Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVE: To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. METHODS: Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80-0.97], 0.86 [0.79-0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78-0.90]), renal outcome (RR [95% CI]; 0.67 [0.60-0.74], HHF (RR [95% CI]; 0.60 [0.53-0.68]), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81-0.91]) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77-0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78-0.94]). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13-1.47], 1.31 [1.07-1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI]; 1.36 [1.16-1.59], 1.49 [1.18-1.89], respectively) in renal outcome and HHF. CONCLUSIONS: In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.

A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.

Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently. To date, why these flaviviruses can be transmitted without mosquito vectors remains poorly understood. To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks. The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks. The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility. The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks. These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos. Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors. We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks. The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks. Our findings provide new knowledge about TMUV transmission among ducks.

Learning EKG Diagnostic Models with Hierarchical Class Label Dependencies.

Electrocardiogram (EKG/ECG) is a key diagnostic tool to assess patient's cardiac condition and is widely used in clinical applications such as patient monitoring, surgery support, and heart medicine research. With recent advances in machine learning (ML) technology there has been a growing interest in the development of models supporting automatic EKG interpretation and diagnosis based on past EKG data. The problem can be modeled as multi-label classification (MLC), where the objective is to learn a function that maps each EKG reading to a vector of diagnostic class labels reflecting the underlying patient condition at different levels of abstraction. In this paper, we propose and investigate an ML model that considers class-label dependency embedded in the hierarchical organization of EKG diagnoses to improve the EKG classification performance. Our model first transforms the EKG signals into a low-dimensional vector, and after that uses the vector to predict different class labels with the help of the conditional tree structured Bayesian network (CTBN) that is able to capture hierarchical dependencies among class variables. We evaluate our model on the publicly available PTB-XL dataset. Our experiments demonstrate that modeling of hierarchical dependencies among class variables improves the diagnostic model performance under multiple classification performance metrics as compared to classification models that predict each class label independently.

Amorphous/Nanocrystalline, Lightweight, Wave-Transparent Boron Nitride Nanobelt Aerogel for Thermal Insulation.

At present, the new generation of aircraft is developing in the direction of high speed, long endurance, high mobility, and repeatability. Some studies have shown that the surface temperature of the radome can reach even 1800 °C as the flight speed of the aircraft increases. However, the antenna inside the radome cannot serve at this temperature. Consequently, a thermal insulation system with electromagnetic wave-transparent ability and high-temperature resistance is urgently needed to protect the antenna from working normally. An aerogel material is known as "solid smoke," with the lowest density currently. Because of its high porosity (>90%) and the characteristics of nanopore size, its application in the field of thermal insulation always draws the attention of researchers. In this work, a novel amorphous/nanocrystalline boron nitride (BN) nanobelt aerogel was synthesized successfully. The BN aerogel shows lightweight (18 mg/cm3), good thermal stability (1400 °C under an inert atmosphere and 750 °C under an air atmosphere), wideband wave-transparent performance (dielectric constant of 1.03 and dielectric loss of 0.016 at 4-18 GHz), and thermal insulation property (43 mW/(m·K) at room temperature and 73 mW/(m·K) at 600 °C). The BN aerogel is a suitable candidate as an electromagnetic wave-transparent thermal insulator and fire-resistant material. What is more, the structural stability of the BN aerogel is good (Young's modulus remains basically constant during the fatigue tests), and the energy loss coefficient (∼0.56) is high; it also has the potential to be a mechanical energy dissipative material. The study on the amorphous/nanocrystalline BN nanobelt aerogel provides a new idea for structure design and performance optimization of a high-temperature electromagnetic functional insulation material.

Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVE: To evaluate the efficacy and safety of finerenone and sodium-glucose cotransporter-2 inhibitors (SGLT2i) on reducing new-onset of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). METHOD: We searched the PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to April 30, 2022. Randomized control trials comparing finerenone or SGLT2i with placebo in patients with T2DM and CKD were selected. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: A total of 10 studies (35,841 patients) were included. Finerenone (RR 0.79, 95% CI 0.62-0.99) was associated with a decreased risk of AF compared with placebo, while SGLT2i were not. SGLT2i were associated with a decreased risk of hospitalization for heart failure (RR 0.78, 95% CI 0.63-0.98) compared with finerenone. They were comparable in AF(RR 0.84, 95% CI 0.48,1.46), major adverse cardiovascular events(MACE) (RR 0.93, 95% CI 0.81,1.06) and nonfatal stroke(RR 0.78, 95% CI 0.58,1.05). They both showed no significant risk of adverse events compared with placebo. CONCLUSION: There was no significant difference in the reduction of new-onset of atrial fibrillation between Finerenone and SGLT2i based on the indirect comparisons of currently available clinical studies. The large-sampled head-to-head trials was needed for the more precise conclusion.

Effect of RG (Coptis root and ginseng) formula in patients with type 2 diabetes mellitus: a study protocol for a randomized controlled and double-blinding trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common metabolic disease with significant health, social, and economic consequences. Traditional Chinese medicine (TCM) could effectively regulate blood sugar and influence gut microbiota in T2DM patients. Preliminary studies showed that the Coptis root and ginseng (RG) formula could relieve insulin resistance and prevent the progression of diabetes in mice. OBJECTIVES: The purpose of this study is to explore the efficacy and safety of RG formula in the treatment of adult patients with T2DM, as well as observing its effects on gut microbiota. METHODS AND ANALYSIS: This trial is a randomized, double-blind, placebo-controlled study. A total of 60 participants will be randomized in a 1:1 ratio into an experiment group (RG formula) and a control group (placebo). Patients in both groups will be given diabetes education and basic blood glucose control. Glucose-lowering drugs with significant influence on gut microbiota will be avoided. This trial will last 25 weeks including 1-week run-in, 12-week intervention, and 12-week follow-up visit. The primary outcome is the change in the HbA1c. The secondary outcomes comprise the change in the fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FIL), fasting C-peptide(C-P), insulin resistance index (IRI), inflammatory factors, and species abundance of gut microbiota between the two groups. Safety of medication will also be evaluated. The correlation analysis will be explored between the glycemic indicators, inflammatory factors, and abundance of gut microbiota. DISCUSSION: This study will provide the clinical evidence for the efficacy of RG formula in regulating blood sugar and influencing gut microbiota, which will be beneficial to form the integrated therapeutic regimen in T2DM with TCM. TRIAL REGISTRATION: "Clinical Study on the Intervention of Coptis Root and Ginseng," Chinese Clinical Trials Registry ChiCTR 2100042126 . Registered on 14 January 2021.

Characterizations of H4 avian influenza viruses isolated from ducks in live poultry markets and farm in Shanghai.

H4 avian influenza virus is one of the most prevalent influenza virus subtypes in birds. The evolution and pathogenicity of H4 AIV in domestic birds of China remain largely unclear. In the present study, a total of eight H4 AIV strains isolated in duck farm and live poultry markets (LPM) were characterized. Phylogenetic analysis indicated that these strains are divided into two groups in the Eurasian lineage. Eight genes of MH-2/H4N6 isolated from a duck farm were closely related to three H4N6 viruses from LPM, suggesting a potential AIV link between farms and LPMs. Additionally, the HA, NA, PB2, NP, and NS genes of two other H4N6 viruses isolated in LPM clustered with that of MH-2/H4N6. However, the remaining genes were more closely related to other sublineages, suggesting that MH-2/H4N6-originated viruses reassorted with other viruses in LPM. All H4 viruses replicated in mouse lungs without prior adaptation and all viruses replicated and transmitted among ducks. 29-1/H4N2, MH-2/H4N6, and 420-2/H4N6 viruses caused systemic infection in infected ducks. However, most of the viruses were not adapted in chickens. The present results indicate a potential correlation of AIV between LPMs and farms and suggest that active surveillance of AIV in LPM is warranted in China.