As China accelerates its efforts in deep space exploration and long-duration space missions, including the operationalization of the Tiangong Space Station and the development of manned lunar missions, safeguarding astronauts’ physiological and cognitive functions under extreme space conditions becomes a pressing scientific imperative. Among the multifactorial stressors of spaceflight, microgravity emerges as a particularly potent disruptor of neurobehavioral homeostasis. Dopamine (DA) plays a central role in regulating behavior under space microgravity by influencing reward processing, motivation, executive function and sensorimotor integration. Changes in gravity disrupt dopaminergic signaling at multiple levels, leading to impairments in motor coordination, cognitive flexibility, and emotional stability. Microgravity exposure induces a cascade of neurobiological changes that challenge dopaminergic stability at multiple levels: from the transcriptional regulation of DA synthesis enzymes and the excitability of DA neurons, to receptor distribution dynamics and the efficiency of downstream signaling pathways. These changes involve downregulation of tyrosine hydroxylase in the substantia nigra, reduced phosphorylation of DA receptors, and alterations in vesicular monoamine transporter expression, all of which compromise synaptic DA availability. Experimental findings from space analog studies and simulated microgravity models suggest that gravitational unloading alters striatal and mesocorticolimbic DA circuitry, resulting in diminished motor coordination, impaired vestibular compensation, and decreased cognitive flexibility. These alterations not only compromise astronauts’ operational performance but also elevate the risk of mood disturbances and motivational deficits during prolonged missions. The review systematically synthesizes current findings across multiple domains: molecular neurobiology, behavioral neuroscience, and gravitational physiology. It highlights that maintaining DA homeostasis is pivotal in preserving neuroplasticity, particularly within brain regions critical to adaptation, such as the basal ganglia, prefrontal cortex, and cerebellum. The paper also discusses the dual-edged nature of DA plasticity: while adaptive remodeling of synapses and receptor sensitivity can serve as compensatory mechanisms under stress, chronic dopaminergic imbalance may lead to maladaptive outcomes, such as cognitive rigidity and motor dysregulation. Furthermore, we propose a conceptual framework that integrates homeostatic neuroregulation with the demands of space environmental adaptation. By drawing from interdisciplinary research, the review underscores the potential of multiple intervention strategies including pharmacological treatment, nutritional support, neural stimulation techniques, and most importantly, structured physical exercise. Recent rodent studies demonstrate that treadmill exercise upregulates DA transporter expression in the dorsal striatum, enhances tyrosine hydroxylase activity, and increases DA release during cognitive tasks, indicating both protective and restorative effects on dopaminergic networks. Thus, exercise is highlighted as a key approach because of its sustained effects on DA production, receptor function, and brain plasticity, making it a strong candidate for developing effective measures to support astronauts in maintaining cognitive and emotional stability during space missions. In conclusion, the paper not only underscores the centrality of DA homeostasis in space neuroscience but also reflects the authors’ broader academic viewpoint: understanding the neurochemical substrates of behavior under microgravity is fundamental to both space health and terrestrial neuroscience. By bridging basic neurobiology with applied space medicine, this work contributes to the emerging field of gravitational neurobiology and provides a foundation for future research into individualized performance optimization in extreme environments.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.

Nuclear medicine plays an indispensable role in the diagnosis,treatment,and prognosis of a wide range of diseases.Nuclear medicine using radionuclides for diagnosis has the advantages of accuracy,speed,high sensitivity and high resolution.Currently,several radionuclides play pivotal roles in disease diagnosis.This article primarily examines the clinical application and research of diagnostic radionuclides,including 18 F,89 Zr,68 Ga,99m Tc,131 I,123 I,and 11 C.The objective is to offer valuable insights for disease diagnosis and staging of diseases.

Vitamin D is a unique fat-soluble vitamin that plays an indispensable role in human health. It exists in various forms, the most significant being vitamin D₂ (derived from plant sources) and vitamin D₃ (synthesized naturally in human skin upon exposure to sunlight). Vitamin D’s primary function is to facilitate the absorption of calcium and phosphorus, which are crucial for maintaining healthy bones. Beyond its role in bone health, vitamin D significantly influences the immune system, muscle function, cardiovascular health, and the regulation of brain functions. A deficiency in vitamin D can lead to various chronic diseases such as rickets, osteoporosis, decreased immunity, increased risk of mental disorders, and cancers. The synthesis of vitamin D in the human body, both peripherally and centrally, relies on sunlight exposure, dietary sources, and various supplements. As a neuroactive steroid, vitamin D impacts both the physiological and pathological processes of the nervous system and plays a key role in brain health. It profoundly affects the brain by regulating neurotransmitter synthesis and maintaining intracellular calcium balance. As an essential chemical molecule, vitamin D participates in complex signal transduction pathways, impacting neurotransmitter functions and synaptic plasticity. Vitamin D’s role in regulating dopamine (DA)—a neurotransmitter critical for motivation, reward perception, and other higher cognitive functions—is particularly noteworthy. Recent studies have revealed that vitamin D not only promotes the synthesis of DA but also plays a role in regulating DA levels within the brain. It exerts neuroprotective effects on DA neurons through anti-inflammatory, antioxidant actions, and neurotrophic support, thereby creating an optimal environment for DA neurons, influencing neuronal structure, and affecting the movement of calcium ions within nerve cells, positively impacting the overall health and functionality of the DA system. Furthermore, vitamin D can regulate the synthesis and release of DA, thus affecting the signal transmission of various DA neural projection pathways in the brain. This function is vital for understanding the complex interactions between neural mechanisms and their effects on key behaviors and cognitive functions. This review aims to delve deeply into the synthesis, metabolism, and pathways of vitamin D’s action, especially its regulatory mechanisms on DA neurons. Through this exploration, this article seeks to provide a solid theoretical foundation and research framework for a deeper understanding of vitamin D’s role in motivation and reward behaviors. This understanding is crucial for appreciating the broader significance of vitamin D in the fields of neuroscience and neurology. In summary, research and discoveries regarding vitamin D’s impact on the nervous system highlight its importance in neural health and function. These insights not only enhance our understanding of the complex workings of the nervous system but also open new avenues for the prevention and treatment of neurological diseases. The exploration of vitamin D’s multifaceted roles offers promising prospects for developing new therapeutic strategies, underscoring the compound’s potential in addressing a range of neural dysfunctions and diseases. As research continues to evolve, the profound implications of vitamin D in the field of neurology and beyond become increasingly apparent, marking it as a key target for ongoing and future scientific inquiry.

Objective:To explore the best treatment for local ablation of colon cancer liver metastases (CRLM) by meta-analysis.Methods:The electronic databases of PubMed, Web of Science, Embase, CNKI and the Cochrane Library were searched from the establishment to August 22, 2022, and studies that report outcomes with comparison between microwave ablation (WMA) and radiofrequency ablation (RFA) in CRLM treatment were selected by inclusion and exclusion criteria. Furthermore, the perioperative and survival data were statistically summarized and analyzed by Review Manager 5.3 software.Results:A total of 5 retrospective studies were included with a total sample size of 648 cases, including 316 cases (48.8%) in the WMA group and 332 cases (51.2%) in the RFA group. The results of meta-analysis showed that locoregional recurrence rate in WMA group was significantly lower than that in RFA group. The 1-year and 2-year disease-free survival (DFS) of the WMA group was significantly better than that of the RFA group with HR of 1.77 ( P=0.04, 95% CI: 1.04-3.02) and 1.60 ( P=0.02, 95% CI: 1.09-2.35), respectively. Conclusion:The local control rate and 1-year and 2-year DFS of WMA were superior to RFA.

The end of the COVID-19 infection peak in 2022 prompts a backlog of cardiovascular surgical patients to gradually return to the hospital, resulting in a surge in cardiovascular surgeries. However, against the backdrop of the COVID-19 pandemic, the clinical practice of cardiovascular surgery faces many problems. Therefore, organized by Beijing Anzhen Hospital, experts in cardiovascular surgery and related fields have formulated hospital expert experience on perioperative treatment principles of cardiovascular surgery for patients infected with COVID-19. This article summarizes the clinical decision-making of patients requiring cardiovascular surgery after COVID-19 infection, and advises on the corresponding recommendations according to the existing evidence-based medical evidence as well as the actual clinical practice experience of relevant experts. The main content of the article includes special requirements for cardiovascular surgical treatment indications in patients with COVID-19 infection, selection of surgical timing, special requirements of preoperative, intraoperative and postoperative management, etc., which aims to provide COVID-19-infected patients with guidance on rational decision-making when receiving cardiovascular surgery.

Drug resistance presents one of the major causes for the failure of cancer chemotherapy. Cancer stem-like cells (CSCs), a population of self-renewal cells with high tumorigenicity and innate chemoresistance, can survive conventional chemotherapy and generate increased resistance. Here, we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent, all-trans retinoic acid and the chemotherapeutic drug, doxorubicin to overcome the CSC-associated chemoresistance. The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation. In the hypoxic CSCs, ATRA is released to induce differentiation of the CSCs, and in the differentiating CSCs with decreased chemoresistance, DOX is released upon elevation of reactive oxygen species to cause subsequent cell death. In the bulk tumor cells, the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect. This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism. We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.