ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Purpose: In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. Methods: Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. Results: Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. Conclusion Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.

Laboratory animal science is an emerging interdisciplinary field supporting life science and medical research, and a key component of talent cultivation and technological innovation in medical colleges. Currently, this field faces challenges such as a significant imbalance between talent supply and demand and a weak systematic training system. To respond to national strategies and societal needs, Shandong First Medical University established the School of Laboratory Animal through industry-education integration during the 14th Five-Year Plan period. The school is based on The Medical Laboratory Technology major, cultivates application-oriented, interdisciplinary professionals in laboratory animal science, and has constructed a three-in-one training system integrating "course learning–scientific research–industry practice". Specific measures for talent cultivation include: optimizing the general education, professional courses, and intensive practical modules in the talent training program, and establishing the "Yellow River Class" integrating industry and education; implementing an undergraduate mentor system, and conducting scientific research training based on The Model Animal Research and Development Engineering Laboratory; collaborating with bases across the entire industrial chain of laboratory animal production, research, application, and quality control, appointing industry mentors, and strengthening practical teaching. Practice has shown that this system has been remarkably effective: a total of 320 undergraduate students have been enrolled since 2020; the employment rate of undergraduate graduates for two consecutive cohorts has reached 100%, and the postgraduate enrollment rate has exceeded 50%; undergraduate students have won numerous national and provincial awards in academic competitions, and have obtained multiple patents and published papers. In the future, the school will further integrate the advantages of medicine, agriculture, and science, optimize the depth and breadth of courses, strengthen the construction of faculty and teaching materials, and improve the undergraduate-master's integrated training mechanism. This article can provide a reference for the training of professionals in laboratory animal science and related biomedical fields in medical colleges.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

ObjectiveThe primary objective of this study was to investigate the effects of carbohydrate intake order on post-exercise recovery and metabolic regulation under heat stress, particularly in models of exercise induced fatigue. Given the increasing significance of optimizing nutritional strategies to support performance in extreme environmental conditions, this study aimed to provide experimental evidence that contributes to a better understanding of how the sequence in which carbohydrates are consumed impacts exercise recovery, metabolic homeostasis, and fatigue alleviation in a high-temperature environment. MethodsA mouse model of exercise-induced fatigue was established under high-temperature (35°C) to simulate heat stress. The subjects were divided into 3 distinct groups based on their carbohydrate intake order: the “mixed intake” group (HOT_MIX), where all macronutrients (carbohydrates, proteins, and fats) were consumed in a balanced ratio; the “carbohydrate-first intake” group (HOT_CHO), where carbohydrates were consumed first followed by other macronutrients; the “carbohydrate-later intake” group (HOT_PRO), where proteins and fats were consumed prior to carbohydrates. Each group underwent a 7 d intervention period with daily intake according to their designated group. Exercise performance was assessed using rotarod retention time test, and biomarkers of muscle damage, such as lactate dehydrogenase (LDH), creatine kinase (CK), lactate (LD), alanine aminotransferase (ALT), and non-esterified fatty acids (NEFA), were measured. Furthermore, targeted metabolomics analyses were conducted to investigate metabolic shifts in response to different dietary strategies, and KEGG pathway enrichment analysis was employed to explore the biological mechanisms underlying these changes. ResultsThe findings demonstrated that the HOT_PRO group exhibited a significantly improved performance in the rotarod test, with a longer retention time compared to both the HOT_MIX and HOT_CHO groups (P<0.05). Additionally, this group showed significantly reduced levels of muscle damage markers such as LDH and CK, indicating that the carbohydrate-later intake strategy helped alleviate exercise-induced muscle injury. Metabolomic profiling of the HOT_PRO group showed marked increases in alanine, creatine, and flavin adenine dinucleotide (FAD), indicating shifts in amino acid metabolism and oxidative metabolism. Conversely, metabolites such as spermidine, cholesterol sulfate, cholesterol, and serine were significantly reduced in the HOT_PRO group, pointing to alterations in lipid and sterol metabolism. Further analysis of the differential metabolites revealed that these changes were primarily associated with key metabolic pathways, including glycine-serine-threonine metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, and steroid hormone biosynthesis. These pathways are essential for energy production, antioxidant defense, and muscle recovery, suggesting that the carbohydrate-later feeding strategy may promote metabolic homeostasis and improve exercise recovery by enhancing these critical metabolic processes. ConclusionThe results of this study support the hypothesis that consuming carbohydrates after proteins and fats during exercise recovery enhances metabolic homeostasis and accelerates recovery under heat stress. This strategy effectively modulates energy, amino acid, and lipid-related pathways, which are crucial for improving endurance performance and mitigating fatigue in high-temperature environments. The findings suggest that carbohydrate-later intake could be a promising nutritional strategy for athletes and individuals exposed to heat during physical activity. Furthermore, the study provides valuable insights into how different nutrient timing strategies can impact exercise recovery and metabolic regulation, paving the way for more personalized and effective nutritional interventions in extreme environmental conditions.

This paper aimed to systematically evaluate the effects of hypoxic training at different fraction of inspired oxygen (FiO₂) on body composition, glucose metabolism, and lipid metabolism in obese individuals, and to determine the optimal oxygen concentration range to provide scientific evidence for personalized and precise hypoxic exercise prescriptions. A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and CNKI databases for randomized controlled trials and pre-post intervention studies published up to March 31, 2025, involving hypoxic training interventions in obese populations. Meta-analysis was performed using RevMan 5.4 software to assess the effects of different fraction of inspired oxygen (FiO₂≤14% vs. FiO₂>14%) on BMI, body fat percentage, waist circumference, fasting blood glucose, insulin, HOMA-IR, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with subgroup analyses based on oxygen concentration. A total of 22 studies involving 292 participants were included. Meta-analysis showed that hypoxic training significantly reduced BMI (mean difference (MD)=-2.29,95%CI: -3.42 to -1.17, P<0.000 1), body fat percentage (MD=-2.32, 95%CI: -3.16 to -1.47, P<0.001), waist circumference (MD=-3.79, 95%CI: -6.73 to -0.85, P=0.01), fasting blood glucose (MD=-3.58, 95%CI: -6.23 to -0.93, P=0.008), insulin (MD=-1.60, 95%CI: -2.98 to -0.22, P=0.02), TG (MD=-0.18, 95%CI: -0.25 to -0.12, P<0.001), and LDL-C (MD=-0.25, 95%CI: -0.39 to -0.11, P=0.000 3). Greater improvements were observed under moderate hypoxic conditions with FiO₂>14%. Changes in HOMA-IR (MD=-0.74, 95%CI: -1.52 to 0.04,P=0.06) and HDL-C (MD=-0.09, 95%CI: -0.21 to 0.02, P=0.11) were not statistically significant. Hypoxic training can significantly improve body composition, glucose metabolism, and lipid metabolism indicators in obese individuals, with greater benefits observed under moderate hypoxia (FiO>14%). As a key parameter in hypoxic exercise interventions, the precise setting of oxygen concentration is crucial for optimizing intervention outcomes.

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral