Evaluation and comparison of efficacy and safety of tirzepatide and semaglutide in patients with type 2 diabetes mellitus: A Bayesian network meta-analysis.

BACKGROUND: As new antidiabetic drugs, tirzepatide (Tir) and semaglutide (Sem) are progressively applied in clinical practice. However, their efficacy and safety profiles have not been comprehensively assessed. Therefore, a Bayesian network meta-analysis was used to evaluate and compare the efficacy and safety of Tir and Sem in treating type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov were systematically searched from inception to April 3rd, 2023. Randomized clinical trials (RCTs) comparing the efficacy and safety of Tir and Sem with placebo or the other antidiabetic drugs in treating T2DM were included. The efficacy outcomes included changes in glycated hemoglobin (HbA1c), body weight (BW), body mass index (BMI), and the proportion of participants with HbA1c< 7 %. The safety outcome was the proportion of participants experiencing gastrointestinal adverse events (GIAEs). RESULTS: A total of 38 studies involving 34,166 participants were included. Compared to 1 mg of subcutaneous Sem (Sem SC), 5 mg, 10 mg and 15 mg of Tir demonstrated superior efficacy in reducing HbA1c (mean difference (MD), [95 % CI], -0.22 [-0.40, -0.03] %, -0.42 [-0.60, -0.24] % and -0.53 [-0.71, -0.35] %, respectively) and BW (MD [95 % CI], -1.48 [-2.53, -0.43] kg, -4.00 [-5.05, -2.95] kg and -5.71 [-6.73, -4.68] kg, respectively). Conversely, 7 mg and 14 mg of oral Sem (Sem PO) displayed inferior efficacy in reducing HbA1c (MD [95 % CI], 0.47 [0.26, 0.68] % and 0.35 [0.16, 0.54] %, respectively) and BW (MD [95 % CI], 2.36 [1.24, 3.48] kg and 1.11 [0.10, 2.13] kg). However, 20 mg and 40 mg of Sem PO were non-inferior in reducing HbA1c (MD [95 % CI], 0.13 [-0.29, 0.55] % and 0.01 [-0.38, 0.40] %, respectively) and BW (MD [95 % CI], -0.41 [-2.71, 1.90] kg and -1.32 [-3.58, 0.92] kg). In terms of safety, compared to 1 mg of Sem SC, 5 mg, 10 mg and 15 mg of Tir did not significantly increase the incidence of GIAEs (odd ratio (OR) [95 % CI], 0.70 [0.42, 1.10], 0.87 [0.52, 1.36] and 0.99 [0.60, 1.54], respectively), while 7 mg of Sem PO showed a lower incidence of GIAEs (OR [95 % CI], 0.48 [0.25, 0.83]). Compared to insulin, 0.5 mg of Sem SC, 1 mg of Sem SC, 5 mg of Tir, 10 mg of Tir and 15 mg of Tir displayed better efficacy in lowering HbA1c (MD [95 % CI], -0.40 [-0.63, -0.18] %, -0.69 [-0.90, -0.48] %, -0.91 [-1.10, -0.72] %, -1.11 [-1.30, -0.92] % and -1.22 [-1.41, -1.03] %, respectively) and BW (MD [95 % CI], -5.34[-6.60, -4.09] kg, -6.70 [-7.90,-5.51] kg, -8.18 [-9.27, -7.10] kg, -10.70 [-11.79, -9.61] kg and -12.41 [-13.49,-11.33] kg, respectively). According to the surface under the cumulative ranking curve (SUCRA) value, among all the included interventions, 15 mg of Tir exhibited the most potent effect in reducing HbA1c (99.81 %) and BW (99.98 %), followed by 10 mg of Tir (96.83 % and 95.72 %), 5 mg of Tir (92.88 % and 86.04 %), 1 mg of Sem SC (85.85 % and 74.97 %), 40 mg of Sem PO (83.66 % and 84.31 %), 20 mg of Sem PO (76.98 % and 77.12 %), 300 mg of Can (49.93 % and 60.89 %), insulin (36.38 % and 0.22 %) and 100 mg of Sit (12.28 % and 18.51 %) respectively. Meanwhile, 5 mg, 10 mg, and 15 mg of Tir (48.32 %, 30.96 %, and 21.07 %, respectively), 0.5 mg and 1 mg of Sem SC (33.54 % and 24.77 %, respectively) significantly increased the incidence of GIAEs. CONCLUSION: Both Tir and Sem demonstrated favorable antidiabetic effects and were particularly suitable for T2DM patients who were obese or overweight. Despite a high incidence of GIAEs, their safety profile was deemed acceptable. Tir was the best option among all the included interventions.

Spatiotemporal distribution of the planktonic microbiome and antibiotic resistance genes in a typical urban river contaminated by macrolide antibiotics.

The widespread application of macrolide antibiotics has caused antibiotic resistance pollution, threatening the river ecological health. In this study, five macrolide antibiotics (azithromycin, clarithromycin, roxithromycin, erythromycin, and anhydro erythromycin A) were monitored in the Zao River across three hydrological periods (April, July, and December). Simultaneously, the changes in antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and planktonic bacterial communities were determined using metagenomic sequencing. A clear pollution gradient was observed for azithromycin and roxithromycin, with the concentrations in the dry season surpassing those in other seasons. The highest concentration was observed for azithromycin (1.36 µg/L). The abundance of MLS resistance genes increased along the Zao River during the dry season, whereas the opposite trend was obtained during the wet season. A significant correlation between the levels of MLS resistance genes and macrolide antibiotics was identified during the dry season. Notably, compared with the reference site, the abundance of transposase in the effluent from wastewater treatment plants (WWTPs) was significantly elevated in both dry and wet seasons, whereas the abundance of insertion sequences (IS) and plasmids declined during the dry season. The exposure to wastewater containing macrolide antibiotics altered the diversity of planktonic bacterial communities. The bacterial host for ARGs appeared to be Pseudomonas, primarily associated with multidrug subtypes. Moreover, the ARG subtypes were highly correlated with MGEs (transposase and istA). The partial least-squares path model (PLS-PM) demonstrated a positive correlation between the abundance of MGEs and ARGs, indicating the significance of horizontal gene transfer (HGT) in the dissemination of ARGs within the Zao River. Environmental variables, such as TN and NO3--N, were significantly correlated with the abundance of MGEs, ARGs, and bacteria. Collectively, our findings could provide insights into the shift patterns of the microbiome and ARGs across the contamination gradient of AZI and ROX in the river.

Detection and Recognition of Tilted Characters on Railroad Wagon Wheelsets Based on Deep Learning.

The quality of railroad wheelsets is an important guarantee for the safe operation of wagons, and mastering the production information of wheelsets plays a vital role in vehicle scheduling and railroad transportation safety. However, when using objection detection methods to detect the production information of wheelsets, there are situations that affect detection such as character tilting and unfixed position. Therefore, this paper proposes a deep learning-based method for accurately detecting and recognizing tilted character information on railroad wagon wheelsets. It covers three parts. Firstly, we construct a tilted character detection network based on Faster RCNN for generating a wheelset's character candidate regions. Secondly, we design a tilted character correction network to classify and correct the orientation of flipped characters. Finally, a character recognition network is constructed based on convolutional recurrent neural network (CRNN) to realize the task of recognizing a wheelset's characters. The result shows that the method can quickly and effectively detect and identify the information of tilted characters on wheelsets in images.

Improved Self-Heating in Short-Channel Monolayer WS2 Transistors with High-Thermal Conductivity BeO Dielectrics.

Two-dimensional semiconducting transition metal dichalcogenides (TMDs) enable ultimate channel length scaling of transistor technology due to their atomic-thin body nature, which also brings the challenge of a pronounced self-heating effect inside the ultrathin channel. In particular, high current density under high electric field could lead to negative differential resistance behavior due to self-heating, not only limiting the current carrying capability of the TMDs transistors but also leading to severe reliability issues. Here, we report high-performance monolayer WS2 transistors on a high-thermal-conductivity BeO dielectric with effective suppression of the self-heating effects, eliminating the negative differential resistance behavior at high field, as observed in the case of the HfO2 dielectric. The monolayer CVD WS2 device on BeO with a 50 nm channel length exhibits a record-high on-state current of 325 µA/µm, transconductance (gm) of 150 µS/µm, and a on/off ratio of 1.8 × 108 at Vds = 1 V, far exceeding previous results.

Metabolomic profiles in a green alga (Raphidocelis subcapitata) following erythromycin treatment: ABC transporters and energy metabolism.

A recent study showed that erythromycin (ERY) exposure caused hormesis in a model alga (Raphidocelis subcapitata) where the growth was promoted at an environmentally realistic concentration (4 µg/L) but inhibited at two higher concentrations (80 and 120 µg/L), associated with opposite actions of certain signaling pathways (e.g., xenobiotic metabolism, DNA replication). However, these transcriptional alterations remain to be investigated and verified at the metabolomic level. This study uncovered metabolomic profiles and detailed toxic mechanisms of ERY in R. subcapitata using untargeted metabolomics. The metabolomic analysis showed that metabolomic pathways including ABC transporters, fatty acid biosynthesis and purine metabolism were associated with growth promotion in algae treated with 4 µg/L ERY. An overcompensation was possibly activated by the low level of ERY in algae where more resources were reallocated to efficiently restore the temporary impairments, ultimately leading to the outperformance of growth. By contrast, algal growth inhibition in the 80 and 120 µg/L ERY treatments was likely attributed to the dysfunction of metabolomic pathways related to ABC transporters, energy metabolism and metabolism of nucleosides. Apart from binding of ERY to the 50S subunit of ribosomes to inhibit protein translation as in bacteria, the data presented here indicate that inhibition of protein translation and growth performance of algae by ERY may also result from the suppression of amino acid biosynthesis and aminoacyl-tRNA biosynthesis. This study provides novel insights into the dose-dependent toxicity of ERY on R. subcapitata.

Zinc oxide nanoparticles alleviate the arsenic toxicity and decrease the accumulation of arsenic in rice (Oryza sativa L.).

BACKGROUND: Rice is particularly effective, compared to other cereals, at accumulating arsenic (As), a nonthreshold, class 1 human carcinogen in shoot and grain. Nano-zinc oxide is gradually used in agricultural production due to its adsorption capacity and as a nutrient element. An experiment was performed to explore the effects of zinc oxide nanoparticles (nZnO) on arsenic (As) toxicity and bioaccumulation in rice. Rice seedlings were treated with different levels of nZnO (0, 10, 20, 50, 100 mg/L) and As (0, and 2 mg/L) for 7 days. RESULTS: The research showed that 2 mg/L of As treatment represented a stress condition, which was evidenced by phenotypic images, seedling dry weight, chlorophyll, and antioxidant enzyme activity of rice shoot. The addition of nZnO (10-100 mg/L) enhanced the growth and photosynthesis of rice seedlings. As concentrations in the shoots and roots were decreased by a maximum of 40.7 and 31.6% compared to the control, respectively. Arsenite [As (III)] was the main species in both roots (98.5-99.5%) and shoots (95.0-99.6%) when exposed to different treatments. Phytochelatins (PCs) content up-regulated in the roots induced more As (III)-PC to be complexed and reduced As (III) mobility for transport to shoots by nZnO addition. CONCLUSION: The results confirmed that nZnO could improve rice growth and decrease As accumulation in shoots, and it performs best at a concentration of 100 mg/L.

Biological soil crusts alleviate the stress of arsenic on rice germination and the underlying immobilization mechanisms.

The high concentration of arsenic (As) in paddy soil has seriously threatened the growth of rice and human food safety. Biological soil crusts (BSC), which are ubiquitous in paddy fields, have been shown a high ability to capture trace metal elements. In the present study, we investigated the effectiveness and mechanism of BSC for immobilizing As, and tested their potential to alleviate the stress of As on rice germination. It is found that BSC can remove 77.8% of arsenic in solution with 3.5 mg L-1 initial As concentration. The As content in BSC reached 514.5 mg kg-1 after 216 h exposure, and the entrapped As was mainly distributed in BSC as a non-EDTA-exchangeable fraction, which might be intracellularly accumulated. Proteobacteria and Bacteroidetes were the dominant phyla in BSC after being exposed to As, playing a significant role in tolerating As and As biogeochemical cycling. The presence of BSC notably promoted the germination rate (18.3%) and dry biomass (103.4%) of rice seeds under 3.5 mg L-1 As stress while reducing the As content in plant roots (8.2-34.3%) and shoots (8.7-47.6%). These findings demonstrate that BSC have a great entrapping effect on As and highlight the importance of BSC in alleviating the stress on rice germination by As, providing a potential nature-based and low-cost strategy to decontaminate paddy fields polluted with As.

CacyBP/SIP inhibits the migration and invasion behaviors of glioblastoma cells through activating Siah1 mediated ubiquitination and degradation of cytoplasmic p27.

Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) has been reported to be up-regulated and plays an important role in promoting cell proliferation in human glioma. However, the effect of CacyBP/SIP on glioma cell motility is still unclear. Here, to our surprise, CacyBP/SIP was found to inhibit the migration and invasion of glioma cells U251 and U87. Silencing of CacyBP/SIP significantly promoted the migration and invasion behaviors of glioma cells. On the contrary, overexpression of CacyBP/SIP obviously suppressed them. Further investigation indicated that silencing of CacyBP/SIP significantly reduced the interaction between Siah1 and cytoplasmic p27, which in turn attenuated the ubiquitination and degradation of cytoplasmic p27. In contrast, overexpression of CacyBP/SIP promoted the interaction between Siah1 and cytoplasmic p27, which in turn increased the ubiquitination and degradation of cytoplasmic p27. Importantly, the degradation of p27 could be blocked by Siah1 knockdown. Finally, we found that CacyBP/SIP was reversely related to cytoplasmic p27 in human normal brain tissues and glioma tissues. Taken together, these results suggest that CacyBP/SIP plays an important role in inhibiting glioma cell migration and invasion through promoting the degradation of cytoplasmic p27.

Mechanical amplification mechanism of kinesin's ß-domain.

Conventional kinesin's force generation process always takes place on the leading head and the generated force is transmitted to the trailing head through two neck linkers. To guarantee a strong force to be transmitted to the trailing head so that it can be detached from microtubule surface, the neck linker of the leading head must have a large enough forward displacement, which is proposed to be achieved by the amplifying function of the ß-domain. However, the experimental result shows that the forward displacement of the ß-domain itself appears too small. To elucidate the function of the ß-domain, we make a detailed analysis of the mechanical relationship between the two motor heads and, based on the results of molecular dynamics simulation and mechanical analysis, we calculate the forward displacement of the neck linker of the leading head during the ATP binding induced motor head rotation. We show that ß-domain achieves its amplifying function together with ß0, so that neck linker can have a forward displacement during motor head rotation. This displacement of neck linker is large enough to cause detachment of the trailing head. Based on these results, a possible initiation mechanism of neck linker docking is proposed.

Deciphering Internal Regulatory Patterns within the p53 Core Tetramer: Insights from Community Network Analysis.

Gene therapy is one of the most effective strategies for cancer treatment. The p53 protein, commonly known as the "guardian of the genome", plays a critical role in gene activation and tumor suppression. Tetramerization of the p53 core domain is an essential allosteric process that supports its suppression functions. This letter presents a framework to analyze the structure, function, and dynamic connectivity of the p53 tetramer, using community network analysis based on all-atom molecular dynamics simulations. The communities within the p53 monomer exhibit distinct functional roles, while interactions between molecules establish a symmetrical network structure. We identified direct evidence of single, double, and multiple pathway regulations within the p53 tetramer and crucial residue pairs involved in these connections. Our study provides a comprehensive framework to understand the community network of the p53 tetramer, offering new insights into the stable formation of the p53 core tetramer.

Photocatalytic H2 O2 Generation Reaction with a Benchmark Rate at Air-Liquid-Solid Joint Interfaces.

The rapid charge recombination, low selectivity for two-electron oxygen reduction reaction (ORR), and limited O2 diffusion rate hinder the practical applications of photocatalytic H2 O2 generation. Herein, a triphase photocatalytic system in which the H2 O2 generation occurs at the air-liquid-solid joint interfaces is developed, using polymeric carbon nitride (PCN). The introduction of pyrrole units and cyano group into PCN can promote the activation of oxygen molecules and facilitate the spatial separation of HOMO and LUMO orbits, hence improving the charge carrier separation efficiency and enhancing the formation of H2 O2 . Importantly, the gas-liquid-solid triphase interface system allows for the rapid transport of oxygen from the air to the reaction interface, overcoming the low solubility and slow diffusion of oxygen in the water in conventional liquid reaction systems. The triphase system shows a benchmark H2 O2 generation rate over PCN-based materials in pure water (2063.21 µmol g-1 h-1 ), which is an approximate tenfold enhancement as compared to powder photocatalyst (215.44 µmol g-1 h-1 ). Simulation and electrochemical tests reveal that the rapid oxygen diffusion rate of triphase interface can promote charge separation and provide more O2 to generate H2 O2 . This work provides a promising strategy for constructing an efficient and sustainable H2 O2 production system.

Bioinspired Graphene Aerogels with Hybrid Wettability for Solar-Driven Purification of Complex Wastewater.

Salt deposition and pollutant enrichment greatly hamper efficient and sustainable water production for a solar evaporator. Inspired by the desert beetle, a dual-region hydrophobic graphene/hydrophilic titanium dioxide (TiO2) aerogel (GTA) with internal hydrophilic-hydrophobic hybrid wettability structure is prepared via a facile freeze-drying and thermal reduction method. The evaporator shows adjustable wettability, optimized water content, and a low energy loss in the evaporation process. Simultaneously, the hybrid wetting structure in aerogel subjects salt to a dynamic crystallization-dissolution process to prevent salt deposition. The GTA solar evaporator achieves an evaporation rate of 1.52 kg·m-2·h-1 with a 91.02% efficiency under 1 sun irradiation. Furthermore, GTAs achieve a stable evaporation rate in high salinity brine (25 wt % NaCl) under 1 sun irradiation for 100 h, which could compete well with other most advanced photothermal evaporation materials. Moreover, the synergistic effect of graphene and TiO2 endows GTAs with excellent photocatalytic degradation and self-cleaning properties, which can effectively reduce the enrichment of contaminants on the evaporator. Therefore, GTA evaporators can efficiently and stably obtain clean water from seawater and wastewater, which provides a feasible strategy for the purification of complex wastewater.

The new morphologic classification of the hand motor cortex with magnetic resonance imaging in glioma patients.

Purpose: The hand motor cortex (HMC) is a reliable anatomical landmark for identifying the precentral gyrus. The current study aimed to investigate the morphology of HMC on axial MRI of glioma patients, propose a new morphological classification of HMC and analyze the effect of tumors on the morphology of HMC. Methods: A retrospective study of 276 adult right-handed glioma patients was conducted. The morphology of HMC was assessed using T2 axial images. Subsequently, the distribution of morphological subtypes was compared between the bilateral hemispheres and the tumor-affected and healthy hemispheres. Finally, the influence of tumor pathology on the morphology of HMC was investigated. Results: A new morphological classification of HMC with four subtypes (Ω, ε, Ω-ε and ε-Ω) was proposed. No significant difference was identified in the distribution of morphological subtypes between the bilateral hemispheres (p = 0.0901, Chi-square test), or between the tumor-affected and healthy hemispheres (p = 0.3507, Chi-square test), and the morphology of HMC between the bilateral hemispheres were consistent (p < 0.0001, Kappa test). In addition, a significant difference was identified in the distribution of morphological subtypes between astrocytic and oligodendroglial tumors (p = 0.0135, Chi-square test). Conclusion: In the current study, we proposed a new morphological classification of HMC, and found that tumor could affect the morphology of HMC in glioma patients. The results can help our clinical practice, enabling us to further understand the spatial structure of the cerebral hemispheres.

Effects of erythromycin and roxithromycin on river periphyton: Structure, functions and metabolic pathways.

Macrolides have been frequently detected in the surface waters worldwide, posing a threat to the aquatic microbes. Several studies have evaluated the ecotoxicological effects of macrolides on single algal and bacterial strains. However, without considering the species interaction in the aquatic microbial community, these results cannot be extrapolated to the field. Thus, the present study aimed to evaluate the effects of two macrolides (erythromycin and roxithromycin) on the structure, photosynthetic process, carbon utilization capacity, and the antibiotic metabolic pathways in river periphyton. The colonized periphyton was exposed to the graded concentration (0 µg/L (control), 0.5 µg/L (low), 5 µg/L (medium), 50 µg/L (high)) of ERY and ROX, respectively, for 7 days. Herein, high levels of ERY and ROX altered the community composition by reducing the relative abundance of Chlorophyta in the eukaryotic community. Also, the Shannon and Simpson diversity indexes of prokaryotes were reduced, although similar effects were seldomly detected in the low and medium groups. In contrast to the unchanged carbon utilization capacity, the PSII reaction center involved in the periphytic photosynthesis was significantly inhibited by macrolides at high levels. In addition, both antibiotics had been degraded by periphyton, with the removal rate of 51.63-66.87% and 41.85-48.27% for ERY and ROX, respectively, wherein the side chain and ring cleavage were the main degradation pathways. Overall, this study provides an insight into the structural and functional toxicity and degradation processes of macrolides in river periphyton.

Distribution, Sources and Risk Assessment of Polychlorinated Biphenyls in Sediments from Beiluo River.

The distribution and source of polychlorinated biphenyls (PCBs) pollution in the Beiluo River, the secondary tributary of the Yellow River, still remain unclear. With the purpose of determining the distribution, origins, and pollution levels of PCBs and their consequences on ecological risks, the concentrations of 27 PCBs at 17 locations in the sediments of the Beiluo River were examined in this study. The results showed that the mass concentrations of ∑PCBs in the sediment ranged from 0.12 to 1.25 ng∙g-1 (DW), with the highest point at sampling site B13 downstream of the river. Compared to most river sediments, both domestically and internationally, the concentration of PCBs in the sediment of the Beiluo River was at a low level, with 10-PCB and 6-PCB as the main components, indicating that the PCBs that are difficult to volatilise and degrade are more likely to remain in the sediment. The origins of PCBs in the sediments of the Beiluo River were examined by using positive matrix factorisation (PMF). The results revealed that the contamination of PCBs in the sediments of the Beiluo River mainly resulted from industrial emissions, technical PCB mixtures, and coal and wood combustion. The results of the ecological risk assessment indicated that PCBs in the sediments of the study area rarely contribute to adverse biological effects and the potential low risk to the environment.

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis.

Background: As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients with HF or cardiovascular (CV) risk factors have not been systematically evaluated. The aim of this study is to evaluate the cardiovascular benefits and safety of sotagliflozin in T2DM patients with HF or CV risk factors using Bayesian network meta-analysis. Methods: Data were retrieved from PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library from their inception to 16 August 2023. Randomized controlled trials (RCTs) comparing sotagliflozin with a placebo, dapagliflozin, and empagliflozin in adult T2DM patients with HF or CV risks for at least 12 weeks were included in the study. Data analysis was conducted using R 4.2.3 and Stata 17.0. Cardiovascular efficacy outcomes included HF events (hospitalization or urgent visits for HF), MACE (deaths from CV causes, hospitalizations for HF, nonfatal myocardial infarctions, and strokes), cardiovascular death, the decrease in SBP, and weight loss. Safety outcomes are urinary tract infection, diarrhea, and diabetic ketoacidosis. Results: Eleven studies with 30,952 patients were included. Compared to dapagliflozin and empagliflozin, 200 mg of sotagliflozin showed the best effect in reducing HF events [OR (95% CI), 0.79 (0.66, 0.94) and 0.90 (0.63, 1.27)]. Compared to dapagliflozin, 200 mg of sotagliflozin [OR (95% CI), 0.76 (0.66, 0.87)] was superior in preventing MACE. Compared to empagliflozin, 200 mg of sotagliflozin [OR (95% CI), 1.46 (1.04, 2.05)] was inferior in preventing CV death. Sotagliflozin showed a poorer SBP decreasing effect than empagliflozin and dapagliflozin [MD (95% CI), 1.30 (0.03, 2.56) and 2.25 (0.35, 4.14), respectively]. There was no significant difference between sotagliflozin and other interventions in weight loss. Sotagliflozin exhibited no increased risk for diabetic ketoacidosis or urinary tract infection among all interventions, however, it showed a mild risk for diarrhea than placebo [OR (95% CI), 1.47 (1.28, 1.69)]. Conclusion: Sotagliflozin displayed moderate CV benefits and acceptable safety. Sotagliflozin can be one of the recommended options for T2DM patients with HF or CV risk factors, which will be important for evidence-based use of sotagliflozin as well as decision-making of T2DM medication.

Bis[1-cyclo-propyl-6-fluoro-4-oxo-7-(1-piperazin-4-ium-1-yl)-1,4-dihydro-quinoline-3-carboxyl-ate-κO,O]bis-(nitrato-κO)copper(II).

In the title complex, [Cu(NO(3))(2)(C(17)H(18)FN(3)O(3))(2)], the Cu(II) ion is located on an inversion center. It exhibits a distorted octa-hedral geometry, being coordinated by six O atoms, four from two ciprofloxacin ligand mol-ecules (L), which act as bidentate ligands, and two from two nitrate anions. In the ligand, the piperazine ring has a chair conformation and the quinoline system is essentially planar [maximum deviation = 0.097 (2) Å]. One of the nitrate O atoms is disordered over two positions [occupancy ratio = 0.51 (6):0.49 (6)]. There is a C-H⋯F inter-action in the complex. In the crystal, mol-ecules are linked via N-H⋯O hydrogen bonds generating a two-dimensional network lying parallel to (111). The presence of C-H⋯O inter-actions leads to the formation of a three-dimensional structure. The title complex was prepared by hydro-thermal synthesis, and the hexa-hydrate form of this complex, synthesized by conventional methods, has been reported previously [Hernandez-Gil et al. (2009 ▶). Polyhedron, 28, 138-144].

4-(1-Cyclo-propyl-6-fluoro-4-oxo-1,4-dihydro-quinolin-7-yl)piperazin-1-ium 2,4,5-tricarb-oxy-benzene-1-carboxyl-ate monohydrate.

In the crystal of title compound, C(16)H(19)FN(3)O(+)·C(10)H(5)O(8) (-)·H(2)O, the water mol-ecule and the ions are connected by inter-molecular N-H⋯O and O-H⋯O hydrogen bonds and π-π stacking [centroid-centroid separation = 3.602 (1) Å] between the benzene ring and the pyridine ring, generating a three-dimensional supra-molecular structure.

cis-Tetra-aqua-bis-{5-[4-(1H-imidazol-1-yl-κN(3))phen-yl]tetra-zolido}manganese(II) dihydrate.

In the title compound, [Mn(C(10)H(7)N(6))(2)(H(2)O)(4)]·2H(2)O, the complex unit comprises an Mn(2+) ion, coordinated by two imidazole N atoms from cis-related monodentate 5-[4-(imidazol-1-yl)phen-yl]tetra-zolide ligands and four water mol-ecules, together with two water mol-ecules of solvation. The Mn(2+) ion lies on a twofold rotation axis and has a slightly distorted octa-hedral geometry. The mol-ecules are connected by O-H⋯N and O-H⋯O hydrogen bonds involving both coordinated and solvent water mol-ecules, generating a three-dimensional structure. Two C atoms of the imidazole ring of the ligand are each disordered over two sites with occupancy factors of 0.75 and 0.25.

Deep Convolutional Neural Network-Based Brain Magnetic Resonance Imaging Applied in Glioma Diagnosis and Tumor Region Identification.

The aim of this study was to explore the application value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on a convolutional neural network (CNN) algorithm in glioma diagnosis and tumor segmentation. 66 patients with gliomas who were diagnosed and treated in the hospital were selected as the research objects. The patients were rolled into the high-grade glioma group (HGG, 46 cases) and the low-grade glioma group (LGG, 20 cases) according to the World Health Organization glioma grading standard. All patients received a conventional plain scan and a DCE-MRI. Parameters such as volume transfer constant (K trans), rate constant (K ep ), extracellular volume (V e ), and mean plasma volume (V p ) were calculated, and the parameters of patients of each grade were analyzed. The efficacy of each parameter in diagnosing glioma was analyzed through a receiver operating characteristic curve. All images were segmented by the CNN algorithm. The CNN algorithm showed good performance in DCE-MRI image segmentation. The mean, standard deviation, kurtosis, and skewness of K trans and V e , the standard deviation and skewness of K ep , and the mean and standard deviation of V p were statistically considerable in differentiating HGG and LGG (P < 0.05). ROC analysis showed that the standard deviation of K trans (0.885) had the highest diagnostic accuracy in distinguishing HGG and LGG. The values of K trans, V e , and V p were positively correlated with Ki-67 (r = 0.346, P = 0.014; r = 0.335, P = 0.017; r = 0.323, P = 0.022). In summary, the CNN-based DCE-MRI technology had high application value in glioma diagnosis and tumor segmentation.