carbon growth. Hydrogen energy, as a renewable energy with “zero carbon emission”, can be efficiently converted into hydrogen energy and electric energy by electrolysis of water to hydrogen technology. Anion-exchange membrane water electrolysis (AEMWE), substantially advanced by nonprecious metal electrocatalysts, is among the most cost-effective and promising water electrolysis technologies, combining the advantages of proton exchange membranes with the proven technology of traditional alkaline water electrolysis and potentially eliminating the disadvantages of both. In this paper, the latest results of AEMWE research in recent years are summarized, including the AEMWE mechanism study and the hot issues of low-cost transition metal hydrogen evolution reaction and oxygen evolution reaction electrocatalyst design in recent years. The key factors affecting the performance of AEMWE are pointed out, and further challenges and opportunities encountered in large-scale industrialization are discussed. Finally, this review provides strong guidance for advancing AEMWE.

Gastric cancer (GC) is one of the most common cancers worldwide particularly in Asian populations, and certain diets have been associated with increased risk of GC. Recent advances in microbial profiling technology have facilitated investigations on microbes residing on the gastric mucosa and increasing evidence has revealed the critical roles of non-Helicobacter pylori gastric microbes in gastric tumorigenesis. On the other hand, diets can affect microbial communities, causing compositional and functional shift of the microbiota. In this review, we summarize the influence of various diets including processed meat, salt-preserved food, high-fat diet, and alcohol on the development and progression of GC. We also explore microbial metabolites and host–microbe interactions in gastric tumorigenesis, alongside dietary interventions targeting the microbiota for the prevention and management against GC.

Cuproptosis represents a novel mechanism of cellular demise characterized by the intracellular buildup of copper ions. Unlike other cell death mechanisms, its distinct process has drawn considerable interest for its promising applications in managing inflammatory bowel disease (IBD) and colorectal cancer (CRC). Emerging evidence indicates that copper metabolism and cuproptosis may exert dual regulatory effects within pathological cellular environments, specifically modulating oxidative stress responses, metabolic reprogramming, and immunotherapeutic efficacy. An appropriate level of copper may promote disease progression and exert synergistic effects, but exceeding a certain threshold, copper can inhibit disease development by inducing cuproptosis in pathological cells. This makes abnormal copper levels a potential new therapeutic target for IBD and CRC. This review emphasizes the dual function of copper metabolism and cuproptosis in the progression of IBD and CRC, while also exploring the potential application of copper-based therapies in disease treatment. The analysis further delineates the modulatory influence of tumor immune microenvironment on cuproptosis dynamics, while establishing the therapeutic potential of cuproptosis-targeted strategies in circumventing resistance to both conventional chemotherapeutic agents and emerging immunotherapies. This provides new research directions for the development of future cuproptosis inducers. Finally, this article discusses the latest advances in potential molecular targets of cuproptosis and their related genes in the treatment of IBD and CRC, highlighting future research priorities and unresolved issues.

Mechanical overload is a critical contributor to cartilage degeneration in osteoarthritis (OA) pathogenesis. Circular RNA (circRNA) is expected to provide a long-lasting therapy for OA. However, the involvement of the circRNA-associated competitive endogenous RNA network in chondrocyte senescence induced by mechanical overloading remains unestablished. A mechanical overloading-induced chondrocyte senescence model in human primary chondrocytes is constructed, and differences in the expression of circRNAs and miRNAs were analyzed. The biological roles of circKIAA0586/miR-335-5p in chondrocyte senescence and OA progression under mechanical overloading and its downstream targets were determined using gain- and loss-of-function experiments in various biochemical assays in human chondrocytes. The in vivo effects of circKIAA0586 overexpression were also determined in destabilization of the medial meniscus (DMM) OA mice and aged spontaneous OA mice. The mechanical overloading-induced chondrocyte senescence was aggravated by miR-335-5p or circKIAA0586 knockdown. Accumulated DNA damage response was observed following mechanical overloading, which reduced after miR-335-5p inhibition or circKIAA0586 supplementation. MiR-335-5p was regulated by circKIA0586 adsorption. HELLS was prominently down-regulated following mechanical overloading treatment. Moreover, miR-335-5p bound to lymphoid-specific helicase (HELLS) mRNA during mechanical overloading was demonstrated to mediate the nonhomologous end joining (NHEJ) pathway, thereby inducing DNA damage and senescence. In addition, the senescence delaying and cartilage protective functions of circKIAA0586 and HELLS were validated in DMM OA mice and aged spontaneous OA mice. Our findings suggest that miR-335-5p, which escapes circKIAA0586 adsorption, facilitates mechanical overloading-induced chondrocyte senescence and OA progression by impairing the NHEJ pathway through HELLS inhibition. Overall, targeting circKIAA0586/miR-335-5p/HELLS signaling provides a novel therapeutic approach for OA.

To improve the treatment outcomes for large bone defects and osteoporosis, researchers have been committed to reducing bone loss and accelerating bone regeneration through cell transplantation, biomaterial intervention, and biophysical stimulation over the past few decades. Magnetism, as a noninvasive biophysical stimulus, has been employed in the repair of the musculoskeletal system, achieving a series of promising results. In this review, we provide a retrospective analysis and perspective of research on magnetic-driven bone regeneration and functional reconstruction. This review aims to delineate safe and efficient magnetic application modalities and to summarize the potential mechanisms by which magnetism regulates the behavior of skeletal lineage cells, thereby providing insights for the expansion and translational application of magnetic-driven regenerative medicine.

Estrogen fluctuations have been implicated in various mood disorders, including perimenopausal and postpartum depression (PPD), likely through complex neural networks. γ-aminobutyric acid-ergic (GABAergic) neurons in the medial preoptic area (MPOA) that express estrogen receptor 1 (ESR1) are essential for the development and expression of depressive-like behaviors in ovarian hormone withdrawal (HW) mice. However, the precise circuit mechanisms through which MPOA GABAergic neurons influence behavior remain incompletely understood. Here, we identified robust projections from MPOA GABAergic neurons to the paraventricular nucleus of the hypothalamus (PVN). In HW mice, chemogenetic activation of MPOA GABAergic neurons targeting PVN attenuated depressive-like behaviors. Conversely, in nonhormone withdrawal (NHW) control mice (which received continuous estrogen), suppression of MPOA GABAergic projections to PVN exacerbated depressive-like behaviors. Further analyses using quantitative polymerase chain reaction and immunostaining identified arginine vasopressin (AVP) as a key neuropeptide in this pathway in the HW mouse model. Chemogenetic inhibition of PVN^AVP neurons significantly alleviated depressive-like behaviors in HW mice, while their activation in NHW mice worsened depressive-like behaviors. These behaviors were dependent on AVP expression in PVN^AVP neurons. Moreover, in HW mice, chemogenetic inhibition of PVN^AVP neurons receiving MPOA input mitigated depressive-like behaviors. Conversely, in NHW mice, activation of these neurons exacerbated depressive-like behaviors. Electrophysiological recordings demonstrated that MPOA GABAergic neurons directly inhibit PVN^AVP neurons. Thus, our findings suggest that PVN^AVP neurons serve as downstream effectors of MPOA GABAergic neurons via monosynaptic inhibitory signaling to regulate depressive-like behaviors. Targeting this circuit may offer a novel therapeutic strategy for PPD.

The development of biodegradable mulch film is an effective means to address plastic pollution and promote modern green agriculture. In this work, with compounding sodium carboxymethyl cellulose (CMC) and quaternized lignin (QL), a biodegradable liquid mulch film (PVA@CMC/QL) was constructed by introducing polyvinyl alcohol (PVA) and a selenium-containing cross-linking agent through electrostatic interaction. The effect of sodium carboxymethyl cellulose and QL on different liquid mulch films was examined. PVA@CMC/QL had exceptional spray-film-forming properties of liquid mulch film and was capable of generating a dense mulch film above the soil/on top of the soil under natural conditions. PVA@CMC/QL exhibited excellent oxygen transmission rate (60.2 cm³·m⁻²·d⁻¹·Pa⁻¹) and water vapor transmission rate (753.4 g·m⁻²·d⁻¹). Soil temperature and humidity increased by 0.4 to 2.1 °C and 0.5% to 2.8%, respectively, in the soil covered with PVA@CMC/QL compared to those in other controls, thereby confirming its exceptional moisture retention and insulation capabilities. PVA@CMC/QL combined remarkable weed suppression with only 13.3% weed germination under the mulch. Optimal rhizome growth of pak choi seedlings was observed under the PVA@CMC/QL cover, as demonstrated by the planting of both pak choi seedlings and weeds. Roots and stems increased by 3.8 ± 0.3 and 1.2 ± 0.3 cm, respectively. The weed suppression mechanism of PVA@CMC/QL was explained through the lens of density functional theory. In addition, the selenium content of pak choi seedlings under PVA@CMC/QL cover could reach 28.5 μg/kg, making the mulch film both degradable and highly reusable. This work not only improved the value-added utilization of bamboo residues but also gave new insight into the research on multifunctional bamboo–plastic mulch film.

Nitrite reductases (NiRs) are natural enzymes that facilitate the reduction of nitrite. They are essential for the microbial nitrogen cycle and play a vital role in regulating numerous physiological and pathological processes associated with nitric oxide (NO) in living organisms. By the merits of protein engineering, a variety of artificial NiR mimics have been developed. These include traditional artificial proteins, metal-azacycle complexes, and nanozymes such as metal, metal oxide/sulfide nanoparticles, metal-organic frameworks, bioinorganic nanohybrids, and advanced single-atom nanozymes. This development marks an important milestone in broadening the application of enzyme-like catalytic nitrite reduction across various fields, such as biomedicine, biosensing, food science, and environmental science. In this review, we first outline the different types of NiRs, along with their active center structures and catalytic mechanisms, drawing from recent research and discoveries. We then classify the reported NiR mimic materials, discussing their active center structures and enzyme-like catalytic mechanisms. Additionally, we explore the potential future applications and challenges facing NiR mimics in the field of biomedicine.