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Abstract As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage response (DDR) in colorectal cancer remains unclear. GL exposure significantly reduced cell colony formation and viability with a concomitant increase in DNA fragmentation in CRC, meanwhile GL induced apoptosis by activating caspase-3. Moreover, GL induced cell cycle arrest in CRC cells at S phase, which was associated with decreased cyclin D1 in vitro. GL treatment significantly ameliorated tumor growth and promoted DDR in vivo. Mechanism analysis revealed that GL significantly downregulated the NHEJ pathway via inhibiting HMGB1. Finally, the expression of HMGB1 was abnormal regulated in CRC tissue than in adjacent normal tissues and associated with TNM stage and overall survival. Our findings indicate that HMGB1 may be a novel therapeutic target in CRC, a result that GL may serve as a promising drug for CRC treatment.

Abstract In this study, the necessity of radiotherapy (RT) for hormone receptor-negative older breast cancer patients after breast-conserving surgery (BCS) was investigated. The data of hormone receptor-negative invasive breast cancer patients who underwent BCS were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All patients were separated into two groups, namely, the RT group and the no radiotherapy (No RT) group. The 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were compared between the No RT and RT groups after propensity score matching (PSM). The nomograms for predicting the survival of patients were constructed from variables identified by univariate or multivariate Cox regression analysis. A total of 2504 patients were enrolled in the training cohort, and 630 patients were included in the validation cohort. After PSM, 738 patients were enrolled in the No RT group and RT group. We noted that RT can improve survival in hormone receptor-negative older breast cancer patients who undergo BCS. Based on the results of multivariate Cox analysis, age, race, tumour grade, receipt of RT and chemotherapy, pathological T stage, N status, M status and HER2 status were linked to OS and CSS for these patients, and nomograms for predicting OS and CSS were constructed and validated. Moreover, RT improved OS and CSS in hormone receptor-negative older breast cancer patients who underwent BCS. In addition, the proposed nomograms more accurately predicted OS and CSS for hormone receptor-negative older breast cancer patients after BCS.

Abstract Background Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. Methods Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. Results Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. Conclusions Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

Abstract The traffic flow prediction is the key to alleviate traffic congestion, yet very challenging due to the complex influence factors. Currently, the most of deep learning models are designed to dig out the intricate dependency in continuous standardized sequences, which are dependent to high requirements for data continuity and regularized distribution. However, the data discontinuity and irregular distribution are inevitable in the real-world practical application, then we need find a way to utilize the powerful effect of the multi-feature fusion rather than continuous relation in standardized sequences. To this end, we conduct the prediction based on the multiple traffic features reflecting the complex influence factors. Firstly, we propose the ATFEM, an adaptive traffic features extraction mechanism, which can select important influence factors to construct joint temporal features matrix and global spatial features matrix according to the traffic condition. In this way, the feature’s representation ability can be improved. Secondly, we propose the MFSTN, a multi-feature spatial–temporal fusion network, which include the temporal transformer encoder and graph attention network to obtain the latent representation of spatial–temporal features. Especially, we design the scaled spatial–temporal fusion module, which can automatically learn optimal fusion weights, further adapt to inconsistent spatial–temporal dimensions. Finally, the multi-layer perceptron gets the mapping function between these comprehensive features and traffic flow. This method helps to improve the interpretability of the prediction. Experimental results show that the proposed model outperforms a variety of baselines, and it can accurately predict the traffic flow when the data missing rate is high.

ObjectPerimenopause depression disorder (PDD) is a very common problem in clinical practice and is characterized by depression and autonomic nervous symptoms, including hot flashes, palpitation, and night sweating. In addition, the comorbidity of menopause depression has long been an integral component of the estradiol (E2) shortage. Previous studies have suggested that the mechanisms underlying this comorbidity involved overlap of endocrine and cerebellar networks. Emerging evidence has shown that the endocrine–brain–gut–microbiota axis plays a key role in the regulation of affective disorders. Yangyin-ningshen formula (YYNS) is a traditional Chinese decoction tailored by Yijintang for menopausal depression intervention. Thus, we hypothesized that the YYNS may be involved in the menopause depression alleviation through the endocrine–brain–gut–microbiota axis.MethodsTo verify this, we constructed a bilateral ovariectomy (OVX) mouse model to simulate menopausal-related depression. Subsequently, behavioral tests including the open field test (OFT) and the forced swimming test (FST) were conducted to examine the depression state post-OVX. With YYNS or E2 intervention, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum sex hormones level. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) were used to analyze the microbiome of the colon samples collected from mice in the sham surgery group (CSH), the OVX model group (CMD), the OVX with E2 hormone intervention group (CHM), and the OVX with YYNS intervention group (CYYNS). One week after OVX, CMD, CHM, and CYYNS showed depression in OFT, FST. Three weeks post-OVX, CHM and CYYNS showed a notable relief of depression; CMD shaped the OTUs shrinkage; and OTUs were raised in the sham, CHM, and CYYNS group. The CMD group showed that the abundance of Actinobiota decreased but that of Bacteriodia increased. The relative abundance of the genus varied in each group. Moreover, functional correlation of changes in sex hormone and gut microbes between different groups showed that the PRL level was negatively correlated with Odoribacter. T level was positively correlated with Lachnospiraceae NK4A136 group and Odoribacter abundance (p < 0.05).ConclusionOur results not only offer novel insights into the sex hormones and depression with OVX mice but also build an important basis for E2 or YYNS therapeutic efficacy on PDD, which provide for future research on this etiology through the endocrine–brain–gut–microbiota network.

Bioactive peptides have rich nutritional value and multiple biological functions, which plays a crucial role in health of aquatic animals. In this study, we screened crayfish shell bioactive peptides based on molecular simulation, and analyzed their effects on oxidative stress and lipid metabolism disorders induced by excessive copper (Cu) diet in zebrafish. The protein hydrolysates were prepared by enzymatic hydrolysis of crayfish shell protein using trypsin, and the peptide sequences were determined by LC-MS/MS. The peptide LPLWPY (LY-6, the molecular weight is 787.94 Da) identified using peptide database PeptideRanker prediction and molecular docking showed strong antioxidant potential. In vivo experiments of zebrafish showed that dietary supplementation of LY-6 peptide significantly improved the adverse effects of oxidative stress and abnormal lipid metabolism caused by excessive Cu diet. The results of zebrafish primary hepatocytes revealed that LY-6 peptide promoted the antioxidant capacity and lipid metabolism normalization of cells by regulating nrf2 and pparγ signaling pathways, thereby reducing oxidative stress and lipid accumulation. The findings of this study revealed that antioxidant peptide LPLWPY with strong from crayfish shell protein hydrolysates could alleviate oxidative stress and lipid metabolism abnormalities caused by excessive Cu diet in zebrafish, thus could be recommended as a potential functional feed ingredient for fish nutrition. It provides theoretical basis and reference for aquatic animal nutrition regulation and development of novel feed additives.

Cadmium (Cd) is a toxic heavy metal pollutant in the environment. Excessive Cd in water has toxic effects on fish, endangering their healthy growth and ultimately affecting the quality and safety of aquatic products. To evaluate the toxicity of excessive Cd to fish through potential oxidative damage, Siniperca chuatsi was exposed to Cd in water for 15 days. It was found that Cd exposure significantly decreased the survival rate of S. chuatsi and Cd was detected in their muscle. Meanwhile, Cd disrupts the redox balance by reducing antioxidant enzyme activities, increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle, and promoting oxidative damage. Histomorphology showed that enlargement of muscle fiber gaps, cell swelling and vacuolar degeneration after Cd exposure. In addition, Cd toxicity induced up-regulating the expression of miR-216a, while down-regulation of Nrf2 protein and its downstream antioxidant enzyme genes expression. Further analysis revealed that miR-216a was significantly negatively correlated with the expression of Nrf2, and injection of miR-216a antagomir significantly enhanced the expression of Nrf2 and antioxidant enzyme genes, as well as the activity of antioxidant enzymes, thereby reducing the damage of Cd to fish. These results suggested that miR-216a-mediated Nrf2 signaling pathway plays an important role in Cd-induced oxidative stress of S. chuatsi muscle.

Abstract As China grapples with the dual policy challenges of declining birth rates and the pursuit of individual happiness, understanding the relationship between these two factors is important. This study empirically examined the influence of sibling size on happiness in China, distinguishing between direct and indirect channels of impact. Using data from the 2008 Chinese General Social Survey, this analysis focused on how sibling size shapes individual income and education levels, which are both key determinants of happiness. It addressed the endogeneity issue inherent in sibling size by employing variations in the implementation of family planning policies across provinces in the 1970s as instrumental variables. The findings revealed an indirect relationship between sibling size and happiness; an increase in sibling size negatively affected both income and education levels, subsequently reducing happiness. This study contributes to the ongoing dialogue on the relationship between family size and individual happiness in China by offering nuanced insights into the channels through which these effects occur. This study also highlights the policy implications, suggesting that initiatives to raise the birth rate should be accompanied by efforts to enhance income and educational opportunities to foster individual happiness.

E-governance is capable of driving the transition of government from an administrative power allocation of public resources to a citizen-service-oriented governance model. However, during this transformation, various governmental bodies often face the challenge of "data silos" caused by factors such as cross-regional, cross-business, and cross-departmental operations. Without altering the existing information platforms, transparent access technology serves as a key solution for data access within egovernance systems. It enables convenient access to information resources stored in different mediums and formats, facilitating the sharing and consolidation of information and data within and between governmental departments, thereby addressing the issue of "data silos" and enhancing the comprehensive service capabilities of e-governance. This paper firstly provides an overview of the concept, levels, characteristics, and application scenarios of transparent access to government big data. Secondly, it conducts a comprehensive comparative analysis of transparent access technologies in the context of cloud computing and big data. Lastly, based on the requirements of various transparent access technologies and the application of transparent access to government big data, this paper proposes a visionary framework for transparent access to government big data based on cross-domain semantics and channel coupling. This framework includes modules for cross-domain semantic interoperability, coupling of heterogeneous information channels based on knowledge graph, and tracing of multi-source heterogeneous data, aiming to provide innovative solutions for achieving transparent access to government big data.

Abstract Inflammation in the testes induced by infection and autoimmunity contributes significantly to male infertility, a public health issue. Current therapies using antibiotics and broad-spectrum anti-inflammatory drugs are ineffective against non-bacterial orchitis and induce side effects. This highlights the need to explore the pathogenesis of orchitis and develop alternative therapeutic strategies. In this study, we demonstrated that Gasdermin D (GSDMD) was activated in the testes during uropathogenic Escherichia coli (UPEC)-induced acute orchitis, and that GSDMD in macrophages induced inflammation and affected spermatogenesis during acute and chronic orchitis. In testicular macrophages, GSDMD promoted inflammation and antigen presentation, thereby enhancing the T-cell response after orchitis. Furthermore, the pharmacological inhibition of GSDMD alleviated the symptoms of UPEC-induced acute orchitis. Collectively, these findings provide the first demonstration of GSDMD’s role in driving orchitis and suggest that GSDMD may be a potential therapeutic target for treating orchitis.

Chlorophyll-a (Chl-a) is an important parameter in water bodies. Due to the complexity of optics in water bodies, it is difficult to accurately predict Chl-a concentrations in water bodies by current traditional methods. In this paper, using Sentinel-2 remote sensing images as the data source combined with measured data, taking Wuliangsu Lake as the study area, a new intelligent algorithm is proposed for prediction of Chl-a concentration, which uses the adaptive ant colony exhaustive optimization algorithm (A-ACEO) for feature selection and the gray wolf optimization algorithm (GWO) to optimize support vector regression (SVR) to achieve Chl-a concentration prediction. The ant colony optimization algorithm is improved to select remote sensing feature bands for Chl-a concentration by introducing relevant optimization strategies. The GWO-SVR model is built by optimizing SVR using GWO with the selected feature bands as input and comparing it with the traditional SVR model. The results show that the usage of feature bands selected by the presented A-ACEO algorithm as inputs can effectively reduce complexity and improve the prediction performance of the model, under the condition of the same model, which can provide valuable references for monitoring the Chl-a concentration in Wuliangsu Lake. HIGHLIGHTS Second derivative as a pretreatment method can improve the prediction accuracy of machine learning.; Adaptive ant colony exhaustive optimization algorithm can more effectively select the feature bands related to Chl-a.; Combining gray wolf optimization algorithm with support vector regression can achieve better prediction accuracy.; The prediction method provides a new way for predicting Chl-a concentration in lake wetlands.;

Abstract Background Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined. Methods BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen. The anti-inflammatory mechanisms were investigated using depletion and adoptive transfer experiments as well as transcriptome analysis and isolated lung CD11chigh macrophages. Results We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80+CD11chigh macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11high macrophages. PepN pre-programmed the macrophages during maturation to an anti-inflammatory phenotype by shaping the metabolic preference for oxidative phosphorylation (OXPHOS) and also inhibited the inflammatory response of macrophages by activating AMP-activated protein kinase. Furthermore, PepN treated macrophages also exhibited high-level costimulatory signaling molecules which directed the differentiation into Treg. Conclusion Our results demonstrated that the expansion of CD11chigh macrophages in lungs and the OXPHOS metabolic bias of macrophages are associated with reduced allergic airway inflammation after PepN exposure, which paves the way for its application in preventing allergic asthma.

Early blight and ladybug beetle infestation are important factors threatening potato yields. The current research on disease classification using the spectral differences between the healthy and disease-stressed leaves of plants has achieved good progress in a variety of crops, but less research has been conducted on early blight in potato. This paper proposes a CARS-SPA-GA feature selection method. First, the raw spectral data of potato leaves in the visible/near-infrared light region were preprocessed. Then, the feature wavelengths were selected via competitive adaptive reweighted sampling (CARS) and the successive projection algorithm (SPA), respectively. Then, the two sets of wavelengths were reorganized and duplicates were removed, and secondary feature selection was conducted with genetic algorithm (GA). Finally, the feature wavelengths were fed into different classifiers and the parameters were optimized using a real-coded genetic algorithm (RCGA). The experimental results show that the feature wavelengths selected by the CARS-SPA-GA method accounted only for 9% of the full band, and the classification accuracy of the RCGA-optimized support vector machine (SVM) classification model reached 98.366%. These results show that it is feasible to classify early blight and ladybug beetle infestation in potato using visible/near-infrared spectral data, and the CARS-SPA-GA method can substantially improve the accuracy and detection efficiency of potato pest and disease classification.

The fast growth of the Internet has made network security problems more noticeable, so intrusion detection systems (IDSs) have become a crucial tool for maintaining network security. IDSs guarantee the normal operation of the network by tracking network traffic and spotting possible assaults, thereby safeguarding data security. However, traditional intrusion detection methods encounter several issues such as low detection efficiency and prolonged detection time when dealing with massive and high-dimensional data. Therefore, feature selection (FS) is particularly important in IDSs. By selecting the most representative features, it can not only improve the detection accuracy but also significantly reduce the computational complexity and attack detection time. This work proposes a new FS approach, BPSO-SA, that is based on the Binary Particle Swarm Optimization (BPSO) and Simulated Annealing (SA) algorithms. It combines these with the Gray Wolf Optimization (GWO) algorithm to optimize the LightGBM model, thereby building a new type of reflective Distributed Denial of Service (DDoS) attack detection model. The BPSO-SA algorithm enhances the global search capability of Particle Swarm Optimization (PSO) using the SA mechanism and effectively screens out the optimal feature subset; the GWO algorithm optimizes the hyperparameters of LightGBM by simulating the group hunting behavior of gray wolves to enhance the detection performance of the model. While showing great resilience and generalizing power, the experimental results show that the proposed reflective DDoS attack detection model surpasses conventional methods in terms of detection accuracy, precision, recall, F1-score, and prediction time.

With the increasing popularity of Android smartphones, malware targeting the Android platform is showing explosive growth. Currently, mainstream detection methods use static analysis methods to extract features of the software and apply machine learning algorithms for detection. However, static analysis methods can be less effective when faced with Android malware that employs sophisticated obfuscation techniques such as altering code structure. In order to effectively detect Android malware and improve the detection accuracy, this paper proposes a dynamic detection model for Android malware based on the combination of an Improved Zebra Optimization Algorithm (IZOA) and Light Gradient Boosting Machine (LightGBM) model, called IZOA-LightGBM. By introducing elite opposition-based learning and firefly perturbation strategies, IZOA enhances the convergence speed and search capability of the traditional zebra optimization algorithm. Then, the IZOA is employed to optimize the LightGBM model hyperparameters for the dynamic detection of Android malware multi-classification. The results from experiments indicate that the overall accuracy of the proposed IZOA-LightGBM model on the CICMalDroid-2020, CCCS-CIC-AndMal-2020, and CIC-AAGM-2017 datasets is 99.75%, 98.86%, and 97.95%, respectively, which are higher than the other comparative models.

In this study, the influence of fasting on hepatic glucose and lipid metabolism was explored by examining biochemical, antioxidative, and morphological indicators and transcriptional expression in the liver of javelin goby (Synechogobius hasta) after 0, 3, 7, or 14 days of starvation. Marked reductions in hepatic glycogen and triglycerides occurred from the seventh day of starvation until the end of the trial (p < 0.05). However, no alterations in hepatic cholesterol or protein were detected throughout the entire experiment (p > 0.05). During fasting, the activities of pyruvate kinase, lactate dehydrogenase, and glycogen phosphorylase a all rose firstly and then fell (p < 0.05). The activities of hepatic fatty acid synthase and acetyl-CoA carboxylase were minimized to their lowest levels at the end of food deprivation (p < 0.05), while lipase was elevated after 7–14 days of fasting (p < 0.05). Catalase, glutathione, and the total antioxidative capacity were increased and maintained their higher values in the later stage of fasting (p < 0.05), whereas malondialdehyde was not significantly changed (p > 0.05). Hepatic vein congestion, remarkable cytoplasmic vacuoles, and irregular cell shape were present in S. hasta which endured 3–7 days of fasting and were less pronounced when food shortage was prolonged. In terms of genes associated with glucose and lipid metabolism, the hepatic phosphofructokinase gene was constantly up-regulated during fasting (p < 0.05). However, the mRNA levels of glycogen synthase and glucose-6-phosphatase were obviously lower when the food scarcity extended to 7 days or more (p < 0.05). Fatty acid synthase, stearoyl-CoA desaturase 1, and peroxisome proliferator-activated receptor γ were substantially down-regulated in S. hasta livers after 7–14 days of food deprivation (p < 0.05). However, genes involved in lipolysis and fatty acid transport were transcriptionally enhanced to varying extents and peaked at the end of fasting (p < 0.05). Overall, starvation lasting 7 days or more could concurrently mobilize hepatic carbohydrates and fat as energy resources and diminished their hepatic accumulation by suppressing biosynthesis and enhancing catabolism and transport, ultimately metabolically and structurally perturbing the liver in S. hasta. This work presents preliminary data on the dynamic characteristics of hepatic glucose and lipid metabolism in S. hasta in response to starvation, which may shed light on the sophisticated mechanisms of energetic homeostasis in fish facing nutrient unavailability and may benefit the utilization/conservation of S. hasta.

Lipids are necessary nutrients for fish and play an important role in growth and metabolism. This study analyzed the effects of dietary lipid levels on growth performance, flesh quality, antioxidant status, and lipid metabolism of juvenile rice flower carp (Cyprinus carpio). The results showed that the weight gain rate and specific growth rate increased initially and then decreased with increasing dietary lipid levels, which 5.82 % dietary lipid level had the best growth in rice flower carp. Dietary lipid levels also affect the nutrition and quality of fish flesh. With the increase of dietary lipid levels, the hardness, adhesiveness, springiness, gumminess and chewiness of muscle showed a trend of increase and then decrease. Moreover, there are similar changes in the activity of antioxidant enzymes in the muscle, and the content of ROS and MDA was significantly higher than other levels at 11.80 % dietary lipid level. The expression of Nrf2 mRNA and some downstream antioxidant enzyme genes was the contrary. Furthermore, the content of TG, TC, and LDL-C in serum and liver increased with increasing dietary lipid levels. Meanwhile, it was observed that the lipid accumulation increased in the liver. The mRNA expression of ATGL and CPT1 genes associated with lipid metabolism in liver increased firstly and then decreased, the expression of FASN, PPARγ, and SREBP1 gradually increased, and reached its maximum at 11.8 % dietary lipid level. The above results showed that the growth performance of juvenile rice flower carp was optimal when the dietary lipid level of 5.82 %, and the nutrition and quality of fish flesh also has good effects. However, the dietary lipid level of 11.80 % inhibited the weight gain and induced oxidative stress and lipid metabolism disorders of rice flower carp, which can affect their flesh quality and health.

With the increasingly severe challenge of Software Supply Chain (SSC) security, the rising trend in guarding against security risks has attracted widespread attention. Existing techniques still face challenges in both accuracy and efficiency when detecting malware in SSC. To meet this challenge, this paper introduces two novel models, named the Bayesian Optimization-based Support Vector Machine (BO-SVM) and the Long Short-Term Memory–BO-SVM (LSTM-BO-SVM). The BO-SVM model is constructed on an SVM foundation, with its hyperparameters optimized by Bayesian Optimization. To further enhance its accuracy and efficiency, the LSTM-BO-SVM model is proposed, building upon BO-SVM and employing LSTM networks for pre-classification. Extensive experiments were conducted on two datasets: the balanced ClaMP dataset and the unbalanced CICMalDroid-2020 dataset. The experimental results indicate that the BO-SVM model is superior to other models in terms of accuracy; the accuracy of the LSTM-BO-SVM model on the two datasets is 98.2% and 98.6%, respectively, which is 2.9% and 2.2% higher than that of the BO-SVM on these two datasets.

As 5G technology becomes more widespread, the significant improvement in network speed and connection density has introduced more challenges to network security. In particular, distributed denial of service (DDoS) attacks have become more frequent and complex in software-defined network (SDN) environments. The complexity and diversity of 5G networks result in a great deal of unnecessary features, which may introduce noise into the detection process of an intrusion detection system (IDS) and reduce the generalization ability of the model. This paper aims to improve the performance of the IDS in 5G networks, especially in terms of detection speed and accuracy. It proposes an innovative feature selection (FS) method to filter out the most representative and distinguishing features from network traffic data to improve the robustness and detection efficiency of the IDS. To confirm the suggested method’s efficacy, this paper uses four common machine learning (ML) models to evaluate the InSDN, CICIDS2017, and CICIDS2018 datasets and conducts real-time DDoS attack detection on the simulation platform. According to experimental results, the suggested FS technique may match 5G network requirements for high speed and high reliability of the IDS while also drastically cutting down on detection time and preserving or improving DDoS detection accuracy.

Chlorophyll-a (Chl-a) concentration is one of the important indicators in water bodies for assessing the ecological health of water quality. In this paper, an OGolden-DBO-XGBoost Chl-a concentration inversion model is proposed using Wuliangsu Lake as the study area, and by combining the Sentinel-2 remote-sensing satellite images and measured Chl-a concentration data in Wuliangsu Lake, the XGBoost model is optimized using the hybrid-strategy-improved dung beetle optimization algorithm (OGolden-DBO), and an OGolden-DBO-XGBoost Chl-a concentration inversion model. The OGolden-DBO-XGBoost model’s coefficients of determination (R2s) were 0.8936 and 0.8850 on the training set and test set, according to the results. The root mean squared errors (RMSEs) were 3.1353 and 2.9659 μg/L, and the mean absolute errors (MAEs) were 1.8918 and 2.4282 μg/L. The model performed well and provided a strong support for the detection of Chl-a concentration in Wuliangsu Lake.

Soybean oil (SO), an important plant-derived lipid, is routinely used in aquafeed as a partial substitute for fish oil. However, the effect of various contents of SO in a SO-based aquafeed on specific aquatic animals and the underlying mechanisms are unclear. In this study, five isonitrogenous diets containing different SO contents (0 %, 3 %, 6 %, 9 %, and 12 %, named as S0, S3, S6, S9, and S12, respectively) were prepared with SO as the predominant lipid source, and 12-week feeding experiments were conducted on juvenile grass carp (Ctenopharyngodon idella) (initial weight: 12.54 ± 0.08 g). Apart from lower feed conversion ratio in the S6 and S9 groups (P 0.05). The S12 group exhibited significant decrease in the final weight and weight gain rate and increase in the viscerosomatic index (P

The utilization of ear tags for identifying breeding pigs is a widely used technique in the field of animal production. Ear tag dropout can lead to the loss of pig identity information, resulting in missing data and ambiguity in production management and genetic breeding data. Therefore, the identification of ear tag dropout is crucial for intelligent breeding in pig farms. In the production environment, promptly detecting breeding pigs with missing ear tags is challenging due to clustering overlap, small tag targets, and uneven sample distributions. This study proposes a method for detecting the dropout of breeding pigs’ ear tags in a complex environment by integrating an attention mechanism. Firstly, the approach involves designing a lightweight feature extraction module called IRDSC using depthwise separable convolution and an inverted residual structure; secondly, the SENet channel attention mechanism is integrated for enhancing deep semantic features; and finally, the IRDSC and SENet modules are incorporated into the backbone network of Cascade Mask R-CNN and the loss function is optimized with Focal Loss. The proposed algorithm, Cascade-TagLossDetector, achieves an accuracy of 90.02% in detecting ear tag dropout in breeding pigs, with a detection speed of 25.33 frames per second (fps), representing a 2.95% improvement in accuracy, and a 3.69 fps increase in speed compared to the previous method. The model size is reduced to 443.03 MB, a decrease of 72.90 MB, which enables real-time and accurate dropout detection while minimizing the storage requirements and providing technical support for the intelligent breeding of pigs.

This work fabricated a series of microstructures consisting of different equiaxed α (αeq) and β phase contents to investigated the effect of phase content on mechanical properties and deformation mechanism, including slip initiation, slip transfer, stress-induced martensite (SIM) and crack nucleation of TC21 titanium alloy. The results show that, with the decrease of αeq phase content, the YS of the alloy firstly decreases and then increases, the UTS gradually increases, and the EL gradually decreases. The significant variation of mechanical properties is closely related to the deformation mechanism of microstructures with different αeq phase contents. In sample with high αeq phase content, αeq phase is deformed by slip prior to β phase, and with the increase of strain, β phase can coordinate deformation by slip initiation and exhibits a better ability to coordinate plastic deformation. In samples with medium αeq phase content, the stability of β phase decreases, slip in αeq grain and SIM in β grain can be initiated simultaneously. However, the formation of SIM would harden β phase, and with the increase of strain, it would restrain the ability of β phase to further coordinate plastic deformation. In samples with low αeq phase content, the stability of β phase decreases sharply, which could induce the precipitation of fine-lamellar secondary α (αs) and acicular martensite α'' in β grain during annealing. These precipitated αs and α'' can not only inhibit the formation of SIM, but also dramatically reduce the ability of β phase to coordinate plastic deformation. Meanwhile, the evolution of deformation mechanism in different samples can significantly influence the crack nucleation location (slip band or αeq/β interface) during deformation. This paper analyzes in detail the effect of αeq phase content on mechanical properties of TC21 titanium alloy based on deformation mechanism, it would contribute to the establishment of a relationship among phase content, deformation mechanism and mechanical properties.

Chlorophyll-a (Chl-a) is an important parameter of water bodies, but due to the complexity of optics in water bodies, it is currently difficult to accurately predict Chl-a concentration in water bodies by traditional methods. In this paper, Sentinel-2 remote sensing images is used as the data source combined with measured data, and Ulansuhai Lake is taken as the study area. An adaptive ant colony exhaustive optimization (A-ACEO) algorithm is proposed for feature selection and combined with a novel intelligent algorithm of optimizing support vector regression (SVR) by genetic algorithm (GA) for prediction of Chl-a concentration. The ant colony optimization (ACO) algorithm is improved to select remote sensing feature bands for Chl-a concentration by introducing relevant optimization strategies. The GA-SVR model is built by optimizing SVR using GA with the selected feature bands as input, and comparing with the traditional SVR model. The simulation results show that under the same conditions, using A-ACEO algorithm to select feature bands as inputs can effectively reduce the model complexity, and improve the model prediction performance, which provides a valuable reference for monitoring Chl-a concentration in lakes.

Tamusu mudstone formation, located in the Alxa area in western Inner Mongolia, is considered a potential host formation for high-level radioactive waste (HLW) underground disposal in China. In this study, complementary analyses with X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), mercury intrusion porosimetry (MIP), and N2 physisorption isotherm were conducted on the Tamusu mudstone to characterize its physical characteristics and microstructural features, such as mineral compositions and pore structure. Several minerals, including carbonates, feldspar, clays and analcime, were identified in Tamusu mudstone by XRD. Images from FE-SEM show that pores in the Tamusu mudstone were dominantly on nanometer scale and generally located within their mineral matrix or at the interface with non-porous minerals. The combination of the MIP and N2 physisorption curves indicated that the Tamusu mudstone has diverse pore sizes, a porosity varying from 2.34% to 2.84%, and a total pore volume in the range of 0.0065–0.0222 cm3/g with the average pore diameter ranging from 9.6 nm to 19.23 nm. The specific surface area measured by MIP (2.572–5.861 m2/g) was generally higher than that by N2 physisorption (1.29–3.04 m2/g), due to the pore network effect, pore shape (e.g. ink-bottle shape), or technique limits. The results related to pore information can be applied as an input in the future to model single- or multi-phase fluid flow and the transport of radionuclides in porous geomedium by migration and diffusion.

Tamusu mudstone, located in Bayin Gobi Basin in Inner Mongolia of China, has been selected as a potential host rock for high-level radioactive waste (HLW) disposal in China. A series of tests has been carried out, including X-ray diffraction (XRD) tests, scanning electron microscopy (SEM) tests, disintegration tests, permeability tests and triaxial compression tests, to estimate the physico-mechanical properties of Tamusu mudstone in this work. The mineral composition of Tamusu mudstone was analyzed and it was considered as a stable rock due to its low disintegration rate, i.e. approximately 0.11% after several wet/dry cycles. Based on the results of permeability test, it was found that Tamusu mudstone has a low permeability, with the magnitude of about 10–20 m2. The low permeability makes the mudstone well prevent nuclide migration and diffusion, and might be influenced by temperature. The triaxial tests show that Tamusu mudstone is a stiff mudstone with high compressive strength, which means that the excavation disturbed zone would be smaller compared to other types of mudstone due to construction and operation of HLW repositories. Finally, the properties of Tamusu mudstone were compared with those of Opalinus clay, Callovo-Oxfordian (COx) argillite, and Boom clay to further discuss the possibility of using Tamusu mudstone as a potential nuclear waste disposal medium.

Simultaneous spatio-temporal description of tumor microvasculature, blood-brain barrier, and immune activity is pivotal to understanding the evolution mechanisms of highly aggressive glioblastoma, one of the most common primary brain tumors in adults. However, the existing intravital imaging modalities are still difficult to achieve it in one step. Here, we present a dual-scale multi-wavelength photoacoustic imaging approach cooperative with/without unique optical dyes to overcome this dilemma. Label-free photoacoustic imaging depicted the multiple heterogeneous features of neovascularization in tumor progression. In combination with classic Evans blue assay, the microelectromechanical system based photoacoustic microscopy enabled dynamic quantification of BBB dysfunction. Concurrently, using self-fabricated targeted protein probe (αCD11b-HSA@A1094) for tumor-associated myeloid cells, unparalleled imaging contrast of cells infiltration associated with tumor progression was visualized by differential photoacoustic imaging in the second near-infrared window at dual scale. Our photoacoustic imaging approach has great potential for tumor-immune microenvironment visualization to systematically reveal the tumor infiltration, heterogeneity, and metastasis in intracranial tumors.

As the unique identifier of individual breeding pigs, the loss of ear tags can result in the loss of breeding pigs’ identity information, leading to data gaps and confusion in production and genetic breeding records, which can have catastrophic consequences for breeding efforts. Detecting the loss of ear tags in breeding pigs can be challenging in production environments due to factors such as overlapping breeding pig clusters, imbalanced pig-to-tag ratios, and relatively small-sized ear tags. This study proposes an improved method for the detection of lost ear tags in breeding pigs based on Cascade Mask R-CNN. Firstly, the model utilizes ResNeXt combined with a feature pyramid network (FPN) as the feature extractor; secondly, the classification branch incorporates the online hard example mining (OHEM) technique to improve the utilization of ear tags and low-confidence samples; finally, the regression branch employs a decay factor of Soft-NMS to reduce the overlap of redundant bounding boxes. The experiment employs a sliding window detection method to evaluate the algorithm’s performance in detecting lost ear tags in breeding pigs in a production environment. The results show that the accuracy of the detection can reach 92.86%. This improvement effectively enhances the accuracy and real-time performance of lost ear tag detection, which is highly significant for the production and breeding of breeding pigs.

Urban water demand forecasting is the key component of smart water, which plays an important role in building a smart city. Although various methods have been proposed to improve forecast accuracy, most of these methods lack the ability to model spatio-temporal correlations. When dealing with the rich water demand monitoring data currently, it is difficult to achieve the desired prediction results. To address this issue from the perspective of improving the ability to extract temporal and spatial features, we propose a dynamic graph convolution-based spatio-temporal feature network (DG-STFN) model. Our model contains two major components, one is the dynamic graph generation module, which builds the dynamic graph structure based on the attention mechanism, and the other is the spatio-temporal feature block, which extracts the spatial and temporal features through graph convolution and conventional convolution. Based on the Shenzhen urban water supply dataset, five models SARIMAX, LSTM, STGCN, DCRNN, and ASTGCN are used to compare with DG-STFN proposed. The results show that DG-STFN outperforms the other models.

Abstract This paper aimed to investigate the multi‐objective optimization and decision‐making of the combined control law of guide vane (CCLGV) and pressure regulating valve (PRV) for hydroelectric unit under load rejection. Firstly, the multi‐objective optimization problem of CCLGV‐PRV is formulated. Then, a new multi‐objective gravitation search algorithm with non‐dominated screening and chaos mutation (NCMOGSA) is adopted to solve it. Moreover, an improved entropy weight method and relative objective proximity method are applied to select suitable solution. Finally, a comprehensive comparative study is carried out to reveal the mechanism between the CCLGV‐PRV and several basic parameters. The results indicate that replacing surge tank with PRV can effectively solve the contradictory between water pressure at the bottom of volute and rotational speed under load rejection. The NCMOGSA shows excellent performance in solving the multi‐objective optimization problem of CCLGV‐PRV and get a group of Pareto set. The improved entropy weight and relative objective proximity method make the final scheme clear. The rise rate of rotational speed is completely determined by the guide vane (GV), and the water pressure is jointly determined by the control law of the GV and PRV. The two‐stage closing and two‐stage opening (TCTO) is the final recommendation for CCLGV‐PRV.

The design and long-term safety of geological repositories for high-level radioactive waste (HLW) are dependent on the precise determination of the thermophysical parameters of mudstone. However, there is no relevant literature on the study of the thermophysical properties of Tamusu mudstone, a prospective rock for HLW disposal in China under the complex HLW disposal conditions. Therefore, in this paper, Tamusu mudstone is examined, and its thermophysical properties are tested at temperatures in the range of 25–80 °C with and without the influence of external forces. The thermophysical parameters exhibited significant anisotropic characteristics and were strongly correlated with temperature. The increase in temperature increases the specific heat capacity while lowering the thermal diffusivity. Due to the external force, the anisotropy of the thermophysical parameters decreases, enhancing the ability of the mudstone to transfer thermal energy. Furthermore, the aforementioned phenomena were interpreted from a microscopic perspective. This work can aid in the thermal-related physical phenomena of argillaceous rock and provide key input parameters for both analytical and numerical modeling in the safety assessment of HLW repositories, and other underground facilities at high temperatures.

The overall survival benefits of perioperative chemotherapy (PCT) and perioperative chemoradiotherapy (PCRT) for patients with locally advanced gastric cancer (GC) have not been fully explored. The aim of this study was to compare the benefits of PCT and PCRT in GC patients and determine the factors affecting survival rate using directed acyclic graphs (DAGs). The data of 1,442 patients with stage II-IV GC who received PCT or PCRT from 2000 to 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. First, the least absolute shrinkage and selection operator (LASSO) was used to identify possible influencing factors for overall survival. Second, the variables that were selected by LASSO were then used in univariate and Cox regression analyses. Third, corrective analyses for confounding factors were selected based on DAGs that show the possible association between advanced GC patients and outcomes and evaluate the prognosis. Patients who received PCRT had longer overall survival than those who received PCT treatment (P = 0.015). The median length of overall survival of the PCRT group was 36.5 (15.0 - 53.0) months longer than that of the PCT group (34.6 (16.0 - 48.0) months). PCRT is more likely to benefit patients who are aged ≤ 65, male, white, and have regional tumors (P

Tamusu mudstone is a candidate geological medium for high-level radioactive waste disposal in China. This paper investigates its anisotropic hydraulic properties. Permeability measurements were conducted on two kinds of samples, i.e., along the directions perpendicular and parallel to the beddings, under different stress conditions with heating-cooling cycles (20 → 40→60 → 80→60 → 40→20 °C). The results confirmed the hydraulic anisotropy of Tamusu mudstone. Increasing lithostatic pressure decreases the intrinsic permeability k and hydraulic conductivity K and decreases the hydraulic anisotropy of Tamusu mudstone. The temperature significantly affects the hydraulic properties: the k values exhibit a negative correlation with temperature. A notable variation in parallel hydraulic properties upon temperature elevation indicates that the thermal effect is more crucial in the direction parallel at low lithostatic pressure. A notable effect of thermal paths on the hydraulic properties of Tamusu mudstone was exhibited through the different K or k at the same temperatures before and after heating-cooling cycles.

Protein hydrolysates are rich in amino acids and bioactive peptides, beneficial for the organism health. This study analyzed not only the effects of dietary supplementation with P. clarkii shell protein hydrolysates (PCSPHs) on the growth performance, muscle biochemical indices and histological characteristics of zebrafish, but also the changes of muscle antioxidant capacity and circadian clock genes expression were also evaluated. After feeding, the final body weight, weight gain rate and specific growth rate of zebrafish fed with PCSPHs supplementation were significantly higher than normal diet, and reduced contents of muscle triglyceride and aspartate aminotransferase. Meanwhile, dietary supplementation with PCSPHs improved total amino acid contents and myofiber structure of zebrafish. Antioxidant enzyme activities of total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) content, and the expression of antioxidant related genes increased with PCSPHs supplementation. Furthermore, the expression of Nrf2 protein showed a significantly up-regulated trend with the increasing of dietary PCSPHs levels. However, it was interesting that the expression of circadian rhythm related genes was also affected by dietary PCSPHs levels, and showed a significant up-regulated and down-regulated trend. The above results showed that dietary supplementation with PCSPHs could promote the growth performance, muscle amino acid contents and myofiber structure of zebrafish, but also enhance the muscle antioxidant capacity and regulates the expression of circadian clock genes. It is hypothesized that this may be related to the expression of antioxidant signaling pathway Nrf2/Keap1. Our study will provide a theoretical basis for improving the muscle quality and health of aquatic animals.

Abstract Background Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. Results ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. Conclusions YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

To investigate the difference of microbial communities among Diannan small-ear (DNSE), Dahe black (DHB) and Yorkshire (YS) pigs, we compared the microbial taxonomic and functional composition using a metagenomic approach. A total of 1,002,362 non-redundant microbial genes were identified, DHB and YS pigs had more similar genetic makeup compared with DNSE pigs. Bacteroidetes, Firmicutes and Spirochetes were the three most abundant phyla for all pig breeds, and DNSE pigs had a higher abundance of Prevotella genus than DHB and YS pigs. The functional profiles varied among the three pig breeds, DNSE pigs had more active carbohydrate metabolism and more abundant antibiotic resistance genes than the other two pig breeds. Moreover, we found that peptide and macrolide resistances genes in DNSE pigs were more abundant than that in DHB pigs (p < 0.05). This study will help to provide a theoretical basis for the development of native pig breeds in Yunnan Province, China.

Photodynamic therapy (PDT) is a promising alternative and palliative therapeutic strategy for colorectal cancer (CRC). A novel photosensitizer with higher selectivity for CRC and fewer side effects is vital for clinical application. Given that the overexpression of hydrogen sulfide (H2S) in CRC, it is expected to provide a selective stimulus for activatable photosensitizers that in respond to the specific microenvironment. Herein, we report a novel development of metal-organic frameworks (MOFs) composed of meso-Tetra (4-carboxyphenyl) porphine (TCPP) and ferric ion (Fe3+) through a facile one-pot process. Experiments both in vitro and in vivo reveal that the MOF is capable of depredating in response to the high content of H2S in tumor microenvironment of CRC. Accompanying with the degradation and release of TCPP, the fluorescence and photosensitivity effect is switched from “off” to “on”, enabling the MOF to serve as a H2S activatable nano-photosensitizer for real-time fluorescence imaging-guided and targeted PDT of CRC.

Nasopharyngeal carcinoma occurs in many parts of the pars nasalis pharyngis, and the pathological type is mainly squamous cell carcinoma. Because of the special position of nasopharynx, breathing, pronunciation and daily life will be seriously affected. At present, the research direction of nasopharyngeal carcinoma is mainly to explore the law of tumor cell proliferation and migration, study the molecular mechanism, master its biological behavior and clinical significance, try to find therapeutic targets, and further improve the level of tumor treatment. However, the pathologic structure and molecular mechanism of nasopharyngeal carcinoma have not been fully elucidated. In this study, the Lentivirus-mediated EIF3C shRNA vector (L.V-shEIF3C) was constructed to down-regulate the expression of EIF3C in human pharyngeal squamous carcinoma cell FaDu and the human nasopharyngeal carcinoma cell 5-8F, it was found that down-regulation of EIF3C could significantly inhibit the cell proliferation, promote cell apoptosis, induce cell cycle arrest, and inhibit the formation and growth of tumors in mouse models. This study provides strong evidence that EIF3C is a key gene driving the development and progression of head and neck cancer, which is of great significance for the diagnosis, prognosis or treatment of tumors, suggesting that EIF3C may become a valuable therapeutic development and intervention target.

Human hepatocyte transplantation for liver disease treatment have been hampered by the lack of quality human hepatocytes. Pigs with their large body size, longevity and physiological similarities with human are appropriate animal models for the in vivo expansion of human hepatocytes. Here we report on the generation of RAG2-/-IL2Rγ-/YFAH-/- (RGFKO) pigs via CRISPR/Cas9 system and somatic cell nuclear transfer. We showed that thymic and splenic development in RGFKO pigs was impaired. V(D)J recombination processes were also inactivated. Consequently, RGFKO pigs had significantly reduced numbers of porcine T, B and NK cells. Moreover, due to the loss of FAH, porcine hepatocytes continuously undergo apoptosis and consequently suffer hepatic damage. Thus, RGFKO pigs are both immune deficient and constantly suffer liver injury in the absence of NTBC supplementation. These results suggest that RGFKO pigs have the potential to be engrafted with human hepatocytes without immune rejection, thereby allowing for large scale expansion of human hepatocytes.

Government investment, as a major government function, is closely related to national development and economic growth. It plays a key role to maximize the benefits of this fund, which requires the government to choose the optimal investment plan. Considering the complex and uncertain decision-making environment, we propose the nested probabilistic linguistic preference relation (NPLPR) based on the nested probabilistic linguistic term sets (NPLTSs), to express preference information from the qualitative and quantitative angle. According to graph theory, we define a consistency index and an acceptable consistency of NPLPR to measure the additive consistency. Based on which, we establish a novel algorithm for unacceptable consistent NPLPR to meet the acceptable consistency. Finally, projects in government investment are evaluated by the proposed decision-making method, and some comparative analyses, discussions, and implications are provided from three angles. This study provides a new perspective for scholars to make scientific and rational decisions with the help of technological and economic development in various fields.

Background: To study the association between indoor environment (MiE), blood trace elements (BTE), and immune globulin (PRO) among workers from vegetables plastic greenhouse, and to assess the mediate effects on MiE and PRO by BTE. Methods: Overall, 168 practitioner and corresponding sheds were included from cross-sectional study in 2016. BTE and PRO were determined by physical test and MiE data from field and laboratory measurement. The association was assessed using canonical correlation analysis. The direct and indirect effects between MiE, PRO and BTE were conducted by structural equation model. 5000 times bootstrap methods were performed to estimate coefficient and 95% confidence interval. Results: MiE was moderately correlated with BTE (canonical coefficient = 0.439), and BTE was strongly correlated with PRO (canonical coefficient = 0.514 and 0.481). No statistical evidence was found for the overall impact of MiE on PRO, and BTE as an intermediary affecting its relevance was not confirmed. Only the path way of the BTE impact on PRO had a significant positive effect (P=0.012). Conclusion: BTE was positively associated with PRO, therefore, reducing exposure in greenhouse is a pathway to remain blood trace elements, and further effect the immune protein in human body.

A core concern in the research on deep geological disposal of high-level radioactive waste is the migration of radionuclides in geological bodies. Most studies on radionuclide migration consider the role of only the rock fissures without incorporating the influence of the rock matrix. In this paper, the rock mass for geological disposal of high-level radioactive waste is regarded as a fissure-pore medium. Considering the influences of radionuclide diffusion and fluid transport on radionuclide migration in the process of disposal, the governing equation of radionuclide migration and evolution in the pore-fissure medium is established. The numerical scheme of the governing equation is given based on the mixed finite volume method (FVM), using our program solution module written in C++. On this basis, the numerical test model with fissures was developed, which analyzed the radionuclide migration law in clayey rocks under various fissure and rock matrix diffusion coefficients and hydraulic conductivities. The simulation results are compared with finite element method results, revealing the superiority of the mixed FVM method in solving problems of radionuclide migration in discontinuous geological bodies containing hiatuses, mutations, and fissures. The study provides a theoretical basis for evaluating the safety, feasibility, and suitability of geological disposal repositories for high-level radioactive waste in terms of radionuclide migration.

The europium sorption on Tamusu clay was investigated by batch sorption experiments and spectroscopic study under the condition of strong ionic strength. The results demonstrated that europium sorption on Tamusu clay increased rapidly with pH value, but decreased with the ionic strength of solution increased. The europium sorption also increased in the presence of humic acid, especially at low pH value. The sorption could be fitted by Freundlich isotherm model and the europium sorption on clay was spontaneous and endothermic reaction. Besides, the result indicates that ion exchange was the main process at low pH value, while inner-sphere surface complexation dominated the sorption process at high pH value. The Backscatter electron scanning/Energy Dispersive Spectrometer(BSE/EDS) and the effect of Na for europium sorption results further suggested that europium sorption on Tamusu clay mainly competed with Na at low pH value. Overall, the results in this research were of significance to understand the sorption behavior of europium on the geological media under high ionic strength.

Activation of human immune T-cells by swine leukocyte antigens class I (SLA-I) and class II (SLA-II) leads to xenograft destruction. Here, we generated the GGTA1, B2M, and CIITA (GBC) triple-gene-modified Diannan miniature pigs, analyzed the transcriptome of GBC-modified peripheral blood mononuclear cells (PBMCs) in the pig's spleen, and investigated their effectiveness in anti-immunological rejection. A total of six cloned piglets were successfully generated using somatic cell nuclear transfer, one of them carrying the heterozygous mutations in triple genes and the other five piglets carrying the homozygous mutations in GGTA1 and CIITA genes, but have the heterozygous mutation in the B2M gene. The autopsy of GBC-modified pigs revealed that a lot of spot bleeding in the kidney, severe suppuration and necrosis in the lungs, enlarged peripulmonary lymph nodes, and adhesion between the lungs and chest wall were found. Phenotyping data showed that the mRNA expressions of triple genes and protein expressions of B2M and CIITA genes were still detectable and comparable with wild-type (WT) pigs in multiple tissues, but α1,3-galactosyltransferase was eliminated, SLA-I was significantly decreased, and four subtypes of SLA-II were absent in GBC-modified pigs. In addition, even in swine umbilical vein endothelial cells (SUVEC) induced by recombinant porcine interferon gamma (IFN-γ), the expression of SLA-I in GBC-modified pig was lower than that in WT pigs. Similarly, the expression of SLA-II DR and DQ also cannot be induced by recombinant porcine IFN-γ. Through RNA sequencing (RNA-seq), 150 differentially expressed genes were identified in the PBMCs of the pig's spleen, and most of them were involved in immune- and infection-relevant pathways that include antigen processing and presentation and viral myocarditis, resulting in the pigs with GBC modification being susceptible to pathogenic microorganism. Furthermore, the numbers of human IgM binding to the fibroblast cells of GBC-modified pigs were obviously reduced. The GBC-modified porcine PBMCs triggered the weaker proliferation of human PBMCs than WT PBMCs. These findings indicated that the absence of the expression of α1,3-galactosyltransferase and SLA-II and the downregulation of SLA-I enhanced the ability of immunological tolerance in pig-to-human xenotransplantation.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

Abstract Background Optic atrophy 1 (OPA1) gene mutations are associated with dominantly inherited optic neuropathy resulting in a progressive loss of visual acuity. Compound heterozygous or homozygous variants that lead to severe phenotypes, including Behr syndrome, have been reported rarely. Case presentation Here, we present a 14-month-old boy with early onset optic atrophy, congenital cataracts, neuromuscular disorders, mental retardation, and developmental delay. Combined genetic testing, including whole exome sequencing (WES) and chromosomal microarray analysis, revealed a concurrent OPA1 variant (c.2189 T > C p.Leu730Ser) and de novo chromosome 3q deletion as pathogenic variants leading to the severe phenotype. Conclusions Our case is the first reporting a novel missense OPA1 variant co-occurring with a chromosomal microdeletion leading to a severe phenotype reminiscent of Behr syndrome. This expands the mutation spectrum of OPA1 and inheritance patterns of this disease.

Abstract Acute respiratory distress syndrome virus-2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) infection, which causes global public health emergencies, has sped widely for more than 5 months and has the risk of long-term transmission. No effective treatment has been discovered to date. In the cases we report, the patient continued to deteriorate even after administration of antiviral drugs such as lopinavir/ritonavir, interferon-α, and ribavirin, as well as intravenous injection of meropenem, methylprednisolone, and immunoglobulin. So, we infused the patient with convalescent plasma (CP), and the absolute lymphocyte count increased the next day and returned to normal on the fourth day. Followed by intravenous infusion of mesenchymal stem cells (MSCs), bilateral infiltrates were absorbed and the pulmonary function was significantly improved. We note that the intravenous infusion of CP and MSCs for the treatment of severe COVID-19 patients may have synergistic characteristics in inhibiting cytokine storm, promoting the repair of lung injury, and recovering pulmonary function. We hope to provide a reference for the research direction of COVID-19 clinical strategies.

Abstract Background Esophageal cancer (EC) is one of the most common human cancers, with a particularly aggressive behavior and increased incidence worldwide. The aim of this study was to assess the associations of single-nucleotide polymorphisms (SNPs) in IL-1B with the risk of EC in a northwest Chinese Han population. Methods In order to evaluate the correlations between IL-1B polymorphisms and EC risk, an Agena MassARRAY platform was used to determine the genotype of the candidate SNPs among 384 EC patients and 499 controls. The associations between IL-1B variants and EC risk were examined using logistic regression analysis with adjustment for gender and age. Haplotype construction and analysis were performed to detect the potential associations between haplotypes within IL-1B and EC susceptibility. Additionally, bioinformatics databases were used for gene expression analysis and SNP functional prediction. Results A significant relationship was found between IL-1B rs2853550 and an increased risk of EC in the allele model [odds ratio (OR) = 1.38, 95% confidence interval (95% CI): 1.01–1.89, p = 0.041), the codominant model (A/G, OR = 1.63, 95% CI: 1.10–2.42, p = 0.011), and the dominant model (OR = 1.49, 95% CI: 1.02–2.18, p = 0.041). Functional analysis revealed the potential effects of rs2853550, which further reinforced its influence on EC susceptibility. However, there were no statistically significant differences for other SNPs or haplotypes between EC cases and healthy controls. Expression analysis conducted with dataset indicated that the expression level of IL-1B was higher in EC cases than that in normal samples. Conclusions This study demonstrated that rs2853550 in IL-1B might increase EC susceptibility in the Chinese Han population of Northwest China.

Abstract Background Parathyroid protection and central neck dissection (CND) are basic points of thyroid cancer surgery and draw persistent concern. We aimed to evaluate the value of carbon nanoparticles (CNs) for parathyroid gland protection and CND in thyroid surgery for thyroid cancer patients. Methods A total of 386 consecutive thyroid cancer patients were enrolled in the retrospective study. Three hundred thirty-four patients using CNs intraoperatively were included in the CN group, and 52 patients without using CNs or any other helping agent were included in the control group. Intact parathyroid hormone (iPTH) was examined. Medical records and histopathologic reports were reviewed. Histopathologic examination was performed. Results There were no statistical significances in demographic and basic surgical information, preoperative iPTH, and serum calcium between the two groups (P > 0.05). In the CN group, the thyroid tissue and central neck lymph nodes were stained black by CNs, while the parathyroid glands were not. Histopathological examination showed that the carbon nanoparticles might accumulated in the subcapsular sinus of lymph nodes compared with the none-stained samples. The staining with CNs did not impact the histopathological examination. There were no significant differences in postoperative hypocalcemia and hypoPT at day 1, 1 month, and half year after surgery between the two groups, respectively. There was a big decline of iPTH level after surgery, whereas the perioperative decreasing amplitude of PTH was not statistically different between the CNs and control group (57.2 ± 28.6 vs 55.7 ± 27.8, P = 0.710). There were 43 patients occurring incidental parathyroidectomy in the CN group (43/334, 12.9%) and 7 patients in the control group (7/52, 13.5%), without significant difference (P = 0.907). There was no significant difference in the number of lymph nodes identified by pathology per patient between the CNs and control group regardless of unilateral and bilateral CND. Conclusions Carbon nanoparticles help highlight parathyroid glands and lymph nodes in thyroidectomy, but generate no significant benefit for parathyroid glands protection and lymph node dissection. The value of carbon nanoparticles in thyroid cancer surgery should not be exaggerated and needs further evaluation.