摘要: A survey of small mammals conducted on the Qinghai-Xizang Plateau in August 2023 yielded a series of specimens of a distinctive and previously unidentified Neodon species from high-altitude shrubland and grassland habitats at elevations of 2800–4000 m in Lhozhag County, Xizang, China. This study employed an integrative approach, combining molecular and morphological evidence to determine the taxonomic placement of the species. Results confirmed that these specimens represent a new species, formally described herein as Neodon lhozhagensis sp. nov. The new species can be distinguished from all other Neodon species based on larger body size, longer tail, five closed triangles in first lower molar, and obvious interorbital crest. Molecular analysis strongly supported Neodon lhozhagensis sp. nov. as a monophyletic clade that diverged from its sister taxon, Neodon tsonaensis, approximately 0.89–1.68 million years ago. Kimura-2-parameter genetic distances of the complete cytochrome b gene between Neodon lhozhagensis sp. nov. and other nominal Neodon species ranged from 9.3% to 12.8%. This discovery underscores the importance of continued efforts to investigate and document the biodiversity of the Himalayan region.

摘要: Six new genera, Pengaraneus gen. nov., Songaraneus gen. nov., Tangaraneus gen. nov., Wangaraneus gen. nov., Yinaraneus gen. nov. and Zhuaraneus gen. nov., and twenty species, including sixteen new, of the family Araneidae from Xishuangbanna, Yunnan, south-west China are described: Cyclosa anjing sp. nov. (♂♀), C. daodai sp. nov. (♂♀), C. longquan sp. nov. (♂♀), C. xingqing sp. nov. (♂♀), Gasteracantha diadesmia Thorell, 1887 (♂♀), Guizygiella huahai sp. nov. (♂♀), Neoscona jinghongensis Yin, Wang, Xie & Peng, 1990 (♂♀), N. piaoyi sp. nov. (♂♀), N. wuding sp. nov. (♂♀), Pengaraneus qingtian sp. nov. (♂♀), Poltys waipo sp. nov. (♂♀), Songaraneus jiekou sp. nov. (♂♀), S. tuihou sp. nov. (♂♀), Talthybia depressa Thorell, 1898 (♂♀), Tangaraneus geqian sp. nov. (♂♀), Wangaraneus yequ sp. nov. (♂♀), W. zioni (Mi, Li & Pham, 2023) (♂♀) comb. nov., Yinaraneus anhao sp. nov. (♂♀), Y. caihong sp. nov. (♂♀), Zhuaraneus daoxiang sp. nov. (♂♀). Wangaraneus zioni is newly recorded in China. Mature males of the monotypic genus Talthybia Thorell, 1898 (for the type species T. depressa) and Gasteracantha diadesmia, W. zioni, N. jinghongensis are described for the first time. Four new synonyms are proposed, Neoscona nautica (L. Koch, 1875)=Neoscona polyspinipes Yin, Wang, Xie & Peng, 1990 syn. nov., Neoscona nautica (L. Koch, 1875)=Neoscona flavescens Zhang & Zhang, 2011 syn. nov., Neoscona vigilans (Blackwall, 1865)=Neoscona xiquanensis Barrion, Barrion-Dupo & Heong, 2013 syn. nov, and Songaraneus ejusmodi (Bösenberg & Strand, 1906)=Araneus qianshan Zhu, Zhang & Gao, 1998 syn. nov. Six new combinations are proposed, Songaraneus ejusmodi (Bösenberg & Strand, 1906) comb. nov., S. perpolita (Thorell, 1893) comb. nov., Wangaraneus ryani (Mi, Li & Pham, 2023) comb. nov., W. zioni (Mi, Li & Pham, 2023) comb. nov., Zhuaraneus ethani (Mi, Li & Pham, 2023) comb. nov. and Z. eugenei (Mi, Li & Pham, 2023) comb. nov.

摘要: Animal models constructed using pathogenic factors have significantly advanced drug development for Alzheimer's disease(AD). These predominantly transgenic models,mainly in mice, replicate pathological phenotypes through gene mutations associated with familial AD cases, thus serving as vital tools for assessing drug efficacy and for performing mechanistic studies. However, the speciesspecific differences and complex, heterogeneous nature of AD etiology pose considerable challenges for the translatability of these animal models, limiting their utility in drug development. This review offers a comprehensive analysis of widely employed rodent(mice and rats) and non-rodent models(Danio rerio(zebrafish), Drosophila melanogaster, and Caenorhabditis elegans), detailing their phenotypic features and specific research applications.This review also examines the limitations inherent in these models and introduces various strategies for expanding AD modeling across diverse species, emphasizing recent advancement in non-human primates(NHPs) as valuable models. Furthermore, potential insights from the integration of innovative technologies in AD research are discussed, while providing valuable perspectives on the future development of AD animal models.

摘要: Stroke is a major cause of death and disability worldwide,with the majority of cases resulting from ischemic events due to arterial occlusion. Current therapeutic approaches focus on rapid reperfusion through intravenous thrombolysis and intravascular thrombectomy. Although these interventions can mitigate long-term disability,reperfusion itself may induce neuronal injury. The exact mechanisms underlying neuronal damage following cerebral ischemia have yet to be reported. Recent research suggests that ferroptosis may play a significant role in post-ischemic neuronal death, which can be targeted to prevent neuronal loss. This review explores the three essential hallmarks of ferroptosis: the presence of redox-active iron, the peroxidation of polyunsaturated fatty acid-containing phospholipids, and the loss of lipid peroxide repair capacity. The involvement of ferroptosis in neuronal injury following ischemic stroke is also explored,along with an overview of ferroptosis-associated changes in different ischemic stroke animal models. Furthermore,recent therapeutic interventions targeting the ferroptosis pathway, as well as the opportunities, difficulties, and future directions of ferroptosis-targeted therapies in ischemic stroke, are discussed.

摘要: Individuals with diabetes frequently face serious challenges, including delayed wound healing and increased risk of infection. Notably, the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair, reducing the risk of infection, and enhancing overall skin health. Research has predominantly emphasized the re-epithelialization of diabetic wounds, with a paucity of in-depth studies on hair follicle regeneration. In the current study, we explored the effects of a bioactive amphibian-derived peptide,Cy_RL-QN15, on promoting hair regeneration in a diabetic skin model. In vivo experiments demonstrated that local treatment with Cy_RL-QN15 not only accelerated wound healing of scalded skin on the backs of diabetic Kunming（KM） mice but also improved growth of damaged hair follicles. Additionally, back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy_RL-QN15treatment. Further analysis indicated that the hairregenerating effects of Cy_RL-QN15 were closely associated with the proliferation and migration of hair follicle stem cells（HFSCs）. Cy_RL-QN15 enhanced intracellular β-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs. The up-regulation in β-catenin modulated the levels of downstream proteins, such as cMYC, Cyclin D1, and Lef1, ultimately inducing hair regeneration. This study not only reveals the robust effects of the bioactive peptide Cy_RL-QN15 in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.

摘要: Isocitrate dehydrogenase 2(IDH2) and glutamate dehydrogenase 1(GLUD1) are key enzymes involved in the production of α-ketoglutarate(α-KG), a metabolite central to the tricarboxylic acid cycle and glutamine metabolism. In this study, we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown(KD) via doublestranded RNA(dsRNA) microinjection. Results showed that KD reduced α-KG levels, leading to delayed embryonic development, decreased blastocyst formation,increased apoptosis, reduced blastomere proliferation, and pluripotency. Additionally, IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4(H4K20me3) at the 4-cell stage, likely resulting in transcriptional repression of embryonic genome activation(EGA)-related genes. Notably, KD of lysine methyltransferase 5C(KMT5C) and supplementation with exogenous α-KG reduced H4K20me3 expression and partially rescued these defects, suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos. Overall, this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence on α-KG production and subsequent epigenetic modifications.

摘要: As an essential transcriptional activator, PDX1 plays a crucial role in pancreatic development and β-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4) and neonatal diabetes mellitus. However, the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models. In this study, three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology, all of which succumbed shortly postpartum, exhibiting pancreatic agenesis. Notably, one tri-allelic PDX1-mutant cynomolgus macaque(designated as M4) developed a pancreas, whereas the two monoallelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation. RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions, indicating developmental delay and PDX1haploinsufficiency. A marked change in m6A methylation was identified in the M4 pancreas, confirmed through cultured PDX1-mutantisletorganoids.Notably,overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids.This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.

摘要: Animals deploy diverse color-based defenses against predators, including crypsis, mimicry, aposematism, and masquerade. While crypsis, mimicry, aposematism have beenextensivelystudied,thestrategyof masquerade —where organisms imitate inedible or inanimate objects such as leaves, twigs, stones, and bird droppings—remainscomparativelyunderexplored,particularly in adult butterflies. The Indian oakleaf butterfly(Kallima inachus) exemplifies this phenomenon, with its wings resembling dead leaves, providing a classic example of natural selection. Although it has long been postulated that these butterflies evade predation by being misidentified as dead leaves, direct experimental evidence is lacking. In the current study, using domestic chicks as predators, we manipulated their prior experience with dead leaves(model objects) while maintaining constant exposure to butterflies to test whether dead-leaf masquerade provides a protective advantage by preventing recognition. Results showed a marked delay in the initiation of attacks by chicks familiar with dead leaves compared to those with no prior exposure or those exposed to visually altered leaves. Chicks with prior deadleaf experience required a similar amount of time to attack the butterflies as they did to attack dead leaves. These findings provide the first empirical demonstration of deadleaf masquerade in Kallima butterflies, shedding light on its evolutionary significance. Our study highlights the effectivenessofmasqueradeininducingthe misclassification of butterflies as inanimate objects,showcasing the precise mimicry achieved by these organisms when viewed in isolation from the model objects. This study advances our understanding of the evolution of masquerade and its role as a potent antipredator strategy in nature.

摘要: High-altitude and marine mammals inhabit distinct ecosystems but share a common challenge: hypoxia. To survive in low-oxygen environments, these species have evolved similar phenotypic pulmonary adaptations,characterized by a high density of elastic fibers. In this study, we explored the molecular mechanisms underlying these adaptations, focusing on pulmonary fibrosis and hypoxia tolerance through comparative genomics and convergent evolution analyses. We observed significant expansions and contractions in certain gene families across both high-altitude and marine mammals, closely associated with processes involved in pulmonary fibrosis.Notably, members of the keratin gene family, such as KRT17 and KRT14, appear to be associated with the development of the dense elastic fiber phenotype observed in the lungs of hypoxia-tolerant mammals.Through selection pressure and amino acid substitution analyses, we identified multiple genes exhibiting convergent accelerated evolution, positive selection, and amino acid substitution in these species, associated with adaptation to hypoxic environments. Specifically, the convergent evolution of ZFP36L1, FN1, and NEDD9 was found to contribute to the high density of elastic fibers in the lungs of both high-altitude and marine mammals,facilitating their hypoxia tolerance. Additionally, we identified convergent amino acid substitutions and gene loss events associated with sperm development,differentiation, and spermatogenesis, such as amino acid substitutions in SLC26A3 and pseudogenization of CFAP47, as confirmed by PCR. These genetic alterations may be linked to changes in the reproductive capabilities of these animals. Overall, this study offers novel perspectives on the genetic and molecular adaptations of high-altitude and marine mammals to hypoxic environments, with a particular emphasis on pulmonary fibrosis.

摘要: Maternal sleep deprivation(MSD) has emerged as a significant public health concern, yet its effects on offspring metabolism remain poorly understood. This study investigated the metabolomic implications of MSD on offspring cognitive development, with a particular focus on alterations in glutamate metabolism. Pregnant rats were subjected to sleep deprivation during late gestation.Plasma and brain samples from their offspring were collected at different postnatal days(P1, P7, P14, and P56) and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry. Metabolomic analysis revealed significant differences in various amino acids, including L-glutamate, L-phenylalanine, L-tyrosine,and L-tryptophan, which are crucial for cognitive function.Subsequent differential analysis and partial least squares discriminant analysis(sPLS-DA) demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development. KEGG pathway analysis revealed differential regulation of several pathways, including alanine, aspartate, and glutamate metabolism, glutathione metabolism, arginine biosynthesis,aminoacyl-tRNA biosynthesis, histidine metabolism, and taurine and hypotaurine metabolism, at different developmental stages. Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes,Ruminococcus＿1,Ruminococcaceae＿UCG-005,and Eubacterium＿coprostanoligenes＿group.Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway. Collectively, these findings suggest that MSD not only affects maternal wellbeing but also has enduring metabolic consequences for offspring, particularly impacting pathways linked to cognitive function. This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.