Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression.

Growing evidence suggests that the exposure of bisphenol A (BPA), an endocrine disruptor that commonly present in the environment, can impair reproduction. However, conflicting results have been reported, and the underlying mechanism has not been fully understood. In this study, 3-week-old male mice were oral exposed to 50 mg/kg/d BPA or equivalent corn oil for 28 days. Their testis and epididymis were then collected for morphology examination by HE stains. The number of sperm was counted, and the morphology was analyzed by PNA (peptide nucleic acid) and pap staining. Fertilization capacity and successful rate were analyzed after mating with wide-type females. Spermatid DNA damage and apoptosis were evaluated by DFI, γH2AX stain, and TUNEL assay. RNA sequencing analysis was conducted to identify differentially expressed genes in testicular tissue of mice exposed to BPA. RNA interference was used to verify the regulatory mechanism of BPA exposure on gene expression in GC-2 cells. Our data showed that the total number of sperm was decreased and the morphology was impaired in BPA-exposed mice. In addition, the serum testosterone level and fertilization efficiency were also reduced. Mechanism studies showed that BPA could suppress the expression of PCBP2, a key regulatory gene in spermatid development, by activating the EZH2/H3K27me3. In conclusion, we found that BPA exposure can impair spermatid development via affecting key gene expression that is at least partially due to epigenetic modification.

BPA induces placental trophoblast proliferation inhibition and fetal growth restriction by inhibiting the expression of SRB1.

Bisphenol-A (BPA) is a common environmental toxicant that is known to be associated with fetal growth restriction (FGR). However, the mechanisms of how BPA induce FGR is poorly characterized. We conducted proteomics to identify the abnormal expression of SRB1 in female placental tissues with high BPA-induced FGR and further verified its decreased expression in human placenta and BeWo cells. Next, the effect of BPA on fetal development was further confirmed in pregnant C57BL/6 mice. The expression of SRB1 was consistently downregulated in human FGR placentas, BPA-exposed trophoblasts and mouse placentas. In addition, we found that SRB1 interacted with PCNA, and BPA exposure indirectly reduced the expression of PCNA and further inhibited placental proliferation. In vitro studies showed that BPA exposure reduced the expression of CDK1, CDK2, cyclin B and phosphorylated Rb in placental trophoblast cells, indicating cell cycle arrest after exposure to BPA. In addition, the expression of γ-H2AX and phosphorylated ATM was upregulated in BPA-exposed trophoblasts, indicating increased DNA damage. Our results indicate that BPA-induced FGR is achieved by reducing the expression of SRB1, inhibiting placental proliferation and increasing DNA damage. Our findings not only explain the mechanism of BPA-associated developmental toxicity but also shed light upon developing novel therapeutic targets.

Effect of the vertical facial pattern on the developmental relationship between the nasal bone and maxillary central incisors.

BACKGROUND: This study aimed to investigate the effect of vertical facial patterns on the developmental relationship between the nasal bone and maxillary central incisors. METHODS: In this retrospective comparative study, the lateral cephalograms of 213 subjects (51 Males, 162 Females) with skeletal Class I malocclusion (aged 18-32 years) were classified into three equal groups: (1) hyperdivergent, (2) normodivergent, and (3) hypodivergent facial patterns based on the mandibular plane inclination (S-N/Go-Me). Several sets of measurements were extracted: (1) gradient and length of the nasal bone and maxillary central incisor, (2) the distance from apex and root of the nasal bone, and (3) maxillary central incisor to the true perpendicular from the digitized lateral cephalograms. The significance level was considered at P < 0.05. RESULTS: The inclination angle and length between nasal bone and maxillary central incisor were positively correlated independent of vertical facial type. The inclination angle of the nasal bone in the hypodivergent group was significantly larger than the other two vertical facial patterns. The inclination angle of the maxillary central incisor increased successively in the hyperdivergent, normodivergent, and hypodivergent groups. The length of the nasal bone in the hyperdivergent group was significantly longer than that in the hypodivergent and normodivergent groups. The maxillary central incisor length in the hyperdivergent group was significantly longer than in the hypodivergent group. CONCLUSION: A correlation between nasal bone and maxillary central incisors during the growth and development of the maxillofacial region was found. In Class I malocclusion subjects, hypodivergent patients were more likely to have a prominent and relatively short nasal bone and maxillary central incisors and vice versa.

Mandibular asymmetry in patients with skeletal class I and skeletal class II Malocclusions: A cone-beam computed tomography study.

OBJECTIVE: To study the difference in mandibular asymmetry between patients with skeletal Class I and skeletal Class II malocclusions and analyze the correlation between mandibular asymmetry and different facial skeletal sagittal patterns based on CBCT measurements. METHODS: One hundred and twenty patients were selected according to the inclusion and exclusion criteria. Patients were divided into two groups (60 in the skeletal Class I group and 60 in the skeletal Class II group) based on ANB angles and Wits values. Patients' CBCT data were collected. Dolphin Imaging 11.0 was used to determine the mandibular anatomic landmarks and calculate the linear distance in patients in the two groups. RESULTS: Intragroup comparison: in skeletal Class I group, measurements of the most posterior point of the condyle (Cdpost), the outer lateral point of the condyle (Cdlat), sigmoid notch point (Sn)), coronoid process point (Cop), gonion point (GO) and antimony notch point (Ag), right>left (P<0.05); in skeletal Class II group, measurements of Cdpost and Cop, right>left (P<0.05). Intergroup comparison: for measurements of GO and Ag, skeletal Class I group>skeletal Class II group (P<0.05). The asymmetry of the Ag and GO points was negatively correlated with the ANB angle (p<0.05). CONCLUSION: Mandibular asymmetry was significantly different between patients with skeletal Class I and skeletal Class II malocclusions. The asymmetry of the mandible angle region in the former group was greater than that in the latter group, and the asymmetry of the mandibular angle was negatively correlated with the ANB angle.

Distribution of lean mass and mortality risk in patients with type 2 diabetes.

AIMS: The aim of the study is to evaluate the association of distribution of lean mass with the risk of all-cause mortality among patients with type 2 diabetes. METHODS: The present cohort study included 2 335 patients with type 2 diabetes. Lean mass was assessed by dual energy X-ray absorptiometry. Cox proportional hazards regressions were used to estimate the association of lean mass distribution on the risk of mortality. RESULTS: The average age of the patients was 58 years at baseline and 51.4% of patients were women. During a median follow-up of 4.31 years, 128 patients died. The multivariable-adjusted hazards ratios for all-cause mortality were 1.00, 1.63 (0.89-2.99), and 2.68(1.51-4.76) across the tertiles of android-to-gynoid lean mass ratio (P for trend < 0.001), respectively. The positive association of android-to-gynoid lean mass ratio with the risk of all-cause mortality was present among patients of different ages, body mass index ≥ 24 kg/m2, hemoglobin A1c ≥ 7.0%, nonsmokers, men, patients using insulin, and patients with diabetes durations of more than 10 years. CONCLUSIONS: Higher android-to-gynoid lean mass ratio, assessed by dual energy X-ray absorptiometry, was significantly associated with increased risk of all-cause mortality among patients with type 2 diabetes.

Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts.

The lung is a complex organ with various cell types having distinct roles. Antisense oligonucleotides (ASOs) have been studied in the lung, but it has been challenging to determine their effectiveness in each cell type due to the lack of appropriate analytical methods. We employed three distinct approaches to study silencing efficacy within different cell types. First, we used lineage markers to identify cell types in flow cytometry, and simultaneously measured ASO-induced silencing of cell-surface proteins CD47 or CD98. Second, we applied single-cell RNA sequencing (scRNA-seq) to measure silencing efficacy in distinct cell types; to the best of our knowledge, this is the first time scRNA-seq has been applied to measure the efficacy of oligonucleotide therapeutics. In both approaches, fibroblasts were the most susceptible to locally delivered ASOs, with significant silencing also in endothelial cells. Third, we confirmed that the robust silencing in fibroblasts is broadly applicable by silencing two targets expressed mainly in fibroblasts, Mfap4 and Adam33. Across independent approaches, we demonstrate that intratracheally administered LNA gapmer ASOs robustly induce gene silencing in lung fibroblasts. ASO-induced gene silencing in fibroblasts was durable, lasting 4-8 weeks after a single dose. Thus, lung fibroblasts are well aligned with ASOs as therapeutics.

CDKN2AIP is critical for spermiogenesis and germ cell development.

BACKGROUND: As a member of RNA-binding protein, CDKN2AIP has been shown to play a critical role in stem cell pluripotency and somatic differentiation. Recent studies indicate that Cdkn2aip is essential for spermatogonial self-renewal and proliferation through the activating Wnt-signaling pathway. However, the mechanisms of how Cdkn2aip regulate spermatogenesis is poorly characterized. RESULTS: We discovered that the CDKN2AIP was expressed in spermatocyte as well as spermatids and participated in spermiogenesis. Cdkn2aip-/- mice exhibited multiple sperm head defects accompanied by age dependent germ cell loss that might be result of protamine replacement failure and impaired SUN1 expression. Loss of Cdkn2aip expression in male mice resulted in synapsis failure in 19% of all spermatocytes and increased apoptosis due to damaged DNA double-strand break (DSB) repair and crossover formation. In vitro, knockdown of Cdkn2aip was associated with extended S phase, increased DNA damage and apoptosis. CONCLUSIONS: Our findings not only identified the importance of CDKN2AIP in spermiogenesis and germ cell development, but also provided insight upon the driving mechanism.

CDKN2AIP-induced cell senescence and apoptosis of testicular seminoma are associated with CARM1 and eIF4ß.

Testicular seminoma is a relatively rare tumor which is mostly detected in male population aged from 15 to 35 years old. Although several molecular biomarkers have been identified to be associated with testicular seminoma pathogenesis, the exact mechanism for testicular seminoma progression remains largely unknown. CDKN2A interacting protein (CDKN2AIP) has previously been identified as a tumor suppressor in multiple malignant diseases. In this study, we aimed to further explore its role in testicular seminoma as well as the underlying molecular mechanisms. Retrospective testicular seminoma clinical samples, normal tissues, NTERA-2 cell line, and mouse xenograft models were used in this study. RT-qPCR, western blot analysis, immunofluorescence microscopy, Co-IP and IP-MS experiments were performed to detect the expression of CDKN2AIP and its interaction with CARM1 and eIF4ß. SA-ß-gal staining assay and H3K9me3 activity experiments were used to subsequently evaluate the cell senescence and apoptosis. Mouse xenograft animal model was used for in vivo study. The results showed that CDKN2AIP is highly expressed in normal testis samples, and is significantly suppressed in testicular seminoma clinical samples and cell line model. Up-regulation of CDKN2AIP is significantly associated with the inhibition of testicular seminoma tumor growth and the increase of cell senescence and apoptosis. CDKN2AIP exhibits anti-tumor activity by interacting with CARM1 and eIF4ß. CDKN2AIP induces testicular seminoma cell senescence by suppressing CARM1 expression and eIF4ß phosphorylation. The CDKN2AIP-CARM1 and CDKN2AIP-eIF4ß interactions, which induce tumor cell senescence and apoptosis, may be the potential druggable molecular pathways in testicular seminoma tumor pathogenesis and progression.

Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis.

An association between endometriosis and luteinized unruptured follicle syndrome (LUFs) has long been identified. Although inactivating mutation of luteinizing hormone/choriogonadotropin receptor (LHGCR) results in LUFs, whether LHCGR contributes to promoting LUFs in endometriosis remains elusive. To investigate the effect of LHCGR signaling in the development of endometriosis-associated LUFs and dissect the underlying mechanism in vivo mouse endometriosis model was established to measure the effect on ovarian folliculogenesis. In vitro cultures of primary human GCs collected from patients undergoing in vitro fertilization were performed and treated with human chorionic gonadotropin (hCG), dibutyryl cyclic-AMP (db-cAMP), LHCGR or CCAAT/enhancer binding protein-α (C/EBPα) small interfering RNA to identify the potential mechanisms. KGN cell line was used to investigate the mechanistic features of transcriptional regulation. Results showed an increased incidence of LUFs was observed in mice with endometriosis. The expression of LHCGR was decreased in the GCs of endometriosis mice. In in vitro cell models, LHCGR signaling increased the expression of C/EBPα and cyclooxygenase-2(COX-2), while inhibiting C/EBPα mitigated the induced COX-2 expression. Mechanically, C/EBPα bounded to the promoter region of COX-2 and increased the transcriptional activity under the stimulation of hCG or db-cAMP. Taken together, this study demonstrated that the LHCGR signaling was reduced in GCs of endometriosis and resulted in a decrease in gonadotropin-induced COX-2 expression. Our study might provide new insights into the dysfunction of GCs in endometriosis.

Small RNA sequencing reveals placenta-derived exosomal microRNAs associated with preeclampsia.

OBJECTIVE: Preeclampsia is one of the most important complications during pregnancy and the leading cause of maternal morbidity and mortality; however, the pathogenesis of preeclampsia remains partially misunderstood. The aim of this study was to identify placenta-derived exosomal microRNAs (miRNAs) involved in the preeclampsia process. METHODS: Peripheral blood was collected from normal and preeclampsia pregnant women, and placenta-derived exosomes were extracted. Small RNA sequencing was performed to identify the exosomal miRNAs involved in preeclampsia. The function of a differentially expressed exosomal miRNA was verified. RESULTS: The extracted exosomes presented round or ovallike structures with diameters of approximately 80 nm and could be recognized by antibodies against CD9, CD81, and placental alkaline phosphatase. A total of 1013 exosomal miRNAs were identified by small RNA sequencing, of which 946 were known miRNAs and 67 were novel miRNAs. Twenty-six miRNAs were identified as differentially expressed when comparing the data of the preeclampsia and normal groups. One of the differentially expressed miRNAs, hsa-miR-370-3p, which was upregulated in the preeclampsia group, was shown to bind to the 3' untranslated region of C-X-C motif chemokine 12, a chemokine that plays important role during preeclampsia process. Moreover, functional analysis revealed that hsamiR-370-3p could inhibit proliferation, migration, and invasion while promoting apoptosis of HTR-8/SVneo cells. CONCLUSION: A total of 1013 placenta-derived exosomal miRNAs were identified by small RNA sequencing, of which 26 were differentially expressed. The function of one differentially expressed miRNA (hsa-miR-370-3p) was verified. Our results provide new perspectives on the pathogenesis of preeclampsia and potential biomarkers for preeclampsia diagnosis.

Maternal exposure to bisphenol A induces fetal growth restriction via upregulating the expression of estrogen receptors.

Bisphenol A (BPA) accumulation in the placenta leads to fetal growth restriction (FGR). Here we aimed to explore the effect and the underlying mechanism of BPA exposure on fetal development. ELISA was performed to measure estrogen levels in human placenta and BeWo cells. qRT-PCR and Western blotting were conducted to determine the expression of estrogen receptors (ERs), breast cancer resistance protein (BCRP), the key enzymes for ER synthesis, and DNA methyltransferases (DNMTs). Bisulfite-sequencing PCR analysis was performed to measure CpG methylation in ER genes. Flow cytometry was used to examine cell apoptosis. We found that human FGR placentae had significantly increased BPA and estrogen levels and decreased BCRP levels compared with healthy placentae. BPA downregulated BCRP expression via ERs, and BCRP silencing promoted ER expression in BeWo cells. Compared with vehicle treatment, BPA treatment significantly enhanced the expression of key enzymes for estrogen synthesis and ERs in BeWo cells. BPA treatment inhibited CpG methylation in ER genes, along with downregulated DNMT1 expression and upregulated DNMT3a and DNMT3b expression. BPA treatment significantly promoted BeWo cell apoptosis compared with vehicle treatment. Importantly, ER inhibitor ICI-182780 significantly reversed all the BPA-induced effects on BeWo cells. In conclusion, BPA promotes estrogen production and cell apoptosis in BeWo cells via upregulating ER expression, leading to FGR.

PSPC1 regulates CHK1 phosphorylation through phase separation and participates in mouse oocyte maturation.

Liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in mammal cells. However, there are few reports that focus on the correlation of mouse oocyte maturation with LLPS. Previous studies have reported that paraspeckle component 1 (PSPC1) is related to the occurrence and development of tumors, but whether PSPC1 functions in mouse oocyte maturation is still unclear. Sequence analysis of PSPC1 protein showed that it contains a prion-like domain (PrLD) that is required for phase separation of proteins. In this study, we found that PSPC1 could undergo phase separation. Moreover, the loss of PrLD domain of PSPC1 could greatly weaken its phase separation ability. The immunofluorescence assays showed that PSPC1 is present in mouse oocytes in the germinal vesicle (GV) stage. Knockdown of PSPC1 significantly impeded the maturation of mouse oocytes in vitro. CHK1 has been reported to play important roles in the GV stage of mouse oocytes. Co-IP experiment revealed that PSPC1 could interact with phosphatase serine/threonine-protein phosphatase 5 (PPP5C), which regulates CHK1 phosphorylation. Western blot analysis revealed that PSPC1 could regulate the phosphorylation of CHK1 through PPP5C; however, PSPC1 without PrLD domain was inactive, suggesting that the lack of phase separation ability led to the abnormal function of PSPC1 in regulating CHK1 phosphorylation. Thus, we conclude that PSPC1 may undergo phase separation to regulate the phosphorylation level of CHK1 via PPP5C and participate in mouse oocyte maturation. Our study provides new insights into the mechanism of mouse oocyte maturation.

Different Indicators of Adiposity and Fat Distribution and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes.

OBJECTIVE: This study aimed to evaluate the effect of adiposity and fat distribution on the odds of elevated cardiovascular risk factors among adults with type 2 diabetes mellitus. METHODS: The present cross-sectional study included 2,427 adults with type 2 diabetes mellitus. Body fat was assessed by dual-energy x-ray absorptiometry. Multivariate-adjusted logistic regression was used to estimate effects of adiposity parameters on elevated hemoglobin A1c (HbA1c , ≥7.0%), hypertension (blood pressure ≥140/90 mmHg), and elevated low-density lipoprotein (LDL) cholesterol (≥2.6 mmol/L). RESULTS: The multivariable-adjusted odds ratio (OR) for elevated HbA1c was 0.82 (95% CI: 0.70-0.96) for each SD increase in leg fat mass. The multivariable-adjusted OR for hypertension was 1.15 (95% CI: 1.00-1.32) for each SD increase in android fat mass. Multivariable-adjusted ORs for elevated LDL cholesterol ranged from 1.16 (95% CI: 1.00-1.35) to 1.27 (95% CI: 1.06-1.51) for each SD increase in arm and android fat mass and percentage of total, truncal, arm, and android fat. Each SD increase in BMI, truncal-to-leg fat ratio, and android-to-gynoid fat ratio was significantly associated with increased risks of elevated HbA1c , hypertension, and elevated LDL cholesterol. CONCLUSIONS: Subcutaneous fat in the lower body was associated with a more favorable glycemic profile, but not blood pressure or lipid profile, whereas central adiposity was associated with poor control of cardiovascular risk factors among patients with type 2 diabetes mellitus.

Pregnancy or Psychological Outcomes of Psychotherapy Interventions for Infertility: A Meta-Analysis.

Background: The pregnancy and psychological status of infertile couples has always been a concern, but there is no clear evidence for the efficacy of psychotherapy for infertile couples. This study aimed to summarize the current evidence of the effects of psychotherapy on psychological and pregnancy outcomes for infertile couples. Method: We searched Ovid MEDLINE, Ovid EMbase, The Cochrane Library, and Web of Science (ISI) for articles published from 1946 to June 26, 2020. The pregnancy outcomes, psychological outcomes, and acceptability were involved in the study. Results: Overall, 29 studies with a combined total of 3,522 adult participants were included in the meta-analysis. Compared with a placebo, psychotherapy was associated with the pregnancy rate [risk ratio (RR) = 1.43, 95% CI [1.07, 1.93]], total psychological scales associated with infertility [standardized mean difference (SMD) = -0.33 95% CI [-0.63, -0.02]], subsymptoms of psychological scores using the 28-item version of GHQ (including social function [MD = -3.10, 95% CI [-4.30, -1.90]] and depression [MD = -3.90, 95% CI [-5.36, -2.44]], and depression [MD = 3.60, 95% CI [2.25, 4.95]] using the 14-item version of Hospital Anxiety and Depression Scale, but it had no statistically significant association with the other outcomes. In the stratified analyses, the pregnancy rate using assisted reproduction, cognitive behavioral therapy (CBT), and the integrative body-mind-spirit (BMS); total psychological scales associated with infertility using other treatments and more than a month; and anxiety using BMS had significant statistical significance. The funnel plots of all outcomes were approximately symmetrical, and no significant publication bias was found. Conclusions: The study showed that psychotherapy can lead to improvements in the pregnancy rate for infertile patients, especially for patients receiving assisted fertility. In addition, it may help improve total psychological scales associated with infertility and depression. CBT and BMS play an important role in improving rate of pregnancy, and BMS is associated with reducing anxiety. Although psychological interventions had limited effects on the pregnancy outcomes of infertility, our study still recommended that psychotherapies, in particular CBT and BMS, were applied to the therapeutic regimen for infertility, especially for patients receiving assisted fertility.

Pregnant women's psychological state and influence factors: anxiety, and depression during COVID-19 outbreak.

OBJECTIVES: The outbreak of COVID-19 affects both physical and mental health of pregnant women. This study focuses on their psychological status, and analyzes the main factors affecting their emotions of pregnant women so as to provide guidance for psychological counseling and social intervention during epidemics. METHODS: Multiple researchers distributed a questionnaire online via the Internet. Pregnant women volunteered, and the questionnaire was automatically collected in the background. RESULTS: The 298 valid questionnaires recovered showed that 82 cases of pregnant women were in states of anxiety, accounting for 27.51%, of which 78.05% were mild (82 cases), 19.51% were moderate (16 cases), and 2.44% were severe (2 cases). Moreover, 31.21% of pregnant women were in states of depression (93 cases), of which 52.69% were mild (49 cases), 40.86% were moderate (38 cases), and 6.45% were severe (6 cases). The risk factors for states of anxiety or depression were fear of fetal malformation or genetic disease, history of adverse pregnancy, can't do routine prenatal examination, and insufficient support and care from husbands and families. Besides, 16 cases had sought psychological help during the epidemic, among whom 62.50% (10 cases) experienced anxiety, 68.75% (11 cases) had depression. CONCLUSIONS: During the outbreak of COVID-19, obstetricians may take use of the Internet, based on the advantages in epidemic prevention, controlling health education, and popularizing science. In addition, husbands and family members should provide greater care for pregnant women, to protect their mental health during public health incidents.

Transient Early Fine Motor Abnormalities in Infants Born to COVID-19 Mothers Are Associated With Placental Hypoxia and Ischemia.

Background: Long-term effects of Coronavirus Disease 2019 (COVID-19) on infants born to infected mothers are not clear. Fine motor skills are crucial for the development of infant emotional regulation, learning ability and social skills. Methods: Clinical information of 100 infants born to 98 mothers (COVID-19 n = 31, non-COVID-19 n = 67) were collected. Infants were follow-up up to 9 months post-partum. The placental tissues were examined for SARS-CoV-2 infection, pathological changes, cytokines, and mtDNA content. Results: Decreased placental oxygen and nutrient transport capacity were found in infected pregnant women. Increased IL-2, IL-6, TNF-α, and IFN-γ were detected in trophoblast cells and maternal blood of COVID-19 placentas. Elevated early fine motor abnormal-ities and increased serum TNI (troponin I) levels at delivery were observed in infants born to mothers with COVID-19. Increased abnormal mitochondria and elevated mtDNA content were found in the placentas from infected mothers. The placental mtDNA content of three infants with abnormal DDST were increased by 4, 7, and 10%, respectively, compared to the mean of the COVID-19 group. The Maternal Vascular Malperfusion (MVM), elevated cytokines and increased placental mtDNA content in mothers with COVID-19 might be associated with transient early fine motor abnormalities in infants. These abnormalities are only temporary, and they could be corrected by daily training. Conclusions: Babies born to COVID-19 mothers with mild symptoms appeared to have little or no excess long-term risks of abnormal physical and neurobehavioral development as compared with the infants delivered by non-COVID-19 mothers.

Midwifery and Nursing Strategies to protect against COVID-19 During the Third Trimester of Pregnancy.

OBJECTIVE: The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents significant challenges to midwives and nurses. This study aimed to explore midwifery and nursing interventions to limit the transmission of COVID-19 among women in their third trimester of pregnancy, to reduce the incidence of nosocomial infection and promote safety of care for women and their infants. METHOD: We completed a retrospective review of medical records from 35 women in their third trimester of pregnancy with SARS-CoV-2, admitted to one hospital in Wuhan, China in January and February 2020. We investigated the clinical characteristics of the COVID-19 infection in pregnancy, and the individualized midwifery and nursing care offered, including environmental protection, prevention of nosocomial infection, maternal observations, monitoring of signs and symptoms of COVID-19, and psychological care. RESULT: Thirty-one women had a caesarean section, and four had vaginal births. Retrospective analysis of midwifery and nursing strategies implemented to care for these women showed no maternal complications or nosocomial infections. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The care strategies we implemented could prevent complications and nosocomial infection in the third trimester of pregnancy, thus ensuring the safety of women and their infants. Further research needs to determine treatment priorities for women infected with COVID-19 during pregnancy and the postnatal period.

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats.

Subacute exposure to manganese (Mn) produced Parkinson's disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1ß, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters.

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Expression and Functional Analysis of CXCL12 and Its Receptors in Human Term Trophoblast Cells.

Chemokine CXCL12 and its receptors CXCR4/CXCR7 play a pivotal role in many physiological and pathological situations, while the expression and function in human term trophoblast cells remain largely unknown. In the study, the expression and function of CXCL12 and its receptors CXCR4/CXCR7 in human term trophoblast cells were investigated. Immunocytochemistry and flow cytometry showed that the expression of CXCL12/CXCR4/CXCR7 could be detected in term trophoblast cells while expression level differed. The secretion of CXCL12 in human term trophoblast cells was confirmed by enzyme-linked immunosorbent assay (ELISA). In order to reveal the function of CXCL12, exogenetic recombinant human CXCL12 protein (rhCXCL12) was added to the cultured term trophoblast cells; results showed that cell proliferation ability was increased while cell apoptosis rate was decreased. Moreover, the effects of rhCXCL12 on term trophoblast cells could be diminished or attenuated by antibodies against CXCL12, CXCR4, or CXCR7, respectively. Therefore, these results revealed the important role of CXCL12 on human term trophoblast cells. Our study will provide new insights into understanding the role of CXCL12 on human term trophoblast cells.