Upregulation of α enolase (ENO1) crotonylation in colorectal cancer and its promoting effect on cancer cell metastasis.

Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.

Machine-learning intervention progress in the field of organic waste composting: Simulation, prediction, optimization, and challenges.

Aerobic composting stands as a widely-adopted method for treating organic solid waste (OSW), simultaneously producing organic fertilizers and soil amendments. This biologically-driven biochemical reaction process, however, presents challenges due to its complex non-linear metabolism and the heterogeneous nature of the solid medium. These characteristics inherently limit the simulation accuracy and efficiency optimization in aerobic composting. Recently, significant efforts have been made to simulate and control composting process parameters, as well as predicting and optimizing composting product quality. Notably, the integration of machine learning (ML) in aerobic composting of organic waste has garnered considerable attention for its applicability and predictive capability in exploring the complex non-linear relationships of organic waste composting parameters. Despite numerous studies on ML applications in OSW composting, a systematic review of research findings in this field is lacking. This study offers a systematic overview of the application level, current status, and versatility of ML in OSW composting. It spans various aspects, such as compost maturity, environmental pollutants, nutrients, moisture, heat loss, and microbial metabolism. The survey reveals that ML-intervention predominantly focuses on compost maturity and environmental pollutants, followed by nutrients, moisture, heat loss, and microbial activity. The most commonly employed predictive models and optimization algorithms are artificial neural networks (47%) and genetic algorithms (10%). These demonstrate high prediction accuracy and maximize composting efficiency in the simulation and prediction of organic waste composting, alongside regulation of key parameters. Deep neural networks and ensemble learning models prove effective in achieving superior predictive performance by selecting feature variables in compost maturity and pollutant residue prediction of organic waste composting in a simpler and more objective manner.

Novel perspective on qualitative assessment of swine manure compost maturity using organic carbon density fractions.

Mature compost is safe and stable, yet quality assessments are challenging owing to current maturity indicators' limitations. This study employed density fractionation to separate organic carbon into light and heavy fractions, offering a new perspective for assessing maturity. Results showed that light fraction organic carbon progressively transitioned into heavy fraction during composting, reducing the proportion of total organic carbon from 82.82% to 44.03%, while heavy fraction organic carbon increased to 48.58%. During the first seven days, the reduction rate of light fraction organic carbon decreased slowly, while the increase rate of heavy fraction declined sharply, levelling off thereafter. Light/heavy fraction organic carbon ratio was significantly correlated with existing maturity indicators (carbon/nitrogen ratio, humic acid/fulvic acid ratio, biological growth-related indicators), with the ratio below 1.33 serving as a potential compost maturity marker. Thus, given its simplicity and reliability, organic carbon density fractions is an innovative indicator for compost maturity assessments.

Histone crotonylation of peripheral blood mononuclear cells is a potential biomarker for diagnosis of colorectal cancer.

BACKGROUND: Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC). RESULTS: Western blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins. The correlation of crotonylation with tumor staging and diagnostic efficacy were analyzed. Crotonylation of H2BK12 (H2BK12cr) was identified significantly upregulated in the PBMCs of CRC patients compared to healthy controls, and were closely related to distant metastasis (P = 0.0478) and late TNM stage (P = 0.0201). Receiver operator characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) of H2BK12cr was 0.8488, the sensitivity was 70%, and the specificity was 92.5%. The H2BK12cr parameter significantly increased the diagnostic effectiveness of CRC compared with the commercial carcinoembryonic antigen assays. CONCLUSIONS: The H2BK12cr level in PBMCs of CRC patients has a potential to be a biomarker for distinguishing CRC patients from healthy controls with the advantages of easy operation and high diagnostic efficacy.

A Numerical Simulation Method Considering Solid Phase Transformation and the Experimental Verification of Ti6Al4V Titanium Alloy Sheet Welding Processes.

A prediction model of the welding process of Ti-6Al-4V titanium alloy was established by using the finite element method, which was used to evaluate the phase composition, residual stress and deformation of the welded joints of Ti-6Al-4V sheets with different processes (including tungsten inert gas welding, TIG, and laser beam welding, LBW). The Ti-6Al-4V structures of TIG welding and LBW are widely used in marine engineering. In order to quantitatively study the effects of different welding processes (including TIG welding and LBW) on the microstructure evolution, macro residual stress and deformation of Ti6Al4V titanium alloy sheets during welding, a unified prediction model considering solid-state phase transformation was established based on the ABAQUS subroutine. In this paper, LBW and TIG welding experiments of 1.6 mm thick Ti-6Al-4V titanium alloy sheets were designed. The microstructure distribution of the welded joints observed in the experiment was consistent with the phase composition predicted by the model, and the hardness measurement experiment could also verify the phase composition and proportion. From the residual stress measured by experiment and the residual stress and deformation calculated by finite element simulation of LBW and TIG weldments, it is concluded that the effect of phase transformation on residual stress is mainly in the weld area, which has an effect on the distribution of tensile and compressive stress in the weld area. The overall deformation of the welded joint is mainly related to the welding process, and the phase transformation only affects the local volume change of the weld seam. Importantly, the phase composition and residual stress, which are scalar fields, calculated by the established model can be introduced into the numerical analysis of structural fracture failure as input influence factors.

Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/ß2-adrenoceptor/YKL-40 signaling pathway.

Objective: This study aimed to address the status, role, and mechanism of sympathetic nerve infiltration in the progression of stomach adenocarcinoma (STAD). Methods: Sympathetic nerve and its neurotransmitter NE, ß-ARs, and associated signaling molecules in the STAD tissues and the adjacent tissues from 46 STAD patients were examined using immunostaining, HPLC, and western blotting. The effects and mechanisms of ß2-AR activation on the proliferation, migration and invasion of AGS and SGC-7901 gastric cancer (GC) cell lines were examined using CCK-8, transwell, and western blotting assays. Correlations between genes and STAD survival were analyzed using bioinformatics. Results: Striking sympathetic nerve infiltration, elevations of NGF, TrkA, GAP43, TH, S100, NE, ß2-AR, YKL-40, syndecan-1, MMP9, CD206, and CD31 were observed in the STAD tissues compared to the adjacent tissues. Activation of ß2-AR in the two GC cell lines significantly amplified the expressions of NGF, YKL-40, MMP9, syndecan-1, p-STAT3 and p-ERK, and increased GC cell proliferation, migration and invasion. Bioinformatic analyses revealed positive correlations of NGF, ß2-AR, syndecan-1, and macrophage infiltration, respectively, with low survival of STAD, of ß2-AR respectively with STAT3, ERK1/2 (MAPK1/3), YKL-40, MMP9, and syndecan-1, and of YKL-40 with MMP9. Conclusion: Sympathetic nerves significantly infiltrated into human STAD tissues as a result of high NGF and TrkA expressions; elevated NE led to overactivation of ß2-AR-STAT3/ERK-YKL-40 signaling pathway, and finally caused cancer cell growth and invasion, M2 macrophage infiltration, angiogenesis, matrix degradation and STAD metastasis and progression.

Emerging roles of non-histone protein crotonylation in biomedicine.

Crotonylation of proteins is a newly found type of post-translational modifications (PTMs) which occurs leadingly on the lysine residue, namely, lysine crotonylation (Kcr). Kcr is conserved and is regulated by a series of enzymes and co-enzymes including lysine crotonyltransferase (writer), lysine decrotonylase (eraser), certain YEATS proteins (reader), and crotonyl-coenzyme A (donor). Histone Kcr has been substantially studied since 2011, but the Kcr of non-histone proteins is just an emerging field since its finding in 2017. Recent advances in the identification and quantification of non-histone protein Kcr by mass spectrometry have increased our understanding of Kcr. In this review, we summarized the main proteomic characteristics of non-histone protein Kcr and discussed its biological functions, including gene transcription, DNA damage response, enzymes regulation, metabolic pathways, cell cycle, and localization of heterochromatin in cells. We further proposed the performance of non-histone protein Kcr in diseases and the prospect of Kcr manipulators as potential therapeutic candidates in the diseases.

High Expression of Interleukin-2 Receptor Subunit Gamma Reveals Poor Prognosis in Human Gastric Cancer.

Precision medicine for gastric cancer (GC) is still an unsolved issue, because most available target drugs are not specifically designed for GC. Exploring novel signaling molecules with target value for GC is in urgent need. This study aimed to reveal that interleukin-2 receptor subunit gamma (IL2RG) is such a key molecule in human GC progression. GC tissues and paracancerous gastric tissues were collected from 7 patients (5 males and 2 females) during tumor radical excision surgery. These tissues were used to identify the differentially expressed genes (DEGs) with RNA-seq and serial bioinformatics analyses including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene expression profiling interactive analysis (GEPIA), and survival analysis. RT-qPCR and western blotting were performed to compare the mRNA and protein expression levels of IL2RG between GC tissues and adjacent normal gastric tissues as well as between GC cell line SGC-7901 and normal gastric epithelial cell line GES-1. Results showed striking elevations of IL2RG both in the mRNA and protein levels in GC tissues and human gastric cancer SGC-7901 cell line compared, respectively, with the adjacent normal gastric tissues and normal GES-1 cells, and higher IL2RG expression was associated with lower survival. Analyses on the GSE29272 and GSE15459 datasets from Gene Expression Omnibus verified that IL2RG was highly expressed in GC patients and was associated with poor overall survival. In addition, molecular docking showed that a small molecule, resatorvid (TAK 242), might be an inhibitor of IL2RG. We conclude that IL2RG is overexpressed in advanced GC and is associated with low survival. IL2RG may serve as a biomarker of GC progression and poor prognosis.

[A study of paternity testing with considering mutation].

OBJECTIVE: To formulate recommendations in the evaluation of results of genetic analyses in paternity testing under considering mutations. METHODS: A total of 15 short tandem repeat(STR) loci were employed for this study, which were included CSF1PO, FGA, TH01, TPOX, VWA, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, PentaD and PentaE. Both 100 cases of true trio and 100 cases of false trio were investigated. RESULTS: The numbers of mismatch alleles in different STR loci were observed in 100 cases of false trio. The different distributions of paternity index were obtained, including the changes of paternity index in each case of true trio under simulated mutations. CONCLUSION: In order to avoid the effect of mutations, the exclusion of paternity was never considered on the basis of a single locus. The threshold values of the combined probability of exclusion and the paternity index were important for both exclusion and inclusion of paternity. The scientific evidence for paternity testing can be obtained when both the combined probability of exclusion and the paternity index meet the threshold values. However, when either the combined probability of exclusion or the paternity index can not meet the threshold values, more genetic markers should be added.