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Abstract Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups had statistically significant HbA1c reductions from baseline of −1.81%, −1.90%, and −2.39%, respectively, compared to −0.55% for placebo (P

Background: Cancer is the most common cause of death and is still a serious public health problem. Alkaloids, a class of bioactive compounds widely diffused in plants, especially Chinese herbs, are used as functional ingredients, precursors, and lead compounds in food and clinical applications. Among them, aporphine alkaloids (AAs), as an important class of isoquinoline alkaloids, exert a strong anticancer effect on multiple cancer types. Aim of review: This review aims to comprehensively summarize the phytochemistry, pharmacokinetics, and bioavailability of seven subtypes of AAs and their derivatives from various plants and highlight their anticancer bioactivities and mechanisms of action.Key Scientific Concepts of Review.The chemical structures and botanical diversity of AAs are elucidated, and promising results are highlighted regarding the potent anticancer activities of AAs and their derivatives, contributing to their pharmacological benefits. This work provides a better understanding of AAs and combinational anticancer therapies involving them, thereby improving the development of functional food containing plant-derived AA and the clinical application of AAs.

Olfaction, the sense of smell, is crucial for animal survival, especially in localizing prey or food. However, little is known about the fish behavioral responses to specific food odors and which olfactory receptor might be activated by the food odors. Here, we examined the evolutionary relationships and classified the subfamilies of olfactory receptors (ORs), and conducted behavioral and gene expression analysis in grass carp (Ctenopharyngodon idellus). We identified 196 intact ORs in the grass carp genome and classified them into 8 subfamilies: β, δ, ε, η, γ, κ, θ, and ζ. 12 representative ORs (4 β, 4 δ, and 4 ε) were highly expressed in the olfactory epithelium (OE) of 24-month-old grass carp. Behavioral exploration found that grass carp showed different behaviors to different food odors at a series of concentrations. Specifically, 0.01 μmol/L amino acid mixtures and 0.005 × Hydrilla verticillata extracts strongly changed the preference index and swimming trajectories in 6-month-old grass carp. In addition, the two food odors stimulation differentially induced ORs expression in three tissues, especially strong in the olfactory bulb and brain. Altogether, our results suggest that olfaction plays an important role in the regulation of fish feeding behavior and provide a basis for further studies on the function and specific recognition of olfactory receptors in fish.

Abstract Background Anlotinib is a targeted therapy indicated for some malignancies, including advanced non-small cell lung cancer (NSCLC). However, noninvasive biomarkers for identifying patients who will benefit from this disease remain lacking. Methods Here, we investigated the potential of small extracellular vesicle (sEV) microRNAs (miRNAs) as predictive biomarkers for anlotinib efficacy. A total of 20 advanced NSCLC patients were enrolled. Patients were classified as having stable disease (SD) or progressive disease (PD) after the initial efficacy assessment. Results Seven differentially expressed miRNAs (DEMs) were identified. Among them, miR-941 was significantly upregulated in the PD group, while the others were downregulated. Furthermore, these six downregulated miRNAs (miR-30a-3p, miR-150-5p, miR-122-5p, miR-10b-5p, miR-92a-3p, and miR-150-3p) were more pronounced in nonsmoking patients. Conclusions It was found that sEV miRNAs have the potential to predict the benefit of anlotinib.

Abstract Background Tracheobronchial injuries caused by blunt chest trauma are rare in children, and such injuries usually involve multiple organs. Most cases involve respiratory failure on the way to the hospital, and the mortality rate is high. Herein, we describe the case of a 5-year-old patient who fell from an electric vehicle, causing complete rupture of the bilateral main bronchus. Case presentation We treated a 5-year-old patient with complete bilateral main bronchus rupture. Chest computed tomography (CT) failed to detect bronchial rupture. Continuous closed thoracic drainage resulted in a large amount of bubble overflow. Tracheal rupture was suspected. Fibreoptic bronchoscopy revealed complete rupture of the right main bronchus and rupture of the left main bronchus. Emergency tracheoplasty was performed under cardiopulmonary bypass (CPB). During the operation, we found that the bilateral main bronchi were completely ruptured. Postoperative recovery was smooth. The traditional surgical method for treating these injuries is lateral thoracotomy. However, a median sternotomy provides a better opportunity for selective repair. Extracorporeal circulation-assisted surgery is required for patients with unstable breathing. Conclusion Complete fractures of the bilateral main bronchi are rare. Bronchial rupture should be suspected in the presence of expansion defect-dropped lungs and massive air leakage despite tube thoracostomy in haemopneumothorax developing after thoracic trauma. Extracorporeal circulation-assisted tracheoplasty is a relatively safe option for children whose respiratory system is difficult to maintain, thus ensuring oxygenation ventilation and a clear surgical field.

Abstract Background Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. Methods This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. Results Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. Conclusion Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. Trial registration NCT04507906 August 11, 2020.

Abstract Background ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear. Results This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities. Conclusions The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.

Abstract With the accelerated deployment of 5G massive multi‐input multi‐output (MIMO)‐structured base stations (BSs), accurate and efficient testing of massive MIMO arrays is essential to ensure that the 5G massive MIMO antenna array can perform as expected. The increasing trend of both antenna element and array physical size makes massive MIMO antenna pattern measurement in the direct‐far‐field OTA environment unrealistic due to the signal attenuation, long measurement time, and ultra‐high test system construction cost. Therefore, the necessity of a compact, efficient, low‐complex, yet accurate OTA test method is evident, especially for 5G massive MIMO BS arrays. This paper proposes a novel multi‐probe‐enabled midfield (MF) OTA test method for 5G massive MIMO devices in compact measurement settings where antenna pattern measurement can be efficiently performed. The detailed theoretical analysis for the 5G massive MIMO array MF antenna pattern reconstruction method is presented, and the simulated validation results based on the typical 5G BS antenna arrays are provided and analysed, which demonstrate the effectiveness of the proposed MF OTA test method and can provide insights into the radio frequency parametric measurement for 5G massive MIMO devices.

Dust deposition can supply nutrients to the upper ocean, and subsequently affect primary production and biodiversity in planktonic ecosystem, but the differential response among taxa and their interactions are not fully understood. Here, we performed 7-day onboard incubation experiment amended with different dust loadings (0, 0.2 and 2 mg L-1) in the Kuroshio-Oyashio transition region of the Northwest Pacific Ocean and characterized the community structure and microbial network of a planktonic microbiome in response to dust addition. Chlorophyll a and nutrient analysis indicated that dust-derived nitrogen promoted the growth of phytoplankton (165.8–293.6%) and phytoplankton size structure shifted towards larger cells (>3 μm). Metabarcoding sequencing, targeting prokaryotic and eukaryotic microbes, revealed the changes in community structure and co-occurrence network in response to dust addition. Dust induced a shift from dinoflagellate dominance toward diatom dominance in phytoplankton, and favored members of Cercozoa, Labyrinthulomycetes and Saprospirae, which showed positive correlation with diatom. Temporal response patterns among taxa were categorized into five clusters, and collectively pointed to a more sensitive microeukaryotic community than prokaryotic one in response to dust. The community turnover during the incubation was dominated by moderate taxa with 55.71-62.26% moderate OTUs transitioning to abundant or rare taxa, and dust addition stimulated the transitions of rare taxa. Moreover, biotic factors shaped planktonic microbiome more than abiotic factors, particularly the cross-domain interaction significantly affected microeukaryotic community. Notably, dust addition enhanced the co-occurrence network complexity, with the number of keystone taxa increased, suggesting more interspecies interactions were induced by dust. With integrated analysis, our findings highlight the differential sensitivity of planktonic microbiome to dust deposition and the effects could pass on other organisms through interspecies interaction.

To study the breakup process of fuel jets in air crossflow with a positive velocity gradient, the Volume of Fluid (VOF) method and adaptive grid technology are combined to simulate the two-phase flow of gas and liquid. A comparative analysis is conducted on the breakup and corresponding flow characteristics of direct fuel jets under uniform and positive velocity gradient airflow. The simulation results demonstrate that the morphological changes of the fuel column are caused by factors such as gas-liquid shear and asymmetric airflow vortices. The fuel jet undergoes primary breakup, which mainly contains columnar and surface breakup. The columnar breakup is dominated by Rayleigh-Taylor (R-T) instability, while the surface breakup is dominated by Kelvin-Helmholtz (K-H) instability. Compared with uniform flow, the expansion angle in the positive velocity gradient incoming flow increases by an average of 9.2%, and the wavelength of the surface wave increases by an average of 34%.

The grain preferential orientation has a significant influence on the mechanical properties of silicon nitride (Si3N4) ceramics. Based on the Jeffery’s theory, a grain rotation model under uniaxial compression is created to predict the texture evolution mechanism during sintering of Si3N4 ceramics. With deformation, the grain orientation was predicted to rotate towards the plane perpendicular to the pressure direction, and large strain was favorable for the formation of strong texture. According to guidance of the model, the weakly textured microstructure prepared by normal hot pressing is attributed to the limited strain, due to the constrains of graphite die. Therefore, a new PHIP (pseudo-hot isostatic pressing) process with the large deformation is guided to fabricate the strongly textured ceramics by promoting the grain rotation and dynamic grain growth. Generally, the experimental results are well accordance with the model prediction. Furthermore, this model could be applied to guide the design and fabrication of other isotropic and anisotropic ceramic materials.

The Qianyingzi Coalmine is located on the west of the Suxian Mining area of the Huaibei Coalfield, adjacent to the outer edge of the southern segment of the Xu-Su Arc Nappe Belt. Methods Based on the latest geological exploration and production data, this paper analysed the structural framework and coal-controlled structural patterns of the Qianyingzi Coalmine, divided the tectonic stages, and discussed the geotectonic background of the coalmine structures, Objective which provides an important geological basis for the understanding of the tectonic deformation and evolution of the coalmine, the geodynamic mechanism and the prediction of exploration directions. Results The results show that the Carboniferous-Permian coal-bearing formations in the mine are generally a gentle syncline with an NNE-trending axis. The faults in the mine are well developed, and the number of reverse faults is greater than that of normal faults. Both of these faults are mainly NE to NNE, followed by NS. The structural framework of this mine is significantly controlled by several large NS to NE-striking faults and is segmented from west to east by major faults, including the Nanping, F22, F17, DF200 and Shuangdui faults, which exhibit the characteristic of east and west zonation. The coal-controlled structural patterns in the mine can be classified into three types, namely, compressional, extensional and strike-slip. And the coal-controlled patterns can be further divided into nine subtypes, namely, thrust drag folds, hedge structures, pop-up structures, imbricate structures, grabens, horsts, step faults, positive flower structures and pinnated en-echelon structures. The analysis of structural combinations shows that the F17 fault has not only thrusting motion but also significant transcurrent activity. Conclusion The structural deformation of coal-bearing formation in the Qianyingzi Coalmine can be divided into five stages: the Fengjia Syncline with an NNE-trending axis, nearly NS-striking reverse faults, NNE-striking reverse-sinistral faults and NE-striking reverse faults, nearly NS-striking normal faults, and NW-SE-striking normal faults. Combined with the results of previous studies on the regional tectonic background, the first and second shortening structures in this mine are the results of foreland deformation during the convergence of the North China Craton and South China Plate and subsequent continent-continent collisional deformation during the Indosinian period. The third stage compresso-shear structures are related to the rapid oblique subduction of the Izanagi Plate toward the East Asian continental margin at the beginning of the Early Cretaceous in the Western Pacific. The fourth and fifth stage extensional structures developed against a strong extensional background in eastern China during the Early Cretaceous.

The presence of high-density defects is rarely observed in bulk 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) ceramics obtained through conventional pressureless sintering. In the present work, fine-grained dense 147 nm 3Y-TZP ceramics were prepared by pressureless sintering of commercial 0.25 wt% alumina-doped zirconia powders at 1300 ℃. A novel discovery was reported in which large amounts of defects were present in the grain interiors of the sample. The phenomenon was further examined using three types of powder samples, and the reasons for defect formation were investigated by microstructural characterization using high-resolution transmission electron microscopy (HRTEM) analysis and Rietveld refinement. The results confirmed the essential dependence of the defect formation on the alumina addition. The authors attributed the defect formation to the significant difference in ionic radii of the solvent and solute during the dissolution of alumina into the zirconia lattice. The sintering kinetics were proposed to be enhanced by the presence of substantial defects, which consequently favored the low-temperature sintering of the alumina-doped zirconia ceramics.

As building electrification is recognised as an important opportunity to reduce greenhouse gas emissions, the integration of solar energy and heat pump represents a promising solution towards net-zero carbon buildings. This paper presents a hybrid multifunctional solar-assisted heat pump (SAHP) system that can provide space heating, space cooling, domestic hot water, and onsite electricity generation. Photovoltaic-thermal collectors are used for electricity generation, heat collection, and radiative cooling. The system design and controls support fourteen operational modes involving different components. TRNSYS software is used to model and simulate the multifunctional SAHP system. With a 2-m3 storage tank and 30-m2 PVT collectors, the multifunctional SAHP system has a seasonal performance factor of 2.7 in Baltimore and 3.7 in Las Vegas. The onsite electricity generation can cover 53% of the building’s electricity needs in Baltimore and 83% in Las Vegas.

Abstract Automotive antennas are gaining importance due to their increasingly important role for autonomous driving with the development of the Internet of Vehicles. However, over‐the‐air testing on automotive antennas is difficult owing to its large volume and complex body structure. Plane wave generators can approximate uniform plane waves in the near field of the device under test, which can greatly reduce the measurement distance and thereby decreasing the cost compared with direct far‐field solutions. This letter designs three plane wave generators for three quiet zone sizes selected according to the vehicle structure at 5.9 GHz, achieving quiet zone sizes of 1.45 m ×0.23 m, 2.9m ×0.56 m, and 3.9 m ×1.27 m, respectively. Within the three quiet zones, amplitude deviations of 0.82, 0.34, and 0.34 dB and phase deviations of 9.4∘, 6.72∘ and 1.42∘ are realized, respectively, according to the numerical simulations. Uncertainty analysis is further implemented to investigate the robustness of the designed PWGs proposed in this letter.

Abstract Targeted delivery of glutamine metabolism inhibitors holds promise for cholangiocarcinoma therapy, yet effective delivery vehicles remain a challenge. This study reports the development of a biomimetic nanosystem, termed R‐CM@MSN@BC, integrating mesoporous organosilicon nanoparticles with reactive oxygen species‐responsive diselenide bonds for controlled release of the glutamine metabolism inhibitor bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl) ethyl sulfide (BPTES) and the photosensitizer Ce6. Erythrocyte membrane coating, engineered with Arg‐Gly‐Asp (RGD) peptides, not only enhanced biocompatibility but also improved tumor targeting and tissue penetration. Upon laser irradiation, R‐CM@MSN@BC executed both photodynamic and glutamine‐metabolic therapies, inducing necroptosis in tumor cells and triggering significant immunogenic cell death. Time‐of‐flight mass cytometry analysis revealed that R‐CM@MSN@BC can remodel the immunosuppressive tumor microenvironment by polarizing M1‐type macrophages, reducing infiltration of M2‐type and CX3CR1+ macrophages, and decreasing T cell exhaustion, thereby increasing the effectiveness of anti‐programmed cell death ligand 1 immunotherapy. This strategy proposed in this study presents a viable and promising approach for the treatment of cholangiocarcinoma.

This study summarized and evaluated the cost-benefit analysis methods for typical water environment pollution control measures in China. We conducted a comprehensive comparison of these measures, whose advantages and disadvantages were examined, so the application models and characteristics can be delved into. Through integrating methods and analyzing application cases, we refined a combination of measures with high efficiency and low cost in controlling China’s water environment. In our analysis of cost-benefit, we emphasized the importance of implementing scientifically designed control measures and employing rigorous methods to addressing water environment pollution. In order to achieve rapid response and efficient treatment of China’s environmental problems, we advocated for establishing a cross regional pollution control mechanism. That is, the collaborative platform and scientific suggestions for all participants in this field should be provided, through interdisciplinary integration, development of domestic models, and expansion of databases.

Abstract Reconfigurable intelligent surface (RIS), equipped with a large number of small, low‐cost, and re‐configurable elements, is envisioned as a potential enabler for the upcoming 5G‐Advanced and 6G networks. Here, based on a flexibly tunable and readily programmable RIS, the capability of beamforming toward arbitrary desired directions and coverage enhancement are investigated and experimentally demonstrated. The theory of RIS‐based beamforming is introduced, the simulated beamforming radiation patterns are provided, and an over‐the‐air radiated testing platform is designed for characterizing RIS beamforming performance. The RIS beam steering radiation performance tests are conducted, and the radiation patterns for different directions are extracted and analyzed. In addition, the indoor field trials on the RIS performance evaluation of enhancing coverage are reported. The field trials for multiple RIS‐deployed scenarios, including RIS mirror placement, RIS non‐mirror placement, and non‐RIS assisted scenarios, are conducted, and the channel characteristics for those scenarios are extracted and modelled. Significant improvements in overcoming path loss and shadow fading in typical coverage holes can be observed. The proposed testing method and measurement results may provide some insights into the design and optimization of RIS‐aided wireless communications.

Environmental exposure to the cadmium (Cd) has been shown to be a risk factor for colorectal cancer (CRC) progression, but the exact mechanism has not been fully elucidated. In this study, we found that chronic Cd (3 μM) exposure promoted the proliferation, adhesion, migration, and invasion of CRC cells in vitro, as well as lung metastasis in vivo. RNA-seq and TCGA-COAD datasets revealed that decreased hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) expression may be a crucial factor in Cd-induced CRC progression. Further analysis using qRT-PCR and tissue microarrays from CRC patients showed that HADHB expression was significantly reduced in CRC tissues compared to adjacent normal tissues, and low HADHB expression was associated with adverse clinical features and poor overall survival, either directly or through TNM stage. Furthermore, HADHB was found to play an important role in the Cd-induced malignant metastatic phenotype of CRC cells and lung metastasis in mice. Mechanistically, we discovered that chronic Cd exposure resulted in hypermethylation of the HADHB promoter region via inhibition of DNA demethylase tet methylcytosine dioxygenase 2 (TET2), which then led to decreased HADHB expression and activation of the FAK signaling pathway, and ultimately contributed to CRC progression. In conclusion, this study provided a new potential insight and evaluable biomarker for Cd exposure-induced CRC progression and treatment.

The giant freshwater prawn (GFP), Macrobrachium rosenbergii, stands out as a vital species in freshwater shrimp aquaculture. However, its susceptibility to cold conditions has increased the cost of aquaculture and limited the growth of GFP cultivation. To furnish insights at the molecular level to enhance GFP's cold tolerance, transcriptome sequencing and physiological analysis of the hepatopancreas were performed in our study. Initially, we identified 4909 differentially expressed genes (DEGs) between experimental (15 °C, 24 h) and control groups (25 °C, 24 h). These DEGs were significantly enriched in the proteasome, spliceosome, lysosome, peroxisome, and lipid metabolism-related pathways including glycerolipid metabolism, sphingolipid metabolism, linoleic acid metabolism as well as steroid hormone biosynthesis. Histological examination following various stress durations revealed a notable increase in hepatocyte vacuoles after 6 h of cold stress. Hepatocyte structure deterioration occurred in the later phase (48 h), coinciding with a significant increase in cell apoptosis. Subsequent analyses demonstrated an initial increase followed by a decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) content, while malonaldehyde (MDA) content rose with stress duration. Furthermore, a significant increase in triglyceride content and no significant change in cholesterol content was observed. RT-qPCR results unveiled significant down-regulated expression of FAS, TAGL, ACOX1, ACS and significant up-regulated expression of GPAT and DEGS. These findings suggest that oxidative stress and impaired lipid metabolism underlie the poor cold tolerance of GFP.

Finding reliable photocatalysts capable of driving reactions using only sunlight is more needed than ever. A variety of strategies to harvest sunlight and convert it into chemical energy have been successfully utilized such as synthesizing nanostructures, using metal nanoparticles, doping, and others. In this work, we discover a facile way to anchor CuS nanoplatelets on 2D MoS2 by the solvothermal method using ethylene glycol (EG) as both a reduction agent and an exfoliating agent of bulk MoS2. Using CuS as a co-catalysis on MoS2 with their huge surface areas, led to improved photocatalytic activity for three different applications including H2 evolution, CO2 reduction, and endosulfan degradation. Specifically, Cu–S@MoS2 3% nanocomposite produced 9.86 μmol g−1 h−1 of H2, 0.48 μmol g−1 h−1 of CO and full decomposition of endosulfan within 6 h. The Cu-loaded MoS2 nanocomposites were thoroughly characterized by spectroscopic (including synchrotron-based spectroscopy) and microscopic methods to understand the formation of Cu–S during the solvothermal process. Moreover, the role of the EG during the synthetic procedure was revealed experimentally and studied theoretically via DFT simulations.

Summary: Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18–65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin −10% (2.69%; 95% CI −4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (−3.25; 95% CI −5.56, −0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP

Fire has consistently posed a significant disaster risk worldwide. Current fire detection methods primarily rely on traditional physical sensors such as light, smoke, and temperature detectors, which often struggle in complex environments. The susceptibility of existing fire detection technologies to background interference frequently results in false alarms, missed detections, and low detection accuracy. To address these issues, this paper proposes a fire detection algorithm based on an improved YOLOv8 model. First, to enhance the detection capabilities for large-scale fire and smoke targets, a large target detection head is added to the backbone of the YOLOv8 model. This modification enhances the network’s receptive field, allowing it to capture a broader range of contextual information and identify fires over extensive areas. Secondly, an efficient multi-scale attention mechanism, EMA (Efficient Multi-Scale Attention Module), based on cross-space learning is integrated into the FPN (Feature Pyramid Network) part of the model. This mechanism highlights target features while suppressing background interference. Additionally, a PAN-Bag (Path Aggregation Network Bag) structure is proposed to help the model more accurately detect objects such as fire and smoke, which have uneven feature distributions and variable morphologies. With these improvements, we introduce the YOLOv8-FEP algorithm, which offers higher detection accuracy. Experimental results demonstrate that the YOLOv8-FEP algorithm improves the mAP by 3.1% and the accuracy by 5.8% compared to the original YOLOv8 algorithm, proving the effectiveness of the enhanced algorithm.

Bound states in the continuum (BICs) with exceptionally high quality factors ($Q$ factors) have become focal points in photonic device research, finding applications in nonlinear enhancement, laser generation, sensing, and beyond. In this study, we systematically investigate the intricate relationship between the in-plane symmetry groups of photonic crystals and symmetry-protected BICs (SP-BICs) using a rigorous group theory approach. By modifying the spatial distribution of refractive indices to perturb the $C_{2}$ and $C_{3}$ symmetries within a $C_{6v}$ photonic crystal slab, we introduce a novel method to enable precise tuning of BIC resonances, including the BIC frequency, $Q$ factor, and polarization state. The proposed group theory approach and tuning mechanism establish a pioneering pathway for the design and tunability of BICs, opening avenues for the development of advanced photonic devices with tailored functionalities such as tunable lasers and optical sensors with enhanced performance.

Abstract Introduction Durvalumab is a check‐point inhibitor against programmed death ligand‐1 (PD‐L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES‐SCLC patients. Methods This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum‐based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Discussion We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES‐SCLC patients.

Impacts of economy-society-environment on surface water resource in China are complex and unclear. Revealing these connections is vital to understand responses of surface water quality to anthropogenic activities. This study made an attempt to explore potential indications on surface water quality from economic, social and environmental factors in eight separate regions of China during the period of 2000–2019. Five machine learning models were employed including Greedy Thick Thinning Bayesian Belief Network, Naive Bayes, Augmented Naive Bayes (ANB), Logistic Regression and Random Forest. A total of 8 economic variables, 5 social variables and 8 environmental variables were introduced into the models. Results showed that ANB presented the best performance in estimating the surface water quality class with the highest accuracies of 81%, 75% and 87% for three surface water quality groups (Class I–III, Class IV–V and worse than Class V), respectively. The higher the surface water environmental carrying capacity in a region, the better the estimation performance of ANB on the surface water quality class. Surface water quality with Class I–III was more closely related to economic and social development, while environmental variables largely interpreted the quality of surface water with Class IV–V in most regions. The critical factors filtered by the importance analysis were indicative on surface water quality. This study provided a feasible framework in revealing the economy-society-environment nexus in the context of comprehensive management on regional surface water quality.

The marine ecosystem is one of the most extensive and abundant ecosystems on Earth. Marine plankton is an important component, and its abundance, number of species, and dominant species are regarded as important monitoring indicators. Aiming at the problems of low accuracy and high complexity in identifying plankton based on convolutional neural networks, this study proposes a lightweight identification algorithm for plankton images based on the improved MobileNetV2. Firstly, the network layer structure is extracted by redesigning features to balance the depth and width of the network to reduce the model parameters; secondly, the lightweight coordinate attention (CA) mechanism is introduced to strengthen the attention and extraction ability of key areas; in addition, the structure of the network classifier is optimized to improve the utilization efficiency of the model parameters. The results show that the model achieves a 95.46% accuracy and 94.48% recall in 12 kinds of images. Compared with the initial MobileNetV2, the parameters and calculation amount are reduced by 72.47% and 52.09%, respectively, and the reasoning time for a single image is 6.15 ms. The model realizes the accurate identification of plankton in situ under the premise of ensuring it is lightweight. Combining time information and depth data, it is of great significance for marine ecological environment monitoring and prediction to obtain the abundance of various plankton.

Abstract Photodynamic therapy (PDT) is a minimally invasive and controllable local cancer treatment for cholangiocarcinoma (CCA). However, the efficacy of PDT is hindered by intratumoral hypoxia and the presence of an antioxidant microenvironment. To address these limitations, combining PDT with gas therapy may be a promising strategy to enhance tumor oxygenation. Moreover, the augmentation of oxidative damage induced by PDT and gas therapy can be achieved by inhibiting NRF2, a core regulatory molecule involved in the antioxidant response. In this study, an integrated nanotherapeutic platform called CMArg@Lip, incorporating PDT and gas therapies using ROS‐responsive liposomes encapsulating the photosensitizer Ce6, the NO gas‐generating agent L‐arginine, and the NRF2 inhibitor ML385, is successfully developed. The utilization of CMArg@Lip effectively deals with challenges posed by tumor hypoxia and antioxidant microenvironment, resulting in elevated levels of oxidative damage and subsequent induction of ferroptosis in CCA. Additionally, these findings suggest that CMArg@Lip exhibits notable immunomodulatory effects, including the promotion of immunogenic cell death and facilitation of dendritic cell maturation. Furthermore, it contributes to the anti‐tumor function of cytotoxic T lymphocytes through the downregulation of PD‐L1 expression in tumor cells and the activation of the STING signaling pathway in myeloid‐derived suppressor cells, thereby reprogramming the immunosuppressive microenvironment via various mechanisms.

Inhibition of checkpoint kinase 1 (Chk1) has shown to overcome resistance to poly (ADP-ribose) polymerase (PARP) inhibitors and expand the clinical utility of PARP inhibitors in a broad range of human cancers. Pristimerin, a naturally occurring pentacyclic triterpenoid, has been the focus of intensive studies for its anticancer potential. However, it is not yet known whether low dose of pristimerin can be combined with PARP inhibitors by targeting Chk1 signaling pathway. In this study, we investigated the efficacy, safety and molecular mechanisms of the synergistic effect produced by the combination olaparib and pristimerin in TP53-deficient and BRCA-proficient cell models. As a result, an increased expression of Chk1 was correlated with TP53 mutation, and pristimerin preferentially sensitized p53-defective cells to olaparib. The combination of olaparib and pristimerin resulted in a more pronounced abrogation of DNA synthesis and induction of DNA double-strand breaks (DSBs). Moreover, pristimerin disrupted the constitutional levels of Chk1 and DSB repair activities. Mechanistically, pristimerin promoted K48-linked polyubiquitination and proteasomal degradation of Chk1 while not affecting its kinase domain and activity. Importantly, combinatorial therapy led to a higher rate of tumor growth inhibition without apparent hematological toxicities. In addition, pristimerin suppressed olaparib-induced upregulation of Chk1 and enhanced olaparib-induced DSB marker γΗ2ΑΧ in vivo. Taken together, inhibition of Chk1 by pristimerin has been observed to induce DNA repair deficiency, which may expand the application of olaparib in BRCA-proficient cancers harboring TP53 mutations. Thus, pristimerin can be combined for PARP inhibitor-based therapy.

In this work, nanocrystalline high-entropy ceramics (HECs) were prepared by the combination of combustion synthesis and ultra-high pressure sintering. The prepared high-entropy (La0.2Nd0.2Sm0.2Eu0.2Gd0.2)2Zr2O7 ceramic powder had the average grain size of 11 nm and displayed the disordered defective fluorite structure. The HECs sintered under ultra-high pressure showed the defective fluorite structure, whereas the control samples fabricated by pressureless sintering showed the ordered pyrochlore structure. The HECs sintered under pressure of 10 GPa possessed much smaller grain size than that obtained by pressureless sintering. In particular, the grain size of ceramics sintered under 10 GPa at 600 °C was not significantly larger than that of raw powder and its Vickers hardness was 11.9 GPa. Ultra-high pressure sintering could remarkably increase the density of ceramics and restrain the growth of grains. The plastic deformation under ultra-high pressure was believed as the main densification mechanism for the grain refinement and performance improvement.

Abstract In this study, we examined the impact of demyelinating and neuroinflammation on trigeminal neuralgia (TN) by utilizing models of chronic constriction injury to the infraorbital nerve (CCI). The CCI rats were treated with either VX-765 (an inhibitor of caspase-1) or a control solution of PBS/DMSO to observe the effects on neurobehavioral and neuropathological outcomes. The histochemical changes, pyroptosis-related proteins were assessed using immunohistochemistry, Elisa, and western blotting. RSC96 cells were pretreated with belnacasan (VX-765, an inhibitor of caspase-1), Gasdermin D(GSDMD)-targeting siRNAs, cobalt protoporphyrin (CoPP) or zinc protoporphyrin (Znpp) before being exposed to H2O2. Following these treatments, the Reactive oxygen species (ROS) level, cell viability, percentage of pyroptosis, pyroptosis-related proteins, nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 level was measured. The scanning electron microscopy revealed increased ball-like bulge and membrane pore formation in the CCI group. In the CCI and CCI+ Vehicle groups, we found ROS level and expression of pyroptosis-related proteins increased. While, treatment with VX-765resulted in a decreased expression of GSDMD, IL-1, IL-18, and caspase-1 decreased. In the in-vitro study, RSC96 cells showed mild pyroptosis and overall mild edema after being exposed to H2O2. The ROS level, percentage of pyroptosis, pyroptosis-related proteins, Nrf2 and HO-1 level increased significantly in the H2O2 group. While, the percentage of pyroptosis and pyroptosis-related proteins decreased significantly in the H2O2 + VX-765 group, H2O2 + siRNA group, and H2O2 + VX-765 + siRNA group. After treatment with HO-1-inhibitor Znpp and HO-1-activator Copp, the percentage of pyroptosis and pyroptosis-related proteins increased and decreased significantly respectively. In conclusions, the pyroptosis of Schwann cell in the CCI model generated the demyelination of TN nerve. The ROS is an upstream event of NLRP3 inflammasome activation which induced eventual pyroptosis. The Nrf2/HO-1 signaling pathway could protect the H2O2-induced pyroptosis in RSC96 cells.

Stress drop measures the stress release level over a fault during an earthquake rupture. As one of the important parameters for characterizing source mechanisms and predicting strong ground motions, the stress drop is controlled by the tectonic environment, focal mechanism, and type of earthquake sequence. The stress drop measurements from the seismic data also depend on the observation frequency band. Therefore, the values obtained from various seismic phases, such as body and surface waves, may be different. Previous studies have often used indirect methods to remove the attenuation effects along the propagation path to obtain the source spectra and then estimate the stress drops. Using a broadband high-resolution Lg-wave attenuation model, the attenuation effect can be directly corrected to obtain the Lg-wave source excitation spectra. By fitting the observed spectra to the theoretical source model, we can calculate the seismic moments and corner frequencies from which the stress drops can be calculated. Taking a typical tectonic earthquake and a potentially induced earthquake, that is, the 2017 MS7.0 Jiuzhaigou earthquake sequence and the 2019 MS 6.0 Changning earthquake sequence, in the eastern margin of the Tibetan Plateau as examples, we explored the potential physical differences between tectonic and induced earthquakes. The stress drop in the 2017 Jiuzhaigou mainshock was approximately 27 MPa. The stress drops, and the magnitude of its aftershocks rapidly decay. However, for the 2019 Changning earthquake sequence, the temporal variation of stress drops declined slowly, with two aftershocks having stress drops comparable to the main shock. For an area with long-term water injection, it takes a long time to recover to its equilibrium status once a large earthquake disturbs the regional stress field. Given that no apparent difference in the absolute level of stress drops can be observed between the two types of earthquake sequences, the stress drops alone cannot be used to distinguish between induced and tectonic earthquakes in this area. The increasingly accumulated underground water may have created pathways linking multiple fault systems in the changing salt mining. Thus, the possibility of future induced earthquakes cannot be ruled out.

Metallic glass is being gradually recognized for its unique disordered atomic configuration and excellent catalytic activity, so is of great significance in the field of catalysis. Recent reports have demonstrated that Fe-based metallic glass, as a competitive new catalyst, has good catalytic activity for the fields of environment and energy, including high catalytic efficiency and stability. This review introduces the latest developments in metallic glasses with various atomic components and their excellent catalytic properties as catalysts. In this article, the influence of Fe-based metallic glass catalysts on the catalytic activity of dye wastewater treatment and water-splitting is discussed. The catalytic performance in different atomic composition systems and different water environment systems, and the preparation parameters to improve the surface activity of catalysts, are reviewed. This review also describes several prospects in the future development and practical application of Fe-based metallic glass catalysts and provides a new reference for the synthesis of novel catalysts.