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In order to investigate changes in flavor substances of lightly-pickled cucumbers during storage, volatile compounds were analyzed by electronic nose and gas chromatography-ion mobility spectrometry (GC-IMS). The results showed that flavor characteristics of lightly-pickled cucumbers changed obviously during storage. A total of 56 volatile organic compounds (VOCs) were detected by GC-IMS, including 10 alcohols, 30 aldehydes, 8 ketones, 5 esters, 1 furan, 1 acid, and 1 alkane. With the extension of storage period, the relative contents of aldehydes, alcohols and ketones decreased significantly, while the contents of esters increased significantly (P1), including cis-6-nonenal, nonenal, 1-penten-3-one, isobutyraldehyde, trans-2,cis-6-nonadienal, and trans-2-octenal. Among them, trans-2-octenal increased with the relative extension of storage time, which might be the main off-flavor compound for flavor deterioration. This study can provide a theoretical basis for flavor quality evaluation of lightly-pickled cucumbers during storage.

Land and soil resources are scarce in the Tibetan Plateau, and the region is facing ecological pressure from climate warming and increasing human activities. As a major ecological problem, gully erosion is destroying land and soil resources on the Tibetan Plateau, but related research is limited, and susceptibility areas and influencing factors are unclear. Machine learning methods are often applied to study gully initiation susceptibility, but they require a programming foundation. Therefore, the Redui watershed on the southern Tibetan Plateau with severe gully erosion was selected to evaluate the susceptibility and influencing factors of gully initiation through 12 influencing factors including topography, human activity, and underlying surface conditions, and all 2310 gully headcut sites. Two non-code nonlinear modeling methods, the categorical Regression (CATREG) and geographical detector (Geodetector) methods, were first used in the spatial modeling of gully initiation susceptibility. The results showed that the gully initiation susceptibility of the hillslope around the alluvial fan was highest. The very high susceptibility areas of the CATREG model and Geodetector model account for 18.2% and 16% of the total, respectively. The main influencing factors of gully initiation were elevation, relief, and soil type recognized by CATREG, and elevation, human footprint, and soil type recognized by Geodetector. Elevation is the primary factor controlling downstream susceptibility in both models. The primary factors in the upper and middle reaches are soil type and relief identified by CATREG. Human footprint, soil type, and distance to road are primary factors in the upper and middle reaches identified by Geodetector. The explanatory power of elevation, elevation-relief interaction, Geodetector model and CATREG model were 39%, 54%, 46.4% and 73.8%, respectively, at extremely significant levels (P

Abstract Background Energy allocation between growth and reproduction determines puberty onset and fertility. In mammals, peripheral hormones such as leptin, insulin and ghrelin signal metabolic information to the higher centres controlling gonadotrophin-releasing hormone neurone activity. However, these observations could not be confirmed in lower vertebrates, suggesting that other factors may mediate the energetic trade-off between growth and reproduction. A bioinformatic and experimental study suggested co-regulation of the circadian clock, reproductive axis and growth-regulating genes in zebrafish. While loss-of-function of most of the identified co-regulated genes had no effect or only had mild effects on reproduction, no such information existed about the co-regulated somatostatin, well-known for its actions on growth and metabolism. Results We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20–30% increase in embryonic primordial germ cells, and sst1.2 −/− adults laid 40% more eggs than their wild-type siblings. The sst1.1 −/− and sst1.2 −/− mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass. Conclusions We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility.

Abstract Background Eukaryotic genes contain introns that are removed by the spliceosomal machinery during mRNA maturation. Introns impose a huge energetic burden on a cell; therefore, they must play an essential role in maintaining genome stability and/or regulating gene expression. Many genes (> 50%) in Plasmodium parasites contain predicted introns, including introns in 5′ and 3′ untranslated regions (UTR). However, the roles of UTR introns in the gene expression of malaria parasites remain unknown. Methods In this study, an episomal dual-luciferase assay was developed to evaluate gene expression driven by promoters with or without a 5′UTR intron from four Plasmodium yoelii genes. To investigate the effect of the 5′UTR intron on endogenous gene expression, the pytctp gene was tagged with 3xHA at the N-terminal of the coding region, and parasites with or without the 5′UTR intron were generated using the CRISPR/Cas9 system. Results We showed that promoters with 5′UTR introns had higher activities in driving gene expression than those without 5′UTR introns. The results were confirmed in recombinant parasites expressing an HA-tagged gene (pytctp) driven by promoter with or without 5′UTR intron. The enhancement of gene expression was intron size dependent, but not the DNA sequence, e.g. the longer the intron, the higher levels of expression. Similar results were observed when a promoter from one strain of P. yoelii was introduced into different parasite strains. Finally, the 5′UTR introns were alternatively spliced in different parasite development stages, suggesting an active mechanism employed by the parasites to regulate gene expression in various developmental stages. Conclusions Plasmodium 5′UTR introns enhance gene expression in a size-dependent manner; the presence of alternatively spliced mRNAs in different parasite developmental stages suggests that alternative slicing of 5′UTR introns is one of the key mechanisms in regulating parasite gene expression and differentiation. Graphical Abstract

Abstract The stability of anthocyanins is poor, seriously affecting their biological activity. The effect of bovine serum albumin (BSA) on the stability of purple sweet potato anthocyanins (PSPA) and its mechanism of action was investigated. Eleven anthocyanins in purple sweet potato were identified, and the stability of PSPAs with different structures combined with BSA was analyzed separately. The results showed an interaction between BSA and PSPA by UV absorption and fluorescence spectra, in which PSPA could cause a fluorescence burst of BSA, and the binding of PSPA to BSA was in the form of 1:1. In addition, the interactions are spontaneous, and hydrophobic interactions dominate. The binding amount study showed that 1 mol/L of BSA binds 3 mol/L of PSPA. The results of zeta potential and particle size showed that the absolute value of the possibility was around 30 mV, and BSA could combine with PSPA to form nanoparticles with high stability. Molecular docking analysis showed that PSPA could be well embedded in the structural cavities of BSA. The binding sites were near sites I and II, hydrogen bonding and hydrophobic interactions act as the main drivers of binding. Finally, after binding, BSA could effectively improve the stability of PSPA, especially for different structures of PSPA. The binding of diacylated anthocyanins was more stable than monoacylated ones, peonidin was more stable than cyanidin, and caffeoyl was more stable compared to p‐hydroxybenzoyl and feruloyl.

ObjectiveTo explore the association between circadian syndrome (CircS) and Metabolic Syndrome (MetS) with psoriasis. Compare the performance of MetS and CircS in predicting psoriasis.MethodsAn observational study used data from the NHANES surveys conducted in 2005–2006 and 2009–2014. We constructed three multiple logistic regression models to investigate the relationship between MetS, CircS, and their components with psoriasis. The performance of MetS and CircS in predicting psoriasis was compared using five machine-learning algorithms, and the best-performing model was explained via SHAP. Then, bidirectional Mendelian randomization analyses with the inverse variance weighted (IVW) as the primary method were employed to determine the causal effects of each component.ResultA total of 9,531 participants were eligible for the study. Both the MetS (OR = 1.53, 95%CI: 1.07–2.17, P = 0.02) and CircS (OR = 1.40, 95%CI: 1.02–1.91, P = 0.039) positively correlated with psoriasis. Each CircS algorithmic model performs better than MetS, with Categorical Features+Gradient Boosting for CircS (the area under the precision-recall curve = 0.969) having the best prediction effect on psoriasis. Among the components of CircS, elevated blood pressure, depression symptoms, elevated waist circumference (WC), and short sleep contributed more to predicting psoriasis. Under the IVW methods, there were significant causal relationships between WC (OR = 1.52, 95%CI: 1.34−1.73, P = 1.35e-10), hypertension (OR = 1.68, 95%CI: 1.19−2.37, P = 0.003), depression symptoms (OR = 1.39, 95%CI: 1.17−1.65, P = 1.51e-4), and short sleep (OR = 2.03, 95%CI: 1.21–3.39, p = 0.007) with psoriasis risk.ConclusionCircS demonstrated superior predictive ability for prevalent psoriasis compared to MetS, with elevated blood pressure, depression symptoms, and elevated WC contributing more to the prediction.

Radish (Raphanus sativus L.) undergoes texture changes in their phy-chemical properties during the long-term dry-salting process. In our study, we found that during the 60-day salting period, the hardness and crispness of radish decreased significantly. In further investigation, we observed that the collaborative action of pectin methylesterase (PME) and polygalacturonase (PG) significantly decreased the total pectin, alkali-soluble pectin (ASP), and chelator-soluble pectin (CSP) content, while increasing the water-soluble pectin (WSP) content. Furthermore, the elevated activities of cellulase and hemicellulase directly led to the notable fragmentation of cellulose and hemicellulose. The above reactions jointly induced the depolymerization and degradation of cell wall polysaccharides, resulting in an enlargement of intercellular spaces and shrinkage of the cell wall, which ultimately led to a reduction in the hardness and crispness of the salted radish. This study provided key insights and guidance for better maintaining textural properties during the dry-salting process of radish.

Nucleic acid drugs are attracting significant attention as prospective therapeutics. However, their efficacy is hindered by challenges in penetrating cell membranes and reaching target tissues, limiting their applications. Nucleotidyl lipids, with their specific intermolecular interactions such as H-bonding and π-π stacking, offer a promising solution as gene delivery vehicles. In this study, a novel series of nucleotide-based amphiphiles were synthesized. These lipid molecules possess the ability to self-assemble into spherical vesicles of appropriate size and zeta potential in aqueous solution. Furthermore, their complexes with oligonucleotides demonstrated favorable biocompatibility and exhibited antiproliferative effects against a broad range of cancer cells. Additionally, when combined with the cationic lipid CLD, these complexes displayed promising in vitro performance and in vivo efficacy. By incorporating DSPE-PEGylated cRGD into the formulation, targeted accumulation of siG12D in pancreatic cancer cells increased from approximately 6% to 18%, leading to effective treatment outcomes (intravenous administration, 1 mg/kg). This finding holds significant importance for the liposomal delivery of nucleic acid drugs to extrahepatic tissues.

Abstract Background Heart failure (HF) seriously threatens human health worldwide. However, the pathological mechanisms underlying HF are still not fully clear. Results In this study, we performed proteomics and transcriptomics analyses on samples from human HF patients and healthy donors to obtain an overview of the detailed changes in protein and mRNA expression that occur during HF. We found substantial differences in protein expression changes between the atria and ventricles of myocardial tissues from patients with HF. Interestingly, the metabolic state of ventricular tissues was altered in HF samples, and inflammatory pathways were activated in atrial tissues. Through analysis of differentially expressed genes in HF samples, we found that several glutathione S-transferase (GST) family members, especially glutathione S-transferase M2-2 (GSTM2), were decreased in all the ventricular samples. Furthermore, GSTM2 overexpression effectively relieved the progression of cardiac hypertrophy in a transverse aortic constriction (TAC) surgery-induced HF mouse model. Moreover, we found that GSTM2 attenuated DNA damage and extrachromosomal circular DNA (eccDNA) production in cardiomyocytes, thereby ameliorating interferon-I-stimulated macrophage inflammation in heart tissues. Conclusions Our study establishes a proteomic and transcriptomic map of human HF tissues, highlights the functional importance of GSTM2 in HF progression, and provides a novel therapeutic target for HF.

Glypicans are closely associated with organ development and tumorigenesis in animals. Dally-like (Dlp), a membrane-bound glypican, plays pivotal roles in various biological processes in Drosophila. In this study, we observed that an excess of Dlp led to the malformation of legs, particularly affecting the distal part. Accordingly, the leg disc was shrunken and frequently exhibited aberrant morphology. In addition, elevated Dlp levels induced ectopic cell death with no apparent cell proliferation changes. Furthermore, Dlp overexpression in the posterior compartment significantly altered Wingless (Wg) distribution. We observed a marked expansion of Wg distribution within the posterior compartment, accompanied by a corresponding decrease in the anterior compartment. It appears that excess Dlp guides Wg to diffuse to cells with higher Dlp levels. In addition, the distal-less (dll) gene, which is crucial for leg patterning, was up-regulated significantly. Notably, dachshund (dac) and homothorax (hth) expression, also essential for leg patterning and development, only appeared to be negligibly affected. Based on these findings, we speculate that excess Dlp may contribute to malformations of the distal leg region of Drosophila, possibly through its influence on Wg distribution, dll expression and induced cell death. Our research advances the understanding of Dlp function in Drosophila leg development.

Abstract Background Aging is a dynamic and heterogeneous process that may better be captured by trajectories of aging biomarkers. Biological age has been advocated as a better biomarker of aging than chronological age, and plant-based dietary patterns have been found to be linked to aging. However, the associations of biological age trajectories with mortality and plant-based dietary patterns remained unclear. Methods Using group-based trajectory modeling approach, we identified distinctive aging trajectory groups among 12,784 participants based on a recently developed biological aging measure acquired at four-time points within an 8-year period. We then examined associations between aging trajectories and quintiles of plant-based dietary patterns assessed by overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) among 10,191 participants who had complete data on dietary intake, using multivariable multinomial logistics regression adjusting for sociodemographic and lifestyles factors. Cox proportional hazards regression models were applied to investigate the association between aging trajectories and all-cause mortality. Results We identified three latent classes of accelerated aging trajectories: slow aging, medium-degree, and high-degree accelerated aging trajectories. Participants who had higher PDI or hPDI had lower odds of being in medium-degree (OR = 0.75, 95% CI: 0.65, 0.86 for PDI; OR = 0.73, 95% CI: 0.62, 0.85 for hPDI) or high-degree (OR = 0.63, 95% CI: 0.46, 0.86 for PDI; OR = 0.62, 95% CI: 0.44, 0.88 for hPDI) accelerated aging trajectories. Participants in the highest quintile of uPDI were more likely to be in medium-degree (OR = 1.72, 95% CI: 1.48, 1.99) or high-degree (OR = 1.70, 95% CI: 1.21, 2.38) accelerated aging trajectories. With a mean follow-up time of 8.40 years and 803 (6.28%) participants died by the end of follow-up, we found that participants in medium-degree (HR = 1.56, 95% CI: 1.29, 1.89) or high-degree (HR = 3.72, 95% CI: 2.73, 5.08) accelerated aging trajectory groups had higher risks of death than those in the slow aging trajectory. Conclusions We identified three distinctive aging trajectories in a large Asian cohort and found that adopting a plant-based dietary pattern, especially when rich in healthful plant foods, was associated with substantially lowered pace of aging.

Fresh agricultural products are frequently contaminated with Listeria monocytogenes (L. monocytogenes), which threatens consumer health. The mechanism of the inhibitory effect of ultrasound and sodium hypochlorite (US-NaClO) on L. monocytogenes on fresh-cut cucumber remains poorly understood. Therefore, the bactericidal ability and mechanism of US-NaClO treatment on L. monocytogenes were studied on fresh-cut cucumber during storage using various approaches such as determination of intracellular material leakage, scanning electron microscopy, flow cytometry, and expression analysis of virulence genes. The results showed that the number of L. monocytogenes on fresh-cut cucumber was significantly reduced after ultrasound treatment for 5 min in combined with 75 ppm sodium hypochlorite treatment(P

This study explored the potential of polysaccharides from Actium lappa (ALPs) as natural wall materials for producing ALP-based nanoparticles to deliver poorly water-soluble oleanolic acid (OA) and ursolic acid (UA). Encapsulating OA+UA with ALPs (ALP:OA+UA, 50:1; OA:UA, 1:1) changed the crystalline nature to a more amorphous state through hydrogen bonding and involving O–H/C–O/O–C–O groups. ALP-OA/UA nanoparticles had a particle size and zeta potential (in water) of 199.1 nm/–7.15 mV, with a narrow unimodal size distribution, and excellent pH, salt solution, temperature and storage stability. Compared with ALPs, ALP-OA/UA nanoparticles showed enhanced anti-inflammatory activity (especially at a dose of 100 μg/mL) in a CuSO4-induced zebrafish inflammation model via down-regulating the NF-κB signalling pathway and gene expression of associated transcription factors and cytokines (TNF-α, IL-1β and IL-8). Therefore, ALP-based nanoparticles are natural and anti-inflammatory carriers for hydrophobic bioactive molecules.

Background: A hospital-based case-control study was carried out to elucidate the association of Matrix metalloproteinase-2 (MMP-2) gene candidate polymorphisms with the susceptibility to Alzheimer’s disease (AD) in the Chinese Han population. Methods: A total of 200 AD cases and an equal number of healthy controls were recruited to undergo genotyping of specific loci within the MMP-2 gene loci (rs243866, rs2285053, rs243865). Logistic regression analysis was applied to examine the association of the genotypes and alleles of MMP-2 gene polymorphisms with AD after adjusting clinical confounding factors. Results: Within AD group, a high proportion of rs243866 genotype carriers were found, and the difference remained significant despite adjusting for other clinical indicators. Among individuals with the rs243866 AA genotype and rs243865 TT genotype, the onset age of AD occurred at a younger age. Early-onset AD risk in rs243866 AA genotype carriers was 6.528 times higher than those in GG genotype carriers, and individuals with rs243865 TT genotype faced a 4.048-fold increased risk compared to those with CC genotype. Conclusions: MMP-2 gene rs243866 and rs243865 polymorphisms were closely associated with the onset age of AD. The presence of rs243866 AA genotype emerged as a crucial predictor of AD risk.

BackgroundDespite the well-grounded benefits of physical activity (PA), poor compliance with the PA guidelines has been reported among head and neck cancer (HNC) patients. Mobile health (mHealth)-based interventions can help cancer survivors increase their PA levels and increase the reach or efficiency of rehabilitation services. However, there is limited knowledge about the needs and perceptions of HNC patients regarding these interventions. This study explored the perceptions and needs of HNC patients regarding mHealth-based PA programs before developing such interventions to ensure their improved effectiveness.Study designA constructivist qualitative study.MethodsWe purposively selected 17 adult HNC patients aged 40–80 years to determine their needs and perceptions of future mHealth-based PA programs. Semi-structured face-to-face interviews were conducted, and the data were analyzed via thematic analysis. The report followed the Consolidated Criteria for Qualitative Research Reports guidelines.ResultsFour themes were analyzed from the interview transcripts regarding the needs and perceptions of mHealth-based PA programs: (1) functionality needs; (2) system usage requirements; (3) social support; and (4) perceived barriers and facilitators. HNC patients expect highly customized and specialized mHealth interventions that consider individual factors, address their concerns about security, network, and cost, and prefer improved comfort. Moreover, they expect to receive support from their healthcare providers, families, and peers.ConclusionThe study provides pragmatic ready-to-use recommendations to design interventions for inactive HNC patients to achieve the recommended PA levels. Future mHealth interventions should be tailored according to the needs of the HNC patients by utilizing perceived facilitators and removing perceived barriers to help them engage in PA actively.

Background: The Fangji Dihuang formulation (FJDHF) is a widely recognized Traditional Chinese Medicine (TCM) formula that consists of five plant drugs: Stephaniae Tetrandrae Radix, Cinnamomi Ramulus, Rehmanniae Radix, Saposhnikoviae Radix, and Glycyrrhiza Urensis Fisch. This formulation has been known to exhibit clinical therapeutic effects in the treatment of inflammatory skin diseases. However, there is a lack of pharmacological research on its anti-atopic dermatitis (AD) activity.Methods: To investigate the potential anti-AD activity of FJDHF, DNCB was used to induce AD-like skin inflammation in the back of mice. Following successful modeling, the mice were administered FJDHF orally. The extent of the inflammatory skin lesions was recorded at day 4, 7, 14 and 28. UHPLC-Q-Exactive Orbitrap MS was used to identify and match the compounds present in FJDHF with ITCM, TCMIP and TCMSID. In silico predictions of potential target proteins of the identified compounds were obtained from SwishTargetPrediction, ITCM and TargetNet databases. AD-related genes were identified from GSE32924 data set, and FJDHF anti-AD hub genes were identified by MCODE algorithm. ClueGo enrichment analysis was employed to identify the core pathway of FJDHF’s anti-AD effect. To further investigate the anti-AD effect of FJDHF, single-cell RNA sequencing data set (GSE148196) from AD patients was analyzed to determine the target cells and signaling pathways of FJDHF in AD. Finally, rt-PCR, flow cytometry, and mouse back skin RNA sequencing were utilized to validate our findings.Results: FJDHF was found to be effective in improving the degree of the AD-like lesions in the mice. Network pharmacological analysis revealed the core pathway of FJDHF to be the IL-17 signaling pathway, which is interactively associated with cytokines. Single-cell RNA sequencing analysis suggested that FJDHF may play an anti-AD role by influencing dendritic cells. Flow cytometry and rt-PCR results showed that FJDHF can reduce the influence of AD sample of IL-4, IFN-γ and the expression of IL-17. The RNA sequencing of mouse back skin also confirmed our conclusion.Conclusion: FJDHF may inhibit DNCB-induced AD-like skin inflammation in mice by inhibiting the IL-17 signaling pathway. Thus, FJDHF can be considered as a potential therapeutic agent for AD.

This study demonstrates that the curvature of the cell membrane directly regulates the spatial distribution of Piezo1, a widely expressed mechanosensitive ion channel. Piezo1 may flatten upon activation and can mechanically inhibit membrane dynamics

In order to explore the effect of the compound probiotic powder of Lactobacillus rhamnosus and Bifidobacterium lactis on the immunity of mice and its food safety. In this study, low, medium and high doses (1.00, 0.67, 0.34g/kg BW) of compound probiotic powder were orally administered to mice to observe the organ/weight ratio, cellular immune function, humoral immune function, monocyte-macrophage function, NK cell activity and other indicators, comprehensively evaluate the effect of compound probiotic powder on the immune function of mice for 30 d. In addition, rat acute toxicity test, genetic toxicity test (mouse bone marrow cell micronucleus test, mouse sperm deformity test, Ames test) and 30-day feeding test for rats were used for food safety research. The results showed that, compared with the negative control group, the high-dose group mice had significantly increased delayed-type hypersensitivity (DTH), antibody cell production (PFC), serum hemolysin levels, and the phagocytosis index of carbon clearance in mice (P0.05). The growth and development of rats were good, and there was no significant difference in each index compared with the solvent control group (P>0.05). Therefore, the compound probiotic powder of Lactobacillus rhamnosus and Bifidobacterium lactis could enhance immunity without acute toxicity, genetic toxicity and subacute toxicity, and had high edible safety.

Introduction: Emodin (EMO), a natural derivative of the anthraquinone family mainly extracted from rhubarb (Rheum palmatum), has previously been demonstrated to possess superior anti-inflammatory properties from a single target or pathway. In order to explore the underlying mechanism of action of EMO against rheumatoid arthritis (RA), a network pharmacology approach was employed.Methods: A gene expression profile from GSE55457 available from the Gene Expression Omnibus (GEO) database was used to identify the targets of EMO action. Further, single cell RNA sequencing data from GEO database of RA patients (GSE159117) were downloaded and analysed. To further investigate the anti-RA effect of EMO on MH7A cells, the expression of IL-6 and IL-1β were monitored. Finally, RNA-seq analyses were conducted on synovial fibroblasts from EMO-treated.Result: We screened the key targets of EMO against RA using network pharmacology methods, including HMGB1, STAT1, EGR1, NR3C1, EGFR, MAPK14, CASP3, CASP1, IL4, IL13, IKBKB and FN1, and their reliability was verified using ROC curve. Single-cell RNA sequencing data analysis showed that these core target proteins mainly played a role by modulating monocytes. The anti-RA effect of EMO was further verified with MH7A cells, which showed that EMO could block cell differentiation and reduce the expression of IL-6 and IL-1β. WB experiments confirmed that EMO could affect the expression of COX2, HMBG1 and the phosphorylation of p38. Finally, sequencing of synovial fibroblasts from rats treated with EMO showed consistent results with those predicted and verified, further proving the anti-inflammatory effect of EMO.Conclusion: Our research shows that EMO inhibits inflammatory response of rheumatoid arthritis (RA) by targeting HMGB1, STAT1, EGR1, NR3C1, EGFR, MAPK14, CASP3, CASP1, IL4, IL13, IKBKB, FN1 and Monocytes/macrophages.

Chronic metabolic disease is a serious global health issue, which is accompanied by impaired insulin resistance. Tomato pectin (TP) is a naturally soluble complex hetero-polysaccharide with various biological functions. However, the impact of TP on hepatic insulin resistance in a high-fat diet (HFD) and its potential mechanism remains largely unknown. The results revealed that TP treatment significantly decreased the liver weight, hepatic fat accumulation and hepatic injury in HFD-fed mice. TP also improved fasting blood glucose levels and glucose tolerance in HFD-fed mice. The underlying mechanisms involved in the inflammation, oxidative stress and insulin signaling in the liver were also investigated by RT-qPCR and western blot, which indicated that TP ameliorated hepatic insulin resistance by regulating the PI3K/AKT/GSK-3β pathway, increasing the expression of GLUT4, decreasing the expression of PECK and G6P as well as restoring antioxidant activities and suppressing the inflammation statues in HFD-fed mice. Our data showed that dietary TP has profound effects on hepatic insulin resistance, inflammation and oxidative stress, demonstrating that TP might be a promising therapeutic agent against insulin resistance and related chronic metabolic disease.

BackgroundImmune checkpoint inhibition holds promise as a novel treatment for pancreatic ductal adenocarcinoma (PDAC). The clinical significance of soluble immune checkpoint (ICK) related proteins have not yet fully explored in PDAC.MethodsWe comprehensively profiled 14 soluble ICK-related proteins in plasma in 70 PDAC patients and 70 matched healthy controls. Epidemiological data of all subjects were obtained through structured interviews, and patients’ clinical data were retrieved from electronical health records. We evaluated the associations between the biomarkers with the risk of PDAC using unconditional multivariate logistic regression. Consensus clustering (k-means algorithm) with significant biomarkers was performed to identify immune subtypes in PDAC patients. Prediction models for overall survival (OS) in PDAC patients were developed using multivariate Cox proportional hazards regression. Harrell’s concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve and calibration curve were utilized to evaluate performance of prediction models. Gene expressions of the identified ICK-related proteins in tumors from TCGA were analyzed to provide insight into underlying mechanisms.ResultsSoluble BTLA, CD28, CD137, GITR and LAG-3 were significantly upregulated in PDAC patients (all q < 0.05), and elevation of each of them was correlated with PDAC increased risk (all p < 0.05). PDAC patients were classified into soluble immune-high and soluble immune-low subtypes, using these 5 biomarkers. Patients in soluble immune-high subtype had significantly poorer OS than those in soluble immune-low subtype (log-rank p = 9.7E-03). The model with clinical variables and soluble immune subtypes had excellent predictive power (C-index = 0.809) for the OS of PDAC patients. Furthermore, the immune subtypes identified with corresponding genes’ expression in PDAC tumor samples in TCGA showed an opposite correlation with OS to that of immune subtypes based on blood soluble ICK-related proteins (log-rank p =0.02). The immune-high subtype tumors displayed higher cytolytic activity (CYT) score than immune-low subtype tumors (p < 2E-16).ConclusionFive soluble ICK-related proteins were identified to be significantly associated with the risk and prognosis of PDAC. Patients who were classified as soluble immune-low subtype based on these biomarkers had better overall survival than those of the soluble immune-high subtype.

IntroductionLead is a ubiquitous environmental and industrial pollutant. Its nonbiodegradable toxicity induces a plethora of human diseases. A novel bioactive glycoprotein containing 1.15% carbohydrate, with the ability of adsorbing lead and effecting detoxification, has been purified from Auricularia polytricha and designated as APL. Besides, its mechanisms related to regulation of hepatic metabolic derangements at the proteome level were analyzed in this study.MethodsChromatographic techniques were utilized to purify APL in the current study. For investigating the protective effects of APL, Sprague-Dawley rats were given daily intraperitoneal injections of lead acetate for establishment of an animal model, and different dosages of APL were gastrically irrigated for study of protection from lead detoxification. Liver samples were prepared for proteomic analyses to explore the detoxification mechanisms.Results and discussionThe detoxifying glycoprotein APL displayed unique molecular properties with molecular weight of 252-kDa, was isolated from fruiting bodies of the edible fungus A. polytricha. The serum concentrations of lead and the liver function biomarkers aspartate and alanine aminotransferases were significantly (p

Abstract Background and objectives The prevalence of non-suicidal self-injury (NSSI) is high among adolescents. Parents have significant impact on the development of NSSI. Many quantitative studies have demonstrated the relationship between parental factors such as parenting behaviors and adolescents’ NSSI. However, few studies have explored parents’ responses and adolescent-parent reciprocal interaction during repeated NSSI. This study aimed to explore parents’ cognition, behaviors and adolescent-parent reciprocal interaction during repeated NSSI. Methods This is a phenomenological study. By purposive sampling, 24 parents of adolescents with repeated NSSI were recruited from a child and adolescent psychiatric ward in a mental health center in Chengdu, China. Semi-structured interviews were conducted and audio-recorded. Audio-recordings were transcribed verbatim and analyzed using thematic analysis. Findings Three themes were identified: parents’ attribution, perceptions and coping behaviors of NSSI. Chronic stress of adolescents and triggers of NSSI were associated with parental expectations. Parents initially perceived NSSI as a manifestation of puberty, a way of making needs met or a coping strategy of negative emotions, and gradually realized that it was a condition requiring psychological assistance. Parents’ coping behaviors of NSSI were divided into 4 stages, namely denial, dissuasion, reflection and adaptation, and working as a team. To be more specific, parents’ coping strategies at dissuasion stage included criticizing and conciliating, while those at reflection and adaptation stage included neglecting, avoiding conflicts and increasing control. Conclusions These findings suggest that adjusting parents’ expectation and negative perceptions of NSSI is beneficial to reduce adolescent-parent conflict and adolescents’ inner conflict and prevent NSSI. Furthermore, it’s necessary to publicize NSSI related knowledge to promote the early detection and treatment of NSSI.

BackgroundAs a common primary intracranial tumor, the diagnosis and therapy of low-grade glioma (LGG) remains a pivotal barrier. Cuproptosis, a new way induces cell death, has attracted worldwide attention. However, the relationship between cuproptosis and LGG remains unknown. Our study is all about finding out if there are any genes related to coproptosis that can be used to predict the outcome of LGG.MethodsRNA data and clinical information were selected from Cancer Genome Atlas (TCGA) datasets and the Genotype-Tissue Expression (GTEx), 5 lncRNAs (GAS5.AS1, MYLK.AS1, AC142472.1, AC011346.1, AL359643.3) were identified by Cox univariate and multivariate regression, as well as LASSO Cox regression. In the training and test sets, a dual validation of the predictive signature comprised of these 5 lncRNAs was undertaken. The findings demonstrate that the risk model is able to predict the survival regression of LGG patients and has a good performance in either the KM curve approach or the ROC curve. GO, GSEA and KEGG were carried out to explore the possible molecular processes that affecting the prognosis of LGG. The characteristics of immune microenvironment were investigated by using CIBERSORT, ESTIMATE and ssGSEA.ResultsWe identified five lncRNAs related with cuproptosis that were closely associated with the prognosis of LGG and used these five lncRNAs to develop a risk model. Using this risk model, LGG patients were then divided into high-risk and low-risk groups. The two patient groups had significantly distinct survival characteristics. Analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the differential genes of the two patient groups were primarily concentrated in neural active ligand-receptor interaction and cytokine-cytokine receptor interaction. The ssGSEA score determined the information related to immune infiltration, and the two groups were differentially expressed in immune subpopulations such as T cells and B cells as well.ConclusionOur study discovered 5 cuproptosis-related lncRNAs which contribute to predicting patients’ survival of LGG and provide ideas for the exploration of new targets for LGG in the future.

Background. Ventilator-associated pneumonia (VAP) is among the most important hospital-acquired infections in an intensive-care unit setting. However, clinical practice lacks effective theoretical tools for preventing VAP in the elderly. Aim. To describe the independent factors associated with VAP in elderly intensive-care unit (ICU) patients on mechanical ventilation (MV) and to construct a risk prediction model. Methods. A total of 1851 elderly patients with MV in ICUs from January 2015 to September 2019 were selected from 12 tertiary hospitals. Study subjects were divided into a model group (n = 1219) and a validation group (n = 632). Two groups of patients were divided into a VAP group and a non-VAP group and compared. Univariate and logistic regression analyses were used to explore influencing factors for VAP in elderly ICU patients with MV, establish a risk prediction model, and draw a nomogram. We used the area under the receiver operating characteristic curve (AUROC) and the Hosmer–Lemeshow goodness-of-fit test to evaluate the predictive effect of the model. Findings regarding the length of ICU stay, surgery, C-reactive protein (CRP), and the number of reintubations were independent risk factors for VAP in elderly ICU patients with MV. Predictive-model verification results showed that the area under the curve (AUC) of VAP risk after MV in the modeling and verification groups was 0.859 and 0.813 (P

Background: Paeoniflorin (PF) is the main active component of Chinese herbaceous peony that has been shown to have an anti-tumor effect. However, there are few studies on the prevention and treatment of pancreatic cancer with PF.Methods: We gathered Microarray data pertaining to paeoniflorin intervention in pancreatic cancer by utilizing the GEO database (GSE97124). Then, the DEGs were filtered by the 33R program. RNA-seq data of pancreatic cancer and normal tissue samples were taken from the TCGA and GTEx databases, respectively, and the WGCNA technique was utilized to examine the pancreatic cancer-specific genes. Paeoniflorin target genes for the treatment of pancreatic cancer were determined based on the overlap between DEGs and WGCNA. GO and KEGG enrichment analyses were then performed on paeoniflorin target genes to discover which biological processes were impacted. Using the 3 hierarchical methods included in the Cytohubba plugin, we re-screened the hub genes in the target genes to find the genes most relevant to paeoniflorin treatment. The overall survival effects of hub genes were confirmed using the TCGA database. Finally, the paeoniflorin targets identified by the network pharmacology analysis were validated using PANC-1 and Capan-2 cells.Results: We identified 148 main potential PF targets, and gene enrichment analysis suggested that the aforementioned targets play a crucial role in the regulation of MAPK, PI3K-AKT, and other pathways. The further screening of the prospective targets resulted in the identification of 39 hub genes. Using the TCGA database, it was determined that around 33.33% of the hub gene’s high expression was linked with a bad prognosis. Finally, we demonstrated that PF inhibits IL-6 and IL-10 expression and p38 phosphorylation in pancreatic cancer cells, thereby reducing inflammation.Conclusion: PF may regulate inflammatory factors mainly through the p38 MAPK signal pathway. These findings provide theoretical and experimental evidence suggesting the PF as a promising natural source of anti-tumor compounds for pancreatic cancer.

Triboelectric nanogenerators (TENGs) possess significant attributes, such as a simple structure, high energy conversion efficiency, and ease of fabrication, rendering them crucial for powering mobile and distributed low-power electronic devices. In this study, a multilayer spring TENG with a cushion layer structure is proposed that enhances the output performance of the basic TENG structure. The fundamental topology of the energy harvesting circuit is chosen based on the electrical performance parameters of the generator and optimizes the selection of each electronic component in the actual circuit. This allows the small-size TENG (2 cm3) to have a high storable power density (5.45 mW m−2). Finally, the fabrication method of the small-size TENG and how to choose suitable electronic components based on the intrinsic electrical parameters of the TENG were summarized. This work provides valuable guidance for designing and fabricating self-powered IoT node devices.

Abstract Zinc oxide nanoparticles (ZnO NPs) are used in a wide range of applications including industry, commercial products and medicine field. Numerous mechanistic studies for ZnO NPs’ toxicity were performed on pristine (fresh) NPs. However, the cytotoxicity induced by the transformed (aged) ZnO NPs and the underlying mechanisms remain unclear. Here, we observed the physicochemical transformation of ZnO NPs underwent over time, followed by evaluating the cytotoxicity of fresh and aged NPs. We found that fresh ZnO NPs induced higher apoptosis level than their aged counterparts. Accordingly, RNA sequencing data from aged ZnO NP-treated human–hamster hybrid (A L) cells showed that p53, PI3k–Akt, FoXO, Glutathione, ErbB, HIF-1, Oxytocin and Jak-STAT signaling pathways were enriched but no apoptosis pathway. Quantitative PCR results revealed the significantly higher mRNA level of IL1B and CD69 in fresh NP-treated groups compared to that of aged ZnO NP- and zinc chloride-treated groups. The above results indicated that the lower cytotoxicity of aged ZnO NPs is partially attributed to their reduced potency in inducing apoptosis. The transcriptional regulation of multiple signal pathways activated by aged NPs may help to build the cellular homeostasis. Taken together, our findings highlight the influence of aging (environmental transformation) process of ZnO NPs on their toxicities and biological consequences.

Abstract Background Pathological cardiac hypertrophy is a major contributor of heart failure (HF), which seriously threatens human’s health world widely. Deregulation of m6A RNA methylation, and m6A methyltransferases and de-methyltransferases have been demonstrated to act essential roles in cardiac hypertrophy and HF. Here, we studied the potential roles and its underlying mechanisms of m6A Reader YTHDF proteins in HF. In this study, we constructed HF mouse model by transverse aortic constriction surgery. Primary cardiomyocytes were isolated and stimulated with isoproterenol (ISO) or phenylephrine (PHE) to induce myocardial hypertrophy. Results Through single-cell RNA-seq analysis, immunofluorescent staining, HE staining, Western blotting, and real time-PCR detections, we found that YTHDF2 mRNA and protein level, but not YTHDF1 or YTHDF3, was significantly increased during HF development. YTHDF2 overexpression could efficiently alleviate cardiac hypertrophy. Furthermore, through immunoprecipitation accompanied with mass spectrometry analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that ISO stimulation did not evidently affect YTHDF2-interacting proteins. However, ISO or PHE stimulation significantly increased YTHDF2 protein interacting with Myh7 (beta-myosin heavy chain) mRNA, an important cardiac hypertrophy marker, in an m6A-dependent manner. Knockdown of Myh7 or deletion of the YTH domain of YTHDF2 reversed the protective effects of YTHDF2 on cardiac hypertrophy. Finally, we found that ISO or PHE stimulation promoted YTHDF2 protein expression through enhancing Ythdf2 mRNA stability in an m6A-dependent manner in cardiomyocytes. Conclusions Overall, our results indicate that the m6A Reader YTHDF2 suppresses cardiac hypertrophy via Myh7 mRNA decoy in an m6A-dependent manner. This study highlights the functional importance of YTHDF2-dependent cardiac m6A mRNA regulation during cardiac hypertrophy, and provides a novel mechanistic insight into the therapeutic mechanisms of YTHDF2.

In the current social media environment, emotional branding communication has become a common marketing tool for brand owners, and therefore it has become particularly important and urgent to study it. Based on the perspective of brand equity theory, combined with the new characteristics of marketing communication in the social media environment, this paper constructed an emotional branding communication model in the social media environment. The system dynamics (SD) method was used to simulate and analyze the new product marketing system to assess whether it could stir the emotional needs of the consumers and resonate within their hearts. This paper discusses the asymmetric communication of different brands regarding the same commodity to determine the impact of this exchange mechanism, that is, only the weak brands in the market initially adopt marketing methods, while the strong brands do not participate in social marketing activities. It was found that the influence of marketing frequency and marketing intensity on symmetric and asymmetric communications was different. In the face of different types of competitors, the marketing strategy of weak brands needs emphasis. Through unit consistency test, structure verification test, effectiveness, and rationality test, it was proven that the emotional branding communication model and new product sales interaction simulation model established in this paper were reasonable and effective.

Aiming at the problem of the ambiguity and specificity of the tumor information on the non-contrast image, this paper proposes the use of multi-modality non-contrast MRI image information to complete the segmentation and detection of liver tumors. First, the multi-scale feature extraction block (MsFEB) extracts deep semantic features for tumors of different modalities. The network further fuses the features to obtain a multi-modal fusion feature with characterization ability. Second, the segmentation path uses the fusion feature to restore the tumor layer by layer to obtain the segmentation result; the detection path uses the fusion feature to complete the tumor b-box and classification. Finally, the network completes the training of segmentation and detection at the same time under the constraint of the joint multi-task loss function. The test results on 250 clinical MRI images of liver without contrast agent show that the segmentation dice coefficient reaches (81.98±1.07)%, the pixel accuracy reaches (93.72±0.97)%, the intersection ratio between the b-box of the detection and the gold standard reaches (80.19±1.46)%, and the classification accuracy rate reaches (90.36±0.61)%, which demonstrate that the the proposed method can segment and detect liver tumors in MRI images without contrast agent at the same time.

Abstract Background Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Methods We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses. Results We used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment. Conclusions Acute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.

Abstract Background Macrophages are the most common infiltrating immune cells in gliomas and play a wide variety of pro-tumor and anti-tumor roles. However, the different subpopulations of macrophages and their effects on the tumor microenvironment remain poorly understood. Methods We combined new and previously published single-cell RNA-seq data from 98,015 single cells from a total of 66 gliomas to profile 19,331 individual macrophages. Results Unsupervised clustering revealed a pro-tumor subpopulation of bone marrow-derived macrophages characterized by the scavenger receptor MARCO, which is almost exclusively found in IDH1-wild-type glioblastomas. Previous studies have implicated MARCO as an unfavorable marker in melanoma and non-small cell lung cancer; here, we find that bulk MARCO expression is associated with worse prognosis and mesenchymal subtype. Furthermore, MARCO expression is significantly altered over the course of treatment with anti-PD1 checkpoint inhibitors in a response-dependent manner, which we validate with immunofluorescence imaging. Conclusions These findings illustrate a novel macrophage subpopulation that drives tumor progression in glioblastomas and suggest potential therapeutic targets to prevent their recruitment.

Vascular inflammation triggers the development of thoracic aortic dissection (TAD). Zinc deficiency could dampen tissue inflammation. However, the role of zinc as a nutritional intervention in the progression of TAD remains elusive. In this study, we employed a classical β-aminopropionitrile monofumarate (BAPN)-induced TAD model in mice treated with low zinc and observed that the TAD progression was greatly ameliorated under low zinc conditions. Our results showed that low zinc could significantly improve aortic dissection and rupture (BAPN + low zinc vs. BAPN, 36% vs. 100%) and reduce mortality (BAPN + low zinc vs. BAPN, 22% vs. 57%). Mechanically, low zinc attenuated the infiltration of macrophages and inhibited the expression of inflammatory cytokines, suppressed the phenotype switch of vascular smooth muscle cells from contractile to synthetic types, and eventually alleviated the development of TAD. In conclusion, this study suggested that low zinc may serve as a potential nutritional intervention approach for TAD prevention.

Objective Gancao Nourish-Yin Decoction (GNYD) has been applied to clinical rheumatoid arthritis (RA) patients, and it had shown effectiveness not only in disease activity controlling but also in improving patients' physical status. However, its mechanism of function has not been investigated. Metabolic perturbations have been associated with RA, and targeting the metabolic profile is one of the ways to manage the disease. The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factor α (hTNF-α) transgenic arthritic model mice.

To investigate the effect of lactic acid bacteria fermentation on jujube bioactivity, Streptococcus thermophilus was used to ferment jujube puree. The number of viable bacteria cells, physicochemical properties, phenolics profile and antioxidant capacity were analyzed, and their correlation were investigated. Streptococcus thermophilus exhibited a high growth capacity in jujube puree, and significantly (p

Allium cepa L. var. agrogatum Don (ALAP) is commonly consumed in China as well as other regions and has various beneficial health effects. A novel acidic polysaccharide (named ALAP-21) was obtained from ALAP by ultrasonic and microwave-assisted extraction and purification using DEAE-52 anion exchange and Sephadex G-100 columns. The monosaccharide composition, structural and antioxidative properties of ALAP-21 were investigated by GC–MS chromatography, FT-IR and NMR spectroscopies and three antioxidative activity tests in vitro. The results showed that ALAP-21 was a heteropolysaccharide composed of glucose, galacturonic acid, mannose, galactose, arabinose, rhamnose, xylose, fructose and glucuronic acid with a relative molar ratio of 26.282: 27.546: 11.400: 4.781: 2.467: 2.445: 3.622: 1.106: 1.753, owning (1→4)-α-d-Glcp, (1→4)-α-d-GalAp6Me3OA, (1→4)-β-d-Galp6OMe, (1→2)-α-l-Rhap, (1→4)-β-d-Manp glycosidic linkages. (1→4)-α-d-Glcp and (1→4)-α-d-GalAp6Me3OA residues might be the main components of the sugar chain backbone of ALAP-21. Furthermore, ALAP-21 exhibited high potential for DPPH radicals (82.02%), hydroxyl radicals (53.33%) and superoxide anion radicals (50.28%). These results provide a reference for further research and rational development of ALAP polysaccharides. Keywords: Polysaccharides, Allium cepa L. var. agrogatum Don, Structural characterization, Antioxidative property

The influence of ultrasound combined with sodium hypochlorite (US-NaClO) treatment on microorganisms and quality of fresh-cut cucumber during storage were investigated. Ultrasound (400 W, 40 kHz, US: 5, 10 and 15 min) and sodium hypochlorite (NaClO: 50, 75, 100 ppm) were used to treat fresh-cut cucumber in a single or combined treatment and stored at 4 °C for 8 days and analyzed for texture, color and flavor. The results showed that US-NaClO treatment had a synergistic effect on the inhibition of microorganisms during storage. It could significantly reduce (p < 0.05) the number of microorganisms by 1.73 to 2.17 log CFU/g. In addition, US-NaClO treatment reduced the accumulation of malondialdehyde (MDA) during storage (4.42 nmol/g) and water mobility, and maintained the integrity of the cell membrane, delayed the increase of weight loss (3.21%), reduced water loss, thus slowing down the decline of firmness (9.20%) of fresh-cut cucumber during storage. The degradation of chlorophyll (6.41%) was reduced to maintain the color of freshly cut cucumbers. At the same time, US-NaClO could maintain the content of aldehydes, the main aromatic substance of cucumber, and reduced the content of alcohols and ketones during storage. Combined with the electronic nose results, it could maintain the cucumber flavor at the end of the storage period and reduce the odor produced by microorganisms. Overall, US-NaClO was helpful to inhibit the growth of microorganisms during storage, improve the quality of fresh-cut cucumber.

Internal blue discoloration in cherry radish (Raphanus sativus L. var. radculus pers) roots can appear after harvest. The antioxidant system and content of reactive oxygen species (ROS) will affect the blue discoloration. Currently, the reason for the blue discoloration is not yet clear. In order to reveal the mechanism of the blue discoloration of cherry radish, we selected the blue discolored cherry radish as the research object and the white cherry radish as the control. The difference in the antioxidant system between them were compared, including related enzymes and non-enzymatic antioxidants in this system. Meanwhile, the changes in the contents of 4-hydroxyglucobrassicin as a precursor substance and ROS were compared. The results showed that the activities of typical antioxidant enzymes decreased and the cycle of Glutathione peroxidase (GPX) and Ascorbic acid–Glutathione (ASA–GSH) was disturbed, leading to the reduction of antioxidant effect and the failure of timely and effective decomposition of superoxide anions (O2•−) and hydrogen peroxide (H2O2). In addition, the elevated level of O2•− and H2O2 led to the disorder of the antioxidant system, while the 4-hydroxybrassinoside was oxidized under the catalysis of peroxidase (POD) and eventually led to the internal blue discoloration in cherry radish. These results can provide a theoretical basis for solving the blue discoloration problem.

Trajectory generation can help predict the future road network state and properly deal with the privacy issues of trajectory data usage. To solve the problem that routes with very few journeys (ultra-low-frequency journey routes) are difficult to generate in the large-scale complex road network scenarios, the study designs a framework focusing on ultra-low-frequency route generation, ULF-TrajGAIL, and proposes an original trajectory-augmentation method called the combined expansion method. The specific original trajectory-augmentation method is determined by the pre-trajectory-generation experiment, and high-quality synthetic trajectories with higher diversity and similarity are output based on the final generation experiments which take the augmented trajectories as references. Based on the real trajectories of a complex road network in a region of Guangzhou, the quality of synthetic trajectories under different original trajectory-augmentation methods from the route, link and origin and destination pairs levels has been compared. The results show that the method can generate more ultra-low-frequency routes and help improve the overall diversity of routes and the similarity between routes and the number of journeys as well.

Tumor-infiltrating CD8+T lymphocytes are mostly associated with a favorable prognosis in numerous cancers, including hepatocellular carcinoma (HCC). Biejiajian Pill (BJJP) is a common type of traditional Chinese medicine that is widely used in the treatment of HCC in China. Previous studies showed that BJJP suppressed the growth of HCC cells both in vivo and in vitro, by exerting direct cytotoxic effects on tumor cells. The present study demonstrated that in addition to direct cytotoxicity, BJJP inhibits the growth of tumor cells by promoting the infiltration of CD8+T cells into the tumor in H22-bearing mice. Mechanistically, chemokine ligand 5 (CCL5) was identified as one of the most highly expressed chemokines by tumor cells in vivo after treatment with BJJP. Additionally, CCL5 was knocked down in H22 cells and the results showed that knockdown of the gene significantly impaired the infiltration of CD8+T cells in vivo. Furthermore, the effects of BJJP on human HCC cell lines were assessed in vitro. Similarly, cells treated with BJJP had higher expression of CCL5 mRNA, which was consistent with increased levels of CCL5 protein in human tumor cells. These findings provide new insights into the anticancer effects of BJJP, which regulated the expression of CCL5 and the infiltration of CD8+T cells. The results, therefore, suggest that BJJP has great potential application in clinical practice.

Sulfoxaflor is a novel sulfoximine insecticide which is widely used to control crop pests. Risk assessments have reported its high toxicity to pollinators. However, sulfoxaflor is not persistent in the environment and few studies have addressed its negative effects on larval and newly emerged honeybees at environmentally relevant concentrations. In the present study, the sublethal effects of a sulfoxaflor commercial product, Isoclast™ Active, were evaluated in the laboratory using larvae and newly emerged worker honeybees. The results of 96-h acute toxicity showed that Isoclast is moderately toxic to adult bees, and it could induce significant death and growth failure of larvae after continuous dietary intake. In addition, Isoclast induced significant changes in antioxidative (SOD, CAT), lipid peroxidation (POD, LPO, MDA), detoxification (GST, GR, GSH) and signal transduction-related (AChE, ACh) enzymes or products both in larvae and adult honey bees under residue levels. Here we firstly reported the lethal and sublethal effects of commercial sulfoxaflor to honeybees’ larvae and young workers. All these findings revealed the potential risks of sulfoxaflor residue in environment to honey bees, and may also to other pollinators. This is a laboratory mimic studies, and further studies are still needed to investigate the risks and in-depth mechanisms of sulfoxaflor to bees in field.

Due to mega-ships, increasing container throughput, and nonuniform truck arrivals, many container terminals face challenges of unbalanced workloads of yard equipment, shortage of equipment resources in peak hours, and congestion problem. To solve such issues, we propose a mixed-integer bilevel programming model to optimize the vessel-dependent time windows for inbound trucks and yard crane deployment simultaneously. In the proposed bilevel model, the upper level aims to minimize the total truck waiting time at the container terminal gate and yard, while the lower level is formulated to minimize the total workload overflow to next shift in the whole container yard. The optimal yard crane deployment obtained in the lower level will transfer to the upper level problem to determine the waiting time of trucks in the yard and then affect the truck arrivals pattern. To solve the model, a hybrid algorithm—called hybrid genetic algorithm, based on collective decision optimization—is put forward by combining the genetic algorithm and the collective decision optimization algorithm. Numerical experiments are conducted to validate the proposed approach is effective to simultaneously flatten truck arrivals and improve the efficiency of yard cranes. The proposed approach can significantly reduce container terminals’ truck waiting time.

In this paper, a thermochromic complex was prepared from crystal violet lactone (CVL), bisphenol A (BPA) and tetradecanol. The color-changing temperature of the color-changing compound was found to be 25 °C by orthogonal experiment. Microcapsules coated with a thermochromic compound were added into alkyd resin at different mass concentrations. With the increase in temperature and mass fraction of microcapsules in the coating, the color difference of the coating showed an upward trend. The highest variation in the coating’s color difference occurs when there were 10% microcapsules. When the mass fraction of microcapsules was 15.0~25.0%, there was little change to the gloss of the coating. With the increase in the mass fraction of the coating microcapsules, the hardness of the coating gradually increased. The hardness was at its best when the microcapsule concentration was 25%. When the microcapsule concentration was 20%, the impact resistance of the coating was at its best. The coating had good cold-liquid resistance to acetic acid, ethanol, and NaCl solutions, and there was basically no mark on the coating surface before and after the cold-liquid-resistance test. The addition of microcapsules did not change the chemical composition of the coating, and it improved the performance of the coating. When the microcapsule concentration was 10%, the overall performance of the coating was at its best, which laid the technical foundation for thermochromic coating on the metal surface.

Somatostatin (SST) plays important roles in growth and development. In teleost fishes six SST encoding genes (sst1 to sst6) have been identified although few studies have addressed their function. Here we aim to determine the function of the teleost specific sst4 in the zebrafish. A CRISPR/Cas9 sst4 zebrafish mutant with loss of function (sst4−/−) was produced which grew significantly faster and was heavier at the onset of gonadal maturation than the wild type (WT). Consistent with their faster growth, liver igf1, igf2a and igf2b expression was significantly upregulated in the sst4−/− fish compared to the WT. Histological examination of the ovaries and testis indicated that sst4−/− fish had slightly delayed testicular gametogenesis compared to the WT. Significantly lower expression of igf3, amh, insl3, hsd17b3, hsd11b2, hsd20b, cyp11b and cyp17 was consistently observed in the sst4−/− testis. In contrast, the ovaries had lower expression of igf1, igf2a and cyp19a1a but increased expression of igf2b and hsd20b. The gonadotrophin beta subunits (fshb and lhb) in the brain were downregulated indicating the brain-pituitary-gonadal axis was downregulated in the sst4−/− fish and suggesting that the steroid production is compromised in the maturing gonads. In addition, analysis of sst1 and sst3 mRNA levels in sst4−/− fish suggests a dosage compensation effect of sst1 in the brain and liver. Altogether, the results from the zebrafish sst4−/− line support the idea that sst4 is involved in the regulation of igf signalling, somatic growth and reproduction since steroidogenesis and gametogenesis at pubertal onset were compromised. Keywords: Somatostatin 4, Gametogenesis, Zebrafish, Gonadotrophin, Puberty

Research on facial expression recognition (FER) technology can promote the development of theoretical and practical applications for our daily life. Currently, most of the related works on this technology are focused on un-occluded FER. However, in real life, facial expression images often have partial occlusion; therefore, the accurate recognition of occluded facial expression images is a topic that should be explored. In this paper, we proposed a novel Wasserstein generative adversarial network-based method to perform occluded FER. After complementing the face occlusion image with complex facial expression information, the recognition is achieved by learning the facial expression features of the images. This method consists of a generator G and two discriminators D1 and D2. The generator naturally complements occlusion in the expression image under the triple constraints of weighted reconstruction loss lwr, triplet loss lt, and adversarial loss la. We optimize the discriminator D1 to distinguish between real and fake by constructing an adversarial loss la between the generated complementing images, original un-occluded images, and small-scale-occluded images based on the Wasserstein distance. Finally, the FER is completed by introducing classification loss lc into D2. To verify the effectiveness of the proposed method, an experimental analysis was performed on the AffectNet and RAF-DB datasets. The visual occlusion complementing results, comparison of recognition rates of facial expression images with and without de-occlusion processing, and T-distributed stochastic neighbor embedding visual analysis of facial expression features all prove the effectiveness of the proposed method. The experimental results show that the proposed method is better than the existing state-of-the-art methods.