Exogenous hydrogen sulfide prevents necroptosis by inhibiting p38MAPK pathway activation in JEG-3 trophoblast cells: A role in preeclampsia.

Setting 7 subsection in abstract Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high-glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study was aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE. DESIGN: This is an in vitro experimental study. PARTICIPANTS: A total of 10 pregnant women with severe preeclampsia (PE) and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. METHODS: The expression and localization of necrotic proteins were assayed in human placenta samples and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor). RESULTS: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine-ß-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. LIMITATIONS: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of preeclampsia. CONCLUSIONS: we proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1, and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H2S protected cytotrophoblasts against CER-induced necroptosis via the p38MAPK pathway.

Association of prepregnancy body mass index and gestational weight gain trajectory with adverse pregnancy outcomes-a prospective cohort study in Shanghai.

OBJECTIVES: The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs). DESIGN: This was a prospective cohort study. SETTING: This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China. PRIMARY AND SECONDARY OUTCOME MEASURES: A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model. RESULTS: The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP. CONCLUSIONS: As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.

Coastal distribution and driving factors for blue carbon fractions in the surface soil of a warm-temperate salt marsh in China.

A better understanding of blue carbon (BC) sequestration can not only contribute to a better elucidation of global carbon cycle processes but can also lay the foundation for the incorporation of BC ecosystems into regional and global carbon offset schemes. In this study, the surface soils of seven plots along a landward to seaward distance gradient were analyzed for the concentrations and stocks of soil organic carbon (SOC), soil inorganic carbon (SIC), dissolved organic carbon (DOC), and dissolved inorganic carbon (DIC), as well as soil physical (bulk density, texture, moisture), chemical (pH, electrical conductivity), and microbiological (phospholipid fatty acid) properties in the coastal wetlands. Correlation, variation partition and random forest (RF) analyses were used to identify key variables correlating with BC fraction distribution patterns. The results suggested that SIC, DIC, and DOC, exhibited similar landward-increasing trends but the driving factors were distinct from each other. Based on correlation and RF analysis, both SIC and DIC were closely related to soil moisture and clay contents, but microbial indicators of arbuscular mycorrhizal fungi and actinomycete, were found to be associated with SIC, and abiotic properties played less important but still substantial roles in predicting DIC dynamics. In contrast with the other three investigated BC fractions, SOC showed a slight tendency toward enrichment in the seaward direction, and SIC was identified as the main driving factor. DOC showed no significant correlations with the other BC fractions, and its variation could not be explained well by the selected edaphic parameters. The soils in the YRD's tidal Suaeda salsa salt marshes showed a significant negative coupled SOC-SIC correlation, which was potentially related to divergent sedimentary processes and potential biotransformation between SOC and SIC. These results highlight the importance of integrating multiple BC fractions and their interactions into attempts to explore key mechanisms of BC cycling.

Inferior plant competitor allocates more biomass to belowground as a result of greater competition for resources in heterogeneous habitats.

Nutrient heterogeneity in soil widely exists in nature and can have significant impacts on plant growth, biomass allocation, and competitive interactions. However, limited research has been done to investigate the interspecific competitive intensity between two clonal species in a heterogeneous habitat. Therefore, this greenhouse experiment was conducted with two clonal species, Phragmites australis and Scirpus planiculumis, exposed to heterogeneous and homogeneous patches of soil nutrients at five different planting ratios (0:4, 1:3, 2:2, 3:1 and 4:0), to assess the effects of both soil heterogeneity and interspecific competition on plant growth. It was found that soil nutrient heterogeneity significantly enhanced P. australis' interspecific competitive capacity and biomass by promoting a 20% increase in belowground allocation. Interestingly, the planting ratio did not affect the magnitude of this net outcome. In contrast, the superior competitor S. planiculumis did not exhibit significant change of growth indicators to the heterogeneous soil patches. These findings imply that the uncertainties associated with human-induced redistribution of plant species may lead to a shift in dominance from other species to those like P. australis, which have strong nutrient foraging abilities in response to heterogeneity in emergent wetland plant communities.

Is Chemerin Associated with Gestational Diabetes Mellitus? A Case-Control Study.

Purpose: The aim of this study was to investigate the relationship between gestational diabetes mellitus (GDM) and Chemerin by analyzing chemerin levels in peripheral blood and cord blood, and chemerin mRNA and its protein expression in placenta and adipose tissue. Methods: A case-control study was conducted in 110 women with GDM and 110 controls without GDM who received regular prenatal services and delivered at Shanghai Pudong New Area Healthcare Hospital for Women and Children from June 2019 to December 2020. Results: The age, pre-pregnancy weight, pre-pregnancy BMI, antepartum BMI, TG/HDL ratio and TG levels in pregnant women with GDM were significantly higher than those in women without GDM, and HDL levels were significantly lower than those in the normal group. Chemerin in the umbilical cord blood of the GDM group was significantly higher than in that of the normal group, but there was no difference in chemerin levels in peripheral blood. In the two groups, the chemerin concentration in peripheral blood was significantly higher than that in umbilical cord blood (P<0.001). The Chemerin mRNA and protein expression levels in the placenta and adipose tissue of pregnant women in the GDM group were significantly higher than those in the normal group (P <0.001). In the GDM group, the expression of chemerin protein in adipose tissue was significantly higher than that in placental tissue. Regression analysis showed that the expression level of chemerin protein in placental tissue and adipose tissue was positively correlated with the risk of GDM. Conclusion: Elevated chemerin is closely related to the risk of GDM, and the placenta may be an important secretion of chemotactic factor sources in addition to adipose tissue and participate in the development of GDM.

Increasing the Mechanical Stability of Polymer-Gold Interfacial Connection: A Parallel Covalent Strategy.

Thiol-gold (S-Au) chemistry has been widely used in coating and functionalizing gold surfaces because it is robust and highly efficient. However, recent studies have shown that the S-Au-based self-assembled monolayers can lead to significant instability under external mechanical loading (e.g., in a swelled polymer film). Such instability limits further applications of S-Au chemistry-based functional materials. Here, we report a surface-modifying procedure based on a parallel covalent strategy. By employing dendritic macromolecules as a "middle layer" between the gold surface and polymer, the interfacial connecting strength increased by at least 350% as revealed by atomic force microscopy-based single molecule force spectroscopy (AFM-SMFS). The ultimate cleavage structure is confirmed to be an amide bond by control SMFS experiments, fluorescent microscopy, and dynamic force spectroscopy. This study/concept paves the way to prepare stable stimuli-responsive polymer brushes on solid surfaces and study mechanophores with high force stability.

Host Defense Peptides in Nutrition and Diseases: A Contributor of Immunology Modulation.

Host defense peptides (HDPs) are primary components of the innate immune system with diverse biological functions, such as antibacterial ability and immunomodulatory function. HDPs are produced and released by immune and epithelial cells against microbial invasion, which are widely distributed in humans, animals, plants, and microbes. Notably, there are great differences in endogenous HDP distribution and expression in humans and animals. Moreover, HDP expression could be regulated by exogenous substances, such as nutrients, and different physiological statuses in health and disease. In this review, we systematically assessed the regulation of expression and mechanism of endogenous HDPs from nutrition and disease perspectives, providing a basis to identify the specificity and regularity of HDP expression. Furthermore, the regulation mechanism of HDP expression was summarized systematically, and the differences in the regulation between nutrients and diseases were explored. From this review, we provide novel ideas targeted the immune regulation of HDPs for protecting host health in nutrition and practical and effective new ideas using the immune regulation theory for further research on protecting host health from pathogenic infection and excessive immunity diseases under the global challenge of the antibiotic-abuse-induced series of problems, including food security and microbial resistance.

Sodium butyrate alleviates LPS-induced kidney injury via inhibiting TLR2/4 to regulate rBD2 expression.

Defensins represent an integral part of the innate immune system to ward off potential pathogens. The study used a rat model to investigate mechanisms by which sodium butyrate (NaB) regulates ß-defensin to inhibit lipopolysaccharide (LPS)-induced nephrotoxicity. We found that NaB alleviated LPS-induced renal structural damage, as judged by reduced renal lesions and improved glomerular vascular structure. In addition, elevated levels of indicators of kidney damage creatinine and blood urine nitrogen, inflammatory mediators TNF-α, and IL-6 dropped after NaB administration. Rat ß-defensin 2 (rBD2), as estimated by mRNA level, was significantly higher in LPS-treated kidneys, whereas the changes of rBD2 reduced in NaB-treated kidneys. In addition, NaB alleviated LPS-induced increase in TLRs mRNA expression. Mechanistically, the present study indicates that NaB has nephroprotective activity resulting from modulation of TLR2/4 to regulate rBD2 expression hence curbing inflammation. PRACTICAL APPLICATIONS: In practice, adding NaB to diet can improve animal performance. Our results suggest that dietary supplementation of NaB increases animal feed intake and improves the body's defense ability to relieve inflammation caused by bacteria. Especially in the age of resistance prohibition, sodium butyrate can partially replace antibiotics to induce the expression of body defensin. It may become a health care product to enhance the body's immunity.

Sodium butyrate alleviates intestinal injury and microbial flora disturbance induced by lipopolysaccharides in rats.

Bacterial endotoxin invasion reduces intestinal barrier functions, such as intestinal bacterial translocation and enteric infection. In this study, we investigated whether sodium butyrate (NaB) alleviates lipopolysaccharide (LPS)-induced inflammation by reducing intestinal damage and regulating the microflora. Rats were divided into four groups for the intraperitoneal injection of LPSs and intragastric gavage with NaB: Con, LPS, LPS + NaB, and NaB. The results showed that NaB alleviated intestinal villus injury and inflammatory infiltration caused by LPS. NaB supplementation decreased the mRNA levels of toll-like receptor (TLR)-4, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the trend was most pronounced in the jejunum. The morphology of the intestinal nucleus and mitochondria was further observed by transmission electron microscopy. The results showed that NaB supplementation alleviated LPS-induced nuclear atrophy, apoptosis, mitochondrial damage, and rupture. Moreover, NaB improved the LPS-induced inflammatory response by regulating the intestinal barrier. Furthermore, 16S rRNA sequencing showed that the LPS increased the abundance of the harmful bacterium Bacteroides, while the abundance of beneficial bacteria decreased. In the LPS + NaB group, the intestinal microbiota destroyed by the LPS was rebalanced, including a decrease in Bacteroides and an increase in Bifidobacterium and Odoribacter. In conclusion, NaB alleviates LPS-induced enteritis by regulating inflammatory cytokines, maintaining the mucosal barrier, and restoring the microbiota changes.

Chemical Fuel Mediated Self-Regulatory Polymer Brushes for Autonomous Fluorescence Modulator and Wettability Switcher.

Synthetic systems of nonequilibrium self-assembly have made considerable progress; however, the achievement of innovative materials with self-regulated functions analogous to living systems remains a grand challenge. Herein, a versatile nonequilibrium system of polymer brushes with spatiotemporally programmable properties and functions driven by chemical fuels is reported. By combining a responsive polymer with an autonomous pH regulator, the polymer brushes self-regulate their swelling and deswelling process with tunable lifetimes. By using patterned copolymer brushes with pH-responsive fluorescence moiety, an autonomous fluorescence modulator is created that self-regulates its fluorescence in spatiotemporally programmable fashion driven by a chemical or an enzymatic reaction. Furthermore, a self-regulated wettability switcher of polymer brushes both in air and in an aqueous solution is implemented. The methodology and results in the work provide a useful avenue into the exploration of nonequilibrium synthetic materials with programmable functions and would accelerate the transformative developments of nonequilibrium materials and systems in practical applications.

Tryptophan Promotes Intestinal Immune Defense through Calcium-Sensing Receptor (CaSR)-Dependent Metabolic Pathways.

The gastrointestinal tract forms a robust line of defense against invading pathogens through the production of endogenous antimicrobial peptides (AMPs), which are crucial molecules of the innate defense system. Tryptophan could modulate intestinal immunity through promoting the expression of AMPs. However, the precise mechanism needs to be further clarified. In this study, we show that treatment with tryptophan for 24 h triggers (p < 0.05) the expression of porcine ß-defensin (pBD) 1 (62.67 ± 3.10 pg/mL) and pBD2 (74.41 ± 1.33 pg/mL) in the porcine intestinal epithelial cells (IPEC-J2) though calcium-sensing receptor (CaSR)-tryptophan metabolic pathways. Meanwhile, tryptophan alleviates (p < 0.05) intestinal inflammation induced by lipopolysaccharide (LPS) through induction of the defensins and activation of the CaSR-AMP-activated protein kinase (AMPK) pathways in vitro and in vivo. Moreover, the activation of CaSR induces the expression of defensins and decreases the levels of IL-1ß (75.26 ± 2.74 pg/mL) and TNF-α (449.8 ± 23.31 pg/mL) induced by LPS (p < 0.05). Importantly, tryptophan maintains kynurenine homeostasis through the activation of CaSR during the inflammatory response. To that end, the work identifies a regulatory circuit between CaSR signaling and tryptophan metabolic pathways involved in the tryptophan-trigged AMP expression, which contributes to improving intestinal immune defense.

Changes in soil microbial community composition during Phragmites australis straw decomposition in salt marshes with freshwater pumping.

The dynamic changes of soil microorganisms after Phragmites australis straw addition in the incubation tubes were analyzed by phospholipid fatty acid stable isotope probing (PLFA-SIP). After comparing soils from different freshwater pumping areas in the Yellow River Estuary (10-year pumping area, 15-year pumping area and natural salt marsh without pumping), the results showed that the total PLFA contents significantly increased by 59.99%-146.93% after the addition of straw to surface soils (0-10 cm) in the pumping areas, whereas the changes in deeper soils (10-20 cm) were not significant. In particular, the PLFA results showed that bacteria and fungi were significantly increased after 10 days with straw addition. Straw treatment also improved the ratio of fungi to bacteria (F:B) in the surface soils of all sampling sites. The soil microorganisms directly absorbed straw-derived 13C, where Gram-negative bacteria (GN) were found to have the highest PLFA-13C values during the 40-day decomposition process. Soil characteristics can significantly affect microbial community composition. Accordingly, soil organic carbon (SOC) was found to be significantly positively related to bacterial, fungal and other microbial biomasses, while moisture, electric conductivity (EC) and soil aggregate composition were important factors of influence on the microbial community. The findings indicated that both fungi and bacteria were essential microbial communities in straw decomposition, the significant increase of fungi biomass and the absorption of straw-derived 13C by bacteria were the main changes of microbial community. Long-term freshwater pumping can promote straw decomposition by increasing microbial biomass and changing microbial community composition.

The association of elevated serum ferritin concentration in early pregnancy with gestational diabetes mellitus: a prospective observational study.

BACKGROUND/OBJECTIVES: The results linking body iron stores to the risk of gestational diabetes mellitus (GDM) are conflicting. We aimed to measure the serum ferritin level of women in early pregnancy and evaluate the risk of GDM in a Chinese urban population. SUBJECTS/METHODS: In total, 851 pregnant women between 10 and 20 weeks of gestation took part in the prospective, observational study conducted. The women were divided into four groups by quartiles of serum ferritin levels (Q1-4). Their blood samples were collected and assayed for several biochemical variables at the beginning of the study, and the women were followed up with a 75-g oral glucose tolerance test at 24-28 weeks of gestation. RESULTS: The participants had an average serum ferritin concentration of 65.67 µg/L. GDM prevalence within each serum ferritin quartile was 9.4%, 14.6%, 18.8% and 19.3%, respectively, (P = 0.016). The odds ratio for GDM in the ferritin Q2-4 was 1.64 (CI: 0.90-2.99), 2.23 (CI: 1.26-3.96) and 2.31 (CI: 1.30-4.10), compared with Q1, respectively. This association persisted after adjusting for potential confounders factors. In addition, in Q4, pregnant women with a pre-pregnancy body mass index ≥24 kg/m2, maternal age ≤35 years old or haemoglobin≥ 110 g/L did have an increased risk of developing GDM. CONCLUSIONS: Elevated serum ferritin concentrations in early gestation are associated with an increased risk of GDM, especially in pregnant women who have a high baseline iron storage status with no anaemia or who are overweight/obese. Individual iron supplementation should be considered to minimize the risk of GDM.

Quantifying the Mechanical Anisotropy in Poly(3-hexylthiophene) Nanofibers.

Correlating the structure with nanomechanical property of semicrystalline conjugated-polymer crystal is of essential importance for the performance improvement and design of flexible electronic devices. Although it is well-known that the semicrystalline conjugated-polymer crystal exhibits anisotropic structure owing to the π-π and layer stacking of highly coplanar conjugated backbones, the structure-nanomechanical property relationship is missing. Here, we investigated the axial mechanical anisotropy of the P3HT nanofiber by using thermal shape-fluctuation analysis and a three-point bending test based on atomic force microscopy. Our results show that Young's modulus in the layer-stacking direction (EL) is 1-2 orders of magnitude greater than that in the π-conjugated backbone direction (EB). We attribute this mechanical anisotropy to the π-stacking of the P3HT backbone, but the layer stacking will decrease EL, which weakens the mechanical anisotropy. Moreover, we demonstrated that the P3HT nanofiber shows a loading-rate-independent Young's modulus and deformation-dependent resilience in the layer-stacking direction.

Quantifying the Chain Folding in Polymer Single Crystals by Single-Molecule Force Spectroscopy.

Chain folding is a motif of polymer crystallization, which is essential for determining the crystallization kinetics. However, the experimental quantification of the chain folding remains a challenge because of limited instrumental resolution. Here, we quantify chain folding in solution-grown single crystals by using atomic force microscopy (AFM)-based single-molecule force spectroscopy. The fingerprint spectrum of force-induced chain motion allows us to decipher the adjacent and nonadjacent re-entry folding with spatial resolution of subnanometers. The average fractions of adjacent re-entry folds ⟨f⟩ are in the range 91-95% for polycaprolactone, poly-l-lactic acid, and polyamide 66, which is higher than the values determined by other classical technologies. The established single-molecule method is applicable to a broad range of crystalline polymer systems with different chain conformations or compositions.

The utility of HbA1c combined with haematocrit for early screening of gestational diabetes mellitus.

AIMS: To evaluate the utility of glycated haemoglobin A1c (HbA1c) alone and in combination with haematocrit (HCT) for screening gestational diabetes mellitus (GDM) between 12-16 gestational weeks. METHODS: This prospective study was carried out in the Obstetrics and Gynaecology Hospital of Fudan University from November 2014 to February 2015. In total, 690 pregnant women between 20 and 35 years old were included in this study. All subjects received a routine blood examination for HbA1c and HCT at 12-16 gestational weeks (gw) and a 75-g oral glucose tolerance test at 24-28 gw. Threshold values for the diagnosis of GDM were a plasma glucose concentration of 5.1 mmol/L after fasting, 10.0 mmol/L at 60 min, and 8.5 mmol/L at 120 min. Receiver operating characteristic curves were used to evaluate the diagnostic performance of HbA1c with or without HCT. RESULTS: One hundred seven women were diagnosis with GDM at 24-28 gw. An HbA1c cutoff value < 4.55% at 12-16 gw showed adequate sensitivity to exclude GDM (85.0%) but low specificity (17.3%), while an HbA1c cutoff value ≥ 5.25% presented adequate specificity (96.6%) but low sensitivity (13.3%) in diagnosing GDM. The area under the receiver operating characteristic curve for HbA1c (12-16 gw) detection of GDM was 0.563 (95% confidence interval [CI], 0.50-0.625). When combined HbA1c with HCT ( > 38.8%) for the screening of GDM, the area under the receiver operating characteristic curve was 0.604 (95% [CI] 0.509, 0.701). CONCLUSIONS: Whether the adoption of HbA1c as a screening test for GDM would benefit pregnant women remains to be determined. However, combining HbA1c with HCT for the screening of GDM may be a useful tool to predict GDM.

Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: A randomized controlled trial.

It has previously been reported that the influence of vitamin D on the metabolism of calcium and phosphorus is associated with diabetes, cardiovascular disease, Alzheimer's disease, cancer and other systemic diseases, and is considered an important indicator of general health. The present study was conducted to determine the effect of various doses of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation and the levels of oxidative stress of pregnant women with gestational diabetes mellitus (GDM). The present randomized, double-blind placebo-controlled clinical trial was conducted on 133 pregnant women with GDM during weeks 24-28 of pregnancy. The patients were randomly divided into four groups. The control group (n=20) received a placebo (sucrose; one granule/day), the low dosage group (n=38) received the daily recommended intake of 200 IU vitamin D (calciferol) daily, the medium dosage group (n=38) received 50,000 IU monthly (2,000 IU daily for 25 days) and the high dosage group (n=37) received 50,000 IU every 2 weeks (4,000 IU daily for 12.5 days). The general characteristics and dietary intakes of the patients with GDM were similar between each group. Using ELISA kits, it was determined that insulin, homeostatic model assessment-insulin resistance and total cholesterol were significantly reduced by high dosage vitamin D supplementation (P<0.05). Total antioxidant capacity and total glutathione levels were significantly elevated as a result of high dosage vitamin D supplementation (P<0.01). In conclusion, high-dose vitamin D supplementation (50,000 IU every 2 weeks) significantly improved insulin resistance in pregnant women with GDM.