Identification and validation of stable reference genes for RT-qPCR analyses of Kobresia littledalei seedlings.

BACKGROUND: Kobreisa littledalei, belonging to the Cyperaceae family is the first Kobresia species with a reference genome and the most dominant species in Qinghai-Tibet Plateau alpine meadows. It has several resistance genes which could be used to breed improved crop varieties. Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) is a popular and accurate gene expression analysis method. Its reliability depends on the expression levels of reference genes, which vary by species, tissues and environments. However, K.littledalei lacks a stable and normalized reference gene for RT-qPCR analysis. RESULTS: The stability of 13 potential reference genes was tested and the stable reference genes were selected for RT-qPCR normalization for the expression analysis in the different tissues of K. littledalei under two abiotic stresses (salt and drought) and two hormonal treatments (abscisic acid (ABA) and gibberellin (GA)). Five algorithms were used to assess the stability of putative reference genes. The results showed a variation amongst the methods, and the same reference genes showed tissue expression differences under the same conditions. The stability of combining two reference genes was better than a single one. The expression levels of ACTIN were stable in leaves and stems under normal conditions, in leaves under drought stress and in roots under ABA treatment. The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression was stable in the roots under the control conditions and salt stress and in stems exposed to drought stress. Expression levels of superoxide dismutase (SOD) were stable in stems of ABA-treated plants and in the roots under drought stress. Moreover, RPL6 expression was stable in the leaves and stems under salt stress and in the stems of the GA-treated plants. EF1-alpha expression was stable in leaves under ABA and GA treatments. The expression levels of 28 S were stable in the roots under GA treatment. In general, ACTIN and GAPDH could be employed as housekeeping genes for K. littledalei under different treatments. CONCLUSION: This study identified the best RT-qPCR reference genes for different K. littledalei tissues under five experimental conditions. ACTIN and GAPDH genes can be employed as the ideal housekeeping genes for expression analysis under different conditions. This is the first study to investigate the stable reference genes for normalized gene expression analysis of K. littledalei under different conditions. The results could aid molecular biology and gene function research on Kobresia and other related species.

Risk factors for high-stage histological chorioamnionitis among pregnancies with cervical incompetence.

AIM: The study aimed to identify predictive risk factor to identify high-stage histological chorioamnionitis (HCA) in pregnancies with cervical incompetence (CIC). METHODS: A retrospective cohort study was conducted by including 116 pregnant women with cervical incompetence that required prophylactical and therapeutical cerclage. The histopathology examination on placenta was conducted with informed patient consent. All the cases included in this study were divided based on the severity degree of HCA. The demographic characteristic and the parameters related to maternal and fetal outcome were all analyzed. Besides, perioperative parameters of cerclage, including cervical length, cervical morphology, and laboratory indexes were also compared between two groups. Univariate and multivariate logistic regression analysis were used to determine the risk factor of severe chorioamnionitis. RESULTS: Severe HCA was significantly associated with cervical morphology, cerclage indication, cerclage type, and cervical length measured via ultrasound and vaginal examination. After adjusted for confounders, V-type funneling and short cervix was indicated as independent risk factors of severe HCA by multivariate logistic regression analysis, respectively. CONCLUSIONS: V-type funneling and short cervix may indicate the elevated risk of high-stage HCA. Due to the negative outcomes related with high-stage HCA, appropriate prenatal treatment would improve the pregnancy outcomes in cerclaged population. To facilitate postpartum treatment, placental histological examination should be routinely recommended to identify the high-stage HCA, especially in high risk pregnancies.

Phosphoethanolamine cytidylyltransferase ameliorates mitochondrial function and apoptosis in hepatocytes in T2DM in vitro.

Liver function indicators are often impaired in patients with type 2 diabetes mellitus (T2DM), who present higher concentrations of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase than individuals without diabetes. However, the mechanism of liver injury in patients with T2DM has not been clearly elucidated. In this study, we performed a lipidomics analysis on the liver of T2DM mice, and we found that phosphatidylethanolamine (PE) levels were low in T2DM, along with an increase in diglyceride, which may be due to a decrease in the levels of phosphoethanolamine cytidylyltransferase (Pcyt2), thus likely affecting the de novo synthesis of PE. The phosphatidylserine decarboxylase pathway did not change significantly in the T2DM model, although both pathways are critical sources of PE. Supplementation with CDP-ethanolamine (CDP-etn) to increase the production of PE from the CDP-etn pathway reversed high glucose and FFA (HG&FFA)-induced mitochondrial damage including increased apoptosis, decreased ATP synthesis, decreased mitochondrial membrane potential, and increased reactive oxygen species, whereas supplementation with lysophosphatidylethanolamine, which can increase PE production in the phosphatidylserine decarboxylase pathway, did not. Additionally, we found that overexpression of PCYT2 significantly ameliorated ATP synthesis and abnormal mitochondrial morphology induced by HG&FFA. Finally, the BAX/Bcl-2/caspase3 apoptosis pathway was activated in hepatocytes of the T2DM model, which could also be reversed by CDP-etn supplements and PCYT2 overexpression. In summary, in the liver of T2DM mice, Pcyt2 reduction may lead to a decrease in the levels of PE, whereas CDP-etn supplementation and PCYT2 overexpression ameliorate partial mitochondrial function and apoptosis in HG&FFA-stimulated L02 cells.

Iron delivery systems for controlled release of iron and enhancement of iron absorption and bioavailability.

Iron deficiency is a global nutritional problem, and adding iron salts directly to food will have certain side effects on the human body. Therefore, there is growing interest in food-grade iron delivery systems. This review provides an overview of iron delivery systems, with emphasis on the controlled release of iron during gastrointestinal digestion, as well as the enhancement of iron absorption and bioavailability. Iron-bearing proteins are easily degraded by digestive enzymes and absorbed through receptor-mediated endocytosis. Instead, protein aggregates are slowly degraded in the stomach, which delays iron release and serves as a potential iron supplement. Amino acids, peptides and polysaccharides can bind iron through iron binding sites, but the formed compounds are prone to dissociation in the stomach. Moreover, peptides and polysaccharides can deliver iron by mediating the formation of ferric oxyhydroxide which is absorbed through endocytosis or bivalent transporter 1. In addition, liposomes are unstable during gastric digestion and iron is released in large quantities. Complexes formed by polysaccharides and proteins, and microcapsules formed by polysaccharides can delay the release of iron in the gastric environment and prolong iron release in the intestinal environment. This review is conducive to the development of iron functional ingredients and dietary supplements.

Contribution of κ-/ι-carrageenan on the gelling properties of shrimp myofibrillar protein and their interaction mechanism exploration.

BACKGROUND: The contribution and mechanism of κ-/ι-carrageenan (CG) with different hydration characteristics on the gelling properties of shrimp myofibrillar protein (MP) gelation was studied. RESULTS: The gel strength, water-holding capacity and viscoelastic properties of MP gels were significantly enhanced by 1.0% κ-/ι-CG (P < 0.05), but the microstructure showed that excessive carrageenan caused fragmentation of the gel network and a corresponding decrease in gel properties. Compared to MP-ιCG, MP-κCG showed larger breaking force and shorter breaking distance, thus enhancing the hardness and brittleness of the gel, which might be ascribed to a reinforced network skeleton and a tighter binding of κCG-myosin. However, MP-ιCG stabilized more moisture in the gel network, thereby improving the tenderness of the gel, which might be related to the electrostatic repulsion observed between the sulfate groups of ιCG and the myosin observed by molecular docking. In addition, the ß-sheet content and intermolecular interactions might be positively correlated with gel properties. CONCLUSION: In this study, a composite gel system was constructed based on the interaction of MP and CG. The quality differences of two kinds of CG-MP gels were clarified, which will provide guidance for the application of different kinds of carrageenan and the development of recombinant meat products with specific quality. © 2022 Society of Chemical Industry.

Non-Destructive Extraction and Separation of Nano- and Microplastics from Environmental Samples by Density Gradient Ultracentrifugation.

Nano-/microplastics (NMPs, particle diameter < 5 mm) are widespread emerging pollutants causing diverse impacts on organisms due to their sizes, shapes, and chemical properties. Despite the fast increase in NMP research, an effective method to separate and identify NMP types from environmental samples is still lacking. Here, we developed a simple and effective approach for the non-destructive extraction and separation of various types of NMPs from environmental samples by density gradient ultracentrifugation (DGU). For the first time, DGU was capable to separate various NMPs from the complex matrix with high selectivity (100%), purity (93%), and applicability. Through a gradually changing density of the density gradient medium by changing the concentrations or volumes of CsCl/water solution (from 0.00065 to 0.01989 g cm-3 mm-1), various NMPs (with particle sizes as little as 50 nm) could be extracted and separated from soil samples with high recovery (78.5-96.0%). We confirmed the effectiveness and compatibility of DGU through a correct identification of all types of NMPs separated from artificial soil samples with Raman spectroscopy, simultaneous thermal analysis (STA), and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). DGU is compatible with all analytical processes compared to other existing methods with much less sample pretreatment time (0.5 h). Overall, DGU is an effective and cheap method (2.2 USD/sample) to separate NMPs from environmental samples such as soil and water and, hence, can facilitate research on NMPs related to terrestrial and marine environments as well as human health.

Hyperuricemia induces liver injury by upregulating HIF-1α and inhibiting arginine biosynthesis pathway in mouse liver and human L02 hepatocytes.

The molecular mechanisms of uric acid (UA)-induced liver injury has not been clearly elucidated. In this study, we aimed to investigate the effect and action mechanisms of UA in liver injury. We analyzed the damaging effect of UA on mouse liver and L02 cells and subsequently performed metabolomics studies on L02 cells to identify abnormal metabolic pathways. Finally, we verified transcription factors that regulate related metabolic enzymes. UA directly activated the hepatic NLRP3 inflammasome and Bax apoptosis pathway invivo and invitro. Related metabolites in the arginine biosynthesis pathway (or urea cycle), l-arginine and l-argininosuccinate were decreased, and ammonia was increased in UA-stimulated L02 cells, which was mediated by carbamoyl phosphate synthase 1 (CPS1), argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) downregulation. UA upregulated hypoxia inducible factor-1alpha (HIF-1α) invivo and invitro, and HIF-1α inhibition alleviated the UA-induced ASS downregulation and hepatocyte injury. In conclusion, UA upregulates HIF-1α and inhibits urea cycle enzymes (UCEs). This leads to liver injury, with evidence of hepatocyte inflammation, apoptosis and oxidative stress.

Green nanopriming: responses of alfalfa (Medicago sativa L.) seedlings to alfalfa extracts capped and light-induced silver nanoparticles.

The application of nanotechnology in agriculture can remarkably improve the cultivation and growth of crop plants. Many studies showed that nanoparticles (NPs) made plants grow more vigorously. Light can make NPs aggregated, leading to the reduction of the NPs toxicity. In addition, treatment with NPs had a "hormesis effect" on plants. In this study, light-induced silver nanoparticles (AgNPs) were synthesized by using the alfalfa (Medicago sativa L.) extracts, and then the optimal synthetic condition was determined. Light-induced AgNPs were aggregated, spherical and pink, and they were coated with esters, phenols, acids, terpenes, amino acids and sugars, which were the compositions of alfalfa extracts. The concentration of free Ag+ was less than 2 % of the AgNPs concentration. Through nanopriming, Ag+ got into the seedlings and caused the impact of AgNPs on alfalfa. Compared with the control group, low concentration of light-induced AgNPs had a positive effect on the photosynthesis. It was also harmless to the leaf cells, and there was no elongation effect on shoots. Although high concentration of AgNPs was especially beneficial to root elongation, it had a slight toxic effect on seedlings due to the accumulation of silver. With the increase of AgNPs concentration, the content of silver in the seedlings increased and the silver enriched in plants was at the mg/kg level. Just as available research reported the toxicity of NPs can be reduced by using suitable synthesis and application methods, the present light induction, active material encapsulation and nanopriming minimized the toxicity of AgNPs to plants, enhancing the antioxidant enzyme system.

Simultaneous measurement of refractive index, strain, and temperature based on a Mach-Zehnder interferometer with hybrid structure optical fiber.

An optical fiber sensor based on a Mach-Zehnder interferometer with hybrid structure optical fiber for simultaneous measurement of refractive index (RI), strain, and temperature is proposed and demonstrated. The proposed structure is a hybrid structure based on a non-core fiber combined with few-mode fiber. The possibility of simultaneously measuring RI, strain, and temperature relies on the different sensitivity responses of three resonance peaks in the transmission spectrum. Thus, simultaneous measurement of RI, strain, and temperature is realized by calculating the wavelength shift of the three resonance peaks. The experimental results show that the sensitivities of RI are 22.9 pm/RIU, 24.6 pm/RIU, and 97 pm/RIU when RI changes from 1.3707 to 1.39809, respectively. The sensitivities of strain are $ - {3.5}\,\, \text{pm}/ \unicode{x00B5}\unicode{x03B5}$-3.5pm/µÎµ, $ - {1.9}\,\, \text{pm}/ \unicode{x00B5} \unicode{x03B5}$-1.9pm/µÎµ, and $ - {4.1}\,\, \text{pm}/ \unicode{x00B5} \unicode{x03B5}$-4.1pm/µÎµ in the range from 0 to 1400 pm/µ$\unicode{x03B5}$ε. The sensitivities of temperature ranging from 35°C to 55°C are 162 pm/°C, 194 pm/°C, and 162 pm/°C, respectively. The proposed sensor, with advantages of simple configuration, compact structure, and high sensitivity, exhibits great potential in fields of multi-parameter measurement.

Hysteroscopic Resection of Endometrial Polyps and Assisted Reproductive Technology Pregnancy Outcomes Compared with No Treatment: A Systematic Review.

Endometrial polyps are frequently encountered in the uterine cavity of infertile women. There is much debate regarding the treatment of endometrial polyps in patients who are undergoing assisted reproductive technology (ART). A systematic review was performed by searching PubMed, Embase, and the Cochrane Library for retrospective or prospective studies that compared the effect of hysteroscopic resection of polyps with no treatment on pregnancy outcomes of patients who underwent ART. The primary outcomes were clinical pregnancy, live birth, miscarriage, and implantation rates after ART. Eight studies with a total of 2267 patients were included. The results showed that hysteroscopic resection of endometrial polyps (mean size <2 cm) was associated with an increased rate of clinical pregnancy in patients who underwent intrauterine insemination. No clear benefit was observed for clinical pregnancy, live birth, miscarriage, or implantation rates in patients who underwent in vitro fertilization/intracytoplasmic sperm injection cycles. In conclusion, the effect of hysteroscopic polypectomy on pregnancy outcomes of patients who have undergone ART remains unclear. More prospective, randomized controlled trials are warranted to determine appropriate treatment.

Ultralow loss graphene-based hybrid plasmonic waveguide with deep-subwavelength confinement.

In this paper, we theoretically propose a novel graphene-based hybrid plasmonic waveguide (GHPW) consisting of a low-index rectangle waveguide between a high-index cylindrical dielectric waveguide and the substrate with coated graphene on the surface. The geometric dependence of the mode characteristics on the proposed structure is analyzed in detail, showing that the proposed GHPW has a low loss and consequently a relatively long propagation distance. For TM polarization, highly confined modes guided in the low-index gap region between the graphene and the high-index GaAs and the normalized modal area is as small as 0.0018 (λ2/4) at 3 THz. In addition to enabling the building of high-density integration of the proposed structure are examined by analyzing crosstalk in a directional coupler composed of two GHPWs. This structure also exhibits ultra-low crosstalk when a center-to-center separation between adjacent GHPWs is 32µm, which shows great promise for constructing various terahertz integrated devices.

Dynamical manipulation of Cosine-Gauss beams in a graphene plasmonic waveguide.

In this paper, we theoretically propose for the first time that graphene monolayer can be used to manipulate the Cosine-Gauss beams (CGBs). We show that both the transverse oscillation period and propagation length of a CGB can be dynamically manipulated by utilizing the tunability of the graphene's chemical potential. The graphene-based planar plasmonic waveguide provides a good platform to investigate the propagation properties of CGBs, which is potentially compatible to the microelectronic technology.

Increased Thyroid DPP4 Expression Is Associated With Inflammatory Process in Patients With Hashimoto Thyroiditis.

CONTEXT: Dipeptidyl peptidase-4 (DPP4) is originally described as a surface protein in lymphocytes. Lymphocyte infiltration and subsequent destruction of thyroid tissue have been considered as the central pathological mechanism in Hashimoto thyroiditis (HT). OBJECTIVE: The present study aimed to investigate DPP4 expression in peripheral blood and thyroid tissue in HT patients, and explore the role of DPP4 in the pathophysiological process of HT. METHODS: This case-control study recruited 40 drug-naive HT patients and 81 control individuals. Peripheral blood and thyroid specimens were collected for assessing the expression and activity of DPP4. Moreover, single-cell RNA sequencing (scRNA-seq) analysis of 6 "para-tumor tissues" samples from scRNA-seq data set GSE184362 and in vitro cell experiments were also conducted. RESULTS: The HT patients had similar DPP4 serum concentration and activity as the controls. However, the expression and activity of DPP4 was significantly increased in the thyroid of the HT group than in the control group. The scRNA-seq analysis showed that DPP4 expression was significantly increased in the HT group, and mainly expressed in T cells. Further in vitro studies showed that inhibition of lymphocyte DPP4 activity with sitagliptin downregulated the production of inflammatory factors in co-cultured thyroid cells. CONCLUSION: DPP4 expression was significantly increased in the thyroid of the HT group compared with the control group, and was mainly localized in the lymphocytes. Inhibition of lymphocyte DPP4 activity reduced the production of inflammatory factors in co-cultured thyroid cells. Therefore, inhibition of DPP4 may have a beneficial effect by alleviating inflammatory reactions in HT patients.

Characterization and in vitro calcium release of the novel calcium-loaded complexes using Antarctic krill protein and pectin: Effect of different blending sequences.

Food-grade biopolymer-based complexes are of particular interest in the field of biologic ingredient delivery owing to unique controlled-release properties. Herein, three calcium-loaded complexes using Antarctic krill protein (P) and pectin (HMP) with different blending sequences were designed, named P + Ca + HMP, P + HMP + Ca and HMP + Ca + P, respectively. The calcium-loaded capacity, structural properties, and in vitro gastrointestinal calcium release of the complexes were investigated. The results demonstrated that the calcium binding rate and content of the P + Ca + HMP complex were the highest, reaching to 90.3 % and 39.0 mg/g, respectively. Particularly, the P + Ca + HMP complex exhibited a more stable fruit tree-like structure. Furthermore, the structural analysis confirmed that the primary interaction forces involved hydrogen bond, electrostatic, hydrophobic and ionic bond interaction. Ultimately, the P + Ca + HMP complex demonstrated superior calcium delivery. In conclusion, a novel calcium delivery system was successfully developed based on optimized the self-assembly sequence, which held significant importance in promoting the high-value utilization of Antarctic krill protein and enhancing the in vitro bioaccessibility of calcium.

Parathyroid Hormone is Negatively Correlated with Glycated Hemoglobin in Newly Diagnosed Type 2 Diabetic Patients.

Objective: The growing evidence shows that parathyroid hormone (PTH) may affect glucose metabolism. However, the relationship between them is still controversial among diabetic patients. The current study aimed to investigate the relationship between PTH and glucose metabolism in the patients with newly diagnosed type 2 diabetes (T2D). Methods: A total of 532 participants, including 387 patients with newly diagnosed T2D and 145 healthy controls, were recruited in the present study. PTH and metabolic parameters were measured in all participants. Results: The PTH levels were significantly lower in the newly diagnosed T2D patients compared with the control group (35.10 (25.90, 47.20) vs. 47.15 (35.83, 58.65) pg/ml, P < 0.001). The T2D patients with a higher glycated hemoglobin (HbA1c) tertile had lower PTH levels than the patients with a lower HbA1c tertile (32.90 (24.85, 41.40) vs. 37.50 (26.10, 54.55) pg/ml, P < 0.001). Spearman correlation analysis showed that PTH was positively correlated with the body mass index (BMI), fasting insulin (FINS), homeostasis model assessment of ß-cell function (HOMA-ß), and homeostasis model assessment of insulin resistance (HOMA-IR) and negatively correlated with HbA1c, blood calcium (Ca), blood phosphorus (P), and 25-hydroxyvitamin D3 (25-OH-D3). Multiple linear regression analysis demonstrated that PTH was significantly associated with HbA1c (ß = -1.475, P=0.003) and HOMA-ß (ß = 0.090, P=0.001) after adjusting for age, sex, BMI, season, 25-OH-D3, Ca, and P. Conclusion: PTH was negatively correlated with HbA1c in the newly diagnosed T2D patients. Our results suggested that the PTH level within the reference range is related to islet ß-cell function and hyperglycemia.

Plastic pollution in agricultural landscapes: an overlooked threat to pollination, biocontrol and food security.

Ecosystem services such as pollination and biocontrol may be severely affected by emerging nano/micro-plastics (NMP) pollution. Here, we synthesize the little-known effects of NMP on pollinators and biocontrol agents on the organismal, farm and landscape scale. Ingested NMP trigger organismal changes from gene expression, organ damage to behavior modifications. At the farm and landscape level, NMP will likely amplify synergistic effects with other threats such as pathogens, and may alter floral resource distributions in high NMP concentration areas. Understanding exposure pathways of NMP on pollinators and biocontrol agents is critical to evaluate future risks for agricultural ecosystems and food security.

Molecular Mechanisms of Iron Transport and Homeostasis Regulated by Antarctic Krill-Derived Heptapeptide-Iron Complex.

In this study, the molecular mechanisms of iron transport and homeostasis regulated by the Antarctic krill-derived heptapeptide-iron (LVDDHFL-iron) complex were explored. LVDDHFL-iron significantly increased the hemoglobin, serum iron, total iron binding capacity levels, and iron contents in the liver and spleen to normal levels, regulated the gene expressions of iron homeostasis, and enhanced in vivo antioxidant capacity in iron-deficiency anemia mice (P < 0.05). The results revealed that iron ions within LVDDHFL-iron can be transported via the heme transporter and divalent metal transporter-1, and the absorption of LVDDHFL-iron involved receptor-mediated endocytosis. We also found that the transport of LVDDHFL-iron across cells via phagocytosis was facilitated by the up-regulation of the high mobility group protein, heat shock protein ß, and V-type proton ATPase subunit, accompanied by the regulatory mechanism of autophagy. These findings provided deeper understandings of the mechanism of LVDDHFL-iron facilitating iron absorption.

Mechanism of YJKL Decoction in Treating of PCOS Infertility by Integrative Approach of Network Pharmacology and Experimental Verification.

Purpose: Currently, there is still no clear treatment for polycystic ovary syndrome (PCOS). YJKL has better therapeutic effects and lower toxic side effects for PCOS type infertility. This study aims to clarify the potential mechanism of YJKL Decoction in the treatment of PCOS based on network pharmacology and experiments verification. Patients and Methods: Network pharmacology and experimental validation approach were used to investigate the bioactive ingredients, critical targets and potential mechanisms of YJKL Decoction against PCOS. Firstly, we use network pharmacology methods to collect core targets, and then validate their effects on diseases through experiments. Results: Five core targets were screened, Threonine kinase 1 (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Albumin (ALB) and Vascular endothelial growthfactor A (VEGFA). KEGG analysis showed that YJKL treatment for PCOS mainly include AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway and HIF-1 signaling pathway. The molecular docking results showed that compounds have higher affinity with targets. Finally, experimental results had shown that YJKL Decoction had an better therapeutic effects in the treatment of PCOS. Conclusion: Based on a systematic network pharmacology approach and experimental verification, our results comprehensively illustrated the active ingredients, potential targets, and molecular mechanism of YJKL for application to PCOS and helps to illustrate mechanism of action on a comprehensive level.

Analysis of stochastic disease including predator-prey model with fear factor and Lévy jump.

In this paper, we investigate the dynamical properties of a stochastic predator-prey model with a fear effect. We also introduce infectious disease factors into prey populations and distinguish prey populations into susceptible prey and infected prey populations. Then, we discuss the effect of Lévy noise on the population considering extreme environmental situations. First of all, we prove the existence of a unique global positive solution for this system. Second, we demonstrate the conditions for the extinction of three populations. Under the conditions that infectious diseases are effectively prevented, the conditions for the existence and extinction of susceptible prey populations and predator populations are explored. Third, the stochastic ultimate boundedness of system and the ergodic stationary distribution without Lévy noise are also demonstrated. Finally, we use numerical simulations to verify the conclusions obtained and summarize the work of the paper.

Effect of dapagliflozin on proteomics and metabolomics of serum from patients with type 2 diabetes.

BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduced the risk of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D), but the underlying mechanism has not been well elucidated. The circulating levels of proteins and metabolites reflect the overall state of the human body. This study aimed to evaluate the effect of dapagliflozin on the proteome and metabolome in patients with newly diagnosed T2D. METHODS: A total of 57 newly diagnosed T2D patients were enrolled, and received 12 weeks of dapagliflozin treatment (10 mg/d, AstraZeneca). Serum proteome and metabolome were investigated at the baseline and after dapagliflozin treatment. RESULTS: Dapagliflozin significantly decreased HbA1c, BMI, and HOMA-IR in T2D patients (all p < 0.01). Multivariate models indicated clear separations of proteomics and metabolomics data between the baseline and after dapagliflozin treatment. A total of 38 differentially abundant proteins including 23 increased and 15 decreased proteins, and 35 differentially abundant metabolites including 17 increased and 18 decreased metabolites, were identified. In addition to influencing glucose metabolism (glycolysis/gluconeogenesis and pentose phosphate pathway), dapagliflozin significantly increased sex hormone-binding globulin, transferrin receptor protein 1, disintegrin, and metalloprotease-like decysin-1 and apolipoprotein A-IV levels, and decreased complement C3, fibronectin, afamin, attractin, xanthine, and uric acid levels. CONCLUSIONS: The circulating proteome and metabolome in newly diagnosed T2D patients were significantly changed after dapagliflozin treatment. These changes in proteins and metabolites might be associated with the beneficial effect of dapagliflozin on cardiovascular and renal outcomes.