The Relationship Between Perceived Stress, Impulsivity, Executive Dysfunction and Non-Suicidal Self-Injury Thoughts Among Chinese College Students: A Gender Difference Study.

Background: The present study aimed to investigate the potential role of perceived stress, impulsivity trait, executive dysfunction in non-suicidal self-injury (NSSI) thoughts among college students, as well as the gender differences. Methods: A sample of 890 university students completed self-report measures of NSSI thoughts in the past month, the level of perceived stress, impulsivity traits, and executive dysfunction. Results: Compared to those with low level of perceived stress, participants with high level of perceived stress reported significant higher levels of impulsivity trait and executive dysfunction, and higher frequency of NSSI thoughts, and there were no gender differences. Male participants with NSSI thoughts, compared to males without NSSI thoughts, reported significant higher levels of perceived stress and executive dysfunction. Female participants with NSSI thoughts, compared to females without NSSI thoughts, reported significant higher levels of perceived stress, impulsivity trait, and executive dysfunction. Hierarchical regression analysis revealed only executive dysfunction was associated with NSSI thoughts in males, while only perceived stress was associated with NSSI thoughts in females. Conclusion: This study revealed different influence factors for NSSI thoughts in male and female college students. NSSI thoughts in males were more likely associated with executive dysfunction while in females were due to recently perceived stress.

Impetigo herpetiformis in the second trimester: a case report and review of the literature.

Impetigo herpetiformis is a rare skin disease that most often occurs in the third trimester of pregnancy. It is currently considered as a form of generalized pustular psoriasis and the typical skin lesions comprise small sterile pustules. Here, a case of impetigo herpetiformis in the second trimester of pregnancy after 7 weeks of hydroxychloroquine administration for suspected Sjogren's syndrome is reported. Treatment with anti-infective, anti-inflammatory and immunosuppressive medication did not improve the patient's condition. Following delivery of a live male by emergency caesarean section at 29 weeks' gestation, the rash was reported to be completely resolved by 3 months postpartum. Previously published cases of impetigo herpetiformis in the second trimester of pregnancy that were retrieved from a search of the PubMed database are also reviewed and discussed.

A model to predict delivery time following induction of labor at term with a dinoprostone vaginal insert: a retrospective study.

BACKGROUND: Dinoprostone vaginal insert is the most common pharmacological method for induction of labor (IOL); however, studies on assessing the time to vaginal delivery (DT) following dinoprostone administration are limited. AIMS: We sought to identify the primary factors influencing DT in women from central China, at or beyond term, who underwent IOL with dinoprostone vaginal inserts. METHODS: In this retrospective observational study, we analyzed the data of 1562 women at 37 weeks 0 days to 41 weeks 6 days of gestation who underwent dinoprostone-induced labor between January 1st, 2019, and December 31st, 2021. The outcomes of interest were vaginal or cesarean delivery and factors influencing DT, including maternal complications and neonatal characteristics. RESULTS: Among the enrolled women, 71% (1109/1562) delivered vaginally, with median DT of 740.50 min (interquartile range 443.25 to 1264.50 min). Of the remaining 29% (453/1562), who delivered by cesarean section, 11.9% (54/453) were multiparous. Multiple linear regression analysis showed that multiparity, advanced maternal age, fetal macrosomia, premature rupture of membranes (PROM), and daytime insertion of dinoprostone were the factors that significantly influenced DT. Time to vaginal delivery increased with advanced maternal age and fetal macrosomia and decreased with multiparity, PROM, and daytime insertion of dinoprostone. A mathematical model was developed to integrate these factors for predicting DT: Y = 804.478 - 125.284 × multiparity + 765.637 × advanced maternal age + 411.511 × fetal macrosomia-593.358 × daytime insertion of dinoprostone - 125.284 × PROM. CONCLUSIONS: Our findings may help obstetricians estimate the DT before placing a dinoprostone insert, which may improve patient management in busy maternity wards and minimize potential risks.

Physiological and transcriptomic analysis reveal the crucial factors in heat stress response of red raspberry 'Polka' seedlings.

With global climate warming, recurring extreme heat and high temperatures irreversibly damage plants. Raspberries, known for their nutritional and medicinal value, are in high demand worldwide. Thus, it is important to study how high-temperature stress (HTS) affects raspberries. The physiological and biochemical responses and molecular genetic mechanisms of raspberry leaves to different HTS treatments were investigated: mild high temperature at 35°C (HT35), severe high temperature at 40°C (HT40), and the control at room temperature of 25°C (CK). The physiological results suggested that leaves in both the 35°C and 40°C treatments showed maximum relative conductivity at 4 d of stress, increasing by 28.54% and 43.36%, respectively, compared to CK. Throughout the stress period (0-4 d), malondialdehyde (MDA) and soluble protein contents of raspberry leaves increased under HT35 and HT40 treatments, while soluble sugar content first decreased and then increased. Catalase (CAT) activity increased, superoxide dismutase (SOD) activity first increased and then decreased, and peroxidase (POD) activity gradually decreased. Photosynthetic and fluorescence responses of raspberry leaves showed the most severe impairment after 4 d of stress. Transcriptomics results revealed significant alterations in 42 HSP family genes, two SOD-related differentially expressed genes (DEGs), 25 POD-related DEGs, three CAT-related DEGs, and 38 photosynthesis-related DEGs under HTS. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly enriched in photosynthesis-antenna proteins, pentose and glucuronide interconversion, phenylpropane biosynthesis, and indole alkaloid biosynthesis. HTS induced excessive ROS accumulation in raspberry leaves, causing oxidative damage in plant cells and subsequently reducing photosynthesis in raspberry leaves. This reduction in photosynthesis, in turn, affects photosynthetic carbon fixation and starch and sucrose metabolism, which, combined with phenol propane biosynthesis, mitigates the HTS-induced damage.

Effect of physiological pH on the molecular characteristics, rheological behavior, and molecular dynamics of κ-carrageenan/casein.

Introduction: During gastrointestinal digestion, κ-carrageenan (κ-CGN) undergoes physicochemical changes, which associated with the risk of colitis. Methods: To understand the effect of physiological pH on the conformational transition and binding stability of κ-CGN and κ-carrageenan/casein (κ-CC), we conducted experiments at pH 3.0 (gastric environment) and pH 7.0 (intestinal environment). We evaluated zeta potential, free sulfate group content, Fourier transform infrared spectroscopy, thermodynamic properties, microstructure, and molecular mechanism. Results and Discussion: Our results revealed that the helical conformation of κ-CGN and κ-CC were more ordered and stable, and sulfate group exposure both lower in the intestinal environment (pH 7.0). However, in gastric environment (pH 3.0), the charge density of κ-CGN decreased, accompanied by random curling conformation and free sulfate group content increased. In contrast, the intermolecular interactions between κ-CGN and casein increased in gastric acid environments due to casein flocculation and secondary structure folding, and significantly reduced the exposure of free sulfate groups of κ-CGN. Our research results provide an important theoretical basis for elucidating the molecular mechanism and structure-activity relationship of κ-CGN under casein matrix to protect the mucosal barrier and inhibit colitis, and are of great significance for guiding and expanding the safe application of κ-CGN, thus assisting food nutrition to be absorbed.

How does carrageenan cause colitis? A review.

Carrageenan is a common additive, but mounting studies have reported that it may cause or aggravate inflammation in the intestines. The safety of carrageenan remains controversial and its inflammatory mechanisms are unclear. In this review, the pathogenesis of colitis by carrageenans was discussed. We analyzed the pathogenesis of inflammatory bowel disease, followed that line of thought, the existing evidence of carrageenans causing colitis in cellular and animal models was summarized to draw its colitis pathogenesis. Two pathways were described including: 1) carrageenan changed the composition of intestinal microbiota, especially Akkermansia muciniphila, which destroyed the mucosal barrier and triggered the inflammatory immune response; and 2) carrageenan directly contacted with receptors on epithelial cells and activated the NF-κB inflammatory pathway. This review aim to provide guidance for exploring the treatment of colitis caused by carrageenan, and safe processing and utilization of carrageenan in food industry, which is worthy of study in the future.

Association of low birthweight and small for gestational age with maternal ferritin levels: A retrospective cohort study in China.

Background: Birthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial. Objective: This retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA). Methods: Newborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose-response manners of ferritin level and birthweight outcomes. Results: A total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37-2.32) for LBW and 1.87 (95% CI 1.38-2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03-4.47) for Quartile 2, 3.13 (95% CI 1.47-6.69) for Quartile 3, and 3.63 (95% CI 1.52-8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively. Conclusions: Our findings found a linear dose-response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.

Bacterial Succession in Microbial Biofilm as a Potential Indicator for Postmortem Submersion Interval Estimation.

Bacteria acts as the main decomposer during the process of biodegradation by microbial communities in the ecosystem. Numerous studies have revealed the bacterial succession patterns during carcass decomposition in the terrestrial setting. The machine learning algorithm-generated models based on such temporal succession patterns have been developed for the postmortem interval (PMI) estimation. However, the bacterial succession that occurs on decomposing carcasses in the aquatic environment is poorly understood. In the forensic practice, the postmortem submersion interval (PMSI), which approximately equals to the PMI in most of the common drowning cases, has long been problematic to determine. In the present study, bacterial successions in the epinecrotic biofilm samples collected from the decomposing swine cadavers submerged in water were analyzed by sequencing the variable region 4 (V4) of 16S rDNA. The succession patterns between the repeated experimental settings were repeatable. Using the machine learning algorithm for establishing random forest (RF) models, the microbial community succession patterns in the epinecrotic biofilm samples taken during the 56-day winter trial and 21-day summer trial were determined to be used as the PMSI predictors with the mean absolute error (MAE) of 17.87 ± 2.48 ADD (≈1.3 day) and 20.59 ± 4.89 ADD (≈0.7 day), respectively. Significant differences were observed between the seasons and between the substrates. The data presented in this research suggested that the influences of the environmental factors and the aquatic bacterioplankton on succession patterns of the biofilm bacteria were of great significance. The related mechanisms of such influence need to be further studied and clarified in depth to consider epinecrotic biofilm as a reliable predictor in the forensic investigations.

Identification of Independent and Shared Metabolic Responses to High-Fiber and Antibiotic Treatments in Fecal Metabolome of Grow-Finish Pigs.

Feeding high-fiber (HF) coproducts to grow-finish pigs as a cost-saving practice could compromise growth performance, while the inclusion of antibiotic growth promoters (AGPs) may improve it. The hindgut is a shared site of actions between fiber and AGPs. However, whether the metabolic interactions between them could occur in the digestive tract of pigs and then become detectable in feces have not been well-examined. In this study, wheat middling (WM), a HF coproduct, and bacitracin, a peptide antibiotic (AB), were fed to 128 grow-finish pigs for 98 days following a 2 × 2 factorial design, including antibiotic-free (AF) + low fiber (LF); AF + HF; AB + LF, and AB + HF, for growth and metabolic responses. The growth performance of the pigs was compromised by HF feedings but not by AB. A metabolomic analysis of fecal samples collected on day 28 of feeding showed that WM elicited comprehensive metabolic changes, especially in amino acids, fatty acids, and their microbial metabolites, while bacitracin caused selective metabolic changes, including in secondary bile acids. Limited metabolic interactions occurred between fiber and AB treatments. Moreover, the correlations between individual fecal metabolites and growth support the usage of fecal metabolome as a source of biomarkers for monitoring and predicting the metabolic performance of grow-finish pigs.

Proteomic Analysis of Human Milk Reveals Nutritional and Immune Benefits in the Colostrum from Mothers with COVID-19.

Despite the well-known benefits of breastfeeding and the World Health Organization's breastfeeding recommendations for COVID-19 infected mothers, whether these mothers should be encouraged to breastfeed is under debate due to concern about the risk of virus transmission and lack of evidence of breastmilk's protective effects against the virus. Here, we provide a molecular basis for the breastfeeding recommendation through mass spectrometry (MS)-based proteomics and glycosylation analysis of immune-related proteins in both colostrum and mature breastmilk collected from COVID-19 patients and healthy donors. The total protein amounts in the COVID-19 colostrum group were significantly higher than in the control group. While casein proteins in COVID-19 colostrum exhibited significantly lower abundances, immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, were upregulated. These proteins were detected with unique site-specific glycan structures and improved glycosylation diversity that are beneficial for recognizing epitopes and blocking viral entry. Such adaptive differences in milk from COVID-19 mothers tended to fade in mature milk from the same mothers one month postpartum. These results suggest that feeding infants colostrum from COVID-19 mothers confers both nutritional and immune benefits, and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.

Gut Microbiome Alterations and Hepatic Metabolic Flexibility in the Gansu Zokor, Eospalax cansus: Adaptation to Hypoxic Niches.

The Gansu zokor (Eospalax cansus), a typical subterranean rodent endemic to the Chinese Loess Plateau, spends almost its whole life in its self-constructed underground burrows and has strong adaptability to ambient hypoxia. Energy adaptation is the key to supporting hypoxia tolerance, and recent studies have shown that the intestinal microbiota has an evident effect on energy metabolism. However, how the gut microbiome of Gansu zokor will change in response to hypoxia and the metabolic role played by the microbiome have not been reported. Thus, we exposed Gansu zokors to severe hypoxia of 6.5% of O2 (6 or 44 h) or moderate hypoxia of 10.5% of O2 (44 h or 4 weeks), and then analyzed 16S rRNA sequencing, metagenomic sequencing, metagenomic binning, liver carbohydrate metabolites, and the related molecular levels. Our results showed that the hypoxia altered the microbiota composition of Gansu zokor, and the relative contribution of Ileibacterium to carbohydrate metabolism became increased under hypoxia, such as glycolysis and fructose metabolism. Furthermore, Gansu zokor liver enhanced carbohydrate metabolism under the short-term (6 or 44 h) hypoxia but it was suppressed under the long-term (4 weeks) hypoxia. Interestingly, under all hypoxia conditions, Gansu zokor liver exhibited enhanced fructose-driven metabolism through increased expression of the GLUT5 fructose transporter, ketohexokinase (KHK), aldolase B (ALDOB), and aldolase C (ALDOC), as well as increased KHK enzymatic activity and fructose utilization. Overall, our results suggest that the altered gut microbiota mediates the carbohydrate metabolic pattern under hypoxia, possibly contributing to the hepatic metabolic flexibility in Gansu zokor, which leads to better adaptation to hypoxic environments.

Ultrasound-assisted solubilization of calcium from micrometer-scale ground fish bone particles.

In order to promote the extraction of biological calcium from fish bone, ultrasonication was used to process micrometer-scale fish bone particles (MFPs) and investigate the mechanism of action in relation to bone structure. With ultrasonication treatment (300 W, 60°C, 2 h), the content of calcium release increased by 25.6%. Calcium release reached 94.0% of total calcium after 24-h treatment. The surface of the MFPs was significantly damaged by ultrasound-induced cavitation, resulting in holes and separation of the layered structure. X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) analysis demonstrated that the crystalline structure of hydroxyapatite was disrupted, the triple helical structure of mineralized collagen fibrils (MCFs) was loosened, and hydrogen bonding in collagen decreased, facilitating the release of hydroxyapatite crystals. Thus, ultrasonication may be a practical alternative to nanomilling for industrial processing of waste fish bones to produce soluble calcium as an ingredient in calcium supplements and supplemented foods.

Identification, diagnosis, and early intervention of children with developmental language disorder in Ningxia.

Background: It is reported that the incidence of language development disorder in children at the age of 2 is as high as 17.0%. Timely discovery of the high-risk factors of language development disorder in children and early intervention can greatly reduce the incidence of language development disorder and shorten the course and condition of the patients with language development disorder. Therefore, in order to facilitate prompt diagnosis and early interventions for children with language development disorder (DLD) and improve their language ability, this study explored the influence of perinatal factors on the language development of children in Ningxia and identified the unfavorable and favorable factors that influenced language development. Methods: Children diagnosed in the General Hospital of Ningxia Medical University during 2018-2021 who met the screening criteria for DLD and practical pediatric diagnostic criteria for DLD were enrolled in this study. Perinatal factors (gestational age, weight, sex, delivery mode, maternal age, presence of intrauterine infection, asphyxia) were retrospectively analyzed. The perinatal factors affecting language development were assessed using a one-way analysis of variance (ANOVA). Results: Among 1,500 children aged 0-3, 240 cases (16.00%) had language delay. Of these, 122 were male and 118 were female. There were 115 cases of comprehension and expression disorder, 30 cases of articulation disorder, and 90 cases of mixed manifestation. And there were 194 cases with definite intrauterine and perinatal high-risk factors or neonatal diseases, accounting for 80.83% of the total number of children with language delay. Conclusions: In Ningxia, factors in the neonatal period are the main cause of DLD, followed by fetal and maternal factors. Ischemic encephalopathy is the most common factor.

Application Effect of Doctor-Nurse-Patient Integration Model Based on Heart Rate Management Strategies in Middle-Aged and Young Outpatients with Hypertension.

Objective: In this study, a doctor-nurse-patient integration management scheme based on heart rate (HR) management strategies was constructed to explore its application effect in the health management of young and middle-aged outpatients with hypertension. Methods: A total of 75 young and middle-aged patients with essential hypertension admitted to the Outpatient Department of Cardiology of Heji Hospital Affiliated to Changzhi Medical College, Shanxi Province, from October 2019 to July 2020 were selected and divided into an observation group (n = 37) and a control group (n = 38) according to different treatment methods. The control group was treated with routine health education, basis on which, the observation group was additionally intervened by the doctor-nurse-patient integration model established upon HR management strategies. The resting heart rate (RHR) awareness, medication compliance, RHR, systolic/diastolic blood pressure (SBP/DBP), and self-management ability were compared between the two groups before and 3 months after intervention. The diet control rate, hypertension awareness rate, and regular review rate were also compared. Results: The RHR awareness and medication compliance were significantly higher in the observation group compared with the control group after intervention (P < 0.05). There were 29 patients with high compliance in the observation group and 19 in the control group, with a significant difference between the two groups (P < 0.05). The mean RHR, as well as the mean SBP and DBP in the observation group, were significantly lower than those in the control group (P < 0.05). In terms of health behavior assessment, the observation group outperformed the control group in the score of each dimension of self-actualization, health responsibility, stress management, interpersonal support, exercise, and nutrition (P < 0.05). In addition, the self-management ability of diet, exercise, medication, blood pressure (BP) monitoring, and disease awareness was significantly higher in the observation group compared with the control group. Conclusions: For middle-aged and young outpatients with hypertension, the doctor-nurse-patient integration model based on HR management strategies can improve the RHR awareness of patients and improve their medication compliance and self-management ability, thus better controlling the levels of RHR and BP.

Identification and Functional Analysis of lncRNAs Responsive to Hypoxia in Eospalax fontanierii.

Subterranean rodents could maintain their normal activities in hypoxic environments underground. Eospalax fontanierii, as one kind of subterranean rodent found in China can survive very low oxygen concentration in labs. It has been demonstrated that long non-coding RNAs (lncRNAs) have important roles in gene expression regulations at different levels and some lncRNAs were found as hypoxia-regulated lncRNAs in cancers. We predicted thousands of lncRNAs in the liver and heart tissues by analyzing RNA-Seq data in Eospalax fontanierii. Those lncRNAs often have shorter lengths, lower expression levels, and lower GC contents than mRNAs. Majors of lncRNAs have expression peaks in hypoxia conditions. We found 1128 DE-lncRNAs (differential expressed lncRNAs) responding to hypoxia. To search the miRNA regulation network for lncRNAs, we predicted 471 and 92 DE-lncRNAs acting as potential miRNA target and target mimics, respectively. We also predicted the functions of DE-lncRNAs based on the co-expression networks of lncRNA-mRNA. The DE-lncRNAs participated in the functions of biological regulation, signaling, development, oxoacid metabolic process, lipid metabolic/biosynthetic process, and catalytic activity. As the first study of lncRNAs in Eospalax fontanierii, our results show that lncRNAs are popular in transcriptome widely and can participate in multiple biological processes in hypoxia responses.

Facial Fabrication of Large-Scale SERS-Active Substrate Based on Self-Assembled Monolayer of Silver Nanoparticles on CTAB-Modified Silicon for Analytical Applications.

Surface-enhanced Raman spectroscopy (SERS) has been proven to be a promising analytical technique with sensitivity at the single-molecule level. However, one of the key problems preventing its real-world application lies in the great challenges that are encountered in the preparation of large-scale, reproducible, and highly sensitive SERS-active substrates. In this work, a new strategy is developed to fabricate an Ag collide SERS substrate by using cetyltrimethylammonium bromide (CTAB) as a connection agent. The developed SERS substrate can be developed on a large scale and is highly efficient, and it has high-density "hot spots" that enhance the yield enormously. We employed 4-methylbenzenethiol(4-MBT) as the SERS probe due to the strong Ag-S linkage. The SERS enhancement factor (EF) was calculated to be ~2.6 × 106. The efficacy of the proposed substrate is demonstrated for the detection of malachite green (MG) as an example. The limit of detection (LOD) for the MG assay is brought down to 1.0 × 10-11 M, and the relative standard deviation (RSD) for the intensity of the main Raman vibration modes (1620, 1038 cm-1) is less than 20%.

P-gp expression inhibition mediates placental glucocorticoid barrier opening and fetal weight loss.

BACKGROUND: Prenatal adverse environments can cause fetal intrauterine growth retardation (IUGR) and higher susceptibility to multiple diseases after birth, related to multi-organ development programming changes mediated by intrauterine overexposure to maternal glucocorticoids. As a glucocorticoid barrier, P-glycoprotein (P-gp) is highly expressed in placental syncytiotrophoblasts; however, the effect of P-gp on the occurrence of IUGR remains unclear. METHODS: Human placenta and fetal cord blood samples of IUGR fetuses were collected, and the related indexes were detected. Pregnant Wistar rats were administered with 30 mg/kg·d (low dose) and 120 mg/kg·d (high dose) caffeine from gestational day (GD) 9 to 20 to construct the rat IUGR model. Pregnant mice were administered with caffeine (120 mg/kg·d) separately or combined with sodium ferulate (50 mg/kg·d) from gestational day GD 9 to 18 to confirm the intervention target on fetal weight loss caused by prenatal caffeine exposure (PCE). The fetal serum/placental corticosterone level, placental P-gp expression, and related indicator changes were analyzed. In vitro, primary human trophoblasts and BeWo cells were used to confirm the effect of caffeine on P-gp and its mechanism. RESULTS: The placental P-gp expression was significantly reduced, but the umbilical cord blood cortisol level was increased in clinical samples of the IUGR neonates, which were positively and negatively correlated with the neonatal birth weight, respectively. Meanwhile, in the PCE-induced IUGR rat model, the placental P-gp expression of IUGR rats was decreased while the corticosterone levels of the placentas/fetal blood were increased, which were positively and negatively correlated with the decreased placental/fetal weights, respectively. Combined with the PCE-induced IUGR rat model, in vitro caffeine-treated placental trophoblasts, we confirmed that caffeine decreased the histone acetylation and expression of P-gp via RYR/JNK/YB-1/P300 pathway, which inhibited placental and fetal development. We further demonstrated that P-gp inducer sodium ferulate could reverse the inhibitory effect of caffeine on the fetal body/placental weight. Finally, clinical specimens and other animal models of IUGR also confirmed that the JNK/YB-1 pathway is a co-regulatory mechanism of P-gp expression inhibition, among which the expression of YB-1 is the most stable. Therefore, we proposed that YB-1 could be used as the potential early warning target for the opening of the placental glucocorticoid barrier, the occurrence of IUGR, and the susceptibility of a variety of diseases. CONCLUSIONS: This study, for the first time, clarified the critical role and epigenetic regulation mechanism of P-gp in mediating the opening mechanism of the placental glucocorticoid barrier, providing a novel idea for exploring the early warning, prevention, and treatment strategies of IUGR.

Oxidative Stress and Its Related Factors in Latent Autoimmune Diabetes in Adults.

AIMS: Few research was reported to explore oxidative stress in individuals with latent autoimmune diabetes in adults (LADA). Therefore, our goal is to study oxidative stress and related factors in LADA patients. METHODS: In this study, 250 Chinese inpatients were diagnosed with LADA (n = 110) and type 2 diabetes mellitus (n = 140) and 140 healthy volunteers were recruited. Moreover, individuals with LADA were followed for 6 months to evaluate whether short-term glycemic control during hospitalization can improve oxidative stress. Clinical and laboratory measurements of height, weight, blood pressure, glycosylated hemoglobin (HbA1c), blood lipids, 8-isoprostaglandin F2α (8-iso-PGF2α), and superoxide dismutase (SOD) were performed. Stepwise multiple regression analyses were used to assess factors that related to oxidative stress in individuals with LADA. RESULTS: Compared with patients with type 2 diabetes, individuals with LADA have better oxidative stress and worse oxidative stress than healthy volunteers. After multiple regression analyses, systolic blood pressure, HbA1c, duration of diabetes, and diabetic retinopathy were associated with 8-iso-PGF2α and HbA1c. Diabetic retinopathy and diabetic ketosis were associated with SOD in individuals with LADA. Our results also revealed that, after 6 months of follow-up, oxidative stress was improved to some extent in persons with LADA. CONCLUSIONS: Our results show that compared with type 2 diabetes, LADA means less oxidative stress, and compared with healthy volunteers, it means more oxidative stress. Systolic blood pressure, HbA1c, duration of diabetes, diabetic retinopathy, and ketosis were associated with oxidative stress in individuals with LADA. Furthermore, short-term glycemic control can improve oxidative stress to some extent in individuals with LADA.

Prenatal ethanol exposure increases maternal bile acids through placental transport pathway.

High maternal serum bile acid level is common and sometimes harmful to the gravida. This study aimed to confirm the bile acid phenotypic change caused by prenatal ethanol exposure (PEE) and elucidate its placental mechanism. Pregnant Wistar rats were administered intragastrically with ethanol 4 g/kg⋅d from gestational day 9-20. Total bile acids (TBA) were detected in maternal, fetal serum and placental tissues, increasing significantly in the serum but no significant change in the placental tissues. Meta-analysis was performed and verified the efficacy of the PEE-induced model based on published data from several relevant studies. Mining of microarray data from human and rat placental sources identified the involvement of bile acid metabolism and its significant genes, which were verified by RT-qPCR and western blotting on tissues and treated BeWo cells with the administration of FXR/PXR siRNAs or FXR/PXR agonists. Our examination, consistent with microarray data and wet experiments, showed that organic anion transporter polypeptide-related protein 2B1 (Oatp2b1), multidrug resistance-associated proteins 3 (Mrp3) and breast cancer resistance protein (Bcrp) expression were increased, while nuclear receptor farnesoid X receptor (Fxr) was decreased but pregnane X receptor (Pxr) was increased. Furthermore, the interventional experiments confirmed that FXR regulated Bcrp while PXR regulated Oatp2b1 and Mrp3. In summary, PEE could induce high bile acid level in maternal serum and its mechanism is associated with the high expression of BCRP/MRP3/OATP2B1 in the placenta through up-regulating PXR and down-regulating FXR, thereby leading to an excessive bile acid transport to maternal blood via the placenta. Our study provides a novel perspective in terms of placenta, explaining the increased maternal blood bile acids under the toxicity of PEE.