INTRODUCTION:Muscle atrophy is a critical health challenge during spaceflight. This study investigated the mechanism of muscle atrophy induced by 21-d hindlimb unloading (HLU) and metabolomic changes in rat gastrocnemius muscle (GM) and plasma. METHODS:The rat tail-suspended model was used to simulate microgravity. The effects of HLU on GM atrophy were assessed by measuring morphological changes, levels of oxidative stress factors and proinflammatory cytokines, and the expression of key proteins in the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase/Ak strain transforming and nuclear factor-κB (NF-κB) signaling pathways. Metabolomic analysis of GM tissue and plasma was conducted to screen for differential metabolites associated with muscle atrophy under HLU conditions. RESULTS:HLU reduced the cross-sectional area of GM fibers and increased inflammatory factors interleukin-1β and tumor necrosis factor-α levels by 11.85% and 42.18%, respectively. Levels of oxidative stress markers hydrogen peroxide and malondialdehyde in GM were increased by 17.95% and 112.19%, respectively. The HLU activated the NF-κB signaling pathway in GM and inhibited the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase/Ak strain transforming pathway. Metabolomic analysis revealed nicotinamide and arachidonic acid levels were dramatically decreased and the kynurenic acid and glutaric acid levels were increased, which reduced peroxisome proliferator-activated receptor γ coactivator 1α and peroxisome proliferator-activated receptor γ protein expression, activating the NF-κB signaling pathway to promote proteolysis. DISCUSSION:The present study elucidated the potential mechanism of HLU-induced muscle atrophy at the metabolic level. These findings may supply potential biomarkers for astronaut health monitoring and be useful for clinical muscle atrophy treatment. Liu L, Cui Y, Wu R, Yang J, Li Y. Mechanisms of rat gastrocnemius muscular atrophy induced by hindlimb unloading. Aerosp Med Hum Perform. 2026; 97(4):226-234.

Bacillus licheniformis (BL) is used for clinical treatment of acute and chronic enteritis and diarrhea. The present study explored the physiological characteristics and proteomes of BL response to 6-month spaceflight aboard the China Space Station. 6-month spaceflight delayed BL lag phase, reduced cell wall thickness, and impaired BL biofilm formation and adhesion capacity to Caco-2 cells. After 6-month spaceflight, activity of β-amylase, alkaline protease and lipase in BL was increased by 21.6%,67.3% and 42.5%. The alkaline resistance of BL at pH 11.0 was increased by 29.6%. Proteomics identified 6051 proteins in the BL. Of these, 62 of differentially abundant proteins (DAPs) groups were screened based on fold change (FC) > 1.5 and < 0.667 (P < 0.05). Thirty-six DAP groups exhibited an up-regulation trend with the maximum FC reaching 9.53. Twenty-six DAP groups were down-regulated. The molecular functions of DAPs were mainly classified into the transport of nutrients and ions, cell wall biosynthesis, mRNA metabolism and protein translation. These results revealed that 6-month spaceflight led to notably changes of physiological characteristics and proteins in BL. The novel findings may supply new insights into BL response to long-term complex space environment. SIGNIFICANCE OF STUDY: Complex space environment could lead to gastrointestinal system disorders of astronauts and enhance the risk of intestinal infections. BL, a Gram-positive probiotic bacterium, has potential to protect intestinal health of astronauts. To date, space microbiology studies on probiotic Gram-positive bacteria is rather limited. Physiological properties of BL onboard spaceflight missions are still lacking. The effect of long-term spaceflight on proteomes of BL has not been reported. The functional changes of DAPs in BL exposed to complex space environment remains unelucidated. Thus, it is urgent to carry out comprehensive study on spaceflight-BL. The purpose of present study was to explore the physiological characteristics and proteomic changes in BL abord the Shenzhou-15 spaceship into the China Space Station for 6 months. The novel findings are helpful to understand the response patterns of BL to spaceflight and provide a scientific support for the intestinal health protection of astronauts and the in-orbit application of this probiotic.

Abstract During launch phase, hypergravity and vibration can potentially damage cell models used in space medical research. This will compromise the success of subsequent biomedicine research. Bioinks and bioprinting play a pivotal role in the successful delivery of cell models and the fabrication of tissue models for space biomedicine research. In order to streamline the process and conserve valuable resources, it is crucial to examine the storability of bioink and high survival human cells under space conditions. This study investigated the effects of hypergravity and vibration on blood‒brain barrier (BBB)‐related cells cultured in two‐dimensional (2D) monolayers and three‐dimensional (3D) decellularized matrices. Subsequently, cell proliferation, viability, and gene expression were assessed. Present study confirmed 3D embedded cells showed marked tolerance to launch‐associated mechanical factors, compared with the disruption on 2D adherent cells. In addition, the present study provided methods for storing hybrid bioink (decellularized extracellular matrix of mammalian soft tissue) and high viability of cells loaded in bioink under the existing storage conditions of space station. Printability, rheological property and ultrastructure of bioink is maintained after storage in 4°C for 4 weeks. Three types of BBB‐related cells can maintain their viability and function under the cryopreservation of preservatives. This study verified the feasibility of storing bioink and cells in orbit under low‐temperature conditions. It addresses the challenges associated with maintaining cell viability, limited experimental window, and susceptibility to launch processes in space‐based cell experiments. These findings provide a foundation for efficient and reproducible bioprinting in space.

The gut-brain axis (GBA) interaction is important for human health and disease prevention. Organ chips are considered a solution for GBA research. Three-dimensional (3D) cultures and microfluidics engineered in an organ chip could improve the scientific knowledge in the GBA interactions field. In this study, a novel organ chip is developed, which achieves multicellular three-dimensional cultivation by utilizing a decellularized matrix. In addition, this paper reports the rapid prototyping process of the GBA microfluidic chip in polydimethylsiloxane (PDMS) using 3D printing interconnecting poly(ethylene/vinyl acetate) (PEVA) microchannel templates. In comparison to the static culture system of the transwell model, the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) models on our chip demonstrated superior barrier function and the efflux functionality of transporters under appropriate fluidic conditions. Additionally, it is observed that butyrate protected against BBB dysfunction induced by gut-derived lipopolysaccharide (LPS) via enhancing intestinal barrier function. These results demonstrate that this multicellular, three-dimensional cultivation integrated with a fluidic shear stress simulation chip offers a promising tool for gut-brain interaction study to predict therapy of intestinal and neurological disorders.

Inhibiting permeability glycoprotein (P-gp) efflux is a strategy to enhance drug efficacy or overcome multidrug resistance in tumors. However, whether P-gp aptamer (APTP-gp, an 81 bp ssDNA) inhibits P-gp efflux is unknown. Increased Rho123 uptake was observed in the rat brain and intestine. Bidirectional transport of Rho123 indicated that 100 nM of APTP-gp inhibited P-gp activity with inhibition ratios of 75.0 % in Caco-2 and 60.5 % in hCMEC/D3 cells. The apparent permeability coefficients (Papp) from the apical (AP) to basolateral (BL) sides significantly increased by 129.4 % in Caco-2 and 8.0 % in hCMEC/D3 cells, respectively. The Papp from the BL→AP sides in the two cell lines decreased. P-gp mRNA and protein expression in the rat ileum, brain, and two cell lines markedly decreased following APTP-gp exposure. APTP-gp downregulated Wnt3, pho-Dvl2, β-catenin expression and decreased the ratio of pho-GSK-3β to GSK-3β in the rat ileum and brain. Molecular docking analysis suggested that APTP-gp interact with Wnt/β-catenin signaling pathway proteins at various amino acid sites. The present study reports a novel a novel nucleic acid-based P-gp inhibitor, which may benefit for enhancing drug efficacy or overcome multidrug resistance in clinical application.

Inflammation-induced intestinal epithelial barrier (IEB) dysfunction is one of the important reasons for the occurrence and development of intestinal inflammatory-related diseases, including ulcerative colitis (UC), Crohn’s disease and necrotizing enterocolitis (NEC). Dragon’s blood (DB) is a traditional Chinese medicine and has been clinically used to treat UC. However, the protective mechanism of DB on intestinal inflammatory-related diseases has still not been elucidated. The present study aimed to explore the protection mechanism of DB on IEB dysfunction in rat ileum and human colorectal adenocarcinoma cells (Caco-2)/human umbilical vein endothelial cells (HUVECs) coculture system induced by lipopolysaccharide (LPS). DB could ameliorate rat ileum mucosa morphological injury, reduce the accumulation of lipid-peroxidation products and increase the expression of junction proteins. DB also alleviated LPS-induced Caco-2 cells barrier integrity destruction in Caco-2/ HUVECs coculture system, leading to increased trans-endothelial electrical resistance (TEER), reduced cell permeability, and upregulation of expressions of F-actin and junction proteins. DB contributed to the assembly of actin cytoskeleton by upregulating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway and contributed to the formation of intercellular junctions by downregulating TLR4-MyD88-NF-κB pathway, thus reversing LPS-induced IEB dysfunction. These novel findings illustrated the potential protective mechanism of DB on intestinal inflammatory-related diseases and might be useful for further clinical application of DB.

The impact of the microgravity environment on gut bacteria has been widely recognized to induce notable gastrointestinal pathology during extended spaceflight. However, most current studies for gut microbiome homeostasis profiling are based on the 16S rRNA gene sequencing of fecal samples; this technology faces challenges in analyzing gut bacterial alterations in situ, dynamically, and with high spatiotemporal resolution. Herein, we present the utilization of bioorthogonal metabolic labeling for noninvasive imaging of gut bacterial macroscopic changes in simulated microgravity (SMG) rats. After being subsequently labeled with the metabolic reporters d-Ala-N3 and ICG-DBCO through click chemistry, it was shown that SMG can trigger obvious perturbation of gut bacteria, evidenced by the significant increase in the total bacterial content and spatial distribution variations. Such a difference was accompanied by the occurrence of intestinal inflammation and tissue damage. Compared with 16S rRNA genome analysis focusing on composition and diversity, the metabolic labeling strategy provides unprecedented insights into the macroscopic changes of the gut bacterial content and distribution under SMG. Our study will be helpful for investigating the biological implication of SMG-induced imbalance in gut bacteria, potentially promoting the deep investigation of the complex gastrointestinal pathology in space biomedicine.

The drug efflux transporter permeability glycoprotein (P-gp) plays an important role in oral drug absorption and distribution. Under microgravity (MG), the changes in P-gp efflux function may alter the efficacy of oral drugs or lead to unexpected effects. Oral drugs are currently used to protect and treat multisystem physiological damage caused by MG; whether P-gp efflux function changes under MG remains unclear. This study aimed to investigate the alteration of P-gp efflux function, expression, and potential signaling pathway in rats and cells under different simulated MG (SMG) duration. The altered P-gp efflux function was verified by the in vivo intestinal perfusion and the brain distribution of P-gp substrate drugs. Results showed that the efflux function of P-gp was inhibited in the 7 and 21 day SMG-treated rat intestine and brain and 72 h SMG-treated human colon adenocarcinoma cells and human cerebral microvascular endothelial cells. P-gp protein and gene expression levels were continually down-regulated in rat intestine and up-regulated in rat brain by SMG. P-gp expression was regulated by the Wnt/β-catenin signaling pathway under SMG, verified by a pathway-specific agonist and inhibitor. The elevated intestinal absorption and brain distribution of acetaminophen levels also confirmed the inhibited P-gp efflux function in rat intestine and brain under SMG. This study revealed that SMG alters the efflux function of P-gp and regulates the Wnt/β-catenin signaling pathway in the intestine and the brain. These findings may be helpful in guiding the use of P-gp substrate drugs during spaceflight.

基于配体指数富集系统进化技术筛选闭锁连接蛋白-1的核酸适配体,最终筛选到 15条ZO-1的核酸适配体(APTZO-1).排除线性结构与相似结构后,采用酶联免疫吸附法表征了 9条APTZO-1 与 ZO-1亲和力的大小,排序依次为:APTZO-1 8>APTZO-1 2>APTZO-1 7>APTZO-1 13>APTZO-1 1>APTZO-1 5>APTZO-1 15>APTZO-1 12>APTZO-1 4.采用Cy5荧光基团标记APTZO-1 8(Cy5-APTZO-1 8),证实了其能对人结直肠腺癌细胞(Caco-2)与人脑微管内皮细胞(hCMEC/D3)的ZO-1进行荧光定位与半定量分析,且与基于ZO-1抗体法的免疫荧光与蛋白印迹实验结果基本相似.本研究首次筛选到了ZO-1的系列核酸适配体,有望为ZO-1的荧光标记与半定量分析提供一种新型的、特异性高的工具分子.

Dragon’s blood (DB) has shown a protective effect on neurological diseases. Microgravity (MG) or simulated MG (SMG) can induce blood–brain barrier (BBB) dysfunction, which is a characteristic feature of neurological disorders. This study’s purpose was to evaluate the effect of DB on SMG-induced BBB dysfunction and explore its signaling pathway. Both DB and vitamin C (Vc) were administered orally for tail-suspended rats within 3 weeks. DB and Vc solutions were added to human brain microvascular endothelial cells (HCMEC/D3) cells, which were then exposed to SMG for 24 h. The protective effect of DB was assessed by hematoxylin and eosin and Nissl staining, ultrastructure observation, and permeability in rats. Cell apoptosis and the distribution of tight junction (TJ) and adherens junction (AJ) proteins and filamentous actin (F-actin) were examined in HCMEC/D3. The oxidative stress and inflammation, and TJ and AJ protein expressions were determined in rat brain and HCMEC/D3. The focal adhesion kinase (FAK) signaling pathway proteins were determined. DB protected SMG-induced rat BBB disruption by improving neuronal apoptosis, repairing widened intercellular space, and decreasing BBB permeability. DB effectively relieved SMG-induced HCMEC/D3 damage by inhibiting cell apoptosis and restoring F-actin spindle distribution. High doses of DB upregulated TJ and AJ protein expressions and decreased oxidative stress and proinflammatory cytokine levels in rat brain and HCMEC/D3. DB enhanced the expressions of FAK signal transduction proteins and F-actin/globular actin (G-actin) ratio in rat brain and HCMEC/D3, suggesting that DB promotes actin cytoskeleton polymerization, benefits the endothelial cell–cell and cell–extracellular matrix adhesion, and, in consequence, contributes to BBB integrity.

目的 介绍可评估化合物成药性的在线程序,为提高新药研发效率提供参考.方法 列举各类成药性评估的在线程序,重点介绍其中pkCSM、SwissADME、Molsoft三个网站的提交方法,分析化合物的吸收、分布、代谢、排泄以及毒性性质数据,并以上市药物布洛芬为例,解读三个网站的预测结果,综合评估其成药性,包括pkCSM网站的7种表征吸收项目、4种表征分布项目、7种表征代谢项目、2种表征消除项目、10种表征毒性项目的数据解读;SwissADME网站的鸡蛋图、生物利用度雷达、药物化学性质预测等数据解读;Molsoft网站的类药性评分等数据解读.结果 与结论基于ADME/T理论的预测模型,能够简单、快速、准确地判断化合物的成药性和安全性,建议科研工作者能够充分利用在线程序,加快新药研发进程.

杜梨(Pyrus betulifolia Bunge)抗逆性强,叶色随季节变化而改变,被广泛用于沿海滩涂景观改造,是园林绿化中常用树种.为了解杜梨色叶相关基因调控途径,对杜梨叶片进行转录组测序,共获得67.7 Gb测序数据,通过组装共得到60 611个基因,其中包含1 059个新基因;与8个功能数据库进行比对分析,共57 669个基因得到了功能注释,注释效率为95.15％;GO分析发现,已注释的差异表达基因共涉及49个功能组,主要集中在膜(细胞组分)、催化活性(分子功能)、代谢过程(生物学过程)等中;KEGG分析发现,差异表达基因主要富集在碳代谢和植物-病原体相互作用等生物学过程中;共筛选出10个与类黄酮相关的基因,分别属于UDPGT等6个基因家族;在杜梨叶片转录组中共筛选出452 501个SNP位点,碱基转换类型所占比例远远高于颠换类型,表明杜梨具有丰富的SNP位点信息.本研究结果可为探究杜梨色叶分子机制等提供理论依据.

Semen Ziziphi Spinosae (SZS) has been extensively used in the daily diet as a functional food for neuroprotective health-benefit in China for many years. However, the neuroprotective mechanism of SZS associated with blood-brain barrier (BBB) integrity remains unexplored. The present study suggests SZS could protect against lipopolysaccharide (LPS)-induced BBB dysfunction. Proteomics indicate that 135 proteins in rat brain are significantly altered by SZS. These differentially expressed proteins are mainly clustered into cell-cell adhesion and adherens junctions, which are closely related with BBB integrity. SZS reversed LPS-induces BBB breakdown by activating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway. Molecular docking between signaling pathway proteins and identified SZS components in rat plasma reveals that 6"'-feruloylspinosin, spinosin, and swertisin strongly binds to signaling proteins at multiple amino acid sites. These novel findings suggest a health benefit of SZS in prevention of cerebral diseases and contributes to the further application of SZS as a functional food.

Background Medicinal dendrobiums are used popularly in traditional Chinese medicine for the treatment of diabetes, while their active compounds and mechanism remain unclear. This review aimed to evaluate the mechanism and active compounds of medicinal dendrobiums in diabetes management through a systematic approach. Methods A systematic approach was conducted to search for the mechanism and active phytochemicals in Dendrobium responsible for anti-diabetic actions using databases PubMed, Embase, and SciFinder. Results Current literature indicates polysaccharides, bibenzyls, phenanthrene, and alkaloids are commonly isolated in Dendrobium genusin which polysaccharides and bibenzyls are most aboundant. Many animal studies have shown that polysaccharides from the species of Dendrobium provide with antidiabetic effects by lowering glucose level and reversing chronic inflammation of T2DM taken orally at 200 mg/kg. Dendrobium polysaccharides protect pancreatic β-cell dysfunction and insulin resistance in liver. Dendrobium polysaccharides up-regulate the abundance of short-chain fatty acid to stimulate GLP-1 secretion through gut microbiota. Bibenzyls also have great potency to inhibit the progression of the chronic inflammation in cellular studies. Conclusion Polysaccharides and bibenzyls are the major active compounds in medicinal dendrobiums for diabetic management through the mechanisms of lowering glucose level and reversing chronic inflammation of T2DM by modulating pancreatic β-cell dysfunction and insulin resistance in liver as a result from gut microbita regulation.

With the further advancement of China's major manned spaceflight project, the national space labora-tory was successfully built. China has also made considerable progress and breakthroughs in the field of space life sciences. This paper reviews the related biological effects under space flight conditions, mainly including epigenet-ic effects, skeleton remodeling and peripheral body fluid circulation effects, as well as the research and application of space life science related biotechnology in the field of microbial culture and biological regeneration life support system.

The blood-brain barrier (BBB) is critical to maintaining central nervous system (CNS) homeostasis. However, the effects of microgravity (MG) on the BBB remain unclear. This study aimed to investigate the influence of simulated MG (SMG) on the BBB and explore its potential mechanism using a proteomic approach. Rats were tail-suspended to simulate MG for 21 days. SMG could disrupt the BBB, including increased oxidative stress levels, proinflammatory cytokine levels, and permeability, damaged BBB ultrastructure, and downregulated tight junctions (TJs) and adherens junctions (AJs) protein expression in the rat brain. A total of 554 differentially expressed proteins (DEPs) induced by SMG were determined based on the label-free quantitative proteomic strategy. The bioinformatics analysis suggested that DEPs were mainly enriched in regulating the cell–cell junction and cell–extracellular matrix biological pathways. The inhibited Ras-related C3 botulinum toxin substrate 1 (Rac1)/Wiskott–Aldrich syndrome protein family verprolin-homologous protein 2 (Wave2)/actin-related protein 3 (Arp3) pathway and the decreased ratio of filamentous actin (F-actin) to globular actin contributed to BBB dysfunction induced by SMG. In the human brain microvascular endothelial cell (HBMECs), SMG increased the oxidative stress levels and proinflammatory cytokine levels, promoted apoptosis, and arrested the cell cycle phase. Expression of TJs and AJs proteins were downregulated and the distribution of F-actin was altered in SMG-treated HBMECs. The key role of the Rac1/Wave2/Arp3 pathway in BBB dysfunction was confirmed in HBMECs with a specific Rac1 agonist. This study demonstrated that SMG induced BBB dysfunction and revealed that Rac1/Wave2/Arp3 could be a potential signaling pathway responsible for BBB disruption under SMG. These results might shed a novel light on maintaining astronaut CNS homeostasis during space travel.

P-glycoprotein (P-gp) could maintain stability of the nerve system by effluxing toxins out of the blood-brain barrier. Whether it plays a very important role in drug brain distribution during space travel is not yet known. The present study was aimed at investigating P-gp function, expression, and its interacting proteins in a rat brain under simulated microgravity (SMG) by comparative proteomics approach. Rats were tail-suspended to induce short- (7-day) and long-term (21-day) microgravity. P-gp function was assessed by measuring the P-gp ATPase activity and the brain-to-plasma concentration ratio of rhodamine 123. P-gp expression was evaluated by Western blot. 21d-SMG significantly enhanced P-gp efflux activity and expression in rats. Label-free proteomics strategy identified 26 common differentially expressed proteins (DEPs) interacting with P-gp in 7d- and 21d-SMG groups. Most of the DEPs mainly regulated ATP hydrolysis coupled transmembrane transport and so on. Interaction analysis showed that P-gp might potentially interact with heat shock proteins, sodium/potassium ATP enzyme, ATP synthase, microtubule-associated proteins, and vesicle fusion ATPase. The present study firstly reported P-gp function, expression, and its potentially interacting proteins exposed to simulated microgravity. These findings might be helpful not only for further study on nerve system stability but also for the safe and effective use of P-gp substrate drugs during space travel.

空间飞行期间,失重是威胁航天员健康的主要因素之一.肝脏是人体的重要器官,具有物质代谢、蛋白质合成、解毒等许多重要的生理功能.失重/模拟失重可造成人体肝脏血流动力学改变、鼠肝脏形态结构异常、鼠和金鱼氧化应激损伤,抑制鼠肝细胞增殖,鼠的糖、脂肪、酶等物质代谢紊乱.失重或模拟失重对动物肝脏组织形态、细胞增殖分化、氧化应激反应、物质代谢等造成的影响,可能进一步导致动物物质代谢功能、免疫功能、蛋白质合成功能出现障碍.通过综述失重/模拟失重对肝脏影响的研究进展,以期探讨失重对肝脏影响的机理,为制定航天员健康防护措施提供基础数据.

[目的]旨在全面了解叶色多彩明亮、抗逆性强的美国红枫SSR位点信息及序列特征,为开发新的功能基因相关且多态性良好的SSR标记提供依据.[方法]以美国红枫不同叶色的叶片为试验材料,经转录组测序后,利用MISA软件对美国红枫1 kb以上的Unigene进行SSR位点搜索;通过Excel软件进行SSR分布和序列特征分析并用Prime 3软件设计引物.[结果]从美国红枫转录组测序数据中共获得Unigene 78571条,其中长度≥1 kb的Unigene共23278条.对长度≥1 kb的Unigene进行SSR位点搜索和分析,共获得12974个SSR位点,出现频率为55.75％,平均约3.7 kb出现1个SSR位点;美国红枫转录组SSR重复碱基类型共有7种,其中单碱基为主要重复类型,占总SSR的54.12％,其次为双碱基和三碱基重复类型,分别占总SSR的20.64％和16.19％,其他的碱基重复类型较低,仅占总SSR的9.05％.A/T、AT/TA与GAA/TTC分别为单碱基到三碱基的优势重复基元,分别占总SSR的53.95％、8.00％与1.65％,而四碱基的重复基元均较低,在0.05％以下;单碱基到六碱基各基元重复次数集中在5～22次之间,序列长度变化在10～48 bp之间,平均长度为18.43 bp;筛选出10751个SSR符合引物设计要求,共设计出32253对引物,占总SSR的82.87％.[结论]根据转录组测序结果,美国红枫转录组中SSR位点分布频率高,基序类型丰富,具有较高的多态性,在美国红枫遗传多样性和分子标记辅助育种中具有较大的应用潜力.