SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

Insights into the antimicrobial effects of tafenoquine against Enterococcus and its biofilms.

AIM: The purpose of this study is to assess the in vitro antimicrobial and anti-biofilm effects of the anti-protozoal agent tafenoquine (TAF) on Enterococcus and elucidate its underlying mode of action. METHODS AND RESULTS: The present work investigated the susceptibility of TAF on 3 type strains and 11 clinical isolates of enterococci. The results indicated that TAF exhibited powerful antimicrobial activity against both of Enterococcus faecalis and Enterococcus faecium with minimum inhibitory and bactericidal concentrations ranging from 8 to 16 µg ml-1. Meanwhile, biofilm inhibition and eradication assays showed that TAF exhibited potent anti-biofilm activity against E. faecalis ATCC 29212 and E. faecium ATCC 19434. Ultra-microscopic observations revealed significant changes in bacterial morphology and structure caused by TAF, particularly for the disruption of plasma membrane. Mechanistic investigations also revealed that TAF altered both membrane permeability and potential while also impacting adenosine triphosphate production as well as reactive oxygen species generation. In addition, no detectable cytotoxicity of TAF on human cells was observed at concentrations near the minimal inhibitory concentration. CONCLUSIONS: In summary, this study confirmed that TAF could effectively inhibit Enterococcus as well as its biofilm formation.

Big data development and agricultural carbon emissions: Exacerbation or suppression? A quasi-natural experiment based on the establishment of the National Big Data Comprehensive Pilot Zone.

As a strategic resource, big data has become a key force affecting carbon emission reduction in agriculture. However, its impacts remain controversial, and relevant empirical evidence remains to be explored. Based on quasi-natural experimental analysis, this study explored the impact and mechanism of the construction of the National Big Data Comprehensive Pilot Zone (NBDCPZ) on agricultural carbon emissions (ACE) in China and adopted a difference-in-difference (DID) model using China's provincial panel data from 2003 to 2020. The results showed that the ACE in the NBDCPZ establishment area was significantly reduced by 11.91%, a finding that remained robust following the parallel trend test and the placebo test, among others. Mechanism analysis showed that the ACE was reduced through industrial upgrading and technological innovation. Heterogeneity analysis showed that more pronounced policy gains were achieved in China's central-eastern regions as well as in non-major grain-producing areas compared to western and major grain-producing areas. This research provided supporting evidence for the prospect of big data application in ACE and provided useful guidance regarding the promotion of green and sustainable agricultural development.

A Hydrogen Evolution Catalyst [Co2O2] Metallacycle Enables Regioselective Allene C(sp2)-H Functionalization.

Selective functionalization of allenic C(sp2)-H is an ideal approach to upgrading simple allenes to synthetically useful allenes, albeit suffering from challenges associated with inert reactivity and inferior selectivity. Inspired by energy chemistry, a catalytic hydrogen evolution reaction (HER) strategy was leveraged to selectively activate weakly acidic allene C(sp2)-H bonds in a reductive mode. An array of [Co2O2] metallacycle complexes were readily devised starting from amino acids, and they were demonstrated as robust HER catalysts, which would selectively break allenic C(sp2)-H bonds to release hydrogen. With the newly developed HER catalyst, regioselective electrochemical functionalization of allenic C(sp2)-H with alcoholic α C(sp3)-H was unprecedentedly achieved. This strategy features excellent regioselectivity, unconventional chemoselectivity, good functional-group tolerance (62 examples), and mild conditions. Mechanism experiments revealed a reactive hydroxy-coordinated cobalt(II) species in the reaction. Density functional theory (DFT) calculations were also conducted to rationalize the regioselectivity observed in the reaction.

Wheat VQ Motif-Containing Protein VQ25-A Facilitates Leaf Senescence via the Abscisic Acid Pathway.

Leaf senescence is an important factor affecting the functional transition from nutrient assimilation to nutrient remobilization in crops. The senescence of wheat leaves is of great significance for its yield and quality. In the leaf senescence process, transcriptional regulation is a committed step in integrating various senescence-related signals. Although the plant-specific transcriptional regulation factor valine-glutamine (VQ) gene family is known to participate in different physiological processes, its role in leaf senescence is poorly understood. We isolated TaVQ25-A and studied its function in leaf senescence regulation. TaVQ25-A was mainly expressed in the roots and leaves of wheat. The TaVQ25-A-GFP fusion protein was localized in the nuclei and cytoplasm of wheat protoplasts. A delayed senescence phenotype was observed after dark and abscisic acid (ABA) treatment in TaVQ25-A-silenced wheat plants. Conversely, overexpression of TaVQ25-A accelerated leaf senescence and led to hypersensitivity in ABA-induced leaf senescence in Arabidopsis. A WRKY type transcription factor, TaWRKY133, which is tightly related to the ABA pathway and affects the expression of some ABA-related genes, was found to interact with TaVQ25-A both in vitro and in vivo. Results of this study indicate that TaVQ25-A is a positive regulator of ABA-related leaf senescence and can be used as a candidate gene for wheat molecular breeding.

The Functional Roles of ISG15/ISGylation in Cancer.

The protein ISG15 encoded by interferon-stimulated gene (ISG) 15 is the first identified member of the ubiquitin-like protein family and exists in the form of monomers and conjugated complexes. Like ubiquitin, ISG15 can mediate an ubiquitin-like modification by covalently modifying other proteins, known as ISGylation. There is growing evidence showing that both the free and conjugated ISG15 are involved in multiple key cellular processes, including autophagy, exosome secretion, DNA repair, immune regulation, and cancer occurrence and progression. In this review, we aim to further clarify the function of ISG15 and ISGylation in cancer, demonstrate the important relationship between ISG15/ISGylation and cancer, and emphasize new insights into the different roles of ISG15/ISGylation in cancer progression. This review may contribute to therapeutic intervention in cancer. However, due to the limitations of current research, the regulation of ISG15/ISGylation on cancer progression is not completely clear, thus further comprehensive and sufficient correlation studies are still needed.

Mapping leprosy-associated coding variants of interleukin genes by targeted sequencing.

Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10-8 , odds ratio [OR] = 1.748) and IL1RN (rs45507693, p.A106T, p = 1.45 × 10-5 , OR = 3.629) were significantly associated with leprosy risk. mRNA levels of IL27 and IL1RN were upregulated in whole blood cells after M. leprae stimulation. These data showed that IL27 and IL1RN are leprosy risk genes. Further functional study is required for characterizing the exact role of ILs in leprosy.

The correlated expression of immune and energy metabolism related genes in the response to Salmonella enterica serovar Enteritidis inoculation in chicken.

BACKGROUND: Salmonella enterica serovar Enteritidis (SE) is one of the food-borne pathogenic bacteria, which affects poultry production and poses severe threat to human health. The correlation of immune system and metabolism in chicken after SE inoculation is important but not clear. In the current study, we identified the expression of immune and energy metabolism related genes using quantitative PCR to evaluate the correlation between immune system and energy metabolism against SE inoculation in Jining Bairi chicken. RESULTS: ATP5G1, ATP5G3 and ND2 were significantly up-regulated at 1 dpi (day post inoculation), and ATP5E, ATP5G1, ATP5G3 were significantly down-regulated at 7 dpi (P < 0.05). IL-8 and IL-1ß were significantly down-regulated at 1 dpi, IL-8 and IL-18 were significantly down-regulated at 3 dpi, IL-8 and BCL10 were significantly up-regulated at 7 dpi (P < 0.05). CONCLUSIONS: These findings indicate that the correlation between immune and energy metabolism related genes gradually change with time points post SE inoculation, from one homeostasis to an opposite homeostasis with 3 dpi as a turning point. These results will pave the foundation for the relationship between immune system and energy metabolism in the response to SE inoculation in chicken.

Metabolome-Wide Mendelian Randomization Assessing the Causal Relationship Between Blood Metabolites and Sarcopenia-Related Traits.

Sarcopenia is among the most common musculoskeletal illnesses, yet its underlying biochemical mechanisms remain incompletely understood. In this study, we used Mendelian randomization (MR) to investigate the causal relationship between the genetically determined blood metabolites and sarcopenia, with the overall objective of identifying likely molecular pathways for sarcopenia. We used 2-sample MR to investigate the effects of blood metabolites on sarcopenia-related traits. 452 metabolites were exposure, and 3 sarcopenia-related traits as the outcomes: handgrip strength, appendicular lean mass, and walking pace. The inverse-variance weighted (IVW) causal estimates were determined. For sensitivity analysis, methods such as MR-Egger regression, the weighted median, the weighted mode, and the heterogeneity test were used. Additionally, for complementation, we performed replication, meta-analysis, and metabolic pathway analyses. Candidate biomarkers were defined by meeting one of the following criteria: (1) significant metabolites are defined as pIVW < pBonferroni [1.11 × 10-4 (.05/452)]; (2) strong metabolites are defined as 4 MR methods p < .05; and (3) suggestive metabolites are defined as passing sensitivity analysis. Three metabolites (creatine, 1-arachidonoylglycerophosphocholine, and pentadecanoate [15:0]) with significant causality, 3 metabolites (glycine, 1-arachidonoylglycerophosphocholine, and epiandrosterone sulfate) with strong causality, and 25 metabolites (including leucylleucin, pyruvic acid, etc.) with suggestive causality were associated with sarcopenia-related traits. After further replication analyses and meta-analysis, these metabolites maintained substantial effects on sarcopenia-related traits. We additionally identified 14 important sarcopenia-related trait metabolic pathways. By combining metabolomics with genomics, these candidate metabolites and metabolic pathways identified in our study may provide new clues regarding the mechanisms underlying sarcopenia.

Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.

There are few tumor cell subpopulations with stem cell characteristics in tumor tissue, defined as cancer stem cells (CSCs) or cancer stem-like cells (CSLCs), which can reconstruct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited generation. The microenvironment that CSCs depend on consists of various cellular components and corresponding medium components. Among these factors existing at a variety of levels and forms, cytokine networks and numerous signal pathways play an important role in signaling transduction. These factors promote or maintain cancer cell stemness, and participate in cancer recurrence, metastasis, and resistance. This review aims to summarize the recent molecular data concerning the multilayered relationship between CSCs and CSC-favorable microenvironments. We also discuss the therapeutic implications of targeting this synergistic interplay, hoping to give an insight into targeting cancer cell stemness for tumor therapy and prognosis.

Pretreatment CT-based machine learning radiomics model predicts response in unresectable hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors and interventional therapy.

BACKGROUND: Lenvatinib plus PD-1 inhibitors and interventional (LPI) therapy have demonstrated promising treatment effects in unresectable hepatocellular carcinoma (HCC). However, biomarkers for predicting the response to LPI therapy remain to be further explored. We aimed to develop a radiomics model to noninvasively predict the efficacy of LPI therapy. METHODS: Clinical data of patients with HCC receiving LPI therapy were collected in our institution. The clinical model was built with clinical information. Nine machine learning classifiers were tested and the multilayer perceptron classifier with optimal performance was used as the radiomics model. The clinical-radiomics model was constructed by integrating clinical and radiomics scores through logistic regression analysis. RESULTS: 151 patients were enrolled in this study (2:1 randomization, 101 and 50 in the training and validation cohorts), of which three achieved complete response, 69 showed partial response, 46 showed stable disease, and 33 showed progressive disease. The objective response rate, disease control rate, and conversion resection rates were 47.7, 78.1 and 23.2%. 14 features were selected from the initially extracted 1223 for radiomics model construction. The area under the curves of the radiomics model (0.900 for training and 0.893 for validation) were comparable to that of the clinical-radiomics model (0.912 for training and 0.892 for validation), and both were superior to the clinical model (0.669 for training and 0.585 for validation). Meanwhile, the radiomics model can categorize participants into high-risk and low-risk groups for progression-free survival (PFS) and overall survival (OS) in the training (HR 1.913, 95% CI 1.121 to 3.265, p=0.016 for PFS; HR 4.252, 95% CI 2.051 to 8.816, p=0.001 for OS) and validation sets (HR 2.347, 95% CI 1.095 to 5.031, p=0.012 for PFS; HR 2.592, 95% CI 1.050 to 6.394, p=0.019 for OS). CONCLUSION: The promising machine learning radiomics model was developed and validated to predict the efficacy of LPI therapy for patients with HCC and perform risk stratification, with comparable performance to clinical-radiomics model.

A Mendelian randomization study to examine the causal associations of circulating micronutrient levels with frailty risk.

Background: Observational studies have shown that micronutrients can affect the occurrence of frailty. However, it is not clear whether there is a causal relationship between the two. This study aimed to explore the causal relationship between circulating micronutrient levels and frailty risk using a two-sample Mendelian randomization (TSMR) approach. Methods: We gathered and screened instrumental variables (IVs) for six circulating micronutrients, including vitamin B12, vitamin B6, folate, vitamin C, vitamin D, and vitamin E, from published genome-wide association studies (GWAS) and the IEU OpenGWAS open database. Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We performed two independent TSMR analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between circulating micronutrientn and frailty. Results: Our study found, no causal relationship between genetically predicted vitamin D (ß = -0.059, p = 0.35), vitamin B6 (ß = 0.006, p = 0.80), vitamin E (ß = -0.011, p = 0.79), vitamin C (ß = -0.044, p = 0.06), vitamin B12 (ß = -0.027, p = 0.37), and folate (ß = 0.029, p = 0.17), with frailty. Conclusion: This study showed that these six micronutrients did not reduce the risk of developing frailty. However, we think it is necessary further to investigate the relationship and mechanisms between micronutrients and frailty using methods such as randomized controlled trials.

Simeprevir restores the anti-Staphylococcus activity of polymyxins.

Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a severe threat to global public health due to its high mortality. Currently, polymyxins are mainly used for the treatment of Gram-negative bacterial-related infection, while exhibiting limited antibacterial activities against Staphylococcus aureus (S. aureus). However, the combination of antibiotics with antibiotic adjuvants is a feasible strategy for the hard-treated infection and toxicity reducing. We will investigate the antibacterial activity of simeprevir (SIM), which treated for genotype 1 and 4 chronic hepatitis C, combined with polymyxins against MRSA through high-throughput screening technology. In our study, the synergistic antibacterial effect of SIM and polymyxins against S. aureus in vitro was found by checkerboard assay and time-growth curve. The cytotoxicity of SIM combined with polymyxin B sulfate [PB(S)] or polymyxin E (PE) in vitro was evaluated using CCK-8, human RBC hemolysis and scratch assays. In addition, we investigated the eradication of biofilm formation of S. aureus by biofilm inhibition assay and the killing of persister cells. Moreover, we evaluated the therapeutic effect and in vivo toxicity of the combination against MRSA in murine subcutaneous abscess model. Furthermore, it was preliminarily found that SIM significantly enhanced the destruction of MRSA membrane by SYTOX Green and DISC3(5) probes. In summary, these results reveal that the therapy of SIM combined with polymyxins (especially PE) is promising for the treatment of MRSA infection.

A novel nomogram based on preoperative parameters to predict posthepatectomy liver failure in patients with hepatocellular carcinoma.

BACKGROUND: Posthepatectomy liver failure is one of the main causes of death in patients after hepatectomy. This study intends to establish a prediction model to predict the risk of posthepatectomy liver failure and provide a scientific basis for further reducing the incidence of posthepatectomy liver failure. METHODS: This was a retrospective analysis of 1,172 patients with hepatocellular carcinoma undergoing partial hepatectomy. Using univariate and multivariate logistic regression analyses and stepwise regression, a prediction model for posthepatectomy liver failure was established based on the independent risk factors for posthepatectomy liver failure and validated by bootstrapping with 100 resamples, and the receiver operating characteristic curve was used to evaluate the predictive value of the prediction model. RESULTS: The incidence rate of posthepatectomy liver failure was 22.7% (266/1172). The results showed that the indocyanine green retention rate at 15 minutes (odds ratio = 1.05, P = .002), alanine transaminase (odds ratio = 1.02, P < .001), albumin rate (odds ratio = 0.92, P < .001), total bilirubin (odds ratio = 1.04, P < .001), prothrombin time (odds ratio = 2.44, P < .001), aspartate aminotransferase-neutrophil ratio (odds ratio = 0.95, P < .001), and liver fibrosis index (odds ratio = 1.35, P < .001) were associated with posthepatectomy liver failure. These 7 independent risk factors for posthepatectomy liver failure were integrated into a nomogram prediction model, the predictive efficiency for posthepatectomy liver failure (area under the curve = 0.818, 95% confidence interval 0.789-0.848) was significantly higher than in other predictive models with a liver fibrosis index (area under the curve = 0.651), indocyanine green R15 (area under the curve = 0.669), albumin-bilirubin score (area under the curve = 0.709), albumin-indocyanine green evaluation score (area under the curve = 0.706), model for end-stage liver disease score (area under the curve = 0.636), and Child‒Pugh (area under the curve = 0.551) (all P < .001). The risk of posthepatectomy liver failure in the high-risk posthepatectomy liver failure group (score ≥152) was higher than that in the posthepatectomy liver failure low-risk group (score <152). CONCLUSION: This study developed and validated a nomogram model to predict the risk of posthepatectomy liver failure before surgery that can effectively predict the risk of posthepatectomy liver failure in patients with hepatocellular carcinoma.

GP73 blockade alleviates abnormal glucose homeostasis in diabetic mice.

Golgi protein 73 (GP73), also called Golgi membrane protein 1 (GOLM1), is a resident Golgi type II transmembrane protein and is considered as a serum marker for the detection of a variety of cancers. A recent work revealed the role of the secreted GP73 in stimulating liver glucose production and systemic glucose homeostasis. Since exaggerated hepatic glucose production plays a key role in the pathogenesis of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), GP73 may thus represent a potential therapeutic target for treating diabetic patients with pathologically elevated levels. Here, in this study, we found that the circulating GP73 levels were significantly elevated in T2DM and positively correlated with hemoglobin A1c. Notably, the aberrantly upregulated GP73 levels were indispensable for the enhanced protein kinase A signaling pathway associated with diabetes. In diet-induced obese mouse model, GP73 siRNA primarily targeting liver tissue was potently effective in alleviating abnormal glucose metabolism. Ablation of GP73 from whole animals also exerted a profound glucose-lowering effect. Importantly, neutralizing circulating GP73 improved glucose metabolism in streptozotocin (STZ) and high-fat diet/STZ-induced diabetic mice. We thus concluded that GP73 was a feasible therapeutic target for the treatment of diabetes.

Effects of 1,2,4-trichlorobenzene on the enzyme activities and ultrastructure of earthworm Eisenia fetida.

Adult Eisenia fetida earthworms were exposed to sub-lethal concentrations of 1,2,4-trichlorobenzene to assess the toxicity of contaminated soils. The LC50 of 1,2,4-TCB at 7 and 14 d were 945±175 and 890±169 mg kg⁻¹. A lower dose of 1,2,4-TCB (25 mg g⁻¹) had stimulatory effects on SOD and AChE activities, but AChE activities were significantly inhibited at higher treatment levels (100 and 400 mg g⁻¹). SOD activities increased after 2, 7, and 14 d of exposure, but AChE activities were significantly inhibited at 400 mg/kg 1,2,4-TCB after 2, 7, and 14 d of exposure, and the inhibition rates were 25.41%, 28.65%, and 25.05%. Ultrastructural observation of the intestinal epithelium at three concentrations (control, 50, and 400 mg g⁻¹) revealed that the epicuticle, cuticle layer, and microvilli were damaged with increasing 1,2,4-TCB concentration. At 400 mg kg⁻¹, mitochondria were seriously injured and the smooth endoplasmic reticulum was seriously dilated.

catena-Poly[3,3'-diethyl-1,1'-(propane-1,3-di-yl)di(1H-imidazol-3-ium) [silver(I)-di-µ-iodido-silver(I)-di-µ-iodido]].

The title compound, {(C(13)H(22)N(4))[Ag(2)I(4)]}(n), was prepared by reaction of 1,3-bis-(N-ethyl-imidazolium-1-yl)propane iodide with silver (I) oxide. In the 3,3'-diethyl-1,1'-(propane-1,3-di-yl)di(1H-imidazol-3-ium) cation, the dihedral angle between the imidazole rings is 49.3 (1)°. In the [Ag(2)I(4)](2-) anion, each Ag(I) atom is bonded to three iodide anions, the two Ag(I) atoms and two of the iodides forming Ag(2)I(2) square-planar (r.m.s. deviation = 0.01 Å) units·The remaining two iodides, which are placed on opposite sides of the square, together with their centrosymmetric counterparts, link the square-planar Ag(2)I(2) units into {[Ag(2)I(4)](2-)}(n) polymeric chains via Ag-I bonds.

Design and Implementation of Internet of Things Technology in College Students' Innovation and Entrepreneurship Integration System.

In order to improve the operation efficiency of the innovation and entrepreneurship integration system of college students, this document proposes to formulate and implement the innovation and entrepreneurship integration system of college students based on "Internet technology." The web front end is implemented by Django technology, the back end is developed by Apache server pycharm, the database is written in Python, and the database is MySQL. The system meets the expected objectives of implementing, monitoring, and managing innovation and entrepreneurship projects. How the system realizes the functions of repeated comparison projects, easy tracking projects, and fast search, and how managers can make progress at any time. By creating different account function permissions, the system realizes the login, declaration, management, and other functions required by the users of the innovation and entrepreneurship project management system. It is very suitable for college students to improve the project application, information review, and application process. At the same time, it is helpful to supervise and select teachers and greatly improve management efficiency. The test results show that the minimum values of 30, 80, and 150 simulated users in the system performance test are 4, 5, and 7, respectively. The maximum users of the system performance test model are 30, 80, 150, 64, 284, and 398. The system performance tests are taken under the conditions of 30, 80, and 150 user bandwidth, with the results of 113/min, 104/min, and 90/min. The system basically meets the daily work management standards and fully achieves the expected system design goals. The development and use of this system are related to the development of college students' innovation and entrepreneurship project management and have a clear reference for the development of innovation and entrepreneurship project management systems similar to manage workflow in the future.

Phosphoproteomics Profile of Chicken Cecum in the Response to Salmonella enterica Serovar Enteritidis Inoculation.

Salmonella enterica serovar Enteritidis (S. Enteritidis) is a foodborne pathogen, which can cause great threats to human health through the consumption of contaminated poultry products. This research combines TMT labeling, HPLC and mass-spectrometry-based phosphoproteomics on cecum of the F1 cross of Guangxi Yao chicken and Jining Bairi chicken. The treated group was inoculated with 0.3 mL inoculum S. Enteritidis, and the control group was inoculated with 0.3 mL phosphate-buffered saline (PBS). A total of 338 differentially phosphorylated modification sites in 243 differentially phosphorylated proteins (DPPs) were chosen for downstream analyses. A total of 213 sites in 146 DPPs were up-regulated and 125 sites in 97 DPPs were down-regulated. Functional analysis was performed for DPPs based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the protein domain. The DPPs were mainly enriched in immune- and metabolic-related GO-BP (biological process) and KEGG pathways. We predicted and classified the subcellular structure and COG/KOG of DPPs. Furthermore, protein-protein interaction network analyses were performed by using multiple algorithms. We identified 71 motifs of the phosphorylated modification sites and selected 18 sites randomly to detect the expression level through parallel reaction monitoring (PRM). S. Enteritidis inoculation caused phosphorylation alteration in immune- and metabolic-related proteins. The invasion of S. Enteritidis may be actualized by inducing cecum cell apoptosis through the endoplasmic reticulum pathway, and chickens could resist the invasion of S. Enteritidis by affecting the function of ECM receptors. The findings herein provide a crucial theoretical foundation to understand the molecular mechanism and epigenetic regulation in response to S. Enteritidis inoculation in chickens.

CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3ß/ß-catenin signaling pathway.

Circular RNAs have been reported to play essential roles in the tumorigenesis and progression of various cancers. However, the biological processes and mechanisms involved in hepatocellular carcinoma (HCC) remain unclear. Initial RNA-sequencing data and qRT-PCR results in our cohort showed that hsa_circ_0072309 (also called circLIFR) was markedly downregulated in HCC tissues. Kaplan-Meier analysis indicated that higher levels of circLIFR in HCC patients correlated with favorable overall survival and recurrence-free survival rates. Both in vitro and in vivo experiments indicated that circLIFR inhibited the proliferation and invasion abilities of HCC cells. We therefore conducted related experiments to explore the mechanism of circLIFR in HCC. Fluorescence in situ hybridization results revealed that circLIFR was mainly located in the cytoplasm, and RNA immunoprecipitation assays indicated that circLIFR was significantly enriched by Ago2 protein. These results suggested that circLIFR may function as a sponge of miRNAs to regulate HCC progression. We further conducted bioinformatics prediction as well as dual-luciferase reporter assays, and the results of which showed that circLIFR could sponge miR-624-5p to stabilize glycogen synthase kinase 3ß (GSK-3ß) expression. Loss and gain of function experiments demonstrated that regulation of the expression of miR-624-5p or GSK-3ß markedly affected HCC progression induced by circLIFR. Importantly, we also proved that circLIFR could facilitate the degradation of ß-catenin and prevent its translocation to the nucleus in HCC cells. Overall, our study demonstrated that circLIFR acts as a tumor suppressor in HCC by regulating miR-624-5p and inactivating the GSK-3ß/ß-catenin signaling pathway.