A Peritrophin-44 gene in Litopenaeus vannamei is involved in disease resistance.

Peritrophic membrane (PM) is a pellicle structure present in the midgut of some invertebrates, such as insects and crustaceans. It could isolate harmful components and pathogens in food from intestinal epithelial cells; and it also plays a role in improving digestion and absorption efficiency. So PM is important for survival of its owner. In current study, 44 PM proteins were identified in Litopenaeus vannamei by PM proteome analysis. Among these PM proteins, the Peritrophin-44 homologous protein (LvPT44) was further studied. Chitin-binding assay indicated that LvPT44 could bind to colloidal chitin, and immunoeletron microscopy analysis shown that it was located to PM of L. vannamei. Furthermore, LvPT44 promoter was found to be activated by L. vannamei STAT and c-Jun. Besides, LvPT44 was induced by ER-stress as well as white spot syndrome virus infection. Knocked-down expression of LvPT44 by RNA inference increased the cumulative mortality of shrimp that caused by ER-stress or white spot syndrome virus. These results suggested that LvPT44 has an important role in disease resistance.

Predicting risk of preterm birth in singleton pregnancies using machine learning algorithms.

We aimed to develop, train, and validate machine learning models for predicting preterm birth (<37 weeks' gestation) in singleton pregnancies at different gestational intervals. Models were developed based on complete data from 22,603 singleton pregnancies from a prospective population-based cohort study that was conducted in 51 midwifery clinics and hospitals in Wenzhou City of China between 2014 and 2016. We applied Catboost, Random Forest, Stacked Model, Deep Neural Networks (DNN), and Support Vector Machine (SVM) algorithms, as well as logistic regression, to conduct feature selection and predictive modeling. Feature selection was implemented based on permutation-based feature importance lists derived from the machine learning models including all features, using a balanced training data set. To develop prediction models, the top 10%, 25%, and 50% most important predictive features were selected. Prediction models were developed with the training data set with 5-fold cross-validation for internal validation. Model performance was assessed using area under the receiver operating curve (AUC) values. The CatBoost-based prediction model after 26 weeks' gestation performed best with an AUC value of 0.70 (0.67, 0.73), accuracy of 0.81, sensitivity of 0.47, and specificity of 0.83. Number of antenatal care visits before 24 weeks' gestation, aspartate aminotransferase level at registration, symphysis fundal height, maternal weight, abdominal circumference, and blood pressure emerged as strong predictors after 26 completed weeks. The application of machine learning on pregnancy surveillance data is a promising approach to predict preterm birth and we identified several modifiable antenatal predictors.

Effect of prehabilitation on postoperative outcomes in the frail older people: A systematic review and meta-analysis.

OBJECTIVE: The study investigates the impact of preoperative rehabilitation on the surgical prognosis of frail older patients. METHOD: The effect sizes of all studies retrieved and included by the nine databases were analyzed and expressed as RR and WMD. RESULTS: 8 studies with 902 participants met the criteria for inclusion. A significant reduction in total complications (RR = 0.84, 95 % CI = 0.73 to 0.97, P = 0.021) and the 6MWT after surgery (WMD = 74.76, 95 % CI = 44.75 to 104.77, P = 0.000) was observed in the prehabilitation group. But it had no differences in mortality(RR = 1.89, 95 % CI = 0.75 to 4.72, P = 0.176), readmission rates(RR = 1.04, 95 % CI = 0.56 to 1.91, P = 0.906) and LOS(WMD = -0.24, 95 % CI = -1.00 to 0.52, P = 0.540). CONCLUSIONS: Prehabilitation had positive effect on postoperative complications and functional recovery in frail older patients.

Functional Characterization of A Deformed Epidermal Autoregulatory Factor 1 Gene in Litopenaeus vannamei.

Innate immunity is crucial for invertebrate defense against pathogenic infections. Numerous studies have indicated that the Toll-NF-κB pathway plays an important role in this process, particularly in anti-bacterial and anti-fungal immunity. Although the function of this pathway has been studied extensively, there are still uncertainties regarding its role in shrimp. In this study, we investigated the functions of Deformed Epidermal Autoregulatory Factor 1 (LvDEAF1) in Litopenaeus vannamei, a member of the Toll-NF-κB pathway. Our findings revealed that LvDEAF1 interacts with L. vannamei Pellino1 (LvPellino1). LvDEAF1 enhances the promoter activity of certain antimicrobial peptide genes, such as Metchnikowin and Drosomycin, in Drosophila Schneider 2 (S2) cells by binding to the NF-κB binding site. LvDEAF1 and LvPellino1 exhibit positive and synergistic effects. Additionally, the expression of LvDEAF1 is induced by Vibrio parahaemolyticus infection and lipopolysaccharides or zymosan treatment. Knockdown LvDEAF1 expression resulted in a decrease in Penaeidins 4 expression and an increase in the cumulative mortality of shrimp infected with V. parahaemolyticus. These findings indicate that LvDEAF1 plays an important role in the Toll-NF-κB pathway of L. vannamei and is essential for its immune response against pathogens.

Effects of Bedaquiline Combined with Fluoroquinolone and/or Clofazimine on QT Interval in Patients with Multidrug-Resistant Tuberculosis: a Retrospective Study.

With the application of bedaquiline (Bdq), the success rate of multidrug-resistant tuberculosis (MDR-TB) treatment has been significantly improved; however, the cardiac safety of the patients during treatment cannot be ignored. Hence, this study compared the effects of bedaquiline alone and bedaquiline combined with fluoroquinolones (FQs) and/or clofazimine (CFZ) on the QT interval. This single-center retrospective cohort study analyzed the clinical data of MDR-TB patients treated with bedaquiline for 24 weeks from January 2020 to May 2021 in Xi'an Chest Hospital and compared the changes in QTcF between the two groups. Eighty-five patients were included in the study and grouped by types of anti-TB drugs affecting the QT interval they used. Group A included bedaquiline (n = 33), and group B included bedaquiline in combination with fluoroquinolones and/or clofazimine (n = 52). Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 2.4% (2/85) experienced a postbaseline QTcF of ≥500 ms, and 24.7% (21/85) had at least one change of QTcF of ≥60 ms from baseline. In group A, 9.1% (3/33) had at least one ΔQTcF of >60 ms, as did 34.6% (18/52) of group B. Multivariate Cox regression analysis showed that the adjusted risk of QT prolongation was 4.82 times higher in group B (95% confidence interval [CI], 1.406 to 16.488). Bedaquiline combined with other anti-TB drugs affecting QT interval significantly increased the incidence of grade 3 or 4 QT prolongation; however, no serious ventricular arrhythmia and permanent drug withdrawal occurred. The use of bedaquiline combined with fluoroquinolone and/or clofazimine is an independent risk factor affecting QT interval. IMPORTANCE Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. The emergence of MDR-TB is caused by an organism that is resistant to at least isoniazid and rifampin and is currently considered the major challenge for the global control of TB. Bedaquiline is the first new TB drug in 50 years with a unique mechanism of action, strong anti-M. tuberculosis activity. Yet unexplained excess deaths in the bedaquiline arms have been found in some phase II clinical trials; thus, the FDA has issued a "boxed warning." However, the cardiac safety of the patients during treatment cannot be ignored. Accordingly, further investigations are needed to establish whether bedaquiline combined with clofazimine, fluoroquinolones, or anti-TB drugs affecting the QT interval in a long-course or short-course treatment increases the risk of QT prolongation.

Idiopathic calcinosis cutis of the buttocks: A case report and review of the literature.

RATIONALE: Calcinosis cutis is a rare skin disease, and idiopathic cases are rarely reported. It is characterized by the deposition of insoluble calcium salts in the skin, subcutaneous tissue, superficial muscles, and tendon sheaths. However, no abnormal changes were found in the bone. In this article, we introduce a case of idiopathic calcinosis cutis of the buttocks with a long course and large lesion area. PATIENT CONCERNS: A 51-year-old male patient was admitted to the hospital with a chief complaint of 'Due to the discovery of hard nodules with pruritus in the buttocks for 32 years. The patient was a male who was 51 years old. He has been in good health and reported no history of surgery, trauma, infection, metabolic disease, tumor, or other diseases. There was no family history. It is worth noting that the patient has the occupation of driving trucks, which keeps him sedentary. DIAGNOSES: The accurate diagnosis of calcinosis cutis was confirmed by postoperative histopathological examination with many local calcifications and multinucleated giant cells in subcutaneous tissue. INTERVENTIONS: The patient underwent skin lesion excision and autologous skin grafting under general anesthesia. A medium-thickness skin graft from the left lateral thigh was transplanted into the hip operation area, and a bolus tie-over pressure dressing was applied. After the operation, the patient received anti-infection treatment and was advised to rest in the prone position to prevent extrusion of the operation area. OUTCOMES: The postoperative recovery was good, and there was no recurrence after 4 months of follow-up. LESSONS: The incidence rate of cutaneous calcinosis is not clear. This patient had a large lesion area, long onset time, an invasion of the fat layer, and the onset site was located in the sacrococcygeal region. It is necessary to choose appropriate treatment methods.

Association of placental PPARα/γ and miR-27b expression with macrosomia in healthy pregnancy.

BACKGROUND: Peroxisomal proliferator-activated receptors (PPARs) and microRNAs (miRNAs) play important roles in the development of fetuses, whereas expression changes of PPARs and three miRNAs (miR-17, miR-27b and miR-34a) and whether these miRNAs regulate PPARs in non-GDM macrosomia placenta is unclear. METHODS: A case-control study was performed to collect information and placental tissues on mothers and newborns of non-GDM macrosomia and normal-birth-weight infants. In vitro HTR8-SVneo cellular model was used to detect the effects of miRNAs on PPARs expression. Quantitative real-time PCR (qRT-PCR) and western blot was applied to examine the expression levels of PPARs, miR-17, miR-27b, and miR-34a in placental tissues and cells. RESULTS: The PPARα/γ mRNA and protein levels were significantly up-regulated and miR-27b was down-regulated in the placenta of macrosomia group compared with in the control group, while no difference was observed in PPARß, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPARα/γ mRNA expression still increased the risk of macrosomia. The PPARα/γ protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor. CONCLUSIONS: Placental PPARα/γ and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPARα/γ protein. IMPACT: Low miR-27b and high PPARα/γ mRNA expression in the placenta were associated with higher risk of macrosomia. In vitro HTR8-SVneo cell experiment supported that miR-27b could negatively regulate the expression of PPARα and PPARγ protein. MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPARα/γ protein.

Genetically predicted selenium concentrations and thyroid function: A two-sample Mendelian randomization study.

OBJECTIVE: The impact of selenium (Se) on human thyroid function remains unclear, with inconsistent results from recent epidemiological studies. Moreover, the observed associations are prone to bias due to potential confounding and reverse causation. Mendelian randomization (MR) analysis facilitates the large minimization of biases produced by environmental and lifestyle influences, providing unconfounded estimates of causal effects using instrumental variables. We aim to examine the association between Se concentrations and human thyroid function using a two-sample MR analysis. DESIGN AND METHODS: Genetic instruments for Se concentrations, including toenail and blood (TAB) and blood Se concentrations, were identified from a genome-wide association study (GWAS) of blood Se (n = 5477) and toenail Se levels (n = 4162). GWAS summary statistics on thyroid phenotypes were downloaded from the ThyroidOmics consortium, including thyroid-stimulating hormone (TSH) (n = 54,288), free thyroxin (FT4) (n = 49,269), hypo (n = 53,423), and hyperthyroidism (n = 51,823). The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with the weighted median and the mode-based method. RESULTS: Genetically determined TAB Se was negatively associated with FT4 (ß = -.067; 95% confidence interval [CI] = -0.106, -0.028; p = 0.001) using the IVW analyses, as well in the additional analyses using the weighted median and weighted-mode methods. No evidence in heterogeneity, pleiotropy or outlier single-nucleotide polymorphisms was detected (all p > 0.05). Suggestive casual association between increased genetically determined TAB Se concentrations and decreased hypothyroidism risk was found by the IVW method (odds ratio [OR] = 0.847; 95% CI = 0.728, 0.985; p = 0.031). The causal effect of TAB Se on FT4 was observed in women (ß = -.076; 95% CI = -0.129, -0.024; p = 0.004). However, the influence of genetically determined higher Se concentrations on TSH levels and hyperthyroidism revealed insignificance in the primary and sensitivity analyses. CONCLUSIONS: The present MR study indicated that high Se concentration enable the decreasing of FT4 levels, and the effects of Se concentrations on FT4 remain sex-specific.

Preliminary study of the intranuclear function of Sma and Mad related protein 5 gene in Litopenaeus vannamei.

Litopenaeus vannamei Smad5 (LvSmad5) in cytoplasm has been proved to be involved in environmental stress response. As LvSmad5 could also locate in nucleus under specific stress, it was conjectured that LvSmad5 might participate in environmental stress response. While, the experimental evidence is still lacking. In this study, cytosolic LvSmad5 mutant or nuclear LvSmad5 mutant was expressed in Drosophila S2 cells, and then transcriptomic analysis of mentioned cells was performed using Illumina HiSeq based RNA-Seq, to reveal the function of LvSmad5 in nucleus. By comparing the two groups of cDNA libraries from S2 cells with cytosolic or nucleus LvSmad5 mutant, 86 differentially expressed genes as well as 765 differentially expressed transcripts were found. It was revealed that genes in the ER-stress response pathway, such as unfolded protein response and ER-associated degradation (ERAD) were enriched. Additionally, some kinds of metabolic reprogramming occurred in S2 cells with over-expressing nuclear LvSmad5, for significant changes in the expression of some metabolism-related genes. To test our infer that nuclear LvSmad5 was engaged in environmental stress response, homologous gene of Drosophila translocation in renal carcinoma on chromosome 8 in L.vannamei (LvTRC8) was chosen for further investigation. And studies about LvTRC8, a member of ERAD showed that it was induced by ER-stress or heat shock treatment. Suppressed the expression of LvTRC8 increased the cumulative mortality of shrimp upon stress. In some degree, these results support our speculation that nuclear LvSmad5 are involved in the environmental stress response of L. vannamei in fact.

Educational attainment and offspring birth weight: A bidirectional Mendelian randomization study.

Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW. Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome. Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10-3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis. Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.

Treatment Outcomes and Risk Factors of Multidrug-Resistant Tuberculosis Patients in Xi'an China, a Retrospective Cohort Study.

Background: Long-term regimens are widely used for multidrug-resistant tuberculosis (MDR-TB) in North-West China; however, risk factors associated with the treatment outcomes are not well known. Methods: This was a retrospective cohort study of MDR-TB patients treated with longer regimen in Xi'an from 2017 to 2019. Risk factors associated with the treatment outcome were analyzed using multiple logistic regression. Results: Of the 446 patients with MDR-TB included, 215 were cured, 84 completed treatment, 23 failed treatment, 108 were lost to follow-up, and 16 died. Unfavorable outcome risk factors were age >40 years (OR = 3.25, 95% CI = 2.12-4.98), male sex (OR = 2.53, 95% CI = 1.52-4.22), and re-treated tuberculosis (OR = 1.70, 95% CI = 1.11-2.61), whereas poor treatment outcome risk factors were age >40 years (OR = 5.51, 95% CI = 2.52-12.07), fluoroquinolones not used in the regimen (OR = 3.31, 95% CI = 1.45-7.51), and smear-positive (OR = 4.0, 95% CI = 1.47-10.8). Conclusion: In Xi'an, MDR-TB treatments with long-term regimens had low success rates, and age, sex, and tuberculosis treatment history were risk factors of MDR-TB treatment outcomes.

Transcriptome analysis endoplasmic reticulum-stress response in Litopenaeus vannamei hemocytes.

Numerous studies have proved that endoplasmic reticulum (ER)-stress is an important cause of aquatic animal diseases. Therefore, for effectively preventing and controlling aquatic animal diseases, a systematic and in-depth understanding of the environmental stress response in aquatic animals is necessary. In present study, the influence of ER-stress in Litopenaeus vannamei was investigated using Illumina HiSeq based RNA-Seq. Comparing to the cDNA library of hemocytes treated with DMSO in L. vannamei, 286 unigenes were significantly upregulated and 473 unigenes were significantly down-regulated in the Thapsigargin treated group. KEGG analysis indicated that the differentially expressed genes (DEGs) are mainly related to ER-stress, immune as well as metabolism. Besides the classical ER-stress response pathways, the regulation of cell cycle and DNA replication are also important measures of ER-stress response. It has been suggested that the influence of ER-stress on immune genes might be an important factor in environmental stress inducing shrimp disease. Our investigation exhibited that immune-related DEG Prophenoloxidase activating enzyme 2 (LvPPAE2) roled in anti-pathogen immunity of shrimp. This study provides a solid foundation for uncovering the environmental adaptation response and especially its relationship with L. vannamei immune system.

Associations between seasonal ambient air pollution and adverse perinatal outcomes: a retrospective cohort study in Wenzhou, China.

Prenatal exposure to ambient air pollution has been associated with adverse perinatal outcomes in previous studies. However, few studies have examined the interaction between air pollution and the season of conception on term low birth weight (TLBW) or macrosomia. Birth registry data of singleton live births in Wenzhou, China, between January 2015 and December 2016 were accessed from the Wenzhou Maternal and Child Health Information Management platform, and data on the ambient air pollutants in Wenzhou were obtained from the Chinese Air Quality Online Monitoring and Analysis Platform. Single-/two-pollutant binary logistic regression models were used to assess the associations between ambient air pollutants (PM2.5, PM10, NO2, SO2, and O3) and TLBW/macrosomia, further exploring whether the season of conception interacts with air pollution to impact birth weight. Finally, 213,959 term newborns were selected, including 2452 (1.1%) infants with TLBW and 13,173 (6.1%) infants with macrosomia. In the single-/two-pollutant models, we observed an increased risk of TLBW associated with maternal exposure to PM2.5, PM10, SO2, and NO2 during the entire pregnancy, especially in the 2nd trimester. Maternal exposure to O3 during the 1st trimester was associated with increased macrosomia risk, and O3 exposure during the 3rd trimester was associated with increased TLBW risk. Pregnant women who conceive in the warm season may experience a more adverse ambient air environment that is related to the risks of TLBW. These findings add to the evidence suggesting that air pollution and the season of conception may have synergistic effects on adverse perinatal outcomes, especially TLBW. Further prospective cohort studies are needed to validate our results.

Placental mtDNA copy number and methylation in association with macrosomia in healthy pregnancy.

INTRODUCTION: Fetal growth and development depend on metabolic energy from placental mitochondria. However, the impact of placental mitochondria on the occurrence of macrosomia remains unclear. We aimed to explore the association between macrosomia without gestational diabetes mellitus (non-GDM) and changes in placental mitochondrial DNA (mtDNA) copy number and methylation. METHODS: Fifty-four newborns with macrosomia and 54 normal birthweight controls were enrolled in this study. Placental mtDNA copy number and mRNA expression of nuclear genes related to mitochondrial replication or ATP synthesis-related genes were measured by real-time quantitative polymerase chain reaction (qPCR). Methylation levels of the non-coding regulatory region D-loop and ATP synthesis-related genes were detected by targeted bisulfite sequencing. RESULTS: Newborns with macrosomia had lower placental mtDNA copy number and higher methylation rates of the CpG15 site in the D-loop region (D-CpG15) and CpG6 site in the cytochrome C oxidase III (COX3) gene (COX3-CpG6) than normal birth weight newborns. After adjusting for potential covariates (gestational age, prepregnancy BMI, and infant sex), decreased placental mtDNA copy number (adjusted odds ratio [aOR] = 2.09, 95% confidence interval [CI] 1.03-4.25), elevated methylation rate of D-CpG15 (aOR = 2.06, 95% CI 1.03-4.09) and COX3-CpG6 (aOR = 2.13, 95% CI 1.08-4.20) remained significantly associated with a higher risk of macrosomia. DISCUSSION: Reduced mtDNA copy number and increased methylation levels of specific loci at mtDNA would increase the risk of macrosomia. However, the detailed molecular mechanism needs further identification.

Relationships Between Placental Lipid Activated/Transport-Related Factors and Macrosomia in Healthy Pregnancy.

To assess associations between infants with macrosomia and placental expression levels of lipid activated/transport-related factors and umbilical cord blood lipid concentrations in healthy pregnancy. We conducted a case-control study of 38 macrosomic neonates (MS group) and 39 normal-birth-weight newborns (NC group) in a healthy pregnancy. Cord blood lipid levels were measured by automatic biochemical analyzer, mRNA and protein expression levels of placental lipid activated/transport-related factors were determined by real-time polymerase chain reaction and western blot, respectively. Compared with NC group, cord blood total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and non-esterified fatty acid (NEFA) concentrations were decreased in the MS group. The mRNA and protein expression levels of placental peroxisome proliferator-activated receptors (PPARα, PPARγ), plasma membrane fatty acid-binding protein (FABPpm), and fatty acid translocase (FAT/CD36) were significantly higher in the MS group than the NC group. And there was a weak positive correlation between the expression of PPARγ, FABP4, and FABP3 mRNA in the placenta and the HDLC (rs = 0.439; P = 0.005), NEFA (rs = 0.342; P = 0.041), and TG (rs = 0.349; P = 0.034) levels in the cord blood in the MS group, respectively. After multivariate adjustment, the logistic regression analysis showed that high placental PPARα (adjusted odds ratio [AOR] = 3.022; 95% confidence interval [CI] 1.032-8.853) and FAT/CD36 (AOR=2.989; 95%CI 1.029-8.679) and low LDLC concentration in the cord blood (AOR=0.246; 95%CI 0.080-0.759) increased the risk of macrosomia. The increased PPARα and FAT/CD36 expression levels may influence the occurrence of fetal macrosomia through regulating placental lipid transport.

A IFI27 gene contributes to ER-stress mediated apoptosis and benefits for white spot syndrome virus infection in Litopenaeus vannamei.

The interplay between virus and host has been one of the hot spot in virology, and it is also the important aspect of revealing the mechanism of virus infection. Increasing studies revealed that several key molecules took part in the process of virus-host interaction. White spot syndrome virus (WSSV) has been proved to affect several physiological processes of the host cells, especially apoptosis. While the relationship between them still remains unclear. In this study, a IFI27 gene (LvIFI27) of Litopenaeus vannamei was cloned. It is indicated that LvIFI27 was induced upon endoplasmic reticulum (ER)-stress and unfolded protein response activator Thapsigargin. Unlike human IFI27 locating to mitochondria, LvIFI27 lied to ER, and was involved in cell apoptosis process. Moreover, results of cumulative mortality analysis showed that LvIFI27 might contributed to WSSV proliferation by promoting apoptosis during the process of viral infection. Findings in this study enriched our understanding of the relationship between WSSV infection and ER-stress mediated apoptosis.

Cord blood leptin DNA methylation levels are associated with macrosomia during normal pregnancy.

BACKGROUND: We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia. METHOD: We carried out a case-control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500-3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72-4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99-27.75), long gestational age (AOR = 3.18, 95% CI: 1.74-5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34-3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31-11.69) significantly increased the risk of macrosomia. CONCLUSIONS: Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

PURPOSE: To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. METHODS: This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. RESULTS: Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P < 0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). CONCLUSIONS: Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia.

Macrosomia, a birth weight ≥ 4,000 g, is associated with maternal and infant health problems. The dysregulation of microRNAs (miRNAs) in the placenta is associated with adverse birth outcomes, yet whether aberrantly expressed placental miRNAs are associated with macrosomia remains unknown. The aim of the current study was to characterize the expression of three placental miRNAs (miR­6, ­21 and ­143) and evaluate their association with macrosomia. The miRNA expression in placental tissues from 67 macrosomic pregnancies and 64 normal pregnancies were analyzed using reverse transcription­quantitative polymerase chain reaction. The expression of miR­21 was observed to be elevated in macrosomic placenta compared with control samples, while miR­143 expression was significantly lower than in control placenta (P<0.05). No significant differences were identified in the miR­16 expression levels between the groups (P=0.955). Following division of miRNA expression levels by quartile, logistic regression models demonstrated that the odds of macrosomia increased with miR­21 expression quartile: Q2, odds ratio (OR)=6.67 [95% confidence interval (CI), 1.39­32.05]; Q3, OR=4.10 (95% CI, 0.88­19.11); Q4, OR=16.19 (95% CI, 2.46­106.68). Conversely, higher levels of miR­143 expression were protective against macrosomia: Q2, OR=0.22 (95% CI, 0.049­0.98); Q3, OR=0.11 (95% CI, 0.024­0.55), and Q4, OR=0.16 (95% CI, 0.032­0.79). Thus, statistical analysis demonstrated that high levels of miR­21 expression and low levels of miR­143 expression predict the risk for macrosomia, indicating an interaction between the two miRNAs. Bioinformatic analysis suggested that they are likely to function in the mitogen­activated protein kinases signaling pathway to influence the risk of macrosomia. The results of the present study provide evidence that placental miR-21 and -143 are important in the formation of macrosomia.

Birth weight is associated with placental fat mass- and obesity-associated gene expression and promoter methylation in a Chinese population.

OBJECTIVE: To explore the relationship between birth weight and fat mass- and obesity-associated (FTO) gene expression and promoter methylation status in the Chinese population. METHODS: Seventy-five neonates and their mothers were recruited from Yuying Children's Hospital of Wenzhou Medical University. Subjects were divided into three groups by birth weight: low (< 3,500 g, n = 20), medium (3,500-3,999 g, n = 30) and high (≥ 4,000 g, n = 25). Placental FTO transcript levels and promoter methylation were determined by quantitative PCR and Sequenom MassARRAY®. RESULTS: Placental FTO mRNA expression was significantly increased in the high- and medium-weight groups compared to the low-weight group (p = 0.023). Methylation rates of CpG11 sites were significantly decreased in high-birth weight newborns (p = 0.018). Multiple linear regressions showed placental FTO mRNA, maternal pre-pregnancy body mass index (BMI) and CpG11 methylation rate were independently associated with increased fetal birth weight. Additionally, FTO mRNA expression was negatively associated with CpG6.7.8.9 methylation in mothers that underwent C-section. CONCLUSIONS: High placental FTO expression is associated with increased birth weight in Chinese neonates, and FTO promoter methylation level at a specific CpG site is negatively associated with birth weight. Further work is needed to determine the functionality of this CpG site in placentas.