Background/Objectives: Long-term spaceflight in a microgravity environment frequently results in gastrointestinal dysfunction, presenting substantial challenges to astronauts’ health. Hericium erinaceus, a plant recognized for its dual use as food and medicine, contains a key functional component called Hericium erinaceus polysaccharide (HEP), which is purported to promote gastrointestinal health. This study aims to investigate the protective effects of HEP against gastrointestinal disturbances induced by simulated weightlessness and to elucidate its regulatory mechanisms. Methods: Sprague Dawley rats subjected to a tail suspension model were administered either a standard diet or a diet supplemented with 0.125% HEP over a period of 4 weeks (the intake of HEP is approximately 157.5 mg/kg bw/d, n = 8), metagenomics and targeted metabolomics to investigate the effects of HEP on gastrointestinal hormone secretion disorders, gut microbiota dysbiosis, and intestinal barrier damage induced by simulated weightlessness. Results: Dietary supplementation with HEP was observed to significantly alleviate weightlessness-induced gastrointestinal hormone disruptions, enhancing motility and intestinal barrier function while reducing inflammation. In addition, HEP improved gut microbiota by boosting beneficial bacteria as Oscillibacter sp.1-3, Firmicutes bacterium ASF500, and Lactobacillus reuteri, while reducing harmful bacteria like Escherichia coli and Mucispirillum schaedleri at the species level. Furthermore, HEP altered the serum metabolic profile of the rats, reducing inflammation by upregulating the tryptophan metabolism pathway and enhancing the production of short-chain fatty acids. Conclusions: HEP effectively protects against gastrointestinal dysfunction induced by simulated weightlessness by regulating hormone secretion and maintaining intestinal homeostasis.

Recent advances in understanding gut‒liver axis homeostasis has been made because of the promising beneficial effects of these systems on health main

Background:Recent advances in understanding gut‒liver axis homeostasis have been made because of its promising beneficial effects on health maintenance and performance promotion. However, we still have little knowledge about the effects of long-term microgravity exposure on the gut-liver axis or about effective countermeasures to prevent disruptions in gut-liver axis homeostasis. Hence, we conducted a well-controlled study to determine the effects of long-term microgravity exposure on liver activity and the gut microbiota and on gut-liver axis homeostasis via a hindlimb suspension rat model. Results: Interestingly, long-term microgravity exposure increased lipid deposition, oxidative stress and inflammation in the liver; increased proportions of enteric opportunistic pathogens; and disrupted intestinal barrier integrity, paralleling the dysregulation of gut-liver axis homeostasis, which especially underlined portal influx of secondary bile acid (mainly ursodeoxycholic acid and lithocholic acid). Notably, metabolites derived from the liver were strongly correlated with those from the colon, and the gut microbiota played a vital role in the cometabolism pathways of aminoacyl-tRNA biosynthesis, vitamin B6 metabolism, alanine, and aspartate and glutamate metabolism, which may emphasize the critical role of microbial homeostasis in maintaining hepatic synthesis and metabolism of amino acids upon microgravity. Conclusions: Taken together, our findings suggest that gut-liver axis disturbances resulting fromlong-term microgravity exposure should receive additional attention in further studies of manned space.

This article provides a scoping review of various types of functional factors and their mechanisms of action in enhancing physical strength and endurance, focusing on their roles in regulating the central nervous system, improving energy metabolism, reducing metabolite accumulation, enhancing antioxidant and anti-inflammatory capacity, regulating the endocrine system, and improving blood circulation. For functional factors supported by sufficient human evidence, stratified application can be made according to their primary effects. Those applicable to strength-type sports include creatine, HMB, vitamin D, L-arginine, L-citrulline, L-carnitine, curcumin, epicatechin, and golden root extract. Those applicable to endurance-type sports include beta-alanine, taurine, iron, caffeine, eleutheroside, anthocyanins, powdered Montmorency tart cherry, and beetroot concentrate. Those applicable to mixed-discipline sports include BCAAs, glutamine, whey protein, coenzyme Q10, and magnesium. Mechanisms that specifically enhance physical strength include increased blood flow delivery via the NO–sGC–cGMP pathway, attenuation of central nervous system fatigue through LAT1-mediated tryptophan competition, and maintenance of calcium homeostasis via the SERCA–RyR1–VDAC1–MCU axis. Endurance-specific enhancement is achieved primarily by promoting type IIa muscle fiber formation through the AMPK/SIRT1/PGC1-α and PKA–CREB–ERRγ signaling axes. Functional factors that simultaneously improve both outcomes act through reducing oxidative stress via the Nrf2–Keap1–ARE network, regulating energy metabolism via the PI3K/Akt/mTOR and AMPK pathways, suppressing NF-κB-mediated inflammation, and optimizing the gut–liver–muscle axis. In addition, this article points out research challenges such as individual differences and experimental design limitations and suggests that the long-term safety of personalized sports nutrition strategies and functional factors needs to be further explored in the future. The review provides a scientific theoretical basis for sports training and health management, as well as an important reference for the development of novel sports nutrition programs.

Background: Proton radiation is both a core component of the space radiation environment and a pivotal modality for precision clinical tumor radiotherapy. Proton exposure can impair cognitive, learning and memory functions, representing a common concern in the fields of deep space aerospace medicine and clinical radiotherapy. Nevertheless, the cellular and molecular regulatory mechanisms underlying proton-induced cognitive impairment remain incompletely elucidated. Methods: In vivo and in vitro injury models were established via 100 MeV proton radiation. Specifically, an in vivo model of proton radiation-induced cognitive injury was constructed using C57BL/6J mice (male), and an in vitro radiation injury model was established with HT22 hippocampal neuronal cells to systematically investigate the molecular mechanism of cognitive impairment caused by proton radiation. Results: Proton radiation induced a persistent decline in learning and memory capacity in mice, triggered systemic oxidative stress, caused metabolic disturbances of multiple neurotransmitters in the hippocampus, and induced structural mitochondrial damage and decreased mitochondrial membrane potential in hippocampal neurons, suggesting that mitochondria are the key subcellular target of its neurotoxicity. Proton radiation induced oxidative stress in hippocampal neurons. Hyperactivation of mTORC1 inhibited the kinase activity of ULK1 by phosphorylating its Ser757 residue and downregulated ULK1 protein levels, resulting in mitophagy dysfunction and mitophagic flux blockade. Persistent severe oxidative stress prevented damaged mitochondria from being cleared via mitophagy and activated the apoptotic cascade, ultimately leading to hippocampal neuronal death and cognitive impairment. Conclusions: This study reveals the molecular mechanism by which proton radiation induces mitophagy dysfunction and hippocampal neuronal apoptosis and subsequently triggers cognitive impairment, providing a new theoretical basis and potential intervention targets for the prevention and treatment of neurocognitive complications associated with space radiation exposure and clinical radiotherapy.