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Background Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated. Methods The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice. Results Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc− inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Conclusions This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

Background Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treament. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated. Methods The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope.The mechanism in vivo was verified by in situ implantation tumor model in nude mice. Results Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, the combination of the system xc− inhibitor sulfasalazine and metformin can work in a synergistic manner to induced ferroptosis,which inhibits the proliferation of breast cancer. Conclusions This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

Background: Traumatic brain injury (TBI) often results in persistent cognitive impairment and psychiatric symptoms, while lesion location and severity are not consistent with its clinical complaints. Previous studies found cognitive deficits and psychiatric disorders following TBI are considered to be associated with prefrontal and medial temporal lobe lesions, however, the location and extent of contusions often cannot fully explain the patient′s impairments. Thus, we try to find the structural changes of gray matter (GM) and white matter (WM), clarify their correlation with psychiatric symptoms and memory following TBI, and determine the brain regions that primary correlate with clinical measurements. Methods: Overall, 32 TBI individuals and 23 healthy controls were recruited in the study. Cognitive impairment and psychiatric symptoms were examined by Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS), and Wechsler Memory Scale-Chinese Revision (WMS-CR). All MRI data were scanned using a Siemens Prisma 3.0 Tesla MRI system. T1 MRI data and diffusion tensor imaging (DTI) data were processed to analyze GM volume and WM microstructure separately. Results: In the present study, TBI patients underwent widespread decrease of GM volume in both cortical and subcortical regions. Among these regions, four brain areas including the left inferior temporal gyrus and medial temporal lobe, supplementary motor area, thalamus, and anterior cingulate cortex (ACC) were highly implicated in the post-traumatic cognitive impairment and psychiatric complaints. TBI patients also underwent changes of WM microstructure, involving decreased fractional anisotropy (FA) value in widespread WM tracts and increased mean diffusivity (MD) value in the forceps minor. The changes of WM microstructure were significantly correlated with the decrease of GM volume. Conclusions: TBI causes widespread cortical and subcortical alterations including a reduction in GM volume and change in WM microstructure related to clinical manifestation. Lesions in temporal lobe may lead to more serious cognitive and emotional dysfunction, which should attract our high clinical attention.

The purpose of this study was to determine whether the HER2 protein expression level assessed by immunochemistry (IHC) was related to the treatment response in HER2-positive breast cancer patients who received neoadjuvant chemotherapy.167 HER2-positive breast cancer patients who had received neoadjuvant chemotherapy containing trastuzumab were included in this study. There were 27 HER2 2 + and 140 HER2 3 + cases. Using propensity score matching (PSM), the two groups were matched 1:3 by T stage, N stage, hormone receptor (HR) status, Ki67, and targeted therapy regimen. We performed univariate and multivariate analyses of the association between HER2 expression level and pathological complete response (pCR) rate.The overall pCR rate was 43.7% (73/167). The pCR rate in the HER2 3 + group was significantly higher than in the HER2 2 + group (47.9% versus 22.2%, p = 0.014). After propensity score matching, 26 patients in the HER2 2 + group and 59 patients in the HER2 3 + group were matched. The pCR rate in the HER2 3 + group was still higher than in the HER2 2 + group (50.8% versus 19.2%, p = 0.006). Multivariate analysis showed that HER2 protein expression was an independent predictive factor for pCR (OR=5.353, 95% CI 1.649-17.379, p = 0.005). Additionally, the Ki67 index was also a significant factor for pCR (OR=3.702, 95% CI 1.327-10.326, p = 0.012).For HER2-positive breast cancer patients, the HER2 protein expression level detected by IHC may be a good predictive factor for the efficacy of neoadjuvant chemotherapy.

Understanding causal relationships is one of the most important goals of modern science. So far, the causal inference literature has focused almost exclusively on outcomes coming from the Euclidean space $\mathbb{R}^p$. However, it is increasingly common that complex datasets are best summarized as data points in non-linear spaces. In this paper, we present a novel framework of causal effects for outcomes from the Wasserstein space of cumulative distribution functions, which in contrast to the Euclidean space, is non-linear. We develop doubly robust estimators and associated asymptotic theory for these causal effects. As an illustration, we use our framework to quantify the causal effect of marriage on physical activity patterns using wearable device data collected through the National Health and Nutrition Examination Survey., To appear in Journal of the Royal Statistical Society: Series B

Lin28 is involved in the progression of several types of tumors. Data collected from clinical trials have suggested that Lin28 expression is correlated with poor prognosis in thyroid carcinoma. The present study was conducted to investigate the association between Lin28 expression and the clinicopathological parameters of papillary thyroid carcinoma (PTC). Accordingly, the clinical data and diagnostic results from 237 patients with PTC were collected. Immunohistochemical staining was performed to evaluate the Lin28 expression levels in thyroid tissue samples. Associations between the expression levels and clinicopathological parameters were evaluated. Lin28 was expressed in 96/237 (40.5%) of PTC specimens. Compared with patients with no Lin28 expression, patients with expression had higher rates of lymph node metastasis (P

Ferroptosis is a recently discovered distinct type of regulated cell death caused by the accumulation of lipid-based ROS. Metabolism and expression of specific genes affect the occurrence of ferroptosis, making it a promising therapeutic target to manage cancer. Here, we describe the current status of ferroptosis studies in breast cancer and trace the key regulators of ferroptosis back to previous studies. We also compare ferroptosis to common regulated cell death patterns and discuss the sensitivity to ferroptosis in different subtypes of breast cancer. We propose that viewing ferroptosis-related studies from a historical angle will accelerate the development of ferroptosis-based biomarkers and therapeutic strategies in breast cancer.

For comprehensively considering the equipment health index, maintenance cost and equipment failure loss, a decision-making model for maintenance mode selection is proposed in this paper. We define the equipment risk loss is the product of equipment failure loss and equipment failure probability. The equipment fault loss is composed of equipment asset loss and power grid operation loss, and the specific calculation formula of each part is given in this paper. The influence of the composition elements of maintenance cost, calculation methods and different maintenance methods on equipment failure rate are analyzed. The objective is minimizing the sum of maintenance cost and equipment risk loss after maintenance, a quantitative method is used to select the maintenance mode of distribution network equipment, and the maintenance mode selection process of two transformers in a certain state is given as the calculation example and the results verified the effectiveness of the proposed method.

ObjectiveTo identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression.MethodsIn this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale Parts I–III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes.ResultsTwo neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years.ConclusionRobust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation.

BackgroundRecent advances in T cell-related immunotherapy have brought remarkable progress in the treatment of non-small cell lung cancer (NSCLC). However, whether and how genetic variations of T cell cancer immune response genes can influence clinical outcomes of NSCLC patients remain obscure.MethodsIn this multiphase study, we assessed 2450 single-nucleotide polymorphisms (SNPs) from 280 T cell cancer immune response-related genes in 941 early-stage NSCLC patients (discovery n=536; validation n=405) to analyze the variants’ associations with outcomes and to observe the effects on T cell phenotypes.ResultsWe found 14 SNPs in 10 genes were associated with NSCLC outcomes (pTRB:rs1964986 was the most significant variant associated with recurrence risk after meta-analysis (HR 1.84, 95% CI 1.35 to 2.52, p=1.15E-04), while IDO1:rs10108662 was the most significant SNP associated with death risk (HR 1.87, 95% CI 1.40 to 2.51, p=2.17E-05). Analysis of unfavorable genotypes indicated cumulative effects on death and recurrence risks. Seven treatment-specific variants were found to predict opposite outcomes in surgery-only and surgery-plus-chemotherapy subgroups. Expression quantitative trait loci analysis indicated that six SNPs significantly correlated with their corresponding gene expression. T cells from high-risk subjects displayed reduced degranulation (p=0.02) and decreased cytotoxicity against cancer cells (pConclusionsGenetic variations in T cell cancer immune response pathways can impact outcomes and may be served as predictors for treatment efficacy in early-stage NSCLC patients. The correlation between immune genotypes and T cell antitumor immunity suggests a biological link between host immune genetics and NSCLC prognosis.

Mastoscopic axillary lymph node dissection (MALND) is a currently used and safe surgical treatment option for breast cancer. However, the extensive application of MALND is still debatable because of the use of conventional axillary lymph node dissection (CALND). Therefore, in the current study, we aimed to compare the efficacy and safety of MALND and CALND for obtaining evidence-based conclusions about the short-term and long-term outcomes of MALND for patients with breast cancer. PubMed, Web of Science, Cochrane Library, and CNKI were comprehensively searched for articles published between January 1998 and January 2019. Then Newcastle-Ottawa scale was used for quality assessment. The Review Manager software version 5.0 was utilized for generating forest maps and funnel plots. Twelve studies including 2157 patients were selected for the meta-analysis. There were no significant differences in the number of lymph node dissections, tumor recurrence rate, axillary drainage, postoperative hospitalization time, and tumor size between the MALND and CALND groups ( P > .05). In the MALND group, the surgery time was longer, while the incidence of intraoperative bleeding was lesser and the duration of drainage was shorter than those in the CALND group ( P < .01). The complications in the MALND group were also fewer than those in the CALND group ( P < .05). The results of the current study showed that MALND is reliable and feasible for breast cancer owing to the lesser incidence of intraoperative bleeding, shorter drainage duration, and lower incidence of complications compared to CALND.

Background Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM can lead to treatment failure and poor outcome. The underlying molecular mechanisms in ADM resistance in breast cancer remains unclear. PLAC8 is reported as a novel highly-conserved protein and functions as an oncogene or tumor suppressor in various tumors. Methods Here, we analyzed the expression profile of PLAC8 in breast cancer tissues and breast cancer cell lines, and explored the correlation of PLAC8 expression levels with patients’ outcomes and ADM response. One ADM resistant MCF-7 breast cancer cell (MCF-7/ADM) and its parental cell was used as in vitro models to identify the underlying mechanism of PLAC8 and ADM resistance. Breast cancer cells were transfected with PLAC8 knockdown and overexpression vectors, and MTT and colony formation assays were performed to test the cell response to ADM. Then, we tested the effect of PLAC8 on autophagy pathway by flow cytometry and immunofluorescence analysis, and the change of main autophagy-correlated factors expressions: LC3 and p62. Next, combining treatment of autophagy inhibitor/inducer and PLAC8 downregulation/upregulation revealed the participation of PLAC8 in autophagy pathway to synergistically regulate ADM resistance in breast cancer. Results Here, higher PLAC8 expression was correlated with poorer outcome and aggressive phenotype in breast cancer, and breast cancer patients with higher PLAC8 expression showed potential ADM resistance. PLAC8 expression level was also significantly elevated in ADM resistant MCF-7 breast cancer cells (MCF-7/ADM), compared to parental MCF-7 cells. In vitro experiments further confirmed that PLAC8 inhibition by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased the ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADM cell blocked the accumulation of the autophagy-associated protein LC3II, and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. Actually, 3-MA and PLAC8 could synergistically enhance ADM resistance via blocking the autophagy process. Additionally, the downregulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Conclusion Our findings suggest that PLAC8, through participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62/autophagy pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.

Previous studies have demonstrated that in women with breast cancer treated with breast-conserving surgery (BCS), intraoperative frozen section analysis of lumpectomy margins results in a decrease in reoperation rates for margin control. However, the value of intraoperative frozen margin evaluation (FME) in re-excision margin analysis was not fully understood. We conducted a retrospective review of patients who underwent attempted breast-conserving surgery for breast cancer with routine intraoperative frozen margin evaluation at our institution between January 1998 and May 2016. The number of frozen margin evaluation was analyzed. We additionally analyzed factors associated with positive re-excised margins to identify correlations with patient characteristics. A total of 760 patients who underwent attempted breast-conserving surgery were routinely conducted intraoperative frozen margin evaluation, frozen sections were obtained from the initial margin only in 82.5% (n = 627), the initial margin as well as a one-time re-excision analysis in 15.8% (n = 120), or the initial margin and two or more re-excision analyses in 1.7% (n-13). Based on the results of frozen margin evaluation, 727 (95.6%) of the patients underwent breast-conserving surgery, while the remaining 33 (4.4%) converted to mastectomy. Among the patients who underwent breast-conserving surgery, 112 (15.4%) had an initial positive margin on a frozen margin evaluation, underwent one-time margin re-excision and achieved a margin-free status, while 1.6% underwent a second margin resection due to a positive result on the first re-excised margin. In total, 72.7% of the conversions to mastectomy were due to a positive initial margin. Univariate and multivariate analyses showed that patients with the ductal carcinoma in situ (DCIS) histological type were more likely to have repeatedly positive re-excised margins during breast-conserving surgery. Routine intraoperative frozen margin evaluation of re-excised margins provided only limited value in patients who underwent attempted breast-conserving surgery; this method may be beneficial in the subgroup of patients with the ductal carcinoma in situ histological type.

Background: In triple negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NACT), pre-treatment predictors for pathological complete response (pCR) have been reported; however, those for progressive disease (PD) remain unidentified. Methods: We investigated pre-treatment clinicopathological predictors associated with pCR and PD by retrospectively reviewing data for 165 patients treated between 2015 and 2018. Patients with pCR and PD were compared to those without pCR and PD, respectively, using logistic regression and Kaplan-Meier methods. Results: Lack of androgen receptor (AR) was an independent predictor of pCR, while high histological grade, low Ki-67 index, and incomplete NACT courses were independent predictors of PD. Mean disease-free survival and overall survival were significantly poorer in PD patients than in pCR patients (15.7, 21.3 vs. 52.4, 56.3 months). Conclusions: Insights into the chemo-resistance mechanisms and exploration of novel targeted agents in subgroups as per AR and Ki-67 status are needed to improve survival outcomes in TNBC patients.

Background Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. FK506-binding protein (FKBP) family has been demonstrated to possess various functions by interacting with different molecular targets in BC. However, a comprehensive ncRNA-mRNA regulatory axis of FKBP has not yet been reported. Methods FKBP related miRNAs were obtained from miRWalk database. Then, potential lncRNAs, transcription factors as well as mRNAs of screened differentially expressed miRNAs (DE-miRNAs) were analysed by using LncBase v.2, miRGen v3 and miRWalk database. Additionally, differential expression and prognostic analysis of lncRNAs were evaluated using TANRIC database. Next, GO annotation and KEGG pathway analysis were processed using DAVID database. Protein-Protein Interaction (PPI) network was established and hub genes were identified using STRING database. Finally, differential expression and prognostic analysis of hub genes were further conducted using UALCAN and bc-GenExMiner v4.2 database, respectively. Results Eleven DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. 482 predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top twenty lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients’ overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. 320 target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the toppest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients’ OS. Conclusions In current study, we firstly established a predicted FKBP-related ncRNA-mRNA regulatory network, thus exploring a comprehensive interpretation of molecular mechanisms and providing potential clues in seeking novel therapeutics for BC. In the future, much more experiments should be conducted to verify our findings.

The growth of zebrafish's vessels can be used as an indicator of the vascular development process and to study the biological mechanisms. The three-dimensional (3D) structures of zebrafish's trunk vessels could be imaged by state-of-art light-sheet fluorescent microscopy with high efficiency. A large amount of data was then produced. Accurate segmentation of these 3D images becomes a new bottleneck for automatic and quantitative analysis. Here, we propose a Multi-scale 3D U-Net model to perform the segmentation of trunk vessels. The segmentation accuracies of 82.3% and 83.0%, as evaluated by the IoU (Intersection over Union) parameter, were achieved for intersegmental vessels and the dorsal longitudinal anastomotic vessels respectively. The growth of zebrafish vasculature from 42-62 hours was then analyzed quantitatively.

Minjun Dong,1 Liang Luo,2 Xiaogang Ying,3 Xianqiu Lu,3 Jianguo Shen,1 Zhinong Jiang,4 Linbo Wang1 1Department of Surgical Oncology, 2Department of Gastroenterology, Sir Run Run Shaw Hospital, 3Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China Background: Pegylated liposomal doxorubicin (PLD) and epirubicin are both superior variants of doxorubicin and are commonly applied as basic chemotherapeutics in breast cancer. However, the direct comparison of their efficacy and side effects has not been adequately reported. This study aimed to compare the efficacy and toxicity of PLD and epirubicin as neoadjuvant chemotherapy for invasive breast cancer. Patients and methods: Women (n = 43) with invasive breast cancer who received neoadjuvant chemotherapy with the regimens containing PLD (PLD group) were analyzed and 1:2 matched with those (n = 86) who received regimens containing epirubicin (epirubicin group) according to clinical TNM staging and taxane combination. Results: The PLD group achieved similar clinical response rate in neoadjuvant chemotherapy compared to the epirubicin group (76.7% vs 75.6%). The PLD group had a lower rate of grade 3 & 4 neutropenia (30.2% vs 60.5%), vomiting (7.0% vs 28.0%), and grade 3 & 4 alopecia (9.3% vs 43.0%), yet a higher rate of mouth ulceration (46.5% vs 11.7%). For the cardiac toxicity, the PLD group had a significantly lower rate of ventricular premature beat compared with the epirubicin group (7.0% vs 20.9%, p = 0.043), and cardiac ultrasonography monitoring showed non-significantly less PLD group patients’ left ventricular ejection fraction decline more than 10% compared with the epirubicin group (4.7% vs 8.1%, p = 0.463). Conclusion: In neoadjuvant chemotherapy for invasive breast cancer, PLD provides potentially similar efficacy and relatively less toxicity compared to epirubicin. Keywords: neoadjuvant chemotherapy, pegylated liposomal doxorubicin, epirubicin, breast cancer, efficacy

Abscisic acid (ABA) regulates plant stress responses and development. However, how the ABA signal is transmitted in response to stresses remains largely unclear, especially in monocots. In this study, we found that rice (Oryza sativa) OsPM1 (PLASMA MEMBRANE PROTEIN1), encoded by a gene of AWPM-19 like family, mediates ABA influx through the plasma membrane. OsPM1 is predominantly expressed in vascular tissues, guard cells, and mature embryos. Phenotypic analysis of overexpression, RNA interference (RNAi), and knockout (KO) lines showed that OsPM1 is involved in drought responses and seed germination regulation. (3)H-(±)ABA transport activity and fluorescence resonance energy transfer assays both demonstrated that OsPM1 facilitates ABA uptake into cells. The physiological isomer of ABA, (+)-ABA, is the preferred substrate of OsPM1. Higher ABA accumulation and faster stomatal closure in response to ABA treatment were observed in the overexpression lines compared with the wild-type control. Many ABA-responsive genes were upregulated more in the OsPM1-overexpression lines but less in the RNAi lines compared with wild-type plants. Further investigation revealed that OsPM1 expression is regulated by the AREB/ABF family transcription factor OsbZIP46. Our results thus revealed that OsPM1 is an ABA influx carrier that plays an important role in drought responses.

We propose a three-dimensional (3D) omnidirectional underwater acoustic concentrator based on the concept of an acoustic prison, which can realize a substantial enhancement of underwater sound signals in broadband ranges. This device mainly employs the non-resonant multiple reflection characteristics of the semi-enclosed geometric space, so it has a wide working frequency bandwidth. Compared with previously reported concentrators based on transform acoustic mechanisms, the structure is more simple and, most importantly, it can realize omnidirectional signal enhancement in a 3D space. Moreover, the working frequency band of this acoustic concentrator depends on the size of the concentrator, so it can be changed directly through size scaling, which is convenient for engineering applications. In general, the designed underwater acoustic concentrator has the advantages of a simple structure, scalability, large bandwidth of working frequency, and high signal gain. It has potential applications in underwater target detection and other aspects.

Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Firstly, higher expression of KLF4 correlated with increased TAM sensitivity in breast cancer cells, and analysis of GEO datasets indicated that KLF4 expression was positively correlated with ERα and enhanced expression of KLF4 sensitized breast cancer patients to endocrine therapy. Knockdown of KLF4 in MCF-7 and BCAP37 cells led to increased TAM resistance, while ectopic KLF4 expression promoted the responsiveness to TAM in T47D and TAM-resistant MCF-7/TAM cells. Secondly, ectopic KLF4 overexpression suppressed MCF-7/TAM cell growth, invasion and migration. Moreover, KLF4 expression was down-regulated in breast cancer tumor tissues and high expression of KLF4 was associated with favorable outcomes. Mechanistically, KLF4 may enhance the responsiveness of breast cancer cells to TAM through suppressing mitogen-activated protein kinase (MAPK) signaling pathway. We found that ERK and p38 were more activated in MCF-7/TAM compared with MCF-7, and treatment with MAPK-specific inhibitors significantly suppressed cell viability. Knockdown of KLF4 activated ERK and p38 and drove MCF-7 cells to become resistant to TAM. Conversely, overexpression of KLF4 in MCF-7/TAM cells suppressed ERK and p38 signaling and resulted in increased sensitivity to TAM. Therefore, our findings suggested that KLF4 contributed to TAM sensitivity in breast cancer via phosphorylation modification of ERK and p38 signaling. Collectively, this study highlighted the significance of KLF4/MAPK signal interaction in regulating TAM resistance of breast cancer, and suggested that targeting KLF4/MAPK signaling may be a potential therapeutic strategy for breast cancer treatment, especially for the TAM-resistant patients.

Summary Instrumental variables are widely used for estimating causal effects in the presence of unmeasured confounding. Under the standard instrumental variable model, however, the average treatment effect is only partially identifiable. To address this, we propose novel assumptions that enable identification of the average treatment effect. Our identification assumptions are clearly separated from model assumptions that are needed for estimation, so researchers are not required to commit to a specific observed data model in establishing identification. We then construct multiple estimators that are consistent under three different observed data models, and multiply robust estimators that are consistent in the union of these observed data models. We pay special attention to the case of binary outcomes, for which we obtain bounded estimators of the average treatment effect that are guaranteed to lie between −1 and 1. Our approaches are illustrated with simulations and a data analysis evaluating the causal effect of education on earnings.

Matrix metalloproteinase-1 (MMP1) is a member of the matrix metalloproteinases family, and its aberrant expression is implicated in tumor invasion and metastasis. However, the relationship between MMP1 abnormal expression and clinical outcome in breast cancer patients remains to be elucidated. To address this issue, we conducted immunohistochemistry in breast cancer and adjacent normal tissues, and mined the transcriptional and survival data of MMP1 in breast cancer patients through Oncomine, Kaplan-Meier Plotter, bc-GenExMiner, COSMIC and cBioPortal databases. First, we found that both protein and mRNA levels of MMP1 expression were significantly higher in breast cancer tissues. Second, high MMP1 mRNA expression correlated with worse overall survival among grade II (HR = 1.75; p = 0.011), nodal-negative (HR = 2.00; p = 0.00028), ER-positive (HR = 1.61; p = 0.00027) and HER2-negative (HR = 3.17; p = 0.029) patients with breast cancer by using Kaplan-Meier plotter database. Third, the overexpression of MMP1 was associated with unfavorable survival results including overall survival (HR = 1.6; p = 1.6e-05), relapse free survival (HR = 1.78; p < 1e-16) and distant metastasis free survival (HR = 1.65; p = 5.3e-05) in patients with breast cancer. Taken together, the expression status of MMP1 is a significant prognostic indicator and a potential drug target for breast cancer.

It is common in medical studies that the outcome of interest is truncated by death, meaning that a subject has died before the outcome could be measured. In this case, restricted analysis among survivors may be subject to selection bias. Hence, it is of interest to estimate the survivor average causal effect, defined as the average causal effect among the subgroup consisting of subjects who would survive under either exposure. In this paper, we consider the identification and estimation problems of the survivor average causal effect. We propose to use a substitution variable in place of the latent membership in the always-survivor group. The identification conditions required for a substitution variable are conceptually similar to conditions for a conditional instrumental variable, and may apply to both randomized and observational studies. We show that the survivor average causal effect is identifiable with use of such a substitution variable, and propose novel model parameterizations for estimation of the survivor average causal effect under our identification assumptions. Our approaches are illustrated via simulation studies and a data analysis., Comment: Correct a typo in equation (8)

In order to prohibit the formation of large Y-Al-O precipitates, Ti hydride nanoparticles (NPs) were prepared and used to replace Ti as raw particles to fabricate the oxide dispersion strengthened (ODS) Fe-14Cr-3Al-2W-0.35Y2O3 steels by mechanical alloying (MA) and hot isostatic pressing (HIP). As the content of Ti hydride increases from 0.1 to 0.5 and 1.0 wt%, the oxide nanoprecipitates in the ODS steels changes from Y3Al5O12 phase to Y2Ti2O7 phase (semicoherent with the matrix), and the particle size is successfully reduced. The tensile strength of the ODS steel increases remarkably with increasing Ti hydride content. The sample with 1.0 wt% Ti hydride exhibits a high strength of 1049 MPa at 25 °C and 278 MPa at 700 °C. The creation of Y2Ti2O7 nanoprecipitates by adding Ti hydride NPs opens a new way to control the structure and size of the oxide precipitates in the ODS steels.

Cox's proportional hazards model is one of the most popular statistical models to evaluate associations of exposure with a censored failure time outcome. When confounding factors are not fully observed, the exposure hazard ratio estimated using a Cox model is subject to unmeasured confounding bias. To address this, we propose a novel approach for the identification and estimation of the causal hazard ratio in the presence of unmeasured confounding factors. Our approach is based on a binary instrumental variable, and an additional no-interaction assumption in a first-stage regression of the treatment on the IV and unmeasured confounders. We propose, to the best of our knowledge, the first consistent estimator of the (population) causal hazard ratio within an instrumental variable framework. A version of our estimator admits a closed-form representation. We derive the asymptotic distribution of our estimator and provide a consistent estimator for its asymptotic variance. Our approach is illustrated via simulation studies and a data application.

Long non‑coding RNA (lncRNA) H19 and Lin28 protein have been shown to participate in various pathophysiological processes, including cellular proliferation, autophagy and epithelial‑mesenchymal transition (EMT). A number of studies have investigated lncRNAs, microRNAs and mRNAs, and their roles in the initiation and progression of cancer, in doing so identifying competitive endogenous RNA (ceRNA) networks, including the H19/let‑7/Lin28 network. However, whether the H19/let‑7/Lin28 ceRNA network is involved in autophagy and EMT in breast cancer (BC) remains unclear. The present study demonstrated that the H19/let‑7/Lin28 loop was required for the downregulation of autophagy in BC cells via western blot analysis, reverse transcription‑quantitative PCR and autophagy flux monitoring. Using wound healing, migration and invasion assays, and morphological assays, the H19/let‑7/Lin28 loop was revealed to promote EMT in BC cells. Moreover, the H19/let‑7/Lin28 network was found to contribute to autophagy by inhibiting EMT in BC cells. To the best of our knowledge, the present study is the first to suggest the important roles of the H19/let‑7/Lin28 ceRNA network in BC autophagy and EMT, thus providing insight for the use of these molecules as prognostic biomarkers and therapeutic targets in BC metastasis.

Supplemental Material, CCX-19-0313.R2_-_prisma_2009_checklist for Contrast of Mastoscopic and Conventional Axillary Lymph Node Dissection of Patients With Breast Cancer: Meta-Analysis by Hanchu Xiong, Zihan Chen, Ling Xu, Cong Chen, Qingshuang Fu, Rongyue Teng, Jida Chen, Shuduo Xie, Linbo Wang, Xiao-Fang Yu and Jichun Zhou in Cancer Control

Supplemental Material, CCX-19-0313_prisma_2009_checklist for Contrast of Mastoscopic and Conventional Axillary Lymph Node Dissection of Patients With Breast Cancer: Meta-Analysis by Hanchu Xiong, Zihan Chen, Ling Xu, Cong Chen, Qingshuang Fu, Rongyue Teng, Jida Chen, Shuduo Xie, Linbo Wang, Xiao-Fang Yu and Jichun Zhou in Cancer Control

Supplemental Material, Ethical_Statement for Contrast of Mastoscopic and Conventional Axillary Lymph Node Dissection of Patients With Breast Cancer: Meta-Analysis by Hanchu Xiong, Zihan Chen, Ling Xu, Cong Chen, Qingshuang Fu, Rongyue Teng, Jida Chen, Shuduo Xie, Linbo Wang, Xiao-Fang Yu and Jichun Zhou in Cancer Control

Traditional distribution network equipment operation and maintenance is more passive and has obvious contradictions with manpower insufficiency, heavy tasks and large increments. Exploring new technology based on the collaborative development of Internet of Things and intelligent operation and maintenance, comprehensively improving the ability of remote control such as information acquisition, abnormal alarm, fault diagnosis, etc., and expanding the application of modern distribution network intelligent rapid operation and maintenance integration practice technology has great prospects. However, the traditional Homogeneous Network Environments are supplied by the same vendor or compatible devices, which run under the same operating system or network operating system. With the popularity of personal computers and the wide application of Internet of Things technology, the Homogeneous Network Environments has been unable to meet the relevant business needs. In addition, Guizhou is located in Karst Landform, complex terrain and scarce power supply, which brings great challenges to distribution network communication. Therefore, this paper focuses on exploring the key communication technologies involved in the application of wireless multi-mode technology in the field of rapid operation and maintenance of distribution network equipment, so as to build a communication technology foundation for the intelligent development of Guizhou intelligent distribution network.

It is important to draw causal inference from observational studies, which, however, becomes challenging if the confounders have missing values. Generally, causal effects are not identifiable if the confounders are missing not at random. We propose a novel framework to nonparametrically identify causal effects with confounders subject to an outcome-independent missingness, that is, the missing data mechanism is independent of the outcome, given the treatment and possibly missing confounders. We then propose a nonparametric two-stage least squares estimator and a parametric estimator for causal effects., Comment: 42 pages, 1 figure

Personnel training is the basic function of colleges and universities. Postgraduate education is also an important part of personnel training, and is an important task of colleges and universities. In view of the current situation and shortcomings of the quality evaluation of professional postgraduate training in China, this paper puts forward the evaluation model of graduate training quality based on analytic hierarchy process and utility theory. By constructing the graduate training quality evaluation system, using the analytic hierarchy process to determine the weight of the index, the utility theory is used to calculate the utility value. The training mode and quality of the disabled graduate students.

Purpose In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). Methods A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter®, a microfluidic‐based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. Results Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P, Circulating tumor cells were successfully isolated in breast cancer (BC) patients using CytoSorter® system. Circulating tumor cells can be used to differentiate BC patients from the patients with benign breast diseases or healthy volunteers, and as a diagnostic aid for early cancer diagnosis and cancer staging.

Aiming at the problems that the current distribution system have poor real-time performance and unreasonable operation and maintenance resource allocation, a state maintenance decision-making method based on real-time health status evaluation and risk assessment results of distribution equipment is proposed. Firstly, the real-time health index is evaluated based on distribution equipment status assessment result, and the real-time failure rate is calculated based on exponential model. Secondly, the average real-time failure rate of all equipment is calculated by the feeder partition method; the importance of equipment is determined by the loss cost of failure assets, including the cost of users’ loss during power outages, the equipment cost and environmental damage cost. Finally, the relative risk cost of each device is calculated based on the risk loss cost of each device. According to the indicator, the operation and maintenance mode and operation and maintenance sequence of different devices are determined, and a differentiated operation and maintenance strategy is formulated. The validity of the proposed model is verified by an example.

The cysteine‐rich lysosomal protein placenta‐specific 8 (PLAC8), also called onzin, has been shown to be involved in many types of cancers, and its role is highly dependent on cellular and physiological contexts. However, the precise function of PLAC8 in breast cancer (BC) progression remains unclear. In this study, we investigated both the clinical significance and biological functions of PLAC8 in BC progression. First, high PLAC8 expression was observed in primary BC tissues compared with adjacent normal tissues through immunohistochemistry analysis. The results of in vitro and in vivo assays further confirmed that PLAC8 overexpression promotes cell proliferation and suppress BC cell apoptosis, whereas PLAC8 silencing has the opposite effect. In addition, the forced expression of PLAC8 greatly induces cell migration, partially by affecting the EMT‐related genes, including down‐regulating E‐cadherin expression and facilitating vimentin expression. Further mechanistic analysis confirmed that PLAC8 contributes to cell proliferation and suppresses cell apoptosis in BC by activating the PI3K/AKT/NF‐κB pathway. The results of our study provide new insights into an oncogenic role of PLAC8 and reveal a novel PLAC8/ PI3K/AKT/NF‐κB pathway as a potential therapeutic target for BC.

During studies on related substances in coenzyme Q

// Ji Wang 1, 2, * , Chenyang Ye 3, * , Cong Chen 1, 2 , Hanchu Xiong 1, 2 , Binbin Xie 1, 2 , Jichun Zhou 1, 2 , Yongxia Chen 1, 2 , Shu Zheng 3, 4 , Linbo Wang 1, 2 1 Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China 2 Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, 310016, China 3 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China 4 Reseach Center for Air Pollution and Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China * These authors contributed equally to this work Correspondence to: Linbo Wang, email: linbo.wang@aliyun.com Shu Zheng, email: zhengshu@zju.edu.cn Keywords: GLUT1, solid tumors, prognosis, overall survival, disease-free survival Received: November 17, 2016 Accepted: January 26, 2017 Published: February 07, 2017 ABSTRACT Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and frequently expressed in a significant proportion of human cancers. Numerous studies have reported paradoxical evidence of the relationship between GLUT1 expression and prognosis in solid human tumors. To address this discrepancy, we conducted a thorough search of Pubmed and Web of Science for studies evaluating the expression of GLUT1 and overall survival (OS) and disease-free survival (DFS) in patients with solid cancer from 1993 to April 2016. Data from published researches were extracted and computed into odds ratio (OR). A total of 26 studies including 2948 patients met our search criteria and were evaluated. Overexpression of GLUT1 was found to significantly correlate with poor 3-year OS (OR: 2.86; 95% CI, 1.90–4.32, P < 0.00001) and 5-year OS (OR: 2.52; 95% CI, 1.75–3.61, P < 0.00001) of solid tumors. Similar results were observed when analysis of DFS was performed. Subgroup analysis revealed that elevated GLUT1 expression was associated with worse prognosis of oral squamous cell carcinoma and breast cancer. Taken together, overexpression of GLUT1 is correlated with poor survival in most solid tumors, suggesting that the expression status of GLUT1 is a vital prognostic indicator and promising therapeutic target in solid tumors.

// Qinchuan Wang 1 , Xiang Shu 4 , Yong Dong 2 , Jichun Zhou 1 , Rongyue Teng 1 , Jianguo Shen 1 , Yongxia Chen 1 , Mingjun Dong 1 , Wenjun Zhang 3 , Yasheng Huang 5 , Shuduo Xie 1 , Qun Wei 1 , Wenhe Zhao 1 , Wenjun Chen 1 , Xiaoming Yuan 1 , Xu Qi 1 and Linbo Wang 1 1 Department of Surgical Oncology, Affiliated Sir Runrun Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China 2 Department of Oncology, Affiliated Sir Runrun Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China 3 Zhejiang Academy of Medical Science, Zhejiang University School of Medicine, Hangzhou, China 4 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA 5 Department of Unrology, Hangzhou Chinese Medicine Hospital, Hangzhou, China Correspondence to: Linbo Wang, email: wanglinbo@medmail.com.cn Keywords: gamma-glutamyl transpeptidase, gastric cancer, prognosis, serum, chemotherapy Received: November 01, 2016 Accepted: January 24, 2017 Published: February 22, 2017 ABSTRACT Background: Gastric Cancer is one of the most lethal malignancies worldwide. Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular glutathione homeostasis. We aim to explore the clinical value of GGT in gastric cancer. Results: Among 322 patients enrolled, 65/82 patients were determined as GGT positive in serum/tumor, respectively. High tumor GGT expression is significantly associated with lymph node metastasis, histological subtype, and Her2 expression. Kaplan-Meier curve shows that high tumor GGT patients have shorter overall survival ( P log-rank =0.001) and progress-free survival ( P log-rank =0.001). Patients with both high tumor and serum GGT have the poorest prognosis. The multivariable Cox analysis shows that the hazard ratio of overall survival for high tumor GGT is 1.69 (95% CI 1.19-2.37). High serum GGT is a poor prognostic factor in adjuvant chemotherapy hazard ratio=2.18, 95%CI (1.15-4.47). These findings were further validated in six online datasets. Gene Sets Enrichment Analysis showed that GGT promotes cancer progression through EMT, KRAS, SRC and PKCA pathways. Methods: Tumor GGT and serum GGT levels were evaluated with immuno-histochemistry staining and enzymatic assay, respectively. Kaplan-Meier curve and Cox regression model were used to test the association between GGT and gastric cancer prognosis. Independent datasets from Gene Expression Omnibus and Gene Sets Enrichment Analysis were applied to validate the findings and explore the potential mechanisms. Conclusion: Both tumor GGT and serum GGT are poor prognostic factors in gastric cancer. Patients with high tumor and serum GGT levels require more intense treatment and follow-up.

Microporous Co nanoparticles (NPs) with pore diameters of 0.38 nm have been prepared by dealloying Co–Al alloy NPs, which were subsequently annealed at different temperatures to synthesize microporous Co3O4–Co nanocomposites as electrode materials for pseudocapacitors. The NPs annealed at 423 K are made of Co3O4 and Co phases, and become pure Co3O4 after being annealed at 473 and 573 K. The pore diameter of the NPs does not change significantly upon increasing the annealing temperature from 423 to 573 K, whereas the specific surface area decreases from 39.25 to 26.68 m2 g−1 due to the sintering effect. The pseudocapacitive behavior of the microporous Co3O4–Co nanocomposites were investigated by cyclic voltammetry (CV) and chronopotentiometry (CP) tests. The microporous Co3O4–Co nanocomposite annealed at 423 K exhibits outstanding pseudocapacitive performance with a high specific capacitance (SC) of 507 F g−1 at 1 A g−1 and good cycling stability (93% retention of its initial specific capacitance after 1000 cycles). The SC value decreases to 77 F g−1 for the sample annealed at 573 K. The charge–discharge mechanism is discussed in terms of the microporous structure and the existence of the Co phase. The novel microporous material may open a new route to high performance pseudocapacitors.

// Hanchu Xiong 1,2,* , Wenhe Zhao 1,2,* , Ji Wang 1,2,* , Benjamin J. Seifer 3 , Chenyang Ye 4 , Yongxia Chen 1,2 , Yunlu Jia 1,2 , Cong Chen 1,2 , Jianguo Shen 1,2 , Linbo Wang 1,2 , Xinbing Sui 2,5 and Jichun Zhou 1,2 1 Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China 2 Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China 3 USF Health Morsani College of Medicine, Tampa, FL, USA 4 Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education), Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China 5 Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China * These authors have contributed equally to this work Correspondence to: Linbo Wang, email: // Xinbing Sui, email: // Jichun Zhou, email: // Keywords : Lin28; Let-7; breast cancer; metastasis; drug resistance Received : November 09, 2016 Accepted : January 11, 2017 Published : January 29, 2017 Abstract The RNA binding protein Lin28 is best known for the critical role in cell development, recent researches also have implied its oncogenic function in various human cancers, including breast cancer. Specifically, aberrant Lin28 participates in multiple pathological processes, such as proliferation, metastasis, radiotherapy and chemotherapy resistance, metabolism, immunity and inflammation as well as stemness. In this review, we summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss our present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer.

Long non-coding RNAs (lncRNAs), which occupy nearly 98% of genome, have crucial roles in cancer development, including breast cancer. Breast cancer is a disease with high incidence. Despite of recent progress in understanding the molecular mechanisms and combined therapy strategies, the functions and mechanisms of lncRNAs in breast cancer remains unclear. This review presents the currently basic knowledge and research approaches of lncRNAs. We also highlight the latest advances of seven classic lncRNAs and three novel lncRNAs in breast cancer, elucidating their mechanisms and possible therapeutic targets. Additionally, association between lncRNA and specific molecular subtype of breast cancer is reported. Lastly, we briefly delineate the potential roles of lncRNAs in clinical applications as biomarkers and treatment targets.

Ji-Chun Zhou,1 Ju-Feng Guo,1,2 Rong-Yue Teng,1 Qin-Chuan Wang,1 Ji Wang,1 Qun Wei,1,3 Zi-Duo Li,1,4 Jian-Guo Shen,1 Lin-Bo Wang1,5 1Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 2Department of Surgical Oncology, Hangzhou First People’s Hospital, Hangzhou, People’s Republic of China; 3Department of International Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Dendritic Cell Biology and Therapeutic Group, ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia; 5Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, People’s Republic of China Background: Although the correlation between metabolic abnormality and gastric cancer has been extensively investigated, the question of whether metabolic parameters might influence the efficacy of chemotherapy in locally advanced gastric cancer is still unanswered. In our present study, we investigated the relationship between serum fasting glucose, lipid levels, and histopathological response of neoadjuvant chemotherapy (NAC) in locally advanced gastric cancers. Patients and methods: A total of 128 patients were identified from a prospectively maintained database of patients with locally advanced gastric cancer who received NAC between July 2004 and December 2012. Histopathological response after NAC was analyzed according to Becker’s tumor-regression grade. Univariate analyses and multivariable regression analyses were performed to determine the correlation between tumor size, differentiation, fasting glucose, lipid levels, and tumor histopathological response after NAC. Results: Univariate analysis revealed that low-density lipoprotein level and total cholesterol, as well as tumor size and differentiation, correlated significantly with histopathological response. Low-density lipoprotein levels and tumor size were found to be independent predictors for histopathological response, according to multivariable regression analyses. Conclusion: In this observational, hypothesis-generating study, serum low-density lipoprotein measurement was found to be useful in predicting chemosensitivity to locally advanced gastric cancer patients undergoing NAC. Incorporation of serum low-density lipoprotein levels into individualized treatment protocols could be considered in clinical practice. Keywords: gastric cancer, neoadjuvant chemotherapy, low-density lipoprotein, histopathological response, predictive biomarker

The Y–Ti hydrides nanoparticles were prepared by hydrogen plasma-metal reaction (HPMR) method. Transmission electron microscopy (TEM) observation revealed that they were spherical in shape and ranged from 5 to 75 nm with a mean diameter of 31 nm. Each nanoparticle contained different hydride phases (YH2, YH3 and TiH1.924), and there existed dislocations to relax lattice misfit strain and minimize the interfacial energy. The hydride nanocomposite started to oxidize at 218 °C during annealing in air, and the pyrochlore-type Y2Ti2O7 nanoparticles of single crystalline were fabricated successfully at a low sintering temperature of 900 °C for 1 h. The Y2Ti2O7 nanoparticles of axiolitic shape had an average size of 70 nm, much smaller than the conventional Y2Ti2O7 prepared by sintering Y and Ti oxides above 1300 °C. The formation of Y2Ti2O7 nanoparticles from the hydride nanocomposite at a low temperature and short reaction time can be attributed to the very short diffusion distance of Y and Ti at nanoscale, and the accelerated diffusion rate due to the strained interface of different hydride phases. The novel strategy opens a new way to prepare the nanosized pyrochlore-type oxides at a low temperature.

Benzodiazepine (BZD) use may be associated with dementia. However, differing opinions exist regarding the effect of BZDs on long-term changes in cognition. We evaluated the association between BZD use and cognitive decline in the elderly with normal cognition from the National Alzheimer's Disease Coordinating Center's Uniform Data Set. The study exposure, BZD use, was classified 2 ways: any-use [reported BZD use at a minimum of 1 Alzheimer's disease center (ADC) visit] and always-use (reported BZD use at all ADC visits). The reference group included participants without any declared BZD use at any Alzheimer's Disease Center (ADC) visit. The main outcome measures were Clinical Dementia Rating Sum of Boxes score and Mini-Mental State Examination score. We observed a decline in cognitive status over time in the 2 comparison groups. All participants who reported taking BZDs had poorer cognitive performance at all visits than nonusers. However, cognitive decline was statistically similar among all participants. We found no evidence of an association between BZD use and cognitive decline. The poor cognitive performance in BZD users may be due to prodromal symptoms caused by preclinical dementia processes.

Aluminum was added at different percentages of 1.5, 3 and 4.5 wt.% into the Y2Ti2O7-dispersed Fe-14Cr ferritic alloy to improve its oxidation resistance. The oxidation behavior of the oxide dispersion strengthened (ODS) alloys was investigated at 1100 °C in air up to 200 h. Al plays the key role in improving the oxidation resistance of the ODS alloys by generating alumina protection scale. Y2Ti2O7 is of importance to form stable alumina layer. To produce a compact and continuous alumina layer on the surface of Fe-14Cr ODS alloys, the concentration of Al should not be less than 4.5 wt.%.

Understanding how a customer perceives an undefined commodity problem is important for online retailers so that they can address problems and satisfy and gain customers. Data mining technological maturation and developments in online review systems means that it is now possible to mine for customer perceptions on commodity problems from structured and unstructured data. This research, therefore, mainly used an unsupervised machine learning, stacked denoising autoencoder-K-means, to resolve the customer perception process for undefined commodity problems. It was found that: 1) textual reviews and quantitative scores are mutually complementary when analysing online buyer perceptions; 2) customer perception systems have a typical line-of-sight to capture the undefined commodity problem attributions. Although the attributions related to undefined commodity problems are very scattered, a highly unified strategy, providing after-sales service, was found to exist within each group, which was agreed through group consensus by about 98% of the consumers.