Maternal high-fat diet (HFD) increases the risk of metabolic disorders in offspring. Placental inflammation acts as a critical mediator with poorly addressed etiology. Recently HFD-induced gut dysbiosis is demonstrated to be a key driver of systemic inflammation. Whether inflammatory signals triggered by HFD-induced gut dysbiosis are transmitted to the placenta via the maternal-fetal axis warrant further investigation. This study aims to elucidate the mechanistic connection between maternal gut dysbiosis and placental inflammation, thereby offering insights into microbiota-mediated developmental origins of metabolic diseases in offspring. Female C57BL/6 mice were exposed to high fat diet (HFD) for 5 weeks prior to mating with male mice. Gut microbiota was profiled by using 16 S rRNA sequencing and fecal short-chain fatty acids (SCFAs) were quantified by GC-MS from HFD pregnant mice at gestational day 18.5 (G18.5). Mice were sacrificed at G18.5, and placenta histopathological analysis as well as inflammatory markers and lipopolysaccharide (LPS) level were analyzed. Anti-inflammatory effects of butyrate were evaluated in vitro by using HTR-8/Svneo cells and in vivo through gestational supplementation (0.3 mg/g body weight) in HFD-fed dams. Maternal HFD exposure induced significant placental inflammation as well as hepatic steatosis in the offspring. HFD-fed dams exhibited distinct gut dysbiosis with reduced fecal and serum SCFAs, which was accompanied by elevated placental LPS levels and exacerbated inflammatory responses. Butyrate treatment suppressed the expression of inflammatory cytokines in vitro through down-regulating the phosphorylation of NF-κB, ERK1/2 signaling pathways via G-protein-coupled receptor 41 (GPR41). Furthermore, gestational butyrate intervention effectively alleviated placental inflammation and mitigated fetal hepatic lipid deposition in HFD-exposed offspring. Placental inflammation caused by maternal HFD is closely associated with gut microbiota dysbiosis. Butyrate supplementation during gestation reduces placental inflammation and ameliorated offspring hepatic steatosis, highlighting the therapeutic potential of butyrate for mitigating the adverse metabolic programming effects upon maternal HFD exposure.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the lower two flow cytometric plots shown in Fig. 3A on p. 809 (namely, the plots for the 'anti‑TLR4+LPS' and 'TLR4‑shRNA+LPS' experiments), these appeared to show similar groupings of dots, which would not have been anticipated if these experiments had been performed discretely under different experimental conditions, suggesting a fundamental flaw either in the way in which these experiments were performed, or in how the results were outputted. The Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 15: 805‑812, 2017; DOI: 10.3892/mmr.2016.6097].

Background The prevalence of childhood metabolic diseases has markedly increased in recent decades whereas the effects of maternal nutrients affecting the placental microenvironment are not clearly addressed. Methods In the present study, female C57BL/6J mice were fed with a high-fat diet (HFD) or control diet (CON) for 5 weeks prior to mating and then during pregnancy. Single-cell RNA sequencing (scRNA-seq) was used to dissect the placental cell atlas at embryonic day(E) 18.5. Results Maternal HFD led to a reduction in the composition of placental labyrinth zone (LZ) trophoblast cells and endothelial cells, together with a diminished LZ area and narrowed fetal vessels, related to a decreased placental efficiency. Pro-inflammatory placental NK1 cells and M1-like macrophages were more apparent in the placenta from HFD dams with inflammation features. Increased glycogen deposition and glycogen trophoblast cells were also detectable in the HFD placenta, likely associated with the altered metabolism of placental NK cells and macrophages. Conclusions Maternal HFD before and during pregnancy leads to an altered placental microenvironment with more inflammatory features and abnormal metabolic properties, which provides a better understanding on the mechanisms of intergenerational inheritance.

Objective·To investigate the changes of adipose tissues in mice after high-fat diet before and during pregnancy and the potential effects on adipose tissues in their offspring.Methods·C57BL/6J female mice were randomly assigned to the normal diet (CON group, n=12) or the high-fat diet (HFD group, n=12) for 5 weeks. The two groups were further subdivided according to pregnancy: a normal diet non-pregnancy group (CON-UN group), a normal diet pregnancy group (CON-P group), a high-fat diet non-pregnancy group (HFD-UN group), and a high-fat diet pregnancy group (HFD-P group). The original diet was maintained during pregnancy and lactation. White adipose tissues (WAT) and brown adipose tissues (BAT) were collected from visceral and scapula of mice after 5 weeks of feeding or E18.5d. Offspring from both dietary groups were placed on a normal diet after weaning, and their adipose tissues were collected at the 11th week. H-E staining was used to observe the changes of adipocytes. Flow cytometry was employed to detect the proportions of CD4+T cells, CD8+T cells, total T cells, CD4+T/CD8+T and NK cells in WAT. RT-PCR was used to assess the expression of IL-6 and IL-1β mRNA in WAT.Results·After 5 weeks on a high-fat diet, the body weight of female mice in the HFD group was higher than that in the CON group (P<0.05). Both WAT and BAT weights were markedly increased in the HFD groups before and during pregnancy (both P<0.05). In the WAT from HFD-UN and HFD-P groups, the number of cells within the same visual field decreased, the size of adipose cells varied, the proportion of fat droplets increased and the cell volume expanded. The proportion of lipid drop area to total visual field in the HFD-UN group and HFD-P group was compared with the CON-UN group and CON-P group, respectively, and the difference was statistically significant (all P<0.05). BAT in the HFD-UN and HFD-P groups showed a relatively chaotic arrangement and varying adipocyte sizes, although cell volume remained unchanged. The proportions of CD8+T cells and total T cells in adipose tissues were elevated in the HFD-UN and HFD-P groups, accompanied by increased mRNA levels of IL-6 and IL-1β, respectively, compared with the CON-UN and CON-P groups, and the differences were statistically significant (all P<0.05). NK cells proportions decreased at reproductive age (HFD-UN group) but increased significantly during pregnancy (HFD-P group), showing a divergent trend. Despite a return to a normal diet after weaning, offspring from the high-fat diet group had significantly higher weight of body, WAT and BAT, compared to those of normal diet (all P<0.05), and the volume of WAT was significantly enlarged.Conclusion·A high-fat diet can induce the changes of adipocyte structure and immune cell ratio, and elevate inflammation levels in adipose tissues before and during pregnancy, which also impacts the adipose structure in offspring. Adipose tissue may be a new vector mediating the intergenerational transmission of obesity.

Objective·To analyze the effects of maternal high-fat diet on placental phenotype, and investigate the role of placental microenvironment in the intergenerational transmission.Methods·The 3-week-old C57BL/6J female mice were fed with either the high-fat diet (HFD group) or the control diet (CD group) for 5 weeks before mating and throughout gestation. Placentas and fetal liver tissues were collected from maternal mice after 20 d of gestation. The effects of maternal HFD on the placental inflammation and placental structure were investigated by hematoxylin-eosin staining (H-E staining), immunohistochemistry, Western blotting and RT-PCR. The lipid deposition levels in fetal livers were also detected. Body weight changes, fasting blood glucose and glucose tolerance levels of the 3-week-old weaned mice were also detected.Results·The body weight of female mice in the HFD group increased significantly, and the liver triacylglycerol (TAG) and total cholesterol (TC) levels were higher than those in the CD group (all P<0.05). Compared to the CD group, the liver cells of fetus in the HFD group showed steatosis, lipid vacuoles of different sizes, and the content of TAG in the fetal livers in the HFD group increased, but the difference was not statistically significant (P>0.05). Compared to the CD group, the body weight, fasting blood glucose level and the area under the glucose tolerance curve of the 3-week-old weaned mice of the HFD group were increased significantly (all P<0.05). The immunohistochemical results showed that the levels of interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the placenta in the HFD group were significantly increased (both P<0.05), and the level of IL-1β did not change significantly. In addition, H-E staining of placentas showed that the area proportion of the labyrinth zone (the maternal-fetal exchange area) in the HFD group decreased significantly, which was statistically significant by ImageJ software (P<0.05). The intervascular membrane thickened, and the maternal blood sinuses were narrow. RT-PCR results showed the expressions of placental tight-junction-related protein Zo-1 (zonula occludens 1) and claudin were increased (both P<0.05).Conclusion·Maternal high-fat diet may result in placental inflammation and abnormal structure, which may be related to glucose and lipid metabolism disorder in offspring.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the prevailing chronic liver disease in the pediatric population due to the global obesity pandemic. Evidence shows that prenatal and postnatal exposure to maternal abnormalities leads to a higher risk of pediatric NAFLD through persistent alterations in developmental programming. Gestational diabetes mellitus (GDM) is a hyperglycemic syndrome which has become the most prevalent complication in pregnant women. An increasing number of both epidemiologic investigations and animal model studies have validated adverse and long-term outcomes in offspring following GDM exposure in utero. Similarly, GDM is considered a crucial risk factor for pediatric NAFLD. This review aimed to summarize currently published studies concerning the inductive roles of GDM in offspring NAFLD development during childhood and adolescence. Dysregulations in hepatic lipid metabolism and gut microbiota in offspring, as well as dysfunctions in the placenta are potential factors in the pathogenesis of GDM-associated pediatric NAFLD. In addition, potentially effective interventions for GDM-associated offspring NAFLD are also discussed in this review. However, most of these therapeutic approaches still require further clinical research for validation.

Lipotoxicity can lead to beta-cell dysfunction and apoptosis because it induces oxidative stress. Recent studies have found that Irisin prevents pancreatic beta-cell dysfunction induced by palmitic acid (PA). However, an association between the protection against oxidative stress conferred by Irisin and beta-cell dysfunction has not been fully elucidated. In this study, we observed that Irisin treatment prevented INS-1 cell apoptosis induced by PA treatment and preserved the insulin-secreting function of INS-1 cells in vitro. These effects probably resulted from the Irisin-induced decrease in intracellular ROS levels triggered by PA treatment. In addition, PA treatment induced oxidative stress partially by inhibiting the activation of thioredoxin 2 (Trx2) through its increase of thioredoxin-interacting protein (Txnip) expression. However, Irisin administration blocked the increase in Txnip expression, which reversed the PA-induced inactivation of Trx2. Irisin also increased the nuclear translocation of Stat3, and the inhibition of Stat3 by siRNAs blocked Irisin-induced Trx2 expression, indicating that both Txnip and Stat3 are involved in Irisin-induced activation of Trx2. Furthermore, blockade of Stat3 by siRNAs led to the decreased gene expression of MafA and Ins and to cessation of glucose-induced insulin secretion that had been enhanced by Irisin. In vivo, HFD treatment led to reduced glucose tolerance and an increase in the level of the oxidative marker malondialdehyde (MDA) compared to that in the control group. However, these effects were ameliorated by Irisin injection due to the inhibition of beta-cell apoptosis and the activation of Trx2, probably through Txnip inhibition and Stat3 activation. In conclusion, our results reveal a possible mechanism for Irisin-induced beta-cell protection, which is mediated through Txnip inhibition and activation of the Stat3-Trx2 pathway.

博士专业学位研究生是培养高层次应用型人才的有效途径,我院从2016年起开始口腔医学博士专业学位研究生的招生与培养,围绕课程体系建设、考核体系建设和学位论文质量控制体系建设3个方面进行实践和总结,并在此基础上提出了问题与思考,为进一步完善博士专业学位与专科医师规范化培训制度的有机衔接提供了实证基础.

Exposure to adverse events in early life increases the risk of chronic metabolic disease in adulthood. The objective of this study was to determine the significance of milk fat globule membrane (MFGM)-mediated alterations in the gut microbiome to the metabolic health of offspring in the long-term. Female C57BL/6 mice were fed either a high-fat diet (HFD) or a control diet for 3 weeks before pregnancy and throughout pregnancy and lactation. During lactation, pups from the HFD group were breast-fed with or without 1,000 mg/kg BW/day MFGM supplementation (HFD and HFD-MS group, respectively). After weaning, the offspring in each group were divided into male and female subgroups. The weaned mice were then shifted to a control diet for 8 weeks. At the eleventh week, stool samples were collected for 16S rRNA gene sequencing. Serum biochemical parameters were analyzed, and intraperitoneal glucose and insulin tolerance tests were performed. Neonatal supplementation with MFGM ameliorated metabolic disorder and improved glucose tolerance in offspring exposed to maternal HFD in a sex-specific manner. Furthermore, maternal HFD induced gut microbiota perturbation in offspring in adulthood. Neonatal MFGM supplementation significantly enriched g-Parabacteroides, g-Bifidobacterium, g-Faecalibaculum, and g-Lactobacillus in male offspring exposed to maternal HFD, while significantly enriched g-Parabacteroides and g-Alistipes in female offspring exposed to maternal HFD. These bacteria may be associated with the favorable changes in metabolism that occur in adulthood. Sex differences in the changes of metagenomic pathways related to oxidative phosphorylation, citrate cycle, electron transfer carries, and ubiquinone biosynthesis were also observed in the offspring. Maternal HFD has an adverse effect on the metabolism of offspring in later life. Neonatal MFGM supplementation could modulate the structure of gut microbiota communities and may have long-term protective effects on lipid and glucose metabolism, but these effects are sex dimorphic.

Bronchial asthma is a common chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), inflammatory cell infiltration, and airway remodeling. F-box/WD repeat-containing protein 7 (FBXW7), an E3 ubiquitin ligase, is required for various endothelial functions, such as cell migration, inflammation, and endothelial integrity. This study aimed to investigate the role of FBXW7 in lipopolysaccharide (LPS)-induced epithelial barrier impairment in bronchial epithelial cells in vitro. By using lentivirus-based technology, FBXW7 was overexpressed or silenced (24 h) in human bronchial epithelial (16HBE) cells, which were treated with LPS or not (24 h). Immunoprecipitation (IP) detection and Western blot analysis were used to evaluate the interaction of target proteins. Cell permeability was measured using transepithelial electrical resistance and FITC dextran flux (48 h). IL-1 beta, IL-18 and TNF-alpha in cell supernatants were measured using ELISA (48 h). The results showed that LPS stimulation suppressed FBXW7 expression in a time- and dose-dependent manner. LPS exposure decreased cell proliferation, elevated IL-1 beta, IL-18 and TNF-alpha, increased epithelial permeability, and p38 phosphorylation. These LPS-induced changes were partly compromised by FBXW7 overexpression. Similar to LPS stimulation, FBXW7 knockdown increased epithelial permeability and levels of inflammatory cytokines and p38 phosphorylation, which were, in part, blocked by apoptosis signal-regulating kinase (ASK) 1 knockdown or p38 pathway inhibition. IP and Western blot analysis showed that FBXW7 interacted with ASK1. ASK1 expression was inversely associated with FBXW7 expression. FBXW7 overexpression markedly enhanced ASK1 ubiquitination. These data revealed that FBXW7 counter against inflammation and protects epithelial barrier integrity in bronchial epithelial cells by promoting ubiquitination-mediated degradation of ASK1 via the p38 pathway.

Background: The nucleus accumbens associated 1 (NACC1) gene is a transcription factor member of the BTB/POZ family. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. Case Presentation: We report a new case with a neurodevelopmental disorder characterized by severe intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. Brain MRI reveals brain dysplasia. We observe a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 gene in this case. Now, the child regularly goes to the hospital for rehabilitation training (once a month). Sodium Valproate (10 mg/kg/day) and Clobazam (10 mg/kg/day) are used in the treatment of epilepsy. A total of three articles were screened, and two papers were excluded. The search revealed one article related to a syndrome caused by a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1; they screened the main clinical features of eight cases of a syndrome, which were summarized and analyzed. Conclusions: The NACC1 gene is a member of the BTB/POZ family of transcription factors. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. At present, there is no effective cure. In the future, we need more cases to determine the phenotype–genotype correlation of NACC1 variants. Many questions remain to be answered, and many challenges remain to be faced. Future transcriptional studies may further clarify this rare, recurrent variant, and could potentially lead to targeted therapies.

目的:构建医院临床医学学术型研究生导师定性及动态定量考核体系,并分析考核结果.方法:对64名博士生导师及55名硕士生导师进行考核.构建定性及动态定量考核体系,前者考核内容为教书育人基本规范(计10分);后者包括科学研究能力(计35分)、科学研究成果(35分)、导师所指导研究生的学术能力(20分).此外,另设独立加分项及扣分项.结果:博士生导师的考核平均得分为76.31分,导致其中部分导师考核不合格的原因主要在于未获得国家级课题资助.硕士生导师的考核平均得分为51.30分,导师在科学研究成果这一指标上的得分率最高,而其中部分导师考核不合格的原因主要在于科学研究成果方面存在不足.结论:构建科学的导师考核体系,定性联合动态考核评价医院临床医学学术型研究生导师,对保证研究生培养质量十分重要.本次考核结果提示,博士生导师需要重视提高国家级课题的申请能力,硕士生导师则需重视科学研究成果的提升.

BACKGROUNDExposure to a maternal high-fat diet (HFD) predisposes offspring to nonalcoholic fatty liver disease.OBJECTIVESThe aim of this study was to explore whether milk fat globule membrane (MFGM) supplementation during suckling exerts a long-term protective effect on hepatic lipid metabolism in adult offspring exposed to maternal HFD.METHODSWe fed 5-week-old female C57BL/6J mice either a HFD (60% kcal fat) or control diet (CD; 16.7% kcal fat) for 3 weeks before mating, as well as throughout gestation and lactation. After delivery, male offspring from HFD dams were supplemented with 1 g/(kg body weight·day) MFGM (HFD + MFGM group) or the same volume of vehicle (HFD group) during suckling. Male offspring from CD dams were also supplemented with vehicle during suckling (CD group). All offspring were weaned onto CD for 8 weeks. Histopathology, metabolic parameters, lipogenic level, oxidative stress, and mitochondria function in the liver were analyzed. A 1-way ANOVA and a Kruskal-Wallis test were used for multi-group comparisons.RESULTSAs compared to the CD group, the HFD group had more lipid droplets in livers, and exhibited ∼100% higher serum triglycerides, ∼38% higher hepatic triglycerides, ∼75% higher serum aspartate aminotransferase, and ∼130% higher fasting blood glucose (P < 0.05). The changes of these metabolic parameters were normalized in the HFD + MFGM group. Phosphorylated mammalian targets of rapamycin and AKT were downregulated, but phosphorylated adenosine monophosphate-activated protein kinase was upregulated in the HFD + MFGM group as compared to the HFD group (P < 0.05). As compared to the CD group, the HFD group showed an ∼80% higher malondialdehyde level, and ∼20% lower superoxide dismutase activity (P < 0.05), which were normalized in the HFD + MFGM group. Additionally, mitochondria function was also impaired in the HFD group and normalized in the HFD + MFGM group.CONCLUSIONSMFGM supplementation during suckling ameliorates maternal HFD-induced hepatic steatosis in mice via suppressing de novo lipogenesis, reinforcing antioxidant defenses and improving mitochondrial function.

Long non-coding RNAs (lncRNAs) are involved in a variety of biological functions through transcriptional and post-transcriptional regulation. However, little is known about their functions in the process of insect mediated virus transmission. In the present study, we analyzed using RNA-Seq, the lncRNAs that were differentially expressed in response to Rice black-streaked dwarf virus (RBSDV) infection in Laodelphax striatellus (Fallén) midgut. A total of 13,927 lncRNAs were identified and over 69% were assigned to intergenic regions. Among them, 176 lncRNAs were differentially expressed and predicted to target 168 trans-regulatory genes. Ten differentially expressed lncRNAs were selected and their expression changes were validated by RT-qPCR. KEGG analysis showed that these target genes were enriched in the essential biological process, such as Purine metabolism, Valine, leucine and isoleucine degradation, and Fatty acid elongation. The expression levels of the differentially expressed lncRNAs and the predicted target genes that were significantly enriched in the Human papillomavirus infection pathway were analyzed by RT-qPCR. The results showed that several lncRNAs were co-expressed with their target genes. One of the lncRNAs called MSTRG15394 and its target gene, encoding a secreted protease inhibitor (PI), were up-regulated at the transcriptional level after RBSDV infection. Knockdown of MSTRG15394 could down-regulate the PI expression at mRNA level. Inhibition of either MSTRG15394 or PI expression by RNA interference promoted RBSDV accumulation in L. striatellus midgut. Our finding provides new insights into the function of lncRNAs in regulating virus infection in an important insect vector.

PURPOSE:To investigate the role of thioredoxin 2 (Trx2) inhibition induced by intracellular methylglyoxal (MGO) in pancreatic beta-cell mitochondrial dysfunction and apoptosis.METHODS:Rat pancreatic beta-cell line INS-1 cells were treated with Glo1 siRNAs or exogenous MGO to increase intracellular MGO. AGEs formation was detected by ELISA and mitochondrial ROS was detected by probe MitoSOX. Transmission electron microscopy (TEM) analysis and ATP content were measured to evaluate mitochondrial function. Trx2 expression was manipulated by overexpression with recombinant Trx2 lentivirus or knockdown with Trx2 siRNAs, and effects on apoptosis and insulin secretion were measured by flow cytometry and ELISA, respectively.RESULTS:The increase of intracellular MGO by Glo1 blockage or MGO treatment led to advanced glycation end products (AGEs) overproduction, mitochondrial ROS increase, and insulin secretion paralysis. These were probably due to MGO-induced inhibition of mitochondrial Trx2. Trx2 inhibition by blockage of either Glo1 or Trx2 impaired mitochondrial integrity, inhibited cytochrome C oxidases subunit 1 and 4 (Cox1 and Cox4) expression and further reduced ATP generation, and all of these might lead to insulin paralysis; whereas Trx2 overexpression partially reversed MGO-induced oxidative stress, attenuated insulin secretion by preventing mitochondrial damage. Trx2 overexpression also retarded MGO-induced apoptosis of INS-1 cell through inhibiting ASK1 activation and downregulation of the ASK1-p38 MAPK pathway.CONCLUSIONS:Our results reveal a possible mechanism for beta-cell oxidative damage upon intracellular MGO-induced Trx2 inactivation and mitochondrial dysfunction and apoptosis.

OBJECTIVE:To elucidate the potential roles of the lncRNA-mediated competitive endogenous RNA (ceRNA) network in the pathogenesis of bronchopulmonary dysplasia (BPD), we performed an integrated bioinformatics analysis based on miRNA and mRNA microarray datasets between BPD and normal samples.STUDY DESIGN:The mRNA and miRNA expression profiles of BPD were downloaded from the Gene Expression Omnibus (GEO) database to perform an integrated analysis. The limma package was used to identify differentially expressed genes (DEGs) and differentially expressed miRNA (DEmiRs), followed by functional enrichment analysis of DEGs. DEmiR-DEG and DEmiRNA-lncRNA interactions were predicted. Subsequently, the lncRNA-related ceRNA network was structured. Finally, a newborn BPD mouse model was established, and quantitative real-time PCR (qPCR) was used to validate the expression of the selected mRNAs, miRNAs, and lncRNAs.RESULTS:A total of 445 DEGs and 155 DEmiRs were obtained by comparing BPD samples and normal samples. Functional enrichment analysis showed that DEGs were primarily enriched in GO terms such as cell division and inflammatory response; and DEGs were mainly involved in the p53 signaling pathway. The miR17hg-miR-130b-3p-roundabout guidance receptor 2 (Robo2) and GM20455-miR-34a-5p-BMP/retinoic acid-inducible neural specific 1 (Brinp1) ceRNA axes were obtained by constructing the ceRNA network. In addition, the upregulation of Robo2 and miR17hg while the downregulation of miR-130b-3p; as well as the upregulation of Brinp1 and GM20455 but the downregulation of miR-34a-5p were validated by qPCR.CONCLUSION:The miR17hg-miR-130b-3p-Robo2 and GM20455-miR-34a-5p-Brinp1 axes may serve important role in the development of BPD. These findings might provide novel insight for a comprehensive understanding of molecular mechanisms in BPD, and genes in the ceRNA network might be considered as potential biomarkers and therapeutic targets against BPD.

Amynthas triastriatus (Oligochaete: Megascolecidae) is a widely distributed endemic species in Southern China. To shed light on the population genetic diversity and to elucidate the population differentiation and dispersal of A. triastriatus, a population genetic structure study was undertaken based on samples from 35 locations collected from 2010 to 2016. Two exclusive lineages within A. triastriatus-lineage A and lineage B-were revealed. Lineage A was mainly distributed at high altitudes while lineage B was mainly distributed at low altitudes in Southeast China. The genetic diversity indices indicated that the populations of A. triastriatus had a strong genetic structure and distinct dispersal histories underlying the haplogroups observed in this study. Combined with morphological differences, these results indicated a new cryptic subspecies of A. triastriatus. Lineage A was almost degenerated to parthenogenesis and lineage B had a trend to parthenogenesis, which suggested that parthenogenesis could be an internal factor that influenced the differentiation and dispersal of A. triastriatus. The divergence time estimates showed that A. triastriatus originated around Guangxi and Guangdong provinces and generated into two main lineages 2.97 Ma (95%: 2.17-3.15 Ma) at the time of Quaternary glaciation (2.58 Ma), which suggested that the Quaternary glaciation may have been one of main factors that promoted the colonization of A. triastriatus.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children, with evidence that the maternal diet and the early life nutritional environment are potential risk for such disease. This study was aimed to investigate the effects of maternal high-fat diet (HFD) on the occurrence of NAFLD in offspring rats and the underlying mechanisms. In this study, the incidence of NAFLD was compared in F1 offspring rats between the maternal HFD group and standard chow (SC) group. In addition, the expression levels of inflammatory cytokines in the placenta, in the umbilical cord blood, and in the livers of neonate offsprings were compared between two groups. HepG2 cells were treated with recombinant IL6 (rIL6) to assess stearoyl-CoA desaturase 1 (SCD1) expression and lipid synthesis in an inflammatory condition. Lipid accumulation was assayed in both SCD1 overexpression and interference HepG2 cells as well as in neonatal rats. Our results showed that HFD exposure before and throughout the pregnancy induced the elevated hepatic TG content of F1 neonates. The levels of inflammatory cytokines in the placenta, umbilical cord blood, and the livers of HFD F1 neonates were significantly higher than those of the SC group. In addition, rIL6 treatment led to TG accumulation accompanied by the upregulation of SCD1 in HepG2 cell lines. Overexpression of SCD1 led to the accumulation of TG contents in HepG2 cells, whereas Scd1 knockdown attenuated the effects of rIL6 treatment. Overexpression of SCD1 in F1 neonatal rats led to hepatic lipid accumulation. Our study indicated that maternal HFD led to intrauterine inflammation, which subsequently caused transgenerationally abnormal hepatic lipid metabolism of F1 neonates. This modulation might be mediated by upregulating SCD1 expression in hepatic cells.

Despite the ecological function of earthworms being of undeniable importance, little is known about their population genetic diversity, dispersal, and gene flow patterns. Here, we applied 769,957 single-nucleotide polymorphisms (SNPs) gathered by restriction site-associated DNA sequencing (RAD-seq) to unearth the genetic variability of populations of the earthworm Amynthas_YN2017 sp. collected from Western Yunnan, China. The neighbor-joining (NJ) tree method revealed that 30 individuals strongly clustered into three lineages (G2, G3, and G5 lineages) that coincided with the geographic distribution proximity of the sampling locations. There was a low level of genetic differentiation among these lineages with an average genetic differentiation (F-ST) value ranging from 0.080 to 0.135. Clustering analysis demonstrated a clear population genetic structure with a low level of admixture. There was only one migration edge in the population from the G3 lineage to the G2 lineage. Therefore, we presume that a reduction in gene flow caused by geographic isolation influences the population genetic differentiation of Amynthas_YN2017 sp. Additionally, the presence of river (Nujiang River) as geographical barrier is likely to have limited the gene flow. Overall, the large number of SNPs gathered by RAD-seq reveals a significant population genetic structure over a restricted geographic scale, highlighting that the RAD-seq approach could be used to explore the population phylogenetic relationships and population genetic diversity of earthworms.

The core of standardized training for residents is the cultivation of clinical practice ability,which is also the main content of the professional degree graduate training.With the integration of professional degree graduate training and standardized training of residents,the evaluation system of professional degree graduate tutors should be included in the quality index of graduate clinical skills training.Through the methods of document retrieval and expert consultation,the index structure,the examination content and the weight were set up,and the detailed rules for the evaluation of the professional degree graduate tutors were established to guide them strengthen the training of clinical skills for graduates and improve the cultivation quality of professional degree graduates.