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Background and objective Neoantigen reactive T cell (NRT) has the ability to inhibit the growth of tumors expressing specific neoantigens. However, due to the difficult immune infiltration and the inhibition of tumor microenvironment, the therapeutic effect of NRT in solid tumors is limited. In this study, we designed NRT cells (7×19 NRT) that can express both interleukin-7 (IL-7) and chemokine C-C motif ligand 19 (CCL19) in mouse lung cancer cells, and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells. Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma (LLC), prepared RNA vaccine, cultured NRT cells, constructed retroviral vectors encoding IL-7 and CCL19, transduced NRT cells and IL-7 and CCL19 were successfully expressed, and 7×19 NRT was successfully obtained. The anti-tumor effect was evaluated in vivo and in vitro in mice. Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19, achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice. The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment. In addition, both 7×19 NRT treatment and conventional NRT treatment were safe. Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19, which is a safe and effective genetic modification of NRT.

Abstract The regional industry network (RIN) is a type of financial network derived from industry networks that possess the capability to describe the connections between specific industries within a particular region. For most investors and financial analysts lacking extensive experience, the decision-support information provided by industry networks may be too vague. Conversely, RINs express more detailed and specific industry connections both within and outside the region. As RIN analysis is domain-specific and current financial network analysis tools are designed for generalized analytical tasks and cannot be directly applied to RINs, new visual analysis approaches are needed to enhance information exploration efficiency. In this study, we collaborated with domain experts and proposed V4RIN, an interactive visualization analysis system that integrates predefined domain knowledge and data processing methods to support users in uploading custom data. Through multiple views in the system panel, users can comprehensively explore the structure, geographical distribution, and spatiotemporal variations of the RIN. Two case studies were conducted and a set of expert interviews with five domain experts to validate the usability and reliability of our system.

Abstract Background Exploring novel biomarkers for gastric cancer holds promise for enhancing patients’ therapy and survival rates. lncRNAs and miRNAs have emerged as important biomarkers for various human cancers. However, the role of lncRNA RMST (RMST) in gastric cancer development and the mechanism underlying its function remains unclear. Results Significant upregulation of RMST was observed in gastric cancer tumor tissues. RMST levels showed strong correlation with patients’ lymph node metastasis and TNM stage and serving as a predictor of adverse prognosis RMST negatively regulated miR-204-5p, which in turn mediated the inhibitory effects of RMST knockdown on gastric cancer cell growth and metastasis. Conclusion RMST served as both a prognostic biomarker and tumor promoter by modulating miR-204-5p. Inhibiting RMST could represent a novel and potential therapeutic strategy for gastric cancer.

Abstract To assess the anatomy of the inferior mesenteric artery (IMA) and its branches by reviewing laparoscopic left-sided colorectal cancer surgery videos and comparing them with preoperative three-dimensional computed tomography (3D-CT) angiography, to verify the accuracy of 3D-CT vascular reconstruction techniques. High-definition surgical videos and preoperative imaging data of 200 patients who underwent laparoscopic left-sided colorectal cancer surgery were analysed, and the alignment of the IMA and its branches in relation to the inferior mesenteric vein (IMV) was observed and summarized. The above two methods were used to measure the length of the IMA and its branches. Of 200 patients, 47.0% had the sigmoid arteries (SAs) arise from the common trunk with the superior rectal artery (SRA), and 30.5% had the SAs arise from the common trunk with the left colic artery (LCA). In 3.5% of patients, the SAs arising from both the LCA and SRA. The LCA, SA, and SRA emanated from the same point in 13.5% of patients, and the LCA was absent in 5.5% of patients. The range of D cm (IMA length measured by intraoperative silk thread) and d cm (IMA length measured by 3D-CT vascular reconstruction) in all cases was 1.84–6.62 cm and 1.85–6.52 cm, respectively, and there was a significant difference between them. (p

Abstract Background Inflammation is a part of tumours, and inflammatory cells can affect the proliferation, invasion, and development of tumour cells. An increasing number of peripheral blood inflammatory markers have been found to play very important roles in the treatment and prognosis of cancer patients. The systemic inflammatory response index (SIRI) is a newer inflammatory marker, and its role in colorectal cancer, especially in locally advanced rectal cancer, is still unclear. Methods From 2015 to 2020, 198 patients with locally advanced rectal cancer (LARC) who underwent surgery following neoadjuvant chemoradiotherapy (Neo-CRT) were analysed. Patients were categorized into good- and poor- response groups according to their pathological results, and clinical characteristics and baseline parameters were compared between the two groups. The optimal cutoff values for inflammatory indicators were determined using receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using the Cox proportional hazard model. Survival analysis was performed via the Kaplan‒Meier method. Results After patients were grouped into good and poor response groups, indicator differences were found in CEA, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and SIRI. According to the ROC analysis, the NLR (P = 0.015), SII (P = 0.001), and SIRI (P = 0.029) were significant prognostic factors. After univariate and multivariate analyses of the Cox proportional hazards regression model, only the SIRI was found to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Finally, Kaplan‒Meier survival curves also confirmed the ability of the SIRI to predict survival. Conclusion The preoperative SIRI can be used to predict the response to Neo-CRT in LARC patients and is an independent predictor of OS and DFS in postoperative patients. A high SIRI was associated with poor radiotherapy response and predicted poor OS and DFS.

Abstract Objectives Soybean is an important feed and oil crop in the world due to its high protein and oil content. China has a collection of more than 43,000 soybean germplasm resources, which provides a rich genetic diversity for soybean breeding. However, the rich genetic diversity poses great challenges to the genetic improvement of soybean. This study reports on the de novo genome assembly of HJ117, a soybean variety with high protein content of 52.99%. These data will prove to be valuable resources for further soybean quality improvement research, and will aid in the elucidation of regulatory mechanisms underlying soybean protein content. Data description We generated a contiguous reference genome of 1041.94 Mb for HJ117 using a combination of Illumina short reads (23.38 Gb) and PacBio long reads (25.58 Gb), with high-quality sequence coverage of approximately 22.44× and 24.55×, respectively. HJ117 was developed through backcross breeding, using Jidou 12 as the recurrent parent and Chamoshidou as the donor parent. The assembly was further assisted by 114.5 Gb Hi-C data (109.9×), resulting in a contig N50 of 19.32 Mb and scaffold N50 of 51.43 Mb. Notably, Core Eukaryotic Genes Mapping Approach (CEGMA) assessment and Benchmarking Universal Single-Copy Orthologs (BUSCO) assessment results indicated that most core eukaryotic genes (97.18%) and genes in the BUSCO dataset (99.4%) were identified, and 96.44% of the genomic sequences were anchored onto twenty pseudochromosomes.

Abstract Wireless and battery-free radio-frequency (RF) sensors can be used to create physical spaces that ambiently sense and respond to human activities. Making such sensors ultra-flexible and transparent is important to preserve the aesthetics of living environments, accommodate daily activities, and functionally integrate with objects. However, existing RF sensors are unable to simultaneously achieve high transparency, flexibility, and the electrical conductivity required for remote room-scale operation. Here, we report 4.5 µm RF tag sensors achieving transparency exceeding 90% that provide capabilities in room-scale ambient wireless sensing. We develop a laser-assisted water-based adhesion-reversion process to digitally realize computer-aided RF design at scale. By individually tagging multiple objects and regions of the human body, we demonstrate multiplexed wireless tracking of human-environment interactions and physiological signals at a range of up to 8 m. These radio-frequency identification sensors open opportunities for non-intrusive wireless sensing of daily living spaces for applications in health monitoring and elderly care.

Fish protein hydrolysates (FPH) were applied in a 8-week feeding experiment with juvenile common carp (Cyprinus carpio) (initial body weight 8.75±0.05 g), to preliminarily investigate their effects on growth performance and feed utilization and potential influence on intestinal antioxidant status, expressions of protein synthesis gene and microflora. Common carp were fed with 0%, 0.5%, 1%, 1.5%, and 2% FPH (named as FPH-0, FPH-0.5, FPH-1, FPH-1.5, and FPH-2) respectively, substituting 0%, 13.33%, 28.33%, 41.66%, and 55.00% of dietary fish meal. Each diet was randomly fed to triplicate groups of 25 fish per aquarium. Feeding experimental results revealed that final body weight, weight gain rate and protein efficiency ratio in the FPH-0.5 treatment were significant higher than those in other treatments. The FPH-0.5 treatment had highest crude protein level when compared to the FPH-1.5 and FPH-2 treatments (P

Diploid rainbow trout gonadal development occurs at the expense of stored energy and nutrients, lipid mobilization supplies energy required for this process. However, triploid rainbow trout gonads are not developed, the lipid and fatty acid metabolism might be different. However, which metabolic pathways and key metabolites regulate fatty acid metabolism have not been clarified. To identify the metabolism difference between diploid and triploid rainbow trout, we use the LC-MS technology based metabolomics to detect the metabolites in positive and negative ion mode. As far as it was evaluated, there are 174 metabolites with statistically significant differences, including 13 lipids and lipid-like molecules. Among the different metabolites, linoleic acid (LA), oleic acid (OA) and arachidonic acid (ARA) were related to the biosynthesis of unsaturated fatty acids, LA and OA were related to linoleic acid metabolism. The two metabolic pathways related to Polyunsaturated fatty acid (PUFA) metabolism might be associated with the differences in PUFA contents in diploid and triploid rainbow trout serum. Gene expression results validated that and pointed that the desaturation process maybe more crucial process in the differential metabolic pathways between diploid and triploid rainbow trout. The study provide a theoretical explanation for PUFA metabolism differences between diploid and triploid rainbow trout, identify the crucial metabolites as biomarkers to differentiate the metabolic mechanisms of PUFA metabolism in rainbow trout.

The Amur grayling (Thymallus arcticus grubei Dybowski, 1869), a species of potentially economic and research value, is renowned for its tender meat, exquisite flavor, and high nutritional contents. This study was conducted to investigate the physiological adaptation mechanisms to dietary lipids in Amur grayling fry (with average initial weight 4.64±0.03 g). This study involved a 56-day feeding trial with diets containing varying lipid levels (9.07%, 12.17%, 15.26%, 18.09%, 21.16%, and 24.07%, designated as GL1 through GL6, respectively) to explore the impact of dietary lipids on growth performance, intestinal digestion, liver antioxidative function, and transcriptomic profiles. Results showed that The group receiving 18% dietary lipid exhibited a markedly higher weight gain rate (WGR) and specific growth rate compared to other groups, alongside a reduced feed conversion ratio (FCR), except in comparison to the 15% lipid group. Activities of lipase in pancreatic secretion and amylase in stomach mucosa peaked in the 18% lipid treatment group, indicating enhanced digestive efficiency. The liver of fish in this group also showed increased activities of antioxidative enzymes and higher levels of glutathione and total antioxidative capacity, along with reduced malondialdehyde content compared to the 9% and 24% lipid treatments. Additionally, serum high-density lipoprotein cholesterol levels were highest in the 18% group. Transcriptomic analysis revealed four significant metabolic pathways affected: Cholesterol metabolism, Fat digestion and absorption, PPAR signaling, and Fatty acid degradation, involving key genes such as Lipase, Lipoprotein lipase, Fatty acid-binding protein, and Carnitine palmitoyltransferase I. These findings suggest that the liver of Amur grayling employs adaptive mechanisms to manage excessive dietary lipids. Quadratic regression analysis determined the optimal dietary lipid levels to be 16.62% and 16.52%, based on WGR and FCR, respectively. The optimal dietary lipid level for juvenile Amur grayling appears to be around 18%, as evidenced by improved growth performance, digestive function, balanced serum lipid profile, and enhanced liver antioxidative capacity. Exceeding this lipid threshold triggers both adaptive and potentially detrimental liver responses.

Use of high-concentrate carbohydrate in fish diets will bring negative influence on the growth and glycometabolism. The current research, with common carp, was designed to investigate the efficiency of alternate feeding between high- and low- carbohydrate based diets in weakening these negative effects. Two control groups were, respectively, fed to the low carbohydrate diets (LC group, 100 g/kg cassava starch) and the high carbohydrate diets (HC group, 400 g/kg cassava starch) for 56 d, meanwhile other groups were subjected to every 1 d, 7 d, 14 d and 28 d alternation between the HC and LC diets, respectively (referred as R1, R7, R14 and R28). All experimental diets were fed to triplicate groups of 30 common carp (initial weight 1.17 ± 0.03 g). All four alternate groups achieved optimal growth and feed efficiency compared to the HC group. The R14 group possessed significantly higher weight growth rate, protein efficiency ratio, specific growth rate, intestinal index and condition factor, and significantly lower feed conversion ratio compared to the HC group. Fish in that group had higher protein content in whole body, higher expressions of growth hormone and insulin-like growth factor 1 in hepatopancreas and elevated intestinal activities of trypsin, amylase and alkaline phosphatase. Relative expressions of rapamycin, phosphatidylinositol 3-kinase, protein kinase B, Forkhead frame protein 1 A/1B, hexokinase, pyruvate kinase, glucokinase, phosphofructokinase, glucose transporter 2, glucose transporter 4, and sodium glucose cotransporter were also enhanced in the R14 group compared to HC group. Additionally, there was no difference in growth parameters between the LC group and four alternate groups. Alternate feeding between different carbohydrate level diets could enhance the growth, improve the digestive capacity and strengthen the glycometabolism to heighten the utilization ability of fish to high-carbohydrate diets, but this alternate cycle should be within reasonable limits. Briefly, it was concluded that the alternate cycle of 14 d was best.

With the rapid development and construction of urban subways, various risks associated with human health and wellbeing within subway microenvironments have seriously increased. However, only a few intelligent systems have been validated as suitable for facilitating the management of subway environments. Field tests can be time-consuming and inefficient, and questionnaires often lack true intuitiveness for participants. Therefore, to enhance subway environment management, this study proposed intelligent systems that integrate building information modeling (BIM) and virtual reality (VR) for managing health risks in urban subway microenvironments. The systems were developed using Revit 2021, Navisworks 2020, Unity 2019, MYSQL 8.0, and Visual Studio 2019. Additionally, they were applied in scenarios for environmental assessment and passenger coping capability enhancement, differentiated into an expert visual-based health risk assessment system and a gamified simulation system for passenger risk prevention. The feasibility of the approach was validated with the case of Xinzhuang subway station of Line 3 in Nanjing, China. The findings revealed that the assessment system enabled experts to have a better and straight understanding of subway microenvironmental health risks and the gamification simulation system significantly enhanced the passengers’ coping capacity. The integration of BIM and VR, with its design features such as visibility, optimization, and simulation, compensated for BIM’s lack of providing an immersive experience for systems. The intelligent systems introduced in this study present novel models for environmental assessment and passenger training, catering to both subway operators and researchers. The innovative systems serve as a cornerstone in guaranteeing the health and safety of public transportation operations.

In this work, microstructural characteristics, dynamic recrystallization and mechanical properties of the hot-rolled AZ31B were investigated. The results indicated that the different mechanisms of recrystallization are responsible for the microstructural evolution during the rolling deformation. It was found, as for the specimens with the rolling reduction of 30%, large number of twins are formed within the deformed matrix and the recrystallized grains are usually formed nearby the twins. This indicated that the mechanism of the twin-induced nucleation mainly dominates the recrystallization process of the specimens with the 30% reduction. As for the specimens with the rolling reduction of 75%, the recrystallized grains are nucleated on the bulged boundaries or within the deformed grains. This indicates that the mechanisms of the stress-induced grain boundary migration (SIBM) and the sub-grain growth mainly dominate the recrystallization process of the specimens with the reduction of 75%. The recrystallization process contributes to the grain refinement and to the improvement of mechanical properties of alloys. Eventually, the specimens with the rolling reduction of 75% obtain an excellent strength-ductility balance. The results of this work not only elaborate underlying knowledge on the correlation relationship between the recrystallization mechanisms and the mechanical properties, but provide an effective approach to optimize the microstructure-mechanical properties of alloys.

Genomic selection (GS) is a marker-based selection method used to improve the genetic gain of quantitative traits in plant breeding. A large number of breeding datasets are available in the soybean database, and the application of these public datasets in GS will improve breeding efficiency and reduce time and cost. However, the most important problem to be solved is how to improve the ability of across-population prediction. The objectives of this study were to perform genomic prediction (GP) and estimate the prediction ability (PA) for seed oil and protein contents in soybean using available public datasets to predict breeding populations in current, ongoing breeding programs. In this study, six public datasets of USDA GRIN soybean germplasm accessions with available phenotypic data of seed oil and protein contents from different experimental populations and their genotypic data of single-nucleotide polymorphisms (SNPs) were used to perform GP and to predict a bi-parent-derived breeding population in our experiment. The average PA was 0.55 and 0.50 for seed oil and protein contents within the bi-parents population according to the within-population prediction; and 0.45 for oil and 0.39 for protein content when the six USDA populations were combined and employed as training sets to predict the bi-parent-derived population. The results showed that four USDA-cultivated populations can be used as a training set individually or combined to predict oil and protein contents in GS when using 800 or more USDA germplasm accessions as a training set. The smaller the genetic distance between training population and testing population, the higher the PA. The PA increased as the population size increased. In across-population prediction, no significant difference was observed in PA for oil and protein content among different models. The PA increased as the SNP number increased until a marker set consisted of 10,000 SNPs. This study provides reasonable suggestions and methods for breeders to utilize public datasets for GS. It will aid breeders in developing GS-assisted breeding strategies to develop elite soybean cultivars with high oil and protein contents.

The application of cottonseed protein concentrate (CPC) is an effective strategy to moderate the shortage of fish meal (FM) for the aquafeed industry. However, little attention has been paid to the effects of replacing fishmeal with CPC on cyprinid fish. This study used common carp (Cyprinus carpio) as the biological model and assessed the potential of applying CPC as a substitute for fishmeal in the diet of common carp. The proportion of fish meal substituted with CPC in the six diets was 0% (CPC0), 25% (CPC25), 50% (CPC50), 75% (CPC75), and 100% (CPC100). Each diet was fed to three replicate groups of common carp (4.17 ± 0.02 g) for 56 days. Results revealed that the CPC50 group significantly increased the growth indexes via up-regulating the genes of the GH/IGF axis and the TOR pathway. The intestinal digestive ability was also elevated in the CPC50 group via markedly increasing intestinal villus height, protease and lipase activities in the whole intestine, and the amylase activity of the foregut and midgut. The CPC50 group captured significantly higher activities and gene expressions of antioxidant enzymes and lower malonaldehyde contents via evoking the Nrf2/Keap1 signal pathway. The CPC50 group enhance the intestinal mechanical barrier via up-regulating the gene expressions of tight junction proteins and heighten the intestinal biological barrier by increasing the probiotics (Lactococcus) and decreasing the harmful bacteria (Enterococcus). But excessive substitution levels (75% and 100%) would compromise growth performance, intestinal antioxidant capacity, and immune function. The optimum substitution level was estimated to be 46.47%, 47.72%, and 46.43% using broken-line regression analyses based on mass gain rate, protein efficiency ratio, and feed conversion rate. Overall, the fishmeal in common carp feed could be substituted up to 50% by CPC without negative influence on growth, feed utilization, and or intestinal health.

The effectiveness of soybean meal (SBM) substitution with fermented peanut meal (FPM) were appraised in common carp juveniles. A diet containing 30 % SBM was perceived as the control diet, then 25 %, 50 %, 75 % and 100 % of SBM was replaced by the FPM (FPM0, FPM25, FPM50, FPM75, FPM100 groups). Each group was fed to three replicate groups of common carp (4.83 ± 0.02 g) for 56 days. Results exhibited that FPM50 group attained the significantly higher mass gain rate and specific growth rate than those of the other groups except for FPM25, higher protein efficiency ratio and lower feed conversion rate than those of the FPM75 and FPM100 groups. The FPM50 group significantly increased the contents of serum total protein and albumin and decreased the content of serum urea nitrogen. The activity of hindgut protease was significantly enhanced in the FPM50 group. Significantly higher and lower intestinal villi height was, respectively, observed in the FPM50 and FPM100 group. The FPM50 group significantly enhanced the gene expression and activities of antioxidant enzymes in the intestine, reversely decreased the content of malonaldehyde. Significant increments in the occludin, myosin light chain kinase and claudin3 gene expressions in the FPM50 group improved the increase of intestinal permeability induced by pro-inflammatory factor related genes interleukin 1β, interleukin 6 and tumor necrosis factor α. Staphylococcus and Enterococcus in the intestine abundances were effectively suppressed in the FPM50 group, and Lactococcus became the dominant intestinal bacteria genera. The optimum substitution level was estimated to be 50.93 % and 49.89 % using broken-line regression analyses based on MGR and FCR. Overall, the soybean meal in common carp feed could be substituted up to 50 % by FBM without negative influence on growth, feed utilization and intestinal health.

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

BackgroundVessels encapsulating tumor clusters (VETC) have been considered an important cause of hepatocellular carcinoma (HCC) metastasis.PurposeTo compare the potential of various diffusion parameters derived from the monoexponential model and four non-Gaussian models (DKI, SEM, FROC, and CTRW) in preoperatively predicting the VETC of HCC.Methods86 HCC patients (40 VETC-positive and 46 VETC-negative) were prospectively enrolled. Diffusion-weighted images were acquired using six b-values (range from 0 to 3000 s/mm2). Various diffusion parameters derived from diffusion kurtosis (DK), stretched-exponential (SE), fractional-order calculus (FROC), and continuous-time random walk (CTRW) models, together with the conventional apparent diffusion coefficient (ADC) derived from the monoexponential model were calculated. All parameters were compared between VETC-positive and VETC-negative groups using an independent sample t-test or Mann-Whitney U test, and then the parameters with significant differences between the two groups were combined to establish a predictive model by binary logistic regression. Receiver operating characteristic (ROC) analyses were used to assess diagnostic performance.ResultsAmong all studied diffusion parameters, only DKI_K and CTRW_α significantly differed between groups (P=0.002 and 0.004, respectively). For predicting the presence of VETC in HCC patients, the combination of DKI_K and CTRW_α had the larger area under the ROC curve (AUC) than the two parameters individually (AUC=0.747 vs. 0.678 and 0.672, respectively).ConclusionDKI_K and CTRW_α outperformed traditional ADC for predicting the VETC of HCC.

Abstract Molecularly-targeted agents are still urgently needed for better non-small cell lung cancer (NSCLC) therapy. CC-115 is a potent DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) dual blocker. We evaluated its activity in different human NSCLC cells. In various primary human NSCLC cells and A549 cells, CC-115 potently inhibited viability, cell proliferation, cell cycle progression, and hindered cell migration/invasion. Apoptosis was provoked in CC-115-stimulated NSCLC cells. The dual inhibitor, however, was unable to induce significant cytotoxic and pro-apoptotic activity in the lung epithelial cells. In primary NSCLC cells, CC-115 blocked activation of mTORC1/2 and DNA-PK. Yet, CC-115-induced primary NSCLC cell death was more potent than combined inhibition of DNA-PK plus mTOR. Further studies found that CC-115 provoked robust oxidative injury in primary NSCLC cells, which appeared independent of mTOR-DNA-PK dual blockage. In vivo studies showed that CC-115 oral administration in nude mice remarkably suppressed primary NSCLC cell xenograft growth. In CC-115-treated NSCLC xenograft tissues, mTOR-DNA-PK dual inhibition and oxidative injury were detected. Together, CC-115 potently inhibits NSCLC cell growth.

Existing wetting theories have difficulty accurately describing advancing/receding processes on micro-structured surfaces. A strategy is proposed to solve this problem by recognizing it as a liquid–vapor interface geometrical question. The wetting chip method is proposed to realize the microscopic observation of liquid–vapor interface variations. A wetting model based on the liquid–vapor interface shape (LVIS model) is established to describe the analytical relationships between the apparent contact angles, liquid–vapor interface radius, substrate geometry, and chemical nature of liquid. The LVIS model is divided into four typical time points and three transition stages, and its predictions agree with the experimental measurements. In contrast to traditional theories, the apparent contact angles in a quasi-equilibrium state should be separated into advancing and receding processes, and in this state, apparent contact angles vary with changes in the parameters of micro-pillar width and spacing. This strategy has the potential to accurately describe the wetting process on micro-structure surfaces.

Spectral sensing is an emerging field driven by the need for fast and non-invasive methods for the chemical analysis of materials in agri-food, healthcare, and industrial applications. We demonstrate a near-infrared spectral sensor, based on a scalable fabrication process and combining high responsivity, narrow linewidth, and low noise. The sensor consists of 16 resonant-cavity-enhanced photodetectors, each showing a unique spectral response consisting of narrow peaks. The spectral sensor thereby covers the wavelength range between 890 and 1650 nm, where organic materials show relevant spectral features from first and second overtones. For the fabrication of the detector arrays, we propose a simple and scalable fabrication approach that yields largely improved device characteristics with respect to the grey-scale electron-beam lithography process reported earlier. Through a series of five optical lithography steps, tuning layers of silicon nitride are deposited stepwise to obtain 16 different thicknesses and reduced surface roughness. With this novel fabrication approach, the obtained photodetectors achieve an average peak linewidth of 55 nm, a maximum peak responsivity of 0.3 A/W, and high suppression of the non-resonant background. We also demonstrate the impact of these improvements on the sensing performance for two relevant problems through an experiment and a set of simulations. With lateral dimensions of ∼1.4 × 1.4 mm2, the proposed photodetector array can be the key to robust, portable, and low-cost sensing instrumentation for on-site material analysis in various application fields.

Background: The regulation of target gene mRNA mediated by microRNA may play an important role in glucose metabolism in fish. Previous research findings of our research group revealed that Momordica charantia saponin (MS) administration in a high-starch diet could improve insulin resistance of common carp through renovating insulin signaling pathways, whose fundamental mechanisms have remained unknown by far. To reveal this potential mechanism, we aimed to investigate the difference in miRNA and mRNA expression profiles between common carp fed with high-starch diets containing MS (HS_MS1 and HS_MS2) and common carp fed with high-starch (HS) diets.Results: Through miRNA deep-sequencing, 10 significantly differentially expressed miRNAs in HC and HS_MS1, including one upregulated and nine downregulated miRNAs, were identified, whereas 10 significantly differentially expressed miRNAs in HC and HS_MS2, including four upregulated and six downregulated miRNAs, were identified. These miRNAs may not only be involved in the regulation of insulin signaling pathways and insulin resistance in common carp but also be the markers for liver insulin resistance in MS therapy for the remission of insulin resistance. This study identified 10 potential known miRNAs, namely, ccr-miR-10b, ccr-miR-122, ccr-miR-143, ccr-miR-146a, ccr-miR-155, ccr-miR-16c, ccr-miR-200a, ccr-miR-29a, ccr-miR-34, and ccr-miR-375, as candidates participating in modulating the liver insulin resistance. According to the biopathway enrichment analysis of the 252 target genes using the KEGG classical biopathway database, the relative expression levels of gsk3bb, pik3r1, and pik3r3b were analyzed using RNA-seq. Compared to the HC group, a significant decrease in the relative expression levels of pik3r1 and pik3r3b was observed in HS_MS1 and HS_MS2 groups (p < 0.05). This study raised a presumption of the presence of ccr-miR-29a targeting pik3r1 or ccr-miR-143 targeting pik3r3 playing likely roles in Momordica charantia saponins remitting the liver insulin resistance.Conclusion: The findings will further deepen the understanding of the carbohydrate metabolism of common carp and provide an important scientific basis for the application of Momordica saponins as functional nutrients to alleviate insulin resistance of fish in fish culture.

The cGAS-STING signaling plays pivotal roles not only in host antiviral defense but also in various noninfectious contexts. Compared with protein-coding genes, much less was known about long noncoding RNAs involved in this pathway. Here, we performed an integrative study to elucidate the lncRNA repertoire and the mechanisms modulating lncRNA’s expression following cGAS-STING signaling activation. We uncovered a reliable set of 672 lncRNAs closely linked to cGAS-STING signaling activation (cs-lncRNA), which might be associated with type-I interferon response and infection-related phenotypes. The ChIP-seq analysis demonstrated that cs-lncRNA was strongly regulated at the transcriptional level. We further found N6-methyladenosine (m6A) regulatory machinery was indispensable for establishing cs-lncRNA repertoire via modulating m6A modification on cs-lncRNA transcripts and promoting the expression of signaling transduction key components, including IFNAR1. Loss of IFNAR1 led to the dysregulation of cs-lncRNAs resembled that of loss of an essential subunit of m6A writer METTL14. We also found m6A system affected transcriptional machinery to modulate cs-lncRNAs by targeting multiple crucial transcription factors. Inhibiting an m6A modification regulated transcription factor, EZH2, markedly enhanced the expression pattern of cs-lncRNAs. Taken together, our results uncovered the composition of the cs-lncRNAs and revealed m6A-mediated modulation coupled with transcriptional regulation significantly shaped cs-lncRNA repertoire.

The pressure of climate change and carbon emission reduction has promoted the rapid development of distributed renewable energy. One of the problems is how to connect to the distribution grid economically, efficiently and safely and to achieve the consumption of renewable energy. Meanwhile, the demand response of customers is also an important resource that can be regulated by the distribution grid. Based on this, a bi-level cooperative robust planning model for distributed renewable energy in the distribution grid considering demand response is constructed. In the first layer plan, the position and capacity of distributed renewable energy access is used as decision variables, and the minimum operation cost of the distribution network is minimized. In the second layer plan, the uncertainty of the output of renewable energy is further considered. Aiming at the optimal operating cost of the system and combining with relevant constraints, the lower-level robust optimization model is established by introducing robust optimization, and the optimization iteration is carried out by using SSA algorithm. Finally, the model and the method are verified by an example simulation, and the influence of demand response on the planning results is analyzed. The results show that considering the demand response in the distribution network planning is beneficial to delay the investment cost, enhance the power users’ load flexibility, and effectively avoid load cutting and other problems. The introduction of robust optimized two-level collaborative planning model can effectively promote the consumption of renewable energy and promote the participation of demand response resources in planning.

BackgroundExploring the cancer risks of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARDs) can help detect, evaluate, and treat malignancies at an early stage for these patients. Thus, a comprehensive analysis was conducted to determine the cancer risk of RA patients using different types of DMARDs and analyze their relationship with tumor mutational burdens (TMBs) reflecting immunogenicity.MethodsA thorough search of PubMed, EMBASE, Web of Science, and Medline was conducted up to 20 August 2022. Standardized incidence ratios (SIRs) were constructed with a random-effect model to determine risks for different types of malignancies in comparison with the general population. We also analyzed the correlation between SIRs and TMBs using linear regression (LR).ResultsFrom a total of 22 studies, data on 371,311 RA patients receiving different types of DMARDs, 36 kinds of malignancies, and four regions were available. Overall cancer risks were 1.15 (SIR 1.15; 1.09–1.22; p < 0.001) and 0.91 (SIR 0.91; 0.72–1.14; p = 0.402) in RA populations using conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs), respectively. RA patients taking csDMARDs displayed a 1.77-fold lung cancer risk (SIR 1.77; 1.50–2.09; p < 0.001), a 2.15-fold lymphoma risk (SIR 2.15; 1.78–2.59; p < 0.001), and a 1.72-fold melanoma risk (SIR 1.72; 1.26–2.36; p = 0.001). Correlation coefficients between TMBs and SIRs were 0.22 and 0.29 from those taking csDMARDs and bDMARDs, respectively.ConclusionWe demonstrated a cancer risk spectrum of RA populations using DMARDs. Additionally, TMBs were not associated with elevated cancer risks in RA patients following immunosuppressive therapy, which confirmed that iatrogenic immunosuppression might not increase cancer risks in patients with RA.InterpretationChanges were similar in cancer risk after different immunosuppressive treatments, and there was a lack of correlation between SIRs and TMBs. These suggest that we should look for causes of increased risks from the RA disease itself, rather than using different types of DMARDs.

Abstract Scalar optical hopfions weaved by nested equiphase lines in the shape of a toroidal vortex are theoretically designed and experimentally demonstrated. This category of hopfions manifesting as a spatiotemporally structured pulse propagating in space-time may enable encoding and transferring optical topological information in an additional (temporal) dimension.

Momordica charantia saponins (MCS) was supplemented to a high-starch diet to ssess the effect on the growth performance, glucose homeostasis modulating factors concerning the attenuated hyperglycemia, hyperlipemia and insulin resistance. Five iso-nitrogenous (30.48%) and iso-lipidic (5.41%) diets were formulated containing 30% starch (control group, HS), and were supplemented with 100 mg/kg (HS-MCS100), 400 mg/kg (HS-MCS400), 1600 mg/kg (HS-MCS1600) and 6400 mg/kg (HS-MCS6400) MCS on the basis of the HS diet. 450 common carp weighing (6.43 ± 0.02) g were randomly divided into 5 groups, with three replicates in each group and 30 fish in each replicate. Results revealed that dietary MCS effectively enhanced the growth and feed efficiency and significantly attenuated the glucose homeostasis and insulin resistance triggered by the HS diet. Moreover, 1600 mg/kg of MCS administration fulfilled more efficient and significant improvement of weight gain rate (WGR), specific growth rate (SGR), feed conversion rate (FCR), protein efficiency ratio (PER), protein and lipid deposition in the whole body. Alterations of serum biochemical indices revealed that 1600 mg/kg of MCS administration remarkably suppressed the hyperglycemia and hyperlipemia and elevated the insulin sensitivity. Enzyme activity and gene expression analysis of glycometabolism indicated that 1600 mg/kg of MCS administration could attenuate the hepatopancreas insulin resistance by enhancing glycolysis ability, promoting the glycogen synthesis and inhibiting the gluconeogenesis through activating PI3K/AKT signaling pathway. On all accounts detail, appropriate MCS administration have potential value in the alleviation of insulin resistance, thereby effectually maintain the glucose homeostasis and giving play to growth promoting effect for common carp fed with a high-carbohydrate diet.

Costs associated with the use of soybean as a food source in aquaculture have imposed constraints on its use in this industry. Thus, research is now focusing on alternative sources of protein for use in aquaculture. Here, we assessed the effect of total replacement of soybean meal (SBM) by Clostridium autoethanogenum protein (CAP), Tenebrio molitor meal (TMM), cottonseed protein concentrate (CPC), and chlorella powder (CHP) in diets for small specimens (initial body weight: 239.72 ± 10.75 g) and large specimens (initial body weight: 638.32 ± 12.64 g) of grass carp. For that purpose, five isonitrogenous (300 g/kg) and isoaliphatic (58 g/kg) diets were formulated with SBM, CAP, TMM, CPC, and CHP as the only dietary protein source. Triplicate groups of fish were fed the experimental diets for 56 days. Results showed that irrespective of protein sources, large specimens of grass carp obtained the significantly reduced weight gain rate (WGR), specific growth rate, moisture, crude ash contents, drip loss rate, and gene expressions of muscle S6K, MyoD, and Myf-5, and the significantly increased crude protein and crude lipid contents, hardness, cohesiveness, adhesiveness, springiness, chewiness and shear force of muscles, and gene expressions of muscle TOR, 4EBP1, MyoG, MRF4, and MSTN-1. Regardless of size, the CHP group possessed markedly higher WGR, protein efficiency ratio, crude protein contents, hardness, adhesiveness, chewiness values, and gene expression levels of muscle TOR, 4EBP1, Myf-5, and MRF4, and significantly lower feed conversion rate, drip loss rate, and gene expressions of muscle S6K and MSTN-1. For small specimens or for large specimens, the essential amino acid contents of the CHP group were highest, and CHP markedly elevated the delicious amino acid and glycine contents in comparison with the SBM. Moreover, the CPC group also realized the function of promoting the growth and improving the flesh quality to a certain degree. However, total replacement of soybean meal by CAP and TMM in grass carp diets restrained the growth and damaged the flesh quality in varying degrees. Overall, comparatively, total replacement of SBM with CHP not only improved growth performance and feed use, but also enhanced the flavor and texture of the fish by improving the amino acid composition and water-holding capacity of muscle, as well as improving muscle growth by positively impacting the expression of genes associated with the regulation of growth and development. Therefore, CHP could be a potential protein source to replace SBM in diets for use in the aquaculture of grass carp.

Introduction Hearing loss and cigarette smoking are major challenges that affect public health in China. Revealing the effect of smoking on hearing loss in the Chinese general population is critical for hearing health protection. We investigated the relationship between smoking status and hearing loss in China, especially in stratified sex and age groups. Methods A cross-sectional study was conducted on 4685 individuals aged 20– 80 years in Zhejiang province from 2016 to 2018, with audiometric testing for hearing loss and a structured questionnaire for collecting smoking status and covariates. Logistic regression was used to estimate the association between smoking and hearing loss. Results Cigarette smoking was not significantly associated with hearing loss in females and young males. In middle-aged males, after adjusting for covariates, current smokers and past smokers had a significantly higher prevalence of speechfrequency loss (OR=1.65; 95% CI: 1.17–2.33 and OR=1.88; 95% CI: 1.11–3.17; respectively) and high-frequency hearing loss (OR=2.01; 95% CI: 1.43–2.84 and OR=2.64; 95% CI: 1.50–4.66; respectively). In older males, only past smokers had a significantly higher prevalence of speech-frequency hearing loss than never smokers (OR=2.58; 95% CI: 1.38–4.85). Regarding middle-aged and older current smokers, a dose-dependent relationship between smoking intensity and hearing loss was found. Passive smoking was not significantly associated with an increased hearing loss risk in all the three male groups. Conclusions The relationship between cigarette smoking and hearing loss varied according to gender and age. Therefore, the interventions for smoking need to be tailored according to age in males.

Carbonate alkalinity is a major environmental stress factor affecting aquatic feed configuration, which easily causes oxidative stress and hypoimmunity for fish. Hence, the purpose of the study is to assess the potential effect of phosphorus on growth, intestinal oxidation resistance, physical barrier function, and microflora for Songpu mirror carp (Cyprinus carpio Songpu) (initial average weight of 2.95 ± 0.21 g) reared at the high-concentration carbonate alkalinity environment. A two-factor, three-level (2 × 3) design was applied, in which diets with three different phosphorus levels (3.6, 7.0, and 10.5 g/kg dry matter) were randomly assigned to 0 and 15 mmol/L carbonate alkalinity groups with three replicate aquariums. After the 8-week trial, we found that weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), and lipase and amylase activities in the intestine significantly (p < 0.05) declined with increasing carbonate alkalinity. Carbonate alkalinity of 15 mmol/L significantly reduced glutathione peroxidase (GSHPx) activities in the intestine (p < 0.05). The relative expressions of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), glutathione peroxidase 1a (GPX1a), Clautin3, Clautin11, and tumor necrosis factor β (TNF-β) in the intestine were markedly downregulated by increasing carbonate alkalinity levels (p < 0.05), whilst the relative expressions of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the intestine were markedly upregulated (p < 0.05). At the 15 mmol/L carbonate alkalinity treatment, Songpu mirror carp suffer from hypoimmunity status with failed digestion, antioxidant, inflammation, and immune response, thereby inducing impaired growth. Additionally, significant increments in the abundance of Proteobacteria and a significant decrease in the abundance of Fusobacteria and the Firmicutes/Bacteroidetes ratio were caused due to excessively high carbonate alkalinity (15 mmol/L) and excessively low dietary phosphorus supply (3.6 g/kg). Collectively, 7.0 g/kg dietary phosphorus supplementation was effective in promoting intestinal antioxidant enzyme activities and the corresponding gene expression via the Keap1-Nrf2 signaling pathway and in enhancing intestinal immunity by upregulating anti-inflammatory and downregulating pro-inflammatory genes. Appropriate dietary phosphorus supply could promote the formation of beneficial microflora in freshwater, and it has the potential ability to transfer the adverse effect of carbonate alkalinity stress to the structural composition of intestinal microflora. Hence, consideration should be given to suitable phosphorus supply for fish under the chronic carbonate alkalinity stress.

In this study, a carbon nanotube (CNTs)—supported dummy template molecularly imprinted polymer (DMIPs) material was synthesized and utilized for the detection of amide herbicides in aquatic products via matrix solid-phase dispersion technology (MSPD). The DMIPs material was characterized, and its adsorption kinetics and isotherm were determined, the adsorption model was established, and the selective adsorption coefficient was calculated. The extract parameters of the method were optimized and successfully employed for the separation, analysis and detection of real samples, with satisfactory detection limits and linear ranges obtained. By comparing with other methods, the CNTs@DMIPs combined with MSPD technology established in our study can effectively solve false negative problems caused by insufficient destructive force, using dummy template molecules can also address the issue of false positives caused by template molecule leakage in molecular imprinting. Overall, the method is appropriate for the separation and detection of endogenous substances from highly viscous and poorly dispersed samples and is used as a routine detection tool in the aquaculture industry.

Multiple freeze-thaw cycles due to temperature fluctuations irreversibly damage the muscle tissue of fish, thereby reducing their edibility. The aim of this study was to determine the effects of the number of freeze-thaw (F–T) cycles on protein and lipid oxidation, microstructure, physical index, and nutritional quality of rainbow trout muscle. The results showed that F–T cycles accelerated protein carbonyl formation and thiobarbituric acid reactive substances (TBARS) generation (p < 0.05), as well as increased the loss of total sulfhydryl (SH) groups (p < 0.05). Moreover, transmission electron microscope (TEM) images illustrated that the microstructure of muscle fibers was loosed and disintegrated after the third F–T cycle, causing a reduction in water holding capacity (WHC). In addition, muscles lost the intrinsic color of fresh meat after the fifth cycle, with lightness L* and yellowness b* increasing, while redness a* declined (p < 0.05). The hardness, springiness, and chewiness of muscles decreased, and the shear force first increased and then decreased after the third cycle. Furthermore, the proximate components, essential amino acids (EAAs), and total amino acids (TAAs), decreased significantly after the third cycle (p < 0.05) due to the decrease of WHC as well as protein and lipid oxidation. The results indicated that the quality of rainbow trout muscle changed after the third cycle, deteriorated seriously after the fifth cycle, and was unacceptable after the seventh cycle. Therefore, it is necessary to reduce the temperature fluctuation to less than three times during freezing. The results provided a reference for the identification and classification of frozen aquatic products.

Flexible ferroelectric memories, endowing with high data storage density, provide a chance for the next-generation wearable electronics. Here, flexible inorganic Mn-doped BiFeO3 thin films were directly integrated on fluorophlogopite mica (F-Mica) substrates by an easy and low-cost all solution chemical solution deposition (AS-CSD) route. The integration of LaNiO3 buffer layer can improve the film surface density and uniformity. The flexible characteristic can be achieved by reducing the thickness of F-Mica substrates for the ferroelectric thin films. In contrast to BiFe0·93Mn0·07O3/LaNiO3/Si thin film deposited on rigid substrates (Si), the BiFe0·93Mn0·07O3/LaNiO3/F-mica fabricated on F-Mica show better ferroelectric performances due to the improved crystal growth and less defects. More importantly, the obtained BiFe0·93Mn0·07O3/LaNiO3/F-mica ferroelectric thin films still show large remnant polarization of Pr ∼64 μC/cm2 (deterioration of ∼7.2%), good antifatigue properties up to 1.2 × 108 cycles and outstanding retention behaviors for 1.6 × 104 s after continuous bending. This work will provide a feasible route to fabricate flexible inorganic ferroelectric thin films through low-cost solution method and show attractive comprehensive performances in next-generation wearable smart devices.

Somatic symptom disorder (SSD) is a form of mental illness that causes one or more distressing somatic symptoms leading to a significant disruption to everyday life, characterized by excessive thoughts, feelings, or behaviors related to these symptoms. While SSD is characterized by significant discomfort in some parts of the body, these symptoms are not related to any known medical condition and therefore it cannot be diagnosed using any medical instrument examination. Currently available treatments for SSD, including drug therapy and psychotherapy (such as cognitive behavioral therapy), usually improve psychiatric symptoms, but the results are often disappointing. Furthermore, SSD is often comorbid with anxiety and depression (75.1 and 65.7%, respectively). Importantly, interventions targeting the anterior limb of the internal capsule (ALIC; e.g., deep brain stimulation and thermal ablation) can effectively treat various mental disorders, such as refractory obsessive-compulsive disorder, depression, and eating disorders, suggesting that it may also be effective for treating the depressive symptoms associated with SSD comorbidity. In this report, a 65-year-old woman diagnosed with SSD accompanied with depression and anxiety underwent bilateral anterior capsulotomy. The patient complained of nausea and vomiting, swelling of the hilum of the liver for 14 years, weakness of the limbs for 13 years, and burning pain in the esophagus for 1 year. Psychiatric and neuropsychological assessments were conducted to record the severity of the patients' symptoms and the progression of postoperative symptoms. The patient's somatization, depression, and anxiety symptoms as well as quality of life improved significantly and steadily; thus, anti-depressive and anti-anxiety medication were stopped. However, the patient developed new somatization symptoms, including dizziness, headache, and sternal pain, 10 months after the operation. Therefore, the patient resumed taking flupentixol and melitracen in order to control the new symptoms. This study shows that bilateral anterior capsulotomy appears to be a complementary treatment for refractory SSD with depressive and anxiety symptoms. Furthermore, postoperative use of anxiolytic and antidepressant medications may be useful for controlling future somatization symptoms.

The purpose of this research is to find a traffic light timing optimization scheme. During the research, an intersection between Xi’an Mingguang road and the Fourth FengCheng road was chosen to analyze the crossing time distribution of pedestrians who were separated from west-to-the-right-turn vehicles during which the method of breaking off both ends of pedestrian green light signals was used. The VISSIM software was used for traffic simulation, aimed at improving traffic volume and right-turning vehicle average speed for less vehicle queuing delays, less human-vehicle conflicts, and better security for pedestrians without excessive interruption on their street crossing efficiency. The optimal scheme is obtained and the result shows that (1) the number of passing vehicles remains unchanged, with the queuing delay reduced by 5.78% and crosswalk passing speed increased by 19.01% compared with the original one. (2) As the scheme effect is positively correlated with the increase of right turn vehicle numbers, the scheme could be adopted for urban traffic management based on the local situation, which is not only in peak traffic hours but also in the flat peak time to ensure vehicle efficiency and pedestrian safety in the light of “vehicle yielding to pedestrians” regulation. (3) The scheme could also be adopted in cities with no “vehicle yielding to pedestrians” policy for both people-vehicle separation and pedestrian safety when crossing streets.

Since the recycling of waste original cement-stabilized macadam (OCSM) base has important environmental and economic significance, the addition of emulsified asphalt to OCSM to form emulsified recycled OCSM (ER-OCSM) can improve the flexibility of recycled mixtures. However, the influence of emulsified asphalt on the mechanical performance of such mixtures remains to be investigated. This study presents a gradation design and ER-OCSM established using the step-by-step filling method and investigated the mechanical properties of the ER-OCSM mixture. The apparent characteristics, crushing value and needle-like particle content of the OCSM milling material were tested. Based on step-by-step filling theory, the appropriate test method to achieve a uniform and dense state according to the characteristics of different aggregates was selected, and the dense skeleton gradation design method for recycled cement macadam was obtained. The mechanical properties of the ER-OCSM were analyzed by performing indoor physical laboratory tests. The natural gradation of the OCSM milling material exceeded the gradation range recommended in the Technical Guide for the Promotion of Science and Technology of the Construction Project of the Main Highway in Jiangsu Province (Trial), but the designed gradations were basically within the range. At the same age and temperature, the flexural strength and dynamic elastic modulus of the ER-OCSM decreased gradually with an increase in the emulsified asphalt content. Because ER-OCSM had temperature-sensitive characteristics, the adhesiveness of the asphalt between particles in the mixture decreased with increasing temperature, which was manifested as the unconfined compressive strength, flexural tensile strength and dynamic elastic modulus decreasing with an increase in temperature (the decrease was slight within 5–25°C but noticeable within 25–60°C). Furthermore, a higher emulsified asphalt content caused a more noticeable decrease. The flexural strength of the tested ER-OCSM showed noticeable correlations with the splitting strength, unconfined compressive strength and dynamic elastic modulus. The proper addition of emulsified asphalt can reduce the rigidity of ER-OCSM. However, the emulsified asphalt content should be strictly controlled; otherwise, the mechanical properties of the material will decrease greatly, adversely impacting the comprehensive road use performance.

Erosive rainfall results in the loss of both soil and nutrients, which indirectly triggers soil deterioration and a reduction in land productivity. However, how rainfall affects runoff, soil erosion, and nutrient loss under different crop rotation patterns and topographic factors remains unclear. This experiment observed nine runoff-erosion plots on the Chinese Loess Plateau (CLP) from 2019 to 2020 to determine the effects of crop type, rotation pattern, and slope gradient and length on runoff, soil erosion, and nutrient loss. Runoff, soil erosion, and nutrient loss were highest for the fallow plots; values for these variables for spring corn and winter wheat plots were not significantly different. Crop rotation generated greater runoff, soil erosion, and nutrient loss compared to non-rotation. Soil erosion and associated nutrient loss increased, but not significantly, with slope for gradients of 0.5°, 1°, and 3°, while runoff and associated nutrient loss did not increase. In addition, soil erosion and associated nutrient loss were significantly greater for slope lengths of 20 m vs. 50 m. A structural equation model showed rainfall characteristics significantly impacted runoff and soil erosion and subsequently affected nutrient loss. This study increases the understanding of runoff, soil erosion, and nutrient loss from cropland with gentle slopes on the CLP.

Debris-covered glaciers have contrasting melting mechanisms and climate response patterns if compared with debris-free glaciers and thus show a unique influence on the hydrological process. Based on high-resolution satellite images and unpiloted aerial vehicle surveys, this study investigated the dynamic changes of Zhuxi Glacier, a thick debris-covered glacier in the southeastern Tibetan Plateau. Our result shows that the whole glacier can be divided into the active regime and stagnant regime along the elevation of 3400 m a.s.l. The mean surface velocity of the active regime was 13.1 m yr−1, which was five times higher than that of the stagnant regime. The surface-lowing rate of this debris-covered glacier reaches more than 1 m yr−1 and displays an accelerating trend. The majority of ice loss concentrates around ice cliffs and supraglacial ponds, the ablation hotspots. These hotspots can be roughly classified into three types, including persistent, expanding, and shrinking patterns, at different dynamic regimes on the Zhuxi Glacier. With the evolution of these hotpots and glacier dynamic changes, the supraglacial ponds showed significant change, with the total number fluctuating from 15 to 38 and the total area increasing from 1128 m2 to 95790 m2 during the past decade. The recent exponential expansion of the proglacial lake and the significant downwasting of stagnant ice inside the dammed terminus moraine possibly trigger the glacial lake outburst flood and thus threaten the security of livelihoods and infrastructure downstream.

Iron is an essential trace element for the human body, and its deficiency or excess can induce a variety of biological processes. Plenty of evidences have shown that iron metabolism is closely related to the occurrence and development of tumors. In addition, iron plays an important role in cell death, which is very important for the development of potential strategies for tumor treatment. Here, we reviewed the latest research about iron metabolism disorders in various types of tumors, the functions and properties of iron in ferroptosis and ferritinophagy, and new opportunities for iron-based on treatment methods for tumors, providing more information regarding the prevention and treatment of tumors.

Heart failure caused by cardiac fibrosis has become a major challenge of public health worldwide. Cardiomyocyte programmed cell death (PCD) and activation of fibroblasts are crucial pathological features, both of which are associated with aberrant Ca2+ influx. Transient receptor potential cation channel subfamily M member 7 (TRPM7), the major Ca2+ permeable channel, plays a regulatory role in cardiac fibrosis. In this study, we sought to explore the mechanistic details for sacubitril, a component of sacubitril/valsartan, in treating cardiac fibrosis. We demonstrated that sacubitril/valsartan could effectively ameliorate cardiac dysfunction and reduce cardiac fibrosis induced by isoprotereno (ISO) in vivo. We further investigated the anti-fibrotic effect of sacubitril in fibroblasts. LBQ657, the metabolite of sacubitril, could significantly attenuate transforming growth factor-β 1 (TGF-β1) induced cardiac fibrosis by blocking TRPM7 channel, rather than suppressing its protein expression. In addition, LBQ657 reduced hypoxia-induced cardiomyocyte PCD via suppression of Ca2+ influx regulated by TRPM7. These findings suggested that sacubitril ameliorated cardiac fibrosis by acting on both fibroblasts and cardiomyocytes through inhibiting TRPM7 channel.

Agar accounts for ~60% of the dry weight of some red macroalgae, and the breakdown of this kind of polysaccharide releases high-value compounds; therefore, the resource utilization of agar is of great significance to improve the added value of these macroalgae. Herein, Alteromonas macleodii QZ9-9 isolated from tropical Gracilaria hainanensis in Hainan Island was characterized as an agarolytic bacterium, which displayed a high agar-degrading activity. The highest diameters of the degradation zones of the A. macleodii QZ9-9 and its extracellular-agarase (12.16 U/mL) were 41.46 mm and 22.89 mm, respectively, and the first-order degradation rate constants of those were 0.02 h−1 and 0.77 U−1, respectively. Importantly, the fermentation products of A. macleodii QZ9-9 exhibited antioxidant activity, and the peak of DPPH scavenging activity of 50 h fermentation products of this strain was up to 50.79% in the reaction for 1 h; the DPPH scavenging activity of low molecule metabolites (≤3 kDa) in particular was up to ~85.85%. A total of 766 metabolites were detected in the low molecule metabolites by metabolomics. The peptide-like metabolites, such as prolyl–histidine, isoleucyl–histidine, isoleucyl–proline and arginyl–proline, and the antioxidant maculosin were found in the top 20 metabolites with relatively high abundance. Additionally, the antioxidant activity of maculosin was further verified in this work. We concluded that the low molecule metabolites of A. macleodii QZ9-9 with relatively high antioxidant activity are interesting candidates for preparing desirable non-toxic antioxidants, thereby facilitating the high value-added utilization of macroalgae in the fields of cosmetic, food preservation, and pharmaceutical industries.

For decades, near-infrared (NIR) spectroscopy has been a valuable tool for material analysis in a variety of applications, ranging from industrial process monitoring to quality assessment. Traditional spectrometers are typically bulky, fragile and expensive, which makes them unsuitable for portable and in-field use. Thus, there is a growing interest for miniaturized, robust and low-cost NIR sensors. In this study, we demonstrate a handheld NIR spectral sensor module, based on a fully-integrated multipixel detector array, sensitive in the 850–1700 nm wavelength range. Differently from a spectrometer, the spectral sensor measures a limited number of NIR spectral bands. The capabilities of the spectral sensor module were evaluated alongside a commercially available portable spectrometer for two application cases: to quantify the moisture content in rice grains and to classify plastic types. Both devices achieved the two sensing tasks with comparable performance. Moisture quantification was achieved with a root mean square error (RMSE) prediction of 1.4% and 1.1% by the spectral sensor and spectrometer, respectively. Classification of the plastic type was achieved with a prediction accuracy on unknown samples of 100% and 96.4% by the spectral sensor and spectrometer, respectively. The results from this study are promising and demonstrate the potential for the compact NIR modules to be used in a variety of NIR sensing applications.

Flaxseed cake contains cyanogenic glucosides, which can be metabolized into hydrocyanic acid in an animal's body, leading to asphyxia poisoning in cells. Beta-glucosidase is highly efficient in degrading cyanogenic glucosides. The Cattle may have β-glucosidase-producing strains in the intestinal tract after eating small amounts of flaxseed cake for a long time. This study aimed to isolate of a strain from cow dung that produces β-glucosidase with high activity and can significantly reduce the amount of cyanogenic glucosides. We used cow dung as the microflora source and an esculin agar as the selective medium. After screening with 0.05% esculin and 0.01% ferric citrate, we isolated 5 strains producing high amounts of β-glucosidase. In vitro flaxseed cake fermentation was fermented by these 5 strains, in which the strain M-2 exerted the best effect (P

An eddy is a circular current of water in the ocean that affects the fields of maritime transport, ocean data analysis, and so on. Traditional eddy detection methods are based on numerical simulation data and satellite images and their accuracy is affected greatly by manual threshold adjustment. In this paper, we present a new eddy detection approach via deep neural networks to improve eddy detection accuracy. First, we present a streampath-based approach to build a large-scale eddy image dataset from ocean current data and apply our dataset to eddy detection. Second, by combining the multilayer features in the neural network with the characteristics of the eddies, we achieve a competitive detection result with an mAP of 90.64% and an average SDR of 98.91%, which performs better than the previous methods. Third, through our enhanced eddy visualization approach, we solve the problem that eddies are difficult to detect in the sparse streampath region.

Drought is one of the most important abiotic constraints on agricultural productivity, while global warming leads to the occurrence of more frequent drought events. Cyclocarya paliurus is a multiple-function tree species with medicinal value and timber production, but no information is available on its drought tolerance. In this hydroponic experiment, variations in leaf anatomical morphology, chloroplast ultrastructure, stomatal characteristics, and antioxidant enzyme activities were investigated under six levels of polyethylene glycol 6000 (PEG)-induced drought treatments to assess the drought adaption and physiological response of C. paliurus seedlings. The results showed that PEG-induced drought treatments reduced leaf epidermis, spongy tissue, leaf vein diameter, and spongy ratio, whereas the ratio of palisade tissue to spongy tissue, cell tense ratio, and vein protuberant degree all increased with enhancing the PEG6000 concentrations. Significant differences in stomatal width, stomatal aperture, and stomatal density existed among the treatments (p < 0.01). The stomatal aperture decreased significantly with the increase in PEG6000 concentrations, whereas the greatest stomatal density was observed in the 15% PEG6000 treatment. Compared with the control, higher drought stresses (20% and 25% PEG concentrations) caused damage at the cellular level and chloroplast lysis occurred. PEG6000 treatments also promoted the activities of SOD, POD, and CAT in C. paliurus seedlings, but this increase was insufficient to deal with the membrane lipid peroxidative damage under the high PEG concentrations. Correlation analysis indicated that in most cases there were significant relationships between leaf anatomical characteristics and antioxidant enzyme activities. Our results suggested that C. paliurus seedlings would not survive well when the PEG6000 concentration was over 15% (equal to soil water potential of −0.30 MPa).

Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi–Goutières syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from Perilla frutescens, suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity. Mice treated with PAH are more susceptible to herpes simplex virus type 1 (HSV-1) infection. Moreover, administration with PAH markedly ameliorates self-DNA-induced autoinflammatory responses in a mouse model of AGS. Collectively, our study reveals that PAH can effectively inhibit cGAS-STING signaling and could be developed toward the treatment of cGAS-mediated autoimmune diseases.

The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) has emerged as a fundamental component fueling the anti-pathogen immunity. Because of its pivotal role in initiating innate immune response, the activity of cGAS must be tightly fine-tuned to maintain immune homeostasis in antiviral response. Here, we reported that neddylation modification was indispensable for appropriate cGAS-STING signaling activation. Blocking neddylation pathway using neddylation inhibitor MLN4924 substantially impaired the induction of type I interferon and proinflammatory cytokines, which was selectively dependent on Nedd8 E2 enzyme Ube2m. We further found that deficiency of the Nedd8 E3 ligase Rnf111 greatly attenuated DNA-triggered cGAS activation while not affecting cGAMP induced activation of STING, demonstrating that Rnf111 was the Nedd8 E3 ligase of cGAS. By performing mass spectrometry, we identified Lys231 and Lys421 as essential neddylation sites in human cGAS. Mechanistically, Rnf111 interacted with and polyneddylated cGAS, which in turn promoted its dimerization and enhanced the DNA-binding ability, leading to proper cGAS-STING pathway activation. In the same line, the Ube2m or Rnf111 deficiency mice exhibited severe defects in innate immune response and were susceptible to HSV-1 infection. Collectively, our study uncovered a vital role of the Ube2m-Rnf111 neddylation axis in promoting the activity of the cGAS-STING pathway and highlighted the importance of neddylation modification in antiviral defense.