A universal design of restructured dimer antigens: Development of a superior vaccine against the paramyxovirus in transgenic rice.

The development of vaccines, which induce effective immune responses while ensuring safety and affordability, remains a substantial challenge. In this study, we proposed a vaccine model of a restructured "head-to-tail" dimer to efficiently stimulate B cell response. We also demonstrate the feasibility of using this model to develop a paramyxovirus vaccine through a low-cost rice endosperm expression system. Crystal structure and small-angle X-ray scattering data showed that the restructured hemagglutinin-neuraminidase (HN) formed tetramers with fully exposed quadruple receptor binding domains and neutralizing epitopes. In comparison with the original HN antigen and three traditional commercial whole virus vaccines, the restructured HN facilitated critical epitope exposure and initiated a faster and more potent immune response. Two-dose immunization with 0.5 µg of the restructured antigen (equivalent to one-127th of a rice grain) and one-dose with 5 µg completely protected chickens against a lethal challenge of the virus. These results demonstrate that the restructured HN from transgenic rice seeds is safe, effective, low-dose useful, and inexpensive. We provide a plant platform and a simple restructured model for highly effective vaccine development.

Impact of Varying the Photoanode/Catalyst Interfacial Composition on Solar Water Oxidation: The Case of BiVO4(010)/FeOOH Photoanodes.

Photoanodes used in a water-splitting photoelectrochemical cell are almost always paired with an oxygen evolution catalyst (OEC) to efficiently utilize photon-generated holes for water oxidation because the surfaces of photoanodes are typically not catalytic for the water oxidation reaction. Suppressing electron-hole recombination at the photoanode/OEC interface is critical for the OEC to maximally utilize the holes reaching the interface for water oxidation. In order to explicitly demonstrate and investigate how the detailed features of the photoanode/OEC interface affect interfacial charge transfer and photocurrent generation for water oxidation, we prepared two BiVO4(010)/FeOOH photoanodes with different Bi:V ratios at the outermost layer of the BiVO4 interface (close to stoichiometric vs Bi-rich) while keeping all other factors in the bulk BiVO4 and FeOOH layers identical. The resulting two photoanodes show striking differences in the photocurrent onset potential and photocurrent density for water oxidation. The ambient pressure X-ray photoelectron spectroscopy results show that these two BiVO4(010)/FeOOH photoanodes show drastically different Fe2+:Fe3+ ratios in FeOOH both in the dark and under illumination with water, demonstrating the immense impact of the interfacial composition and structure on interfacial charge transfer. Using computational studies, we reveal the effect of the surface Bi:V ratio on the hydration of the BiVO4 surface and bonding with the FeOOH layer, which in turn affect the band alignments between BiVO4 and FeOOH. These results explain the atomic origin of the experimentally observed differences in electron and hole transfer and solar water oxidation performance of the two photoanodes having different interfacial compositions.

Rice-produced classical swine fever virus glycoprotein E2 with herringbone-dimer design to enhance immune responses.

Pestiviruses, including classical swine fever virus, remain a concern for global animal health and are responsible for major economic losses of livestock worldwide. Despite high levels of vaccination, currently available commercial vaccines are limited by safety concerns, moderate efficacy, and required high doses. The development of new vaccines is therefore essential. Vaccine efforts should focus on optimizing antigen presentation to enhance immune responses. Here, we describe a simple herringbone-dimer strategy for efficient vaccine design, using the classical swine fever virus E2 expressed in a rice endosperm as an example. The expression of rE2 protein was identified, with the rE2 antigen accumulating to 480 mg/kg. Immunological assays in mice, rabbits, and pigs showed high antigenicity of rE2. Two immunizations with 284 ng of the rE2 vaccine or one shot with 5.12 µg provided effective protection in pigs without interference from pre-existing antibodies. Crystal structure and small-angle X-ray scattering results confirmed the stable herringbone dimeric conformation, which had two fully exposed duplex receptor binding domains. Our results demonstrated that rice endosperm is a promising platform for precise vaccine design, and this strategy can be universally applied to other Flaviviridae virus vaccines.

Lessons learned from first-principles calculations of transition metal oxides.

Transition metal oxides (TMOs) are an important class of materials with diverse applications, ranging from memristors to photoelectrochemical cells. First-principles calculations are critical for understanding these complex materials at an atomic level and establishing relationships between atomic and electronic structures, particularly for probing quantities difficult or inaccessible to experiment. Here, we discuss computational strategies used to understand TMOs by focusing on two examples, a photoanode material, BiVO4, and an oxide for low-power electronics, La1-xSrxCoO3. We highlight key aspects required for the modeling of TMOs, namely, the descriptions of how oxygen vacancies, extrinsic doping, the magnetic state, and polaron formation impact their electronic and atomic structures and, consequently, many of the observed properties.

In utero exposure to mixed PAHs causes heart mass reduction in adult male mice.

Polycyclic aromatic hydrocarbons (PAHs) are a risk factor for the occurrence of cardiac diseases. The present study was conducted to investigate the influence of prenatal exposure to a mixed PAHs on heart and the underlying mechanism. Pregnant mice were orally administered with a mixture of 8 kinds of PAHs (0, 5, 50, 500 µg/kg body weight) once every 2 days for a total of 8 dosages. The mixed PAHs contained naphthalene, acenaphthylene, phenanthrene, fluoranthene, pyrene, benzo[a]pyrene, dibenzo[a,h]anthracene and benzo[g,h,i]perylene at a weight ratio of 10: 10: 10: 10: 10: 1: 1: 1. The adult males, not females, showed significantly decreased heart/body weight ratio, which was attributed to the loss of cardiac fiber and the increase of cell apoptosis. The protein expression of transforming growth factor ß1 and its downstream transcription factors, Smad3 and Smad4, was significantly downregulated, which caused the loss of cardiac fiber. The downregulated phosphatidylinositol 3-kinase and AKT led to increased expression of caspase3, caspase9, BAX and reduced expression of Bcl-2, which was responsible for the increased cell apoptosis. Different levels of aromatic hydrocarbon receptor and sex hormone receptors between males and females were associated with the distinct effect on heart.

Integrated paired-end enhancer profiling and whole-genome sequencing reveals recurrent CCNE1 and IGF2 enhancer hijacking in primary gastric adenocarcinoma.

OBJECTIVE: Genomic structural variations (SVs) causing rewiring of cis-regulatory elements remain largely unexplored in gastric cancer (GC). To identify SVs affecting enhancer elements in GC (enhancer-based SVs), we integrated epigenomic enhancer profiles revealed by paired-end H3K27ac ChIP-sequencing from primary GCs with tumour whole-genome sequencing (WGS) data (PeNChIP-seq/WGS). DESIGN: We applied PeNChIP-seq to 11 primary GCs and matched normal tissues combined with WGS profiles of >200 GCs. Epigenome profiles were analysed alongside matched RNA-seq data to identify tumour-associated enhancer-based SVs with altered cancer transcription. Functional validation of candidate enhancer-based SVs was performed using CRISPR/Cas9 genome editing, chromosome conformation capture assays (4C-seq, Capture-C) and Hi-C analysis of primary GCs. RESULTS: PeNChIP-seq/WGS revealed ~150 enhancer-based SVs in GC. The majority (63%) of SVs linked to target gene deregulation were associated with increased tumour expression. Enhancer-based SVs targeting CCNE1, a key driver of therapy resistance, occurred in 8% of patients frequently juxtaposing diverse distal enhancers to CCNE1 proximal regions. CCNE1-rearranged GCs were associated with high CCNE1 expression, disrupted CCNE1 topologically associating domain (TAD) boundaries, and novel TAD interactions in CCNE1-rearranged primary tumours. We also observed IGF2 enhancer-based SVs, previously noted in colorectal cancer, highlighting a common non-coding genetic driver alteration in gastric and colorectal malignancies. CONCLUSION: Integrated paired-end NanoChIP-seq and WGS of gastric tumours reveals tumour-associated regulatory SV in regions associated with both simple and complex genomic rearrangements. Genomic rearrangements may thus exploit enhancer-hijacking as a common mechanism to drive oncogene expression in GC.

Computational modelling of atomic layer etching of chlorinated germanium surfaces by argon.

The atomic layer etching of chlorinated germanium surfaces under argon bombardment was simulated using molecular dynamics with a newly fitted Tersoff potential. The chlorination energy determines the threshold energy for etching and the number of etched atoms in the bombardment phase. Etch rate is determined by bombardment energy.

Transcriptional analysis of immune genes in Epstein-Barr virus-associated gastric cancer and association with clinical outcomes.

BACKGROUND: Epstein-Barr virus-associated gastric cancer (EBVaGC) has traditionally been associated with high expression of PD-L1 and immune infiltration. Correlations between PD-L1 and other immune-related gene (IRG) expressions in EBVaGC have not been previously described. METHODS: We performed NanoString® transcriptomic profiling and PD-L1 immunohistochemistry (IHC) (using the FDA approved Dako PD-L1 IHC 22C3) on EBVaGC samples from gastric cancer patients undergoing primary tumor resections at Samsung Medical Centre, South Korea. For controls, EBV-negative samples from the previously reported Asian Cancer Research Group (EBVnegACRG) cohort were used. Genes tested included PD-L1 and other IRGs related to intra-tumoral cytolytic activity, cytokines and immune checkpoints. Samples with PD-L1 expression > 34th percentile were defined as PD-L1high and the remaining as PD-L1low. RESULTS: We identified 71 cases of EBVaGC and 193 EBV-negative ACRG samples as controls. EBVaGC showed higher expression of all queried immune genes compared to EBVnegACRG samples (p < 0.01). PD-L1 immunohistochemistry expression correlated with PD-L1 transcript expression (r = 0.63, p < 0.001). Tumor-infiltrating lymphocyte patterns were also found to be different between PD-L1low and PD-L1high groups. PD-L1low EBVaGC samples (n = 24, 34%) had consistently decreased expression of all other immune genes, such as CD8A, GZMA and PRF1 and PD-1 (p < 0.001). PD-L1low EBVaGC samples were also associated with worse disease-free survival (HR 5.03, p = 0.032) compared to PD-L1high EBVaGC samples. CONCLUSIONS: A substantial proportion of EBVaGC does not express high levels of PD-L1 and other immune genes. EBVaGCs which have lower transcriptomic expression of PD-L1 tend to have a similarly low expression of other immune genes, IHC scores and a poorer prognosis.

Atomistic modeling of La3+ doping segregation effect on nanocrystalline yttria-stabilized zirconia.

The effect of La3+ doping on the structure and ionic conductivity change in nanocrystalline yttria-stabilized zirconia (YSZ) was studied using a combination of Monte Carlo and molecular dynamics simulations. The simulation revealed the segregation of La3+ at eight tilt grain boundary (GB) structures and predicted an average grain boundary (GB) energy decrease of 0.25 J m-2, which is close to the experimental values reported in the literature. Cation stabilization was found to be the main reason for the GB energy decrease, and energy fluctuations near the grain boundary are smoothed out with La3+ segregation. Both dynamic and energetic analysis on the Σ13(510)/[001] GB structure revealed La3+ doping hinders O2- diffusion in the GB region, where the diffusion coefficient monotonically decreases with increasing La3+ doping concentration. The effect was attributed to the increase in the site-dependent migration barriers for O2- hopping caused by segregated La3+, which also leads to anisotropic diffusion at the GB.

Response to Extreme Temperatures of Mesoporous Silica MCM-41: Porous Structure Transformation Simulation and Modification of Gas Adsorption Properties.

Molecular dynamics (MD) and Monte Carlo (MC) simulations were applied together for the first time to reveal the porous structure transformation mechanisms of mesoporous silica MCM-41 subjected to temperatures up to 2885 K. Silica was experimentally characterized to inform the models and enable prediction of changes in gas adsorption/separation properties. MD simulations suggest that the pore closure process is activated by a collective diffusion of matrix atoms into the porous region, accompanied by bond reformation at the surface. Degradation is kinetically limited, such that complete pore closure is postponed at high heating rates. We experimentally observe decreased gas adsorption with increasing temperature in mesoporous silica heated at fixed rates, due to pore closure and structural degradation consistent with simulation predictions. Applying the Kissinger equation, we find a strong correlation between the simulated pore collapse temperatures and the experimental values which implies an activation energy of 416 ± 17 kJ/mol for pore closure. MC simulations give the adsorption and selectivity for thermally treated MCM-41, for N2, Ar, Kr, and Xe at room temperature within the 1-10 000 kPa pressure range. Relative to pristine MCM-41, we observe that increased surface roughness due to decreasing pore size amplifies the difference of the absolute adsorption amount differently for different adsorbate molecules. In particular, we find that adsorption of strongly interacting molecules can be enhanced in the low-pressure region while adsorption of weakly interacting molecules is inhibited. This then results in higher selectivity in binary mixture adsorption in mesoporous silica.

Abundant copy-number loss of CYCLOPS and STOP genes in gastric adenocarcinoma.

BACKGROUND: Gastric cancer, a leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar health burdens. Our goal is to assess genomic copy-number loss and the possible functional consequences and therapeutic implications thereof across a large series of gastric adenocarcinomas. METHODS: We used high-density single-nucleotide polymorphism microarrays to determine patterns of copy-number loss and allelic imbalance in 74 gastric adenocarcinomas. We investigated whether suppressor of tumorigenesis and/or proliferation (STOP) genes are associated with genomic copy-number loss. We also analyzed the extent to which copy-number loss affects Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes-genes that may be attractive targets for therapeutic inhibition when partially deleted. RESULTS: The proportion of the genome subject to copy-number loss varies considerably from tumor to tumor, with a median of 5.5 %, and a mean of 12 % (range 0-58.5 %). On average, 91 STOP genes were subject to copy-number loss per tumor (median 35, range 0-452), and STOP genes tended to have lower copy-number compared with the rest of the genes. Furthermore, on average, 1.6 CYCLOPS genes per tumor were both subject to copy-number loss and downregulated, and 51.4 % of the tumors had at least one such gene. CONCLUSIONS: The enrichment of STOP genes in regions of copy-number loss indicates that their deletion may contribute to gastric carcinogenesis. Furthermore, the presence of several deleted and downregulated CYCLOPS genes in some tumors suggests potential therapeutic targets in these tumors.

Intertumor heterogeneity of non-small-cell lung carcinomas revealed by multiplexed mutation profiling and integrative genomics.

Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, with a burden of genomic alterations exceeding most other tumors. The goal of our study was to evaluate the frequencies of co-occurring mutations and copy-number aberrations (CNAs) within the same tumor and to evaluate their potential clinical impact. Mass-spectrometry based mutation profiling using a customized lung cancer panel evaluating 214 mutations across 26 key NSCLC genes was performed on 230 nonsquamous NSCLC and integrated with genome-wide CNAs and clinical variables. Among the 138 cases having at least one mutation, one-third (41, 29.7%) showed two or more mutations, either in the same gene (double mutation) or in different genes (co-mutations). In epidermal growth factor receptor (EGFR) mutant cancers, there was a double mutation in 18% and co-mutations in the following genes: TP53 (10%), PIK3CA (8%), STK11 (6%) and MET (4%). Significant relationships were detected between EGFR mutation and 1p, 7p copy gains (harboring the EGFR gene) as well as 13q copy loss. KRAS mutation was significantly related with 1q gain and 3q loss. For Stage I, tumors harboring at least one mutation or PIK3CA mutation were significantly correlated with poor prognosis (p-value = 0.02). When combining CNAs and mutational status, patients having both KRAS mutation and the highest related CNA (3q22.3 copy loss) showed a significant poorer prognosis (p-value = 0.03). Our study highlights the clinical relevance of studying tumor complexity by integrative genomic analysis and the need for developing assays that broadly screen for both "actionable" mutations and copy-number alterations to improve precision of stratified treatment approaches.

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

BACKGROUND & AIMS: Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. METHODS: We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. RESULTS: We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. CONCLUSIONS: Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer.

Controllable light-induced conic structures in silicon nanowire arrays by metal-assisted chemical etching.

Silicon nanowires (SiNWs) have long been considered a promising material due to their extraordinary electrical and optical properties. As a simple, highly efficient fabrication method for SiNWs, metal-assisted chemical etching (MACE) has been intensively studied over recent years. However, effective control by modulation of simple parameters is still a challenging topic and some key questions still remain in the mechanistic processes. In this work, a novel method to manipulate SiNWs with a light-modulated MACE process has been systematically investigated. Conic structures consisting of inclined and clustered SiNWs can be generated and effectively modified by the incident light while new patterns such as 'bamboo shoot' arrays can also be formed under certain conditions. More importantly, detailed study has revealed a new top-down 'diverting etching' model of the conic structures in this process, different from the previously proposed 'bending' model. As a consequence of this mechanism, preferential lateral mass transport of silver particles occurs. Evidence suggests a relationship of this phenomenon to the inhomogeneous distribution of the light-induced electron-hole pairs beneath the etching front. Study on the morphological change and related mechanism will hopefully open new routes to understand and modulate the formation of SiNWs and other nanostructures.

Hydrogen-Induced Topotactic Phase Transformations of Cobaltite Thin Films.

Manipulating physical properties through ion migration in complex oxide thin films is an emerging research direction to achieve tunable materials for advanced applications. While the reduction of complex oxides has been widely reported, few reports exist on the modulation of physical properties through a direct hydrogenation process. Here, we report an unusual mechanism for hydrogen-induced topotactic phase transitions in perovskite La0.7Sr0.3CoO3 thin films. Hydrogenation is performed upon annealing in a pure hydrogen gas environment, offering a direct understanding of the role that hydrogen plays at the atomic scale in these transitions. Topotactic phase transformations from the perovskite (P) to hydrogenated-brownmillerite (H-BM) phase can be induced at temperatures as low as 220 °C, while at higher hydrogenation temperatures (320-400 °C), the progression toward more reduced phases is hindered. Density functional theory calculations suggest that hydroxyl bonds are formed with the introduction of hydrogen ions, which lower the formation energy of oxygen vacancies of the neighboring oxygen, enabling the transition from the P to H-BM phase at low temperatures. Furthermore, the impact on the magnetic and electronic properties of the hydrogenation temperature is investigated. Our research provides a potential pathway for utilizing hydrogen as a basis for low-temperature modulation of complex oxide thin films, with potential applications in neuromorphic computing.

A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets.

OBJECTIVE: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. DESIGN: Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. RESULTS: 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers. CONCLUSION: The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.

Prenatal EGCG consumption causes obesity and perturbs glucose homeostasis in adult mice.

Epigallocatechin gallate (EGCG) has a wide consumption for its health advantages. The current study investigates the effects of prenatal EGCG administration on glucose metabolism and obesity in adulthood. Pregnant C57BL/6J mice were supplemented with EGCG in drinking water (3 µg/mL) for 16 d. Abdominal obesity was observed in both male and female adult mice, which was associated with the upregulation of adipose-specific genes, including C/ebpα and Srebf1 (Srebf1 only in males), and the downregulation of genes related to lipolysis, such as Acox1, Atgl and Pdk4 (only in males) in visceral adipose tissue. Elevated fasting glucose levels and hyperinsulinemia were observed in adult males, while females exhibit lower glucose level in glucose tolerance test, which might be due to reduced glucagon levels. Though hepatic expression of the insulin receptor signaling pathway was upregulated in males and was not altered in females, prenatal treatment with EGCG downregulated the expression of this signaling pathway in the skeletal muscle of adult mice, which was further demonstrated in primary human skeletal muscle cells treated with EGCG. The methylation levels in promotor of genes related to the insulin receptor signaling were matched with their transcription in mice, while the expression of acetylated histones was downregulated in human skeletal muscle cells. These results suggest that EGCG consumption during pregnancy should be a risk factor for the disruption of glucose homeostasis in adulthood.

Selective scandium ion capture through coordination templating in a covalent organic framework.

The use of coordination complexes within covalent organic frameworks can significantly diversify the structures and properties of this class of materials. Here we combined coordination chemistry and reticular chemistry by preparing frameworks that consist of a ditopic (p-phenylenediamine) and mixed tritopic moieties-an organic ligand and a scandium coordination complex of similar sizes and geometries, both bearing terminal phenylamine groups. Changing the ratio of organic ligand to scandium complex enabled the preparation of a series of crystalline covalent organic frameworks with tunable levels of scandium incorporation. Removal of scandium from the material with the highest metal content subsequently resulted in a 'metal-imprinted' covalent organic framework that exhibits a high affinity and capacity for Sc3+ ions in acidic environments and in the presence of competing metal ions. In particular, the selectivity of this framework for Sc3+ over common impurity ions such as La3+ and Fe3+ surpasses that of existing scandium adsorbents.

Long-term exposure to environmental levels of phenanthrene induces emaciation-thirst disease-like syndromes in female mice.

Phenanthrene (Phe) is a polycyclic aromatic hydrocarbon widely present in foods and drinking water. To explore the detrimental effects of Phe on body metabolism, female Kunming mice were treated with Phe in drinking water at concentrations of 0.05, 0.5 and 5 ng/mL. After exposure for 270 d, the animals exhibited dose-dependent reduced body weight and increased water consumption. The dose-dependent accumulation of Phe in the brain decreased hypothalamic neuron numbers, upregulated hypothalamic expression of anaplastic lymphoma kinase, elevated norepinephrine levels in white adipose tissue (WAT) and further activated lipolysis in WAT, leading to a reduction in fat mass. Brown adipose tissue formation was reduced, accompanied by the inhibition of the bone morphogenetic protein signaling pathway. A simultaneous reduced serum levels of antidiuretic hormone (arginine vasopressin) might be one of the reasons for increased water consumption. The present results indicate an environmental etiology and prevention way for the development of emaciation-thirst disease.

EGCG exposure during pregnancy affects uterine histomorphology in F1 female mice and the underlying mechanisms.

Although epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to have many benefits, the effect of EGCG exposure in utero on adult uterine development is unclear. In this study, pregnant C57BL/6 mice were exposed to 1 mg/kg body weight (bw) EGCG dissolved in drinking water from gestational days 0.5-16.5. A significant decrease in uterine weight was observed in the adult female mice, accompanied by uterine atrophy, inflammation, and fibrosis in the endometrium. Uterine atrophy was attributed to the thinning of the endometrial stromal layer and a significant reduction in endometrial cell proliferation. The expression levels of related proteins in the NF-κB and RAF/MEK/ERK signaling pathways were significantly increased, which might be responsible for the occurrence of inflammation. Activation of the transforming growth factor beta (TGF-ß1)/Smad signaling pathway might be involved in the development of endometrial fibrosis. The changes in the expression of estrogen receptor α, ß (ERα, ERß), progesterone receptor (PGR), and androgen receptor (AR) might lead to changes in the aforementioned signaling pathways. The promoter region methylation level of Esr2 was increased, and the expression of DNMT3A was evaluated. Our study indicates a risk of EGCG intake during pregnancy affecting uterine development in offspring.