DFT investigation of the dissolution trends of NiTi alloys with the B2 and B19' phases during the initial oxidation stage.

The selective corrosion of NiTi alloys was studied using density functional theory calculations, and the dissolution trends of the NiTi-B2 and NiTi-B19' phases in the initial oxidation stage were compared to predict their corrosion difference. The dissolution process of Ni and Ti was simulated by creating Ni or Ti vacancies on the unoxidized and oxidized NiTi alloy surfaces. The results show that the surface vacancy formation energy of Ti vacancies is higher than that of Ni vacancies, indicating that Ti is more difficult to dissolve than Ni. Furthermore, oxidation promotes and impedes the dissolution of Ni and Ti, respectively. This study improves the fundamental understanding of the corrosion mechanism of NiTi alloys.

Underwater image restoration based on adaptive parameter optimization of the physical model.

Underwater images have the advantage of carrying high information density and are widely used for marine information acquisition. Due to the complex underwater environment, the captured images are often unsatisfactory and often suffer from color distortion, low contrast, and blurred details. Physical model-based methods are often used in relevant studies to obtain clear underwater images; however, water selectively absorbs light, making the use of a priori knowledge-based methods no longer applicable and thus rendering the restoration of underwater images ineffective. Therefore, this paper proposes an underwater image restoration method based on adaptive parameter optimization of the physical model. Firstly, an adaptive color constancy algorithm is designed to estimate the background light value of underwater image, which effectively guarantees the color and brightness of underwater image. Secondly, aiming at the problem of halo and edge blur in underwater images, a smoothness and uniformity transmittance estimation algorithm is proposed to make the estimated transmittance smooth and uniform, and eliminate the halo and blur of the image. Then, in order to further smooth the edge and texture details of the underwater image, a transmittance optimization algorithm for smoothing edge and texture details is proposed to make the obtained scene transmittance more natural. Finally, combined with the underwater image imaging model and histogram equalization algorithm, the image blurring is eliminated and more image details are retained. The qualitative and quantitative evaluation on the underwater image dataset (UIEBD) shows that the proposed method has obvious advantages in color restoration, contrast and comprehensive effect, and has achieved remarkable results in application testing. It shows that the proposed method can effectively restore underwater degraded images and provide a theoretical basis for the construction of underwater imaging models.

Survival influence of gender on 42,345 patients with gastric cardia adenocarcinoma.

PURPOSE: Some studies indicated that gender is associated with prognostic of cancer, However, currently the prognostic value of gender for gastric cardia adenocarcinoma (GCA) survival is unclear. The aim of our study is to reveal the influence of gender on the prognosis of patients with GCA. PATIENTS AND METHODS: A total of 42,345 cases Chinese GCA patients were enrolled from our previously established GCA and esophageal cancer databases. The clinicopathological characteristics were retrieved from medical records in hospital. The follow-up was performed through letter, telephone or home interview. Among GCA patients, there were 32,544 (76.9%) male patients with the median age 62 years (range 17-97) and 9,801 (23.1%) female patients with the median age 61 years (range 17-95 years). The Chi-square test and Kaplan-Meier method were used to compare the continuous variables and survival. Cox proportional hazards model was used for competing risk analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated. RESULTS: Men had shorter GCA-specific survival than women by multivariate analysis (HR 1.114; 95% CI 1.061 to 1.169; P < 0.001). Whether premenopausal, perimenopausal or postmenopausal, the survival of women was better than that of men (premenopausal vs. male, P < 0.001; perimenopausal vs. male, P < 0.001; postmenopausal vs. male, P = 0.035). It was worth noting that in patients with stages I, II, III, and IV, female patients survive longer than male patients (P = 0.049; P = 0.011; P < 0.001; P = 0.044, respectively). CONCLUSION: Gender is an independent prognostic factor for patients with GCA. In comparison with men, women have a significantly better outcome. Smoking and drinking may be protective factors for male GCA patients.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Mechanical properties and electronic structure of Cu-doped tin: a first-principle study.

Metal doping is an effective method for improving the toughness of ceramic materials and reducing coating fractures. In this study, first-principle calculations based on density functional theory were performed to study the formation energy, elastic constant, and electronic structure of Cu-doped TiN. The results reveal that Cu tends to replace the Ti sites in TiN crystal cells; with an increase in Cu concentration, the formation energy of the Cu-doped TiN system decreases. This indicates that the structural stability of Cu-doped TiN decreases. From the calculated elastic constant and the Voigt-Reuss-Hill approximation, it is evident that the bulk modulus B and shear modulus G decrease as the Cu concentration increases. However, G decreases more rapidly, thus increasing the B/G ratio. According to Paugh's ratio, the increase in B/G indicates an increase in the ductility of TiN. The results of the band structure, density of states, charge density, and Mulliken bond population analysis reveal that Cu doping reduces the covalent bond strength of TiN, enhances metallicity, and reduces the structural stability of the system, enhancing the toughness of TiN. The results of this study will provide theoretical and experimental guidance for improving the toughness of TiN coatings.

Increased prognostic value of clinical-reproductive model in Chinese female patients with esophageal squamous cell carcinoma.

BACKGROUND: In China, it has been well recognized that some female patients with esophageal squamous cell carcinoma (ESCC) have different overall survival (OS) time, even with the same tumor-node-metastasis (TNM) stage, challenging the prognostic value of the TNM system alone. An effective predictive model is needed to accurately evaluate the prognosis of female ESCC patients. AIM: To construct a novel prognostic model with clinical and reproductive data for Chinese female patients with ESCC, and to assess the incremental prognostic value of the full model compared with the clinical model and TNM stage. METHODS: A new prognostic nomogram incorporating clinical and reproductive features was constructed based on univariatie and Cox proportional hazards survival analysis from a training cohort (n = 175). The results were recognized using the internal (n = 111) and independent external (n = 85) validation cohorts. The capability of the clinical-reproductive model was evaluated by Harrell's concordance index (C-index), Kaplan-Meier curve, time-dependent receiver operating characteristic (ROC), calibration curve and decision curve analysis. The correlations between estrogen response and immune-related pathways and some gene markers of immune cells were analyzed using the TIMER 2.0 database. RESULTS: A clinical-reproductive model including incidence area, age, tumor differentiation, lymph node metastasis (N) stage, estrogen receptor alpha (ESR1) and beta (ESR2) expression, menopausal age, and pregnancy number was constructed to predict OS in female ESCC patients. Compared to the clinical model and TNM stage, the time-dependent ROC and C-index of the clinical-reproductive model showed a good discriminative ability for predicting 1-, 3-, and 5-years OS in the primary training, internal and external validation sets. Based on the optimal cut-off value of total prognostic scores, patients were classified into high- and low-risk groups with significantly different OS. The estrogen response was significantly associated with p53 and apoptosis pathways in esophageal cancer. CONCLUSION: The clinical-reproductive prognostic nomogram has an incremental prognostic value compared with the clinical model and TNM stage in predicting OS in Chinese female ESCC patients.

Mitochondrial malic enzyme 2 promotes breast cancer metastasis via stabilizing HIF-1α under hypoxia.

OBJECTIVE: α-ketoglutarate (α-KG) is the substrate to hydroxylate collagen and hypoxia-inducible factor-1α (HIF-1α), which are important for cancer metastasis. Previous studies have shown that the upregulation of collagen prolyl 4-hydroxylase in breast cancer cells stabilizes the expression of HIF-1α by depleting α-KG levels. We hypothesized that mitochondrial malic enzyme 2 (ME2) might also affect HIF-1α expression via modulating α-KG levels in breast cancer cells. METHODS: We evaluated ME2 protein expression in 100 breast cancer patients using immunohistochemistry and correlated with clinicopathological indicators. The effect of ME2 knockout on cancer metastasis was evaluated using an orthotopic breast cancer model. The effect of ME2 knockout or knockdown on the levels of α-KG and HIF-1α proteins in breast cancer cell lines was determined both in vitro and in vivo. RESULTS: ME2 was found to be upregulated in the human breast cancerous tissues compared with the matched precancerous tissues (P<0.001). The elevated expression of ME2 was associated with a poor prognosis (P=0.019). ME2 upregulation was also related to lymph node metastasis (P=0.016), pathological staging (P=0.033), and vascular cancer embolus (P=0.014). Also, ME2 knockout significantly inhibited lung metastasisin vivo. In the tumors formed by ME2 knockout cells, the levels of α-KG were significantly increased and collagen hydroxylation level did not change significantly but HIF-1α protein expression was significantly decreased, compared to the control samples. In cell culture, cells with ME2 knockout or knockdown demonstrated significantly higher α-KG levels but significantly lower HIF-1α protein expression than control cells under hypoxia. Exogenous malate and α-KG exerted similar effect on HIF-1α in breast cancer cells to ME2 knockout or knockdown. Additionally, treatment with malate significantly decreased 4T1 breast cancer lung metastasis. ME2 expression was associated with HIF-1α levels in human breast cancer samples (P=0.008). CONCLUSIONS: Our results provide evidence that upregulation of ME2 is associated with a poor prognosis of breast cancer patients and propose a mechanistic understanding of a link between ME2 and breast cancer metastasis.

Lactate and glutamine support NADPH generation in cancer cells under glucose deprived conditions.

Although glucose, through pentose phosphate pathway (PPP), is the main source to generate NADPH, solid tumors are often deprived of glucose, hence alternative metabolic pathways to maintain NADPH homeostasis in cancer cells are required. Here, we report that lactate and glutamine support NADPH production via isocitrate dehydrogenase 1 (IDH1) and malic enzyme 1 (ME1), respectively, under glucose-deprived conditions. Isotopic tracing demonstrates that lactate participates in the formation of isocitrate. Malate derived from glutamine in mitochondria shuttles to cytosol to produce NADPH. In cells cultured in the absence of glucose, knockout of IDH1 and ME1 decreases NADPH/NADP+ and GSH/GSSG, increases ROS level and facilitates cell necrosis. In 4T1 murine breast tumors, knockout of ME1 retards tumor growth in vivo, with combined ME1/IDH1 knockout more strongly suppressing tumor growth. Our findings reveal two alternative NADPH-producing pathways that cancer cells use to resist glucose starvation, reflecting the metabolic plasticity and flexibility of cancer cells adapting to nutrition stress.

Improving Fructose Utilization and Butanol Production by Clostridium acetobutylicum via Extracellular Redox Potential Regulation and Intracellular Metabolite Analysis.

Jerusalem artichoke (JA) can grow well in marginal lands with high biomass yield, and thus is a potential energy crop for biorefinery. The major biomass of JA is from tubers, which contain inulin that can be easily hydrolyzed into a mixture of fructose and glucose, but fructose utilization for producing butanol as an advanced biofuel is poor compared to glucose-based ABE fermentation by Clostridium acetobutylicum. In this article, the impact of extracellular redox potential (ORP) on the process is studied using a mixture of fructose and glucose to simulate the hydrolysate of JA tubers. When the extracellular ORP is controlled above -460 mV, 13.2 g L-1 butanol is produced from 51.0 g L-1 total sugars (40.1 g L-1 fructose and 10.9 g L-1 glucose), leading to dramatically increased butanol yield and butanol/ABE ratio of 0.26 g g-1 and 0.67, respectively. Intracellular metabolite and q-PCR analysis further indicate that intracellular ATP and NADH availabilities are significantly improved together with the fructose-specific PTS expression at the lag phase, which consequently facilitate fructose transport, metabolic shift toward solventogenesis and carbon flux redistribution for butanol biosynthesis. Therefore, the extracellular ORP control can be an effective strategy to improve butanol production from fructose-based feedstock.

Profiling the dynamic changes of PBMC immune-related indicators in patients with lung cancer after chemotherapy cycles / 中国肿瘤临床

Objective:To explore the optimal time point for combining chemotherapy and immunotherapy and provide an experimen-tal basis for immunotherapy intervention in clinical. Methods:Twenty-three lung cancer patients who completed five chemotherapy cycles between November 2015 and December 2016 in the First Affiliated Hospital of Xinxiang Medical University were enrolled in this study. Numbers of T lymphocyte subsets, B lymphocytes, and NK lymphocytes in peripheral blood were counted. Expression levels of T lymphocyte co-suppression molecule and cytokines in the peripheral blood mononuclear cell were detected using flow cytometry to analyze the dynamic changes of such indicators from one cycle to five cycles of chemotherapy. Results:Significant decreases in the lev-els of CD8+T lymphocytes, CD19+B lymphocytes, and CD16+CD56+NK cells and an increase in CD4+T lymphocytes were observed in the course of multi-cycle chemotherapy for patients with lung cancer. Differences were statistically significant (P<0.05). The co-suppres-sion molecular expression of PD-1, CTLA-4, and CCR-4 with T lymphocytes was downregulated, and the differences were significant (P<0.05). Conclusion:Profiling the dynamic changes of lymphocyte subsets and the expression of T lymphocyte co-suppression molecule are significant in multiple chemotherapy cycles for patients with lung cancer. In the later stage, the combined application of PD-1, PD-L1, CTLA-4, or CCR-4 antibody may exert good therapeutic effects for patients with a high expression level of related immune check-points.

Impact of zinc supplementation on the improved fructose/xylose utilization and butanol production during acetone-butanol-ethanol fermentation.

Lignocellulosic biomass and dedicated energy crops such as Jerusalem artichoke are promising alternatives for biobutanol production by solventogenic clostridia. However, fermentable sugars such as fructose or xylose released from the hydrolysis of these feedstocks were subjected to the incomplete utilization by the strains, leading to relatively low butanol production and productivity. When 0.001 g/L ZnSO4·7H2O was supplemented into the medium containing fructose as sole carbon source, 12.8 g/L of butanol was achieved with butanol productivity of 0.089 g/L/h compared to only 4.5 g/L of butanol produced with butanol productivity of 0.028 g/L/h in the control without zinc supplementation. Micronutrient zinc also led to the improved butanol production up to 8.3 g/L derived from 45.2 g/L xylose as sole carbon source with increasing butanol productivity by 31.7%. Moreover, the decreased acids production was observed under the zinc supplementation condition, resulting in the increased butanol yields of 0.202 g/g-fructose and 0.184 g/g-xylose, respectively. Similar improvements were also observed with increasing butanol production by 130.2 % and 8.5 %, butanol productivity by 203.4% and 18.4%, respectively, in acetone-butanol-ethanol fermentations from sugar mixtures of fructose/glucose (4:1) and xylose/glucose (1:2) simulating the hydrolysates of Jerusalem artichoke tubers and corn stover. The results obtained from transcriptional analysis revealed that zinc may have regulatory mechanisms for the sugar transport and metabolism of Clostridium acetobutylicum L7. Therefore, micronutrient zinc supplementation could be an effective way for economic development of butanol production derived from these low-cost agricultural feedstocks.

Transcriptional analysis of micronutrient zinc-associated response for enhanced carbohydrate utilization and earlier solventogenesis in Clostridium acetobutylicum.

The micronutrient zinc plays vital roles in ABE fermentation by Clostridium acetobutylicum. In order to elucidate the zinc-associated response for enhanced glucose utilization and earlier solventogenesis, transcriptional analysis was performed on cells grown in glucose medium at the exponential growth phase of 16 h without/with supplementary zinc. Correspondingly, the gene glcG (CAC0570) encoding a glucose-specific PTS was significantly upregulated accompanied with the other two genes CAC1353 and CAC1354 for glucose transport in the presence of zinc. Additionally, genes involved in the metabolisms of six other carbohydrates (maltose, cellobiose, fructose, mannose, xylose and arabinose) were differentially expressed, indicating that the regulatory effect of micronutrient zinc is carbohydrate-specific with respects to the improved/inhibited carbohydrate utilization. More importantly, multiple genes responsible for glycolysis (glcK and pykA), acidogenesis (thlA, crt, etfA, etfB and bcd) and solventogenesis (ctfB and bdhA) of C. acetobutylicum prominently responded to the supplementary zinc at differential expression levels. Comparative analysis of intracellular metabolites revealed that the branch node intermediates such as acetyl-CoA, acetoacetyl-CoA, butyl-CoA, and reducing power NADH remained relatively lower whereas more ATP was generated due to enhanced glycolysis pathway and earlier initiation of solventogenesis, suggesting that the micronutrient zinc-associated response for the selected intracellular metabolisms is significantly pleiotropic.

Effect of zinc supplementation on acetone-butanol-ethanol fermentation by Clostridium acetobutylicum.

In this article, effect of zinc supplementation on acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum was studied. It was found that when 0.001 g/L ZnSO4·7H2O was supplemented into the medium, solventogenesis was initiated earlier, with 21.0 g/L ABE (12.6 g/L butanol, 6.7 g/L acetone and 1.7 g/L ethanol) produced with a fermentation time of 40 h, compared to 19.4 g/L ABE (11.7 g/L butanol, 6.4 g/L acetone and 1.3g/L ethanol) produced with a fermentation time of 64 h in the control without zinc supplementation, and correspondingly ABE and butanol productivities were increased to 0.53 and 0.32 g/L/h from 0.30 and 0.18 g/L/h, increases of 76.7% and 77.8%, respectively, but their yields were not compromised. The reason for this phenomenon was attributed to rapid acids re-assimilation for more efficient ABE production, which was in accordance with relatively high pH and ORP levels maintained during the fermentation process. The maximum cell density increased by 23.8%, indicating that zinc supplementation stimulated cell growth, and consequently facilitated glucose utilization. However, more zinc supplementation exhibited an inhibitory effect, indicating that zinc supplementation at very low levels such as 0.001 g/L ZnSO4·7H2O will be an economically competitive strategy for improving butanol production.