Lysosome-related biomarkers in preeclampsia and cancers: Machine learning and bioinformatics analysis.

BACKGROUND: Lysosomes serve as regulatory hubs, and play a pivotal role in human diseases. However, the precise functions and mechanisms of action of lysosome-related genes remain unclear in preeclampsia and cancers. This study aimed to identify lysosome-related biomarkers in preeclampsia, and further explore the biomarkers shared between preeclampsia and cancers. MATERIALS AND METHODS: We obtained GSE60438 and GSE75010 datasets from the Gene Expression Omnibus database, pre-procesed them and merged them into a training cohort. The limma package in R was used to identify the differentially expressed mRNAs between the preeclampsia and normal control groups. Differentially expressed lysosome-related genes were identified by intersecting the differentially expressed mRNAs and lysosome-related genes obtained from Gene Ontology and GSEA databases. Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the DAVID database. The CIBERSORT method was used to analyze immune cell infiltration. Weighted gene co-expression analyses and three machine learning algorithm were used to identify lysosome-related diagnostic biomarkers. Lysosome-related diagnostic biomarkers were further validated in the testing cohort GSE25906. Nomogram diagnostic models for preeclampsia were constructed. In addition, pan-cancer analysis of lysosome-related diagnostic biomarkers were identified by was performed using the TIMER, Sangebox and TISIDB databases. Finally, the Drug-Gene Interaction, TheMarker and DSigDB Databases were used for drug-gene interactions analysis. RESULTS: A total of 11 differentially expressed lysosome-related genes were identified between the preeclampsia and control groups. Three molecular clusters connected to lysosome were identified, and enrichment analysis demonstrated their strong relevance to the development and progression of preeclampsia. Immune infiltration analysis revealed significant immunity heterogeneity among different clusters. GBA, OCRL, TLR7 and HEXB were identified as lysosome-related diagnostic biomarkers with high AUC values, and validated in the testing cohort GSE25906. Nomogram, calibration curve, and decision curve analysis confirmed the accuracy of predicting the occurrence of preeclampsia based on OCRL and HEXB. Pan-cancer analysis showed that GBA, OCRL, TLR7 and HEXB were associated with the prognosis of patients with various tumors and tumor immune cell infiltration. Twelve drugs were identified as potential drugs for the treatment of preeclampsia and cancers. CONCLUSION: This study identified GBA, OCRL, TLR7 and HEXB as potential lysosome-related diagnostic biomarkers shared between preeclampsia and cancers.

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.

UDP-glucose epimerase 1, moonlighting as a transcriptional activator, is essential for tapetum degradation and male fertility in rice.

Multiple enzymes perform moonlighting functions distinct from their main roles. UDP-glucose epimerases (UGEs), a subclass of isomerases, catalyze the interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDP-Gal). We identified a rice male-sterile mutant, osuge1, with delayed tapetum degradation and abortive pollen. The mutant osuge1 protein lacked UDP-glucose epimerase activity, resulting in higher UDP-Gal content and lower UDP-Glc levels in the osuge1 mutant compared with the wild type. Interestingly, we discovered that OsUGE1 participates in the TIP2/bHLH142-TDR-EAT1/DTD transcriptional regulatory cascade involved in tapetum degradation, in which TIP2 and TDR regulate the expression of OsUGE1 while OsUGE1 regulates the expression of EAT1. In addition, we found that OsUGE1 regulates the expression of its own gene by directly binding to an E-box element in the OsUGE1 promoter. Collectively, our results indicate that OsUGE1 not only functions as a UDP-glucose epimerase but also moonlights as a transcriptional activator to promote tapetum degradation, revealing a novel regulatory mechanism of rice reproductive development.

Effect of Crystallographic Orientations on Bendability in a Strongly Textured Mg-9Al Extrusion Plate and Texture Evolution during Three-Point Bending.

The dependence of bendability on crystallographic orientations and texture evolution was investigated in a strongly textured Mg-9Al extrusion plate by bending along four directions. Results show that the bars have relatively small and reasonably close bendability when bent along the extrusion direction, transverse direction, and through-thickness direction. In contrast, the bendability of the 45° bar is much larger. Microstructure examination indicates that twins are prevalent in all bars. Furthermore, a detailed analysis of deformation mechanisms suggests that the initial texture transforms towards a basal texture during bending. Nevertheless, the texture transformation efficiency is drastically lower when basal slip-in contrast to tensile twinning-is the dominant deformation mechanism. The difference in texture evolution efficiency was used to rationalize the varied bendability along different directions. The findings of this provide insights into improving the bendability of magnesium alloys.

Influence of Long-Period Stacked Ordered Phases on Inductive Impedance of Mg-Gd-Y-Zn-Zr-Ag Alloys.

In this paper, the influence of long-period stacked ordered (LPSO) phases on the electrochemical impedance spectroscopy (EIS) of a Mg-Gd-Y-Zn-Zr-Ag alloy in 0.9 wt.% NaCl was investigated. The Mg-6Gd-3Y-1Zn-0.5Zr-0.3Ag (wt.%) alloy samples with and without LPSO phases in the grain interior (HOMO and LPSO, respectively) were prepared using different heat treatments. The EIS results showed that both the HOMO and LPSO samples' Nyquist diagrams contained two inductive loops. However, in the Nyquist plots of the LPSO samples, the inductive loops at 1.71-0.67 Hz appeared in the first quadrant rather than the fourth quadrant. Analysis of the fitting parameters illustrated that the abnormal shape of the inductive loops is related to greater values of the surface film capacitance Cf and double layer capacitance Cdl in the LPSO samples. Further investigations through corrosion morphology observation indicated that the greater values of Cf and Cdl in the LPSO samples resulted from the existence of intragranular LPSO phases that created more film-free areas. The above results show that a better understanding of the relationship between the inductive impedance and corrosion morphology of a Mg-6Gd-3Y-1Zn-0.5Zr-0.3Ag alloy in 0.9 wt.% NaCl solution was attained.

The Effect of Initial Grain Size on the Nanocrystallization of AZ31 Mg Alloy during Rotary Swaging.

Nanograins were obtained in the AZ31 Mg alloy bars with different initial grain sizes via cold rotary swaging. Microstructure evolution during deformation was investigated through electron backscatter diffraction analysis and transmission electron microscopy studies. The results indicate that initial grain size had little effect on the mechanism of grain refinement during swaging. The nanocrystallization process of the alloys with different initial grain sizes included extensive twinning followed by the further refinement of the twin lamellae through the formation of massive dislocation arrays. However, as the initial grain size decreased, the formation rate of nanograins increased, resulting in a higher degree of nanocrystallization after the same swaging pass. The mean grain size and yield strength of the sample with the smallest initial grain size were about 91 nm and 489 MPa, respectively. The slower rate and lower degree of nanocrystallization in the alloy with a larger initial grain size were mainly attributed to the less grain boundary areas and higher activity of twinning.

[Retracted] MicroRNA­155 enhances the activation of Wnt/ß­catenin signaling in colorectal carcinoma by suppressing HMG­box transcription factor 1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blot assay data shown in Figs. 1C and 6A were strikingly similar to data appearing in different form in another article written by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 13: 2221­2228, 2016; DOI: 10.3892/mmr.2016.4788].

OsFLA1 encodes a fasciclin-like arabinogalactan protein and affects pollen exine development in rice.

KEY MESSAGE: OsFLA1 positively regulates pollen exine development, and locates in the cellular membrane. Arabinogalactan proteins are a type of hydroxyproline-rich glycoprotein that are present in all plant tissues and cells and play important roles in plant growth and development. Little information is available on the participation of fasciclin-like arabinogalactan proteins in sexual reproduction in rice. In this study, a rice male-sterile mutant, osfla1, was isolated from an ethylmethanesulfonate-induced mutant library. The osfla1 mutant produced withered, shrunken, and abortive pollen. The gene OsFLA1 encoded a FLA protein and was expressed strongly in the anthers in rice. Subcellular localization showed that OsFLA1 was located in the cellular membrane. In the osfla1 mutant, abnormal Ubisch bodies and a discontinuous nexine layer of the microspore wall were observed, which resulted in pollen abortion and ultimately in male sterility. The results show the important role that OsFLA1 plays in male reproductive development in rice.

Optimization of QuEChERS and high performance liquid chromatography-fluorescence detection conditions to assess the impact of preparation procedures on EU priority PAHs in coffee samples and their PAHs consumption risk.

The good performance conditions for determination of EU priority PAHs in coffee samples were established to evaluate the effects of roasting degree on the PAHs in coffee beans and the brewing methods on the PAHs transfer from coffee beans to their brews. The consumption risk of the PAHs in coffee products was also assessed. The PAHs levels of the roasted coffee beans were in the order: 923.65 ng/g (dark roast) > 132.20 ng/g (medium roast) > 69.28 ng/g (light roast). Compared with general brewing with the drip bag (PAHs content, 0.30-0.62 ng/mL in coffee brews), the coffee machine brewing (set at 4 bar) induced higher PAHs release into coffee brews (PAHs content, 0.36-2.14 ng/g). The PAHs amounts of the commercial brewed and canned coffee products were 0.32-1.23 ng/g and 0.16-0.46 ng/g, respectively. The consumption risk of the PAHs in the coffee brews and products is a low level of concern.

Twinning-Induced Abnormal Strain Rate Sensitivity and Indentation Creep Behavior in Nanocrystalline Mg Alloy.

Nanocrystalline materials exhibit many unique physical and chemical properties with respect to their coarse-grained counterparts due to the high volume fraction of grain boundaries. Research interests on nanocrystalline materials around the world have been lasting over the past decades. In this study, we explored the room temperature strain rate sensitivity and creep behavior of the nanocrystalline Mg-Gd-Y-Zr alloy by using a nanoindentation technique. Results showed that the hardness and creep displacements of the nanocrystalline Mg-Gd-Y-Zr alloy decreased with increasing loading strain rate. That is, the nanocrystalline Mg-Gd-Y-Zr alloy showed negative strain rate sensitivity and its creep behavior also exhibited negative rate dependence. It was revealed that the enhanced twinning activities at higher loading strain rates resulted in reduced hardness and creep displacements. The dominant creep mechanism of the nanocrystalline Mg-Gd-Y-Zr alloy is discussed based on a work-of-indentation theory in this paper.

Maternal and Neonatal Outcomes of Placenta Previa with and without Coverage of a Uterine Scar: A Retrospective Cohort Study in a Tertiary Hospital.

BACKGROUND: To compare the maternal and neonatal outcomes of placenta previa (PP) with and without coverage of a uterine scar in Foshan, China. METHODS: A retrospective cohort study comparing all singleton pregnancies with PP was conducted at a tertiary, university-affiliated medical center from 1 January 2012 to 31 April 2017 in Foshan, China. Demographic, clinical and laboratory data were extracted from electronic medical records (EMRs). Maternal and neonatal outcomes of PP with and without coverage of a uterine scar were compared by statistical method. RESULTS: There were 58,062 deliveries during the study period, of which 726 (1.25%) were complicated PP in singleton pregnancies and were further classified into two groups: the PP with coverage of a uterine scar group (PPCS, n=154) and the PP without coverage of a uterine scar group (Non-PPCS, n=572). Overall, premature birth (<37 weeks, 67.5% vs 54.8%; P=0.019), cesarean section (100% vs 97.6%; P=0.050), intraoperative blood loss >1000 mL (77.9% vs 16.0%; P<0.001) or >3000mL (29.9% vs 3.0%; P<0.001), bleeding within 2-24 hours after delivery (168.2±370.1 ml vs 49.9±58.4 ml; P<0.001), postpartum hemorrhage (48.7% vs 15.7%; P<0.001), transfusion (34.6% vs 16.1%; P<0.001), hemorrhage shock (7.8% vs 1.9%; P<0.001), hysterectomy (2.6% vs 0.5%; P=0.019), fetal distress (35.7% vs 12.1%; P<0.001) and APGAR score at 1 min (15.2% vs 7.1%; P=0.002) had a significant difference between PPCS group and Non-PPCS group. After grouping by whether complicated with placenta accreta spectrum disorders (PASD), we found that PPCS was significant associated with more intraoperative blood loss >1000mL, intraoperative blood loss >3000mL, bleeding within 2-24 hours after delivery and fetal distress than the Non-PPCS group. CONCLUSION: The PPCS group had poorer maternal and neonatal outcomes than the Non-PPCS group after grouping by whether pregnancies complicated with PASD or with different placental positions.

Micro-Shear Bands and Their Enhancement on High Temperature Strength of Mg-Gd-Y-Zr Alloy.

When Mg-Gd-Y-Zr alloy is cold forged, a large number of nano-micro shear bands are formed inside the grains. It is observed that micro-shear bands hinder the sliding of dislocations, resulting in an increase in tensile strength at elevated temperatures. The subsequent aging treatment further strengthens the alloy. Compared with unforged aged alloys, aged samples with pre-generated micro-shear bands exhibit higher strength at room temperature to 250 °C, but exhibit similar properties at higher temperatures. Microstructure characterization and fracture behavior analysis indicate that the transformation of deformation mode from dislocation sliding to grain boundary activity is mainly due to the change of mechanical properties with temperature. In addition, the alloy precipitates with the aid of dislocations during tension, and exhibits higher strength at 200 °C than that at room temperature.

Sevoflurane protects against ischemia-reperfusion injury in mice after total knee arthroplasty via facilitating RASD1-mediated protein kinase A pathway activation.

This study aimed to explore effects of Sevoflurane on ischemia-reperfusion (I/R) injury after total knee arthroplasty (TKA). To explore potential molecular mechanism, Ras related dexamethasone induced 1 (RASD1), a Protein kinase A (PKA) activator, frequently associated with various models of I/R injury, was also investigated. In vivo mouse models with I/R injury after TKA and in vitro cell models with I/R injury were induced. Contents of creatinine kinase (CK), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), serum levels of inflammatory factors, expression of PKA pathway-related genes and cell proliferation and apoptosis were measured. RASD1 was altered and PKA pathway was inhibited in mice and cells to elucidate the involvement of RASD1 and PKA pathway in Sevoflurane treatment on I/R injury. RASD1 was upregulated in I/R injury after TKA. Sevoflurane treatment or silencing RASD1 reduced RASD1 expression, CK, LDH and MDA contents, inflammation, apoptosis, but increased proliferation, SOD content, cAMP expression, and extents of PKA and cAMP responsive element binding protein (CREB) phosphorylation in skeletal muscle cells of I/R injury. Additionally, PKA pathway activation potentiated the therapeutic effect of Sevoflurane on I/R injury after TKA. Altogether, Sevoflurane treatment confines I/R injury after TKA via RASD1-mediated PKA pathway activation.

Deformation Mechanism, Microstructure, and Mechanical Properties Evolution of Mg-Gd-Y-Zr Alloy during Cold Torsion.

Mg-Gd-Y-Zr alloy was subjected to torsion of various strain levels at room temperature. Obvious traces of basal slip were observed in the twisted alloy. Dislocations of were also observed, but there were no signs of significant sliding. Even in the sample whose equivalent strain became 0.294, 101¯0 twinning and 101¯2 twinning were rarely seen. The deformation mode with predominant basal dislocations and subordinate dislocations resulted in a modified Y fiber texture with a basal pole slightly dispersed at about 70° from the twist axis. Mechanical tests revealed that the tensile strength and compressive strengths increased simultaneously after twisting.

Targeting RNF8 effectively reverses cisplatin and doxorubicin resistance in endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the most frequent gynecological malignancy worldwide. However, resistance to chemotherapy remains one of the major difficulties in the treatment of EC. Thus, there is an urgent requirement to understand mechanisms of chemoresistance and identify novel regimens for patients with EC. We found that protein and mRNA expression levels of RNF8 were significantly increased in both cisplatin and doxorubicin resistant EC cells. Cell survival assay showed that RNF deficiency significantly enhanced the sensitivity of resistant EC cells to cisplatin and doxorubicin (P < 0.01). In addition, chemoresistant EC cells exhibited increased NHEJ efficiency. Knockout of RNF8 in chemoresistant EC cells significantly reduced NHEJ efficiency and prolonged Ku80 retention on DSB. Moreover, cisplatin resistant AN3CA xenograft showed that RNF8 deficiency overcame cisplatin resistance. Our in vitro and in vivo assays provide evidence for RNF8, which is a NHEJ factor, serving as a promising, novel target in EC chemotherapy.

Decreased Vascular Bundle 1 affects mitochondrial and plant development in rice.

BACKGROUND: Mitochondria are vital regulators of plant growth and development, constitute the predominant source of ATP, and participate in multiple anabolic and catabolic metabolic pathways. But the mechanism by which dysfunctional mitochondria affect plant growth remains unknown, and more mitochondria-defective mutants need to be identified. RESULTS: A mitochondria-defective mutant decreased vascular bundle 1 (dvb1) was isolated from rice mutant library mutagenized by EMS (ethylmethane sulfonate), which shows dwarfism, narrow leaves, short branches, few vascular bundles, and low fertility. Map-based cloning, genetic complementation, and phylogenetic analysis revealed that DVB1 encodes a structural protein classified in the Mic10 family and is required for the formation of cristae in mitochondria, and was primarily expressed in vascular bundles. The DVB1 protein is partially localized in the mitochondria and capable of forming dimers and polymers. Comparing with the wild type, disruption of amino acid metabolism and increased auxin synthesis were observed in dvb1 mutant which also showed increased sensitivity to the mitochondrial electron transport inhibitors. CONCLUSIONS: DVB1 belongs to Mic10 family and DVB1 is partially localized in the mitochondria. Further studies indicated that DVB1 is important for mitochondrial and plant development in rice.

Mesenchymal Stem Cell-Derived Exosomal microRNA-3940-5p Inhibits Colorectal Cancer Metastasis by Targeting Integrin α6.

BACKGROUND: Exosomes are potential tools for disease control by regulating intercellular communication through carrying proteins and RNAs between cells or remote organs. Exosome activities have aroused wide concerns in cancer biology and malignancy control. AIMS: This study was performed to explore the roles of mesenchymal stem cell (MSC)-derived exosomes in colorectal cancer (CRC) progression. METHODS: MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed, and aberrantly expressed miRNAs in CRC tissues were obtained from the data available on the GEO database. Altered expression of miR-3940-5p was introduced to identify its role in CRC invasion and metastasis in both cell and animal models. The binding relationship between miR-3940-5p and Integrin alpha6 (ITGA6) was predicted on TargetScan and validated through a luciferase assay. The effects of ITGA6 on CRC were figured out. RESULTS: MSC-derived exosomes carried miR-3940-5p into CRC cells. Up-regulation of miR-3940-5p inhibited epithelial-mesenchymal transition (EMT) and invasion of CRC cells, and suppressed the tumor metastasis and growth in vivo. miR-3940-5p was found to directly bind to ITGA6. Overexpression of ITGA6 promoted CRC cell invasion and EMT and tumor progression through upregulating the transforming growth factor-beta1 (TGF-ß1) signaling. A TGF-ß1-specific antagonist, Disitertide, blocked the functions of ITGA6 both in vivo and in vitro. CONCLUSION: MSC-exosomal miR-3940-5p inhibits invasion and EMT of CRC cells as well as growth and metastasis of tumors through targeting ITGA6 and the following TGF-ß1 inactivation. This study may provide novel insights into exosome-based treatment for CRC.

SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner.

OBJECTIVE: Serum response factor (SRF), a sequence-specific transcription factor, is closely related to metastasis of gastric cancer, a digestive tract cancer. Herein, we probed the effect of SRF on metastasis and progression of colon cancer (CC), another digestive tract disorder, and the detailed mechanism. METHODS: Microarray analysis was conducted on tumor and adjacent tissues to filter differentially expressed miRNA, followed by RT-qPCR validation in CC cell lines. The transcription factor and the target gene of microRNA-214 (miR-214) were predicted, and their binding relationships were tested by luciferase reporter assays and ChIP assays. Subsequently, SRF and protein tyrosine kinase 6 (PTK6) expression in CC patients and cells was evaluated by RT-qPCR, while JAK2 and STAT3 expression in cells by Western blot analysis. To further explore functions of miR-214, PTK6 and SRF on CC, CC cells were delivered with si-PTK6, miR-214 mimic and/or SRF overexpression. RESULTS: miR-214 expressed poorly in CC tissues and cell lines, which related to advanced TNM staging and survival. miR-214 mimic inhibited proliferation, migration, invasion, xenograft tumor growth and metastasis of CC cells. SRF, overexpressed in CC samples and cells, suppressed the transcription of miR-214. Meanwhile, SRF upregulation counteracted the inhibitory role of miR-214 mimic in CC cell growth. miR-214 negatively regulated PTK6 expression to impair the JAK2/STAT3 pathway activation, thereby halting CC cell proliferation, migration, invasion, xenograft tumor growth and metastasis. CONCLUSION: Altogether, miR-214 may perform as a tumor suppressor in CC, and the SRF/miR-214/PTK6/JAK2/STAT3 axis could be applied as a biomarker and potential therapeutic target.

Enhanced Mechanical and Corrosion Performance by Forming Micro Shear Bands in Cold Forged Mg-Gd-Y-Zr Alloy.

Forging at room temperature was applied on the per-extruded Mg-Gd-Y-Zr alloy to investigate the effect of cold forging on the microstructure, mechanical properties and corrosion resistance of the alloy. Abundant micro shear bands with misorientations of 2-15° were generated in the as forged alloys. Tremendous enhancement in tensile yield strength was achieved after forging. With a quantitative investigation, micro band boundaries were considered to provide a great contribution to the reinforcement. The ultrafine structure resulting from the formation of micro shear bands led to increased corrosion resistance of the alloy.

Size and Shape of Associations of OGTT as Well as Mediating Effects on Adverse Pregnancy Outcomes Among Women With Gestational Diabetes Mellitus: Population-Based Study From Southern Han Chinese.

Objective: To explore the size and shape association of OGTT values with adverse pregnancy complications among women with gestational diabetes mellitus (GDM) in Southern Han Chinese population and further analyze their mediating effects with maternal age in outcomes. Methods: 6,861 women with GDM were included in the study. Logistic regression was used to identify the correlations between OGTT values and adverse pregnancy outcomes of GDM. Restricted cubic spline nested logistic regression was conducted to investigate potential non-linear and linear associations. Mediating effect among maternal age, OGTT and adverse outcomes were explored. Results: Women with GDM had a mean age of 31.83, and 24.49% had advanced maternal age (≥35 years). In logistic regression with adjustment, compared with lower OGTT0 (<5.1 mmol/L), GDM patients with higher OGTT0 (≥5.1 mmol/L) exhibited 1.891 (95% CI: 1.441-2.298, P < 0.001), 1.284 (1.078-1.529, P = 0.005), 1.285 (1.065-1.550, P = 0.009), and 1.302 (1.067-1.590, P = 0.010) times increased risk of hypertensive disorders of pregnancy (HDP), preterm, neonatal hyperbilirubinemia, and macrosomia, respectively. GDM patients with higher OGTT1 (≥10 mmol/L) had only found to exhibited 1.473-fold (1.162-1.867, P = 0.001) increasing risk of HDP than those with lower OGTT1 (<10 mmol/L). No adverse outcome was identified to associate with higher OGTT2 (≥8.5 mmol/L). Linear relationships (non-linear P > 0.05) were observed between OGTT0 and HDP, preterm, neonatal hyperbilirubinemia, and macrosomia in both maternal age groups (<35 and ≥35 years). Non-linear associations of OGTT1 with incidence of HDP, preterm, and neonatal hyperbilirubinemia were detected in GDM patients younger than 35 years (non-linear P = 0.037, P = 0.049, P = 0.039, respectively), rising more steeply at higher values. Similar non-linearity was noted for OGTT2 with HDP in older patients. All OGTT values had significant mediating effects on some special complications caused by higher age. Conclusion: Higher fasting plasma glucose was more strongly linked to adverse pregnancy outcomes among GDM patients. Both linearity and Non-linearity of associations between glucose and complications should be taken into account. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT is needed.