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Controlling continuous cooling is an important means to control the most important mechanical properties of bainitic steel for frogs in railroad applications. In this paper, a bainitic steel for railway frogs is taken as the research object. By designing different cooling rates in the bainitic transformation medium temperature region, the effect of cooling rate on fatigue crack propagation rate was studied. The results show the sample of 4 °C/s cooling rate exhibits higher strength and impact toughness, while the crack propagation rate near the threshold is significantly lower and the threshold is relatively higher at 0.1 °C/s cooling rate. This is related to the fact that more massive blocky retained austenite and coarse microstructure in the sample at 0.1 °C/s cooling rate are more favorable to the occurrence of crack closure effect, especially in the near-threshold region. The fatigue crack propagation rate of the tested steel in the stable propagation region at 4 °C/s cooling rate is slightly higher than that at 0.1 °C/s. This is related to its complex interface distribution characteristics. However, with the increase of Δ K, the tested steel at 0.1 °C/s cooling rate tends to preferentially fail, which is related to its poor toughness.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive fungal diseases of wheat, and seriously threatens safe production of the crop worldwide. In China, new races historically appeared and rapidly developed to be predominant races and have resulted in ineffectiveness and replacement of wheat resistance cultivars as well as massive reduction in yield. In the present study, the relative parasitic fitness of the two newly-emerged Yr5-virulent races (TSA-6 and TSA-9) were compared with those of four currently predominant Chinese races (CYR31, CYR32, CYR33, and CYR34) based on evaluation on 10 Chinese wheat cultivars. As a result, there were significant differences in the relative parasitic fitness parameters among overall tested races based on multiple comparison (LSD) analysis (PTSA-9 (0.95)>TSA-6 (0.92)>CYR34 (0.29)>CYR31 (–1.54)>CYR33 (–1.77). The results indicated that two Yr5-virulent races TSA-9 and TSA-6 possessed relative parasitic fitness higher than races CYR34, CYR31, and CYR33, but lower than race CYR32, and have potential risks in developing to be predominant races. Therefore, continual monitoring of both Yr5-virulent races, and their variants is needed. The use of wheat cultivars (lines) with Yr5 resistance gene singly in wheat breeding is essential for being avoided, and is suggested to combine with other effective stripe rust resistance genes.

This study aims to investigate the phase composition, microstructure, and mechanical properties of three refractory high-entropy alloys (RHEAs): Al7(NbTiZr)93, Al7(NbTiZrMo)93, and Al7(NbTiZrTa)93. The as-cast Al7(NbTiZr)93 alloy exhibits a single-phase BCC structure, with a yield strength (YS) of 1050 MPa at room temperature. The addition of Mo and Ta leads to the formation of Al7(NbTiZrMo)93 and Al7(NbTiZrTa)93 alloys with BCC-B2 and B2-FCC dual-phase structures, whose YS values reach 1741 MPa and 2350 MPa, respectively. At 800 °C, trace amounts of ordered B2 phase are generated in the Al7(NbTiZr)93 matrix, and the YS decreases from 1050 MPa at room temperature to 219 MPa at 800 °C. In the Al7(NbTiZrMo)93 alloy, the 10 nm B2 precipitates grow to several hundred nanometers, and the YS decreases to 431 MPa after compression at 800 °C. In the Al7(NbTiZrTa)93 alloy, the grid B2-FCC structure at room temperature transforms into a disordered BCC structure at 800 °C, yet possessing the YS of 908 MPa and demonstrating acceptable ductility. Moreover, Ta exhibits the better structural and performance matching than Mo in AlNbTiZr-based RHEAs. Therefore, it opens up new prospects for regulating the structure and high-temperature performance of AlNbTiZr-based RHEAs.

The deformation behavior of the pure aluminum has been studied at 298 K and 77 K to elucidate the mechanism for dual-enhancement effect at cryogenic temperature. The results reveal that as the deformation temperature decreases from 298 K to 77 K, the tensile strength and elongation increase from 67.9 MPa to 49.1% to 142.4 MPa and 61.9%, respectively. The simultaneous increase in strength and ductility at 77 K is attributed to the higher strain hardening rate and more uniform deformation at cryogenic temperature. Results obtained from quasi in-situ EBSD indicate that at cryogenic temperatures, there is a higher density of dislocations that are uniformly distributed within the grains. It helps alleviate dislocation pile-ups and reduces the likelihood of crack initiation at grain boundaries. Moreover, a significant number of grains align their orientation rotation towards at cryogenic temperature. Multiple fine slip systems initiate within these grains, contributing to improved mechanical properties in pure aluminum. In contrast, samples deformed at 298 K exhibit localized strain during deformation, with the initiation of unfavorable, non-uniform coarse slip bands within the grains. The findings of this study offer insights into the mechanisms of the dual-enhancement effect in pure aluminum at cryogenic temperatures.

Background/purpose: The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. Results: There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. Conclusion: This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research.

Background/purpose: Oral submucous fibrosis (OSF) affecting populations is considered a public health issue in South/Southeast Asia. The purpose of this study was to analyze the scientometric characteristics and research trends of OSF. Materials and methods: All the papers on OSF were comprehensively retrieved from the Scopus database. Regional comparison (India versus outside of India) and chronological comparison (before 2015 versus after 2015) were performed. Results: Among all the 1357 papers on OSF, 930 (68.5%) were from India. In India, biology research on antioxidant, oxidative stress, angiogenesis, and extracellular matrix were distinctive keywords. Risk factors of smokeless tobacco and gutkha and the roles of saliva and blood sampling were also distinctive keywords in India. In outside of India, biology research on myofibroblast, alpha smooth muscle actin, microRNA, long untranslated RNA, and protein p53 were distinctive keywords. The trend of biology research on connective tissue, genotype, genetic predisposition, messenger RNA, and cytology before 2015 has changed to research on myofibroblast, biological marker, microRNA, epithelial mesenchymal transition, extracellular matrix, and oxidative stress after 2015. The trend of clinical aspects of surgery and mouth hygiene before 2015 has changed to the aspects of adverse event/effects, complication, and quality of life after 2015. Conclusion: This scientometric study elucidated the current scenario and research trends of OSF, and would help in improving in reciprocal collaboration and communication for this disease control in South/Southeast Asia.

Background: When resuscitating patients with septic shock, cerebrovascular reactivity parameters are calculated by monitoring regional cerebral oxygen saturation (rSO2) using near-infrared spectroscopy to determine the optimal blood pressure. Here, we aimed to analyze the impact of cerebral autoregulation-directed optimal blood pressure management on the incidence of delirium and the prognosis of patients with septic shock. Methods: This prospective randomized controlled clinical study was conducted in the Xiangya Hospital of Central South University, China. Fifty-one patients with septic shock (December 2020–May 2022) were enrolled and randomly allocated to the experimental (n=26) or control group (n=25). Using the ICM+ software, we monitored the dynamic changes in rSO2 and mean arterial pressure (MAP) and calculated the cerebrovascular reactivity parameter tissue oxygen reactivity index to determine the optimal blood pressure to maintain normal cerebral autoregulation function during resuscitation in the experimental group. The control group was treated according to the Surviving Sepsis Campaign Guidelines. Differences in the incidence of delirium and 28-day mortality between the two groups were compared, and the risk factors were analyzed. Results: The 51 patients, including 39 male and 12 female, had a mean age of (57.0±14.9) years. The incidence of delirium was 40.1% (23/51), and the 28-day mortality rate was 29.4% (15/51). The mean MAP during the first 24 h of intensive care unit (ICU) admission was higher ([84.5±12.2] mmHg vs. [77.4±11.8] mmHg, P=0.040), and the incidence of delirium was lower (30.8% vs. 60.0%, P=0.036) in the experimental group than in the control group. The use of cerebral autoregulation-directed optimal blood pressure (odds ratio [OR]=0.090, 95% confidence interval [CI]: 0.009 to 0.923, P=0.043) and length of ICU stay (OR=1.473, 95% CI: 1.093 to 1.985, P=0.011) were risk factors for delirium during septic shock. Vasoactive drug dose (OR=8.445, 95% CI: 1.26 to 56.576, P=0.028) and partial pressure of oxygen (PaO2) (OR=0.958, 95% CI: 0.921 to 0.996, P=0.032) were the risk factors for 28-day mortality. Conclusions: The use of cerebral autoregulation-directed optimal blood pressure management during shock resuscitation reduces the incidence of delirium in patients with septic shock. Trial Registration: ClinicalTrials.gov ldentifer: NCT03879317

Large displacement axial piston pumps (>500 mL/r) are the core power components of large construction machineries' hydraulic system. The demand for higher power in large construction machinery is increasing. High pressure and large displacement are the primary areas of focus for enhancing the power of piston pumps. However, this may exacerbate issues with the pumps' output characteristics, such as flow or pressure pulsation and leakage. This paper uses a cross angle of the swash plate to optimize the pulsation and leakage for the 750 mL/r axial piston pumps. Piston and cylinder dynamics affect flow and pressure pulsations, and leakage is related to cylinder tilting behaviour. The pumps’ flow distribution, kinematics and dynamics of the piston and cylinder, output flow and pressure are analysed. A virtual prototype is built based on the rigid-flexible-hydraulic coupling model. The oil film flexible body of the valve plate pair is added. The maximum principal stress and strain of the oil film flexible body are used as indicators of tilting behaviour. Effects of the cross angle on output characteristics and tilting behaviour are investigated through the numerical solution. Results show that the cross angle of −0.5° can effectively reduce the pressure pulsation rate by 0.89% and the flow pulsation rate by 3.77% while optimizing the tilting behaviour of the cylinder. In addition, the cylinder’s tilting behaviour is verified by the wear detection on the valve plate surface.

Fracture propagation in shale under in situ conditions is a critical but poorly understood mechanical process in hydraulic fracturing for deep shale gas reservoirs. To address this, hydraulic fracturing experiments were conducted on hollow double-wing crack specimens of the Longmaxi shale under conditions simulating the ground surface (confining pressure σcp=0, room temperature (Tr)) and at depths of 1600 m (σcp=40 MPa, Ti=70 °C) and 3300 m (σcp=80 MPa, high temperature Ti=110 °C) in the study area. High in situ stress was found to significantly increase fracture toughness through constrained microcracking and particle frictional bridging mechanisms. Increasing the temperature enhances rather than weakens the fracture resistance because it increases the grain debonding length, which dissipates more plastic energy and enlarges grains to close microdefects and generate compressive stress to inhibit microcracking. Interestingly, the fracture toughness anisotropy in the shale was found to be nearly constant across burial depths, despite reported variations with increasing confining pressure. Heated water was not found to be as important as the in situ environment in influencing shale fracture. These findings emphasize the need to test the fracture toughness of deep shales under coupled in situ stress and temperature conditions rather than focusing on either in situ stress or temperature alone.

The short-term associations of ambient temperature exposure with lung function in middle-aged and elderly Chinese remain obscure. The study included 19,128 participants from the Dongfeng-Tongji cohort's first (2013) and second (2018) follow-ups. The lung function for each subject was determined between April and December 2013 and re-assessed in 2018, with three parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) selected. The China Meteorological Data Sharing Service Center provided temperature data during the study period. In the two follow-ups, a total of 25,511 records (average age: first, 64.57; second, 65.80) were evaluated, including 10,604 males (41.57%). The inversely J-shaped associations between moving average temperatures (lag01–lag07) and FVC, FEV1, and PEF were observed, and the optimum temperatures at lag04 were 16.5 °C, 18.7 °C, and 16.2 °C, respectively. At lag04, every 1 °C increase in temperature was associated with 14.07 mL, 9.78 mL, and 62.72 mL/s increase in FVC, FEV1, and PEF in the low-temperature zone (

Objective: To explore the correlation between mitophagy and the tumor microenvironment (TME) in patients with head and neck squamous cell carcinoma (HNSCC), with an aim to enhance therapeutic efficacy for HNSCC. Methods: A machine learning-based multigene prognostic signature was developed based on mitophagy-related differentially expressed genes (MRGs) identified in The Cancer Genome Atlas cohort. This signature was correlated with the TME using gene set enrichment analysis. The association between this prognostic signature and various immunological features of the TME was explored, including status of tumor-infiltrating immune cells, expression of immune checkpoint molecules, and the immunoscore. Immunohistochemistry validated the expression of hub gene CSNK2A2 and assessed its relationship with immunomarker expression. Quantitative PCR validated CSNK2A2 knockdown in HNSCC cell lines. Functional experiments including Transwell assays to determine cell migration and invasion, Cell Counting Kit 8 assay, and 5-ethynyl-2-deoxyuridine assay were performed to confirm the role of CSNK2A2 in HNSCC. Finally, a subcutaneous xenograft model was generated in C3H mice to validate our findings. Results: The MRG-based prognostic signature showed excellent predictive performance. High-risk patients had significantly shorter progression-free and overall survival (P ​

To explore the thermoformability of Mn–Cr–Ni–Co steel for ball mill liner, isothermal compression tests were performed on Mn–Cr–Ni–Co steel using a Gleeble-3800 thermal compressive testing machine. Flow stress curves at 900 °C–1200 °C and 0.01s−1∼10s−1 were obtained. Results show Mn–Cr–Ni–Co steel has obvious positive strain rate sensitivity, with peak stress decreasing with increasing temperature. A constitutive equation for Mn–Cr–Ni–Co steel was established using the Arrhenius model based on strain compensation, and fitted values were compared to experimental values. A hot working map for Mn–Cr–Ni–Co steel was established and analyzed. Hot working process parameters are: deformation temperature of 980∼1200 °C, strain rate of 0.04–1.78s−1, providing a basis for selecting the hot forging process of the ball mill liner. Forging and forming experiments of the ball mill liner were carried out using the optimal parameters of Mn–Cr–Ni–Co steel from the hot working map. The ball mill liner has good forming quality with a relatively uniform martensitic structure inside. Tensile and impact tests were performed on the ball mill liner. Compared to the mechanical properties of traditional cast Mn13 ball mill liners, results show the tensile strength increased by 159.75%, elongation by 18.8%, and impact capacity by about 16.7%.

To improve the thermal barrier properties of epoxy resin coatings, a composite waterborne aerogel multifunctional coating that possesses both mechanical properties and controllable barrier ability was prepared in this study. This coating incorporates granular silica aerogel, organic montmorillonite, and two flame retardants: aluminum hydroxide (ATH) and magnesium hydroxide (MH). The results showed that montmorillonite, modified with stearyl trimethyl ammonium bromide (STAB), exhibited antisymmetric and symmetric stretching vibrational infrared spectral absorption peaks of –CH3, –CH2, characteristic of the long-chain alkane quaternary ammonium salt. This indicated that the quaternary ammonium salt was intercalated into the montmorillonite interlayer, enhancing the surface lamellae. The coating effectively absorbed energy when stressed, resulting in a strength increase of 146.3%. Incorporating high porosity silica aerogel significantly improved the barrier behavior of the composite coating, enabling controlled thermal insulation and excellent corrosion resistance. The coating reduced heat transfer paths and effectively impeded heat transfer, maintaining a high corrosion inhibition efficiency (99.9%) in a 3.5% NaCl solution. Additionally, the individual actions of the two flame retardants led to highly effective flame retardant properties, with the total heat release rate (THR) reduced by about 43.5% and the total smoke production (TSP) by 40.1%.

To realize an initial objective of the negative ion-based neutral beam injection (N-NBI) at the Comprehensive Research Facility for Fusion Technology (CRAFT) test facility, which targets an H0 beam power of 2 MW at an energy of 200–400 keV and a pulse duration of 100 s, it is crucial to study the cesium dynamics of the negative ion source. Here a numerical simulation program CSFC3D is developed and applied to simulate the distribution and time dynamics of cesium during short pulses. The calculations show that most of the cesium on the plasma grid (PG) area originates from the release of cesium that is accumulated within the ion source in the plasma phase. Increasing the wall temperature reduces the loss of cesium on the wall of the ion source. Furthermore, the thickness of the cesium monolayer is directly influenced by the PG temperature. Both simulated and experimental results demonstrate that maintaining the PG temperature between 180 °C and 200 °C is essential for enhancing the performance of the ion source and optimizing the cesium behavior.

Summary: Stapokibart (CM310) is a humanized IL-4Rα monoclonal antibody currently undergoing phase 3 trials for type 2 inflammatory diseases. In contrast to dupilumab, which bound exclusively to human IL-4Rα, stapokibart demonstrated cross-species reactivity to IL-4Rα from human, cynomolgus monkey, and rat. Stapokibart exhibited comparable blocking activity to dupilumab. Epitope mapping revealed that stapokibart bound to distinct sites on IL-4Rα compared to dupilumab. In vitro assays showed that stapokibart was comparable or numerically superior in blocking IL-4Rα-mediated signaling compared to dupilumab. In vivo studies further demonstrated that stapokibart effectively inhibited the progression of type 2 inflammation. Pharmacokinetic studies revealed a circulating half-life of approximately 298–351 h in cynomolgus monkeys and 55–142 h in rats for stapokibart. Toxicity studies indicated a favorable safety profile in cynomolgus monkeys and rats. The preclinical evaluation of stapokibart supports its clinical development.

Background: Myokines play vital roles in both stable coronary artery disease (SCAD) and depression. Meanwhile, there is a pressing necessity to find effective biomarkers for early predictor of major adverse cardiovascular events (MACE) in SCAD patients with depressive symptoms. Methods: A single-center, 5-year follow-up study was investigated. MACE was defined as composite end points, including cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, coronary artery revascularization, or hospitalization for unstable angina. Results: A total of 116 SCAD patients were enrolled, consisting of 30 cases (25.9%) without depressive symptoms and 86 cases (74.1%) with depressive symptoms. During the follow-up, 3 patients (2.6%) were lost. Out of 113 patients, 51 (45.1%) experienced MACE. In the subgroup of 84 SCAD patients with depressive symptoms, 44 cases (52.4%) of MACE were observed. Finally, mature brain-derived neurotrophic factor (mBDNF), pro-brain-derived neurotrophic factor, receptor activator of nuclear factor-κB ligand, smoking history, hypertension and cystatin C were incorporated into the predictive model. Conclusions: Depressive symptoms represent an independent risk factor for MACE in patients with SCAD. Additionally, low mBDNF expression may be an important early predictor for MACE in SCAD patients with depressive symptoms. The predictive model may exhibit a commendable predictive performance for MACE in SCAD patients with depressive symptoms.

High temperatures and drought present significant abiotic challenges that can limit the survival of many arthropods, including wolf spiders, which are ectothermic and play a crucial role in controlling pest populations. However, the impact of these stress factors on the microbiota of spiders remains poorly understood. In this study, we utilized 16 S rRNA gene sequencing to explore the diversity and composition of bacterial communities within Pardosa pseudoannulata under conditions of high temperature and drought stress. We found that Firmicutes, Bacteroidetes, and Proteobacteria were the predominant bacterial phyla present. Analyses of alpha diversity indicated an increase in bacterial diversity under combined stress conditions, as reflected by various diversity indices such as Ace, Chao1, Shannon, and Simpson. Furthermore, co-occurrence network analysis highlighted intricate interactions among the microbial taxa (e.g., Enterobacter, Chitinophaga, and Eubacterium), revealing the adaptive complexity of the spider's microbiome to environmental stress. Functional prediction analysis suggested that combined stress conditions might enhance key metabolic pathways, particularly those related to oxidative phosphorylation and amino acid metabolism. Using Random Forest analysis, we determined that changes in three heat shock proteins were largely attributed to variations in bacterial communities, with Firmicutes being notably influential. Collectively, this in-depth analysis offers novel insights into the responses of microbial communities within spider microbiomes to combined abiotic stresses, providing valuable information for understanding extreme climate impacts and informing ecological management strategies.

Using loop heat pipes (LHPs) for thermal management of aerospace and ground electronic devices has become an efficient and attractive method in recent years. A 3-D CFD numerical model was proposed for calculating the thermo-hydraulic behavior in a LHP with a square evaporator and the accuracy was verified by experimental results. The evaporation and condensation were addressed by volume of fluid method and a momentum source term derived from flow resistance analysis was incorporated into wick as the capillary force. The simulation results aligned with experimental trends, and errors of heating surface temperature and system thermal resistance were small. Due to structural constraint and gravity effect, two eddies were formed in compensation chamber, causing uneven distribution of temperature on heating surface. Parametric analysis indicated that higher porosity deteriorated the heat transfer from heating surface to wick and enlarged heating surface temperature and system thermal resistance. Higher wick and shell thermal conductivities ensured more heat conduction to the vapor-liquid interface and enhanced the evaporation intensity. However, the higher the thermal conductivity, the lower the improvement that could be obtained. Additionally, lower heat sink temperature and higher condenser heat transfer coefficient both intensified the LHP working performance by elevating the condensation efficiency.

This study investigated the effects of dietary chlorogenic acid (CGA) on the productive and reproductive performance, egg quality, antioxidant function, and intestinal microenvironment of laying hens. Thus, 162 healthy Hy-Line Brown breeding hens (63 weeks old) were randomly allocated to 3 groups, each receiving a basal diet plus supplementation: 0, 250, and 500 mg/kg CGA, respectively. Per the in vitro test, CGA had obvious inhibitory effects on Salmonella enteritis and avian pathogenic Escherichia coli and strong free radical scavenging ability. Per the breeder laying hen experiment, the CGA diets had no significant influence on egg production or reproductive performance (P < 0.05). Nevertheless, compared with the control diet, 250 mg/kg CGA significantly increased eggshell thickness, egg weight, yolk color, and Haugh unit (P < 0.05). Compared with the control diet and 500 mg/kg CGA, 250 mg/kg CGA significantly (P < 0.05) elevated antioxidant capacity by reducing serum malondialdehyde content, upregulating heme oxygenase-1, and downregulating heat shock proteins mRNA levels in the ileum. Compared with the control diet and 500 mg/kg CGA, 250 mg/kg CGA (P < 0.05) enhanced intestinal barrier function, shown by the upregulation of ileal Occludin and Mucin-2 mRNA levels; furthermore, 250 mg/kg CGA (P < 0.05) increased anti-apoptotic capacity by increasing B-cell leukemia/lymphoma 2 gene expression and downregulated Bcl2 Associated X mRNA levels in the liver and ileum of late breeder laying hens (P < 0.05). Lastly, 250 mg/kg CGA (P < 0.05) increased cecal g_CHKCI001 and short-chain fatty acid-producing bacteria g_Prevotellaceae UCG-001, positively related to gut health, and in the cecum, 500 mg/kg CGA significantly (P < 0.05) increased g_Shuttleworthia abundance, negatively related to gut health. Our findings suggest that dietary inclusion of 250 mg/kg CGA promotes egg quality, intestinal microbial composition, gut barrier integrity, and the antioxidant capacity of aged breeder laying hens.

As people's environmental awareness improves, the development of green economy has become an important goal for countries to achieve sustainable development. The extensive generation of greenhouse gases during the cold chain logistics and distribution process poses a significant challenge to the advancement of the green economy. By utilizing an enhanced genetic algorithm (GA), this research examines the expenses associated with distributing fresh agricultural products via the cold chain and constructs a model for optimizing the path of distribution. Simulation experiments show that the total cost of this model constructed in the study is 2323.94 RMB, which is less than 2623.35 RMB of the traditional path planning model, and the carbon emission is 85 kg less. It proves that the path optimization model constructed by the research has high economic and environmental benefits, and the designed and planned path is more in line with the needs of green economy than the traditional path, which has the potential to minimize carbon emissions during the fresh agricultural product cold chain distribution process while simultaneously promoting sustainable development.

Grain of high yield and quality is needed worldwide due to the needs of a rapidly increasing human population. However, diseases caused by some stubborn types of phytopathogenic bacteria can limit the health and yields of crops. Even worse, conventional commercial bactericides have limited efficacy against such diseases. Therefore, exploring some efficacious bactericidal alternatives is urgently needed. In this work, a new type of 3-(piperazin-1-yl)propan-2-ol modified carbazole derivatives was synthesized and assessed for their bactericidal activity. Among them, compound B16 was the optimal active molecule, giving the EC50 values of 3.11 (Xanthomonas oryzae pv. oryzae), 3.20 (Xanthomonas axonopodis pv. citri) and 3.54 μg/mL (Pseudomonas syringae pv. actinidiae). Pot experiments revealed compound B16 to be able to control rice bacterial leaf blight. Some biochemical assays illustrated that our designed compounds could destroy the integrality of bacterial cell membranes and thereby leading to leaking the intracellular protein. These findings may be regard as a reference for the design of novel membrane-targeting antimicrobial agents for managing stubborn plant bacterial diseases.

Objectives: Tai Chi (TC) shows some beneficial effects in reducing pain in knee osteoarthritis (OA). However, the selection of criteria TC forms in previous studies were unclear and inconsistent, possibly accounting for the varying outcomes and rendering the training effects suboptimal. We have selected four optimal TC (OTC) forms based on the knee joint load and its association with pain. This pilot study sought to examine the effect of the OTC forms on reducing knee pain in individuals with knee OA. Methods: Fifteen knee OA participants were recruited. Their knee joint pain level was rated by using the Visual Analogue Scale before and after two weeks of OTC training and compared between these two assessments. Results: The two-week OTC training course was well accepted by our participants. The knee OA pain showed a significant reduction (median pain score: 5 ​cm before training and 1 ​cm post-training, Wilcoxon p ​

The continuous drive for miniaturization and enhanced functionality in micro-electronic devices demands highly integrated circuit (IC) packaging. This trend leads to a dense network of micro-electronic packaging interconnections, facilitated by the reduction in traditional solder interconnection sizes. However, these advancements bring about significant challenges, including thermal expansion differences between materials used in the package and the presence of non-planar substrates. Such issues can lead to thermomechanical stresses in interconnections and warpage, resulting in serious reliability issues. In response, nanostructured compliant interconnections have emerged as a promising solution. These interconnections effectively manage thermal expansion variations and substrate non-coplanarity, mitigating the risks associated with miniaturization and high integration demands in IC packaging. This review explores the latest trends and advancements in developing nanostructured compliant interconnections for modern micro-electronics. The focus is on integrating various interconnection materials, including nanoparticles (via sintering), nanoporous materials, nanowires (NWs) and carbon nanotubes (CNTs). This integration aims to improve the performance and mechanical reliability of interconnections under extreme thermal loading conditions. Advanced bonding techniques and their significant impacts on interconnection reliability are also discussed. Additionally, the study provides insights into future developments of nanostructured compliant interconnections, guiding researchers toward specific technical areas for future exploration.

CDT1, a gene that shows excessive expression in various malignancies, functions as a pivotal regulator of replication licensing. In this study, we observed a positive correlation in expression between CDT1 and E2F2 among patients with lung adenocarcinoma (LUAD). Our findings substantiated that E2F2 directly interacted with the promoter region of CDT1, as confirmed by ChIP-qPCR assays, and depletion of E2F2 resulted in a downregulation of CDT1 expression in LUAD cell lines by gene interference technology. Furthermore, we identified an upregulation of CDT1 mRNA level in Chinese LUAD samples. Notably, in the loss-of-function assays, depletion of CDT1 in LUAD cell lines inhibited cell proliferation, migration, and invasion. Concurrently, it promoted cell apoptosis and induced G0/G1 phase arrest using MTT, flow cytometry, and Transwell assays, reinforcing its role as an oncogene.Furthermore, enhanced tumor ablation was determined in a CDT1-downregulated LUAD tumor-bearing nude mouse model. Collectively, our results strongly suggest that E2F2 positively regulates CDT1 expression and actively participates in the progression of lung adenocarcinoma, thereby providing valuable insights into identifying novel therapeutic targets for LUAD treatment.

Objective: To explore the effective targets of Celecoxib in the treatment of heterotopic ossification using network pharmacology methods. Methods: Potential molecules related to heterotopic ossification were obtained by retrieving the GEO and CTD databases and intersecting them. Potential binding targets of Celecoxib were acquired from the STITCH database. A protein-protein interaction network was constructed between potential binding targets of Celecoxib and potential related molecules of heterotopic ossification using the STRING database. Molecules in the protein-protein interaction network were further analyzed using GO and KEGG enrichment analysis in R software, followed by enrichment analysis of active molecules in the Celecoxib-heterotopic ossification target dataset. Hub genes were selected based on the “degree” value and enrichment within the protein-protein interaction network. The binding affinity of hub genes to Celecoxib was observed using molecular docking techniques. Finally, in vitro experiments were conducted to validate the effectiveness of hub genes and explore their regulatory role in the progression of heterotopic ossification. Additionally, the therapeutic effect of Celecoxib, which modulates the expression of the hub genes, was investigated in the treatment of heterotopic ossification. Results: 568 potential molecules related to heterotopic ossification and 76 potential binding targets of Celecoxib were identified. After intersection, 13 potential functional molecules in Celecoxib's treatment of heterotopic ossification were obtained. KEGG analysis suggested pathways such as Rheumatoid arthritis, NF-kappa B signaling pathway, Pathways in cancer, Antifolate resistance, MicroRNAs in cancer play a role in the treatment of heterotopic ossification by Celecoxib. Further enrichment analysis of the 13 potential functional molecules identified 5 hub genes: IL6, CCND1, PTGS2, IGFBP3, CDH1. Molecular docking results indicated that Celecoxib displayed excellent binding affinity with CCND1 among the 5 hub genes. Experimental validation found that CCND1 is highly expressed in the progression of heterotopic ossification, promoting heterotopic ossification in the early stages and inhibiting it in the later stages, with Celecoxib's treatment of heterotopic ossification depending on CCND1. Conclusion: In the process of treating heterotopic ossification with Celecoxib, immune and inflammatory signaling pathways play a significant role. The therapeutic effect of Celecoxib on heterotopic ossification depends on the hub gene CCND1, which plays different roles at different stages of the progression of heterotopic ossification, ultimately inhibiting the occurrence of heterotopic ossification.

Porcine circovirus type 2 (PCV2) infection leads to multi-system inflammation in pigs, and this effect can be achieved by upregulating host miR-21. The underlying mechanism of miR-21 regulates PCV2-induced inflammation is already known, however, how PCV2 regulates miR-21 levels and function using both autonomic and host factors remains to be further revealed. Here we present the first evidence that PCV2 ORF5 induces an inflammatory response by up-regulating miR-21 level through targeting nuclear miR-30d. In this study, we found that overexpression of ORF5 significantly increased miR-21 level and promoted the expression of inflammatory cytokines and activation of the NF-κB pathway, while ORF5 mutation had the opposite effect. Moreover, the differential expression of miR-21 could significantly change the pro-inflammatory effect of ORF5, indicating that ORF5 promotes inflammatory response by up-regulating miR-21. Bioinformatics analysis and clinical detection found that nuclear miR-30d was significantly down-regulated after ORF5 overexpression and PCV2 infection, and targeted pri-miR-21 and PCV2 ORF5. Functionally, we found that miR-30d inhibited the levels of miR-21 and inflammatory cytokines in cells. Mechanistically, we demonstrated that ORF5 inhibits miR-30d expression levels through direct binding but not via the circRNA pathway, and miR-30d inhibits miR-21 levels by targeting pri-miR-21. In summary, the present study revealed the molecular mechanism of ORF5 upregulation of miR-21, further refined the molecular chain of PCV2-induced inflammatory response and elucidated the role of miRNAs in it.

This study investigated the effects of dietary glutamine on growth performance, antioxidant capacity, and osmoregulation in euryhaline fish (Oreochromis niloticus) under hyperosmotic stress. Nile tilapia was fed four diets with varying glutamine concentrations (0 %, 0.75 %, 1.5 %, and 3 %) at 0 or 16 ppt for 42 days. The results demonstrated that dietary supplementation of 0.75 % glutamine significantly enhanced the growth performance of Nile tilapia under both 0 ppt and 16 ppt salinity. Hyperosmotic stress significantly reduced the crude protein and crude lipid contents while elevated the ash content of the fish. Under hyperosmotic stress, dietary glutamine supplementation significantly increased the antioxidant and immune capacities, and attenuated apoptosis in the liver of tilapia. The expression of ion transporter genes in the gills and kidneys were both significantly increased by dietary glutamine. Meanwhile, glutamine supplementation significantly reduced the levels of inorganic ions in serum while increased serum osmolality. Hyperosmotic stress significantly activated the glycolysis, gluconeogenesis, and pentose phosphate pathways in the liver of tilapia. However, supplementation of glutamine under hyperosmotic stress would significantly enhance the ability of gluconeogenesis of tilapia in the liver. The results of this research suggested that dietary glutamine might promote the growth performance of fish by enhancing their antioxidant capacity and osmoregulation capacity under chronic hyperosmotic stress. This work investigates the role of glutamine in osmolarity regulation and extends the understanding of its mechanism of action, which could provide a reference for hyperosmotic adaptation in aquatic animals.

Summary: Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/β-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.

Objective: This in-vitro study investigates the influence of two different impression techniques and two shoulder designs on the marginal adaptation of computer-aided design/computer-aided manufacturing restorations. Methods: Forty mandibular first premolars were cast into dental arch models for this in vitro study. Fragile cusps and concavities on the mesial–buccal–occlusal surfaces were treated, with 2 mm of the occlusal surface removed. Teeth were categorised into two groups based on shoulder preparation. Digital scanning using a 3Shape 3D scanner identified them further for allocation into conventional and digital impression subgroups. The restorations were created from nanoceramic resin blocks using prescribed guidelines. Microscopic evaluation assessed the restoration's marginal adaptation, with data analysed using SPSS 27.0. The level of significance was set at p ≤ 0.05. Results: Digital intraoral scanning consistently demonstrated smaller marginal gaps than the traditional impression method, regardless of shoulder preparation, with the differences being statistically significant (p

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime–avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.

The frequent occurrence of urban floods (UFs) poses significant threats to citizens’ lives and the national economy. Utilizing machine learning to assess urban flood susceptibility (UFS) provides valuable decision support for UF management. However, the precision of current studies is usually influenced by the variability of temporal factors like extreme rainfall, which limits the accurate identification of urban flood-susceptible regions (UFSRs). To address this issue, we present a novel approach that leverages the spatiotemporal distribution and characteristics of UFS to accurately identify UFSRs. In our case study of the Greater Bay Area (GBA) in China, we employed the Random Forest to assess the spatiotemporal distribution of UFS. We then used the Savitzky-Golay filter to correct UFS data based on the UFS time series from 2011 to 2020. The Theil-Sen median slope, Mann-Kendall test, and Hurst analysis were used to explore the spatiotemporal patterns of UFS. Shapley additive explanation was applied to quantify the contribution of selected variables. Our findings include: (1) UFS in the GBA demonstrates a rising trend, with high susceptibility areas increasing from 6.3 % in 2011 to 7.4 % in 2020; (2) UFSRs, covering approximately 11 % of the GBA, are primarily concentrated in the cities located around the central GBA; and (3) human behavior factors have a more significant influence on UF than natural ones. We believe the presented framework for the accurate extraction of UFSRs provides valuable decision support for sustainable city development.

Osteoarthritis (OA) is a prevalent chronic disease, characterized by chronic inflammation and cartilage degradation. This study aims to deepen the understanding of OA's pathophysiology and to develop novel therapeutic strategies. Our study underscores the pivotal role of Epiphycan (EPYC) and the IL-17 signaling pathway in OA. EPYC, an essential extracellular matrix constituent, has been found to exhibit a positive correlation with the severity of OA. We have discovered that EPYC modulates the activation of the IL-17 signaling pathway within chondrocytes by regulating the interaction between IL-17A and its receptor, IL-17RA. This regulatory mechanism underscores the intricate interplay between the extracellular matrix and immune signaling in the pathogenesis of OA Another finding of our study is the therapeutic effectiveness of protocatechualdehyde (PAH) in OA. PAH significantly reduces chondrocyte hypertrophy and supports cartilage tissue recovery.by targets EPYC. To reduce the side effects of orally administered PAH and maintain its effective drug concentration, we have developed a decellularized matrix hydrogel loaded with PAH for intra-articular injection. This novel drug delivery system is advantageous in minimizing drug-related side effects and ensuring sustained release PAH within the joint cavity.

Disturbances in copper (Cu) homeostasis have been observed in diabetes and associated complications. Cu is an essential micronutrient that plays important roles in various fundamental biological processes. For example, diabetic cardiomyopathy is associated with elevated levels of Cu in the serum and tissues. Therefore, targeting Cu may be a novel treatment strategy for diabetic complications. This review provides an overview of physiological Cu metabolism and homeostasis, followed by a discussion of Cu metabolism disorders observed during the occurrence and progression of diabetic complications. Finally, we discuss the recent therapeutic advances in the use of Cu coordination complexes as treatments for diabetic complications and their potential mechanisms of action. This review contributes to a complete understanding of the role of Cu in diabetic complications and demonstrates the broad application prospects of Cu-coordinated compounds as potential therapeutic agents.

The DC magnetic bias phenomenon in transformers can result in increased noise and harmonic components. This study focuses on the DC magnetic bias generated by stray currents in the DC traction power supply system of neutral grounding transformers under multiple train operation conditions. A two-layer soil model is utilized to calculate geodetic potential, with rail potentials from both mainline and depot serving as sources for stray current within the model. Two paths of stray current intrusion into the transformer via the grounding network and cable armor layer from the Main substation have been modeled and analyzed. A simulation test has been designed to verify that the maximum error between experimental data and model calculation data is 8.87%. The implementation of a blocking connection device between the depot and mainline, as well as a change in grounding strategy for the metal protective layer, can effectively reduce DC bias magnetic current in the substation.

Artificial intelligence (AI) technology has significantly transformed corporate behavior in the energy sector by enhancing the capacity and efficiency of information transmission and big data analysis. However, there is still a limited understanding of how AI influences new market entry mode strategies in overseas energy investments. Drawing on information processing theory, we propose that firms with advanced AI technology exhibit superior data processing capabilities, which can help energy companies mitigate the uncertainties associated with entering a foreign market and encourage them to choose a wholly-owned entry mode. We further hypothesize that the state ownership of firms, the political affinity between home and host countries, and the risk preferences of firm executives serve as moderating factors. Using a sample of Chinese-listed multinational firms in the energy sector from 2010 to 2021, our empirical results strongly support these predictions. These findings contribute to the emerging and crucial literature on the impact of AI technology on firms’ overseas investment behavior, particularly in the energy sector.

Background: Non-alcoholic steatohepatitis (NASH), an escalating global health concern, is a primary factor behind cirrhosis, liver transplantation, and hepatocellular carcinoma. Effective treatments remain elusive. Danggui-Shaoyao-San (DGSY), a classic famous prescription employed in treating NASH, could hold promise, although its molecular underpinnings are still under investigation. This study undertakes an exploration of the impacts of DGSY on NASH and seeks to illuminate the mechanisms at play. Methods: UHPLC-Q-Orbitrap HRMS was employed to identify compounds within DGSY. Mice underwent a 25-week regimen of HFHC diet and high-sugar water, with 4 weeks of DGSY treatment for efficacy and pathogenic mechanism exploration in vivo. L02 cells were cultured with 0.2 mM FFA for 24 h, exposed to DGSY at 1 mg/ml and 2 mg/ml for efficacy and pathogenic mechanism exploration in vitro. Using online databases, we sought potential targets for NASH treatment, and through PPI networks, identified key targets. Expression levels of genes and proteins were examined by western blotting, RT-PCR, and immunofluorescence staining. Results: Thirty-four compounds were identified within DGSY. DGSY brought about marked reductions in biochemical indicators and yielded significant improvements in NASH mice histological features. Additionally, it mitigated hepatic steatosis and inflammation both in vivo and in vitro. The top 10 targets from two network pharmacology analyses, one focusing on structural prediction and the other on literature mining, identified APOE and APP as potential therapeutic targets for DGSY in NASH treatment. PCR validation confirmed that DGSY reduced APP expression after treatment, and further investigation revealed that DGSY significantly suppressed hepatic APP and Aβ expression, indicating its effectiveness in treating NASH. Furthermore, it inhibited Aβ-induced Cathepsin B lysosomal release, reducing hepatic inflammation. Conclusion: Danggui-Shaoyao-San has anti-steatohepatitis effects in ameliorating hepatic APP protein expression, reducing hepatic lysosomal CTSB release, and suppressing hepatic NF-κB activation. The study provided a more theoretical basis for the future clinical application of DGSY.

Summary: The oxidative-stress-related protein Kelch-like ECH-associated protein 1 (KEAP1) is a substrate articulator of E3 ubiquitin ligase, which plays an important role in the ubiquitination modification of proteins. However, the function of KEAP1 in breast cancer and its impact on the survival of patients with breast cancer remain unclear. Our study demonstrates that KEAP1, a positive prognostic factor, plays a crucial role in regulating cell proliferation, apoptosis, and cell cycle transition in breast cancer. We investigate the underlying mechanism using human tumor tissues, high-throughput detection technology, and a mouse xenograft tumor model. KEAP1 serves as a key regulator of cellular metabolism, the reprogramming of which is one of the hallmarks of tumorigenesis. KEAP1 has a significant effect on mitochondrial biogenesis and oxidative phosphorylation by regulating HSPA9 ubiquitination and degradation. These results suggest that KEAP1 could serve as a potential biomarker and therapeutic target in the treatment of breast cancer.

To explore the spatiotemporal evolution characteristics of heat vulnerability in the Pearl River Delta urban agglomeration during heatwave disasters, this research employs the Entropy Weight Method (EWM) to calculate the heat vulnerability assessment results for nine cities in the region spanning from 2001 to 2022. Through the application of kernel density estimation, Moran's I, and the Geographically and Temporally Weighted Regression (GTWR) model, which is proven to be superior to traditional model such as OLS, this study analyzes the dynamic distribution patterns of heat vulnerability in the study area and dissect the trends of influencing factors. The results reveal that from 2001 to 2022, the overall heat vulnerability index in the study area demonstrates a fluctuating downward trend. Key contributors to heat vulnerability include high-frequency and long-duration heatwaves, population sensitivity, and changes in residents' consumption levels. Throughout this period of development, the disparity in heat vulnerability among cities has gradually widened, indicating an overall pattern of uneven development in the region. Future attention should be focused on formulating heat adaptation strategies in areas with high vulnerability to enhance the overall sustainability of the study area.

Summary: This study investigated host responses to long COVID by following up with 89 of the original 144 cohorts for 1-year (N = 73) and 2-year visits (N = 57). Pulmonary long COVID, characterized by fibrous stripes, was observed in 8.7% and 17.8% of patients at the 1-year and 2-year revisits, respectively, while renal long COVID was present in 15.2% and 23.9% of patients, respectively. Pulmonary and renal long COVID at 1-year revisit was predicted using a machine learning model based on clinical and multi-omics data collected during the first month of the disease with an accuracy of 87.5%. Proteomics revealed that lung fibrous stripes were associated with consistent down-regulation of surfactant-associated protein B in the sera, while renal long COVID could be linked to the inhibition of urinary protein expression. This study provides a longitudinal view of the clinical and molecular landscape of COVID-19 and presents a predictive model for pulmonary and renal long COVID.

China faces a healthcare challenge due to its aging population, necessitating an integrated old-age healthcare system considering multiple stakeholders' interests. Conflict and inequality may arise from varying stakeholder interests. This study develops a conflict resolution strategy for the coordination of stakeholders involved in the old-age healthcare service system, promoting harmonization and minimizing conflict to establish an equitable system meeting elderly needs. It contributes to a robust healthcare system for comprehensive, quality care. The focus of the study is to identify relevant stakeholders and decision-makers involved in developing an integrated old-age healthcare service system and explore a feasible solution through stakeholder analysis using the Mitchell score-based technique and stakeholder theory. Decision-makers' preferences are estimated using the Analytic Hierarchy Process (AHP). Solution strategies are developed through multiple stability concepts within the graph model for conflict resolution (GMCR). The conflict resolution analysis based on the integrated AHP-GMCR approach reveals that the development of an integrated old-age healthcare system is feasible by addressing potential conflicts among the stakeholders. Considering the current predicament of comprehensive medical services in China, governments should distribute authority, simplify procedures, and improve the insurance system. Furthermore, medical institutions should explore funding options, expand services, and enhance accessibility. Elderly individuals should prioritize healthy aging and seek suitable healthcare providers. Stakeholder participation is crucial for effective implementation. These recommendations enable China to advance integrated elderly care successfully, addressing challenges posed by the aging population.

Aortic graft infection is an uncommon but highly fatal complication. Correct diagnosis and timely treatment are somewhat challenging. This study presents a case report of successful recognition and treatment of this complication.

In contemporary times, tumors have emerged as the primary cause of mortality in the global population. Ongoing research has shed light on the significance of neurotransmitters in the regulation of tumors. It has been established that neurotransmitters play a pivotal role in tumor cell angiogenesis by triggering the transformation of stromal cells into tumor cells, modulating receptors on tumor stem cells, and even inducing immunosuppression. These actions ultimately foster the proliferation and metastasis of tumor cells. Several major neurotransmitters have been found to exert modulatory effects on tumor cells, including the ability to restrict emergency hematopoiesis and bind to receptors on the postsynaptic membrane, thereby inhibiting malignant progression. The abnormal secretion of neurotransmitters is closely associated with tumor progression, suggesting that focusing on neurotransmitters may yield unexpected breakthroughs in tumor therapy. This article presents an analysis and outlook on the potential of targeting neurotransmitters in tumor therapy.

Organophosphorus compounds (OPs) are widely used as flame retardants (FRs) and plasticizers, yet strategies for comprehensively screening of suspect OPs in environmental samples are still lacking. In this work, a neoteric, robust, and general suspect screening technique was developed to identify novel chemical exposures by use of ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). We firstly established a suspect chemical database which had 7,922 OPs with 4,686 molecular formulas, and then conducted suspect screening in n = 50 indoor dust samples, n = 76 sediment samples, and n = 111 water samples. By use of scoring criteria such as retention time prediction models, we successfully confirmed five compounds by comparison with their authentic standards, and prioritized three OPs candidates including a nitrogen/fluorine-containing compound, that is dimethyl {1H-indol-3-yl[3-(trifluoromethyl)anilino]methyl} phosphonate (DMITFMAMP). Given that the biodegradation half-life values in water (t1/2,w) of DMITFMAMP calculated by EPI Suite is 180 d, it is considered to be potentially persistent. This strategy shows promising potential in environmental pollution assessment, and can be expected to be widely used in future research.

This study focuses on developing a water-in-oil-in-water (W1/O/W2) double emulsion system using high-intensity ultrasound (HIU)-treated pea protein isolate (HIU-PPI) and pectin to encapsulate Lactobacillus plantarum (L. plantarum). The effects of ultrasound treatment on pea protein isolate (PPI) characteristics such as solubility, particle size, emulsification, surface hydrophobicity, and surface free sulfhydryl group were examined, determining optimal HIU processing conditions was 400 W for 10 min. The developed W1/O/W2 double emulsion system based on HIU-PPI demonstrated effective encapsulation and protection of L. plantarum, especially at the HIU-PPI concentration of 4 %, achieving an encapsulation efficiency of 52.65 %. Incorporating both HIU-PPI and pectin as emulsifiers increased the particle size and significantly enhanced the emulsion’s viscosity. The highest bacterial encapsulation efficiency of the emulsion, 59.94 %, was attained at a HIU to pectin concentration ratio of 3:1. These emulsions effectively encapsulate and protect L. plantarum, with the concentration of HIU-PPI being a critical factor in enhancing probiotic survival under simulated gastrointestinal digestion. However, the concurrent utilization of pectin and HIU-PPI as emulsifiers did not provide a notable advantage compared to the exclusive use of HIU-PPI in enhancing probiotic viability during in vitro simulated digestion. This research offers valuable perspectives for the food industry on harnessing environmentally friendly, plant-based proteins as emulsifiers in probiotic delivery systems. It underscores the potential of HIU-modified pea protein and pectin in developing functional food products that promote the health benefits of probiotics.

Copper (Cu) contamination represents a persistent and significant form of heavy metal pollution in agricultural ecosystems, posing serious threats to organisms in current society. Spiders serve as crucial biological indicators for assessing the impact of heavy metals-induced toxicity. However, the specific molecular responses of spiders to Cu exposure and the mechanisms involved are not well understood. In our study, the wolf pond spiders, Pirata subpiraticus, were exposed to Cu for 21 d, resulting in a notable decline in survival rates compared with the control (n = 50, p < 0.05). We observed an increased expression of enzymes like glutathione peroxidase and superoxide dismutase (p < 0.05), signaling a strong oxidative stress response crucial for counteracting the harmful effects of reactive oxygen species. This response was corroborated by a rise in malondialdehyde levels (p < 0.05), a marker of lipid peroxidation and oxidative damage. Transcriptomic and metabolomic analyses revealed 2004 differentially expressed genes (DEGs) and 220 metabolites (DEMs). A significant number of these DEGs were involved in the glutathione biosynthetic process and antioxidant activity. A conjoint analysis revealed that under the Cu stress, several important enzymes and metabolites were altered (e.g., cathepsin A, legumain, and lysosomal acid lipase), affecting the activities of key biological processes and components, such as lysosome and insect hormone biosynthesis. Additionally, the protein interaction network analysis showed an up-regulation of processes like the apoptotic process, glutamate synthase activity, and peroxisome, suggesting that spiders activate cellular protective strategies to cope with stress and maintain homeostasis. This study not only deepens our understanding of spider biology in the context of environmental stress but also makes a significant contribution to the field of environmental stress biology.

Developing an efficient photocatalytic system for hydrogen peroxide (H2O2) activation in Fenton-like processes holds significant promise for advancing water purification technologies. However, challenges such as high carrier recombination rates, limited active sites, and suboptimal H2O2 activation efficiency impede optimal performance. Here we show that single-iron-atom dispersed Bi2WO6 monolayers (SIAD-BWOM), designed through a facile hydrothermal approach, can offer abundant active sites for H2O2 activation. The SIAD-BWOM catalyst demonstrates superior photo-Fenton degradation capabilities, particularly for the persistent pesticide dinotefuran (DNF), showcasing its potential in addressing recalcitrant organic pollutants. We reveal that the incorporation of iron atoms in place of tungsten within the electron-rich [WO4]2− layers significantly facilitates electron transfer processes and boosts the Fe(II)/Fe(III) cycle efficiency. Complementary experimental investigations and theoretical analyses further elucidate how the atomically dispersed iron induces lattice strain in the Bi2WO6 monolayer, thereby modulating the d-band center of iron to improve H2O2 adsorption and activation. Our research provides a practical framework for developing advanced photo-Fenton catalysts, which can be used to treat emerging and refractory organic pollutants more effectively.