Abstract
Background
The evidence on the associations of the timing of maternal gestational diabetes mellitus (GDM) with the comprehensive growth trajectory from perinatal to early childhood in ...offspring is limited. The potential mechanism remains elusive. Our aim is to estimate the associations of the timing of GDM diagnosis and gestational weight gains (GWG) with the growth trajectory of children from perinatal to early childhood.
Methods
A total of 7609 participants are included from the Maternal & Infants Health in Hefei cohort study. Primary predictors were the timing of maternal GDM diagnosis and GWG during pregnancy. The main outcomes included fetal ultrasonic measurements, birth size as well as BMI peak indicators during infancy within 48 months.
Results
GDM diagnosed before 26 weeks was associated with increased risks of overgrowth for fetal abdominal circumference (OR 1.19, 95% CI 1.04–1.36) and birth weight (OR 1.51, 95% CI 1.19–1.91) when compared with unexposed. GDM diagnosis < 26 weeks was related to the higher BMI peak (β 0.16, 95%CI 0.03–0.28) within 48 months. The significantly additive impacts of maternal early GDM diagnosis and excessive gestational weight gains (EGWG) on offspring overgrowth were observed. Women in GDM < 26 weeks with early EGWG group had higher levels of hsCRP compared with GDM > 26 weeks (
P
< 0.001).
Conclusions
Exposure to maternal GDM diagnosed before 26 weeks with early EGWG could lead to shifts and/or disruptions from the typical growth trajectory from perinatal to early childhood in offspring.
Gynostemma pentaphyllum is a herbal medicine widely used in Asian countries, and its saponin extracts have been shown to possess potent anti-inflammatory effects. Gypenoside XVII, an active ...ingredient isolated from Gynostemma pentaphyllum, has been found to alleviate the inflammation induced by LPS in the BV2 microglia, according to our preliminary study. This study aims to evaluate whether Gypenoside XVII could attenuate depression-like symptoms in vivo and tries to demonstrate the involvement of the complement regulation in its antidepressant-like effect. The results showed that Gypenoside XVII significantly attenuated depression-like behaviors in the forced swimming test, tail suspension test and sucrose preference test. It also alleviated the acute stress-induced hyperactivity of serum corticosterone levels. Additionally, Gypenoside XVII significantly inhibited the activation of microglia and the expression of C3 in mice exposed to chronic unpredictable mild stress (CUMS). Meanwhile, the activation of C3aR/STAT3 signaling and the expression of proinflammatory cytokines was reversed by Gypenoside XVII. Moreover, CUMS induced excessive synaptic pruning by activating microglia, while Gypenoside XVII restored it in the prefrontal cortex. Our data demonstrated that Gypenoside XVII, the active ingredient of Gynostemma pentaphyllum, produced the antidepressant-like effects in mice, which was mediated by the inhibition of complement C3/C3aR/STAT3/cytokine signaling in the prefrontal cortex.
We propose a chemical language processing model to predict polymers’ glass transition temperature (Tg) through a polymer language (SMILES, Simplified Molecular Input Line Entry System) embedding and ...recurrent neural network. This model only receives the SMILES strings of a polymer’s repeat units as inputs and considers the SMILES strings as sequential data at the character level. Using this method, there is no need to calculate any additional molecular descriptors or fingerprints of polymers, and thereby, being very computationally efficient. More importantly, it avoids the difficulties to generate molecular descriptors for repeat units containing polymerization point ‘*’. Results show that the trained model demonstrates reasonable prediction performance on unseen polymer’s Tg. Besides, this model is further applied for high-throughput screening on an unlabeled polymer database to identify high-temperature polymers that are desired for applications in extreme environments. Our work demonstrates that the SMILES strings of polymer repeat units can be used as an effective feature representation to develop a chemical language processing model for predictions of polymer Tg. The framework of this model is general and can be used to construct structure–property relationships for other polymer properties.
This paper reports that a novel chirped fiber Bragg grating (FBG), which is made of photosensitive polarization maintaining fiber, is made successfully in China for the first time. An experiment of ...an adaptive PDM compensator, in which this grating is used as a PDM compensator, is performed successfully. The value of PDM compensation is about 40 ps, and the effect is very good.
Diabetes-associated male sexual dysfunction and fertility impairments are both common clinical complications with limited therapeutic options; hence it seriously affects the quality of life of the ...patients, in particular, the patients of reproductive age. Lycium barbarum polysaccharide (LBP) has long being believed to maintain and to promote reproductive functions in the traditional medical practice in China. The current study was to investigate if LBP may contribute to recovery of male sexual dysfunction and fertility impairments in diabetic individuals. The effects of LBP on sexual behaviors and histological changes of testis were studied in the type-1 diabetes male mice induced by intra-peritoneal (i.p.) injection of streptozotocin (STZ). After oral administration of LBP (10, 20 or 40 mg/kg), sildenafil citrate (SC, 5 mg/kg) or saline for 62 consecutive days, the typical abnormal changes in the sperm parameters, in relative weight of reproductive organs and in morphology of testis were observed in diabetic mice. LBP treatment of the diabetic mice considerably reversed those changes and Johnsen’s testicular score, serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) level were also increased to different degrees. Moreover, our data have also shown that a marked improvement in sexual behavior and fertility level after administration of LBP (40 mg/kg) compared to the diabetic group. These results suggested that LBP can exert functional recovery of male sexual dysfunction and fertility damages induced by diabetes in male mice, which is likely to be mediated through regulating the hypothalamus- pituitary-gonadal axis endocrine activity.
The morphology and active site engineering of electrocatalysts is an efficient strategy to improve the intrinsic activity and selectivity of electrocatalytic CO2 reduction. Here the ultralong and ...thin Bi nanobelts (Bi‐NBs) are fabricated, which feature a high edge‐to‐facet ratio and high‐degree connectivity is inherited from the ultrahigh‐aspect‐ratio crystalline bismuth−organic hybrid nanobelts, through a cathodically in situ reconstruction process. The unique nanostructure of Bi‐NBs leads to a significantly enhanced performance for electrocatalytic CO2 reduction with a near‐unity formate selectivity and high formate partial current density, which is far superior to those of the discrete Bi counterparts with low edge‐to‐facet ratios. Notably, Bi‐NBs perform ultrahigh formate selectivity over a broad potential window with a high current density reaching 400 mA cm−2 for formate production in a flow cell. Moreover, it is ultrastable to continuous electrolysis for nearly 23 h at 200 mA cm−2 without compromising the selectivity. Based on calculations, the enhanced performance is closely related to the high edge‐to‐facet ratio of Bi‐NBs, since the rich edge sites are conducive to the stabilization of the key *OCHO intermediate for formate production. In addition, the ultralong and interconnected Bi‐NBs provide “expressways” for electron transfer during CO2 electroreduction, further contributing to the improved performance.
Thin Bi nanobelts inheriting the high edge‐to‐facet ratio and high‐degree connectivity are fabricated by cathodical in situ conversion of bismuth–organic hybrid nanobelts. Such distinctive structure is conducive to stabilization of the key *OCHO intermediate for formate production and acts as “expressways” for electron transfer leading to an excellent electrocatalytic performance toward electrocatalytic CO2 reduction to formate.
Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the ...role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC
values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.
Radiation therapy has been widely applied in cancer treatment.However,it often causes thrombocytopenia （deficiency of white blood cells） as an adverse effect.Recombinant human interleukin-6 （rhIL-6） ...has been found to be a very effective way against this thrombocytopenia,but IL-6 has low stability in blood,which reduces its efficacy.To increases the stability and half-life of rhIL-6,it was modified by polyethylene glycol （PEG）.The pharmacokinetics and the tissue distribution of PEG-rhIL-6 labeled with 125I were examined after subcutaneous injection in rats.The pharmacokinetic pattern of PEG-rhIL-6 was defined with linear-kinetics,and we fitted a one-compartment model with half-lives of 10.44–11.37 h （absorption,t1/2Ka） and 19.77–21.53 h （elimination,t1/2Ke）,and peak concentrations at 20.51–21.96 h （tpeak） in rats.Half-lives and tpeak of PEG-rhIL-6 were longer than those of rhIL-6 previously reported.In the present study,for deposition of PEG-rhIL-6 in rats,the tissue distribution examination showed that blood was the major organ involved,rather than liver.However,as to the elimination of PEG-rhIL-6,the major organ was the kidney.The excretion fraction of the injection dose recovered from urine was 23.32% at 192 h after subcutaneous administration.Less than 6% of PEG-rhIL-6 was eliminated via the feces at 192 h.These results indicate that PEG-rhIL-6 is a good candidate drug formulation for patients with cancer.
Accumulating evidence demonstrates that ferroptosis may be important in the pathophysiological process of traumatic brain injury (TBI). As a major hormone of the pineal gland, melatonin exerts many ...beneficial effects on TBI, but there is no information regarding the effects of melatonin on ferroptosis after TBI. As expected, TBI resulted in the time‐course changes of ferroptosis‐related molecules expression and iron accumulation in the ipsilateral cortex. Importantly, we found that treating with melatonin potently rescued TBI induced the changes mentioned above and improved functional deficits versus vehicle. Similar results were obtained with a ferroptosis inhibitor, liproxstatin‐1. Moreover, the protective effect of melatonin is likely dependent on melatonin receptor 1B (MT2). Although ferritin plays a vital role in iron metabolism by storing excess cellular iron, its precise function in the brain, and whether it involves melatonin's neuroprotection remain unexplored. Considering ferritin H (Fth) is expressed predominantly in the neurons and global loss of Fth in mice induces early embryonic lethality, we then generated neuron‐specific Fth conditional knockout (Fth‐KO) mice, which are viable and fertile but have altered iron metabolism. In addition, Fth‐KO mice were more susceptible to ferroptosis after TBI, and the neuroprotection by melatonin was largely abolished in Fth‐KO mice. In vitro siFth experiments further confirmed the results mentioned above. Taken together, these data indicate that melatonin produces cerebroprotection, at least partly by inhibiting neuronal Fth‐mediated ferroptosis following TBI, supporting the notion that melatonin is an excellent ferroptosis inhibitor and its anti‐ferroptosis provides a potential therapeutic target for treating TBI.
The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct ...proteomics and phosphoproteomics profiling of 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing of 94 tumor-NAT pairs, and RNA sequencing in 83 tumor-NAT pairs. Our analysis reveals an extensively altered proteome and 252 potential druggable proteins in AEG tumors. We identify three proteomic subtypes with significant clinical and molecular differences. The S-II subtype signature protein, FBXO44, is demonstrated to promote tumor progression and metastasis in vitro and in vivo. Our comparative analyses reveal distinct genomic features in AEG subtypes. We find a specific decrease of fibroblasts in the S-III subtype. Further phosphoproteomic comparisons reveal different kinase-phosphosubstrate regulatory networks among AEG subtypes. Our proteogenomics dataset provides valuable resources for understanding molecular mechanisms and developing precision treatment strategies of AEG.
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