Efficacy of mFOLFOX6 plus bevacizumab regimen in advanced colorectal cancer after deep hyperthermia: a single-center retrospective study

BackgroundThis study aimed to explore the clinical efficacy and safety of a modified FOLFOX6 (oxaliplatin + leucovorin + 5-fluorouracil) plus bevacizumab regimen after deep hyperthermia in advanced colorectal cancer.MethodsA total of 80 colorectal cancer patients treated at our hospital were selected as research subjects. According to the random number table method, patients were divided into a control group (mFOLFOX6 plus bevacizumab) and a combination group (mFOLFOX6 plus bevacizumab after deep hyperthermia treatment), with 40 patients in each group. After six cycles of treatment, the objective response rate (ORR), disease control rate (DCR), levels of serum tumor markers carcinoembryonic antigen (CEA), vascular epidermal growth factor (VEGF), Karnofsky performance status (KPS) scores, and the occurrence of adverse events were compared between the two groups.ResultsAfter six cycles of treatment, the ORR in the combination group was higher than that in the control group, but the difference was not statistically significant (P>0.05). The DCR in the combination group was significantly higher than that in the control group (P<0.05). The serum CEA levels in the control and combination groups after treatment were significantly lower than those before treatment, and the serum CEA and VEGF levels in the combination group were significantly lower than those in the control group (all P<0.001). The KPS scores in both groups after treatment were higher than those before treatment, and the KPS scores in the combination group after treatment were significantly higher than those in the control group (all P<0.001). The incidence of fatigue and pain in the combination group was significantly lower than that in the control group (P<0.05).ConclusionmFOLFOX6 plus bevacizumab after deep hyperthermia is effective in advanced colorectal cancer patients, which can effectively improve their quality of life, and the adverse events are controllable and tolerable. A randomized or prospective trial will be required to further prove these data and explore its potentiality, especially if compared to conventional treatment

Probing Allostery through DNA

Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which—together with molecular dynamics simulations—suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.Chemistry and Chemical Biolog

Construction of a cross-species cell landscape at single-cell level.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging

Optimization Model of Pure Electric Vehicle Battery-Swapping Dispatch Based on Transportation Problems

The optimization object of pure electric vehicle battery-swapping service dispatch is making the total cost to be minimum under the condition of meeting the battery-swapping demand. The battery-swapping service requires each charging station to scientifically transport the supplementary batteries of the electricity exchange station. It is a multi-objective optimization decision-making process. With the object of minimizing the total cost of one-time transportation, applying the transportation problems theory, an optimization model of the battery-swapping service between the charging station and the exchange station was established, and a typical example was analyzed. The results show that the battery-swapping service transportation line is one of the main factors affecting the cost of pure electric vehicle battery-swapping service dispatch

Prognostic significance of the epithelial-to-mesenchymal transition markers e-cadherin, vimentin and twist in bladder cancer

ObjectiveThe goal of this study was to utilize long-term patient follow-up to determine whether epithelial-to-mesenchymal transition (EMT)-related markers can predict bladder cancer patient survival and progression of disease.Materials and MethodsThis study included 121 patients with bladder cancer. Sixty-four of these patients presented with non-muscle invasive (NMI, stage T1) bladder cancer and 57 with muscle invasive (MI, stage T2, T3). The patients were diagnosed and treated between May 1998 and July 2012. The EMT markers E-cadherin, Twist, and Vimentin were detected via immunohistochemistry. Univariate and multivariate/Cox analyses were then utilized to determine whether these EMT markers could be useful prognostic markers for predicting bladder cancer patient outcomes.ResultsAnalysis of the 121 bladder cancer patients in this study revealed that the frequency of E-cadherin expression was 59.5% (72/121), Twist was 54.5% (66/121), and Vimentin was 24.8% (30/121). Twist and Vimentin were found to have statistically significant correlations with grade, recurrence, and progression but not with stage, whereas E-cadherin was associated with stage but not with the other parameters. In the univariate analysis, grade (p = 0.02) was the only significant predictor for progression-free survival (PFS). Stage, grade, and expression of E-cadherin, Vimentin and Twist were included in the multivariate analysis of predicting PFS. In this analysis, grade (p = 0.01) and Vimentin expression (p = 0.001) were found to be significant prognostic factors in predicting PFS.ConclusionsGrade and Vimentin are potential independent indicators in predicting bladder cancer progression and survival

Cancer-Associated Fibroblasts Regulate Bladder Cancer Invasion and Metabolic Phenotypes through Autophagy

Recently, both cancer-associated fibroblasts (CAFs) and autophagy have been proven to play an important role in tumor development, including bladder cancer (BCa). However, the real mechanisms remain largely unclear. Here, we reconstruct a mimic tumor microenvironment to explore the interaction between CAFs and the BCa cell line T24 using a coculture system. Autophagy in CAFs was induced or inhibited by rapamycin or siRNA, respectively. After coculture with CAFs, T24 cell proliferation, invasion, and aerobic glycolysis were tested in vitro. Rapamycin induced and siAtg5 inhibited autophagy in CAFs. Enhanced autophagy in CAFs promoted cell proliferation and invasion in T24 cells in vitro, while there was no significant difference between the autophagy-inhibited group and the controls. Lactate concentration was elevated in both rapamycin-treated and siAtg5-treated groups compared with the control group. In addition, the expression levels of MCT1, MCT4, HK2, SLC2A1, and MMP-9 were all increased in T24 cells in the autophagy-enhanced group. Our results indicated that CAFs could regulate BCa invasion and metabolic phenotypes through autophagy, providing us with new alternative treatments for BCa in the future

Sex Differences in the Association between Night Shift Work and the Risk of Cancers: A Meta-Analysis of 57 Articles

Objectives. To identify the association between night shift work and the risk of various cancers with a comprehensive perspective and to explore sex differences in this association. Methods. We searched PubMed, Embase, and Web of Science for studies on the effect of night shift work on cancer, including case-control, cohort, and nested case-control studies. We computed risk estimates with 95% confidence intervals (CIs) in a random or fixed effects model and quantified heterogeneity using the I2 statistic. Subgroup, metaregression, and sensitivity analyses were performed to explore potential sources of heterogeneity. Contour-enhanced funnel plots and the trim and fill method were used together to analyze bias. Linear dose–response analysis was used to quantitatively estimate the accumulative effect of night shift work on the risk of cancer. Results. Fifty-eight studies were eligible for our meta-analysis, including 5,143,838 participants. In the random effects model, the pooled odds ratio (OR) of cancers was 1.15 (95% CI = 1.08–1.22, P<0.001; I2=76.2%). Night shift work increased the cancer risk in both men (OR = 1.14, 95% CI = 1.05–1.25, P=0.003) and women (OR = 1.12, 95% CI = 1.04–1.20, P=0.002). Subgroup analyses showed that night shift work positively increased the risk of breast (OR = 1.22, 95% CI = 1.08–1.38), prostate (OR = 1.26, 95% CI = 1.05–1.52), and digestive system (OR = 1.15, 95% CI = 1.01–1.32) cancers. For every 5 years of night shift work, the cancer risk increased by 3.2% (OR = 1.032, 95% CI = 1.013–1.051). Conclusion. This is the first meta-analysis identifying the positive association between night shift work and the risk of cancer and verifying that there is no sex difference in the effect of night shift work on cancer risk. Cancer risk increases with cumulative years of night shift work

A Matrix Metalloproteinase-1 Polymorphism, MMP1–1607 (1G>2G), Is Associated with Increased Cancer Risk: A Meta-Analysis Including 21,327 Patients

Although the matrix metalloproteinase-1 (MMP1) polymorphism MMP1–1607 (1G>2G) has been associated with susceptibility to various cancers, these findings are controversial. Therefore, we conducted this meta-analysis to explore the association between MMP1–1607 (1G>2G) and cancer risk. A systematic search of literature through PubMed, Embase, ISI Web of Knowledge, and Google Scholar yielded 77 articles with 21,327 cancer patients and 23,245 controls. The association between the MMP1–1607 (1G>2G) polymorphism and cancer risks was detected in an allele model (2G vs. 1G, overall risk [OR]: 1.174, 95% confidence interval [CI]: 1.107–1.244), a dominant model (2G2G/1G2G vs. 1G1G OR, OR: 1.192, 95% CI: 1.090–1.303), and a recessive model (2G2G vs. 1G2G/1G1G, OR: 1.231, 95% CI: 1.141–1.329). In subgroup analysis, these associations were detected in both Asians and Caucasians. After stratification by cancer types, associations were found in lung, colorectal, nervous system, renal, bladder, and nasopharyngeal cancers. This meta-analysis revealed that MMP1–1607 (1G>2G) polymorphism was significantly associated with elevated risk of cancers

Hardness and elastic modulus profiles of hybrid coatings

Instrumented-indentation testing (IIT) provided with a continuous stiffness measurement (CSM) technique was employed to measure hardness and elastic modulus profiles of thin organic/inorganic hybrid coatings on glass surfaces. Hybrids were synthesized by the hydrolytic condensation of (3-methacryloxypropyl) trimethoxysilane (MPMS) or vinyltrimethoxysilane (VMS), with 5–30 wt% tetraethoxysilane (TEOS), in the presence of formic acid. Coatings of 600–800 nm on glass substrates were obtained by dip-coating solutions of these hybrids with benzoyl peroxide (BPO) addition, and curing in an oven following a thermal cycle up to 120∘C. Both hardness and elastic modulus showed a maximum value close to the surface, followed by a plateau and a significant increase at higher penetrations. Hybrids based on MPMS and 20–30 wt% TEOS exhibited a good combination of intrinsic values of hardness (0.50 GPa) and brittle index (0.06–0.07), that makes them suitable for coatings of plastic substrates.Fil: Hu, Lijiang. Harbin Institute Of Technology; ChinaFil: Zhang, Xingwen. Harbin Institute Of Technology; ChinaFil: Sun, Yi. Harbin Institute Of Technology; ChinaFil: Williams, Roberto Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin