Search Results (920)

Spawning diversity plays an essential role in fish survival and reproduction, which contributes to the exceptional diversity of teleosts among vertebrates. Different zona radiata structures reflect the adaptability of fish to the environment of spawning and early embryonic development. The morphological and transcriptional characteristics of fish follicle development between different spawning habits, particularly the zona radiata variations, have been poorly documented. In this study, we integrated histology and transcriptomics to investigate the differences in the zona radiata structure and gene expression profiles among follicles from different spawning habits of Culter alburnus. Our results revealed that stage Ⅲ was the crucial period for zona radiata thickening and structure differentiation. Transcriptomic analyses of adhesive and semi-buoyant eggs at stage Ⅲ revealed a significant upregulation of genes involved in glycoprotein synthesis, extracellular matrix formation, and regulation of protease activity in adhesive eggs, such as the wfdc and a2ml gene family. This upregulation likely underpins the thicker zona radiata in adhesive eggs, facilitating their attachment to substrates. This study represents the first elucidation of the ultrastructure of the zona radiata and gene expression patterns in different developmental stages of adhesive and semi-buoyant eggs of Culter alburnus, offering new perspectives for aquaculture research in understanding fish reproductive adaptations. Full article

To investigate temporal deformation mechanisms of hydraulic asphalt concrete slope flow under evolving temperatures, this study developed a novel temperature-controlled slope flow intelligent test apparatus. Using this apparatus, slope flow tests were conducted at four temperature levels: 20 °C, 35 °C, 50 °C, and 70 °C. By applying nonlinear dynamics theory, the temporal evolution of slope flow deformation and its nonlinear mechanical characteristics under varying temperatures were thoroughly analyzed. Results indicate that the thermal stability of hydraulic asphalt concrete is synergistically governed by the phase-transition behavior between asphalt binder and aggregates. Temporal evolution of slope flow exhibits a distinct three-stage pattern as follows: rapid growth (0~12 h), where sharp temperature rise disrupts the primary skeleton of coarse aggregates; decelerated growth (12~24 h), where an embryonic secondary skeleton forms and progressively resists deformation; stabilization (>24 h), where reorganization of coarse aggregates is completed, establishing structural equilibrium. The thermal stability temperature influence factor (δ) shows a nonlinear concave growth trend with increasing test temperature. Dynamically, this process transitions sequentially through critical stability, nonlinear stability, period-doubling oscillatory stability, and unsteady states. Full article

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk. Full article

The Notch signaling pathway is a critical regulator of embryonic brain development. Among its four mammalian receptors, Notch1 and Notch2 are particularly significant in the developing cortex, yet their roles in human neurodevelopment are not well understood. In murine cortex development, Notch1 primarily regulates early progenitor identity and neurogenesis, while Notch2 is required for maintaining radial glial cells at later stages. However, it is unclear whether these functions are conserved in the human developing brain. In this study, we used cerebral organoids as an in vitro model of early human corticogenesis and conducted lentiviral shRNA-mediated knockdowns of NOTCH1 and NOTCH2. Our findings indicate that NOTCH1 is essential for organoid growth, lumen morphogenesis, radial glial identity, and progenitor proliferation. In contrast, depleting NOTCH2 did not significantly affect these early developmental processes. These results demonstrate that NOTCH1 and NOTCH2 have potentially non-redundant and temporally distinct roles in early human corticogenesis, reflecting receptor-specific specialization within the Notch signaling pathway. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic consequences of BSA deprivation during preimplantation stages in mice. Embryos cultured in BSA-free media during specific time windows exhibited impaired blastocyst formation, with continuous deprivation from the two-pronuclei (2PN) stage significantly reducing trophectoderm (TE) and inner cell mass (ICM) cell numbers (p < 0.05), indicating compromised viability. Short-term BSA deprivation similarly disrupted lineage allocation, underscoring the sensitivity of early embryos to nutrient availability during cell fate determination. Although birth rates remained unaffected, suggesting compensatory mechanisms, longitudinal analysis revealed sex-specific metabolic dysfunction. Male offspring developed progressive glucose intolerance by 16 weeks, exhibiting elevated fasting glucose levels (p < 0.05) and impaired glucose clearance, whereas females showed no significant alterations in glucose metabolism. This study demonstrates that protein restriction during the preimplantation period not only disrupts early embryonic development but also programs long-term metabolic dysfunction, underscoring the importance of optimizing culture conditions in assisted reproductive technologies to minimize future health risks. Full article

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS (n = 18), ARMS (n = 17), and matched healthy controls (n = 18). Differential expression, functional enrichment (GO, KEGG, RaMP-DB), co-expression network analysis (WGCNA/WMCNA), and multi-omics integration (DIABLO, MOFA) revealed distinct molecular signatures for each subtype. ARMS displayed elevated oncogenic and stemness-associated proteins (e.g., cyclin E1, FAP, myotrophin) and metabolites involved in lipid transport, fatty acid metabolism, and polyamine biosynthesis. In contrast, ERMS was enriched in immune-related and myogenic proteins (e.g., myosin-9, SAA2, S100A11) and metabolites linked to glutamate/glycine metabolism and redox homeostasis. Pathway analyses highlighted subtype-specific activation of PI3K-Akt and Hippo signaling in ARMS and immune and coagulation pathways in ERMS. Additionally, the proteomics and metabolomics datasets showed association with clinical parameters, including disease stage, lymph node involvement, and age, demonstrating clear molecular discrimination consistent with clinical observation. Co-expression networks and integrative analyses further reinforced these distinctions, uncovering coordinated protein–metabolite modules. Our findings reveal novel, subtype-specific molecular programs in RMS and propose candidate biomarkers and pathways that may guide precision diagnostics and therapeutic targeting in pediatric sarcomas. Full article

With the rise in immunocompromised individuals and patients with immune-related comorbidities such as COVID-19, the rate of fungal infections is growing. This increase, along with the current plateau in antifungal drug development, has made understanding the pathogenesis and dissemination of these organisms more pertinent than ever. The mouse model of fungal infection, while informative on a basic scientific level, has severe limitations in terms of translation to the human disease. Here we present data supporting the implementation of the human cerebral organoid model, which is generated from human embryonic stem cells and accurately recapitulates relevant brain cell types and structures, to study fungal infection and dissemination to the central nervous system (CNS). This approach provides direct insight into the relevant pathogenesis of specific fungal organisms in human tissues where in vivo models are impossible. With this model system we assessed the specific brain tropisms and cellular effects of fungal pathogens known to cross the blood–brain barrier (BBB), such as Cryptococcus neoformans. We determined the effects of this fungal pathogen on the overall gross morphology, cellular architecture, and cytokine release from these model organoids. Furthermore, we demonstrated that C. neoformans penetrates and invades the organoid tissue and remains present throughout the course of infection. These results demonstrate the utility of this new model to the field and highlight the potential for this system to elucidate fungal pathogenesis to develop new therapeutic strategies to prevent and treat the disseminated stages of fungal diseases such as cryptococcal meningitis. Full article

Background: Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital heart disease characterized by abnormal prenatal development of the left ventricle that has an aberrantly thick trabecular layer and a thinner compacted myocardial layer. However, the underlying molecular mechanisms of LVNC regulated by mitochondrial phosphatase genes remain largely unresolved. Methods: We generated a mouse model with cardiac-specific deletion (CKO) of Ptpmt1, a type of mitochondrial phosphatase gene, using the αMHC-Cre, and investigated the effects of cardiac-specific Ptpmt1 deficiency on cardiac development. Morphological, histological, and immunofluorescent analyses were conducted in Ptpmt1 CKO and littermate controls. A transcriptional atlas was identified by RNA sequencing (RNA-seq) analysis. Results: We found that CKO mice were born at the Mendelian ratio with normal body weights. However, most of the CKO mice died within 24 h after birth, developing spontaneous ventricular tachycardia. Morphological and histological analysis further revealed that newborn CKO mice developed an LVNC phenotype, evidenced by a thicker trabecular layer and a thinner myocardium layer, when compared with the littermate control. We then examined the embryonic hearts and found that such an LVNC phenotype could also be observed in CKO hearts at E15.5 but not at E13.5. We also performed the EdU incorporation assay and demonstrated that cardiac cell proliferation in both myocardium and trabecular layers was significantly reduced in CKO hearts at E15.5, which is also consistent with the dysregulation of genes associated with heart development and cardiomyocyte proliferation in CKO hearts at the same stage, as revealed by both the transcriptome analysis and the quantitative real-time PCR. Deletion of Ptpmt1 in mouse cardiomyocytes also induced an increase in phosphorylated eIF2α and ATF4 levels, indicating a mitochondrial stress response in CKO hearts. Conclusions: Our results demonstrated that Ptpmt1 may play an essential role in regulating left ventricular compaction during mouse heart development. Full article

The ability to model the earliest stages of human embryonic development in vitro using pluripotent stem cells offers researchers new ways to understand and interrogate the intricacies of implantation. It also raises important ethical and regulatory considerations, both those common to research involving human embryos, as well as those unique to stem cell-based embryo and endometrial models. This review examines the underpinning scientific discoveries that have led to the development of this rapidly expanding area of research, and how three-dimensional embryo models could be employed in advancing assisted reproductive technologies and understanding implantation failure. Importantly, we also discuss the ethical and legal implications and explore various governance models that have been proposed to foster responsibility and innovation in this area of research. Given the heightened interest in the scientific community on this topic, we finish on the question of how and when to involve the public in the development of this technology and its regulation. Full article

Traditional villages are irreplaceable cultural heritages, embodying complex human–environment interactions. This study uses historical geography analysis, kernel density estimation, centroid migration modeling, and Geodetector techniques to analyze the 2000-year spatiotemporal evolution and formation mechanisms of 224 nationally designated traditional villages in China’s Qinling-Daba Mountains. The findings are as follows: (1) These villages significantly cluster on sunny slopes of hills and low mountains with moderate gradients. They are also closely located near waterways, ancient roads, and historic cities. (2) From the embryonic stage during the Qin and Han dynasties, through the diffusion and transformation phases in the Wei, Jin, Song, and Yuan dynasties, to the mature stage in the Ming and Qing dynasties, the spatial center of these villages shifted distinctly southwestward. This migration was accompanied by expansion along waterway transport corridors, an enlarged spatial scope, and a decrease in directional concentration. (3) The driving forces evolved from a strong coupling between natural conditions and infrastructure in the early stage to human-dominated adaptation in the later stage. Agricultural innovations, such as terraced fields, and sociopolitical factors, like migration policies, overcame environmental constraints through the synergistic effects of cultural and economic networks. Full article

Microplastics are pervasive in marine ecosystems and have been shown to affect a range of marine organisms, including corals. These particles can develop biofilms, facilitating the transport of pollutants and pathogenic microorganisms. Although the effects of primary microplastics on adult corals have been extensively studied, little is known about the impacts of secondary microplastics on early life stages. This study investigated (1) the effects of different abundances of secondary microplastics on the early development of Orbicella faveolata; (2) the influence of fibers and fragments on the larval settlement of Acropora palmata; and (3) the effects of the microplastic size, abundance, and biofilm presence on the settlement of Favia fragum. For O. faveolata, fertilization, embryogenesis, and settlement were all impaired by fragments, with embryonic development showing a 25.9% reduction in viability. Larval development was unaffected, but post-settlement survival declined by 35.8% with exposure to fibers and fragments. For A. palmata, settlement was reduced by fragments, while for F. fragum, only 2–4 mm fragments significantly decreased settlement rates. This study contributes to the knowledge of the effect of microplastics on the early development of corals, providing valuable information to improve strategies to control microplastic pollution. Full article

Background: Duchenne muscular dystrophy (DMD), which affects 1 in 3500 to 5000 newborn boys worldwide, is characterized by progressive skeletal muscle weakness and degeneration. The reduced muscle regeneration capacity presented by patients is associated with increased fibrosis. Satellite cells (SCs) are skeletal muscle stem cells that play an important role in adult muscle maintenance and regeneration. The absence or mutation of dystrophin in DMD is hypothesized to impair SC asymmetric division, leading to cell cycle arrest. Methods: To overcome the limited availability of biopsies from DMD patients, we used our 3D skeletal muscle organoid (SMO) system, which delivers a stable population of myogenic progenitors (MPs) in dormant, activated, and committed stages, to perform SMO cultures using three DMD patient-derived iPSC lines. Results: The results of scRNA-seq analysis of three DMD SMO cultures versus two healthy, non-isogenic, SMO cultures indicate reduced MP populations with constant activation and differentiation, trending toward embryonic and immature myotubes. Mapping our data onto the human myogenic reference atlas, together with primary SC scRNA-seq data, indicated a more immature developmental stage of DMD organoid-derived MPs. DMD fibro-adipogenic progenitors (FAPs) appear to be activated in SMOs. Conclusions: Our organoid system provides a promising model for studying muscular dystrophies in vitro, especially in the case of early developmental onset, and a methodology for overcoming the bottleneck of limited patient material for skeletal muscle disease modeling. Full article

The undertaking of distant hybridization holds paramount significance for the innovation of tea germplasm resources and the cultivation of superior, specialized tea varieties. However, challenges manifest during the process of tea plant distant hybridization breeding, with reproductive barriers impeding the successful acquisition of hybrid progeny; the precise stages at which these barriers occur remain unclear. In this study, utilizing Camellia sinensis cv. Jinxuan as the maternal parent, as well as C. gymnogyna Chang and C. sinensis cv. Yinghong No.9 as the paternal parents, interspecific distant hybridization (DH) and intraspecific hybridization (IH) were conducted. The investigation involved the observation of pollen germination and pollen tube behavior on the stigma, the scrutiny of the developmental dynamics of the ovary post-hybridization, and the examination of the stages and reasons for reproductive disorders during tea tree distant hybridization. The findings indicate that both IH and DH exhibit pre-fertilization barriers. The pre-embryonic development of hybrids obtained from DH is normal, but there is a significant fruit drop during the stage of fruit development. The germination rate of mature seeds obtained from DH is low, and there are pronounced post-fertilization disorders, which are the primary reasons for the difficulty in achieving successful tea plant distant hybridization. An analysis of the genetic variation in phenotypes and chemical components in the progeny after distant hybridization revealed widespread variation and rich genetic diversity. The identification of progeny with a high amino acid and caffeine content holds promise for future production and breeding, providing valuable theoretical references for the selection of parents in the creation of low-caffeine-content tea germplasm resources. Full article