Chemoproteomic Strategy Identifies PfUCHL3 as the Target of Halofuginone.

The human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Preferences of pregnant individuals to undergo labor after one cesarean in southern China.

BACKGROUND: Labor after cesarean (LAC) remains an optional delivery method among healthy pregnant individuals. Exploring women's attitudes, preferences, reasons for previous cesarean delivery, and the incentives underlying pregnant individuals' preferences could help us understand their choice of delivery mode. In this study we evaluated the preferences and attitudes of eligible pregnant women regarding participation in a LAC in Foshan, China. METHODS: A cross-sectional survey was conducted among 438 pregnant individuals with one prior cesarean delivery (CD) who attended their antenatal examination at a tertiary hospital in southern China, between November 1, 2018, and October 31, 2019. Information on demographic characteristics, obstetric data, preferences for LAC, and incentives for LAC were analyzed. RESULTS: Overall, 85.4% (374/438) of women preferred LAC if they did not have contraindications before delivery, whereas 12.3% (54/438) refused and 2.3% (10/438) were unsure. Participants reported that the most important factors affecting their willingness to undergo LAC were safety indicators (i.e., "ability of hospitals to perform emergency cesarean delivery" [score of 9.28 ± 1.86]), followed by accessibility indicators (i.e., "priority bed arrangements" [score of 9.17 ± 1.84]). Logistic regression analysis indicated that neonatal wellbeing with the prior CD was an independent influencing factor (OR = 2.235 [95%CI: 1.115-4.845], p = 0.024) affecting willingness to access LAC in the subsequent pregnancy. CONCLUSIONS: We found a high preference for LAC among pregnant individuals without contraindications before delivery in southern China. Healthcare providers need to ensure access to LAC and increase pregnant individuals' LAC willingness through high-quality shared decsision-making in alignment with patient preferences.

Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study.

BACKGROUND: Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. METHODS: A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n=13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. RESULTS: Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64-0.89, P = 8.03 × 10-4). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60-0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62-0.93, P = 8.76 × 10-3), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10-3), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10-3), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74-0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. CONCLUSIONS: This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms.

Associations between thyroid function and gestational diabetes mellitus in Chinese pregnant women: a retrospective cohort study.

BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.

Assessment of different thresholds of birthweight discordance for early neonatal outcomes: retrospective analysis of 2348 twin pregnancies.

BACKGROUND: The optimal threshold of birthweight discordance (BWD) remains controversial. This study aimed to evaluate the associations between BWD at different thresholds and early neonatal outcomes and to assess their predictive accuracy. METHODS: This was a retrospective cohort study using a birthweight data with the chorionicity information of 2348 liveborn twin pairs at a gestational age of ≥26 weeks, from 2012 to 2018. The percentage of BWD was calculated by dividing the actual birthweight difference by the weight of the larger twin and multiplying by 100. Outcomes of interest included neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome (NRDS), ventilator support and a composite outcome combining major morbidities and neonatal death. Logistic regression models were performed to estimate the association between neonatal outcomes and BWD with different thresholds (≥15.0%, ≥20.0%, ≥25% and ≥ 30%). Generalized estimated equation (GEE) models were used to address intertwin correlation. Restrictive cubic spline (RCS) models were established to draw the dose-response relationship between BWD and the odds ratios of outcomes. Clustered receiver operating characteristic (ROC) curve analyses were performed to assess the predictive accuracy. RESULTS: Of 2348 twin pairs, including 1946 dichorionic twin pairs and 402 monochorionic twin pairs, BWD was significantly associated with NICU admission, regardless of the thresholds used. The incidence of NRDS, ventilator support and the composite outcome were significantly higher when a threshold of ≥20% or greater was chosen. The dose-response relationship showed nonlinear growth in the risk of adverse neonatal outcomes with increasing BWD. ROC analyses showed a low significant AUROC of 0.569 (95% CI: 0.526-0.612) for predicting NICU admission but no significant AUROCs for predicting other outcomes. A BWD of ≥30% provided a moderate increase in the likelihood of NICU admission [positive likelihood ratio (LR+) = 5.77]. CONCLUSION: Although BWD is independently associated with adverse neonatal outcomes, it is not a single predictor for neonatal outcomes given the weak discriminative ability to predict neonatal outcomes. A cutoff of 30% is more practical for risk stratification among twin gestations.

Is there an optimal inter-delivery interval in women who underwent trial of labor after cesarean delivery (TOLAC)?

BACKGROUND: Inter-delivery interval (IDI) has been proven to be a factor associated with adverse maternal and neonatal outcomes. However, the optimal IDI in trial of labor after cesarean delivery (TOLAC) remains unclear. We aimed to investigate the association between IDI and major maternal and neonatal outcomes in women who underwent TOLAC. METHODS: A multicenter, retrospective cohort study including five hospitals was conducted between January 2018 and December 2019 in Foshan, China. This study included 1080 pregnant women with one or two cesarean deliveries who attempted a TOLAC. Data on maternal and neonatal outcomes were collected from the electronic record system. Maternal and neonatal outcomes in different groups of IDI were compared by univariate and multivariable analyses. RESULTS: A short IDI of < 24 months did not show a statistically significant association with uterine rupture in the univariate analysis (P = 0.668). In multivariable analysis, the incidences of postpartum hemorrhage (OR 19.6, 95% CI:4.4-90.9, P < 0.05), preterm birth (OR 5.5, 95% CI:1.5-21.3, P < 0.05), and low birth weight (OR 3.5, 95% CI:1.2-10.3, P < 0.05) were significantly increased in women with an IDI of < 24 months than in those with a normal interval (24-59 months). Infection morbidity (OR 1.8, 95% CI:1.4-7.9, P < 0.05), transfusion (OR 7.4, 95% CI:1.4-40.0, P < 0.05), and neonatal unit admission (OR 2.6, 95% CI:1.4-5.0, P < 0.05) were significantly increased in women with an IDI of 120 months or more than in those with a normal interval. Postpartum hemorrhage (P = 0.062) had a trend similar to that of a significant IDI of 120 months or more. We found no statistically significant difference in maternal and neonatal outcomes between 24-59 months and 60-119 months. CONCLUSIONS: An IDI of less than 24 months or 120 months or more increased the risk of major maternal and neonatal outcomes. We recommend that the optimal interval for women who underwent TOLAC should be 24 to 119 months.

An inter-delivery interval (IDI) that is too short or too long increases the risk of adverse maternal and neonatal outcomes. However, the optimal IDI for trial of labor after cesarean delivery (TOLAC) remains unclear. We performed a multicenter, electronic medical record-based, retrospective cohort study that included 1080 pregnant women who had one or two cesarean deliveries and underwent TOLAC. Data on maternal and neonatal outcomes were collected from the electronic record system. In multivariable analysis, the incidences of postpartum hemorrhage, preterm birth, and low birth weight were significantly increased in women with an IDI of < 24 months than in those with a normal interval (24­59 months). Infections, transfusion, and neonatal unit admission were significantly increased in women with an IDI of ≥ 120 months than in those with a normal interval. In conclusion, we found that an IDI < 24 months or ≥ 120 months increased the risk of major maternal and neonatal outcomes. We recommend that the optimal interval for women who underwent TOLAC should be 24 to 119 months.

Biomarkers of fatty acids and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

We aimed to quantify and generate comprehensive evidence on the associations of different fatty acids (FAs) with the risk of type 2 diabetes mellitus (T2DM). PubMed, MEDLINE, and Embase were searched for prospective cohort studies that examined the association between FA biomarkers and the risk of T2DM published before 18 May 2020. Random-effects meta-analyses of the effects of FA concentration on T2DM were performed. Thirty-three studies involving 95,810 adults (19,904 cases) were included. Divergent associations of different types of FAs with type 2 diabetes were observed. The pooled relative risk (RRs) of T2DM comparing the top versus the bottom tertile of saturated FAs (C14:0, C16:0, C18:0, total saturated FAs), monounsaturated FA (C16:1 n-7), polyunsaturated FA (C20:3 n-6, C22:4 n-6), and Δ-6-desaturase activities ranged from 1.19 to 1.80. Interestingly, unlike previous studies, we found a negative correlation between odd-chain saturated FAs (C15:0, C17:0), trans-FAs (trans-C16:1 n-7), total n-6, Δ-5-desaturase activities and risk of T2DM. The pooled RRs of T2DM comparing the top versus the bottom tertile of these FAs ranged from 0.62 to 0.78. No associations with T2DM were observed for the other FAs. Considerable heterogeneity was observed in our study, and no definitive conclusions can be made until further investigation has been carried out.

Association between IVF/ICSI treatment and preterm birth and major perinatal outcomes among dichorionic-diamnionic twin pregnancies: A seven-year retrospective cohort study.

INTRODUCTION: This study aimed to evaluate the preterm birth and additional perinatal outcomes between spontaneous and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) dichorionic-diamnionic (DCDA) twin pregnancies. MATERIAL AND METHODS: This retrospective cohort study was conducted in a tertiary university-affiliated medical center. All women with DCDA twin pregnancies were considered for inclusion. The primary outcome of interest was preterm birth <37 weeks of gestation and secondary outcomes included spontaneous preterm birth, iatrogenic (induced) preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, preterm premature rupture of membranes (PPROM), intrahepatic cholestasis of pregnancy, placenta previa, neonatal intensive care unit (NICU) admission, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity. These outcomes were compared between IVF/ICSI and spontaneous twin pregnancies. Multivariable logistic regressions were used to adjust for confounders. General estimated equation models were used to address intertwin correlation. RESULTS: A total of 1297 twin pregnancies, including 213 spontaneous and 1084 IVF/ICSI DCDA pregnancies, met the inclusion criteria. Women with IVF/ICSI pregnancies were older and had higher body mass index, adherence with prenatal care and proportion of nulliparity. After adjustment for confounders, IVF/ICSI pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation (adjusted odds ratio [aOR] 1.72; 95% CI 1.24-2.39), iatrogenic preterm birth <37 weeks of gestation (aOR 1.41; 95% CI 1.00-1.97) as well as NICU admission (aOR 1.34; 95% CI 1.00-1.80). IVF/ICSI pregnancies were associated with a decrease in PPROM (aOR 0.64; 95% CI 0.42-0.99). There were no differences between IVF/ICSI and spontaneous DCDA pregnancies in terms of spontaneous preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity. CONCLUSIONS: IVF/ICSI DCDA twin pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation, iatrogenic preterm birth <37 weeks of gestation, and NICU admission but with a decrease in PPROM. Other outcomes were comparable between IVF/ICSI and spontaneous DCDA twin pregnancies. Multicenter studies with adequate power remain warranted.

Maternal and neonatal outcomes in transverse and vertical skin incision for placenta previa : Skin incision for placenta previa.

BACKGROUND: Placenta previa, a serious obstetric issue, should be managed by experienced teams. The safe and appropriate mode of delivery for placenta previa is by cesarean delivery. However, no studies were found comparing either maternal or neonatal outcomes for different skin incision in women with placenta previa. The aim of this study was to compare maternal and neonatal outcomes by skin incision types (transverse compared with vertical) in a large cohort of women with placenta previa who were undergoing cesarean delivery. METHODS: This was a retrospective cohort study carried out between January 2014 and June 2019. All pregnant women with placenta previa had confirmed by ultrasonologist before delivery and obstetrician at delivery. The primary outcome was the estimated blood loss during the surgery and within the first 24 hours postoperatively. Mean (standard deviation), median (interquartile range) or frequency (percentage) was reported to variables. Appropriate parametric and nonparametric tests were used to analyses. RESULTS: The study included 1098 complete records, 332 (30.24%) cases in the vertical skin incision group and 766 (69.76%) cases in the transverse skin incision group. Those with vertical incision showed a higher percentage of preterm delivery, anterior placenta, abnormally invasive placenta, and history of previous cesarean delivery, and a lower percentage of first pregnancy, in vitro fertilization, and emergency cesarean delivery. After controlling for confounding factors, higher incidence of post-partum hemorrhage (OR 5.47, 95% CI 3.84-7.79), maternal intensive care unit (OR 4.30, 95% CI 2.86-6.45), transfusion (OR 5.97, 95% CI 4.15-8.58), and 5-min APGAR< 7 (OR 9.03, 95% CI 1.83-44.49), a more estimated blood loss (ß 601.85, 95%CI 458.78-744.91), and a longer length of hospital stay after delivery (ß 0.54, 95%CI 0.23-0.86) were found in the vertical skin incision group. CONCLUSIONS: Our data demonstrated that transverse skin incision group showed the better perinatal outcomes in women with placenta previa. Future collaborative studies are needed to be done by centers for placenta previa to have a better understanding of the characteristics and the outcomes of the disease in the choosing skin incision.

Should singleton birth weight standards be applied to identify small-for-gestational age twins?: analysis of a retrospective cohort study.

BACKGROUND: Twin birth weight percentiles are less popular in clinical management among twin pregnancies compared with singleton ones in China. This study aimed to compare the incidence and neonatal outcomes of small for gestational age (SGA) twins between the use of singleton and twin birth weight percentiles. METHODS: This was a retrospective cohort study of 3,027 pregnancies with liveborn twin pairs at gestational age of > 28 weeks. The newborns were categorized as SGA when a birthweight was less than the 10th percentile based on the singleton and twin references derived from Chinese population. Logistic regression models with generalized estimated equation (GEE) were utilized to evaluate the association between SGA twins and neonatal outcomes including neonatal unit admission, neonatal jaundice, neonatal respiratory distress (NRDS), neonatal asphyxia, ventilator support, hypoxic ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intracranial hemorrhage (ICH), culture-proven sepsis, neonatal death within 28 days after birth as well as the composite outcome. RESULTS: The incidence of SGA was 33.1 % based on the singleton reference and 7.3 % based on the twin reference. Both of SGA newborns defined by the singleton and twin references were associated with increases in neonatal unit admission, neonatal jaundice and ventilator support. In addition, SGA newborns defined by the twin reference were associated with increased rates of BPD (aOR, 2.61; 95 % CI: 1.18-5.78) as well as the severe composite outcome (aOR, 1.93; 95 % CI: 1.07-3.47). CONCLUSIONS: The use of singleton birth weight percentiles may result in misdiagnosed SGA newborns in twin gestations and the twin birth weight percentiles would be more useful to identify those who are at risk of adverse outcomes.

Anesthetic management in cesarean delivery of women with placenta previa: a retrospective cohort study.

BACKGROUND: The incidence of placenta preiva is rising. Cesarean delivery is identified as the only safe and appropriate mode of delivery for pregnancies with placenta previa. Anesthesia is important during the cesarean delivery. The aim of this study is to assess maternal and neonatal outcomes of patients with placenta previa managed with neuraxial anesthesia as compared to those who underwent general anesthesia during cesarean delivery. METHODS: A retrospective cohort study was performed of all patients with placenta preiva at our large academic institution from January 1, 2014 to June 30, 2019. Patients were managed neuraxial anesthesia and general anesthesia during cesarean delivery. RESULTS: We identified 1234 patients with placenta previa who underwent cesarean delivery at our institution. Neuraxial anesthesia was performed in 737 (59.7%), and general anesthesia was completed in 497 (40.3%) patients. The mean estimated blood loss at neuraxial anesthesia of 558.96 ± 42.77 ml were significantly lower than the estimated blood loss at general anesthesia of 1952.51 ± 180 ml (p < 0.001). One hundred and forty-six of 737 (19.8%) patients required blood transfusion at neuraxial anesthesia, whereas 381 out of 497 (76.7%) patients required blood transfusion at general anesthesia. The rate neonatal asphyxia and admission to NICU at neuraxial anesthesia was significantly lower than general anesthesia (2.7% vs. 19.5 and 18.2% vs. 44.1%, respectively). After adjusting confounding factors, blood loss was less, Apgar score at 1- and 5-min were higher, and the rate of blood transfusion, neonatal asphyxia, and admission to NICU were lower in the neuraxial group. CONCLUSIONS: Our data demonstrated that neuraxial anesthesia is associated with better maternal and neonatal outcomes during cesarean delivery in women with placenta previa.

Prospective association of metal levels with gestational diabetes mellitus and glucose: A retrospective cohort study from South China.

OBJECTIVE: To explore the prospective correlation between serum metals before 24 weeks' gestation and gestational diabetes mellitus (GDM) or glucose in the late second trimester among southern Chinese pregnant women. METHODS: A total of 8169 pregnant women were included in our retrospective cohort study. Logistic regression was used to investigate the relationships between metals (Manganese [Mn], copper [Cu], lead [Pb], calcium [Ca], zinc [Zn], magnesium [Mg]) and GDM. Quantile regression was performed to detect the shifts and associations with metals and three time-points glucose distribution of oral glucose tolerance test (OGTT) focused on the 10th, 50th, and 90th percentiles. Weighted quantile sum (WQS) regression was used to explore the relationship of metal mixtures and GDM as well as glucose. RESULTS: Maternal serum concentrations of metals were assessed at mean 16.55 ± 2.92 weeks' gestation. Women with under weight might have 25% decreased risk of GDM for every 50% increase in Cu concentration within the safe limits. A 50% increase in Mn and Zn levels was related to a 0.051 µmol/L (95% CI: 0.033-0.070) and 0.059 µmol/L (95% CI: 0.040-0.079) increase in mean fasting plasma glucose of OGTT (OGTT0), respectively. The magnitude of association with Mn was smaller at the upper tail of OGTT0 distribution, while the magnitude of correlation with Zn was greater at the upper tail. However, there was a 0.012 mmol/L (95% CI: -0.017 to -0.008), 0.028 mmol/L (95% CI: -0.049 to -0.007), and 0.036 mmol/L (95% CI: -0.057 to -0.016) decrease in mean OGTT0 levels for every 50% increase in Pb, Ca, and Mg, respectively. The negative association of Pb, Ca, and Mg was greater at the lower tail of OGTT0 distribution. No significant relationship was observed in Cu and mean OGTT0 level (-0.010 mmol/L, 95% CI: -0.021 to 0.001), however, it showed a protective effect at the upper tail (-0.034 mmol/L, 95% CI: -0.049 to -0.017). No obvious correlation was found between metals and postprandial glucose levels (OGTT1 and OGTT2 from OGTT). The WQS index was significantly related to OGTT0 (P < 0.001). The contribution of Mn (80.19%) to metal mixture index was the highest related to OGTT0, followed by Cu (19.81%). CONCLUSIONS: Higher Mn and Zn but lower Pb, Ca, and Mg concentrations within a certain range before 24 weeks' gestation might prospectively impair fasting plasma glucose during pregnancy; a greater focus is required on Mn. It could provide early markers of metal for predicting later glucose and suggest implement intervention for pregnant women.

An Efficient Ring-Closure Method for Preparing Well-Defined Cyclic Polynorbornenes.

An efficient bimolecular ring-closure method is developed to prepare the well-defined cyclic polynorbornenes by combining the living ring-opening metathesis polymerization (ROMP) with the self-accelerating double strain-promoted azide-alkyne cycloaddition (DSPAAC) reaction. In this method, ROMP is used to synthesize the well-defined linear polynorbornenes with both azide terminals by virtue of a N-hydroxysuccinimide-ester-functionalized Grubbs initiator following the modification of polymer end groups. DSPAAC click reaction is then used to ring-close the linear polymer precursors and prepare the corresponding well-defined cyclic polynorbornenes using the sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DIBOD) as small linkers. The self-accelerating DSPAAC ring-closing reaction facilitates this method to efficiently prepare pure cyclic polynorbornenes in the presence of a molar excess of DIBOD small linkers to the linear polynorbornene precursors. This is the first report to prepare well-defined polynorbornenes with cyclic topology based on the ring-closure strategy for cyclic polymers.

Early pregnancy vitamin D and the risk of adverse maternal and infant outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence has suggested that lower gestational vitamin D levels might increase the risks of adverse pregnancy and birth outcomes. The results remain inconsistent and require further exploration. METHODS: A total of 2814 Chinese mother-infant pairs were included in this retrospective cohort study. Serum concentrations of 25(OH)D were reviewed in early pregnancy (16.3 ± 2.3 weeks). Outcomes of maternal gestational diabetes mellitus (GDM), cesarean section, fetal distress, preterm birth, low birth weight (LBW), and macrosomia were extracted from the medical records. Cox regression analysis was used to explore these associations. RESULTS: In total, 19.3% of mothers were pregnant at an advanced age (≥35 years), and 40.3% of pregnant women had vitamin D deficiency (< 50 nmol/L). After adjusting for potential covariates, the hazard ratio (HR) (95% CI) per standard deviation (SD) increase of serum 25(OH)D concentrations was 0.86 (0.779, 0.951) for GDM, 0.844 (0.730, 0.976) for preterm birth, and 0.849 (0.726, 0.993) for LBW. Similar protective associations were found for GDM, cesarean section, and preterm birth for a better vitamin D status when compared with vitamin D deficiency. CONCLUSION: Higher early pregnancy vitamin D was associated with a lower risk of GDM, cesarean section, preterm birth, and LBW.

Poly(ionic liquid)-Modified Magnetic Janus Particles for Dye Degradation.

The Fe3O4@SiO2 paramagnetic Janus particles with phenyl groups and amino groups segmented on two different sides were fabricated by the Pickering emulsion method. Then, the poly(ionic liquid)s were selectively modified onto the amino side via in situ induced ATRP polymerization. Different anions were introduced onto the poly(ionic liquid)s region by exchanging anions to adjust the wettability of the side. Meanwhile, after the PW12O403- anions were employed, the poly(ionic liquid)-modified Fe3O4@SiO2 Janus particles can be used as a catalytic solid emulsifier and degraded water-soluble dyes with the aid of stabilizing emulsion.

The effect of gestational weight gain on perinatal outcomes among Chinese twin gestations based on Institute of Medicine guidelines.

BACKGROUND: Gestational weight gain (GWG) has implications for perinatal outcomes, the guidelines for maternal weight gain, however, remain understudied among twin pregnancies. This study aimed to assess the associations between perinatal outcomes and GWG among twin pregnancies, based on the US institute of Medicine (IOM) 2009 guidelines. METHODS: A retrospective cohort study of pregnant women with viable twins ≥26 weeks of gestation, was conducted in Foshan, China, during July 2015 and June 2018. Maternal BMI was categorized based on Chinese standard and GWG was categorized as below, within and above the IOM 2009 recommendations. Underweight women were excluded for analysis. Perinatal outcomes were compared among these groups. To assess the independent impact of GWG on the perinatal outcomes, conventional multivariable regression and general estimated equation (GEE) were utilized for maternal outcomes and neonatal outcomes, respectively. RESULTS: A total of 645 mothers with twin pregnancies were included, of whom 15.0, 41.4 and 43.6% gained weight below, within and above guidelines, respectively. Compared to weight gain within guidelines, inadequate weight gain was associated with increased risks in spontaneous preterm birth < 37 weeks (aOR:3.55; 95% CI: 1.73-7.28) and < 35 weeks (aOR:2.63; 95% CI: 1.16-5.97). Women who gained weight above guidelines were more likely to have gestational hypertension disorder (aOR: 2.36; 95% CI: 1.32-4.21), pre-eclampsia (aOR: 2.59; 95% CI: 1.29-5.21) and have fetuses weighted >90th percentile and less likely to have fetuses weighted < 2500 g and < 1500 g. CONCLUSIONS: Maintenance of gestational weight gain within the normal range could decrease the risk of adverse perinatal outcomes. However, the causality between pre-eclampsia and gestational weight gain requires further investigations.

Sequential Recognition of Zinc and Pyrophosphate Ions in a Terpyridine-Functionalized Single Nanochannel.

A highly selective recognition system for zinc(II) and pyrophosphate ions is constructed using a single conical nanochannel covalently functionalized with N'-{4-[(2,2':6',2''-terpyridine)-4-yl]benzyl}ethane-1,2-diamine (TPYD). The immobilized TPYD acts as a specific coordination site for Zn2+ to form TPYD-Zn2+ complexes in preference over other metal ions, and subsequently, the resulting Zn2+ -coordinated nanochannel can be used as a selective recognition element for the pyrophosphate ion based on the coordination reaction between hydroxyl oxygen atoms of pyrophosphate and Zn2+ . Ion recognition is monitored by measuring the current-voltage curves of the solutions. The ionic current of the TPYD-functionalized system at -2.0 V undergoes a clear decrease after exposure to Zn2+ ions and is followed with an obvious increase after subsequent treatment with a pyrophosphate solution. The change of ionic current can be primarily attributed to the variation of charge density of the nanochannel. This functionalized single nanochannel might provide a simple and universal means to recognize other targets by modifying different functional molecules onto the inner surfaces of nanochannels.

Efficient Homodifunctional Bimolecular Ring-Closure Method for Cyclic Polymers by Combining RAFT and Self-Accelerating Click Reaction.

An efficient metal-free homodifunctional bimolecular ring-closure method is developed for the formation of cyclic polymers by combining reversible addition-fragmentation chain transfer (RAFT) polymerization and self-accelerating click reaction. In this approach, α,ω-homodifunctional linear polymers with azide terminals are prepared by RAFT polymerization and postmodification of polymer chain end groups. By virtue of sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DBA) as small linkers, well-defined cyclic polymers are then prepared using the self-accelerating double strain-promoted azide-alkyne click (DSPAAC) reaction to ring-close the azide end-functionalized homodifunctional linear polymer precursors. Due to the self-accelerating property of DSPAAC ring-closing reaction, this novel method eliminates the requirement of equimolar amounts of telechelic polymers and small linkers in traditional bimolecular ring-closure methods. It facilitates this method to efficiently and conveniently produce varied pure cyclic polymers by employing an excess molar amount of DBA small linkers.

Sexual dysfunction and mode of delivery in Chinese primiparous women: a systematic review and meta-analysis.

BACKGROUND: Up to now, there is controversy over the effect of delivery mode cesarean delivery and spontaneous vaginal delivery on sexual function. Therefore, we did a systematic review and meta-analysis in postpartum women to explore the mode of delivery, cesarean delivery, and spontaneous vaginal delivery and differences in postpartum sexual function (short- and long-term) in Chinese primiparous women. METHODS: Comprehensive electronic searches of PubMed, EMBASE, Web of Science, Elsevier Science Direct, Cochrane Library, the Chinese Biological Medical Literature database and the Chinese National Knowledge Infrastructure database were conducted to identify any study in each database published to August 31, 2017. The primary outcome was the sexual satisfaction and the secondary outcomes were resumed intercourse and sexual pain in the postpartum. RESULTS: We identified 10 studies with a total population of 2851 in the present meta-analysis. Five and six eligible articles were respectively included for sexual satisfaction in postpartum at 3- and 6 months. Compared with vaginal delivery group, two time points were all not found statistically significance (OR 1.53, 95%CI 0.93-2.49; OR 1.15, 95%CI 0.95-1.39, respectively) in cesarean and spontaneous vaginal delivery group; in resumed intercourse and sexual pain domains, they were all significantly, with an overall OR of 2.05 (95%CI 1.36-3.11) at 3 months, 1.50 (95%CI 1.04-2.16) at 6 months and 0.29 (95%CI 0.24, 0.36) at 3 months, 0.73 (95%CI 0.58, 0.93) at 6 months, respectively. With the passage of time, the gap was closing. Sensitivity analysis was indicated a good stability of the meta-analysis in each domain. CONCLUSIONS: In conclusion, this meta-analysis indicated that the mode of delivery, cesarean and spontaneous vaginal delivery did not affect postpartum sexual satisfaction (short- and long-term) and appeared to have minimal effect on the long-term resumed intercourse and sexual pain in Chinese primiparous women. Primiparous women should be more cautious to choose cesarean section in order to preserve sexual function.