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Transmissible gastroenteritis virus (TGEV) is an etiological agent of enteric disease that results in high mortality rates in piglets. The economic impact of the virus is considerable, causing significant losses to the pig industry. The development of an efficacious subunit vaccine to provide promising protection against TGEV is of the utmost importance. The viral antigen, spike glycoprotein (S), is widely regarded as one of the most effective antigenic components for vaccine research. In this study, we employed immunoinformatics and molecular dynamics approaches to develop an 'ideal' multi-epitope vaccine. Firstly, the dominant, non-toxic, highly antigenic T (Th, CTL) and B cell epitopes predicted from the TGEV S protein were artificially engineered in tandem to design candidate subunit vaccines. Molecular docking and dynamic simulation results demonstrate that it exhibits robust interactions with toll-like receptor 4 (TLR4). Of particular significance was the finding that the vaccine was capable of triggering an immune response in mammals, as evidenced by the immune simulation results. The humoral aspect is typified by elevated levels of IgG and IgM, whereas the cellular immune aspect is capable of eliciting the robust production of interleukins and cytokines (IFN-γ and IL-2). Furthermore, the adoption of E. coli expression systems for the preparation of vaccines will also result in cost savings. This study offers logical guidelines for the development of a secure and efficacious subunit vaccine against TGEV, in addition to providing a novel theoretical foundation and strategy to prevent associated CoV infections. [ABSTRACT FROM AUTHOR]

Background: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. Methods: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. Results: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. Conclusion: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients. [ABSTRACT FROM AUTHOR]

Heterogeneous thermal-catalytic CO2 hydrogenation to alcohols using renewable energy is a highly attractive approach for recycling greenhouse gases into high-value chemicals and fuels, thereby reducing the dependence on fossil fuels, while simultaneously mitigating the CO2 emission and environmental problems. Currently, great advances have been made on the heterogeneous catalysts, but an in-depth and more comprehensive understanding to further promote this reaction process is still lacking. Herein, we highlight the thermodynamic and kinetic analysis of CO2 hydrogenation reaction firstly. Then, various reaction pathways for CO2 hydrogenation to methanol and higher alcohols (C2+ alcohols) have been discussed in detail, respectively, by combining the experimental studies and density functional theory calculations. On this basis, the key factors influencing the reaction performance, such as metal dispersion, support modification, promoter addition and their structural optimization, are summarized on the metal-based and metal-oxide-based catalysts. In addition, the catalytic performance of CO2 hydrogenation to alcohols and the relationship between structure and properties are mainly summarized and analyzed in the past five years. To conclude, the current challenges and potential strategies in catalyst design, structural characterization and reaction mechanisms are presented for CO2 hydrogenation to alcohols. [ABSTRACT FROM AUTHOR]

The T-2 toxin (T2) poses a major threat to the health and productivity of animals. The present study aimed to investigate the regulatory mechanism of Nrf2 derived from broilers against T2-induced oxidative damage. DF-1 cells, including those with normal characteristics, as well as those overexpressing or with a knockout of specific components, were exposed to a 24 h treatment of 50 nM T2. The primary objective was to evaluate the indicators associated with oxidative stress and the expression of downstream antioxidant factors regulated by the Nrf2-ARE signaling pathway, at both the mRNA and protein levels. The findings of this study demonstrated a noteworthy relationship between the up-regulation of the Nrf2 protein and a considerable reduction in the oxidative stress levels within DF-1 cells (p < 0.05). Furthermore, this up-regulation was associated with a notable increase in the mRNA and protein levels of antioxidant factors downstream of the Nrf2-ARE signaling pathway (p < 0.05). Conversely, the down-regulation of the Nrf2 protein was linked to a marked elevation in oxidative stress levels in DF-1 cells (p < 0.05). Additionally, this down-regulation resulted in a significant decrease in both the mRNA and protein expression of antioxidant factors (p < 0.05). This experiment lays a theoretical foundation for investigating the detrimental impacts of T2 on broiler chickens. It also establishes a research framework for employing the Nrf2 protein in broiler chicken production and breeding. Moreover, it introduces novel insights for the prospective management of oxidative stress-related ailments in the livestock and poultry industry. [ABSTRACT FROM AUTHOR]

In China, animal feeds are frequently contaminated with a range of mycotoxins, with Aflatoxin B1 (AFB1) and T-2 toxin (T-2) being two highly toxic mycotoxins. This study investigates the combined nephrotoxicity of AFB1 and T-2 on PK15 cells and murine renal tissues and their related oxidative stress mechanisms. PK15 cells were treated with the respective toxin concentrations for 24 h, and oxidative stress-related indicators were assessed. The results showed that the combination of AFB1 and T-2 led to more severe cellular damage and oxidative stress compared to exposure to the individual toxins (p < 0.05). In the in vivo study, pathological examination revealed that the kidney tissue of mice exposed to the combined toxins showed signs of glomerular atrophy. The contents of oxidative stress-related indicators were significantly increased in the kidney tissue (p < 0.05). These findings suggest that the combined toxins cause significant oxidative damage to mouse kidneys. The study highlights the importance of considering the combined effects of mycotoxins in animal feed, particularly AFB1 and T-2, which can lead to severe nephrotoxicity and oxidative stress in PK15 cells and mouse kidneys. The findings have important implications for animal feed safety and regulatory policy. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis‐derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis‐related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP‐induced bone marrow‐derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL‐1β release as well as the protein level of NLRP3, caspase‐1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS‐induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside‐treated foecal bacterium into flora‐depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive gastrointestinal cancers with high incidence and mortality. Therefore, it is necessary to identify novel sensitive and specific biomarkers for ESCC detection and treatment. Circular RNAs (circRNAs) are a type of noncoding RNAs featured by their covalently closed circular structure. This special structure makes circRNAs more stable in mammalian cells, coupled with their great abundance and tissue specificity, suggesting circRNAs may present enormous potential to be explored as valuable prognostic and diagnostic biomarkers for tumor. Mounting studies verified the critical roles of circRNAs in regulating ESCC cells malignant behaviors. Here, we summarized the current progresses in a handful of aberrantly expressed circRNAs, and elucidated their biological function and clinical significance in ESCC, and introduced a series of databases for circRNA research. With the improved advancement in high-throughput sequencing and bioinformatics technique, new frontiers of circRNAs will pave the path for the development of precision treatment in ESCC. [ABSTRACT FROM AUTHOR]

Background and Aims There is evidence for a disturbed necroptosis function in many inflammatory diseases, but its role in inflammatory bowel diseases [IBD] and the underlying mechanisms are unclear. Here, we studied the functional significance and molecular mechanisms of ABIN3, a ubiquitin-binding protein, in regulating the ubiquitination and activation of necroptosis in IBD. Methods The expression of necroptosis hallmarks and ABIN3 were assessed in inflamed samples of IBD patients, dextran sodium sulphate [DSS]-induced colitis models, and azoxymethane [AOM]/DSS models in mice. ABIN3 was overexpressed and silenced to explore its function in regulating necroptosis, inflammation, and intestinal barrier function. Immuoprecipitiation [IP] and co-IP assays were performed to investigate the cross-talk between ABIN3 and deubiquitinating enzyme A20, and the mechanisms of coordinating ubiquitination modification to regulate necroptosis. Results Excessive necroptosis is an important contributory factor towards the uncontrolled inflammation and intestinal barrier defects in IBD and experimental colitis. Blocking necroptosis by Nec-1s or GSK'872 significantly prevented cell death and alleviated DSS-induced colitis in vivo, whereas in the AOM/DSS model, necroptosis inhibitors aggravated the severity of colitis-associated colon carcinogenesis [CAC]. Mechanistically, ABIN3 is rapidly recruited to the TNF-RSC complex, which interacts and coordinates with deubiquitinating enzyme A20 to control the K63 deubiquitination modification and subsequent activation of the critical necroptosis kinase, RIPK3, to suppress necroptosis. Conclusions ABIN3 regulates inflammatory response and intestinal barrier function by interacting with A20 and coordinating the K63 deubiquitination modification of necroptosis in IBD. [ABSTRACT FROM AUTHOR]

Background. Papillary thyroid carcinoma (PTC) is a common endocrine malignant neoplasm, and its incidence increases continuously worldwide in the recent years. However, efficient clinical biomarkers were still deficient; the present research is aimed at exploring significant core genes of PTC. Methods. We integrated three cohorts to identify hub genes and pathways associated with PTC by comprehensive bioinformatics analysis. Expression profiles GSE33630, GSE35570, and GSE60542, including 114 PTC tissues and 126 normal tissues, were enrolled in this research. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to search for the crucial biological behaviors and pathways involved in PTC carcinogenesis. Protein-protein interaction (PPI) network was constructed, and significant modules were deeply studied. Results. A total of 831 differentially expressed genes (DEGs) were discovered, comprising 410 upregulated and 421 downregulated genes in PTC tissues compared to normal thyroid tissues. PPI network analysis demonstrated the interactions between those DEGs, and top 10 pivotal genes (TGFB1, CXCL8, LRRK2, CD44, CCND1, JUN, DCN, BCL2, ACACB, and CXCL12) with highest degree of connectivity were extracted from the network and verified by TCGA dataset and RT-PCR experiment of PTC samples. Four of the hub genes (CXCL8, DCN, BCL2, and ACACB) were linked to the prognosis of PTC patients and considered as clinically relevant core genes via survival analysis. Conclusion. In conclusion, we propose a series of key genes associated with PTC development and these genes could serve as the diagnostic biomarkers or therapeutic targets in the future treatment for PTC. [ABSTRACT FROM AUTHOR]

Solute carrier family members control essential physiological functions and are tightly linked to human diseases. Solute carrier family 35 member F2 (SLC35F2) is aberrantly activated in several malignancies. However, the biological function and molecular mechanism of SLC35F2 in papillary thyroid carcinoma (PTC) are yet to be fully explored. Here, we showed that SLC35F2 was prominently upregulated in PTC tissues at both protein and mRNA expression level compared with matched adjacent normal tissues. Besides, the high expression of SLC35F2 was significantly associated with lymph node metastasis in patients with PTC. CRISPR/Cas9‐mediated knockout of SLC35F2 attenuated the tumorigenic properties of PTC, including cell proliferation, migration and invasion and induced G1 phase arrest. In contrast, ectopic expression of SLC35F2 brought about aggressive malignant phenotypes of PTC cells. Moreover, SLC35F2 expedited the proliferation and migration of PTC cells by targeting transforming growth factor‐β type I receptor (TGFBR1) and phosphorylation of apoptosis signal‐regulating kinase 1 (p‐ASK‐1), thereby activating the mitogen‐activated protein kinase signaling pathway. The malignant behaviors induced by overexpression of SLC35F2 could be abrogated by silencing of TGFBR1 using a specific inhibitor. We conducted the first study on SLC35F2 in thyroid cancer with the aim of elucidating the functional significance and molecular mechanism of SLC35F2. Our findings suggest that SLC35F2 exerts its oncogenic effect on PTC progression through the mitogen‐activated protein kinase pathway, with dependence on activation of TGFBR‐1 and apoptosis signal‐regulating kinase 1. [ABSTRACT FROM AUTHOR]

Barrett's esophagus (BE) is a premalignant lesion of esophageal adenocarcinoma. The aim of the present study was to investigate the possible mechanisms and biomarkers of BE. To identify the differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) in BE, the miRNA expression profile GSE20099 and the gene expression profiles GSE26886, GSE13083 and GSE34619 were obtained from the Gene Expression Omnibus (GEO) database. DEGs and DEmiRNAs were screened for using the GEO2R tool. Using DAVID, functional and pathway enrichment analysis was performed to explore the biological function of identified DEGs. The protein-protein interaction (PPI) network was detected using STRING and constructed by Cytoscape software. Furthermore, targets of identified DEmiRNAs were predicted by the miRecords database, then integrated with the identified DEGs to obtain key genes involved in BE. In total, 311 DEGs were identified. These genes were significantly enriched in the pancreatic secretion, metabolic pathways and cytochrome P450 drug metabolism pathways. In the PPI network, 16 hub genes, including keratin 16, cystic fibrosis transmembrane conductance regulator, involucrin, protein kinase C a and cadherin 17 were identified. Following integration of the predicted target genes of DEmiRNAs with DEGs, three key BE genes were identified: PRKCA, CDH17 and epiregulin. In conclusion, a comprehensive bioinformatics analysis of identified DEGs and DEmiRNAs was performed to elucidate potential pathways and biomarkers involved in the development of BE. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn’s disease (CD), is a complicated, uncontrolled, and multifactorial disorder characterized by chronic, relapsing, or progressive inflammatory conditions that may involve the entire gastrointestinal tract. The protracted nature has imposed enormous economic burdens on patients with IBD, and the treatment is far from optimal due to the currently limited comprehension of IBD pathogenesis. In spite of the exact etiology still remaining an enigma, four identified components, including personal genetic susceptibility, external environment, internal gut microbiota, and the host immune response, are responsible for IBD pathogenesis, and compelling evidence has suggested that IBD may be triggered by aberrant and continuing immune responses to gut microbiota in genetically susceptibility individuals. The past decade has witnessed the flourishing of research on genetics, gut microbiota, and immunity in patients with IBD. Therefore, in this review, we will comprehensively exhibit a series of novel findings and update the major advances regarding these three fields. Undoubtedly, these novel findings have opened a new horizon and shed bright light on the causality research of IBD. [ABSTRACT FROM AUTHOR]

In the past thirty years, molecular simulation techniques centred on density functional theory (DFT) calculations have quickly become a powerful research and technology development instrument. In particular, the knowledge and theory gained from DFT-based techniques have effectively transformed our understanding of the fundamental surface science, catalysis, and materials science. This review aims to provide a pedagogical narrative of the fundamentals of DFT and relevant computational methods applied for surface chemistry, catalytic reactions, particularly in the realm of heterogeneous and electrochemical catalysis. Several representative case studies in relation to energy and chemicals production are introduced, and relevant computationally driven catalyst design principles are discussed as well. [ABSTRACT FROM AUTHOR]

We used periodic DFT calculations to investigate the effect of alkali promoter on the selectivity of the water-gas shift reaction (WGSR) explicitly on the Ni(111) surface. On clean Ni(111), the WGSR redox and carboxyl pathways are both kinetically competitive. The selectivity of the WGSR can be affected by methanation on Ni, in which the C¢O bond cleavage pathway of CHO is the most competitive. A Ni(111) surface modified with K adatoms was used to further understand the promoter effects on the WGSR selectivity. A combined energetic and kinetic analysis from DFT calculations indicates that the K adatom stabilizes certain reactive intermediates (e.g., H2O, CO) thermodynamically but is energetically neutral or even repulsive toward other intermediates. As a result, WGSR pathways benefit from the presence of K adatoms compared to the competing methanation pathway. This study thus confirmed the promoting effects of alkali metals on the WGSR with DFTbased mechanistic insights. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that long non-coding RNAs play a critical role in the occurrence and development of human malignancies. Nonetheless, it remains unknown whether Gamma-Butyrobetaine Hydroxylase 1-Antisense RNA 1 (BBOX1-AS1) participates in the regulation of esophageal squamous cell carcinoma (ESCC) carcinogenesis. Herein, we validated that BBOX1-AS1 was notably overexpressed in ESCC tissues compared to the adjacent non-tumor tissues and significantly correlated with tumor sizes. BBOX1-AS1 enhanced the malignant behavior of ESCC cells in vitro, such as cell proliferation, migration, and invasion. In addition, knockdown of BBOX1-AS1 augmented the proportion of apoptotic cells in ESCC cells. Mechanistically, BBOX1-AS1 regulated HOXB7 expression, and rescue experiments indicated that silencing of HOXB7 could abolish the malignant phenotypes mediated by BBOX1-AS1 to a certain extent. Moreover, HOXB7 participated in the activation of the Wnt/β-catenin signaling pathway. In summary, our findings substantiated that BBOX1-AS1 could activate the Wnt/β-catenin pathway by upregulating HOXB7 expression to promote ESCC progression, providing a rationale to develop novel therapeutic approaches. • LncRNA BBOX1-AS1 was remarkably upregulated in ESCC tissues. • BBOX1-AS1 facilitated ESCC growth and metastasis by regulating HOXB7/β-catenin axis. • Targeting β-catenin or HOXB7 retarded BBOX1-AS1-mediated ESCC progression. [ABSTRACT FROM AUTHOR]

Kiwifruit canker, caused by Pseudomonas syringae pv. actinidiae (Psa), is a destructive pathogen that globally threatens the kiwifruit industry. Understanding the molecular mechanism of plant-pathogen interaction can accelerate applying resistance breeding and controlling plant diseases. All known effectors secreted by pathogens play an important role in plant-pathogen interaction. However, the effectors in Psa and their function mechanism remain largely unclear. Here, we successfully identified a T3SS effector HopAU1 which had no virulence contribution to Psa, but could, however, induce cell death and activate a series of immune responses by agroinfiltration in Nicotiana benthamiana, including elevated transcripts of immune-related genes, accumulation of reactive oxygen species (ROS), and callose deposition. We found that HopAU1 interacted with a calcium sensing receptor in N. benthamiana (NbCaS) as well as its close homologue in kiwifruit (AcCaS). More importantly, silencing CaS by RNAi in N. benthamiana greatly attenuated HopAU1-triggered cell death, suggesting CaS is a crucial component for HopAU1 detection. Further researches showed that overexpression of NbCaS in N. benthamiana significantly enhanced plant resistance against Sclerotinia sclerotiorum and Phytophthora capsici, indicating that CaS serves as a promising resistance-related gene for disease resistance breeding. We concluded that HopAU1 is an immune elicitor that targets CaS to trigger plant immunity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Approach for anchoring of Pt atoms on isolated Sn4+ is introduced. • Using this approach PtSn/SiO 2 (hexagonal mesoporous silica) catalysts were prepared. • Pt-Sn/atoms/sub nanoclusters were identified on the surface of catalysts. • The catalysts are active, selective, and stable in C 3 H 8 dehydrogenation to C 3 H 6. • Sn is essential to enhance H 2 desorption from Pt that is the rate-limiting step. Owing to propane availability in shale gas and the growing demand for propene, non-oxidative dehydrogenation of this alkane has attracted much attention. Although, catalysts with supported PtSn species are applied on the large scale, a further increase in their activity without loss in propene selectivity at low Pt content would certainly improve process economy. Herein, we introduce a molecularly defined strategy for controlling catalyst activity through anchoring of Pt atoms on isolated Sn4+ firmly confined in the framework of hexagonal mesoporous silica. In addition to the dispersion of Pt species, the presence of Sn4+ in close contact with Pt is essential for increasing the rate of propane dehydrogenation through enhancing H 2 desorption, which is the rate-limiting step. As the anchored Pt atoms/sub nanoclusters do not sinter under reducing conditions, the developed catalysts show high on-stream stability and propene selectivity of above 99 % under industrially relevant conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Highly dispersed VO x species showed high apparent TOF value but low C 3 H 6 selectivity. • VO x species in low-polyvanadate form are deemed to be more active and stable in PDH. • VO x -C 3 H 5 species was speculated to be the important intermedia during PDH. • H 2 formation is deemed as the rate-limiting step over as-prepared V-HMS. Vanadium was introduced to hexagonal mesoporous SiO 2 (HMS) to prepare supported vanadium-based catalysts (V-HMS). Their catalytic performance in the non-oxidative propane dehydrogenation to propylene (PDH) was modulated with V surface density varying from 0.12 to 15.08V atom·nm−2. VO x species with different structure were analyzed by UV–vis spectroscopy, NH 3 -TPD, H 2 -TPR and XPS. High propylene space time yield of 0.73 kg·h−1·kg cat −1 and excellent regeneration behavior were achieved. Correlating VO x polymerization degree with catalytic performance, VO x aggregates, mainly in low-polyvanadate form, were established to reveal high intrinsic activity and stability in comparison with their counterparts, including isolated or/and highly polymerized VO x as well as V 2 O 5. Temporal analysis of products (TAP) identified hydrogen formation as the rate-limiting step in the PDH reaction. In-situ DRIFTS was employed to investigate the reaction mechanism. V species containing C=C bond, i.e., VO x -C 3 H 5 , was proposed to be an intermediate of gas-phase propylene. [ABSTRACT FROM AUTHOR]