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Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the major regions regulating cognitive and emotional behaviors, and found that the neuronal deletion of GHSR reduced DIO-induced neuroinflammation by suppressing proinflammatory chemokines/cytokines and decreasing microglial activation. Furthermore, our data showed that neuronal GHSR deletion suppresses neuroinflammation by downregulating AMPK-autophagy signaling in neurons. In conclusion, our data reveal that neuronal GHSR inhibition protects against DIO-induced depressive-like behavior and spatial cognitive dysfunction, at least in part, through AMPK-autophagy signaling-mediated neuroinflammation.

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph tick saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved in regulating tick evasion of host innate immunity and promoting host colonization by Bb. Recombinant (r) proteins were expressed in Pichia pastoris, and substrate hydrolysis assays were used to determine. Ex vivo (complement and hemostasis function related) and in vivo (paw edema and effect on Bb colonization of C3H/HeN mice organs) assays were conducted to validate function. We demonstrate that rIxsS41 inhibits chymase and cathepsin G, pro-inflammatory proteases that are released by mast cells and neutrophils, the first immune cells at the tick feeding site. Importantly, stoichiometry of inhibition analysis revealed that 2.2 and 2.8 molecules of rIxsS41 are needed to 100% inhibit 1 molecule of chymase and cathepsin G, respectively, suggesting that findings here are likely events at the tick feeding site. Furthermore, chymase-mediated paw edema, induced by the mast cell degranulator, compound 48/80 (C48/80), was blocked by rIxsS41. Likewise, rIxsS41 reduced membrane attack complex (MAC) deposition via the alternative and lectin complement activation pathways and dose-dependently protected Bb from complement killing. Additionally, co-inoculating C3H/HeN mice with Bb together with rIxsS41 or with a mixture (rIxsS41 and C48/80). Findings in this study suggest that IxsS41 markedly contributes to tick feeding and host colonization by Bb. Therefore, we conclude that IxsS41 is a potential candidate for an anti-tick vaccine to prevent transmission of the Lyme disease agent.

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system, characterized by myelin destruction, axonal degeneration, and progressive loss of neurological functions. Remyelination is considered an axonal protection strategy and may enable functional recovery, but the mechanisms of myelin repair, especially after chronic demyelination, remain poorly understood. Here, we used the cuprizone demyelination mouse model to investigate spatiotemporal characteristics of acute and chronic de- and remyelination and motor functional recovery following chronic demyelination. Extensive remyelination occurred after both the acute and chronic insults, but with less robust glial responses and slower myelin recovery in the chronic phase. Axonal damage was found at the ultrastructural level in the chronically demyelinated corpus callosum and in remyelinated axons in the somatosensory cortex. Unexpectedly, we observed the development of functional motor deficits after chronic remyelination. RNA sequencing of isolated brain regions revealed significantly altered transcripts across the corpus callosum, cortex and hippocampus. Pathway analysis identified selective upregulation of extracellular matrix/collagen pathways and synaptic signaling in the chronically de/remyelinating white matter. Our study demonstrates regional differences of intrinsic reparative mechanisms after a chronic demyelinating insult and suggests a potential link between long-term motor function alterations and continued axonal damage during chronic remyelination. Moreover, the transcriptome dataset of three brain regions and over an extended de/remyelination period provides a valuable platform for a better understanding of the mechanisms of myelin repair as well as the identification of potential targets for effective remyelination and neuroprotection for progressive MS.

Tobacco belongs to the family Solanaceae, which easily forms continuous cropping obstacles. Continuous cropping exacerbates the accumulation of autotoxins in tobacco rhizospheric soil, affects the normal metabolism and growth of plants, changes soil microecology, and severely reduces the yield and quality of tobacco. In this study, the types and composition of tobacco autotoxins under continuous cropping systems are summarized, and a model is proposed, suggesting that autotoxins can cause toxicity to tobacco plants at the cell level, plant-growth level, and physiological process level, negatively affecting soil microbial life activities, population number, and community structure and disrupting soil microecology. A combined strategy for managing tobacco autotoxicity is proposed based on the breeding of superior varieties, and this approach can be combined with adjustments to cropping systems, the induction of plant immunity, and the optimization of cultivation and biological control measures. Additionally, future research directions are suggested and challenges associated with autotoxicity are provided. This study aims to serve as a reference and provide inspirations needed to develop green and sustainable strategies and alleviate the continuous cropping obstacles of tobacco. It also acts as a reference for resolving continuous cropping challenges in other crops.

IntroductionA number of evidences have proved that “Nostoc commune” Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of “Nostoc commune” Vauch extracellular matrix– a water-stress protein (WSP) still needs to be elucidated.MethodsIn our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment.ResultsWe found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells.DiscussionGiven the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

A monolayer Caco-2 cell model was established to explore the effects of sea bass sausage digestive juice containing phosphate on calcium ion transport. Differential proteins of Caco-2 cells treated with fish sausage juice were detected and analyzed by gene ontology (GO) functional annotation and kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. Results revealed that after treatment with 0.23 mg/mL digestive juice of perch sausage in vitro, Caco-2 cell viability was the highest at 72 h (99.84%). Additionally, 0.23 mg/mL digestive juice of perch sausage in vitro significantly increased calcium ion transport. The transfer volume was 1.396 μg/well. Fish sausages containing phosphate significantly affected the protein expression levels of Caco-2 cells. Two hundred one differential proteins were detected, including 114 up-regulated and 87 down-regulated proteins. The main differential proteins included P02795, Q9P0W0, Q96PU5, Q9GZT9 and Q5EBL8. The adjustment ratios of the fish sausage group were 0.7485, 1.373, 1.2535, 0.6775, and 0.809, respectively. The pathway analysis showed that phosphate affected calcium ion absorption and transport through the P02795 enrichment pathway. The fish sausage group showed that the immune-related functions of cells were affected. This study expounds the effects of water-retaining agents on the nutritional quality of aquatic products and provides theoretical support for the research and application of surimi products.

Breast cancer (BC) remains the most prevalent malignancy due to its incidence rate, recurrence, and metastasis in women. Conventional strategies of cancer detection– mammography and tissue biopsy lack the capacity to detect the complete cancer genomic landscape. Besides, they often give false- positive or negative results. The presence of this and other disadvantages such as invasiveness, high-cost, and side effects necessitates developing new strategies to overcome the BC burden. Liquid biopsy (LB) has been brought to the fore owing to its early detection, screening, prognosis, simplicity of the technique, and efficient monitoring. Remarkably, microRNAs (miRNAs)– gene expression regulators seem to play a major role as biomarkers detected in the samples of LB. Particularly, miR-21 and miR-155 among other possible candidates seem to serve as favorable biomarkers in the diagnosis and prognosis of BC. Hence, this review will assess the potential utility of miRNAs as biomarkers and will highlight certain promising candidates for the LB approach in the diagnosis and management of BC that may optimize the patient outcome.

Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.weebly.com/). To investigate the association factors that influence the effectiveness of cancer vaccines, these peptide-based cancer vaccines were classified into high (HCR) and low (LCR) clinical responses based on their clinical efficacy. Our study highlights that modified peptides derived from artificially modified proteins are suitable as cancer vaccines, especially for melanoma. It may be possible to advance cancer vaccines by screening for HLA class II affinity peptides may be an effective therapeutic strategy. In addition, the treatment regimen has the potential to influence the clinical response of a cancer vaccine, and Montanide ISA-51 might be an effective adjuvant. Finally, we constructed a high sensitivity and specificity machine learning model to assist in designing peptide-based cancer vaccines capable of providing high clinical responses. Together, our findings illustrate that a high clinical response following peptide-based cancer vaccination is correlated with the right type of peptide, the appropriate adjuvant, and a matched HLA allele, as well as an appropriate treatment regimen. This study would allow for enhanced development of cancer vaccines.

A linalool/polycaprolactone (LL/PCL) antibacterial film was prepared by using a coaxial electrospinning process, and its physical and chemical properties were characterized. The antibacterial film was formed into an active antibacterial gasket, and its effect on salmon preservation was analyzed. The results show that the LL/PCL nanofiber membrane had a well-developed microstructure, and the fiber surface was smooth and uniform. The diameter of the fibers in the PCL membrane without the core material (linalool) was 113.92 ± 23.74 nm. In contrast, the diameter of the coaxial nanofiber membrane with linalool increased, and the diameter of the LL/PCL membranes with 20% and 40% linalool was 220.62 ± 44.01 and 232.22 ± 56.27 nm, respectively. The hydrophobicity and water vapor permeability were enhanced, whereas the tensile strength and elongation at break decreased slightly, while the thermal stability did not differ significantly with the incorporation of linalool. Analysis of the sustained release of linalool showed that the LL/PCL coaxial fiber membranes could release linalool into the reaction system for a long time. The LL/PCL nanofiber film was used to create an antibacterial active gasket for salmon preservation experiments. Sensory evaluation and analyses of the total bacterial count, total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), pH, texture (hardness, elasticity, chewiness, and viscoelasticity), water distribution change, and aroma using an electronic nose were used to determine the quality of salmon. It was found that food-grade tinfoil and the PCL gasket had no significant effect on the freshness of salmon, while the active antibacterial gasket samples containing linalool could decrease the rate of decay salmon and effectively prolong the shelf-life of salmon by releasing linalool.

Pseudomonas fluorescens is a common specific spoilage organism (SSO) of aquatic products. The spoilage ability of SSO can be regulated by the quorum sensing (QS) system. However, the QS system in P. fluorescens and their relationship with the spoilage potential have not been systematically analyzed. In the present study, the complete genome of P. fluorescens PF08 isolated from spoilage turbot was sequenced. The identification of key genes that involved in the QS, enzyme synthesis, sulfur, and amino acid metabolism explained the spoilage potential of P. fluorescens PF08. Results of quantitative real-time PCR revealed the key role of the P. fluorescens PF08 QS system in regulating the transcription of spoilage-related genes and its sensitivity to environmental stress. These findings provide insight into the spoilage features of P. fluorescens PF08 from a genomic perspective. The knowledge may be valuable in the development of new strategies for the targeted inhibition of aquatic product spoilage based on QS interference.

Aeromonas hydrophila is an opportunistic pathogen that is responsible for a variety of infectious diseases both in human and animals, particularly aquatic animals. Moreover, the pathogen has become a foodborne pathogen by transmitting from seafood to human. The abuse of antibiotics in aquaculture results in the emergence of antibiotic resistance and treatment failure. Therefore, novel approaches are urgently needed for managing resistant A. hydrophila associated infections. Aerolysin, an essential virulence factor of pathogenic A. hydrophila strain, has been identified as target developing novel drugs against pathogenesis of A. hydrophila. In the present study, genistein, without anti-A. hydrophila activity, was identified that could decrease the production of aerolysin and biofilm formation at a dose-dependent manner. Transcription of aerolysin encoding gene aerA and quorum sensing related genes ahyI and ahyR was significantly down-regulated when co-cultured with genistein. Cell viability studies demonstrated that genistein could significantly improve aerolysin mediated A549 cell injury. Furthermore, genistein could provide a remarkable protection to channel catfish infected with A. hydrophila. These findings indicate that targeting quorum sensing and virulence can be a useful approach developing drugs against A. hydrophila infections in aquaculture. Moreover, genistein can be chosen as a promising candidate in developing drugs against A. hydrophila.

The effect of the combination of vanillin and chitosan (VC) coating on the microbiota composition and shelf-life of turbot (Scophthalmus maximus) filets during a 15-day storage period at 4 ± 1°day was investigated in this study. The control and coated fish samples were analyzed periodically for sensory and chemical attributes [total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), and pH] and the presence of dominant spoilage microbiota. The results suggested that the sensory and the chemical quality of turbot filets effectively improved after treatment with vanillin (final concentration 2 mg/ml) combined with 1% chitosan, and the shelf-life was prolonged for 6 to 7 days compared with the control group. Furthermore, high-throughput sequencing showed that Proteobacteria (52.2%) and Firmicutes (29.8%) were the dominant bacteria at the phylum level in fresh turbot filets, while Pseudomonadaceae (40.2%) and Lactobacillaceae (39.4%) were the dominant bacteria at the family level in deteriorated turbot filets. However, after VC treatment, the relative abundance of Pseudomonadaceae and Lactobacillaceae decreased significantly due to the growth inhibition of potential bacteria, specifically spoilage bacteria, along with the rich bacterial diversity at the end of storage. Therefore, our data indicated that VC treatment might be effective in decreasing bacteria-induced quality deterioration and in extending the shelf-life of refrigerated turbot filets.

Some bacteria can modulate their spoilage potential by responding to environmental signaling molecules via the quorum sensing (QS) system. However, the ability of Pseudomonas fluorescens, the specific spoilage organism (SSO) of turbot, to response to environmental signaling molecules remains unclear. This study investigated the effects of six synthetic N-acyl homoserine lactones (AHLs) on typical behaviors mediated by QS in P. fluorescens, such as biofilm formation and extracellular protease activity. Total volatile basic nitrogen (TVB-N) was used as a spoilage indicator to evaluate quality changes in AHL-treated turbot filets during storage. The results confirm the enhancing effect of environmental AHLs on QS-dependent factors of P. fluorescens and quality deterioration of turbot filets, with C4-HSL and C14-HSL being the most effective. Moreover, the content decrease of exogenous AHLs was also validated by gas chromatography–mass spectrometry analysis. Further, changes in rhlR transcription levels in P. fluorescens suggest that this bacterium can sense environmental AHLs. Finally, molecular docking analysis demonstrates the potential interactions of RhlR protein with various exogenous AHLs. These findings strongly implicate environmental AHLs in turbot spoilage caused by P. fluorescens, suggesting preservation of turbot should not exclusively consider the elimination of SSO-secreted AHLs.

Human norovirus (NoV) is a major cause of fresh produce associated outbreaks. In this study a non-thermal process, high pressure processing (HPP), was evaluated for efficacy against a human NoV GII.4 strain, and Tulane virus (TV). Virus survival following HPP treatment was determined using direct quantitative reverse transcriptase PCR (RT-qPCR), the porcine gastric mucin magnetic bead (PGM-MB) binding assay followed by RT-qPCR, and plaque assay. HPP (400 MPa) inactivation of human NoV and TV was enhanced in simple mediums at a low initial temperature (4°C) and neutral pH (pH 7). HPP treatment of human NoV and TV in strawberry puree at 400 MPa did not significantly affect the level of RNA detected using the PGM-MB binding assay; increasing the pressure level to 600 MPa lead to inactivation of both human NoV and TV. Overall, HPP inactivation of human NoV GII.4 and TV is enhanced at lower initial temperature and neutral pH, and viruses can be inactivated in the food matrix at commercially acceptable pressure levels.

IncI-complex plasmids can be divided into seven subgroups IncI1, IncI2, IncIγ, IncB/O, IncK1, IncK2, and IncZ. In this study, a replicon-based scheme was proposed for typing IncI-complex plasmids into four separately clustering subgroups IncI2, IncI1/B/O, IncIγ/K1 and IncK2/Z, the last three of which were combined from IncI1 and IncB/O, IncIγ and IncK1, and IncK2 and IncZ, respectively. Four IncIγ/K1 plasmids p205880-NR2, p14E509-CTXM, p11011-CTXM and p61806-CTXM were fully sequenced and compared with IncIγ/K1 reference pCT, IncI2 reference R721, IncI1/B/O reference R64 and IncK2/Z reference pO26-CRL-125. These plasmids shared conserved gene organization in the replication and conjugal transfer regions, but displaying considerable sequence diversity among different subgroups. Remarkable modular differences were observed in the maintenance and transfer leading regions. p205880-NR2 contained no resistance genes or accessory modules, while the other seven plasmids acquired one or more accessory modules, which harbored mobile elements [including unit transposons, insertion sequence (IS)-based transposition units and individual IS elements] and associated resistance markers (especially including those involved in resistance to β-lactams, aminoglycosides, tetracyclins, phenicols, streptomycins, trimethoprims, sulphonamides, tunicamycins and erythromycins). Data presented here provided a deeper insight into diversification and evolution of IncI-complex plasmids.

Quorum sensing (QS), one of the most remarkable microbiological discoveries, is considered a global gene regulatory mechanism for various traits in bacteria, including virulence and spoilage. Hafnia alvei, an opportunistic pathogen and a dominant psychrophile, uses the lux-type QS system to regulate the production of virulence factors and biofilms, which are harmful to the food industry. Based on the QS interference approach, this study aimed to reveal the efficacy of L-carvone at sublethal concentrations on QS-regulated virulence factors and biofilm formation in H. alvei. QS inhibitory activity was demonstrated by the reduction in swinging motility (61.49%), swarming motility (74.94%), biofilm formation (52.41%) and acyl-homoserine lactone (AHL) production (0.5 μL/mL). Additionally, in silico analysis and RT-qPCR studies for AHL synthase HalI and QS transcriptional regulator HalR revealed a plausible molecular mechanism for QS inhibition by L-carvone. These findings suggest that L-carvone (a main component of spearmint essential oils) could be used as a novel quorum sensing inhibitor to control H. alvei in the food industry.

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph tick saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved in regulating tick evasion of host innate immunity and promoting host colonization by Bb. Recombinant (r) proteins were expressed in Pichia pastoris, and substrate hydrolysis assays were used to determine. Ex vivo (complement and hemostasis function related) and in vivo (paw edema and effect on Bb colonization of C3H/HeN mice organs) assays were conducted to validate function. We demonstrate that rIxsS41 inhibits chymase and cathepsin G, pro-inflammatory proteases that are released by mast cells and neutrophils, the first immune cells at the tick feeding site. Importantly, stoichiometry of inhibition analysis revealed that 2.2 and 2.8 molecules of rIxsS41 are needed to 100% inhibit 1 molecule of chymase and cathepsin G, respectively, suggesting that findings here are likely events at the tick feeding site. Furthermore, chymase-mediated paw edema, induced by the mast cell degranulator, compound 48/80 (C48/80), was blocked by rIxsS41. Likewise, rIxsS41 reduced membrane attack complex (MAC) deposition via the alternative and lectin complement activation pathways and dose-dependently protected Bb from complement killing. Additionally, co-inoculating C3H/HeN mice with Bb together with rIxsS41 or with a mixture (rIxsS41 and C48/80). Findings in this study suggest that IxsS41 markedly contributes to tick feeding and host colonization by Bb. Therefore, we conclude that IxsS41 is a potential candidate for an anti-tick vaccine to prevent transmission of the Lyme disease agent. [ABSTRACT FROM AUTHOR]

ObjectiveSepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis.MethodsDatasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN).ResultsAnalysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level.ConclusionCYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.

ObjectiveThe triglyceride-glucose (TyG) index is considered as a pivotal factor for various metabolic, cardiovascular, and cerebrovascular diseases. However, there is currently a paucity of relevant studies on the association between long-term level and change of TyG-index and cardiometabolic diseases (CMDs) risk. We aimed to explore the risk of CMDs in relation to the long-term level and change of TyG-index.MethodsBased on the prospective cohort study, a total of 36359 subjects who were free of CMDs, had complete data of triglyceride (TG) and fasting blood glucose (FBG) and underwent four health check-ups from 2006 to 2012 consecutively were followed up for CMDs until 2021. The associations between long-term level and change of TyG-index and CMDs risk were assessed by Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs). The TyG-index was calculated as ln [TG, mg/dL) × FBG, mg/dL)/2].ResultsDuring the median observation period of 8 years, 4685 subjects were newly diagnosed with CMDs. In multivariable-adjusted models, a graded positive association was observed between CMDs and long-term TyG-index. Compared with the Q1 group, subjects with the Q2-Q4 group had increased progressively risk of CMDs, with corresponding HRs of 1.64(1.47-1.83), 2.36(2.13-2.62), 3.15(2.84-3.49), respectively. The association was marginally attenuated, after further adjustment for the baseline TyG level. In addition, compared with stable TyG level, both loss and gain in TyG level were associated with increased CMDs risk.ConclusionsLong-term elevated level and change of TyG-index are risk factors for the incident CMDs. Elevated TyG-index in the early stage remains to exert cumulative effects on the occurrence of CMDs even after accounting for the baseline TyG-index.

This study aimed to analyze the mediating effect of tolerance of uncertainty (TU) and trait anxiety (TA) on future self-continuity (FSC) and intention to use Internet wealth management (IUIWM) systems. A questionnaire survey was distributed online and a total of 388 participants completed questionnaire, The questionnaire included the following scales: Chinese version of the FSC, Intention to Use the Internet Wealth Management, TU, and TA. Pearson correlation was used to investigate the correlation coefficient between variables while the sequential regression method was used to analyze relationship between variables. To analyze the collected data, the SPSS 26.0 was used. A two-step procedure was applied to analyze the mediation effect. Confirmatory factor analysis (CFA) was conducted to test the measurement model. Afterward, the Maximum Likelihood method was used for path analysis, and the Bias-corrected Bootstrap method was used to investigate determine the estimated value and confidence interval of the mediating effect. To analyze the mediation effect, the Mplus 7.0 was used. The results showed that FSC positively predicted individuals’ Internet wealth management systems. Furthermore, TU and TA played complete serial multiple mediating roles between FSC and IUIWM. The role of TA and TU have negative impact on intention to use. This study provides a theoretical basis in personality psychology that Internet financial product suppliers can use to improve the attractiveness of their products. Product managers can subdivide users according to these personality traits to provide customized products.

Background: The potential role of Neurotrophic factor-3(NTF3) in liver cancer is unknown. Therefore, we aimed to explore the clinical value of NTF3 in hepatocellular carcinoma (HCC).Methods: We used a variety of databases to analyze the expression, relationship with prognosis and immune significance of NTF3 in liver cancer through bioinformatics.Results: NTF3 was low expressed in HCC and was an independent prognostic factor in patients with HCC. CIBERSORT analysis indicated that NTF3 expression was positively correlated with CD4+ cells, mast cells, NK cells, macrophages and B cells in the tumor microenvironment. Furthermore, we found that NTF3 expression was negatively correlated with the immune checkpoints PD-L1, TIGIT and TIM-3. Functional network analysis revealed that NTF3 regulates HCC progression through a variety of cancer-related kinases, transcription factors and signaling pathways.Conclusions: We demonstrate that NTF3 correlates with prognosis and immune infiltration in HCC.

Accumulating evidence shows a close association between various types of bile acids (BAs) and hepatocellular carcinoma (HCC), and they have been revealed to affect tumor immune response and progression mainly by regulating Farnesoid X receptor (FXR). Nevertheless, the roles of Norcholic acid(NorCA) in HCC progression remain unknown yet. In this study, herein we demonstrate that NorCA can promote HCC cell proliferation, migration and invasion through negatively regulating FXR. Additionally, NorCA can increase PD-L1 level on the surfaces of HCC cells and their exosomes, and NorCA-induced exosomes dramatically dampen the function of CD4+T cells, thereby inducing an immunosuppressive microenvironment. Meanwhile, a negative correlation between PD-L1 and FXR expression in human HCC specimens was identified, and HCC patients with FXRlowPD-L1high expression exhibit a rather dismal survival outcome. Importantly, FXR agonist (GW4064) can synergize with anti-PD-1 antibody (Ab) to inhibit HCC growth in tumor-bearing models. Taken together, NorCA can promote HCC progression and immune invasion by inhibiting FXR signaling, implying a superiority of the combination of FXR agonist and anti‐PD‐1 Ab to the monotherapy of immune checkpoint inhibitor in combating HCC. However, more well-designed animal experiments and clinical trials are warranted to further confirm our findings in future due to the limitations in our study.

Manipulation of the distribution and frequency of meiotic recombination events to increase genetic diversity and disrupting genetic interference are long-standing goals in crop breeding. However, attenuation of genetic interference is usually accompanied by a reduction in recombination frequency and subsequent loss of plant fertility. In the present study, we generated null mutants of the ZEP1 gene, which encodes the central component of the meiotic synaptonemal complex (SC), in a hybrid rice using CRISPR/Cas9. The null mutants exhibited absolute male sterility but maintained nearly unaffected female fertility. By pollinating the zep1 null mutants with pollen from indica rice variety 93-11, we successfully conducted genetic analysis and found that genetic recombination frequency was greatly increased and genetic interference was completely eliminated in the absence of ZEP1. The findings provided direct evidence to support the controversial hypothesis that SC is involved in mediating interference. Additionally, the remained female fertility of the null mutants makes it possible to break linkage drag. Our study provides a potential approach to increase genetic diversity and fully eliminate genetic interference in rice breeding.