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.

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.

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.

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.

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.

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.

Autoimmune kidney diseases (AIKDs) depict a range of disorders involving immune-mediated damage to the kidneys, where conventional biologic therapies involving monoclonal antibodies often prove insufficient because of persistent autoreactive B cell reservoirs in lymphoid organs and inflammatory tissues. The appearance of chimeric antigen receptor (CAR)-T cell therapies targeting B cells has shown transformative potential, with recent clinical trials showing the remarkable efficacy of anti-CD19 CAR-T cells in achieving profound B cell depletion, reducing immune complex deposition, and ameliorating renal inflammation in AIKDs. While these results highlight the potential of CAR-T cell therapy in facilitating immune reset and overcoming treatment resistance, further clinical investigations are imperative to establish its long-term safety and sustained therapeutic benefits. This review synthesizes current evidence on CAR-T cell applications in AIKDs, discusses critical considerations for clinical translation, identifies existing limitations and challenges, and proposes strategic directions for therapeutic optimization and advancement.

Achieving high maturity and functionality in in vitro skeletal muscle models is essential for advancing our understanding of muscle biology, disease mechanisms, and drug discovery. However, current models struggle to fully recapitulate key features such as sarcomere structure, muscle fiber composition, and contractile function while also ensuring consistency and rapid production. Adult stem cells residing in muscle tissue are known for their powerful regenerative potential, yet tissue-derived skeletal muscle organoids have not been established. In this study, we introduce droplet-engineered skeletal muscle organoids derived from primary tissue using cascade-tubing microfluidics. These droplet-engineered organoids (DEOs) exhibit high maturity, including well-developed striated sarcomeres, spontaneous and stimulated contractions, and recapitulation of parental muscle fiber types. Notably, DEOs are produced in just 8 d without the need for primary cell culture—substantially accelerating the 50- to 60-d process required by classical organoid models. Additionally, the cascade-tubing microfluidics platform enables high-throughput production of hundreds of uniform DEO replicates from a small tissue sample, providing a scalable and reproducible solution for skeletal muscle research and drug screening.

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.

Background: Osteosarcoma (OS) is a primary malignant bone tumor predominantly affecting adolescents. Chemotherapeutic agents, such as cisplatin, are commonly used in OS treatment; however, drug resistance markedly undermines treatment efficacy and contributes to reduced patient survival. The mechanisms underlying cisplatin resistance remain poorly understood. Recently, palmitoyl-protein thioesterase 1 (PPT1), a depalmitoylation enzyme, has attracted attention for its role in tumorigenesis and drug resistance. Investigating the mechanisms of PPT1 may offer new strategies to overcome resistance. Methods: This study analyzed multiple Gene Expression Omnibus datasets and utilized the OncoPredict tool to demonstrate the elevated expression of PPT1 in OS and its critical role in cisplatin resistance. By combining single-cell analysis with in vitro and in vivo experiments, we explored how PPT1 influences OS development through depalmitoylation and assessed the antitumor effects of the PPT1 inhibitor Ezurpimtrostat (GNS561), as well as its synergistic effects when combined with cisplatin. Results: We demonstrated that Sprouty 4 (SPRY4) undergoes a dynamic palmitoylation cycle regulated by zinc finger DHHC-type palmitoyl transferase 7 (ZDHHC7) and PPT1, which modulates mitogen-activated protein kinase (MAPK) signaling and subsequently affects tumor cell proliferation, migration, apoptosis, and drug resistance. Further validation confirmed the effectiveness of the PPT1 inhibitor GNS561 in overcoming cisplatin resistance. Notably, GNS561 exhibited a significant synergistic effect when used in combination with cisplatin, greatly enhancing the sensitivity of cisplatin-resistant cells. Conclusion: This study highlights the pivotal role of PPT1 in OS resistance mechanisms. PPT1 and ZDHHC7 regulate SPRY4 through a dynamic palmitoylation–depalmitoylation cycle that modulates MAPK signaling activation and contributes to OS cell proliferation, migration, and drug resistance. As a PPT1 inhibitor, GNS561 not only inhibits OS cell proliferation but also demonstrates synergistic effects with cisplatin, significantly enhancing cisplatin sensitivity in resistant cells and promoting apoptosis. Our findings offer a novel approach for targeting PPT1 in therapeutic strategies. GNS561 holds promise as an adjunctive therapy when combined with cisplatin, potentially overcoming resistance and improving efficacy, thereby enhancing the prognosis for OS patients. Future studies should further investigate the clinical potential of GNS561 and optimize OS treatment strategies.