This study aimed to find the association between alanine transaminase-to-aspartate aminotransferase ratio (ALT/AST) and the incidence of gestational diabetes mellitus (GDM).

Ultrasound treatment has been a good hurdle technique for meat curing processing, where both physical and chemical consequences can be involved towards final quality of obtained products. However, the specific correlation between ultrasound parameters and muscle fiber fragmentation and myofibrillar microstructural changes during curing deserve further evaluation. In present study, we comparatively studied the effect of ultrasound-assisted brining (UAB) and static brining (SB) on the muscle proteolysis events and microstructural/morphological variation of porcine meat as well as the physicochemical indices and histological characteristics. The results showed that UAB (20 kHz, 315 W for 1 h) could markedly enhance the muscle proteolysis with higher free-/peptide-bound alpha-amino-nitrogen (α-NH2-N) content (P < 0.05) than SB treatment and greatly improved the fragmentation of muscle fiber tissues of cured meat. Meanwhile, UAB processing favored more opening structures of myofibrillar proteins with more hydrophobic groups being exposed. The quantitative histological analysis revealed that, compared with SB treatment, UAB could significantly increase the gap between muscle fibers and the swelling of the perimysium (P < 0.01), proving an efficient curing process with better textural and water holding properties.

G-protein-signaling modulator 1 (GPSM1) exhibits strong genetic association with Type 2 diabetes (T2D) and Body Mass Index in population studies. However, how GPSM1 carries out such control and in which types of cells are poorly understood. Here, we demonstrate that myeloid GPSM1 promotes metabolic inflammation to accelerate T2D and obesity development. Mice with myeloid-specific GPSM1 ablation are protected against high fat diet-induced insulin resistance, glucose dysregulation, and liver steatosis via repression of adipose tissue pro-inflammatory states. Mechanistically, GPSM1 deficiency mainly promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, thus inhibiting TLR4-induced NF-κB signaling in macrophages. In addition, we identify a small-molecule compound, AN-465/42243987, which suppresses the pro-inflammatory phenotype by inhibiting GPSM1 function, which could make it a candidate for metabolic therapy. Furthermore, GPSM1 expression is upregulated in visceral fat of individuals with obesity and is correlated with clinical metabolic traits. Overall, our findings identify macrophage GPSM1 as a link between metabolic inflammation and systemic homeostasis.

Cytochrome c (Cyt c), one of the most significant proteins acting as an electron transporter, plays an important role during the transferring process of the energy in cells. Apoptosis, one of the major forms of cell death, has been associated with various physiological regularity and pathological mechanisms. It was found that Cyt c can be released from mitochondria to cytosol under different pathological conditions, triggering subsequent cell apoptosis. Herein, we developed a fluorescence nanoprobe based on negatively charged CuInS2-ZnS-GSH quantum dots (QDs) for the sensitive determination of Cyt c. CuInS2-ZnS-GSH QDs with high photochemical stability and favorable hydrophilicity were prepared by a simple hot reflux method and emit a bright orange-red light. The electron-deficient heme group in Cyt c is affiliated with the electron-rich CuInS2-ZnS-GSH QDs through the photo-induced electron transfer process, resulting in a large decrease in fluorescence intensity of QDs. A good linearity for concentration of Cyt c in the range of 0.01-7 μmol L-1 is obtained, and the detection limit of Cyt c is as low as 1.1 nM. The performance on the detection of Cyt c in spiked human serum and fetal bovine serum samples showed good recoveries from 85.5% to 95.0%. Furthermore, CuInS2-ZnS-GSH QDs were applied for the intracellular imaging in HeLa cells showing an extremely lower toxicity and excellent biocompatibility.

The neonatal heart can efficiently regenerate within a short period after birth, whereas the adult mammalian heart has extremely limited capacity to regenerate. The molecular mechanisms underlying neonatal heart regeneration remain elusive. Here, we revealed that as a coreceptor of Wnt signalling, low-density lipoprotein receptor-related protein 5 (LRP5) is required for neonatal heart regeneration by regulating cardiomyocyte proliferation. The expression of LRP5 in the mouse heart gradually decreased after birth, consistent with the time window during which cardiomyocytes withdrew from the cell cycle. LRP5 downregulation reduced the proliferation of neonatal cardiomyocytes, while LRP5 overexpression promoted cardiomyocyte proliferation. The cardiac-specific deletion of Lrp5 disrupted myocardial regeneration after injury, exhibiting extensive fibrotic scars and cardiac dysfunction. Mechanistically, the decreased heart regeneration ability induced by LRP5 deficiency was mainly due to reduced cardiomyocyte proliferation. Further study identified AKT/P21 signalling as the key pathway accounting for the regulation of cardiomyocyte proliferation mediated by LRP5. LRP5 downregulation accelerated the degradation of AKT, leading to increased expression of the cyclin-dependent kinase inhibitor P21. Our study revealed that LRP5 is necessary for cardiomyocyte proliferation and neonatal heart regeneration, providing a potential strategy to repair myocardial injury.

Transglutaminase (TGase) is a regulator of posttranslational modification of protein that provides physiological protection against diverse environmental stresses in plants. Nonetheless, the mechanisms of TGase-mediated salt tolerance remain largely unknown. Here, we found that the transcription of cucumber TGase (CsTGase) was induced in response to light and during leaf development, and the CsTGase protein was expressed in the chloroplast and the cell wall. The overexpression of the CsTGase gene effectively ameliorated salt-induced photoinhibition in tobacco plants, increased the levels of chloroplast polyamines (PAs) and enhanced the abundance of D1 and D2 proteins. TGase also induced the expression of photosynthesis related genes and remodeling of thylakoids under normal conditions. However, salt stress treatment reduced the photosynthesis rate, PSII and PSI related genes expression, D1 and D2 proteins in wild-type (WT) plants, while these effects were alleviated in CsTGase overexpression plants. Taken together, our results indicate that TGase-dependent PA signaling protects the proteins of thylakoids, which plays a critical role in plant response to salt stress. Thus, overexpression of TGase may be an effective strategy for enhancing resistance to salt stress of salt-sensitive crops in agricultural production.

Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for >1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype.

The total glucosides of paeony (TGP) are used to treat psoriasis in the clinic. However, its active components and mechanisms are not clear. Paeoniflorin is the main constituent of TGP. Thus, the anti-psoriasis effect of paeoniflorin was studied, and its mechanism was explored.

Methyl-CpG binding domain proteins (MBD) can specifically bind to methylated CpG sites and play important roles in epigenetic gene regulation. Here, we identified and functionally characterized the MBD protein in Tribolium castaneum. T. castaneum genome encodes only one MBD protein: TcMBD2/3. RNA interference targeting this gene at different developmental stages caused lethal phenotypes including metamorphosis deficiency in larvae and pupae, gastrointestinal system problems and fecundity deficiency in adult. Moreover, Tcmbd2/3 knockdown adult showed progressive reduced locomoter activity, a typical neurodegeneration phenotype. This is a common feature of DNA methylation in mammals and has not been found in other insects. However, band shift assays demonstrated that TcMBD2/3 could not bind to methylated DNA, indicating the essential roles of TcMBD2/3 is independent of DNA methylation. Our study provides Tcmbd2/3 plays important roles in T. castaneum and gives new insights into the potential mechanism of action of MBD proteins in insect.

Autologous stem cell therapy has not been as effective as forecasted from preclinical studies. Patient age was reported as an important contributing factor. The goal of this study was to uncover age-dependent mechanisms of stem cell dysfunction and to investigate possible means to restore the cellular function. Bone marrow mesenchymal stem cells (MSCs) were isolated from cardiovascular patients. Cell proliferation and number of colonies were inversely correlated with patient age. Myogenic differentiation of MSCs in culture was induced with 5-azacytidine. Differentiation correlated with age, with less differentiation in MSCs from aged patients. We performed real-time PCR to identify genes in the WNT/β-catenin signaling network and found that transcript levels of CTNNB1, LEF1, FZD8, WNT3A, and SFRP4 were negatively correlated with age, whereas FOSL1, LRP6, and FZD6 were positively correlated with age. Protein evaluation showed that β-catenin nuclear translocation correlated with age and was lower in aged MSCs. Aged MSCs treated with lithium chloride-to increase the bioavailability of β-catenin-recovered their capacity for myogenic differentiation through myocyte enhancer factor 2C but not with the knockdown of β-catenin using small-interfering RNA. This study may be the first to relate reduced nuclear β-catenin bioavailability in MSCs from aged patients. Most important, this abnormality was potentially recoverable, providing a target for improving the function of bone marrow stem cells and their clinical utility in aged patients.

In recent years, docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy plus concurrent chemoradiotherapy (CCRT) has been commonly applied for locally advanced nasopharyngeal carcinoma (LA-NPC). However, whether TPF+CCRT regimen is the best choice for LA-NPC remains unclear. This meta-analysis aims to elucidate and compare the efficacy and toxicity of TPF+CCRT versus CCRT alone for LA-NPC.

Reprogramming of pancreatic exocrine to insulin-producing cells by viral delivery of the genes encoding transcription factors neurogenin-3 (Ngn3), pancreas/duodenum homeobox protein 1 (Pdx1) and MafA is an efficient method for reversing diabetes in murine models. The variables that modulate reprogramming success are currently ill-defined.

Previous studies have demonstrated that elevated homocysteine (Hcy) level represents an independent risk factor for macrovascular disease. However, the relationship between hyperhomocysteinemia and the progression of diabetic retinopathy in patients remains controversial. Hence, the purpose of this systematic review and meta-analysis was to explore any potential association between Hcy and the risk of diabetic retinopathy.

Objective: To investigate the ability of homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy for predicting gestational diabetes mellitus (GDM) in Chinese women with different first-trimester body mass index (FT-BMI) values. Methods: Baseline characteristics and laboratory tests were collected at the first prenatal visit (6−12 weeks of gestation). GDM was diagnosed by a 75 g oral glucose tolerance test (OGTT) at 24−28 weeks of gestation. Partial correlation analysis and binary logistic regression were applied to identify the association between HOMA-IR and GDM. The cutoff points for predicting GDM were estimated using receiver operating characteristic (ROC) curve analysis. Results: Of the total of 1343 women, 300 (22.34%) were diagnosed with GDM in the 24−28 weeks of gestation. Partial correlation analysis and binary logistic regression verified HOMA-IR as a significant risk factor for GDM in the normal weight subgroup (FT-BMI < 24 kg/m2) (adjusted OR 2.941 [95% CI 2.153, 4.016], P < 0.001), overweight subgroup (24.0 kg/m2 ≤ FT-BMI < 28.0 kg/m2) (adjusted OR 3.188 [95% CI 2.011, 5.055], P < 0.001), and obese subgroup (FT-BMI ≥ 28.0 kg/m2) (adjusted OR 9.415 [95% CI 1.712, 51.770], p = 0.01). The cutoff values of HOMA-IR were 1.52 (area under the curve (AUC) 0.733, 95% CI 0.701−0.765, p < 0.001) for all participants, 1.43 (AUC 0.691, 95% CI 0.651−0.730, p < 0.001) for normal weight women, 2.27 (AUC 0.760, 95% CI 0.703−0.818, p < 0.001) for overweight women, and 2.31 (AUC 0.801, 95% CI 0.696−0.907, p < 0.001) for obese women. Conclusions: Increased HOMA-IR in early pregnancy is a risk factor for GDM, and HOMA-IR can be affected by body weight. The cutoff value of HOMA-IR to predict GDM should be distinguished by different FT-BMI values.

G-protein-signaling modulator 1 (GPSM1) has been proved the potential role in brain tissues, however, whether GPSM1 in hypothalamic nuclei, especially in POMC neurons is essential for the proper regulation of whole-body energy balance remains unknown. The aim of our current study was to explore the role of GPSM1 in POMC neurons in metabolic homeostasis.

Two fermenters, Lactobacillus acidophilus (LA) and the active dry yellow wine yeast (HY), were utilized to ferment cattle bones in order to release calcium. The influences of fermenters and the fermentation process on the calcium release capacity, particle properties, morphology, and chemical composition of bone powders were assessed, and the underlying mechanism was discussed. The results showed that LA had a better capacity of acid production than yeast, and therefore released more calcium during the fermentation of bone powders. The released calcium in the fermentation broth mainly existed in the forms of free Ca2+ ions, organic acid-bound calcium and a small amount of calcium-peptide chelate. For bone powders, the fermentation induced swollen bone particles, increased particle size, and significant changes of the internal chemical structure. Therefore, fermentation has a great potential in the processing of bone-derived products, particularly to provide new ideas for the development of calcium supplement products.