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As an important achievement in agricultural sci-tech innovation, gene-edited animals are not only a basic element for rural revitalization but also the core of promoting the biological breeding industry. Exploring their supervision models and institutional construction is practically significant and supports new productive forces in agriculture. Currently, various research and development achievements have emerged, but China lacks clear legal norms for their transformation and food industry supervision, failing to meet modern breeding needs. Internationally, three main supervision models (strict, open, eclectic) are determined by each country’s technological level, legal soundness and public acceptance. To build China’s sui generis supervision system for gene-edited animals that is independent of both GM animals and gene-edited plants, top-level design should issue categorized supervision policies to clarify research and development and industrialization norms, including relevant principles and procedures; establish a pre-positive ethical review mechanism with strict animal welfare checks; set animal welfare damage as a certification revocation condition; build a traceability platform for gene-edited animals and their products; implement positive food labeling; strengthen public participation to balance technological innovation and risk prevention; safeguard biosafety and public interests; and provide legal support for industrialization of gene-edited animals.

The biophysical factors of biomaterials such as their stiffness regulate stem cell differentiation. Energy metabolism has been revealed an essential role in stem cell lineage commitment. However, whether and how extracellular matrix (ECM) stiffness regulates energy metabolism to determine stem cell differentiation is less known. Here, the study reveals that stiff ECM promotes glycolysis, oxidative phosphorylation, and enhances antioxidant defense system during osteogenic differentiation in MSCs. Stiff ECM increases mitochondrial fusion by enhancing mitofusin 1 and 2 expression and inhibiting the dynamin-related protein 1 activity, which contributes to osteogenesis. Yes-associated protein (YAP) impacts glycolysis, glutamine metabolism, mitochondrial dynamics, and mitochondrial biosynthesis to regulate stiffness-mediated osteogenic differentiation. Furthermore, glycolysis in turn regulates YAP activity through the cytoskeletal tension-mediated deformation of nuclei. Overall, our findings suggest that YAP is an important mechanotransducer to integrate ECM mechanical cues and energy metabolic signaling to affect the fate of MSCs. This offers valuable guidance to improve the scaffold design for bone tissue engineering constructs. [Display omitted] •Glycolysis is the main source of ATP for ECM stiffness-induced osteogenic differentiation in MSCs.•Stiff ECM promotes mitochondrial fusion and biosynthesis.•YAP acts as a mechan-matabolic sensor to regulate osteogenic capacity of MSCs.•ECM stiffness-induced glycolysis regulates YAP via cellular mechanics.

It is of significance to elucidate the groundwater quality and hydrogeochemical processes for sustainable utilization of groundwater resources in water shortage regions. A total of 256 groundwater samples were collected in typical watersheds in Zhangjiakou, northern China. The hydrochemical parameters, conventional ions, and trace elements were measured, and δD and δ 18 O data were collected to delineate the groundwater quality and hydrogeochemical processes. The results showed that 32.91% of the groundwater could be directly used for drinking water sources in the Bashang Plateau, north of the study area. The F − and NO 3 − -N were the main parameters above the standard threshold for drinking water. In contrast, the groundwater quality in the Baxia River Basins, south of the study area, was of a better scenario. Nonetheless, high concentrations of F − , total hardness, and SO 4 2− were still observed. Most samples in the Bashang Plateau had relatively higher salinity than the Baxia River Basins. Both surface water and groundwater in the study area originated from local meteoric water with considerable hydraulic connections. The high-fluoride groundwater was primarily formed by dissolution of fluoride-rich minerals under conditions of high pH and Na + , low Ca 2+ , and rich in HCO 3 − . The dissolution of carbonate and silicate minerals accompanied by strong cation exchange and weak evaporation was the dominant water-rock interaction affecting the hydrochemical composition of groundwater, and anthropogenic NO 3 − input had an extra influence on hydrochemical process. This study provides a scientific guideline for the protection and allocation of local groundwater resources.

Stabilizing the RSV F protein in its prefusion conformation is crucial for effective vaccine development but has remained a significant challenge. Traditional stabilization methods, such as disulfide bonds and cavity-filling mutations, have been labor-intensive and have often resulted in suboptimal expression levels. Here, we report the design of an RSV prefusion F (preF) antigen using a proline-scanning strategy, incorporating seven proline substitutions to achieve stabilization. The resulting variant, preF7P, is structurally and biochemically validated to maintain the correct prefusion state. PreF7P demonstrates superior immunogenicity with a 1.8-fold increase in neutralizing antibody titers when compared to DS-cav2, and provides protection from clinical disease against both RSV A and B strains in female murine and female cotton rat models. In clinical development, preF7P exhibits high expression levels (~10 g/L) in clinical-grade CHO cells. The clinical-grade vaccine elicits robust immunogenic responses across female mice, female SD rats, and both male and female cynomolgus macaques, significantly boosting RSV pre-infection neutralizing antibody titers, and providing sustained protection for at least six months in female mice. This proline-scanning strategy offers a streamlined approach for stabilizing class I fusion proteins, potentially accelerating the development of vaccines for other pathogens. There is a need for improved RSV vaccines to protect populations at risk. Here, the authors developed a proline-scanning strategy to create a highly stable RSV vaccine candidate that achieves enhanced production yields and provides robust protection against both RSV A and B strains in murine animal models.

Extra-intestinal manifestations (EIMs) of the eyes are found in IBD patients, but the underlying pathogenesis remains unknown. To investigate the pathogenesis of IBD-associated retinal dysfunction, chronic colitis was induced in mice by oral administration of dextran sodium sulfate (DSS). Electroretinography (ERG) was performed to evaluate retinal function. Retinal neuron degeneration was analyzed by immunohistochemistry. Colitic mice displayed aberrant amplitudes of ERG a-, b-wave and oscillatory potentials (OP). Importantly, we observed severe degeneration of bipolar and ganglion cells. In contrast, outer retinal neurons (mainly photoreceptor cells) are mildly affected by colitis. Moreover, retinal inflammatory responses were significantly upregulated during colitis, including microglia activation, lymphocyte infiltration and cytokine/chemokine production. Notably, mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in retinal microvessels, especially the superficial and deep plexuses, and recruited gut-homing CD4+ T cells to be co-localized with bipolar and ganglion cells during colitis. Expectedly, in vivo depletion of CD4+ T cells or blockade of MAdCAM-1 greatly alleviated colitis-induced retinal inflammatory responses and neuron degeneration. Therefore, our data provide novel insight into the pathogenesis of IBD-associated retinal dysfunction, and targeted immune therapy directly against MAdCAM-1 might provide a novel approach in the management of eye EIM of IBD.

Simulated microgravity (SMG) poses substantial challenges to astronaut health, particularly impacting osteoblast function and leading to disuse osteoporosis. This study investigates the adverse effects of SMG on osteoblasts, focusing on changes in mitochondrial dynamics and their consequent effects on cellular energy metabolism and mechanotransduction pathways. We discovered that SMG markedly reduced the expression of osteoblast differentiation markers and promoted mitochondrial fission, as indicated by an increase in punctate mitochondria, a decrease in mitochondrial length, and a reduction in cristae density. These mitochondrial alterations are linked to elevated reactive oxygen species levels, a decrease in ΔΨm, and a metabolic shift from oxidative phosphorylation to glycolysis, resulting in decreased adenosine triphosphate production, which are all indicative of mitochondrial dysfunction. Our results showed that treatment with mitochondrial division inhibitor-1 (mdivi-1), a mitochondrial fission inhibitor, effectively inhibited these SMG-induced effects, thereby maintaining mitochondrial structure and function and promoting osteoblast differentiation. Furthermore, SMG disrupted critical mechanotransduction processes, by affecting paxillin expression, the RhoA–ROCK–Myosin II pathway, and actin dynamics, which subsequently altered nuclear morphology and disrupted Yes-associated protein signaling. Notably, treatment with mdivi-1 prevented these disruptions in mechanotransduction pathways. Moreover, our study showed that SMG-induced chromatin remodeling and histone methylation, which are epigenetic barriers to osteogenic differentiation, can be reversed by targeting mitochondrial fission, further highlighting the significance of mitochondrial dynamics in osteoblast function in an SMG environment. Therefore, targeting mitochondrial fission emerges as a promising therapeutic strategy to alleviate osteoblast dysfunction under SMG conditions, providing novel approaches to maintain bone health during prolonged space missions and safeguard the astronaut well-being.

In order to find the best nanometal oxides to alleviate the cadmium-caused toxicity, we chose five kinds of nanometal oxides (MgO NPs, ZnO NPs, α-Fe2O3 NPs, γ-Fe2O3 NPs, and Fe3O4 NPs) tried to research the different effects. In this study, the effects of nanometal oxides on physiological response indicators in wheat seedlings poisoned by cadmium were figured out. The results showed that the properties of nanometal oxides were related to their capacity to mitigate the toxicity induced by cadmium. Comparatively, 30 mg/L MgO NPs showed the best repair effect, as well as it can also alleviate the significant abiotic stress caused by Cd2+ on plants. The activity of antioxidant enzymes had been reduced and the growth of plants had been improved after the addition of MgO NPs. ZnO NPs showed further toxicity to Cd-poisoned wheat seedlings. Among the three nanoiron oxides, Fe3O4 NPs has a relatively good repair effect, which may be related to its Fe(II)—an essential element required for plant growth.

Postbiotics possess various functional activities, closely linked to their source bacterial strains and preparation methods. Therefore, the functional activities of postbiotics need to be evaluated through in vitro and in vivo methods. This study aims to prepare a postbiotic and explore its antihemolytic, anti-inflammatory, antioxidant, and antibacterial activities. Specifically, a postbiotic preparation named PostbioP-6 was prepared by intercepting 1–5 kDa of Lacticaseibacillus paracasei Postbiotic-P6 fermentation broth. The results demonstrate that PostbioP-6 exhibited notable biological activities across multiple assays. It showed significant antihemolytic activity, with a 4.9–48.1% inhibition rate at 10–50% concentrations. Anti-inflammatory effects were observed both in vitro, where 8–40% PostbioP-6 was comparable to 259.1–645.4 μg/mL diclofenac sodium, and in vivo, where 3.5 and 4.0 μL/mL PostbioP-6 significantly reduced neutrophil counts in inflamed zebrafish (p < 0.05). Antioxidant properties were evident through increased reducing power (OD700 increased from 0.279 to 2.322 at 1.25–12.5% concentrations), DPPH radical scavenging activity (38.9–92.4% scavenging rate at 2.5–50% concentrations), and hydroxyl radical scavenging activity (4.66–10.38% scavenging rate at 0.5–4% concentrations). Additionally, PostbioP-6 demonstrated antimicrobial activity against two Gram-positive bacteria, eight Gram-negative bacteria, and one fungus. Furthermore, PostbioP-6 significantly inhibited the increase in peroxide value and malondialdehyde content in cookies, highlighting its potential application in food preservation. In conclusion, we prepared a novel postbiotic, termed PostbioP-6, which proved to have prominent anti-hemolytic, anti-inflammatory, antioxidant, and broad-spectrum antimicrobial activities. The multifunctional properties of PostbioP-6 position it as a potentially effective functional food supplement or preservative. In the future, further research is necessary to elucidate the precise mechanisms of action, identify the active components, and validate its biological activities in animal models or clinical trials.

According to the actual load cases of heavy load locomotive, the material compressing tests of the high polymer parts used in the locomotive are researched. The relationship between stress and strain during the material compressing are acquired by means of comparing the many results of the material compressing tests under different test condition. The relationship between stress and strain during the material compressing is nonlinear in large range of strain, but the relationship is approximately linear in small range of strain. The material of the high polymer made in China and the material of the high polymer imported are compared through the tests. The results show that the compressing property of the material of the high polymer made in China and the material of the high polymer imported are almost same. The research offers the foundation to study the structure elasticity of the draft gear.

Periodontal ligament (PDL) cells are a promising tool for periodontal regeneration therapy. Achieving a sufficient number of PDL cells is essential to PDL regeneration. In our study, appropriate flow shear stress (FSS, 1–6 dyn/cm 2 ) promotes the proliferation of PDL cells. FSS remodels cytoskeleton and focal adhesion in a duration-dependent manner. FSS induces PDL cells to form the actin cap within 10 min, flattens the nuclei, and increases the nuclear pore size, which promotes nuclear translocation of Yes-associated protein (YAP). FSS activates p38, which plays a dual function in YAP regulation. p38 regulates the phosphorylation of Akt and cofilin, as well as induced F-actin polymerization to induce YAP activity. In addition, p38 inhibits pLATS and consecutively regulates angiomotin (AMOT) and YAP phosphorylation. AMOT competitively binds to F-actin and YAP to participate in FSS-mediated YAP nuclear translocation and cell proliferation. Taken collectively, our results provide mechanistic insights into the role of p38-AMOT-YAP in FSS-mediated PDL cells proliferation and indicate potential applications in dental regenerative medicine.