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Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide. The pathogenesis of CRC primarily stems from the gradual accumulation of genetic mutations, which drive oncogene (e.g., KRAS ) activation and tumor suppressor gene (e.g., TP53 ) inactivation. Loss of genetic stability facilitates the conversion of proto-oncogenes into active oncogenes and the functional impairment of tumor suppressors, collectively propelling CRC progression. The tumor suppressor protein p53, a transcription factor, induces cell cycle arrest, apoptosis, and DNA damage repair under cellular stress, and prevents cancer development by regulating various cellular responses. However, in CRC pathogenesis, TP53 mutations (detected in ~ 74% of cases) subvert these protective mechanisms through dual mechanisms: (i) dominant-negative suppression of wild-type p53 (wt-p53) function, and (ii) acquisition of neomorphic pro-tumorigenic activities, termed gain-of-function (GOF) mutations. New evidence from laboratory and clinical trials shows that some new therapeutic strategies have the potential to treat CRC by reactivating and restoring p53 function, depleting p53 mutants, or targeting p53 with immunotherapy. In this review, we summarize the function of p53 and characterize its mutation in CRC, emphasizing the influence of p53 mutation in the pathogenesis of CRC. In addition, we also describe the current therapeutic strategies for targeting p53 mutants in CRC.

LncRNAs are involved in the initiation and progression of cancer. However, the molecular mechanism and diverse clinical prognosis of MIR31HG in head and neck squamous cell carcinoma (HNSCC) are still unclear. Our previous microarray analysis showed that lncRNA MIR31HG interacted with HIF1A may play an oncogenic role in laryngeal squamous cell cancer (LSCC). To determine whether lncRNA MIR31HG served as a poor prognosis factor and targeted HIF1A to facilitate cell proliferation and tumorigenesis in human HNSCC, we found MIR31HG and HIF1A were overexpressed in LSCC, MIR31HG overexpression or co-expression of HIF1A-positive and p21-negative could serve as a poor prognostic factor for LSCC patients. We further confirmed that MIR31HG promoted cell proliferation, cell cycle progression, and inhibited cell apoptosis in vitro and in vivo. The ingenuity pathway analysis and Western blot indicated that MIR31HG regulated cell cycle progression via HIF1A and p21 in HNSCC. The current results provide evidences for the role of MIR31HG in promoting HNSCC progression and identify MIR31HG as a prognostic biomarker and putative therapeutic target in HNSCC.

Understanding and correlation of the multiscale interfacial mass transport behaviors mediated by the additive for liquid/liquid dispersion system is challenging. Here, we propose interfacial mass transfer flux through the quantitative coupling between microscopic interfacial parameters and mesoscopic droplet mass transfer model for H 2 SO 4 -catalyzed isobutane alkylation with emphasis on additive molecular design to industrial process intensification. Microscopic interfacial parameters are incorporated into CFD-PBM model to determine interfacial mass transfer flux of isobutane ( N isobutane ). Based on the ratio of N isobutane in the system with and without the additives, the interfacial enhancement factor E is proposed and validated as an indicator for optimal additive screening. Decoupled N isobutane from apparent kinetic model, mass transfer-free kinetic parameters of isobutane alkylation are determined, quantitatively confirming the reaction is mass transfer controlled. Additive-mediated process intensification reveals PPG400 additive increases alkylate capacity by 24.85% up to 99.83 kt/a from 79.96 kt/a in additive-free system. Understanding the microscale interfacial properties in acid-catalyzed isobutane alkylation is challenging. Here the authors propose an interfacial mass transfer flux through coupling microscopic interfacial parameters and mesoscopic droplet mass transfer model of a liquid/liquid dispersion system.

Background Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death worldwide, with increased carotid intima-media thickness (CIMT) and carotid plaque serving as key markers of subclinical atherosclerosis. The triglyceride glucose (TyG) index, a surrogate for insulin resistance, is linked to cardiovascular risk, but its association with carotid atherosclerosis remains unclear. This study explored the relationship between the TyG index and carotid plaque and increased CIMT in general population. Methods We screened 30,084 participants who received health check-ups at Aerospace Center Hospital between January and December 2019. The TyG index was calculated as Ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Carotid ultrasound assessed CIMT and plaque. Logistic regression and restricted cubic splines were used to examine the associations of TyG index with carotid atherosclerosis, adjusting for confounders. Results Fourteen thousand five hundred thirty-five participants were included in the final analysis. In multivariable logistic regression, the highest TyG index quartile (Q4) was significantly associated with greater odds of carotid plaque compared to normal CIMT (OR = 1.345; 95% CI: 1.098–1.648; P  = 0.004) and increased CIMT (OR = 1.342; 95% CI: 1.067–1.689; P  = 0.012), after adjustment for confounders. Restricted cubic spline analysis confirmed a significant nonlinear association between the TyG index and carotid plaque versus normal CIMT ( P  < 0.001), and a linear association versus increased CIMT ( P  = 0.002). No independent association was observed between the TyG index and increased CIMT versus normal CIMT. Age-stratified analyses showed significant associations between the TyG index and carotid plaque as compared with normal CIMT in individuals aged 40–69 years, and with increased CIMT in those aged 50–69 years ( P  < 0.05). The association with carotid plaque remained significant in both sexes. Conclusions The TyG index is independently associated with carotid plaque but not increased CIMT, particularly in individuals aged 40–69 years. These findings suggest that the TyG index may serve as a useful biomarker for identifying subclinical atherosclerosis, especially in middle-aged individuals.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver diseases. This study sought to evaluate the insulin-sensitizing effect of paeoniflorin (PF) on high-fat diet-induced NAFLD and possible molecular mechanisms. Male Sprague Dawley rats were fed a high-fat diet (HFD) for 10 weeks to establish the NAFLD model, and PF (20 mg/kg/d) was gavaged to the NAFLD rats for another four weeks. Our results demonstrated that HFD resulted in hepatocellular ballooning, micro-/macrovesicular steatosis, and oxidative stress in the liver, accompanied by increased serum total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and homeostasis model of insulin resistance (HOMA-IR) index. PF treatment improved the biochemical and histopathological changes in NAFLD rats. Moreover, we also found that PF could inhibit lipid ectopic deposition via regulating lipid metabolism (inhibiting lipid synthesis of cholesterol and de novo pathway), and exert insulin sensitizing effect by regulating the insulin signaling pathway IRS/Akt/GSK3β and anti-oxidation. The study findings suggest that PF has therapeutic potential against NAFLD and that it acts through multiple signaling pathways.

Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disorder characterized by persistent airflow limitation and pathological features such as airway remodeling. Identifying molecular targets involved in airway epithelial dysfunction is crucial for developing COPD therapies. Crocin, a carotenoid glycoside from saffron ( L.), may exhibit pan-assay interference compounds (PAINS)-like properties owing to its conjugated polyene structure. This can lead to non-specific effects and complicate its pharmacological interpretation. Therefore, a multidimensional assessment strategy (network analysis + + ) is essential to mitigate such limitations. We first employed predictive strategies, including network analysis, to identify common targets of crocin and COPD. Protein-protein interaction (PPI) networks were constructed, and core targets were screened via topology analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict signaling pathways. Molecular docking and dynamics simulations were then used to assess the binding potential between crocin and the core targets. Finally, the function of crocin against COPD was evaluated using the Cellular Thermal Shift Assay (CETSA) and a cigarette smoke-induced mouse model . Network analysis predicted 243 common targets, from which 48 candidate targets were identified. GO and KEGG enrichment analyses suggested the PI3K-AKT signaling pathway as a potentially key mechanism. Among the top-ranked core targets, molecular docking indicated favorable binding energies between crocin and proteins such as ALB and AKT1, a finding further corroborated by molecular dynamics simulations. Subsequent CETSA suggested a direct interaction between crocin and AKT1. experiments demonstrated that crocin administration significantly alleviated lung injury and inflammation and reduced the p-AKT1/AKT1 ratio, consistent with network analysis and CETSA findings, suggesting the observed effects were not solely attributable to PAINS interference. These findings support the therapeutic potential of crocin in COPD through its anti-inflammatory activity and regulation of AKT1. Despite potential PAINS properties, the consistency across network, , and data strengthens the biological relevance of its observed effects.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. In this study, we investigated Ultrahigh Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry and Gas Chromatography Time-of-Flight/Mass Spectrometry-based non-targeted metabolomic profiles of serum samples obtained from early-stage NSCLC patients and healthy controls (HC). Metabolic pathways and the biological relevance of potential biomarkers were extensively studied to gain insights into dysregulated metabolism in NSCLC. The identified biomarker candidates were further externally validated via a targeted metabolomics analysis. The global metabolomics profiles could clearly distinguish NSCLC patients from HC. Phosphatidylcholine (PC) levels were found to be dysregulated in glycerophospholipid (GPL) metabolism, which was the top altered pathway in early-stage NSCLC. Compared with those in HC, significant increases in the levels of saturated and monounsaturated PCs such as PC (15:0/18:1), PC (18:0/16:0) and PC (18:0/20:1) were observed in NSCLC. Additionally, relative to those in HC, the levels of 9 polyunsaturated PCs, namely, PC (17:2/2:0), PC (18:4/3:0), and PC (15:0/18:2), and so on were significantly decreased in NSCLC patients. A panel of 12 altered PCs had good diagnostic performance in differentiating early-stage NSCLC patients from HC, and these PCs may thus be used as serum biomarkers for the early diagnosis of NSCLC.

MgH 2 with a large hydrogen capacity is regarded as a promising hydrogen storage material. However, it still suffers from high thermal stability and sluggish kinetics. In this paper, highly dispersed nano-Ni has been successfully prepared by using the polyol reduction method with an average size of 2.14 nm, which significantly improves the de/rehydrogenation properties of MgH 2 . The MgH 2 —10wt% nano-Ni sample starts releasing H 2 at 497 K, and roughly 6.2wt% H 2 has been liberated at 583 K. The rehydrogenation kinetics of the sample are also greatly improved, and the adsorption capacity reaches 5.3wt% H 2 in 1000 s at 482 K and under 3 MPa hydrogen pressure. Moreover, the activation energies of de/rehydrogenation of the MgH 2 —10wt% nano-Ni sample are reduced to (88 ± 2) and (87 ± 1) kJ·mol −1 , respectively. In addition, the thermal stability of the MgH 2 —10wt% nano-Ni system is reduced by 5.5 kJ per mol H 2 from that of pristine MgH 2 . This finding indicates that nano-Ni significantly improves both the thermodynamic and kinetic performances of the de/rehydrogenation of MgH 2 , serving as a bi-functional additive of both reagent and catalyst.

Background Siberian sturgeon ( Acipenser baeri Brandt) and Beluga sturgeon ( Huso huso ) are two important commercial fish in China, and the feeding habits of them are very different. Diets and feeding habits are two significant factors to affect the gastrointestinal microbiota in fish. The intestinal microbiota has been reported to play a key role in nutrition and immunity. However, it is rarely reported about the relationship between the intestinal microbiota and feeding habits/diets on different Acipenseridae fish. This study is to comparative analysis of gut microbial community in Siberian sturgeon and Beluga sturgeon fed with the same diet/Beluga sturgeon fed with different diets in order to determine the effects of different feeding habits/diets on the fish intestinal microbiota. Results According to the experimental objectives, BL and BH groups were Beluga sturgeon ( Huso huso ) fed with low fishmeal diet and high fishmeal diet, respectively. SH group represented Siberian sturgeon ( Acipenser baeri Brandt) fed with the same diet as BH group. After 16 weeks feeding trial, the intestinal microbiota was examined by 16S rRNA high-throughput sequencing technology. On the phylum level, Proteobacteria and Bacteroidetes were significantly higher in BL group than BH group, and Cyanobacteria showed the opposite trend. Compared with BH group, Proteobacteria and Firmicutes were significantly increased in SH group, whereas Cyanobacteria were clearly decreased. At the genus level, Pseudomonas and Citrobacter in BL group were significantly higher comparing with BH group, while Bacillus , Luteibacter , Staphylococcus and Oceanobacillus was lower in BH group than SH group. Conclusions Alpha and beta diversities indicated that the intestinal microflora were significant difference between Siberian sturgeon and Beluga sturgeon when they fed with the same diet. Meanwhile, Beluga sturgeon fed with low fishmeal diet can increase the species diversity of intestinal microbiota than it fed high fishmeal diet. Therefore, feeding habits clearly affected the gastrointestinal microbiota of sturgeons. Moreover, the impact of changes in food on the gut microbiota of sturgeons should be taken into consideration during the process of sturgeon aquaculture.

Three-dimensional (3D) structure is an important morphological trait of plants for describing their growth and biotic/abiotic stress responses. Various methods have been developed for obtaining 3D plant data, but the data quality and equipment costs are the main factors limiting their development. Here, we propose a method to improve the quality of 3D plant data using the time-of-flight (TOF) camera Kinect V2. A K-dimension (k-d) tree was applied to spatial topological relationships for searching points. Background noise points were then removed with a minimum oriented bounding box (MOBB) with a pass-through filter, while outliers and flying pixel points were removed based on viewpoints and surface normals. After being smoothed with the bilateral filter, the 3D plant data were registered and meshed. We adjusted the mesh patches to eliminate layered points. The results showed that the patches were closer. The average distance between the patches was 1.88 × 10−3 m, and the average angle was 17.64°, which were 54.97% and 48.33% of those values before optimization. The proposed method performed better in reducing noise and the local layered-points phenomenon, and it could help to more accurately determine 3D structure parameters from point clouds and mesh models.