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Gestational diabetes mellitus (GDM) pregnant women are under more psychological stress than normal pregnant women. With the deepening of the study of gestational diabetes mellitus, research has shown that anxiety and depression are also an important cause of gestational diabetes mellitus. Anxiety and depression can cause imbalances in the hormone levels in the body, which has a serious impact on the pregnancy outcome and blood glucose control of pregnant women with GDM. Therefore, the main purpose of this paper is to provide a systematic review of the association between anxiety, depression, and GDM, as well as the adverse effects on pregnant women with GDM. To this end, we searched the PubMed, CNKI, Embase, Cochrane Library, Wanfang, and Weipu databases. Studies on the incidence of anxiety, depression, and GDM, blood glucose in pregnant women with GDM, delivery mode, and maternal and infant outcomes were included to be analyzed, and the source of anxiety and depression in pregnant women with GDM and related treatment measures were discussed.

In quantitative PCR research, appropriate reference genes are key to determining accurate mRNA expression levels. In order to screen the reference genes suitable for detecting gene expression in tissues of the reproductive axis, a total of 420 (males and females = 1:5) 3-year-old Magang geese were selected and subjected to light treatment. The hypothalamus, pituitary and testicular tissues were subsequently collected at different stages. Ten genes including HPRT1 , GAPDH , ACTB , LDHA , SDHA , B2M , TUBB4 , TFRC , RPS2 and RPL4 were selected as candidate reference genes. The expression of these genes in goose reproductive axis tissues was detected by real-time fluorescent quantitative PCR. The ΔCT, geNorm, NormFinder and BestKeeper algorithms were applied to sort gene expression according to stability. The results showed that ACTB and TUBB4 were the most suitable reference genes for the hypothalamic tissue of Magang goose in the three breeding stages; HPRT1 and RPL4 for pituitary tissue; and HPRT1 and LDHA for testicular tissue. For all three reproductive axis tissues, ACTB was the most suitable reference gene, whereas the least stable reference gene was GAPDH . Altogether, these results can provide references for tissue expression studies in geese under light treatment.

Acute glaucoma is a sight-threatening condition characterized by a sudden and substantial rise in intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Angle closure glaucoma, a common cause of glaucoma in Asia that affects tens of millions of people worldwide, often presents acutely with loss of vision, pain, and high IOP. Even when medical and surgical treatment is available, acute angle closure glaucoma can cause permanent and irreversible loss of vision. Toll-like receptor 4 (TLR4) signaling has been previously implicated in the pathogenesis of IOP-induced RGC death, although the underlying mechanisms are largely unknown. In the present study, we used an acute IOP elevation/glaucoma model to investigate the underlying mechanism of RGC death. We found that TLR4 leads to increased caspase-8 expression; this elevation increases IL-1β expression and RGC death via a caspase-1–dependent pathway involving Nod-like receptor family, pyrin domain containing 1 (NLRP1)/NLRP3 inflammasomes and a caspase-1–independent pathway. We show that inhibition of caspase-8 activation significantly attenuates RGC death by down-regulating the activation of NLRP1 and NLRP3, thus demonstrating the pivotal role of caspase-8 in the TLR4-mediated activation of inflammasomes. These findings demonstrate collectively a critical role of caspase-8 in transducing TLR4-mediated IL-1β production and RGC death and highlight signal transduction in a caspase-1–dependent NLRP1/NLRP3 inflammasome pathway and a caspase-1–independent pathway in acute glaucoma. These results provide new insight into the pathogenesis of glaucoma and point to a treatment strategy.

The insights into how genome topology couples with epigenetic states to govern the function and identity of the corneal epithelium are poorly understood. Here, we generate a high-resolution Hi-C interaction map of human limbal stem/progenitor cells (LSCs) and show that chromatin multi-hierarchical organisation is coupled to gene expression. By integrating Hi-C, epigenome and transcriptome data, we characterize the comprehensive 3D epigenomic landscapes of LSCs. We find that super-silencers mediate gene repression associated with corneal development, differentiation and disease via chromatin looping and/or proximity. Super-enhancer (SE) interaction analysis identified a set of SE interactive hubs that contribute to LSC-specific gene activation. These active and inactive element-anchored loop networks occur within the cohesin-occupied CTCF-CTCF loops. We further reveal a coordinated regulatory network of core transcription factors based on SE-promoter interactions. Our results provide detailed insights into the genome organization principle for epigenetic regulation of gene expression in stratified epithelia. Genome topology provides a structural basis for epigenome-mediated transcriptional regulation in eukaryotes. Here the authors characterized the 3D genome of stratified squamous epithelia. They generated a Hi-C map of human limbal stem/progenitor cells (LSCs) and integrated these data with epigenomics, transcription factor binding maps, and transcriptome data.

The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.16 to 4.96; = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; <.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; = .003). The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. = alanine aminotransferase; = antithyroid drug; = confidence interval; = carbimazole; = Graves disease; = methimazole; = methylthiouracil; = Newcastle-Ottawa Scale; = odds ratio; = propylthiouracil; = radioactive iodine.

The escalating global burden of cancer, marked by high incidence and mortality, necessitates more effective therapeutic strategies. A major bottleneck in clinical translation is the long-standing reliance on subcutaneous tumor models, which fail to recapitulate the complex physiological and pathological features of human malignancies. These ectopic models lack organ-specific barriers—such as the prostatic capsule, cervicovaginal mucus, and dense desmoplastic stroma—and cannot reproduce authentic metastatic niches or immune heterogeneity. Consequently, this review advocates a paradigm shift toward orthotopic–TME–informed nanomedicine design. We systematically evaluate recent progress in nanotherapeutics across twelve major malignancies, categorized into three strategic domains: (i) barrier-penetrating platforms engineered to navigate organ-specific physical and biochemical constraints; (ii) metastasis-targeted delivery systems that exploit native lymphovascular pathways; and (iii) microenvironment-responsive mechanisms that adapt to localized stimuli such as hypoxia and acidity. By integrating data from a wide range of studies, we highlight how orthotopic models provide a more rigorous platform for assessing drug penetration and therapeutic efficacy than conventional subcutaneous models. Furthermore, we critically discuss existing challenges, including manufacturing scalability, the bio–nano interface, and long-term toxicological safety. Looking forward, we propose a strategic roadmap that emphasizes the use of patient-derived orthotopic xenografts (PDOX), multi-omics data integration, and the development of closed-loop adaptive nanosystems. By aligning nanomaterial properties with constraints inherent to the orthotopic microenvironment, this review aims to provide a blueprint for the next generation of precision oncology platforms that can successfully bridge the gap from bench to bedside. Graphical Abstract

The epithelial–mesenchymal transition (EMT) is closely associated with Crohn's disease (CD) related intestinal fibrosis, a condition whose prevalence is increasing annually among children. Recently, the CD marker gene microarray screening revealed an upregulation of circ_0001666 in the colon tissues of CD patients, but its underlying mechanisms remain unclear. In this study, we explored the molecular mechanism of circ_0001666 in regulating EMT‐mediated fibrosis in CD in vitro. The levels of circ_0001666 and EMT‐associated proteins were assessed in CD clinical samples, and a CD cell model was established using TGF‐β1 to induce human intestinal epithelial cells (HIECs). Additionally, the expression levels of genes and proteins related to EMT and fibrosis were analyzed by quantitative real‐time PCR and western blot, cell migration, and invasion were assessed via wound healing assay and transwell, respectively, and RNA pull‐down and RNA immunoprecipitation assays were performed to verify the relationship between SRSF1 and BMP7 or circ_0001666. Circ_0001666 was overexpressed in the intestinal mucosal tissues of CD patients and was positively correlated with EMT. Silencing circ_0001666 inhibited the migration, invasion, EMT, and fibrosis of HIECs induced by TGF‐β1. Mechanistically, circ_0001666 regulated BMP7 expression by interacting with SRSF1. Furthermore, the effects of inhibiting circ_0001666 on HIECs could be partially reversed by overexpressing SRSF1 or silencing BMP7. Collectively, circ_0001666 regulates TGF‐β1‐induced HIEC migration, invasion, EMT, and fibrosis. Circ_0001666 also promoted EMT‐mediated fibrosis by interacting with SRSF1 to accelerate BMP7 mRNA decay. These findings provide new insights into the pathogenesis of CD and suggest that circ_0001666 might be a potential therapeutic target for CD.

Tendon disorders, which are commonly presented in the clinical setting, disrupt the patients’ normal work and life routines, and they damage the careers of athletes. However, there is still no effective treatment for tendon disorders. In the field of tissue engineering, the potential of the therapeutic application of exogenous stem cells to treat tendon pathology has been demonstrated to be promising. With the development of stem cell biology and chemical biology, strategies that use inductive tenogenic factors to program stem cell fate in situ are the most easily and readily translatable to clinical applications. In this review, we focus on bioactive molecules that can potentially induce tenogenesis in adult stem cells, and we summarize the various differentiation factors found in comparative studies. Moreover, we discuss the molecular regulatory mechanisms of tenogenesis, and we examine the various challenges in developing standardized protocols for achieving efficient and reproducible tenogenesis. Finally, we discuss and predict future directions for tendon regeneration. Stem Cells Translational Medicine 2018;7:404–414 Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) and transdifferentiated into tendon stem/progenitor cells (TSPCs) by specific small molecules. iPSCs and embryonic stem cells (ESCs) can differentiated into mesenchymal stem cells (MSCs). FGF‐2 could promote cell proliferation. MSCs can differentiate into tendon stem/ progenitor cells in the stimulation of some small molecules, then further develop into mature tenocytes. RAR agonist has been demonstrated to maintain TSPCs phenotype, while TGF‐β1 has the similar effect on tenocytes.

p63 and PAX6 act to specify limbal stem or progenitor cells (LSCs), and WNT7A controls corneal epithelium differentiation through PAX6; loss of WNT7A or PAX6 induces LSCs into epithelium, and transduction of PAX6 in skin epithelial stem cells converts them to LSC-like cells and transplantation in a rabbit corneal injury model can replenish corneal epithelial cells and repair damaged corneal surface. WNT7A and PAX6 signals in corneal pathogenesis The limbal stem cells (LSCs) in the basal limbal epithelium of the eye sustain corneal epithelial homeostasis and regeneration. Their loss due to injury or disease is one of the most common causes of blindness. Hong Ouyang et al . establish a method for culturing LSCs in a feeder-free medium. They identify the WNT7A–PAX6 signalling axis as a determinant of corneal lineage that has potential as a therapeutic target in corneal surface diseases. Transduction of PAX6 in skin epithelial stem cells converts them into LSC-like cells, and transplantation of the reprogrammed cells in a rabbit corneal injury model can repair damaged corneal surface. In a separate study in this issue of Nature , Bruce Ksander et al . identify a marker — the ABC transporter ABCB5 — that is functionally required for LSC maintenance, corneal development and repair, and can be used to identify LSCs in mouse and human eyes. LSC transplantation experiments suggest that ABCB5-expressing cells may have potential in the treatment of corneal disease, particularly corneal blindness due to LSC deficiency. The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs) 1 , 2 , and deficiency in LSCs or corneal epithelium—which turns cornea into a non-transparent, keratinized skin-like epithelium—causes corneal surface disease that leads to blindness in millions of people worldwide 3 . How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A–PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases.

Adult stem cell identity, plasticity, and homeostasis are precisely orchestrated by lineage-restricted epigenetic and transcriptional regulatory networks. Here, by integrating super-enhancer and chromatin accessibility landscapes, we delineate core transcription regulatory circuitries (CRCs) of limbal stem/progenitor cells (LSCs) and find that RUNX1 and SMAD3 are required for maintenance of corneal epithelial identity and homeostasis. RUNX1 or SMAD3 depletion inhibits PAX6 and induces LSCs to differentiate into epidermal-like epithelial cells. RUNX1, PAX6, and SMAD3 (RPS) interact with each other and synergistically establish a CRC to govern the lineage-specific cis -regulatory atlas. Moreover, RUNX1 shapes LSC chromatin architecture via modulating H3K27ac deposition. Disturbance of RPS cooperation results in cell identity switching and dysfunction of the corneal epithelium, which is strongly linked to various human corneal diseases. Our work highlights CRC TF cooperativity for establishment of stem cell identity and lineage commitment, and provides comprehensive regulatory principles for human stratified epithelial homeostasis and pathogenesis. Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.