ADAMTSL2 is a potential prognostic biomarker and immunotherapeutic target for colorectal cancer: Bioinformatic analysis and experimental verification.

The ADAMTS Like 2 (ADAMTSL2) mutation has been identified to be associated with different human genetic diseases. The role of ADAMTSL2 is unclear in colorectal cancer (CRC). The study investigated the expression of ADAMTSL2 in both pan cancer and CRC, using data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The study examined the correlation between ADAMTSL2 expression levels and clinical characteristics, as well as prognosis in CRC. The study explored potential regulatory networks involving ADAMTSL2, including its association with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB) / microsatellite instability (MSI), tumor stemness index (mRNAsi), and drug sensitivity in CRC. ADAMTSL2 expression was validated using GSE71187 and quantitative real-time PCR (qRT-PCR). ADAMTSL2 was aberrantly expressed in pan cancer and CRC. An increased level of ADAMTSL2 expression in patients with CRC was significantly associated with the pathologic N stage (p < 0.001), pathologic stage (p < 0.001), age (p < 0.001), histological type (p < 0.001), and neoplasm type (p = 0.001). The high expression of ADAMTSL2 in patients with CRC was found to be significantly associated with a poorer overall survival (OS) (HR: 1.67; 95% CI: 1.18-2.38; p = 0.004), progression-free survival (PFS) (HR: 1.55; 95% CI: 1.14-2.11; p = 0.005) and disease-specific survival (DSS) (HR: 1.83; 95% CI: 1.16-2.89; p = 0.010). The expression of ADAMTSL2 in patients with CRC (p = 0.009) was identified as an independent prognostic determinant. ADAMTSL2 was associated with extracellular matrix receptor (ECM-receptor) interaction, transforming growth factor ß (TGF-ß) signaling pathway, and more. ADAMTSL2 expression was correlated with immune infiltration, immune checkpoint genes, TMB / MSI and mRNAsi in CRC. ADAMTSL2 expression was significantly and negatively correlated with 1-BET-762, Trametinib, and WZ3105 in CRC. ADAMTSL2 was significantly upregulated in CRC cell lines. The high expression of ADAMTSL2 is significantly correlated with lower OS and immune infiltration of CRC. ADAMTSL2 may be a potential prognostic biomarker and immunotherapeutic target for CRC patients.

Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study.

Background: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. Conclusion: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.

Preoperative C-reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer.

BACKGROUND: Increasing attention has been drawn the prognostic value of inflammatory indices for colorectal cancer (CRC). However, the prognostic value of the preoperative C-reactive protein to prealbumin ratio (CPAR) in CRC remains unclear. METHODS: A retrospective study was conducted with 794 patients who had CRC and underwent radical surgical resection. The predictive performance of the inflammatory indices was analyzed and compared using the area under the time-dependent receiver operating characteristic curve. A competing risk regression model and Cox proportional hazard model were used to analyze the effects of CPAR on disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: Patients with high CPAR (>7.25) had poor survival outcome. The CPAR had the best predictive performance among all inflammatory indices, and was significantly associated with several characteristics of tumor invasion, including histological grade, tumor stage, and tumor size. Multivariate analysis showed that high CPAR was independently associated with poor DFS (subdistribution hazard ratio = 2.28, 95% confidence interval [CI]: 1.74-2.82) and OS (hazard ratio = 1.78, 95% CI: 1.60-1.96). CONCLUSION: Preoperative CPAR assessment could serve as an effective and reliable tool for prognostic prediction in patients with resectable CRC.

Humic Acid Removal from Water with PAC-Al30: Effect of Calcium and Kaolin and the Action Mechanisms.

Polyaluminum chloride with a dominant species of Al30 (PAC-Al30) was prepared in laboratory and used for humic acid (HA) removal from water. The action properties and mechanisms of PAC-Al30, HA, calcium, and kaolin were tested and discussed. The results showed that the existence of calcium or kaolin contributed to the HA removal when the PAC-Al30 dosage was deficient and had no obvious effect when the amount of PAC-Al30 was sufficient. When the PAC-Al30 dosage was 0.01 and 0.02 mmol/L, the HA removal rate was increased by 66.59 and 42.20%, respectively, with a calcium concentration of 2.0 mmol/L, or increased by 53.31 and 40.92%, respectively, with the kaolin particle concentration of 150 mg/L. Calcium could compress the double electrical layers or complex with HA to neutralize a part of the surface negative charge of HA, but could not make the water system reach its isoelectric point. The mechanisms of calcium and kaolin's promoting coagulation effect were adsorption neutralization and collision aggregation respectively, but these actions were much weaker than that of PAC-Al30 with HA. The adsorption neutralization capacity of PAC-Al30 was calculated to be nearly 60 times than that of calcium, and the higher γ value of calcium modified by the Sips equation may indicate that the adsorption or neutralization sites of calcium on HA were pickier than PAC-Al30.

High-poly-aluminum chloride sulfate coagulants and their coagulation performances for removal of humic acid.

High-poly-aluminum chloride sulfate (HPACS) coagulants with different [SO4 2-]/[Al3+] molar ratio (S) were prepared and proved to have high coagulation efficiency for the removal of humic acid and strong stability for storage and application. The results showed that the higher the SO4 2- addition, the bigger the aluminum polymerization particles and the more the polymerization Alc existed in the prepared HPACS coagulants. The HPACS exhibited higher coagulation efficiency, a better aging stability and stronger resistance to the change of pH and Ca2+ concentration of raw water than the polyaluminum chloride (PAC) and poly-aluminum chloride sulfate (PACS) reported before. The Sips adsorption neutralization model was established to illustrate the relationship between coagulant dosage and zeta potential of the water system. The adsorption neutralization capacity was proved to be HPACS (S = 0) > HPACS (S = 0.02) > HPACS (S = 0.06) > HPACS (S = 0.10), which was not completely consistent with the coagulation effect of HPACS with different S values and indicated that in addition to adsorption neutralization, actions like bridge-aggregation, precipitation, and sweep-flocculation also played an important role during HPACS coagulation. Moreover, the negative Gibbs free energy indicated that the coagulant adsorption neutralization reaction was a spontaneous process.

Theoretical Studies of the Hydrogen Abstraction from Poly(oxymethylene) Dimethyl Ethers by O2 in Relation with Cetane Number Data.

Poly(oxymethylene) dimethyl ethers (PODME n , n = 2-6) are novel oxygenated compounds that can be used as promising candidates for new-generation fuels because of their excellent combustion performance. The oxidation of PODME n (n = 2-6) is essential for the understanding of the combustion process. It is necessary to study the relationship between kinetic parameters and cetane number (CN) of PODME n (n = 2-6). In order to predict initiation step rate constants for the oxidation of PODME n (n = 2-6), quantum mechanical calculations are performed using M06-2X/6-311G(d,p) and B3LYP/6-311G(d,p) methods. Structural, energetic, thermodynamics, and kinetics of the automatic ignition process are assessed. The kinetic model based on the conventional transition state theory is used to calculate the initiation step reaction rate constants at 1000 K. In both M06-2X/6-311G(d,p) and B3LYP/6-311G(d,p) methods, the calculated rate constants of the hydrogen abstraction process have an excellent correlation with the experimental CN of PODME n (n = 2-6). Our methodology presented here can be used to simulate chemical kinetics for other fuel additives.

Long non-coding RNA, CHRF, predicts poor prognosis of lung adenocarcinoma and promotes cell proliferation and migration.

Research has demonstrated that long non-coding RNAs (lncRNAs) are crucial factors in carcinogenesis. LncRNA, cardiac hypertrophy-related factor (CHRF), has been demonstrated to act as an oncogene in a variety of types of tumor. However, its biological function in lung adenocarcinoma remains to be elucidated. The present study aimed to examine the level of CHRF expression in lung adenocarcinoma tissues and cell lines, and to analyze the association between CHRF and clinicopathological characteristics, as well prognosis of patients with lung adenocarcinoma. Loss-of-function assays were performed to determine the biological function of CHRF. The expression of CHRF was markedly upregulated in lung adenocarcinoma tissues and cell lines. Patients exhibiting upregulated CHRF also demonstrated advanced Tumor-Node-Metastasis stage, lymph node metastasis and larger tumor size compared with those exhibiting downregulated CHRF. Results of Cox proportional hazards regression analysis suggested that highly-expressed CHRF may be regarded as an independent prognostic factor of prognosis. In addition, loss-of-function assays indicated that downregulation of CHRF suppressed cell proliferation, migration and invasion, and induced cell cycle arrest and apoptosis. Western blotting revealed that the phosphoinositide-3-kinase/Akt signaling pathway activity is reduced in lung adenocarcinoma following the knockdown of CHRF. Together, these results indicate that lncRNA, CHRF, may serve a critical role in the development and progression of lung adenocarcinoma, and may act as a novel prognostic biomarker and therapeutic target in lung adenocarcinoma.

Suppression of RRM2 inhibits cell proliferation, causes cell cycle arrest and promotes the apoptosis of human neuroblastoma cells and in human neuroblastoma RRM2 is suppressed following chemotherapy.

Ribonucleotide reductase regulatory subunit M2 (RRM2) is a rate­limiting enzyme for DNA synthesis and repair. RRM2 has vital roles in controlling the progression of cancer. In the present study, we investigated the RRM2 level in neuroblastoma tissues, analyzed its relationship with clinicopathological characteristics of neuroblastoma patients, and explored the effect of RRM2 on the biological functions of neuroblastoma cells. RRM2 levels in 67 pairs of neuroblastoma and matched adjacent non­cancerous tissues were detected by qRT­PCR, and its association with patient clinicopathological features was assessed. Using RRM2 siRNA, the role of RRM2 in cell viability was detected by CCK­8 assay, and the effects on cell cycle distribution and cell apoptosis were detected by flow cytometry. Hoechst 33342 staining was also performed. For RRM2 protein detection in cells and tissues, western blot analyses were employed. Our results revealed that RRM2 expression was significant higher in neuroblastoma tissues than that noted in adjacent non­cancerous tissues at both the mRNA and protein levels. The increased RRM2 level was significantly associated with clinical stage. RRM2 levels were suppressed in stage III and IV tumors in the chemotherapy subgroup, compared with levels noted in tumors in the preoperative non­chemotherapy subgroup. RRM2 siRNA significantly inhibited cell viability in the SH­5Y5Y cells, induced cell arrest in the G0/G1 phase, and enhanced cell apoptosis. Taken together, overexpression of RRM2 is associated with the genesis and progression of neuroblastoma, and may be a potential chemotherapeutic target.

Adsorption Neutralization Model and Floc Growth Kinetics Properties of Aluminum Coagulants Based on Sips and Boltzmann Equations.

Single-molecule aluminum salt AlCl3, medium polymerized polyaluminum chloride (PAC), and high polymerized polyaluminum chloride (HPAC) were prepared in a laboratory. The characteristics and coagulation properties of these prepared aluminum salts were investigated. The Langmuir, Freundlich, and Sips adsorption isotherms were first used to describe the adsorption neutralization process in coagulation, and the Boltzmann equation was used to fit the reaction kinetics of floc growth in flocculation. It was novel to find that the experimental data fitted well with the Sips and Boltzmann equation, and the significance of parameters in the equations was discussed simultaneously. Through the Sips equation, the adsorption neutralization reaction was proved to be spontaneous and the adsorption neutralization capacity was HPAC > PAC > AlCl3. Sips equation also indicated that the zeta potential of water samples would reach a limit with the increase of coagulant dosage, and the equilibrium zeta potential values were 30.25, 30.23, and 27.25 mV for AlCl3, PAC, and HPAC, respectively. The lower equilibrium zeta potential value of HPAC might be the reason why the water sample was not easy to achieve restabilization at a high coagulant dosage. Through the Boltzmann equation modeling, the maximum average floc size formed by AlCl3, PAC, and HPAC were 196.0, 188.0, and 203.6 µm, respectively, and the halfway time of reactions were 31.23, 17.08, and 9.55 min, respectively. The HPAC showed the strongest floc formation ability and the fastest floc growth rate in the flocculation process, which might be caused by the stronger adsorption and bridging functions of Alb and Alc contained in HPAC.

Theoretical study on the reactions of the cyclic trinitrogen radical toward oxygen and water.

Recently, the detection of the neutral simplest all-nitrogen ring, cyclic-N(3) radical, has been realized via various techniques, which has led to numerous studies on its structures, energetics, and spectroscopy. In particular, it has been postulated as a possible building block of high energy density materials. Yet, its intermolecular reactivity is poorly understood. In this paper, we for the first time studied the reactions of cyclic-N(3) with the widespread oxygen and water at the CCSD(T)/aug-cc-pVTZ //B3LYP/6-311++G(d,p)+ZPVE and G3B3//B3LYP/6-311++G(d,p) (italics) levels. An addition-elimination mechanism was revealed for the cyclic-N(3) + O(2) reaction that results in the elementary product N(2) + NO + (3)O with an overall barrier as high as 11.8 (11.0) kcal/mol. The calculated low rate constants (even at high temperatures) show that the cyclic-N(3) radical is stable against oxygen. The cyclic-N(3) + H(2)O reaction is associated with a quasi H-abstraction mechanism forming the product cyclic-N(3)H + OH with the rather high barrier of 35.7 (36.2) kcal/mol. This indicates that cyclic-N(3) is chemically inert toward H(2)O. Chemical implications of the present work are discussed.

Gaseous reaction mechanism between two H(2)CN radicals.

The self-recombination of the methylene amidogen radical (H(2)CN) is known to be fast and should play an important role in determining the concentration of H(2)CN radicals in both combustion and astrophysical processes. The rate constants of H(2)CN + H(2)CN have been determined by previous experiments, whereas its detailed evolution process and product distribution are still unclear. In this work, by means of quantum chemical and master equation calculations, we for the first time explored theoretically the potential energy surface and kinetics of the H(2)CN + H(2)CN reaction. At the CCSD(T)/6-311++G(2df,p), CCSD(T)/aug-cc-pVTZ and Gaussian-3 single-point levels based on the B3LYP/6-31++G(d,p) structures, the dominant channel was found to be () H(2)CN + H(2)CN --> H(2)CNNCH(2) () --> r-CH(2)NNCH(2) () --> N(2) + C(2)H(4) () with a zero overall barrier. The calculated rate constants are in agreement with available experiments. Of particular interest, since the formed product involves molecular nitrogen, the H(2)CN + H(2)CN reaction might have important contribution to the nitrogen-recycling in a number of conflagrant and astrophysical processes.

Theoretical study on reaction mechanism of fulminic acid HCNO with CN radical.

The HCNO + CN reaction is one potentially important process during the NO-reburning process for the reduction of NOx pollutants from fossil fuel combustion emissions. To compare with the recent experimental study, we performed the first theoretical potential energy surface investigation on the mechanism of HCNO + CN at the G3B3 and CCSD(T)/aug-cc-pVTZ levels based on the B3LYP/6-311++G(d,p) structures, covering various entrance, isomerization, and decomposition channels. The results indicate that the most favorable channel is to barrierlessly form the entrance isomer L1c NCCHNO followed by successive ring closure and concerted CC and NO bond rupture to generate the product P1 HCN + NCO. However, the formation of P4 (3)HCCN + NO, predicted as the only major product in the recent experiment, is kinetically much less competitive. This conclusion is further supported by the master equation rate constant calculation. Future experimental reinvestigations are strongly desired to test the newly predicted mechanism for the CN + HCNO reaction. Implications of the present results are discussed.