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Background: Colon adenocarcinoma (COAD), a type of colon cancer, is among the most common malignant diseases afflicting people globally. Heat shock protein family, including HSPA8, are involved in tumor progression in numerous human cancers, however the association between HSPA8 and COAD has not been explored.Methods: RNA sequencing data and clinical characteristics from TCGA and GTEx, as well as protein data from CPTAC were obtained for analysis of HSPA8 expression in COAD. Furthermore, functional enrichment analysis of HSPA8-related differentially expressed genes (DEGs) was performed via GO/KEGG, immune infiltration analysis, and protein-protein interaction (PPI) network. In addition, the clinical significance of HSPA8 was analyzed by Kaplan-Meier Cox regression and prognosis assessment. R package was employed to analyze incorporated studies.Results: Compared with normal samples, the expression of HSPA8 increased remarkably in various tumors, including COAD, Moreover, high HSPA8 expression was associated with good prognosis in COAD, as well as subgroups with male, T2-T4 stage, no lymphatic and perineural invasion. (P < 0.05). High HSPA8 was a prognostic factor in Cox regression analysis. The diagnostic efficacy of HSPA8 in COAD analyzed by ROC (AUC: 0.889). Furthermore, a total of 3321 DEGs were identified between the high- and the low-expression group, of which 9 genes were up-regulated and 3312 genes were down-regulated.Conclusions: High HSPA8 expression is a potential biomarker for favorable outcomes in COAD. the results might provide clues and guidance for developing novel diagnosis, targeted therapy and prognosis of HSPA8 in COAD.

Herein, we report the mechanism of Ir(III)-catalyzed intermolecular branch-selective allylic C−H amidation, including the influence of substituent effect on yield and regioselectivity. The sequence of amidation reaction is alkene coordination, allylic C−H activation, oxidative addition of methyl dioxazolone, reductive elimination of allyl-Ir-nitrenoid complex, amine protonation and proto-demetallation. The apparent activation energy of amidation between hexene and methyl dioxazolone is 17.8 kcal/mol, and the energy difference between two transition state for formation amide is only 2.8 kcal/mol. The introduction of more electron-deficient groups at the allyl terminal increases the apparent activation energy, conversely, the introduction of electron-donating groups significantly reduces the apparent activation energy. Among them, the apparent activation energy of the reaction between aniline group substituted allyl and methyl dioxazolone is only 13.8 kcal/mol, which further improves the reaction yield. In addition, the introduction of more electron-withdrawing groups on dioxazolone can significantly improve the regioselectivity. When 3,4,5,-trifluorophenyl substituted dioxazolone and hexene occur C−N bond coupling reaction, the energy difference of the two transition states is as high as 9.0 kcal/mol, indicating that the regioselectivity is greatly improved. The mechanism explanation of allylic C−H amidation will provide strong theoretical support for streamlined synthesis of allyl branched amides.

Polymyxin is a critical antibiotic against the infection caused by multidrug-resistant gram-negative bacteria. Neurotoxicity is one of main dose-limiting factors. The present study aimed to investigate the underlying molecular mechanism on colistin induced peripheral neurotoxicity using a mouse model. Forty mice were divided into control, colistin 1-, 3- and 7-day groups, the mice were intravenously injected with saline or colistin (sulfate) at the dose of 15 mg/kg/day for 1, 3 and 7 days, respectively. The results showed that, colistin treatment for 7 days markedly resulted in the demyelination, axonal degeneration and mitochondria swelling in the mice’s sciatic tissues. Colistin treatment induces oxidative stress as well as the increases of mitochondrial permeability transition, decreases of membrane potential (ΔΨm) and activities of mitochondrial respiratory chain in the mice’s sciatic nerve tissues. Furthermore, in the colistin-7 day group, adenosine-triphosphate (ATP) level Na+/K+-ATPase activity decreased to 75.2% (p

To compare the clinical effect between electroacupuncture (EA) at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery.Sixty patients with elective radical esophagectomy were randomly divided into a group A, a group B and a control group, 20 cases in each group. The patients in the group A were treated with injection of 20 mL 0.375% ropivacaine at epidural space 30 min before anesthesia induction, followed by normal anesthesia during operation; the patients in the group B were treated with 30 min EA at bilateral Neima point and Neiguan (PC 6) before anesthesia induction, followed by normal anesthesia during operation; the patients in the control group were treated with general anesthesia alone. Patient-controlled intravenous analgesia was applied for all the patients. The mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before acupuncture/epidural puncture (TThe MAP at TThe preemptive analgesia of EA at Neima point and Neiguan (PC 6) and epidural nerve block could both provide effective perioperative analgesia for thoracic surgery. The EA could better maintain intraoperative hemodynamics and has less physiological disturbance.