Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis

ObjectiveIn the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).MethodWe used Stata 17.0 for the NMA. Eligible Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and Embase databases until December 2022. Two researchers independently screened the available studies. The Cochrane Risk of Bias tool was used to assess the risk of bias in the included studies. We used GRADEprofiler (version3.6) to analyze the evidence certainty. Primary outcomes such as liver fat content (LFC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, as well as secondary outcomes such as γ-glutamyltransferase (γGGT) and body weight, were evaluated. Then, each intervention was ranked by the surface under the cumulative ranking curve (SUCRA). As a supplement, we drew forest plots of subgroup using RevMan (version 5.4).ResultsFourteen RCTs involving 1666 participants were included in the present study. The NMA results showed that exenatide (bid) was the best treatment for improving LFC compared with other agents, liraglutide, dulaglutide, semaglutide (qw) and placebo), and the SUCRA values were 66.8%. Among five interventions (except exenatide (bid) and semaglutide (qw)) evaluated for AST outcome, and six interventions (except exenatide (bid)) evaluated for ALT outcome, semaglutide (qd) was the most effective drug (SUCRA (AST) = 100%, SUCRA (ALT) = 95.6%). The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02]. As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4]. The quality of evidence was assessed as moderate or low.ConclusionThe daily GLP-1RAs may be more effective in primary outcomes. And the daily semaglutide may be the most effective treatment for NAFLD and T2DM among the six interventions

Effect of Bacterial Anaerobic Degradation on Pore Structure and Fractal Characteristics of Bituminous Coal

In order to study the effect of bacterial anaerobic degradation on coal pores and fractal characteristics, the development of coal pores was characterized by high-pressure mercury injection and low-temperature liquid nitrogen adsorption. Menger model and FHH model were used to analyze the fractal characteristics. The results showed that after anaerobic degradation of bacteria, the micro-pores, transitional pores and meso-pores of residual coal were reduced, and the specific surface area was reduced more significantly. But at the same time, the large pore volume was increased. Besides, the dimension was obviously reduced, the surface roughness was reduced, and the pore development tended to be simple. These results showed that after anaerobic degradation, the coalbed methane adsorption capacity of bituminous coal reduced, while the seepage capacity partly increased

Crystal structure of poly[μ2-diaqua-(μ2-2-amino-4,5-dicyano-κ2N:N′-imidazol-1-ide)sodium(I)], C5H6N5O2Na

C5H6N5O2Na, triclinic, P1̄ (no. 2), a = 7.0140(10) Å, b = 7.4328(13) Å, c = 8.9483(16) Å, α = 103.303(7)°, β = 103.719(6)°, γ = 103.634(6)°, V = 419.73(12) Å3, Z = 2, Rgt(F) = 0.0622, wRref(F2) = 0.1795, T = 170(2) K

Mechanism of Glucagon-like Peptide-1 Receptor Agonist Improving Liver Lipid Deposition in a Rat Model of Insulin Resistance Induced by High-fructose Diet

Background The incidence rate of nonalcoholic fatty liver disease is increasing year by year, but there is still no effective cure. Clinical and basic studies show that a type of hypoglycemic drug, namely glucagon-like peptide-1 (GLP-1) receptor agonists can improve liver lipid deposition, but the specific mechanism is unknown. Objective To explore the mechanism of GLP-1 receptor agonists improving liver lipid deposition in a rat model of insulin resistance induced by high-fructose diet. Methods This experiment was carried out from January to April 2016. Thirty-six Wistar rats were randomly divided into a control group (ND) receiving a normal diet and a model group receiving a high-fructose diet. After 8 weeks, a hyperinsulinemic-euglycemic clamp test was performed in the model group to verify the formation of insulin resistance. The rats in the model group were further randomized into a high-fructose (HFD) subgroup and a high fructose with exenatide (HFD+Ex) subgroup. The changes of glucose and lipid levels, insulin resistance, liver lipid deposition, the expression and nuclear translocation of β-catenin and lipid synthesis pathway related factors were observed in HFD+Ex subgroup at four weeks after receiving subcutaneous abdominal injection of exenatide injection. Further changes in cell lipid deposition and lipid synthesis pathway related factors were observed after inhibiting the expression of β-catenin with small interfering RNA (siRNA) by transfection techniques in HepG2 cells. HepG2 cells were treated with 25 mmol/L fructose, 100 nmol/L exendin-4, and non-transfected HepG2 cells were used as controls. ALL of the cells were divided into normal control group (Con) , high-fructose (HF) group, high fructose with exendin-4 (HF+Ex4) group, high fructose with exendin-4 and control siRNA (HF+Ex4+Si-control) group, and high fructose with exendin-4 and β-catenin siRNA (HF+Ex4+Si-β-catenin) group. After the experiment, the rats' weight and liver index, serum concentrations of triglyceride (TG) , total cholesterol (TC) , free fatty acid (FFA) , alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , fasting blood glucose (FBG) , fasting insulin (FINS) and liver TG concentration were measured, and the area under the plasma glucose curve (AUCglu) , and glucose infusion rate (GIR) were calculated, and lipid droplets in liver tissues were observed using Oil Red O staining. The protein expression levels of sterol regulatory element binding protein 1 (SREBP-1) and the key enzymes for downstream lipid synthesis, fatty acid synthase (FAS) , acetyl coenzyme A carboxylase (ACC) , stearoyl-CoA desaturase 1 (SCD-1) and β-catenin of liver tissues and HepG2 cells were also measured. Results (1) After 8-week high-fructose feeding, the model group had significantly higher weight, liver index and liver TG concentration, and lower GIR than the ND group (P<0.05) . After 4 weeks of drug intervention, HFD subgroup demonstrated higher weight, liver index, TG, FFA, ALT, FBG, FINS and AUCglu, and lower GIR than the ND group (P<0.05) . HFD+Ex subgroup showed lower weight, liver index, FFA, ALT, FBG, FINS, and AUCglu, and higher GIR than HFD subgroup (P<0.05) . (2) Compared with ND group, HFD subgroup demonstrated higher concentration of TG in the liver (P<0.05) , and a large number of red lipid droplets in liver cells. HFD+Ex subgroup had lower concentration of TG in the liver (P<0.05) and reduced red lipid droplets in liver cells compared with HFD subgroup. (3) Compared with ND group, the expression of SREBP-1, FAS, SCD-1 and ACC in liver of rats in HFD subgroup increased (P<0.05) . Compared with HFD subgroup, the protein expression of SREBP-1, FAS, SCD-1 and ACC in HFD+Ex subgroup decreased (P<0.05) . (4) Compared with ND group, the expression levels of total protein and nuclear protein of β-catenin in liver of rats in HFD subgroup were significantly decreased (P<0.05) . Compared with HFD subgroup, the expression levels of total protein and nuclear protein of β-catenin increased in HFD+Ex subgroup (P<0.05) . (5) Compared the HepG2 cells treated with HF, HF+Ex4 group had higher expression levels of total protein and nuclear protein of β-catenin and lower levels of serum TG, and so did HF+Ex4+Si-control group (P<0.05) . Compared with HF+Ex4 group, HF+Ex4+Si-β-catenin group had down-regulated expression of total protein and nuclear protein of β-catenin (P<0.05) . The levels of serum TG of HepG2 cells in HF+Ex4+Si-β-catenin group was higher than that in HF+Ex4 group (P<0.05) . (6) HF+Ex4 group had lower protein expression levels of SREBP-1, ACC, FAS, and SCD-1 of HepG2 cells than HF group, and so did the HF+Ex4+Si-control group (P<0.05) . The protein expression levels of SREBP-1, ACC, FAS, and SCD-1 of HepG2 cells in HF+Ex4+Si-β-catenin group were higher than those in HF+Ex4 group (P<0.05) . Conclusion GLP-1 receptor agonists may regulate β-catenin expression to improve liver lipid deposition in rats with insulin resistance, which are potential new drugs for nonalcoholic fatty liver disease. β-catenin may be an important target for drug treatment

A Universal strategy for the facile synthesis of a sandwich-structured Pt-graphene-Pt nanocomposite for salbutamol sensing

In this work, a sandwich-structured Pt-graphene-Pt (P-Gr-P) nanocomposite has been prepared by a two-step method including (i) a chemical and (ii) an electrochemical reduction process. The P-graphene oxide-P (P-GO-P) nanocomposite was firstly synthesized by an in situ growth method, during which platinum nanoparticles (PtNPs) grew on both sides of GO. In the second step, P-GO-P was coated onto a glass carbon electrode (GCE). In this process, GO in the P-GO-P nanocomposite was reduced to a more conductive form of graphene (Gr). The obtained sandwich-structured P-Gr-P can effectively separate the individual layers of Gr sheets from each other, prevent the agglomeration of Gr sheets and improve the conductivity of the Gr film. In addition, the electrocatalytic properties of the as-prepared P-Gr-P nanocomposite towards the oxidation of salbutamol (SAL) were investigated. Results revealed that the sandwich-structured P-Gr-P nanocomposite with higher electrochemically active surface area showed better electrocatalytic activity toward SAL oxidation than PtNPs-Gr prepared by using the one-step electrochemical co-deposition method. On the basis of the excellent electrochemical activity of the P-Gr-P nanocomposite, a highly sensitive electrochemical platform was developed for the rapid detection of SAL. The present work provides an interesting strategy to prepare a Gr-based nanocomposite for electrochemical sensors.8 page(s

LAMP Coupled CRISPR-Cas12a Module for Rapid, Sensitive and Visual Detection of Porcine Circovirus 2

Porcine circovirus 2 (PCV2) is the main pathogen of porcine circovirus-associated disease (PCVAD), which can cause considerable economic loss to the pig industry. The diagnosis of PCVAD is complicated and requires a series of clinical, pathological, and virological methods. Therefore, a rapid, highly sensitive, on-site, and visual diagnostic approach would facilitate dealing with the spread of PCV2. In this study, we intended to establish a new and effective PCV2 detection method through combining the no specific equipment requirement advantage of loop-mediated isothermal amplification (LAMP) with the property of clustered regular interspaced short palindromic repeats (CRISPR)/Cas12a system possessing the huLbCas12a collateral cleavage activity able to cleave single-stranded DNA fluorophore quencher probe sensor (designed as LAPM-CRISPR). Following a series of optimizations of its reaction conditions, this LAMP-CRISPR-based PCV2 detection could be conducted in constant temperature equipment, with the result reflected in a direct visual readout way. This established PCV2 detection approach presented fine sensitivity, rapidity, specificity, and reliability, as demonstrated by a low detectable limit of 1 copy/μL, completed within an hour, no cross-reaction with main porcine DNA or RNA viruses like PCV1, PCV3, and PEDV, and a 100% coincidence rate with that of the quantitative PCR (qPCR) method in the evaluation of 30 clinical blood samples, respectively. Therefore, this novel method makes rapid, on-site, visual, highly sensitive, and specific detection of PCV2 possible, facilitating the prevention of this pathogen in the field

Application of poly(3,4-ethylenedioxythiophene)/manganese dioxide composite-modified electrode for sensitive electrochemical detection of luteolin

In this work, the electrochemical determination of luteolin using poly(3,4-ethylenedioxythiophene)/manganese dioxide nanocomposite modified glassy carbon electrode (PEDOT/MnO₂/GCE) is reported. PEDOT/MnO₂ nanocomposite has been proposed via a simple two-step deposition approach. Electrochemical results revealed that PEDOT/MnO₂ showed enhanced electrocatalytic performance toward luteolin, which might be attributed to good conductivity and accelerated electron transfer of PEDOT and good catalytic effect of MnO₂. Experimental conditions, including pH values and scan rates were optimized. In optimal conditions, a good linear relationship was found between oxidation peak currents and the concentration of luteolin in 5.0 nM-7.0 μM range. The detection limit was calculated to be 1.8 nM at a signal-to-noise ratio of 3. Finally, the applicability for luteolin determination in real samples was successfully demonstrated.10 page(s

Rewritable printing of ionic liquid nanofilm utilizing focused ion beam induced film wetting

Abstract Manipulating liquid flow over open solid substrate at nanoscale is important for printing, sensing, and energy devices. The predominant methods of liquid maneuvering usually involve complicated surface fabrications, while recent attempts employing external stimuli face difficulties in attaining nanoscale flow control. Here we report a largely unexplored ion beam induced film wetting (IBFW) technology for open surface nanofluidics. Local electrostatic forces, which are generated by the unique charging effect of Helium focused ion beam (HFIB), induce precursor film of ionic liquid and the disjoining pressure propels and stabilizes the nanofilm with desired patterns. The IBFW technique eliminates the complicated surface fabrication procedures to achieve nanoscale flow in a controllable and rewritable manner. By combining with electrochemical deposition, various solid materials with desired patterns can be produced

Table_1_Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.XLSX

PurposeSphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH).MethodsData of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis.ResultsPatients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p ConclusionHigher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.</p

Table_2_Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.XLSX

PurposeSphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH).MethodsData of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis.ResultsPatients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p ConclusionHigher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.</p