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In order to apply and develop fluorine‐free slag in steelmaking, it is of great significance to study the effect of composition for fluorine‐free refining slag on the cleanliness of molten steel which affects its performance directly. The effect of composition of fluorine‐free refining slag with medium and high basicity on the contents of impurity elements for sulfur and oxygen, and characteristics of inclusions in SWRS82B hard wire steel, are investigated systematically. Sulfide capacity of refining slag is estimated based on the Royal Swedish Institute of Technology model. Dissolved oxygen content in molten steel equilibrated by refining slag is calculated based on Factsage software and classical thermodynamics. The calculated results are in good agreement with experimental results. The plasticity of inclusions at high temperature and low temperature is analyzed by phase diagram and Young's modulus calculation. The best cleanliness and inclusions of SWRS82B steel are obtained with slag composition of 53%CaO–19%SiO2–19%Al2O3–7%MgO, which has good melting characteristics. The impurity elements sulfur and oxygen in steel can be controlled for 26 and 19 ppm, respectively, and the average size of inclusions is 2.84 μm. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) and atherosclerosis (AS) are widespread diseases predominantly observed in the elderly population. Despite their prevalence, the underlying molecular interconnections between these two conditions are not well understood. Methods: Utilizing meta‐analysis, bioinformatics methodologies, and the GEO database, we systematically analyzed transcriptome data to pinpoint key genes concurrently differentially expressed in AD and AS. Our experimental validations in mouse models highlighted the prominence of two genes, NKRF (NF‐κB‐repressing factor) and ZBTB17 (MYC‐interacting zinc‐finger protein 1). Results: These genes appear to influence the progression of both AD and AS by modulating the NF‐κB signaling pathway, as confirmed through subsequent in vitro and in vivo studies. Conclusions: This research uncovers a novel shared molecular pathway between AD and AS, underscoring the significant roles of NKRF and ZBTB17 in the pathogenesis of these disorders. [ABSTRACT FROM AUTHOR]

Recent studies have shown that chondrocyte ferroptosis contributes importantly to the pathogenesis of osteoarthritis (OA). However, it is largely unknown how it is regulated. In this study, the data sets GSE167852 and GSE190184 were downloaded from the Gene Expression Omnibus (GEO) database, and 161 differentially expressed genes (DEGs) related to ferroptosis were screened by bioinformatics analysis. Subsequently, ADORA2B was screened as a candidate gene from DEGs, which was significantly upregulated in palmitic acid (PA) treated chondrocytes. CCK‐8, EdU, Western blotting, and ferroptosis‐related kits assays demonstrated that knockdown of ADORA2B constrained ferroptosis and promoted viability of chondrocytes. Overexpression of ADORA2B promoted ferroptosis, while the PI3K/Akt pathway inhibitor LY294002 reversed the promotion of ADORA2B on ferroptosis. Dual‐luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assays indicated MYC was a transcription suppressor of ADORA2B, and overexpression of MYC promoted the viability, and inhibited the ferroptosis of chondrocytes, while ADORA2B overexpression abated the promotion of MYC on chondrocyte viability and the inhibition on ferroptosis. In vivo experiments showed that MYC overexpression alleviated cartilage tissue damage in OA mice, which was able to reversed by ADORA2B overexpression. In summary, ADORA2B, transcriptionally suppressing by MYC, promotes ferroptosis of chondrocytes via inhibition of the PI3K/Akt pathway. Thus, ADORA2B can be used as a potential treatment target for ferroptosis‐related diseases. [ABSTRACT FROM AUTHOR]

Deep eutectic solvent (DES) is used as both photocatalyst and solvent for photoinduced reversible complexation‐mediated polymerization (photo‐RCMP), which enables a rapid polymerization to produce polymers with predictable molar mass and low molar mass dispersity (Đ). This work illustrates a comprehensive understanding of DES‐accelerated RCMP's mechanism and kinetic features through quantum chemical calculations and kinetic modeling. According to the results, electrons transferring from hydrogen bond in DES to iodine atom in alkyl iodide (RI) initiator under light irradiation lowers the decomposition free energy of complex RI‐DES. This procedure facilitates the generation of primary radicals, thus contributing to the DES‐accelerated phenomenon. In the meantime, the reaction paths are identified by computation as (i) decomposition of RI‐DES under light irradiation generates active radicals and ·I‐DES complex and (ii) combination of two ·I‐DES releases iodine (I2) and regenerates DES. In addition, kinetic modeling based on the method of moments successfully identifies kinetic features of polymerization in the presence and absence of DES, respectively. Kinetic modeling shows a fast increase in primary radicals concentration and rapid build‐up of the photo‐RCMP activation‐deactivation equilibrium, demonstrating that DES is a beneficial photocatalyst and solvent to enable the rapid generation of primary radicals and accelerate the completion of catalytic cycle. This research provides an in‐depth understanding of DES‐involved photo‐RCMP and lays a theoretical foundation for expanding the application of DES to other polymerization systems. [ABSTRACT FROM AUTHOR]

Enhanced knowledge of the Pamir salient formation can contribute to comprehending the tectonic evolution of Himalaya-Tibetan orogen. However, whether the Pamir salient formed along a linear or a curved southern Asian margin between the Tarim and Tajik cratons remains controversial. Likewise, the role of the two craton blocks during the evolution of the Pamir salient is unclear. Here we present three sandbox experiments exploring the effect of the geometry of the southern Asian margin, as well as the presence of Tarim and Tajik cratons. The results show that the highly curved shape of the Pamir salient, transpressional faults in its wings and strike-slip faults within its interior only form along a curved southern Asian margin. A westward-deflecting arcuate thrust wedge formed along the asymmetric curved southern Asian margin. Together with the Tarim craton and the Tajik craton, this wedge facilitated the westward transfer of materials in the Pamir, and resulted in the westward deflection of the velocity field in Pamir and the formation of the Tajik fold-thrust belt. The oblique slip of arcuate thrust wedge along the western edge of the Tarim craton generated the Kongur extensional system. Moreover, the Tarim and Tajik cratons concentrated deformation mainly along the non-cratonic continental margin and promoted the formation of transpressional faults surrounding the Pamir and the strikeslip faults within the Pamir. [ABSTRACT FROM AUTHOR]

As the body's largest organ, the skin is an integrated multisensory system with self‐healing ability and helps stabilize body temperature. It is herein, inspired by natural skin, a wearable patch made from porous polydimethylsiloxane (PDMS) skeleton, poly(vinyl alcohol) (PVA) hydrogel, and silicon oxide (SiO2) particles, offers a combination of self‐healing properties, along with hybrid radiative and evaporative cooling mechanisms, designed for electromyographic (EMG) signal detection and human‐machine interaction. The patch has both high mid‐infrared (MIR) emittance (96%) and visible to near‐infrared (visNIR) reflectance (80%), coupled with efficient water evaporation from the PVA hydrogel, resulting in a hybrid cooling power of 180 W m−2. It obtains a temperature drop of ≈7.7 °C using this patch under a solar intensity of ≈700 W m−2. Furthermore, the patch demonstrates self‐healing ability with ultrafast recovery of electrical conductivity (1 s) and a self‐healing efficiency (≈71%) of fracture strain. Thus, the wearable patch can detect high‐quality EMG signals and provide cooling effects and self‐healing capabilities that enhance comfortability and durability. These features make the patch an advanced solution for developing next‐generation wearable patches that can meet the rigorous demands of durable body temperature control in various applications. [ABSTRACT FROM AUTHOR]

Dulaglutide 3.0 and 4.5 mg weekly doses were approved for additional glycemic control in adult patients with type 2 diabetes inadequately controlled with metformin and 0.75 or 1.5 mg weekly doses of dulaglutide. Effects such as nausea and vomiting are commonly reported with dulaglutide and other glucagon‐like peptide‐1 receptor agonist therapies. Based on a pharmacokinetic/pharmacodynamic model‐informed approach, a stepwise dose‐escalation scheme with 4‐week intervals between dose increments was suggested to mitigate gastrointestinal events for dulaglutide. These gastrointestinal events are dose dependent and attenuate over time with repeated dosing. A Markov chain Monte Carlo pharmacokinetic/pharmacodynamic joint model was developed using AWARD‐11 data (N = 1842) to optimize dulaglutide dose escalation to 3.0 and 4.5 mg to mitigate gastrointestinal events. Model simulations evaluated probabilities of nausea and vomiting events for various dosing scenarios in patients needing higher doses for additional glycemic control. The model indicated that patients may dose escalate from 1.5 to 3.0 mg, then 4.5 mg weekly after at least 4 weeks on each dose. No clinically meaningful differences in nausea or vomiting events were expected when patients escalated to 3.0 or 4.5 mg following initiation at 0.75 or 1.5 mg dulaglutide. Based on the findings of this model, a minimum 4‐week duration at each dose before escalation was appropriate to reduce gastrointestinal events of dulaglutide, consistent with observed gastrointestinal events data from the AWARD‐11 study and supporting the currently recommended dose‐escalation regimen of dulaglutide doses of 3.0 and 4.5 mg for additional glycemic control. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been well accepted that lactic acid bacteria (LAB) are the main bacterial genera present during the brewing of Chinese rice wine (CRW). LAB plays a decisive role in the flavor quality of CRW; however, its application in CRW has previously been overlooked. Therefore, effects of different LAB as co‐fermenter on the flavor characteristics of CRW were investigated. RESULTS: Co‐fermentation of LAB increased the utilization rate of reducing sugar, concentration of lactic acid, amino acid nitrogen and total acidity, as well as the content of volatile flavor compounds. Different LAB doses had little effect on the flavor profiles of CRW, but the species of LAB greatly affected the flavor characteristic. The flavor of CRW co‐fermented with Lactococcus lactis was characterized by long‐chain fatty acid ethyl esters, while co‐fermentation with Weissella confusa highlighted the ethyl esters of low molecular weight and short carbon chains in the resultant CRW. Alcohol compounds were dominant in the CRW co‐fermented using Pediococcus pentosaceus. CONCLUSION: The co‐fermentation of LAB increased the number of volatile flavor compounds, especially esters. LAB exhibited great potential in the application of CRW industry to enrich the flavor characteristics and enhance the flavor diversity of the final product. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Recent studies have shown that Solute Carrier Family 9 Member A2 (SLC9A2) could serve as a biomarker for cancer. However, its mechanism of action in osteosarcoma (OS) was still unclear. In this study, the data sets GSE154530 and GSE99671 were downloaded from the Gene Expression Omnibus (GEO) database, and 31 differentially expressed genes (DEGs) related to methylation were screened by bioinformatics analysis tools. Subsequently, SLC9A2 was screened as a candidate gene from DEGs, which was significantly downregulated in OS. CCK‐8, transwell, western blotting and Seahorse XFe24 Cell Metabolic Analyzer assays demonstrated that overexpression of SLC9A2 could constrain OS cell proliferation, invasion, and aerobic glycolysis. Dual‐luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assays indicated ETS proto‐oncogene 1 (ETS1) was a transcription suppressor of SLC9A2, and overexpression of ETS1 could promote methylation levels in specific regions of the SLC9A2 promoter. ETS1 could promote the proliferation, invasion, and aerobic glycolysis ability of OS cells, as well as tumor growth in vivo by inhibiting the expression of SLC9A2. In addition, SLC9A2, suppressing by ETS1, restrains growth and invasion of OS via inhibition of aerobic glycolysis. Thus, SLC9A2 can function as a key inhibitory factor in the aerobic glycolysis to inhibit proliferation and invasion of OS. This indicated that SLC9A2 has a potential targeted therapeutic effect on OS. [ABSTRACT FROM AUTHOR]

NASICON‐structured solid‐state electrolytes (SSEs) are highly promising materials for sodium solid‐state metal batteries (NaSMBs). However, the current synthesis methods are often labor‐intensive and inefficient, consuming a significant amount of energy and time. Here, an ultrafast high‐temperature synthesis (UHS) technique is successfully demonstrated to directly synthesize NASICON‐type SSEs from mixed precursor powders, reducing the synthesis time from hours to merely seconds. The intermediate with a Na3PO4 structure plays a critical role in the rapid synthesis of NASICON‐type SSEs, ultimately leading to the formation of the final NASICON phase. Moreover, the UHS‐synthesizes NASICON‐type Na3.3Zr1.7Lu0.3Si2PO12 (NZLSP) exhibits high room temperature ionic conductivity of 7.7 × 10−4 S cm−1, approximately three times that of the undoped Na3Zr2Si2PO12 (NZSP). The Na|NZLSP|Na symmetric cell can sustain highly stable cycling for over 4800 h. This study provides a novel insight and validation in the precise and targeted synthesis of complex oxide solid‐state electrolytes. [ABSTRACT FROM AUTHOR]

More and more attention has been paid to the important roles of external fields in controlled radical polymerization (CRP). However, their essential roles have not been studied thoroughly yet, which hinders the in‐depth understanding of the mechanism and kinetics. Herein, a strategy combining quantum chemical calculations (QCC) and kinetic modeling was adopted to identify the essential roles of light and ultrasonication in the dual‐stimuli regulated bulk atom transfer radical polymerization (ATRP). At the molecular level, the impact of light on Cu‐catalyzed ATRP was investigated. The CuIIBr/Me6TREN has high absorbance at an experimental wavelength of 365 nm (main excitation S0 → D7 accounts for 84.93%). Electron transfer reactions involving Me6TREN are more favorable paths for photochemical reactions, and the mechanism of the copper activation/deactivation pathway is inner sphere electron transfer. At the micro‐scale, a kinetic model based on the method of moment was established with a "series" encounter pair model to consider the influence of ultrasound on diffusional limitation. Simulation results show that the changes of the reaction rate coefficients ka, kda, and kt at high conversion reflect the degree of diffusional limitation by ultrasound. The multiscale modeling strategy applied in this study identifies the essential roles of photo and ultrasonication in dual‐stimuli regulated model systems, which can be extended to other external‐field regulated CRP to improve the mechanistic understanding. [ABSTRACT FROM AUTHOR]

Background and purpose: Having good collaterals is associated with better clinical outcomes in patients undergoing endovascular thrombectomy. This study aims to evaluate whether the effect of collateral status on functional outcomes is modified by volemia at admission. Methods: This is a single‐center, retrospective analysis of patients who had acute proximal anterior circulation occlusion and underwent endovascular thrombectomy between January 2019 and June 2022. Volemia at admission, evaluated by blood urea nitrogen‐to‐creatinine ratio, was used to dichotomize patients into dehydrated and hydrated groups. The primary outcome was functional independence (90‐day modified Rankin Scale score = 0–2). Secondary outcomes were the rates of successful reperfusion, 24‐h symptomatic intracranial hemorrhage, and 90‐day all‐cause mortality. Multivariable logistic regression analysis was used to assess the interaction between collateral status and volemia at admission on outcomes. Results: A total of 290 patients were enrolled, among whom having good collaterals was associated with functional independence (adjusted odds ratio [OR] = 2.71, 95% confidence interval [CI] = 1.41–5.22, p = 0.003). Having good collaterals benefited dehydrated patients (adjusted OR = 3.33, 95% CI = 1.45–7.63, p = 0.004) but not hydrated patients (adjusted OR = 2.21, 95% CI = 0.73–6.68, p = 0.161). However, an interaction between collaterals and volemia at admission on functional independence was not observed (p = 0.319). The rates of successful reperfusion, symptomatic intracerebral hemorrhage, and all‐cause mortality were similar between those with good and poor collaterals in both dehydrated and hydrated patients. Conclusions: The effect of collateral status on the functional independence of patients undergoing thrombectomy is not modified by volemia at admission. [ABSTRACT FROM AUTHOR]

The construction of high‐performance MOF‐based hollow fiber composite membrane (HFCM) modules is a significant, yet challenging task for the biofuel production industry. In this study, a novel approach was taken to fabricate PDMS@ZIF‐8/PVDF HFCMs in modules through a facile ZIF‐8 self‐crystallization synthesis followed by pressure‐assisted PDMS infusion for pervaporation ethanol‐water separation. The as‐prepared HFCMs exhibited an ultrathin separation layer (thickness, 370 ± 35 nm), which was achieved through precise regulation of the ZIF‐8 membrane and defect repair by PDMS infusion. Moreover, the strategy utilized in this study resolved the defect issues arising from MOF agglomeration in conventional composite membranes. Impressively, at the optimal packing density, the prepared membrane demonstrated a remarkable ethanol flux (1.11 kg m−2 h−1) with an PSI value (26.59 kg m−2 h−1) and showed promising long‐term stability for the pervaporation of 5 wt% ethanol aqueous solution at 40°C. [ABSTRACT FROM AUTHOR]

We report the synthesis of a novel spirocyclic quaternary ammonium salt that possesses axial chirality. Enantiopure material was obtained by fractional crystallization of the corresponding (R,R)‐tartrate salt. Application of this chiral quaternary ammonium salt in phase‐transfer catalytic asymmetric alkylation of glycinate Schiff base was examined. [ABSTRACT FROM AUTHOR]

Aims: Although intravenous thrombolysis (IVT) has not shown confirmative effects on the outcomes of patients receiving successful thrombectomy, it might influence the outcomes of a subset of these patients. This study aims to evaluate whether the effects of IVT depend on final reperfusion grade in patients with successful thrombectomy. Methods: This is a single‐center, retrospective analysis of patients with an acute anterior circulation large‐vessel occlusion and a successful thrombectomy between January 2020 and June 2022. Final reperfusion grade was evaluated by the modified Thrombolysis in Cerebral Infarction (mTICI) score, which was dichotomized into incomplete (mTICI 2b) and complete (mTICI 3) reperfusion. The primary outcome was functional independence (90‐day modified Rankin Scale score 0–2). Safety outcomes were 24‐h symptomatic intracranial hemorrhage and 90‐day all‐cause mortality. Multivariable logistic regression analyses were used to assess the interactions between IVT treatment and final reperfusion grade on outcomes. Results: When comparing all 167 patients enrolled in the study, IVT did not influence the extent of functional independence (adjusted OR: 1.38; 95% CI: 0.65–2.95; p = 0.397). The effect of IVT on functional independence depended on final reperfusion grade (p = 0.016). IVT benefited patients with incomplete reperfusion (adjusted OR: 3.70; 95% CI 1.21–11.30; p = 0.022), but not those with complete reperfusion (adjusted OR: 0.48, 95% CI: 0.14–1.59; p = 0.229). IVT was not associated with 24‐h symptomatic intracerebral hemorrhage (p = 0.190) or 90‐day all‐cause mortality (p = 0.545). Conclusions: The effect of IVT on functional independence depended on final reperfusion grade in patients with successful thrombectomy. IVT appeared to benefit patients with incomplete reperfusion, but not those with complete reperfusion. Because reperfusion grade cannot be determined prior to endovascular treatment, this study argues against withholding IVT in IVT‐eligible patients. [ABSTRACT FROM AUTHOR]

Inspired by the fact that the in‐situ fibrillation structure can enhance the polymer's macroscopic mechanical performance, a facile and cost‐effective strategy based on the pressure‐induced flow (PIF) processing was developed to produce ultra‐strong and super‐tough biodegradable poly(lactic acid)/poly(butylene succinate) (PLA/PBS) blends. Under the action of external pressure field, the ductile and flexible PBS droplets deformed along the flow direction (FD) and shifted from spheroid to ellipsoid, eventually to nanofiber as the compression ratio (CR) increased. From the scanning electron microscopy (SEM) results, it was found that the PBS droplets did not in‐situ take shape into nanofibrils until the CR reached to 4, and the PBS nanofibrils served as the central shish to induce the PLA molecular chain to crystallize in the perpendicular direction, resulting in nanohybrid shish‐kebab superstructures. The Raman spectra and differential scanning calorimetry results confirmed the enhancement effect of the CR on the orientation degree, lamellar thickness, and crystallization properties. Benefiting from the abundant interlocked hybrid shish‐kebabs, the tensile strength, tensile modulus, and impact strength of the PIF processing PLA/PBS blend (CR = 4) reached the maximum value of 106.4 MPa, 2332.4 MPa, and 87.4 kJ/m2, respectively, which were 116.7%, 40.1%, and 20.8‐folds higher than those of the common PLA/PBS blend. Overall, it is believed that the proposed methodology put forward a facile and cost‐effective way to produce PLA‐based in‐situ fibrillation reinforced composites for engineering applications. [ABSTRACT FROM AUTHOR]

Summary: Previous studies have reported that PID2, which encodes a B‐lectin receptor‐like kinase, is a key gene in the resistance of rice to Magnaporthe oryzae strain ZB15. However, the PID2‐mediated downstream signalling events remain largely unknown.The U‐box E3 ubiquitin ligase OsPIE3 (PID2‐interacting E3) was isolated and confirmed to play key roles in PID2‐mediated rice blast resistance. Yeast two‐hybrid analysis showed that the armadillo repeat region of OsPIE3 is required for its interaction with PID2. Further investigation demonstrated that OsPIE3 can modify the subcellular localisation of PID2, thus promoting its nuclear recruitment from the plasma membrane for protein degradation in the ubiquitin–proteasome system. Site‐directed mutagenesis of a conserved cysteine site (C230S) within the U‐box domain of OsPIE3 reduces PID2 translocation and ubiquitination.Genetic analysis suggested that OsPIE3 loss‐of‐function mutants exhibited enhanced resistance to M. oryzae isolate ZB15, whereas mutants with overexpressed OsPIE3 exhibited reduced resistance. Furthermore, the OsPIE3/PID2‐double mutant displayed a similar blast phenotype to that of the PID2 single mutant, suggesting that OsPIE3 is a negative regulator and functions along with PID2 in blast disease resistance.Our findings confirm that the E3 ubiquitin ligase OsPIE3 is necessary for PID2‐mediated rice blast disease resistance regulation. [ABSTRACT FROM AUTHOR]

Intersections have been identified as the most complex and accident‐prone traffic scenarios on road. Making appropriate decisions at intersections for driving safety, efficiency, and comfort become a challenging task for autonomous vehicles (AVs). The existing research on AV decision‐making at intersections either considers a single scenario only with discrete behaviour outputs or ignores the requirements for driving efficiency and comfort. To address these problems, this study proposed a deep reinforcement learning based continuous decision‐making method to make AVs drive through intersections. The proposed method establishes an end‐to‐end decision‐making framework by using a convolutional neural network to map the relationship between traffic images and vehicle operations. The interaction between the AV and other vehicles was modelled as a Markov decision process (MDP), and a deep deterministic policy gradient algorithm was employed to solve the MDP problem and obtain the optimal driving policy. The top three accident‐prone crossing path crash scenarios at intersections were realized in CARLA to verify the effectiveness of the proposed method. The experimental results demonstrated that the developed method could provide effective policies to ensure driving safety and efficiency while considering driving comfort for autonomous driving at intersections in all the examined scenarios. [ABSTRACT FROM AUTHOR]

Aim: Studies using oral glucose tolerance tests (OGTT) have shown that impaired glucose metabolism presents in the early stages of schizophrenia (SCZ). However, there is a lack of studies on changes in glucose metabolism with the stage of the disease. We first explored the features of glucose metabolic pattern at different phases of male SCZ. Methods: We recruited 83 male first episode drug‐naïve patients with SCZ (FEDN‐SCZ) and 64 male chronic patients with SCZ (CH‐SCZ), as well as 14 male healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. OGTT, fasting plasma glucose and lipid profiles of all participants were examined. Results: While the impaired glucose tolerance (IGT) rate of male SCZ patients was higher than that of HC (P <.05), there was no difference in IGT prevalence between FEDN‐SCZ and CH‐SCZ. In male FEDN‐SCZ, LDL (OR = 2.64, 95% CI = 1.11–6.29, P =.028) and PANSS total score (OR = 1.03, 95% CI = 1.00–1.06, P =.046) were positively correlated with IGT; in male CH‐SCZ, BMI (OR = 1.7, 95% CI = 1.08–2.67, P =.023), PANSS total score (OR = 0.82, 95% CI = 0.70–0.96, P =.015) and positive symptoms (OR = 0.45, 95% CI = 0.20–0.99, P =.046) were significantly correlated with IGT. Conclusions: Our findings reflect different glucose metabolism patterns in different stages of SCZ. [ABSTRACT FROM AUTHOR]

Aim: To assess cardiovascular, glycaemic, weight and safety outcomes of long‐term treatment with dulaglutide 1.5 mg compared with placebo in patients with a baseline HbA1c of less than 7% versus 7% or higher. Materials and Methods: Intention‐to‐treat analyses were performed on REWIND participants with a baseline HbA1c measurement, using Cox proportional hazards regression and mixed model for repeated measures. Subgroup analyses with factors for baseline HbA1c categories and their interaction with treatment group, as well as analyses within the HbA1c subgroups, were conducted. Additionally, sensitivity analyses were performed for baseline HbA1c subgroups of 6.5% or less and more than 6.5%. Results: Of the 9876 eligible participants, 3921 and 5955 had a baseline HbA1c of less than 7% and 7% or higher, respectively. Mean baseline HbA1c was 6.3% and 8.0% and the mean duration of diabetes was 9.0 and 11.6 years in the respective subgroups. The less than 7% subgroup was slightly older and less frequently insulin‐treated. There was no evidence of a differential dulaglutide treatment effect on body mass index (BMI) reduction, cardiovascular or safety outcomes of interest between the baseline HbA1c subgroups. Treatment‐by‐baseline HbA1c group interaction was significant for HbA1c change from baseline (P <.001), with a greater reduction in the subgroup with higher baseline HbA1c values. Sensitivity analyses by baseline HbA1c subgroups of 6.5% or less and more than 6.5% showed similar results. Conclusions: The reduced incidence of cardiovascular events, and the reduction in BMI in participants treated with once‐weekly dulaglutide, were independent of the baseline HbA1c level. Conversely, participants with a higher baseline HbA1c level had greater reductions in HbA1c. Dulaglutide has a positive benefit–risk profile and can be considered in patients with comparatively well‐controlled HbA1c levels seeking optimal metabolic control and cardiovascular benefits. [ABSTRACT FROM AUTHOR]

Crafting spatially controllable charge transfer channels at the nanoscale level remains an enduring challenge in solar‐to‐chemical conversion technology. Despite the advancements, it still suffers from sluggish interfacial charge transport kinetics and scarcity of strategies to finely modulate charge transport pathways. Herein, this article demonstrates the unexpected charge modulation property of non‐conjugated insulating polymer assisted by a universal layer‐by‐layer self‐assembly tactic. Oppositely charged poly(dimethyl diallyl ammonium chloride) (PDDA) and Ti3C2 MXene quantum dots (MQDs) are periodically attached to the wide bandgap metal oxides (WMOs) to design multilayered heterostructured photoanodes. The intermediate PDDA layer acts as an efficacious charge relay medium to access directional electron flow from WMOs to Ti3C2 MQDs, while Ti3C2 MQDs serve as the electron extractor. Charge transfer cascade is thus stimulated on account of the simultaneous electron‐trapping capabilities of interim PDDA layer and Ti3C2 MQDs, which synergistically favors the conspicuously boosted charge separation over WMOs, affording the WMOs/(PDDA/MQDs)n photoanodes with considerably enhanced photoelectrochemical (PEC) water oxidation performances. Moreover, PEC performances of such photoanodes can be tuned by interface configuration via assembly number and sequence. This work will provide an insightful perspective to craft a directional charge transfer pathway through insulating polymer for solar energy conversion. [ABSTRACT FROM AUTHOR]

Background and purpose: Previous studies have reported the association between frailty and stroke or Alzheimer's disease (AD). However, the causality remains unclear. The aim of the present study was to evaluate whether genetically predicted frailty is associated with the risk of stroke or AD by a Mendelian randomization (MR) study. Methods: Genetic variants associated with the frailty index (FI) were obtained from a large genome‐wide association study (GWAS). Summary‐level data for stroke and AD were adopted from the corresponding large GWAS of individuals of European ancestry. The inverse variance weighted method was used for estimating causal effects. Multivariable analysis was performed for further adjustment. Results: The present MR study indicated a suggestive association between genetically predicted FI and a higher risk of any stroke (odds ratio 1.360, 95% confidence interval 1.006–1.838, p = 0.046). Regarding the subtypes of stroke, genetically predicted FI was associated with a higher risk of large artery atherosclerosis stroke (LAS) (odds ratio 2.487, 95% confidence interval 1.282–4.826, p = 0.007). No causal links were identified between genetically predicted FI and any ischaemic stroke, intracranial haemorrhage, cardioembolic stroke, small artery stroke, AD or AD‐by‐proxy. Multivariable MR analysis indicated that the association of genetically predicted FI with LAS was attenuated after adjustment for inflammatory bowel disease (p = 0.114). Conclusions: The MR study suggested that genetically predicted FI may be associated with an increased risk of any stroke. Subgroup analysis indicated a suggestive association between genetically predicted FI and the risk of LAS. The underlying mechanisms need further investigation. [ABSTRACT FROM AUTHOR]

Perioperative stroke is an ischemic or hemorrhagic cerebral event during or up to 30 days after surgery. It is a feared condition due to a relatively high incidence, difficulties in timely detection, and unfavorable outcome compared to spontaneously occurring stroke. Recent preclinical data suggest that specific pathophysiological mechanisms such as aggravated neuroinflammation contribute to the detrimental impact of perioperative stroke. Conventional treatment options are limited in the perioperative setting due to difficult diagnosis and medications affecting coagulation in may cases. On the contrary, the chance to anticipate cerebrovascular events at the time of surgery may pave the way for prevention strategies. This review provides an overview on perioperative stroke incidence, related problems, and underlying pathophysiological mechanisms. Based on this analysis, we assess experimental stroke treatments including neuroprotective approaches, cell therapies, and conditioning medicine strategies regarding their potential use in perioperative stroke. Interestingly, the specific aspects of perioperative stroke might enable a more effective application of experimental treatment strategies such as classical neuroprotection whereas others including cell therapies may be of limited use. We also discuss experimental diagnostic options for perioperative stroke augmenting classical clinical and imaging stroke diagnosis. While some experimental stroke treatments may have specific advantages in perioperative stroke, the paucity of established guidelines or multicenter clinical research initiatives currently limits their thorough investigation. [ABSTRACT FROM AUTHOR]

The acquisition and evaluation of road cracks are essential to ensure the availability of roads and necessary maintenance. However, the road cracks images have been obsessed with the problem of imbalance in the category and the number of categories. Among them, the category imbalance makes the network focus on the background and the detection result will be complete black. The imbalanced number of categories leads to the missed detection of thin cracks. In addition, a large number of images generated in real time put forward higher requirements on memory and calculations. The RAO‐UNet is built which is an efficient and effective network for crack detection in road images using encoder–decoder and residual attention module‐based image frequency relationship. Compared with otheTr methods, RAO‐UNet could learn multiple‐spatial‐frequency features, thus can enhance the differentiation of high‐frequency features while saving the computational cost. Regarding the space optimisation, a novel balance loss function is proposed, which not only solves the balance problem, but also ensures the stability and consistency in the optimisation process. We evaluated RAO‐UNet on public data sets. Compared with state‐of‐the‐art methods, it achieves better performance on processing speed and detection accuracy. Specifically, RAO‐UNet achieves 98.32% / 97.86% Precision, 97.84% / 95.89% Recall, 97.61% / 97.04% F1 score on CFD and AigleRN data sets, respectively. [ABSTRACT FROM AUTHOR]

Aims Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods and results Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Conclusions Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology. [ABSTRACT FROM AUTHOR]

Our work overcomes the long‐standing challenge to achieve comprehensive improvements in thermo/mechanical properties of poly(lactic acid) (PLA), especially for impact toughness, strength, ductility, stiffness, and heat resistance. Simple deformation or microfibrillation of spherulites can create excellent thermo/mechanical properties making PLA compete against conventional petrochemical‐based polymers. It was performed by pressure‐induced‐flow (PIF) processing, and produced typical deformed spherulite structure and brick‐mud structure. It was found that the critical deformation degree of spherulites was around 2.7, beyond which spherulites would fragment. Through three transition stages of spherulite structures, deformed spherulite structures, and brick‐mud structure, PLA exhibited an enhancement of orientation, storage modulus and glass transition temperature. And a substantial increase was proved in impact strength (105.6 kJ/m2), tensile strength (148.4 MPa) and elongation at break (107.7%), which can be comparable to most engineering plastics. Both the deformed spherulite structures and the brick‐mud structures can enhance the impact toughness of PLA by increasing the fracture path of cracks. Besides, the evolution of the microstructure for a sandwich structure during PIF‐processing was proposed. [ABSTRACT FROM AUTHOR]

Background: The common bed bug, Cimex lectularius L., and the tropical bed bug, Cimex hemipterus (F.), are now widely regarded as important public health pests following their rapid global resurgence, largely due to insecticide resistance and an increased rate of global travel. The insecticide resistance mechanisms are well documented in C. lectularius, however, only one mechanism is validated in C. hemipterus thus far. This demands further understanding on the resistance mechanisms involved in C. hemipterus. Results: Here, we identified differences in resistance to fenitrothion (organophosphate) and imidacloprid (neonicotinoid) related cuticle thickness in C. hemipterus. There is evidence of a possible association between cuticle thickness and resistance, but the association can be tenuous, likely because resistance is multifactorial in C. hemipterus. We also discovered a novel T1011 residue in domain IIS6 of the voltage‐gated sodium channel that likely enhanced susceptibility to deltamethrin (pyrethroid) despite the presence of a L1014F mutation known to confer pyrethroid resistance in C. hemipterus. Our findings also confirmed that the M918I mutation enhanced resistance to pyrethroid when present with the L1014F mutation, which was consistent with a super‐kdr phenotype, as reported previously. Multiple resistance mechanisms can be found within a single C. hemipterus population, and the presence of both M918I + L1014F mutations likely masked the influence of cuticle thickness in conferring resistance against deltamethrin. The elevated metabolic enzyme activities in some strains were not necessarily associated with increased insecticide resistance. Conclusion: This study has enhanced our understanding on the penetration resistance mechanism and target site insensitivity of sodium channels in C. hemipterus. [ABSTRACT FROM AUTHOR]

Floating car data (FCD), characterized by wide spatiotemporal coverage, low collection cost, and immunity to adverse weather conditions, are one of the key approaches for intelligent transportation systems to obtain real‐time urban road network traffic information. The research aims to utilize GPS data from taxis in Shanghai and vector geographic information data of the road network, with urban expressways as the research focus. Based on the different driving characteristics of expressways and the vehicles on the ramps below, a clustering analysis is employed to determine all floating vehicles traveling on the target road. Furthermore, an adaptive buffer zone consistent with the road orientation is established based on road vector geographic data. This allows for the extraction of FCD within segmented areas, and the average vehicle speed for that road segment is obtained through weighted calculations. This method fully exploits the natural characteristics of taxis in urban areas with a wide spatiotemporal distribution. The data effectiveness and coverage reach 90.2% and 85.7%, respectively, significantly surpassing the traditional grid‐based extraction method for FCD. Additionally, to capture the long‐term spatiotemporal dependencies of road network traffic states, a spatial–temporal autoformer (STAF) network based on spatial–temporal sequence autocorrelation is employed for traffic state prediction. The results indicate that the STAF method demonstrates good performance in medium‐ and long‐term prediction. We believe that the proposed FCD mining method in this paper provides a new approach for efficiently extracting large‐scale road network traffic states and conducting medium‐ to long‐term predictions. [ABSTRACT FROM AUTHOR]