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ObjectiveCytokines and cell subsets are important components of the tumor microenvironment. Previous research has revealed that there are differences in cytokines and cell subsets in the peripheral blood of lung cancer (LCA) patients before and after eradication. The purpose of this study is to explore the monitoring value of cytokines and cellular subpopulations as biomarkers in post-immunotherapy monitoring of patients with LCA after surgeryMethodsWe conducted a case-control study using double-antibody sandwich magnetic microsphere flow cytometry with immunofluorescence technology and fluorescent monoclonal antibody multiparameter flow cytometry to detect differences in peripheral blood cytokines and cell subsets between LCA patients after immunotherapy and healthy controls.ResultsOur research results show that there are differences in the levels of IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α in the peripheral blood of LCA patients (n=70) after immunotherapy compared to the healthy controls (n=55) (P

Abstract Compound plant extracts (CPE) are beneficial for aquatic animals on growth performance and antioxidant capacity. A 56‐day experiment was conducted to investigate its positive effect on rice field eel. The fish were fed a commercial diet and supplementing CPE (mainly containing eucommia polysaccharides, reducing sugar) at 0, 0.8, 1.6, 2.4, and 3.2 g/kg. Results showed that dietary CPE significantly increased weight gain and specific growth rate (p

The aim of this study was to investigate the effects of temporal instability and possible heterogeneity on pedestrian accident severity, 48786 accident data from 2018 to 2021 in the UK STATS database were used as the study object, and accident severity was used as the dependent variable, and 49 accident characteristics were selected as independent variables from 6 characteristics of accident pedestrian, driver, vehicle, road, environment and time to construct the pedestrian accident mean heterogeneity random-parameter logit model and examined its temporal stability. The results of model estimation and likelihood ratio tests indicate that the variables affecting pedestrian injury severity are highly variable and not stable over the years. And further demonstrates the potential of models that address unobserved heterogeneity for significant relationships in pedestrian accident severity analyses.

The fascial space of the oral and maxillofacial region contains loose connective tissues, which possess weak anti-infection ability and are often prone to infection, leading to acute suppurative inflammation and sepsis through blood. Although antibiotic use can reduce the probability of bacterial infections, owing to the emergence of antibiotic-resistant bacteria, the search for new antimicrobial drugs is imminent. Herein, we report a metal–organic framework (MOF) antibacterial material designed and synthesized with gallium (Ga) as the central atom, which possesses significant antibacterial, anti-inflammatory, and antioxidant effects. Our data suggested that GA-based MOFs (Ga–MOFs; 1 μg/mL) could sufficiently kill Porphyromonas gingivalis, Streptococcus pyogenes, and Staphylococcus aureus. Ga–MOFs exhibited a bactericidal effect against these three pathogens by disrupting biofilm formation, exopolysaccharide production, and bacterial membrane integrity. In addition, we found that 1 μg/mL of Ga–MOFs was not cytotoxic to human oral epithelial cell (HOEC) lines and it significantly reduced the adhesion of the three pathogens to HOEC. Ga–MOFs protect macrophages from excessive oxidative stress by scavenging excess intracellular reactive oxygen species and upregulating antioxidant gene levels, thereby enhancing cellular antioxidant defense. In addition, Ga–MOFs can promote the transformation of macrophages from the proinflammatory phenotype to the anti-inflammatory phenotype, thereby protecting oral health. Herein, novel Ga–MOF materials were chemically synthesized for therapeutic applications in oral infections, which provides new ideas for the development of novel nonantibiotic drugs to accelerate patient recovery.

The MgO-activated SiO2 system demonstrates potential for a low carbon footprint throughout its lifecycle and is characterized by favorable mechanical properties, low alkalinity, and a high specific surface area, which shows promise in replacing traditional silicate cement in certain applications. The current system faces challenges such as slow early hydration rate, low early strength, and inadequate volume stability, which impede its further development and application. The MgO-activated SiO2 system was improved and optimized through multiple tests using carbonation (CO2 gas/NaHCO3 solution), nanomaterials (whiskers), and fiber (organic/inorganic fiber) composite reinforcement. This paper provides an overview of the hydration mechanism of the MgO-activated SiO2 system, explores modifications and control measures based on this mechanism, and discusses the potential applications and future development of the MgO-activated SiO2 system.

Abstract The detection of tiny defects in industrial products is important for improving the quality of industrial products and maintaining production safety. Currently, image-based defect detection methods are ineffective in detecting tiny and variously shaped defects. Therefore, this paper proposes a tiny defect detection network (TD-Net) for industrial products to improve the effectiveness of tiny defect detection. TD-Net improves the overall defect detection effect, especially the detection effect of tiny defects, by solving the problems of downsampling of tiny defects, pre-filtering of conflicting deep and shallow semantic information, and cascading fusion of multi-scale information. Specifically, this paper proposes the Defect Downsampling (DD) module to realize the defect information supplementation during the backbone downsampling process and improve the problem that the stepwise convolution easily misses the detection of tiny defects. Meanwhile, the Semantic Information Interaction Module (SIIM) is proposed, which fuses deep and shallow semantic features, and is designed to interact the fused features with shallow features to optimize the detection of tiny defects. Finally, the Scale Information Fusion Module (SIFM) is proposed to improve the Path Aggregation Network (PANet) for cascading fusion and information focus on different scale information, which enables further improvement of defect detection performance of TD-Net. Extensive experimental results on the NEU–DET data set (76.8 $$\%$$ % mAP), the Peking University PCB defect data set (96.2 $$\%$$ % mAP) and the GC10-DET data set (71.5 $$\%$$ % mAP) show that the proposed TD-Net achieves competitive results compared with SOTA methods with the equivalent parameter quantity.

Background/Aims: Functional anorectal pain is one of several types of functional anorectal disorders. In this study, we compared the effectiveness of acupuncture (intervention) and biofeedback (control) as treatment for patients with functional anorectal pain. Materials and Methods: This prospective, single-center, randomized, and comparative study examined 68 patients with functional anorectal pain who were recruited from June 2017 to January 2019 at the Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were randomly assigned to receive acupuncture or biofeedback. Patients in the acupuncture group received acupuncture at Zhongliao (BL33), Xialiao (BL34), Ganshu (BL18), Shenshu (BL23), and Dachangshu (BL25). Patients in the biofeedback group received pelvic floor biofeedback therapy, consisting of Kegel pelvic floor muscle training and electrical stimulation. Patients in both groups received 20 treatments over 4 weeks. The primary outcome was pain score on a visual analog scale, and the secondary outcomes were results from the MOS 36-item short-form health survey (SF-36) quality of life questionnaire, the self-rating depression scale, and the self-rating anxiety scale. Results: Visual analog scale pain scores significantly decreased in both of the groups with treatment (both P < .01). The final visual analog scale score was significantly lower in patients with pelvic floor dyssynergia who were treated with biofeedback (1.40 ± 0.97 vs. 5.30 ± 1.70) (P < .05). The 2 groups had similar decreases in self-rating depression scale and self-rating anxiety scale scores. Intriguingly, the acupuncture group had better mental health outcomes (P < .05). Conclusion: Both acupuncture and biofeedback therapy reduced the pain of patients with functional anorectal pain. Biofeedback provided more relief in patients with pelvic floor dyssynergia, and acupuncture provided greater improvements in mental health status.

Abstract Background Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. Methods Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. Results We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. Conclusions Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

Abstract High mortality due to hygrothermal stress during heat waves is mostly linked to cardiovascular malfunction, the most serious of which are malignant arrhythmias. However, the mechanism associated with hygrothermal stress leading to malignant arrhythmias remains unclear. The energy metabolism regulated by liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK) and the electrical signaling based on gap junction protein, connexin43 (Cx43), plays important roles in the development of cardiac arrhythmias. In order to investigate whether hygrothermal stress induces arrhythmias via the LKB1-AMPK-Cx43 pathway, Sprague–Dawley rats were exposed to high temperature and humidity for constructing the hygrothermal stress model. A final choice of 40 °C and 85% humidity was made by pre-exploration based on different gradient environmental conditions with reference to arrhythmia event-inducing stability and risk of sudden death. Then, the incidence of arrhythmic events, as well as the expression, phosphorylation at Ser368, and distribution of Cx43 in the myocardium, were examined. Meanwhile, the adenosine monophosphate-activated protein kinase activator, Acadesine, was also administered to investigate the role played by AMPK in the process. Our results showed that hygrothermal stress induced malignant arrhythmias such as ventricular tachycardia, ventricular fibrillation, and severe atrioventricular block. Besides, hygrothermal stress decreased the phosphorylation of Cx43 at Ser368, induced proarrhythmic redistribution of Cx43 from polar to lateral sides of the cardiomyocytes, and also caused LKB1 and phosphorylated-AMPK expression to be less abundant. While, pretreatment with Acadesine significantly actived the LKB1-AMPK-Cx43 pathway and thus ameliorated malignant arrhythmias, indicating that the hygrothermal stress-induced arrhythmias is associated with the redistribution of gap junctions in cardiomyocytes and the organism's energy metabolism.

Abstract Objective Abdominal aortic calcification (AAC) is an important marker of subclinical atherosclerosis and a predictor of cardiovascular disease. This study aims to explore the association between carotenoid intakes and AAC. Methods We included 2889 participants from the National Health and Nutrition Examination Survey (NHANES). Dietary carotenoid intakes were obtained through 24-h dietary recall interviews. Severe AAC was defined as a Kauppila score > 5. The main analysis utilizes logistic and restricted cubic spline models. Result Severe AAC was detected in 378 (13.08%) participants. In fully adjusted models, the odds ratios (OR) with 95% confidence intervals (CI) of α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein with zeaxanthin and total carotenoid intakes for individuals with severe AAC were 0.53 (0.23–0.77), 0.39 (0.19–0.80), 0.18 (0.05–0.62), 0.40 (0.20–0.78), 0.53 (0.32–0.88) and 0.38 (0.18–0.77) in the highest versus lowest quartile intake, respectively. Dose–response analyses revealed that all of the carotenoids were associated with decreased risk of severe AAC in a nonlinear trend. Total carotenoid intakes of at least 100ug/kg/day were associated with decreased odds for severe AAC. Conclusion α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein with zeaxanthin and total carotenoids were inversely associated with the risk of severe AAC in adults.

Abstract In the context of the 5G era, the rapid development of digital technology and its integration with intangible cultural heritage (ICH) can facilitate the dynamic transmission of ICH.The research purposes to construct a virtual experience platform for handmade ICH using the handmade ICH of East Hubei Province in China—Yangxin Cloth Paste as a case study through Digital Twin technology. It explores the application of digital twin technology in the field of handmade ICH transmission and aids the dynamic transmission of handmade ICH. Firstly, the research collected tangible and procedural data of the Yangxin Cloth Paste. By using photogrammetric techniques, a model of the handicraft was built and an effective digital twin conversion procedure was designed. Next, the research set up a framework for a digital twin platform for handmade ICH, designing systems for the production, display, and transaction of ICH handicrafts. Lastly, its effectiveness was validated by user satisfaction evaluation guiding subsequent optimization direction. The platform innovatively uses digital twin technology to help users visualize handicraft ICH. Through the combination of digital twin technology and virtual reality technology, it creates a realistic virtual reality experience of ICH of handicraft, stimulates users' interest in exploring ICH of handicraft, and contributes to the process protection, dissemination and development of handicraft ICH.

Highlights Digital holography can realize the in situ observation of electrode/electrolyte interface and provide dynamic evolution information of the liquid phase of electrode, which is both efficient and effective in investing the interficial electrochemical mechanism and screening electrolyte additives. Thioacetamide electrolyte additive effectively enhances the electrochemical performance of Zn anode by regulating the interficial ion flux to induce dendrite-free Zn deposition and constructing adsorption molecule layers to inhibit side reactions.

Abstract Background 18F-FDG positron emission tomography (PET) plays a crucial part in the evaluation for pediatric epileptic patients prior to therapy. Short-term scanning holds significant importance, especially for pediatrics epileptic individuals who exhibited involuntary movements. The aim was to evaluate the effects of short acquisition time on image quality and lesion detectability in pediatric epileptic patients using total-body (TB) PET/CT. A total of 25 pediatric patients who underwent TB PET/CT using uEXPLORER scanner with an 18F-FDG administered dose of 3.7 MBq/kg and an acquisition time of 600 s were retrospectively enrolled. Short acquisition times (60 s, 150 and 300 s) were simulated by truncating PET data in list mode to reduce count density. Subjective image quality was scored on a 5-point scale. Regions of interest analysis of suspected epileptogenic zones (EZs), corresponding locations contralateral to EZs, and healthy cerebellar cortex were used to compare the semi-quantitative uptake indices of short-time images and then were compared with 600 s images. The comparison of EZs detectability based on time-dependent PET images was performed. Results Our study demonstrated that a short acquisition time of 150 s is sufficient to maintain subjective image quality and lesion significance. Statistical analysis revealed no significant difference in subjective PET image quality between imaging at 300 s and 150 s (P > 0.05). The overall impression scores of image quality and lesion conspicuity in G60s were both greater than 3 (overall quality, 3.21 ± 0.46; lesion conspicuity, 4.08 ± 0.74). As acquisition time decreased, the changes of SUVmax and SD in the cerebellar cortex gradually increased (P 15% in all groups. In 26 EZs of 25 patients, the lesion detection rate was still 100% when the time was reduced to 60 s. Conclusions This study proposed that TB PET/CT acquisition time could be reduced to 60 s with acceptable lesion detectability. Furthermore, it was suggested that a 150 s acquisition time would be sufficient to achieve diagnostic performance and image quality for children with epilepsy.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells. To address this question, we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1 (ASGR1) promoted SARS-CoV-2 pseudovirus infection of HeLa cells. In Huh-7 cells, simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells, both of which barely expressed ACE2, SARS-CoV-2 pseudovirus could successfully establish an infection. However, after treatment with ASGR1 antibody or siRNA targeting ASGR1, the infection rate significantly dropped, suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism. We confirmed that ASGR1 could interact with Spike protein, which depends on receptor binding domain (RBD) and N-terminal domain (NTD). Finally, we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells. After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA, the infection efficiency of the live virus decreased significantly. Collectively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Considering the influence of process complexity, resource tension, human complexity and external influence on the buffer size, and the relay potential effect of mutual cooperation and cross-construction among processes, a calculation model of critical chain buffer size is proposed, which comprehensively considers the influencing factors of process entropy, resource entropy, human entropy, external entropy and relay potential. This model considers the local correlated complexity of processes, and uses the allowable relative deviation value of process quality characteristic target values as the standard to judge the technical complexity of processes. At the same time, it proposes a resource tension calculation that considers the efficiency of flexible resource substitution, thereby optimizing the calculation of process correlated and technical complexity, as well as the impact of resource tension on buffer size. Through example analysis, it can be concluded that in the case where the model in this article considers more factors than other comparative models, the calculated import buffer value is within the range of import buffer values calculated by other comparative models, and the project buffer and project schedule only increase by an average of about 4 days. Therefore, the model proposed in this article is used to control the buffer size reasonably and effectively reduce the project schedule risk.

With the continuous evolution of tourists' travel preferences, the traditional tourism management and service models are no longer able to satisfy modern tourists' desire for personalized and high-quality travel experiences.To address this issue, the Gansu Province Smart Tourism System has been developed.The relevant research is reviewed firstly, followed by a detailed description of the system's composition and implementation process, including the construction of the Gansu Smart Tourism Big Data Center and the design of the ＆quot;Explore Gansu with One Mobile App＆quot; comprehensive service platform.Using a layered architecture and logical framework, the system achieves the correlated mapping of tourism data and visitor behavior, along with the fusion computation of diverse data.Finally, taking examples such as the highway selfdriving traffic prediction model, the image selection model based on tourism destination impressions, and the analysis model of factors influencing sentiment in tourism reviews, the comprehensive service platform's provision of intelligent services to government, industry, and tourists is elaborated.The application results demonstrate that the system's implementation effectively enhances the quality of tourism services and visitor satisfaction in the Gansu region, further propelling the rapid development of smart tourism in Gansu.

In the field of object detection in large-scale remote sensing images, achieving a good tradeoff between model accuracy and speed has been a long-standing challenge. The majority of inference time is spent on background regions without objects, making real-time detection difficult in practical applications. Common approaches involve partitioning large-scale remote sensing images into smaller patches, followed by using additional classification networks or detectors on the final layer of the backbone's feature map to identify and filter out patches devoid of objects, ultimately enhancing detection efficiency. This article proposes a novel model, called OPD-Swin-Transformer, for ship detection in large-scale remote sensing images. This model integrates a simple and lightweight object presence detector (OPD) at each stage of the Swin-transformer and uses a step-by-step, progressively challenging strategy to filter out background image patches, achieving an overall improvement in detection speed. The model optimizes the entire network end-to-end using a multitask loss function, leading to simultaneous improvements in detection accuracy. By employing an optimal threshold generation strategy based on the weighted Youden index, the model effectively maintains a higher recall rate for ships while filtering out background images, achieving an optimal balance between speed and accuracy. Our OPD-Swin-Transformer is integrated into two mainstream detectors and evaluated on two popular benchmarks for ship detection. The experiments demonstrate that, when compared to other state-of-the-art methods, this approach increases inference speed by more than 40% while also improving detection accuracy.

Abstract Employee retention has attracted the attention of both scholars and practitioners, especially with the gradual entry of Gen Z employees into the workplace. HRM literature indicates that the employee retention research stream in the context of Gen Z employees requires further development. Based on an exploratory study, this research has identified four HRM practices influencing the retention of Gen Z employees: supportive working environment, pay, training and development, and role clarity. An empirical investigation using 529 questionnaires was used to examine the impact of these HRM practices on retaining Gen Z employees with an emphasis on the moderating role of employee gender. The findings of PLS-SEM showed that the four HRM practices have a significant effect on employee retention. The multi-group PLS analysis revealed that a supportive working environment and training and development practices are more important for female employees, whereas pay and role clarity had a salient impact on retaining male employees. Based on the empirical findings, HR managers may devise suitable intervention mechanisms to encourage the retention of Gen Z employees through maintaining a supportive work environment, providing fair and competitive pay, providing effective training and development, and clarifying job duties and responsibilities.

Abstract Background Despite an increase in parathyroid hormone (PTH) has been reported to be associated with a higher risk of hypertension and type 2 diabetes (T2D), the comprehensive evaluation of the dose-response relationship between PTH and hypertension and T2D remains ambiguous. Therefore, a dose-response meta-analysis was performed to quantitatively investigate this association. Methods PubMed, Web of Science, and Embase were systematically searched up to May 2023. Random-effect models were used to estimate the summary odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were used to model the dose-response association. Results Ten articles (including 13 studies) were identified, with a total of 11,878 cases and 51,234 participants in the meta-analysis. Of these studies, eight (five cohort and three cross-sectional) studies investigated the association of PTH with hypertension; five (two cohort and three cross-sectional) studies assessed the association of PTH with T2D. The results showed a positive relationship between PTH and the risk of hypertension (OR,1.24, 95% CI: 1.16–1.33). We found a linear association between PTH and hypertension (P non−linearity= 0.222). In the dose-response analysis, the risk of hypertension increased 5% for every 10 pg/ml increase in PTH (OR,1.05, 95% CI: 1.02–1.08). The pooled OR of T2D risk for a 10 pg/ml increase in PTH was 1.00 (95% CI: 0.98–1.02). Conclusions Elevated PTH is associated with an increased risk of hypertension. However, the evidence of the association between PTH and T2D is limited, and more well-designed studies need to be explored.

Abstract How does vision affect active touch in judgments of surface roughness? We contrasted direct (combination of visual with tactile sensory information) and indirect (vision alters the processes of active touch) effects of vision on touch. Participants judged which of 2 surfaces was rougher using their index finger to make static contact with gratings of spatial period 1580 and 1620 μm. Simultaneously, they viewed the stimulus under one of five visual conditions: No vision, Filtered vision + touch, Veridical vision + touch (where vision alone yielded roughness discrimination at chance), Congruent vision + touch, Incongruent vision + touch. Results from 32 participants showed roughness discrimination for touch with vision was better than touch alone. The visual benefit for touch was strongest in a filtered (spatially non-informative) vision condition, thus results are interpreted in terms of indirect integration. An indirect effect of vision was further indicated by a finding of visual benefit in some but not all visuo-tactile congruency conditions.

Abstract Carbapenem-resistant Escherichia coli (CREC) poses a severe global public health risk. This study reveals the worldwide geographic spreading patterns and spatiotemporal distribution characteristics of resistance genes in 7918 CREC isolates belonging to 497 sequence types (ST) and originating from 75 countries. In the last decade, there has been a transition in the prevailing STs from highly virulent ST131 and ST38 to higher antibiotic-resistant ST410 and ST167. The rise of multi-drug resistant strains of CREC carrying plasmids with extended-spectrum beta-lactamase (ESBL) resistance genes could be attributed to three important instances of host-switching events. The spread of CREC was associated with the changing trends in bla NDM-5, bla KPC-2, and bla OXA-48, as well as the plasmids IncFI, IncFII, and IncI. There were intercontinental geographic transfers of major CREC strains. Various crucial transmission hubs and patterns have been identified for ST131 in the United Kingdom, Italy, the United States, and China, ST167 in India, France, Egypt, and the United States, and ST410 in Thailand, Israel, the United Kingdom, France, and the United States. This work is valuable in managing CREC infections and preventing CREC occurrence and transmission inside healthcare settings and among diverse hosts.

Abstract Background Subclinical hypothyroidism (SCH) is highly correlated with major depressive disorder (MDD). However, the prevalence and risk factors for SCH in older patients with MDD have rarely been reported in China. Methods This cross-sectional study included 266 older MDD patients with SCH was performed. Clinical and anthropometric, biochemical, and thyroid function data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Positive and Negative Syndrome Scale positive subscale, respectively. Results Among older patients with MDD, the prevalence of SCH was 64.7% (172/266). Compared to patients without SCH, older MDD patients with SCH had a longer disease course and higher TSH, A-TG, A-TPO, HDL-C, LDL-C, TC, FPG, and systolic pressure levels (all P ≤ 0.002). Furthermore, disease progression (OR 1.082, 95% CI 1.020–1.147, P = 0.009), A-TG (OR 1.005, 95% CI 1.001–1.009, P = 0.017), TC (OR 2.024, 95% CI 1.213–3.377, P = 0.007), FPG (OR 2.916, 95% CI 1.637–5.194, P

Abstract Background The identification of biomarkers predicting the treatment response of rheumatoid arthritis (RA) is important. [68 Ga]Ga-FAPI-04 showed markedly increased uptake in the joints of patients with RA. The purpose of this study is to investigate whether [68 Ga]Ga-FAPI-04 PET/CT can be a predictor of treatment response in RA. Results Nineteen patients diagnosed with RA in the prospective cohort study were finally enrolled. Both total synovitis uptake (TSU) and metabolic synovitis volume (MSV) in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT of the responders were significantly higher than those in non-responders according to Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) response criteria at 3-months’ follow-up (P cutoff values in [68 Ga]Ga-FAPI-04 PET/CT successfully discriminated CDAI and SDAI responders and non-responders at 3-months’ follow-up. Conclusion [68 Ga]Ga-FAPI-04 uptake at baseline were significantly higher in early responders than those in non-responders. Trial registration ClinicalTrials. NCT04514614. Registered 13 August 2020, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000A4PN&selectaction=Edit&uid=U0001JRW&ts=2&cx=-x9t7cp

Vesicle-associated membrane protein (VAMP)-associated proteins (VAP27s), which are widely expressed in plants and animals, play an important role in metabolism, physiology, growth, and development, disease resistance, and immunity. While the function of this family has been elucidated in model plants like Arabidopsis thaliana and tomato, its role in grapevine remains unclear. In this present study, 12 vesicle-associated protein-membrane protein genes were identified in the grapevine genome by bioinformatics, designated as the VAP27 gene family. A phylogenetic tree, encompassing 53 genes from three model plants, Arabidopsis thaliana, Oryza sativa, and Solanum lycopersicum, revealed the subdivision of the VAP27 gene family into three subfamilies, each presumably serving different functions, besides localizing in endoplasmic reticulum, individual members also localize in nucleus. Additionally, we compared the transcriptional levels and subcellular localizations of the VvVAP27 family members across different plant tissues (flower, leaf, seed, root, fruit, tendril, and stem), indicating site-specific functionalities for different gene members. To investigate the responsiveness of the VAP27 gene family to pathogen infection, particularly Plasmopara viticola on host plants, we analyzed the expression patterns of VAP27 genes post-infection. Our findings revealed divergent expression profiles among different members at different stages of infection. The gene family responded to the infection of downy mildew on grapevine and could inhibit the spread of Phytophthora capsici lesions in Nicotiana benthamiana. These results provide an important basis for further studies delving into the functions of the VAP27 gene family in plant growth and disease resistance.

There is a close relationship between potassium (K) and nitrogen (N). However, the roles of K under high N conditions remain unclear. Using a hydroponics approach, we monitored the morphological, physiological, and molecular changes in M9T337 apple (Malus domestica) rootstocks under different nitrate (10 and 30 mmol·L−1 NO3−) and K supply (0.5, 6, 10, and 20 mmol·L−1 K+) conditions. Results revealed that high nitrate inhibited the root growth of M9T337 rootstocks, downregulated the expressions of K transporter genes (MdPT5, MdHKT1, and MdATK1), and reduced the net NO3− and K+ influx at the surface of roots, thereby resulting in an N/K imbalance in rootstocks. Further investigation showed that 10 mmol·L−1 K increased the activity of N metabolic enzymes (NR, GS, NiR, and GOGAT), upregulated the expressions of genes related to nitrate uptake and transport (MdNRT1.1, MdNRT1.2, MdNRT1.5, and MdNRT2.4), promoted 15N transport from the roots to the shoots, optimized leaf N distribution, and improved photosynthetic N utilization efficiency under high nitrate conditions. These results suggest that the negative effects of high nitrate may be related to the N/K imbalance and that reducing N/K in plants by increasing K supply level can effectively alleviate the inhibition of N assimilation by high nitrate stress.

Two broadband dual-polarized band-notched crossed dipole antennas based on the grounded coplanar waveguide (GCPW) filter for 2G/3G/4G/5G base station are proposed in this paper. Two antennas with two and three radiation nulls are displayed to demonstrate the design innovation. Firstly, a wideband crossed dipole antenna with GCPW feed structure is designed, and its coverage frequency is 1.7-3.6 GHz. Then, a compact GCPW second-order hybrid bandstop filter is designed using defected ground structure (DGS) and defected microstrip structure (DMS). The DGS-DMS filter are embedded inside the antenna radiator to achieve the stopband covering 2.9-3.1 GHz with only one dielectric substrate. At last, a miniaturized GCPW third-order DGS-DMS highly selective bandstop filter is integrated in wideband antenna to realize the stopband of 2.87-3.17 GHz. The proposed band-notched antenna uses only one substrate. Compared with the antenna using second-order filter, the antenna using third-order filter has one more radiation null, wider stopband of 2.87-3.17 GHz and higher selectivity.

The glomerular filtration barrier (GFB), composed of endothelial cells, glomerular basement membrane, and podocytes, is a unique structure for filtering blood while detaining plasma proteins according to size and charge selectivity. Structurally, the fenestrated endothelial cells, which align the capillary loops, are in close proximity to mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and are separated from the endothelial compartment by the glomerular basement membrane. Podocyte-endothelial cell communication or crosstalk is required for the development and maintenance of an efficient filtration process in physiological conditions. In pathological situations, communication also has an essential role in promoting or delaying disease progression. Podocytes and endothelial cells can secrete signaling molecules, which act as crosstalk effectors and, through binding to their target receptors, can trigger bidirectional paracrine or autocrine signal transduction. Moreover, the emerging evidence of extracellular vesicles derived from various cell types engaging in cell communication has also been reported. In this review, we summarize the principal pathways involved in the development and maintenance of the GFB and the progression of kidney disease, particularly in kidney transplantation.

Abstract Delta compression, as a complementary technique for data deduplication, has gained widespread attention in network storage systems. It can eliminate redundant data between non‐duplicate but similar chunks that cannot be identified by data deduplication. The network transmission overhead between servers and clients can be greatly reduced by using data deduplication and delta compression techniques. Resemblance detection is a technique that identifies similar chunks for post‐deduplication delta compression in network storage systems. The existing resemblance detection approaches fail to detect similar chunks with arbitrary similarity by setting a similarity threshold, which can be suboptimal. In this paper, the authors propose Chunk2vec, a resemblance detection scheme for delta compression that utilizes deep learning techniques and Approximate Nearest Neighbour Search technique to detect similar chunks with any given similarity range. Chunk2vec uses a deep neural network, Sentence‐BERT, to extract an approximate feature vector for each chunk while preserving its similarity with other chunks. The experimental results on five real‐world datasets indicate that Chunk2vec improves the accuracy of resemblance detection for delta compression and achieves higher compression ratio than the state‐of‐the‐art resemblance detection technique.

Abstract Polymeric membranes with high permeance and remarkable selectivity for simultaneous H2 purification and CO2 capture under industry-relevant conditions are absent. Herein, sub-micro pores with precise molecular sieving capability are created in ultra-thin (13–30 nm) polymer membranes via controllable transformation of amine-linked polymer (ALP) films into benzimidazole-and-amine-linked polymer (BIALP) layers. The BIALP membranes exhibit stable unprecedented H2/CO2 selectivity of 120 with a H2 permeance of 315 GPU. Furthermore, high pressure (up to 11 bar) and thermal (up to 300 °C) resistance is delivered. This work provides a concept on designing porous polymeric membranes for precise molecular discrimination.

Abstract Background We investigated the synergistic effect of stress and habitual salt preference (SP) on blood pressure (BP) in the hospitalized Omicron-infected patients. Methods From 15,185 hospitalized Omicron-infected patients who reported having high BP or hypertension, we recruited 662 patients. All patients completed an electronic questionnaire on diet and stress, and were required to complete morning BP monitoring at least three times. Results The hypertensive group (n = 309) had higher habitual SP (P = 0.015) and COVID-19 related stress (P

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Abstract Background Here we described a new threading technique for the universal fixation of any posterior chamber intraocular lens (IOL). Methods Twenty-seven eyes of 27 patients whose surgery done by Surgeon A with the needle-guided method or the suture needle retrograde threading (SNRT) method for intrascleral IOL fixation were enrolled in the first group. Thirty-four eyes of 34 patients whose surgery done by Surgeon A, Surgeon B or Surgeon C with the SNRT method for intrascleral IOL fixation were grouped into three sub-groups by surgeon. Information regarding age, sex, best-available visual acuity (BCVA), intraocular pressure (IOP), past ophthalmological history, threading time (from puncturing to externalizing suture) and complications during and after the surgery were gathered. Results The analysis showed that the threading time was less in the SNRT group than needle-guided group by Surgeon A. There was one eye with suture needle slipping from the guide needle when guiding out of the eye. The threading procedure was completed one time without suture ruptures or loop slippage in the SNRT group operated by Surgeon A. And using the SNRT method, Surgeon A, Surgeon B, and Surgeon C did not show any significant difference in threading time. No complications (e.g., vitreous hemorrhage, hyphemia, retinal detachment, suprachoroidal hemorrhage, or hypotony) were observed during surgery or postoperatively in all cases. No leakage occurred at the site of the puncture after the operation. Conclusions The described technique appears to be a safe, simple, easy-to-learn, and universal surgical method, which is suitable for various types of IOLs.

Chlorophyll contributes to tea coloration, which is an important factor in tea quality. Chlorophyll metabolism is induced by light, but the transcriptional regulation responsible for light-induced chlorophyll metabolism is largely unknown in tea leaves. Here, we characterized a chlorophyllase1 gene CsCLH1 from young tea leaves and showed it is essential for chlorophyll metabolism, using transient overexpression and silencing in tea leaves and ectopic overexpression in Arabidopsis. CsCLH1 was significantly induced by high light. The DOF protein CsDOF3, an upstream direct regulator of CsCLH1, was also identified. Acting as a nuclear-localized transcriptional factor, CsDOF3 responded for light and repressed CsCLH1 transcription and increased chlorophyll content by directly binding to the AAAG cis-element in the CsCLH1 promoter. CsDOF3 was able to physically interact with the R2R3-MYB transcription factor CsMYB308 and interfere with transcriptional activity of CsCLH1. In addition, CsMYB308 binds to the CsCLH1 promoter to enhance CsCLH1 expression and decrease chlorophyll content. CsMYB308 and CsDOF3 act as an antagonistic complex to regulate CsCLH1 transcription and chlorophyll in young leaves. Collectively, the study adds to the understanding of the transcriptional regulation of chlorophyll in tea leaves in response to light and provides a basis for improving the appearance of tea.

Abstract A large amount of pumping in the deep foundation pit will reduce the groundwater level and lead to surface cracking, building settlement, ground collapse and spring water cut-off. And the groundwater recharge is a good control measure. An integrated system of dewatering and recharge for the deep foundation pit is developed, and it is mainly composed of a pumping system, an assembled water tank, a variable frequency pressure system, a cleaning and filtering system, a recharge pressure tank, a recharge well system and a central control system. This system can realize intelligent automatic control according to the monitoring data. It does not require staff to operate on site and can be remotely adjusted by computer or mobile phone. Taking a subway station under construction in Jinan as the background, the single well recharge test and the multiple wells recharge test were carried out. It can be found that with the increase of recharge pressure, the recharge volume gradually increases, but the increasing trend is smaller and smaller. The relationship between the groundwater level and the recharge volume is a logarithmic function. Blindly increasing recharge wells may not improve the overall reinjection volume, and the relationship between the number of recharge wells, the diameter of reinjection pipes and the maximum recharge capacity of the variable frequency pressure system needs to be comprehensively considered.

Abstract Background Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT‐determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)‐determined skeletal muscle mass and quality at L1 are associated with mortality in initial‐dialysis patients. Methods This 3‐year multicentric retrospective study included initial‐dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass [by skeletal muscle index, (SMI), cm2/m2] and quality [by skeletal muscle density (SMD), HU]. Skeletal muscle measures at L1 were compared with those at L3. The sex‐specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all‐cause mortality. The outcomes were all‐cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death. Results A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P 0.05). Low L1 SMD (n = 280, 57.73%) was diagnosed based on the optimal cutoff value (

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients. SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance. One-hundred-sixty-two ALS participants dosed daily with primidone (62.5 mg) completed 24-week follow-up. A significant reduction was showed in serum levels of RIPK1 and IL-8, which were significantly higher in ALS patients than that of healthy controls (P

Abstract Background Cancer cells undergo cellular adaptation through metabolic reprogramming to sustain survival and rapid growth under various stress conditions. However, how brain tumors modulate their metabolic flexibility in the naturally serine/glycine (S/G)-deficient brain microenvironment remain unknown. Methods We used a range of primary/stem-like and established glioblastoma (GBM) cell models in vitro and in vivo. To identify the regulatory mechanisms of S/G deprivation-induced metabolic flexibility, we employed high-throughput RNA-sequencing, transcriptomic analysis, metabolic flux analysis, metabolites analysis, chromatin immunoprecipitation (ChIP), luciferase reporter, nuclear fractionation, cycloheximide-chase, and glucose consumption. The clinical significances were analyzed in the genomic database (GSE4290) and in human GBM specimens. Results The high-throughput RNA-sequencing and transcriptomic analysis demonstrate that the de novo serine synthesis pathway (SSP) and glycolysis are highly activated in GBM cells under S/G deprivation conditions. Mechanistically, S/G deprivation rapidly induces reactive oxygen species (ROS)-mediated AMP-activated protein kinase (AMPK) activation and AMPK-dependent hypoxia-inducible factor (HIF)-1α stabilization and transactivation. Activated HIF-1α in turn promotes the expression of SSP enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). In addition, the HIF-1α-induced expression of glycolytic genes (GLUT1, GLUT3, HK2, and PFKFB2) promotes glucose uptake, glycolysis, and glycolytic flux to fuel SSP, leading to elevated de novo serine and glycine biosynthesis, NADPH/NADP+ ratio, and the proliferation and survival of GBM cells. Analyses of human GBM specimens reveal that the levels of overexpressed PHGDH, PSAT1, and PSPH are positively correlated with levels of AMPK T172 phosphorylation and HIF-1α expression and the poor prognosis of GBM patients. Conclusion Our findings reveal that metabolic stress-enhanced glucose-derived de novo serine biosynthesis is a critical metabolic feature of GBM cells, and highlight the potential to target SSP for treating human GBM.

Abstract This meta‐analysis evaluated the potential association of a simultaneously measured inter‐arm systolic blood pressure difference (IASBPD) and all‐cause mortality and cardiovascular mortality. The Medline, Cochrane Library, Embase, and PubMed databases were searched through to April 14, 2023 for relevant literature. The outcomes were the associations of IASBPD with all‐cause and cardiovascular mortality. Finally, 10 cohort studies that included 15 320 individuals were included. An IASBPD of ≥15 mm Hg was associated with increased all‐cause mortality (pooled hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.02–1.61) but an IASBPD of ≥10 mm Hg was not (pooled HR 1.28, 95% CI 0.89–1.85). The pooled HR for cardiovascular mortality was 1.88 (95% CI 1.31–2.71) for an IASBPD of ≥10 mm Hg and 1.93 (95% CI 1.24–2.99) for an IASBPD of ≥15 mm Hg. Subgroup analysis showed that younger patients (HR 9.03, 95% CI 2.00–40.82, p = .004) with an IASBPD ≥15 mm Hg were at higher risk of cardiovascular mortality than older patients (HR 1.67, 95% CI 1.06–2.64, p = .03); the difference between groups was statistically significant (p = .04). In conclusions, our findings show that a simultaneously measured IASBPD ≥15 mm Hg predicts increased all‐cause mortality and an IASBPD of ≥15 mm Hg or ≥10 mm Hg predicts increased cardiovascular mortality. An IASBPD ≥15 mm Hg appears to be more correlated with cardiovascular mortality in younger patients than in older patients.

Abstract The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.

Using quinoa and oat bran as the primary raw materials, this study applied extrusion technology to create a quinoa compound powder, and the nutritional evaluation of the powder was carried out. A one-factor test was used to establish the process parameters. The optimal production process for quinoa blended powder was determined using an orthogonal test with the following parameters: 18% material moisture content, 130℃ extrusion temperature, 280 r/min screw speed, and 20 kg/h feeding speed. The compound powder produced under these conditions had a pleasant flavor and blended well, earning a sensory score of 92.5. The quality of quinoa flour was determined utilizing the nutritional quality index. The results indicated that the ratio of macronutrients to energy supply in quinoa flour was reasonable. Besides calcium, six mineral elements and four vitamins had INQ values greater than 1. With an AI value of 0.1489 and a TI value of 0.243, quinoa compound flour's fatty acids ratio was reasonable and rich in unsaturated fatty acids. Thus, quinoa compound powder is a high-protein, high-dietary-fiber, nutritionally-balanced food.

Community is the vanguard of urban resilience construction, the vanguard of disaster risk reduction and guiding the priority of work. Community residents are the direct victims and main responders of disaster risks. The smooth implementation of community earthquake prevention and disaster reduction work is an important component of the modern earthquake prevention and disaster reduction governance system. However, there are still many difficulties in carrying out community earthquake prevention and disaster reduction. Based on the current situation of earthquake prevention and disaster reduction in a community in Jiaxing, a system construction framework for community earthquake prevention and disaster reduction work is proposed for the eastern region, so as to prevent earthquake disaster in a planned and prepared manner, and avoid and reduce the harm that earthquake may bring to the community to the greatest extent, help community workers and residents to improve their awareness of the risk of earthquake disaster, cultivate community emergency culture for earthquake disaster, and promote the stability and development of communities under their jurisdiction.

AbstractContext Dolichos trilobus Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism.Objective To explore the therapeutic potential of doliroside B (DB) from D. trilobus and its disodium salt (DBDS) and the underlying mechanism in pain.Materials and methods In the writhing test, Kunming mice were orally treated with DB and DBDS at doses of 0.31, 0.62, 1.25, 2.5, and 5 mg/kg. Vehicle, morphine, indomethacin, and acetylsalicylic acid were used as negative and positive control on the nociception-induced models, respectively. In the hot plate test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the formalin test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the meanwhile, lipopolysaccharide-induced inflammatory model in RAW264.7 macrophages was adopted to study the mechanism of pain alleviation for DBDS.Results DBDS (5 mg/kg) inhibited the writhing number by 80.2%, which exhibited the highest antinociceptive activity in pain models. DBDS could selectively inhibite the activity of COX-1. Meanwhile, it also reduced the production of NO, iNOS, and IL-6 by 55.8%, 69.0%, and 49.9% inhibition, respectively. It was found that DBDS also positively modulated the function of GABAA1 receptor.Discussion and conclusions DBDS displayed antinociceptive activity by acting on both the peripheral and central nervous systems, which may act on multitargets. Further work is warranted for developing DBDS into a potential drug for the treatment of pain.

The environmental control of layer houses with multi-tiered cage systems is influenced by factors such as the structure of the henhouses and the heat dissipation of the flock, leading to low precision and large fluctuations in temperature control. Based on a new combined positive- and negative-pressure ventilation (CPNPV) mode, a dynamic temperature model is constructed. Additionally, a temperature control method for a layer house is designed using a variable universe fuzzy PID control algorithm (VFPID). First, based on the principles of energy and mass balance, and by decoupling the relationship between positive- and negative-pressure ventilation volumes, a dynamic temperature model for layer houses under CPNPV was established. Then, the PID parameters and the proportional relationship between positive- and negative-pressure ventilation were optimized through fuzzy rules, and a proportional exponential function was introduced to adjust the scaling of the universe, enabling fine-tuned control. Finally, a temperature control model for the layer house was built using Simulink. The results show that the coefficients of determination (R2) of the constructed dynamic temperature models are between 0.79 and 0.88, respectively, indicating high accuracy. The designed VFPID method outperformed traditional on–off control and improved control precision by 20–23.53% and 10.34–22.22% compared with PID control and fuzzy PID(FPID) control methods, respectively. This study provides new insights for the development of environmental control equipment and precise environmental regulation of layer houses.

With the rapid development of intelligent transportation systems and information technology, the security of road traffic signal systems has increasingly attracted the attention of managers and researchers. This paper proposes a new method for detecting attacks on traffic signal systems based on game theory and Generative Adversarial Networks (GAN). First, a game theory model was used to analyze the strategic game between the attacker and the defender, revealing the diversity and complexity of potential attacks. A Bayesian game model was employed to calculate and analyze the attacker’s choice of position. Then, leveraging the advantages of GAN, an adversarial training framework was designed. This framework can effectively generate attack samples and enhance the robustness of the detection model. Using empirical research, we simulated the mapping of real traffic data, road network data, and network attack data into a simulation environment to validate the effectiveness of this method. In a comparative experiment, we contrasted the method proposed in this paper with the traditional Support Vector Machine (SVM) algorithm, demonstrating that the model presented here can achieve efficient detection and recognition across various attack scenarios, with significantly better recall and F1 scores compared to traditional methods. Finally, this paper also discusses the application prospects of this method and its potential value in future intelligent transportation systems.

Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.

The interruption of transportation on the way to Tibet has brought great losses to the Tibetan region. The work proposed a model that integrated the entropy weight-TOPSIS method with the fuzzy C-means clustering algorithm to discuss the causes and characteristics of traffic interruptions on the four main highways to Tibet. This approach aimed to quantify and grade traffic interruption states. First, the entropy weight-TOPSIS method was used to mitigate dimensions among various indices and quantitatively evaluate the status values of traffic interruptions. Then, the fuzzy C-means clustering algorithm was employed to grade these values. The proposed model graded traffic interruption states into four levels by evaluating the duration, mileage, and severity of traffic interruptions. Moreover, the four-level classification scheme can reflect the severity of traffic blocking events more precisely while maintaining a lower PE (Partition Entropy) value. In the four-level classification, the Sichuan–Tibet Highway and Xinjiang–Tibet Highway experienced more level-3 and level-4 serious interruptions, while most high-level interruptions on the Qinghai–Tibet Highway were classified as level-2 ordinary interruptions. The Yunnan–Tibet Highway, with limited data and primarily level-1 classification, was not analyzed in detail. These findings provide a reference for highway management departments to formulate targeted maintenance and emergency measures, especially the Sichuan–Tibet highway, which needs more attention and resource investment to improve its disaster resistance and reduce the impact of traffic interruptions.

Curcumin is widely recognized for its diverse antitumor properties, ranging from breast cancer to many other types of cancers. However, its role in the tumor microenvironment remains to be elucidated. In this study, we established a 3D tumor spheroids model that can simulate the growth environment of tumor cells and visualized the antitumor metabolic alteration caused by curcumin using mass spectrometry imaging technology. Our results showed that curcumin not only exerts a profound impact on the growth and proliferation of breast cancer cells but in situ multivariate statistical analysis also reveals the significant effect on the overall metabolic profile of tumor spheroids. Meanwhile, our visualization map characterized curcumin metabolic processes of reduction and glucuronidation in tumor spheroids. More importantly, abnormal metabolic pathways related to lipid metabolism and polyamine metabolism were also remodeled at the metabolite and gene levels after curcumin intervention. These insights deepen our comprehension of the regulatory mechanism of curcumin on the tumor metabolic network, furnishing powerful references for antitumor treatment.

High-pressure processing (HPP) technology can significantly improve the texture and flavor of Mercenaria mercenaria. This study aimed to investigate the effect of HPP treatment with varying levels of pressure (100, 200, 300, 400, 500, and 600 MPa) and a holding time of 8 min at 20 °C on the physicochemical properties and volatile flavors of M. mercenaria. The significant changes in hardness, resilience, and water holding capacity occurred with increasing pressure (p < 0.05), resulting in improved meat quality. Scanning electron microscopy (SEM) was utilized to observe the decomposition of muscle fibers in M. mercenaria due to varying pressures, which explains the differences in texture of M. mercenaria. Different pressure treatments also had an influence on the volatile flavor of M. mercenaria, and the quantities of low-molecular-weight aldehydes (hexanal, heptanal, and nonanal) with a fishy taste decreased dramatically following 400 and 500 MPa HPP treatments. Furthermore, the level of 2-Methylbutyraldehyde, which is related to sweetness, increased significantly following 400 MPa HPP treatment. The study found that 400 MPa HPP treatment resulted in minor nutrient losses and enhanced sensory quality. The results of this study provide a theoretical basis for the application of HPP treatment to M. mercenaria.

A nanoliter liquid chromatography–high resolution mass spectrometry-based method was developed for quantitative proteomics analysis of COVID-19 vaccines. It can be used for simultaneous qualitative and quantitative analysis of target proteins and host cell proteins (HCPs) in vaccine samples. This approach can directly provide protein information at the molecular level. Based on this, the proteomes of 15 batches of COVID-19 inactivated vaccine samples from two companies and 12 batches of COVID-19 recombinant protein vaccine samples from one company were successfully analyzed, which provided a significant amount of valuable information. Samples produced in different batches or by different companies can be systematically contrasted in this way, offering powerful supplements for existing quality standards. This strategy paves the way for profiling proteomics in complex samples and provides a novel perspective on the quality evaluation of bio-macromolecular drugs.