RESUMO: A paisagem cultural de Linpan tem sido uma obra-prima de coexistência harmoniosa entre humanos e natureza desde a Engenharia Hidráulica de Dujiangyan, há mais de 2.300 anos. Com a rápida urbanização da planície de Chengdu nos últimos trinta anos, Linpan declinou gradualmente e enfrentou uma crise de desaparecimento. A proteção e utilização do Linpan tornaram-se uma demanda pública urgente. Nossa área de estudo de caso foi na cidade de Dujiangyan. Utilizamos investigações de campo detalhadas, questionários e entrevistas não estruturadas para compreender as percepções dos aldeões sobre o Linpan e explorar como os seus antecedentes socioeconômicos e de recursos afetaram as suas percepções da paisagem. O estudo revelou tendências típicas de perda populacional e envelhecimento nos assentamentos de Linpan, e descobriu que os moradores reconheciam Linpan como uma “obra-prima conjunta do homem e da natureza” e que a maioria dos moradores apoiava a utilização nas áreas rurais de Linpan. Este estudo revelou ainda que os fatores socioeconômicos e de recursos dos habitantes das aldeias tiveram impactos complexos e seletivo nas suas percepções da paisagem. Descobriu também que o fator econômico, especialmente o rendimento mensal, era a variável chave que afetada as percepções paisagísticas dos aldeões. O estudo enriqueceu o estudo da percepção de Linpan, uma paisagem agro cultural única na planície de Chengdu. Forneceu uma referência essencial para o subsequente desenvolvimento sustentável de Linpan com base na participação dos moradores. RESUMO obraprima obra prima Dujiangyan 2300 2 300 2.30 anos desaparecimento tornaramse tornaram se urgente detalhadas econômico mensal 230 30 2.3 23 3 2.

ABSTRACT: The Linpan cultural landscape has been a masterpiece of harmonious coexistence between humans and nature since the Dujiangyan Hydraulic Engineering more than 2,300 years ago. With the rapid urbanization of the Chengdu Plain over the past thirty years, Linpan has gradually declined and faced a disappearance crisis. The protection and utilization of Linpan have become an urgent public demand. Our case study area was in Dujiangyan City. We used detailed field investigations, questionnaires, and unstructured interviews to understand the villagers’ perceptions of the Linpan and explore how their socioeconomic and resource backgrounds affected their landscape perceptions. The study revealed typical population loss and aging trends in Linpan settlements, and it found that the villagers recognized Linpan as a “joint masterpiece of man and nature” and that most villagers supported the utilization in Linpan rural areas. This study further revealed that villagers’ socioeconomic and resource background factors had complex and selective impacts on their landscape perceptions. It also found that economic factor, especially monthly income, was the key variables affecting villagers’ landscape perceptions. The study enriched the perception study of Linpan, a unique agro-cultural landscape in the Chengdu Plain. It provided an essential reference for the subsequent sustainable development of Linpan based on villagers’ participation. ABSTRACT 2300 2 300 2,30 ago crisis demand City investigations questionnaires settlements joint areas factor income agrocultural agro participation 230 30 2,3 23 3 2,

Abstract Lateral Lymph Node Metastasis (LLNM) is common in Papillary Thyroid Carcinoma (PTC) and is associated with a poor prognosis. LLNM without central lymph node metastasis as skip metastasis is not common. We aimed to investigate clinicopathologic and sonographic risk factors for skip metastasis in PTC patients, and to establish a nomogram for predicting the possibility of skip metastasis in order to determine the therapeutic strategy. We retrospectively reviewed the data of 1037 PTC patients who underwent surgery from 2016 to 2020 at a single institution. Univariate and multivariate analyses were used to identify the clinicopathologic and preoperative sonographic risk factors of skip metastasis. A nomogram including the risk factors for predicting skip metastasis was further developed and validated. The incidence of skip metastasis was 10.7%. The univariate and multivariate analyses suggested that gender (p = 0.001), tumor location (p = 0.000), extrathyroidal extension (p = 0.000), and calcification (p = 0.000) were independent risk factors. For papillary thyroid microcarcinoma, tumor location (p = 0.000) and calcification (p = 0.001) were independent risk factors. A nomogram according to the clinicopathologic and sonographic predictors was developed. The receiver operating characteristic curve indicated that AUC was 0.824 and had an excellent consistency. The calibration plot analysis showed a good performance and clinical utility of the model. Decision curve analysis revealed it was clinically useful. A nomogram for predicting the probability of skip metastasis was developed, which exhibited a favorable predictive value and consistency. For the female PTC patient, tumor located at the upper pole is more likely to have skip metastasis. Surgeons and sonographers should pay close attention to the patients who have the risk factors. Evidence level: This article’s evidence level is 3. Level 3 evidence is derived from nonrandomized, controlled clinical trials. In this study, patients who receive an intervention are compared to a control group. Authors may detect a statistically significant and clinically relevant outcome. (LLNM (PTC prognosis strategy 103 201 202 institution validated 107 10 7 10.7% p 0.001, 0001 0.001 , 0 001 0.000, 0000 0.000 000 microcarcinoma 0824 824 0.82 consistency model useful patient articles article s nonrandomized trials study group outcome 20 1 10.7 0.00 00 082 82 0.8 2 10. 0.0 08 8 0.

Abstract The improvement effects of enzymatic polypeptide of Paeonia ostii seed meal (APHP) on model mice of protein-energy malnutrition were evaluated by body weight changes, organ indices, levels of SOD, CAT, MDA, total protein and albumin in serum, staining images of major organs and macrophages phagocytosis. The results indicated the mice body weight recovery was dose-dependent with APHP and the body weight change of model mice fed with high-dose APHP (5.0 g/kg) and normal diet showed a same recovery effect. The model mice had higher thymus and spleen indexes than other groups. And the values of SOD, CAT, MDA, total protein and albumin in serum returned to normal level after 30, 60, 45, 30 and 45 days respectively, which was better than those of normal diet. Our research will provide basic data support for new potential applications of APHP and increase the added value of Paeonia ostii processing enterprises.

Abstract Objective Trastuzumab is the preferred drug for the treatment of breast cancer. However, research on the cellular mechanisms of trastuzumab's potential cardiotoxicity is insufficient. The purpose of this study was to explore the toxic effects and potential mechanism of action of trastuzumab on cardiomyocytes. Method Human Cardiomyocyte (HCM) viability was assessed using the MTT method. HCM apoptosis was detected using the Hoechst33342/PI Fluorescent staining. The LDH and CK activities of the cell were measured using commercially available LDH and CK assay kits. The expression levels of Notch2, JAK2, STAT3, cleaved caspase 3, bax, and bcl 2 in HCMs were detected using western blotting. Results The results showed that 250 mg/L trastuzumab induced cardiomyocyte injury and apoptosis, inhibited viability, activated the Notch2 receptor, and inhibited JAK2/STAT3 expression in HCM. Inhibition of Notch2 expression in HCM by targeted siNotch2 transfection reversed the trastuzumab-induced injury and apoptosis, and the expression of JAK2/STAT3 returned to normal levels. Conclusions Trastuzumab induces Notch2 expression by inhibiting the JAK2/STAT3 pathway of HCMs, promotes cell apoptosis, and causes cardiomyocyteinjury. Notch2 may be a potential target of trastuzumab-inducedmyocardial injury. This experiment reveals the mechanism of trastuzumab-induced cardiotoxicity, providing a theoretical basis for the application of trastuzumab. cancer However trastuzumabs s insufficient cardiomyocytes (HCM method Hoechst33342PI HoechstPI Hoechst33342 PI Hoechst staining kits Notch JAK2 JAK STAT3 STAT 3 bax blotting 25 mgL mg L receptor JAK2STAT3 JAKSTAT JAK2/STAT siNotch trastuzumabinduced cardiomyocyteinjury trastuzumabinducedmyocardial inducedmyocardial Hoechst3334 JAK2STAT Hoechst333 Hoechst33 Hoechst3

Resumo Introdução O tratamento do microcarcinoma papilífero de tireoide permanece controverso. A metástase em linfonodos centrais é comum e é uma consideração importante na seleção da estratégia de tratamento. Objetivo Investigar os fatores de risco clínico-patológicos e as características ultrassonográficas de nódulos tireoidianos para metástase em linfonodos centrais em microcarcinoma papilífero de tireoide. Método Foram analisados retrospectivamente os dados de 599 pacientes com microcarcinoma papilífero de tireoide submetidos à cirurgia de 2005 a 2017 em uma única instituição. Análises univariadas e multivariadas foram usadas para identificar os fatores clínico-patológicos e as características ultrassonográficas pré-operatórias das metástases em linfonodos centrais. Uma análise de curva ROC (receiver-operating characteristic) foi feita para identificar a eficácia das características ultrassonográficas na previsão dessas metástases. Um nomograma baseado nos fatores de risco foi estabelecido para prever a metástase em linfonodos centrais. Resultados A incidência de metástase em linfonodos centrais foi de 22,4%. As análises univariadas e multivariadas sugeriram que sexo, idade, multifocalidade, invasão extratireoidiana e metástase em linfonodos laterais eram fatores de risco independentes para a metástase em linfonodos centrais. As análises univariadas e multivariadas revelaram que o formato nodular, a margem e a calcificação estavam independentemente associadas à metástase em linfonodos centrais. A análise da curva ROC mostrou que a combinação do formato, margem e calcificação apresentou excelente precisão na previsão dessas metástases. O nomograma foi desenvolvido com base nos fatores de risco identificados para predizer a metástase em linfonodos centrais e a análise do gráfico de calibração indicou o bom desempenho e a utilidade clínica do nomograma. Conclusões Em pacientes com microcarcinoma papilífero de tireoide, metástase em linfonodos centrais está associado ao sexo masculino, menor idade ( < 45 anos), invasão extratireoidiana, multifocalidade e presença de metástase em linfonodos laterais. As características ultrassonográficas, como formato irregular, margem mal definida e calcificação, podem melhorar a eficácia da previsão de metástase em linfonodos centrais. Cirurgiões e radiologistas devem ficar mais atentos aos pacientes que apresentam esses fatores de risco. O nomograma pode ajudar a orientar a tomada de decisão cirúrgica para o microcarcinoma papilífero de tireoide.

Abstract Introduction The treatment of papillary thyroid microcarcinoma remains controversial. Central lymph node metastasis is common in papillary thyroid microcarcinoma and it is an important consideration in treatment strategy selection. Objective The aim of this study was to investigate clinicopathologic risk factors and thyroid nodule sonographic characteristics for central lymph node metastasis in papillary thyroid microcarcinoma. Methods We retrospectively reviewed the data of 599 papillary thyroid microcarcinoma patients who underwent surgery from 2005 to 2017 at a single institution. Univariate and multivariate analyses were used to identify the clinicopathologic factors and preoperative sonographic features of central lymph node metastasis. A receiver-operating characteristic, ROC curve analysis, was performed to identify the efficacy of ultrasonographic features in predicting central lymph node metastasis. A nomogram based on the risk factors was established to predict central lymph node metastasis. Results The incidence of central lymph node metastasis was 22.4%. The univariate and multivariate analyses suggested that gender, age, multifocality, extrathyroidal invasion, and lateral lymph node metastasis were independent risk factors for central lymph node metastasis. The univariate and multivariate analyses revealed that nodular shape, margin, and calcification were independently associated with central lymph node metastasis. The ROC curve analysis revealed that the combination of shape, margin and calcification had excellent accuracy in predicting central lymph node metastasis. The nomogram was developed based on the identified risk factors for predicting central lymph node metastasis, and the calibration plot analysis indicated the good performance and clinical utility of the nomogram. Conclusions Central lymph node metastasis is associated with male gender, younger age (<5 years), extrathyroidal invasion, multifocality and lateral lymph node metastasis in papillary thyroid microcarcinoma patients. The ultrasongraphic features, such as irregular shape, ill-defined margin and calcification, may improve the efficacy of predicting central lymph node metastasis. Surgeons and radiologists should pay close attention to the patients who have these risk factors. The nomogram may help guide surgical decision making in papillary thyroid microcarcinoma.

SUMMARY OBJECTIVE: This study aimed to investigate the suboptimal health status or subhealth status and their relationship with mental health and smartphone addiction among Chinese medical students. METHODS: A cross-sectional survey was conducted at Wannan Medical College of China in Wuhu. RESULTS: A total of 2,741 students were surveyed in October 2020. Of 2,741 Chinese medical students who completed the survey, 904 (33%) participants reported to have had subhealth status. Anxiety status (p<0.001), depression status (p<0.001), and smartphone addiction status (p<0.001) have strong association with subhealth status. CONCLUSION: This survey shows that the detection rate of subhealth status in Chinese medical students was 33%. Anxiety, depression, and smartphone addiction students had a higher detection rate of subhealth status. The anxiety, depression, and smartphone addiction of Chinese medical students are associated with subhealth status. OBJECTIVE METHODS crosssectional cross sectional Wuhu RESULTS 2741 2 741 2,74 2020 90 33% 33 (33% p<0.001, p0001 p p<0.001 , 0 001 (p<0.001 CONCLUSION anxiety 274 74 2,7 202 9 3 (33 p000 p<0.00 00 (p<0.00 27 7 2, 20 (3 p00 p<0.0 (p<0.0 ( p0 p<0. (p<0. p<0 (p<0 p< (p< (p

SUMMARY OBJECTIVE: The objective of this study was to explore the molecular mechanism underlying the occurrence of benign bile duct stricture and the target of low-dose paclitaxel in the prevention of benign bile duct stricture. METHODS: Under the stimulation of transforming growth factor beta 1, the expression of collagen type I and connective tissue growth factor were detected on isolated primary fibroblasts. The phosphorylation levels of JNK and Smad2L were detected using Western blot. The effect of low-dose paclitaxel on the transforming growth factor beta 1-induced inhibition of type I collagen and connective tissue growth factor expression and JNK and Smad2L phosphorylation was also observed. RESULTS: Transforming growth factor beta 1 induced the secretion of type I collagen and connective tissue growth factor as well as JNK phosphorylation in biliary fibroblasts. The JNK inhibitor or siRNA-Smad2 inhibited the transforming growth factor beta 1-induced secretion of type I collagen and connective tissue growth factor. Low-dose paclitaxel inhibited the expression of type I collagen induced by transforming growth factor beta 1 and may inhibit the secretion of collagen in biliary fibroblasts. CONCLUSION: The activation of JNK/Smad2L induced by transforming growth factor beta 1 is involved in the occurrence of benign bile duct stricture that is mediated by the overexpression of type I collagen and connective tissue growth factor, and low-dose paclitaxel may inhibit the phosphorylation of JNK/Smad2L. OBJECTIVE lowdose low dose METHODS fibroblasts SmadL Smad L blot 1induced observed RESULTS siRNASmad2 siRNASmad siRNA Smad2 siRNA-Smad Lowdose Low CONCLUSION JNKSmad2L JNKSmadL JNKSmad

Abstract To study the failure modes, bearing capacity, ductility, and sleeve strain of grouted sleeve lapping connectors, 36 specimens were tested under uniaxial tensile load. The test results show that the sleeves are under longitudinal tension at the beginning, which changes to longitudinal compression in the late stage of loading, and the changing load increases gradually with the lap length. The force transmission path and mechanical mechanism of the connectors are analyzed. The distribution and development process of longitudinal sleeve stress is analyzed based on the constitutive model stress, and it is found that the sleeve changes from longitudinal tension to longitudinal compression at the late loading stage, which is consistent with the test results. Based on the test, the calculation formulas of the ultimate bond strength and critical lap length of the grouted sleeve lapping connector are proposed. The research results lay a theoretical foundation for the application of grouted sleeve lapping connectors.

Abstract This study aims to explore the molecular mechanism of neuronal axonal lesions caused by high glucose, and to investigate the protective effect of Lycium barbarum polysaccharide (LBP) on neuronal axon damage with in vitro models. A rat model of type II diabetic encephalopathy was established, and the rats were treated with LBP for 10 weeks. Morris water maze experiment was used to detect spatial learning and memory ability. Neuronal axon lesions were measured by in vivo neuron tracing experiment. Immunohistochemistry and Western-blot technology were employed to detect protein localization and expression. Combined with in vitro primary neuron culture, total internal reflection fluorescence microscopy was used to detect the effects of high glucose and LBP on neuronal axon transport. PI3K inhibitors LY294002 and an activator of insulin signaling pathway were used to investigate the possible molecular mechanism. In vivo and in vitro experiments showed that in the hippocampus tissue of STZ-induced type II diabetic encephalopathy model rats, neuronal axons were damaged, accompanied by hyperphosphorylation of Tau protein, which subsequently resulted in axonal transport damage and cognition dysfunction. LBP significantly reduced peripheral blood glucose and serum insulin levels in type II diabetic encephalopathy model rats, thereby alleviating peripheral insulin resistance. At the same time, LBP can significantly improve the learning and memory impairment and brain neuron axon pathology in model rats. LY294002 treatment can effectively block the PI3K/Akt signaling pathway. The phosphorylation level of Tau protein in the LY294002+ LBP treatment group is higher than that of the LBP intervention group, while the insulin treatment can effectively reverse the blocking effect of LY294002 on LBPs. LBP can reduce the phosphorylation level of Tau protein by up-regulating the PI3K/Akt/GSK3β signaling pathway, with a protective effect on neuronal axon damage, thereby improving the cognitive function performance of type II diabetic encephalopathy model rats.

SUMMARY OBJECTIVE: This study aimed to assess the attitudes of Chinese residents toward COVID-19 vaccines and explore the potential drivers for Chinese residents' vaccine hesitancy. METHODS: A cross-sectional survey was conducted from February 16 to March 16, 2021, by administering an online questionnaire to the Chinese residents. RESULTS: Of 5240 residents who completed the survey, 464 (8.9%) participants reported to have had one shot, and 348 (6.6%) reported to have had 2 shots. At the time the questionnaire was administered, 2298 (43.9%) participants reported they wanted to get vaccinated, while 2255 (43.0%) declared that they still did not know, and 687 (13.1%) respondents declared vaccine refusal. Overall, 2255 (43%) participants were categorized as vaccine hesitancy. Female participants (p=0.000), <20 years old (p=0.000), have low risk of COVID-19 (p=0.000) infection and strong associations of vaccine hesitancy. eHealth literacy was a protective factor. CONCLUSIONS: The results of this study show high rates of vaccine hesitancy in China. This could pose a serious threat to the preventive measures that aimed at controlling COVID-19 spread in the country. The government and different media platforms should encourage the dissemination of correct information about vaccines, the communities and medical staff to improve residents' knowledge about vaccines, and strive to improve residents' electronic health literacy.

ABSTRACT In the present work, the considered hydrogen abstraction (HAT) reactions of CCl3H molecule driven by three different small anions MO− (M = Be, B, and Al) have been investigated using electronic structure calculations. While full geometry optimizations were operated to locate all of the relevant stationary points using the DFT-BHandHLYP/aug-cc-pVTZ level, the potential-energy profiles were constructed using the coupled-cluster theory with extrapolation to complete basis set CCSD(T)/CBS. Our theoretical findings suggest that the most favored pathway determined for the HAT reactions mainly stems from the MO− type, namely, for facilitating the HAT pathway the B atom is predicted to be an inherent key in the BO−-reaction whereas it becomes O atom in both BeO−- and AlO−-reactions. Of the three favored pathways obtained here, the activations of the CCl3H in the presence of both BeO− and AlO− anions are significantly efficient, in which the energy barrier for the cleavage of the C-H bond with the assistance of BeO− was to be relatively low. Again, through the transition state theory the rate constants at 298-1000 K are also evaluated for the most favored HAT reactions studied here, indicating the lower the temperature, the faster the BO− chemical reaction.

SUMMARY OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.

Abstract Background: Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder with no effective treatment that is caused by the loss of dystrophin. Human induced pluripotent stem cells (hiPSCs) offer a promising unlimited resource for cell-based therapies of muscular dystrophy. However, their clinical applications are hindered by inefficient myogenic differentiation, and moreover, the engraftment of non-transgene hiPSC-derived myogenic progenitors has not been examined in the mdx mouse model of DMD. Methods: We investigated the muscle regenerative potential of myogenic progenitors derived from hiPSCs in mdx mice. The hiPSCs were transfected with enhanced green fluorescent protein (EGFP) vector and defined as EGFP hiPSCs. Myogenic differentiation was performed on EGFP hiPSCs with supplementary of basic fibroblast growth factor, forskolin, 6-bromoindirubin-3′-oxime as well as horse serum. EGFP hiPSCs-derived myogenic progenitors were engrafted into mdx mice via both intramuscular and intravenous injection. The restoration of dystrophin expression, the ratio of central nuclear myofibers, and the transplanted cells-derived satellite cells were accessed after intramuscular and systemic transplantation. Results: We report that abundant myogenic progenitors can be generated from hiPSCs after treatment with these three small molecules, with consequent terminal differentiation giving rise to mature myotubes in vitro. Upon intramuscular or systemic transplantation into mdx mice, these myogenic progenitors engrafted and contributed to human-derived myofiber regeneration in host muscles, restored dystrophin expression, ameliorated pathological lesions, and seeded the satellite cell compartment in dystrophic muscles. Conclusions: This study demonstrates the muscle regeneration potential of myogenic progenitors derived from hiPSCs using non-transgenic induction methods. Engraftment of hiPSC-derived myogenic progenitors could be a potential future therapeutic strategy to treat DMD in a clinical setting.

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Abstract Parthenogenetically activated oocytes cannot develop to term in mammals owing to abnormal epigenetic modifications. Methylation of the N6 position of adenosine (m6A) is a post-transcriptional epigenetic modification of RNA. To investigate the role of m6A methylation in parthenogenetic (PA) embryonic development, we analyzed METTL3, METTL14, FTO, ALKBH5, YTHDF2, IGF2BP1, and IGF2BP2 expression by quantitative real-time PCR. These genes were found dynamically expressed during the 2-cell, 4-cell, 8-cell, and blastocyst stages of the embryo. Compared to normally fertilized embryos, the expression of these genes was perturbed in PA embryos, especially at the 8-cell stage. Furthermore, immunofluorescence was used to detect m6A expression. The results demonstrated that m6A expression decreased in the 2-cell stage, whereas it increased in the 8-cell stage of PA embryos. Taken together, these results suggest that the expression of RNA methylation-related genes was perturbed, leading to abnormal m6A modification during early development in PA embryos.