Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

Using Bidirectional Encoder Representations from Transformers (BERT) to predict criminal charges and sentences from Taiwanese court judgments.

People unfamiliar with the law may not know what kind of behavior is considered criminal behavior or the lengths of sentences tied to those behaviors. This study used criminal judgments from the district court in Taiwan to predict the type of crime and sentence length that would be determined. This study pioneers using Taiwanese criminal judgments as a dataset and proposes improvements based on Bidirectional Encoder Representations from Transformers (BERT). This study is divided into two parts: criminal charges prediction and sentence prediction. Injury and public endangerment judgments were used as training data to predict sentences. This study also proposes an effective solution to BERT's 512-token limit. The results show that using the BERT model to train Taiwanese criminal judgments is feasible. Accuracy reached 98.95% in predicting criminal charges and 72.37% in predicting the sentence in injury trials, and 80.93% in predicting the sentence in public endangerment trials.

Research Progress on the Composite Methods of Composite Electrolytes for Solid-State Lithium Batteries.

In the current challenging energy storage and conversion landscape, solid-state lithium metal batteries with high energy conversion efficiency, high energy density, and high safety stand out. Due to the limitations of material properties, it is difficult to achieve the ideal requirements of solid electrolytes with a single-phase electrolyte. A composite solid electrolyte is composed of two or more different materials. Composite electrolytes can simultaneously offer the advantages of multiple materials. Through different composite methods, the merits of various materials can be incorporated into the most essential part of the battery in a specific form. Currently, more and more researchers are focusing on composite methods for combining components in composite electrolytes. The ion transport capacity, interface stability, machinability, and safety of electrolytes can be significantly improved by selecting appropriate composite methods. This review summarizes the composite methods used for the components of composite electrolytes, such as filler blending, embedded framework, and multilayer bonding. It also discusses the future development trends of all-solid-state lithium batteries (ASSLBs).

Full substitution of chemical fertilizer by organic manure decreases soil N2 O emissions driven by ammonia oxidizers and gross nitrogen transformations.

Replacing synthetic fertilizer by organic manure has been shown to reduce emissions of nitrous oxide (N2 O), but the specific roles of ammonia oxidizing microorganisms and gross nitrogen (N) transformation in regulating N2 O remain unclear. Here, we examined the effect of completely replacing chemical fertilizer with organic manure on N2 O emissions, ammonia oxidizers, gross N transformation rates using a 13-year field manipulation experiment. Our results showed that organic manure reduced cumulative N2 O emissions by 16.3%-210.3% compared to chemical fertilizer. The abundance of ammonia oxidizing bacteria (AOB) was significantly lower in organic manure compared with chemical fertilizer during three growth stages of maize. Organic manure also significantly decreased AOB alpha diversity and changed their community structure. However, organic manure substitution increased the abundance of ammonia oxidizing archaea and the alpha diversity of comammox Nitrospira compared to chemical fertilizer. Interestingly, organic manure decreased organic N mineralization by 23.2%-32.9%, and autotrophic nitrification rate by 10.5%-45.4%, when compared with chemical fertilizer. This study also found a positive correlation between AOB abundance, organic N mineralization and gross autotrophic nitrification rate with N2 O emission, and their contribution to N2 O emission was supported by random forest analysis. Our study highlights the key roles of ammonia oxidizers and N transformation rates in predicting cropland N2 O.

The role of the basal forebrain in general anesthesia.

The basal forebrain is a group of nerve nuclei on the ventral side of the ventral ganglion, composed of γ-aminobutyric acid neurons, glutamatergic neurons, cholinergic neurons, and orexigenic neurons. Previous studies have focused on the involvement of the basal forebrain in regulating reward, learning, movement, sleep-awakening, and other neurobiological behaviors, but its role in the regulation of general anesthesia has not been systematically elucidated. Therefore, the different neuronal subtypes in the basal forebrain and projection pathways in general anesthesia will be discussed in this paper. In this paper, we aim to determine and elaborate on the role of the basal forebrain in general anesthesia and the development of theoretical research and provide a new theory.

Does tourism market diversification matter for CO2 emissions? evidence from Singapore.

This research analyzed the effect of tourism market diversification on Singapore's CO2 emissions by measuring the level of concentration of source countries in a foreign tourist basket of Singapore using a Herfindahl-Hirschman index. Our results indicated that the index fell over the period 1978-2020, which means the diversification of source countries of Singapore's foreign tourists increased. By applying the recent bootstrap and quantile ARDL models, we found that tourism market diversification and inward FDI act as stumbling blocks to CO2 emissions. In contrast, economic growth and primary energy consumption increase CO2 emissions. Policy implications are presented and discussed.

Dopamine D1-receptor-expressing pathway from the nucleus accumbens to ventral pallidum-mediated sevoflurane anesthesia in mice.

BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep-wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R-expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. METHODS: In order to analyze the impact of sevoflurane anesthesia on NAcD1R neurons and the NAcD1R -VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1-receptor-expressing neurons located in the nucleus accumbens (NAcD1R neurons) and the NAcD1R -VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAcD1R neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAcD1R neurons and the NAcD1R -VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically-encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. RESULTS: Our findings revealed that sevoflurane administration led to the inhibition of NAcD1R neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAcD1R neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAcD1R -VP pathway exerted opposite effects. CONCLUSION: The NAcD1R -VP pathway serves as a crucial downstream pathway of NAcD1R neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells.

A Robust, Fully Automatic Detection Method and Calculation Technique of Midline Shift in Intracranial Hemorrhage and Its Clinical Application.

A midline shift (MLS) is an important clinical indicator for intracranial hemorrhage. In this study, we proposed a robust, fully automatic neural network-based model for the detection of MLS and compared it with MLSs drawn by clinicians; we also evaluated the clinical applications of the fully automatic model. We recruited 300 consecutive non-contrast CT scans consisting of 7269 slices in this study. Six different types of hemorrhage were included. The automatic detection of MLS was based on modified Keypoint R-CNN with keypoint detection followed by training on the ResNet-FPN-50 backbone. The results were further compared with manually drawn outcomes and manually defined keypoint calculations. Clinical parameters, including Glasgow coma scale (GCS), Glasgow outcome scale (GOS), and 30-day mortality, were also analyzed. The mean absolute error for the automatic detection of an MLS was 0.936 mm compared with the ground truth. The interclass correlation was 0.9899 between the automatic method and MLS drawn by different clinicians. There was high sensitivity and specificity in the detection of MLS at 2 mm (91.7%, 80%) and 5 mm (87.5%, 96.7%) and MLSs greater than 10 mm (85.7%, 97.7%). MLS showed a significant association with initial poor GCS and GCS on day 7 and was inversely correlated with poor 30-day GOS (p < 0.001). In conclusion, automatic detection and calculation of MLS can provide an accurate, robust method for MLS measurement that is clinically comparable to the manually drawn method.

Mesoporous crystalline Ti1-xSnxO2 (0 < x < 1) solid solution for a high-performance photocatalyst under visible light irradiation.

We report a facile and effective inorganic polycondensation combined with aerosol-spray strategy towards high-performance photocatalyst by fabricating mesoporous Ti1-xSnxO2 (0 < x < 1) solid solution. Such Ti1-xSnxO2 nanocrystals with high Sn-doped contents are self-assembled into mesoporous spheres can effectively promote visible-light harvest and high quantum yield, leading a longer lifetime of the photoelectron-hole pairs and less recombination. Such the photocatalysts enhanced photocatalytic activity for the degradation of Rhodamine B (RhB). The representative Ti0.9Sn0.1O2 and Ti0.8Sn0.2O2 compounds reach an optimum degradation of ≈50% and 70%, respectively, after 120 min irradiation under visible irradiation. The mesoporous Ti1-xSnxO2 solid solution could inhibit the recombination of electron-hole pairs, which promote reaction thermodynamics and kinetics for RhB degradation.

Tin-graphene tubes as anodes for lithium-ion batteries with high volumetric and gravimetric energy densities.

Limited by the size of microelectronics, as well as the space of electrical vehicles, there are tremendous demands for lithium-ion batteries with high volumetric energy densities. Current lithium-ion batteries, however, adopt graphite-based anodes with low tap density and gravimetric capacity, resulting in poor volumetric performance metric. Here, by encapsulating nanoparticles of metallic tin in mechanically robust graphene tubes, we show tin anodes with high volumetric and gravimetric capacities, high rate performance, and long cycling life. Pairing with a commercial cathode material LiNi0.6Mn0.2Co0.2O2, full cells exhibit a gravimetric and volumetric energy density of 590 W h Kg-1 and 1,252 W h L-1, respectively, the latter of which doubles that of the cell based on graphite anodes. This work provides an effective route towards lithium-ion batteries with high energy density for a broad range of applications.

Anion-Sorbent Composite Separators for High-Rate Lithium-Ion Batteries.

Novel composite separators containing metal-organic-framework (MOF) particles and poly(vinyl alcohol) are fabricated by the electrospinning process. The MOF particles containing opened metal sites can spontaneously adsorb anions while allowing effective transport of lithium ions in the electrolyte, leading to dramatically improved lithium-ion transference number tLi + (up to 0.79) and lithium-ion conductivity. Meanwhile, the incorporation of the MOF particles alleviates the decomposition of the electrolyte, enhances the electrode reaction kinetics, and reduces the interface resistance between the electrolyte and the electrodes. Implementation of such composite separators in conventional lithium-ion batteries leads to significantly improved rate capability and cycling durability, offering a new prospective toward high-performance lithium-ion batteries.

Controlled Synthesis and Photocatalytic Performance of Au@ZnO Nanospheres with Core-Shell and Yolk-Shell Structures Assisted by Carbonaceous Layers as Intermediate.

Au@ZnO nanospheres with controlled core-shell and yolk-shell features were successfully fabricated through a facile template-based solvothermal method using carbonaceous layers as intermediate. The active carbonaceous layers containing numerous surface functional groups such as OH and C═O play key roles in fabrication of the Au@ZnO nanospheres. The structures of Au@ZnO can easily controlled by adjusting the concentration of Zn ions aqueous solution and/or the size of Au@C microspheres. The synthesis strategy proposed in this paper is also verified to be suitable for fabricating some other Au@metallic oxides nanospheres such as Au@SnO2 and Au@Fe2O3 with controlled structures. Furthermore, due to the synergic effect of the surface plasma resonance effect of Au cores and the large surface area of 122.67 m2 g-1, the Au@ZnO nanospheres with yolk-shell feature exhibite good photocatalytic activity and stability under visible-light irradiation.

Remarkably enhanced photovoltaic effects and first-principles calculations in neodymium doped BiFeO3.

Remarkably enhanced photovoltaic effects have been observed in the heterostructures of p-type A-site Nd3+-doped BiFeO3 (Bi0.9375Nd0.0625)FeO3 (or BFONd) polycrystalline ceramics and the n-type ITO thin film. The maximum power conversion is ~0.82%, which is larger than 0.015% in BiFeO3 (BFO) under blue-ultraviolet irradiation of wavelength λ = 405 nm. The current-voltage (I-V) characteristic curve suggests a p-n junction interface between the ITO thin film and BFO (or BFONd) ceramics. The band gaps calculated from first-principles for BFO and BFONd are respectively 2.25 eV and 2.23 eV, which are consistent with the experimental direct band gaps of 2.24 eV and 2.20 eV measured by optical transmission spectra. The reduction of the band gap in BFONd can be explained by the lower electronic Fermi level due to acceptor states revealed by first-principles calculations. The optical calculations show a larger absorption coefficient in BFONd than in BFO.

Hierarchical Nanostructured WO3 with Biomimetic Proton Channels and Mixed Ionic-Electronic Conductivity for Electrochemical Energy Storage.

Protein channels in biologic systems can effectively transport ions such as proton (H(+)), sodium (Na(+)), and calcium (Ca(+)) ions. However, none of such channels is able to conduct electrons. Inspired by the biologic proton channels, we report a novel hierarchical nanostructured hydrous hexagonal WO3 (h-WO3) which can conduct both protons and electrons. This mixed protonic-electronic conductor (MPEC) can be synthesized by a facile single-step hydrothermal reaction at low temperature, which results in a three-dimensional nanostructure self-assembled from h-WO3 nanorods. Such a unique h-WO3 contains biomimetic proton channels where single-file water chains embedded within the electron-conducting matrix, which is critical for fast electrokinetics. The mixed conductivities, high redox capacitance, and structural robustness afford the h-WO3 with unprecedented electrochemical performance, including high capacitance, fast charge/discharge capability, and very long cycling life (>50,000 cycles without capacitance decay), thus providing a new platform for a broad range of applications.

Mesoporous crystalline-amorphous oxide nanocomposite network for high-performance lithium storage.

Mesoporous nanocomposites composed of crystalline and amorphous oxides network were successfully synthesized by a continuous aerosol spray process; electrodes made from such nanocomposites with a thin-layer of protective oxide coating exhibit high capacity and long cycling life for lithium storage.

Stable lithium-ion cathodes from nanocomposites of VO2 nanowires and CNTs.

A VO(2)(B) nanowire/CNT nanocomposite was fabricated with a stable lithium storage performance resulting in an interpenetrating porous network. This material demonstrated an enhanced Li-ion storage capacity with a significantly improved cycling stability. The capacity of the composite faded by only 6% after 100 cycles at 1 C, suggesting great promise for better lithium-ion cathodes. These results demonstrated that the CNT's network could effectively harvest the charges during the reaction. Moreover, these further prove a general approach to achieve high-capacity electrode materials with long-term cycling stability using intertwined network structures.

Building robust architectures of carbon and metal oxide nanocrystals toward high-performance anodes for lithium-ion batteries.

Design and fabrication of effective electrode structure is essential but is still a challenge for current lithium-ion battery technology. Herein we report the design and fabrication of a class of high-performance robust nanocomposites based on iron oxide spheres and carbon nanotubes (CNTs). An efficient aerosol spray process combined with vacuum filtration was used to synthesize such composite architecture, where oxide nanocrystals were assembled into a continuous carbon skeleton and entangled in porous CNT networks. This material architecture offers many critical features that are required for high-performance anodes, including efficient ion transport, high conductivity, and structure durability, therefore enabling an electrode with outstanding lithium storage performance. For example, such an electrode with a thickness of ∼35 µm could deliver a specific capacity of 994 mA h g(-1) (based on total electrode weight) and high recharging rates. This effective strategy can be extended to construct many other composite electrodes for high-performance lithium-ion batteries.

New flavan and benzil isolated from Fissistigma latifolium.

Further investigation of the methanolic extract of Fissistigma latifolium resulted in two new compounds whose structures were assigned as 2,5,6,7-tetramethoxyflavan (1) and 2'-hydroxy-4',5',6'-trimethoxybenzil (2). These two compounds were determined on the basis of chemical and spectroscopic evidences. Compound 2 is the first report of benzil from Fissistigma species. 2,5,6,7-Tetramethoxyflavan (1) showed a potent inhibitory effect on superoxide anion production in formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)/cytochalasin B (CB)-activated human neutrophils.

The first bis-retrochalcone from Fissistigma latifolium.

Two novel chalconoids, [3-3'']bi-2-hydroxy-4,5,6-trimethoxydihydrochalcone (1) and 4,6-dimethoxy-2,5-quinodihydrochalcone (2), and twelve known compounds were isolated from the methanolic extract of Fissistigma latifolium (Dun.) Merr. The structures of all compounds were determined by spectroscopic methods. Of these, compounds 1, 2, and 2-hydroxy-4,5,6-trimethoxydihydrochalcone (10) belong to an uncommon group of chalconoids, the retrochalcones. Compound 1 is the first bis-retrochalcone to be reported, and compound 2 is a quinoretrochalcone. Furthermore, 2 showed activity against the MDA-MB-231 human breast cancer cell line with an IC (50) value of 7.1 µM.