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Apple chlorotic leaf spot virus (ACLSV; genus Trichovirus) is an economically important virus. Approximately 101 ACLSV whole-genome sequences were obtained from NCBI and used to explore the evolutionary dynamics of ACLSV. The time to the most recent common ancestor of ACLSV based on BEAST analysis appeared on an apple host from Canada in 1918 and then spread around the world in three ways concurrent with host spread. The maximum clade credibility tree of ACLSV shows that the mean evolution rate was 4.92 × 10−4 substitutions per site per year (subs/site/year), and we found that, during host evolution, the rate of evolution was mostly 2.31 × 10−4 to 2.72 × 10−4 subs/site/year. The rate of geographic evolution was 5.51 × 10−4 to 6.17 × 10−4 subs/site/year. To further explore the intrinsic changes in ACLSV during the process of geographic and host spread, we explored the secondary structural changes of the ACLSV coat protein (CP), which were mainly concentrated in four regions—20 to 40, 70 to 90, 120 to 140, and 180 to 193—which are related to the presence or absence and change in length of the β-turn, β strand, coil, and α helix, respectively. We then explored the codon usage preference within the CP across the migration pathways of ACLSV. These comprehensive analyses not only reveal the changes in ACLSV in the last 30 years but also further elucidate the intrinsic evolutionary dynamics of ACLSV. This is also the first report on the intrinsic evolutionary dynamics of ACLSV.

The hypoxic tumor microenvironment promotes both cancer progression and drug resistance.Prolyl hydroxylases are hypoxic sensor proteins that are frequently mutated or heterozygously deleted in breast cancers; however, how prolyl hydroxylation regulates breast cancer progression and drug resistance remains poorly understood. Here, we found that hypoxia promotes cancer progression and resistance to chemotherapy drugs, specifically through prolyl hydroxylation-dependent activation of MAPK signaling. We characterized a pVHL-independent mechanism wherein the prolyl hydroxylase EglN1 catalyzed prolyl hydroxylation of the proline-rich domain of RAS-specific guanine nucleotide exchange factor SOS1, thereby preventing its binding with the growth factor receptor bound protein 2 (GRB2) to block the formation of MAPK signaling microclusters in breast cancer. Inhibition of EglN1’s prolyl hydroxylase function—which occurs in hypoxic conditions and upon accumulation of fumarate—induced cancer-specific dysregulation of MAPK signaling, which promoted both breast cancer growth and resistance to MEK inhibitors. We harnessed this insight and demonstrated a therapeutic strategy that potently inhibits breast cancer growth and drug resistance based on pharmacologically disrupting the prolyl-hydroxylation-mediated interaction between SOS1 and GRB2.

Since the imbalance of gene expression has been demonstrated to tightly related to breast cancer (BRCA) genesis and growth, common genes expressed of BRCA were screened to explore the essence in-between. In current work, most common differentially expressed genes (DEGs) in various subtypes of BRCA were identified. Functional enrichment analysis illustrated the driving factor of deactivation of the cell cycle and the oocyte meiosis, which critically triggers the development of BRCA. Herein, we constructed a 12-gene prognostic risk model relative to differential gene expression. Subsequently, the K-M curves, analysis on time-ROC curve and Cox regression were performed to assess this risk model by determining the respective prognostic value, and the prediction performance were ascertained for both training and validation cohorts. In addition, multivariate Cox regression was analysed to reveal the independence between risk score and prognostic stage, and the accuracy and sensitivity of prognosis are particularly improved after clinical indicators are included into the analysis. In summary, this study offers novel insights into the imbalance of gene expression within BRCA, and highlights 12 selected genes associated with patient prognosis. The risk model can help individualize treatment for patients at different risks, and propose precise strategies and treatments for BRCA therapy.

Interferon (IFN) responses are central to host defense against coronavirus and other virus infections. Manganese (Mn) is capable of inducing IFN production, but its applications are limited by nonspecific distributions and neurotoxicity. Here, we exploit chemical engineering strategy to fabricate a nanodepot of manganese (nanoMn) based on Mn2+. Compared with free Mn2+, nanoMn enhances cellular uptake and persistent release of Mn2+ in a pH-sensitive manner, thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo. Preferentially phagocytosed by macrophages, nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci, eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage. Besides, nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation, suggesting its potential as a vaccine adjuvant. Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese. Therefore, nanoMn offers a simple, safe, and robust nanoparticle-based strategy against coronavirus. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12274-020-3243-5 and is accessible for authorized users.

Electronic properties at the interfaces between different-composition domains of 2D-alloys are key for their optical, electronic, and optoelectronic applications. Understanding the interfacial electronic structures and carrier dynamics is essential for designing and fabricating devices that use these alloys. Here, WS

Objective: Lynch syndrome (LS) predisposes patients to early onset endometrioid endometrial cancer (EEC). However, little is known about LS-related EEC in the Chinese population. The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC. Methods: We applied universal immunohistochemistry screening to detect the expression of mismatch repair (MMR) proteins, which was followed by MLH1 methylation analysis to identify suspected LS cases, next-generation sequencing (NGS) to confirm LS, and microsatellite instability (MSI) analysis to verify LS. Results: We collected 211 samples with EEC. Twenty-seven (27/211, 12.8%) EEC cases had a loss of MMR protein expression. After MLH1 methylation analysis, 16 EEC cases were suggested to be associated with LS. Finally, through NGS and MSI analysis, we determined that 10 EEC (10/209, 4.78%) cases were associated with LS. Among those cases, 3 unreported mutations (1 frameshift and 2 nonsense) were identified. MSH6 c.597_597delC, found in 4 patients, is likely to be a founder mutation in China. Conclusions: We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC, by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis. The novel mutations identified in this study expand knowledge of LS.

Background Platinum‐based chemotherapy is effective in inducing shrinkage of primary lung cancer lesions; however, it shows finite therapeutic efficacy in patients suffering from brain metastasis (BM). The intrinsic changes of BM cells, which contribute to the poor results remain unknown. Methods Platinum drug‐sensitivity was assessed by utilizing a preclinical BM model of PC9 lung adenocarcinoma cells in vitro and in vivo. High consumption of glutathione (GSH) and two associated upregulated proteins (GPX4 and GSTM1) in BM were identified by integrated metabolomics and proteomics in cell lines and verified by clinical serum sample. Gain‐of‐function and rescue experiments were implemented to reveal the impact and mechanism of GPX4 and GSTM1 on the chemosensitivity in BM. The interaction between GPX4 and GSTM1 was examined by immunoblotting and immunoprecipitation. The mechanism of upregulation of GPX4 was further uncovered by luciferase reporter assay, immunoprecipitation, and electrophoretic mobility shift assay. Results The derivative brain metastatic subpopulations (PC9‐BrMs) of parental cells PC9 developed obvious resistance to platinum. Radically altered profiles of BM metabolism and protein expression compared with primary lung cancer cells were described and GPX4 and GSTM1 were identified as being responsible for the high consumption of GSH, leading to decreased chemosensitivity by negatively regulating ferroptosis. Besides, GSTM1 was found regulated by GPX4, which was transcriptionally activated by the Wnt/NR2F2 signaling axis in BM. Conclusions Collectively, our findings demonstrated that Wnt/NR2F2/GPX4 promoted acquired chemoresistance by suppressing ferroptosis with high consumption of GSH. GPX4 inhibitor was found to augment the anticancer effect of platinum drugs in lung cancer BM, providing novel strategies for lung cancer patients with BM., Wnt/NR2F2/GPX4 promoted acquired chemo‐resistance by suppressing ferroptosis with high consumption of GSH and GPX4 inhibitor was found to enhance the anticancer effect of platinum drugs in lung cancer BM, providing novel strategies for lung cancer patients with BM

High levels (> 100 ug/L) of arsenic are known to cause lung cancer; however, whether low (≤ 10 ug/L) and medium (10 to 100 ug/L) doses of arsenic will cause lung cancer or other lung diseases, and whether arsenic has dose-dependent or threshold effects, remains unknown. Summarizing the results of previous studies, we infer that low- and medium-concentration arsenic cause lung diseases in a dose-dependent manner. Arsenic trioxide (ATO) is recognized as a chemotherapeutic drug for acute promyelocytic leukemia (APL), also having a significant effect on lung cancer. The anti-lung cancer mechanisms of ATO include inhibition of proliferation, promotion of apoptosis, anti-angiogenesis, and inhibition of tumor metastasis. In this review, we summarized the role of arsenic in lung disease from both pathogenic and therapeutic perspectives. Understanding the paradoxical effects of arsenic in the lungs may provide some ideas for further research on the occurrence and treatment of lung diseases.

Organic-inorganic hybrid perovskite solar cells (PSCs) have attracted tremendous attention recently because of their excellent photovoltaic performance. High power conversion efficiency (PCE) and long-term stability of PSCs mainly rely on high crystalline quality of perovskite film, good interface contact between functional layers and matching energy level alignment, which can be achieved by crystal growth regulation and interface engineering. Here, we demonstrate a high-performance planar heterojunction PSCs with PCBM/N2200 as double electron transport layers (ETLs). The N2200-based PSCs exhibit an average PCE of 15.50%, which obviously surpass the average PCE of 14.18% of conventional PSCs with only PCBM as ETLs. In comparison with the conventional PSCs, the PCBM/N2200 double ETLs increase built-in potential of devices and decrease interfacial energy barrier of MAPbI3/PCBM and then result in higher Voc. Moreover, non-fullerene material N2200 can efficiently inhibit the aggregation of PC61BM, promote perovskite surface grain growth and passivate perovskite interface defect. All these are beneficial for electron transfer and extraction, and thereby increase the short-circuit current (Jsc) and the Fill Factor (FF) of N2200 PSCs. In addition, N2200 obviously improve the air- and illumination-stability of PSCs. These results could stem from the interaction between PbI2 as Lewis acid and N2200 as Lewis base. This work indicate that N2200/PC61BM as double ETL is an effective way to get high photovoltaic performance for the inverted planar heterojunction PSCs.

Aims: The purposes of this study are (1) to understand the current employment situation of master's graduates in Public Health and Preventive Medicine (PHPM) and (2) to provide evidence for career guidance and training of competent PHPM personnel.Methods: The master's graduates of the School of Public Health from the years 2014–2018 who majored in PHPM were chosen as research subjects. Questionnaires were distributed, and completed questionnaires were collected. The employment situation and characteristics of these graduates were analyzed based on the questionnaire data.Results: The employment rate of these graduates was 95.45%. They were employed mainly in hospitals, followed by colleges and centers for disease control and prevention. The initial salaries were low. Graduates whose jobs barely or not at all matched their areas of specialization were 23.64 or 6.36%, respectively. Nevertheless, the percentage of students who had remained with their jobs since graduation was 82.73%. A total of 40% of the graduates were neutral about or dissatisfied with their jobs. Furthermore, 29% of them claimed that they were undervalued by their employers. Last, but not least, graduates were encouraged to gain experience in creativity, organizational or management skills, social networking experience, and interpersonal and professional skills.Conclusion: Overall, the employment status of master's graduates in PHPM is good. Problems such as low initial salaries, jobs not matching graduates' areas of specialization, and feelings of being undervalued by employers were observed. It is necessary to improve employment outcomes by revising training models, formulating employment policies, and implementing training efforts.

Mitochondrial disease (MD) is a rare mitochondrial respiratory chain disorder with a high mortality and extremely challenging to treat. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of MD, the role of metabolomics in MD, particularly of lipidomics remains unclear. This study was undertaken to identify potential lipid biomarkers of MD. An untargeted lipidomic approach was used to compare the plasma lipid metabolites in 20 MD patients and 20 controls through Liquid Chromatography coupled to Mass Spectrometry. Volcano plot analysis was performed to identify the different metabolites. Receiver operating characteristic (ROC) curves were constructed and the area under the ROC curves (AUC) was calculated to determine the potentially sensitive and specific biomarkers. A total of 41 lipids were significantly different in MD patients and controls. ROC curve analysis showed the top 5 AUC values of lipids (phosphatidylinositols 38:6, lysoPC 20:0, 19:0, 18:0, 17:0) are more than 0.99. Multivariate ROC curve based exploratory analysis showed the AUC of combination of top 5 lipids is 1, indicating they may be potentially sensitive and specific biomarkers for MD. We propose combination of these lipid species may be more valuable in predicting the development and progression of MD, and this will have important implications for the diagnosis and treatment of MD.

Background Migraine is a prevalent, disabling type of primary headache disorder associated with a high socioeconomic burden. The clinical management of migraine is challenging. This study was to identify potential serum lipidomic biomarkers of migraine. Methods The serum lipidomic profile of migraine sufferers was compared with healthy individuals using Liquid Chromatography coupled to Mass Spectrometry (LC-MS). Volcano plot analysis by Student’s t-test was performed to identify the differential metabolites. Receiver operating characteristic (ROC) curves were constructed and the area under ROC curves (AUC) was calculated to evaluate whether the metabolites could be efficiently exploited for constructing a sensitive biomarker of migraine. Results A total of 29 serum metabolites from 4 classes of lipids including acylcarnitines, non-alpha-hydroxy-sphingosine ceramides (Cer_NSs), lysophosphatidylcholines (lysoPCs) and lysophosphatidylethanolamines (lysoPEs) were significantly different in migraine patients and controls. Of note, Cer_NSs were significantly elevated and lysoPEs were significantly decreased in migraine patients. LysoPE 18:1, lysoPE 18:2 and lysoPE 22:5 were found to be decreased in both positive and negative ion mode. Moreover, except for lysoPC 20:0, other lysoPCs were decreased in migraine patients. ROC curve analysis indicated that lysoPC 16:0 and lysoPC 20:0 are potential sensitive and specific biomarkers for migraine. Conclusion LysoPC 16:0 and lysoPC 20:0 may be potential biomarkers for migraine. We suggest therapeutic management of these metabolites may be helpful in the prevention and treatment of migraine. Electronic supplementary material The online version of this article (10.1186/s12944-018-0665-0) contains supplementary material, which is available to authorized users.

Migraine is a highly disabling primary headache associated with a high socioeconomic burden and a generally high prevalence. The clinical management of migraine remains a challenge. This study was undertaken to identify potential serum biomarkers of migraine. Using Liquid Chromatography coupled to Mass Spectrometry (LC-MS), the metabolomic profile of migraine was compared with healthy individuals. Principal component analysis (PCA) and Orthogonal partial least squares-discriminant analysis (orthoPLS-DA) showed the metabolomic profile of migraine is distinguishable from controls. Volcano plot analysis identified 10 serum metabolites significantly decreased during migraine. One of these was serotonin, and the other 9 were amino acids. Pathway analysis and enrichment analysis showed tryptophan metabolism (serotonin metabolism), arginine and proline metabolism, and aminoacyl-tRNA biosynthesis are the three most prominently altered pathways in migraine. ROC curve analysis indicated Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine are potential sensitive and specific biomarkers for migraine. Our results show Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine may be as specific or more specific for migraine than serotonin which is the traditional biomarker of migraine. We propose that therapeutic manipulation of these metabolites or metabolic pathways may be helpful in the prevention and treatment of migraine.

Light-driven phase change materials (PCMs) have received significant attention due to their capacity to convert visible light into thermal energy, storing it as latent heat. However, continuous photo-thermal conversion can cause the PCMs to reach high thermal equilibrium temperatures after phase transition. In our study, a novel light-driven phase change material system with temperature-control properties was constructed using a thermochromic compound. Thermochromic phase change materials (TC-PCMs) were prepared by introducing 2-anilino-6-dibutylamino-3-methylfluoran (ODB-2) and bisphenol A (BPA) into 1-hexadecanol (1-HD) in various proportions. Photo-thermal conversion performance was investigated with solar radiation (low power of 0.09 W/cm2) and a xenon lamp (at a high power of 0.14 W/cm2). The TC-PCMs showed a low equilibrium temperature due to variations in absorbance. Specifically, the temperature of TC-PCM180 (ODB-2, bisphenol A and 1-HD ratio 1:2:180) could stabilize at 54 &deg, C approximately. TC-PCMs exhibited reversibility and repeatability after 20 irradiation and cooling cycles.

Protein 4.1N (4.1N) is a member of the protein 4.1 family and is essential for the regulation of cell adhesion, motility and signaling. Previous studies have suggested that 4.1N may serve a tumor suppressor role. However, the molecular mechanisms remain unclear. In the current study, the role of 4.1N in the downregulation of hypoxia‑induced factor 1α (HIF‑1α) under hypoxic conditions and therefore the suppression of hypoxia induced epithelial‑mesenchymal transition (EMT) was investigated. The data were obtained from overexpressed and knockdown 4.1N epithelial ovarian cancer (EOC) cell lines. It was identified that 4.1N was capable of regulating the sub‑cellular localization and expression levels of HIF‑1α, by which 4.1N served a dominant role in the suppression of hypoxia‑induced EMT and associated genes. Collectively, the data of the current study identified 4.1N as an inhibitor of hypoxia‑induced tumor progression in EOC cells and highlighted its potential role in EOC therapy.

Aims Our aim was to analyse the utility of the algorithm combining PAX8 with clinicopathological characteristics (tumour size, laterality and patient age) in differentiating primary ovarian mucinous tumours (POMTs) from extragenital metastatic mucinous carcinomas involving the ovary (eMOMCs). Methods and results Immunohistochemical staining for PAX8 was performed on formalin fixed, paraffin embedded tissues from 47 POMTs, 18 eMOMCs and 70 extragenital primary mucinous carcinomas (ePMCs) using anti-PAX8 rabbit polyclonal antibody (pAb) and anti-PAX8 rabbit monoclonal antibody (mAb). PAX8 (pAb) positive signals were found in 3/18 eMOMCs and in 32/70 ePMCs. PAX8 (mAb) demonstrated superior specificity, with 0% positivity in both eMOMCs and ePMCs, but unfavourable sensitivity, with 60.9% in ovarian mucinous borderline tumours and 45.8% in POMCs. Although PAX8 (mAb) immunostaining status (66.2%), tumour size (75.4%) and laterality (84.6%) demonstrated unsatisfactory accuracy when they were evaluated individually in differentiating POMTs from eMOMCs, a combination of PAX8 (mAb) immunostaining status, tumour size and laterality markedly increased accuracy (86.2%), with a satisfactory Youden Index (63.7%). Conclusions PAX8 (mAb) was a specific marker in differentiating POMTs from eMOMCs. As a simple, convenient and high performance to price ratio algorithm, a combination of PAX8 (mAb) immunostaining with tumour size and laterality will improve the diagnostic criteria of ovarian mucinous metastasis.

Kindlin-2 functions in the maintenance of homeostasis and in human diseases. This study investigated the interrelationship between Kindlin-2 expression in tissues and the corresponding germ layers from which these tissues originated. Kindlin-2 expression was examined in normal adult human organs and human cancer tissues by immunohistochemical analyses. Analysis of Kindlin-2 mRNA levels in adult human organs in the Oncomine dataset revealed Kindlin-2 is highly expressed in mesoderm-derived organs. However, Kindlin-2 was negative or weakly expressed in endoderm/ectoderm-derived organs. Interestingly, the abnormal expression of Kindlin-2 was observed in a variety of human cancers. In agreement with its expression profile in humans, Kindlin-2 was also highly expressed in mesoderm-derived organs in mouse embryos with the exception of strong Kindlin-2 expression in ectoderm-derived spinal cord and ganglia, tissues that are highly mobile during embryonic development. Importantly, we demonstrated the expression level of Kindlin-2 in adult organs correlated with their embryonic dermal origins and deregulation of Kindlin-2 in tissues is associated with tumor progression. This finding will help us understand the dual role of Kindlin-2 in the regulation of tumor progression and embryonic development.

BACKGROUND Nitrobenzene (NB) is a persistent environmental pollutant difficult to degrade. The aim of this study was to accelerate the reduction of NB by immobilization of nanoscale zero-valent iron (NZVI) on an organobentonite (CTMA-Bent). RESULTS Batch experiments indicated that NB was almost completely reduced by the immobilized iron sample (NZVI/CTMA-Bent), with aniline as the dominant reduction product. While only 60% of NB was reduced by the bare NZVI, and aniline accounted for only half of the NB reduced. Kinetic studies confirmed that the reaction of NB with NZVI was accelerated through CTMA-Bent adsorption. XPS investigations suggested that the improved recycling of the NZVI/CTMA-Bent composite is related to less ferric (hydr)oxides formed during the reaction. CONCLUSION Immobilization of NZVI on the organobentonite CTMA-Bent proved to be an effective method for quick and complete conversion of NB to biodegradable aniline. This novel method to remove recalcitrant organic pollutants may promote the industrial application of NZVI technique in environmental remediation. © 2013 Society of Chemical Industry

Nowadays Collaborative Filtering is the most popular and common algorithm in recommender system, and it devotes to study how to improve the recommendation accuracy to satisfy people's demand according to people's past interests. However, recent study shows that novelty and diversity in recommendations have gained more attention and play an important role in recommender system. In this study, an enhanced collaborative filtering method is proposed, which combined both of the User-Based and Item-Based collaborative filtering to improve diversity. This model divides the two algorithms into different weights, and uses different diversity methods to generate the recommendation lists. Then recommender system provides each user the diversity recommendations under the guarantee of accuracy. Experiments on 100K Movielens have proved that our scheme is effective, which has little increment in accuracy and much more increment in individual diversity and aggregate diversity.

Protein 4.1N (4.1N) is a member of the Protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. In this study, we evaluated the expression of 4.1N protein and its potential roles in epithelial ovarian cancer (EOC) tumorigenesis and progression.4.1N protein expression was investigated in a total of 280 samples including 74 normal tissues, 35 benign, 30 borderline and 141 malignant epithelial ovarian tumors by immunohistochemistry. Correlation between 4.1N expression levels and clinicopathologic features was statistically analyzed. The expression of 4.1N in EOC cell lines was examined by western blotting.Immunohistochemistry analysis revealed that, although there was no loss of 4.1N expression in normal tissues and benign tumors, absence of Protein 4.1N was significantly more common in EOCs (44.0%) than in borderline tumors (3.3%) (p0.001). Furthermore, loss or decreased expression of 4.1N protein expression was correlated with malignant potential of the tumors (14.3% in benign tumors, 56.7% in borderline tumors and 92.9% in malignancy) (p0.001). In EOC samples, loss of 4.1N protein was significantly associated with advanced-stage (p=0.004), ascites (p=0.009), omental metastasis (p=0.018), suboptimal debulking (p=0.024), poorly histological differentiation (p=0.009), high-grade serous carcinoma (p=0.001), short progression-free-survival (p=0.018) and poor chemosensitivity to first-line chemotherapy (p=0.029). Moreover, western blotting analysis revealed that expression of 4.1N protein was lost in 4/8 (50%) EOC cell lines.4.1N protein expression level was significantly decreased during malignant transformation of epithelial ovarian tumors and that loss of 4.1N expression was closely correlated to poorly differentiated and biologically aggressive EOCs.

Cervical metaplastic carcinomas, including most cases of malignant mixed mullerian tumours (MMMTs), or carcinosarcomas, and sarcomatoid carcinomas, are rare biphasic neoplasms.1 ,2 Recent research suggests that both elements share a common epithelial origin, with sarcomatous/sarcomatoid component derived from a metaplastic process.3 We report a series of three cases, one cervical MMMT and two cervical sarcomatoid carcinomas, with their clinicopathological features, immunohistochemical profile and human papillomavirus (HPV) infection status and genotype. Materials and methods are provided in online supplementary appendix 1. ### Clinical history and sequence of events Case 1 was a 45-year-old woman, gravida 2, para 1 (G2P1), who presented with abnormal vaginal bleeding for 6 months. On pelvic examination, a cauliflower-like cervical mass was found. Biopsy and subsequent investigations showed stage IB2 homologous MMMT. The patient underwent neoadjuvant chemotherapy. Then total abdominal hysterectomy, bilateral salpingo-oophorectomy (TAH-BSO) with pelvic and para-aortic lymphadenectomy was performed, followed by concurrent chemoradiotherapy. Six months later, metastatic lesions were found in the vaginal stump, bladder and rectum. Because of poor response to subsequent chemoradiotherapy, she gave up further treatment. Case 2 was a 38-year-old woman, G2P1, who presented with abnormal vaginal bleeding for 3 years. Pelvic examination showed a cervical exophytic mass. Biopsy showed squamous cell carcinoma. The patient then underwent TAH-BSO with pelvic lymphadenectomy. Final pathology confirmed stage IB1 cervical sarcomatoid carcinoma. The patient then received radiochemotherapy and remained disease-free for >5 years. Case 3 was a 61-year-old woman, G2P1, who presented for abnormal pap smear. Pelvic examination …

Lactic acid bacteria that can produce alpha-galactosidase are a promising solution for improving the nutritional value of soy-derived products. For their commercial use in the manufacturing process, it is essential to understand the catabolic mechanisms that facilitate their growth and performance. In this study, we used comparative proteomic analysis to compare catabolism in an engineered isolate of Lactobacillus plantarum P-8 with enhanced raffinose metabolic capacity, with the parent (or wild-type) isolate from which it was derived. When growing on semi-defined medium with raffinose, a total of one hundred and twenty-five proteins were significantly up-regulated (>1.5 fold, P P de novo fatty acid biosynthesis and modification of existing lipid membrane phospholipid acyl chains. Interestingly, aspartate and glutamate metabolism was associated with this acid response. Higher intracellular aspartate and glutamate levels in the engineered isolate compared with the parent isolate were confirmed by further chemical analysis. Our study will underpin the future use of this engineered isolate in the manufacture of soymilk products.

In order to explore whether NF-κB activation correlates to the prognosis, chemoresistance, and sex hormone receptors status in ovarian serous carcinoma, we analyzed the expression of NF-κB, ER, and PR by immunohistochemistry in 72 cases of ovarian serous carcinoma, investigated the association among these markers, and evaluated their relations to clinicopathologic factors and prognosis. The positive rates were 88.9% for NF-κB cytoplasmic expression, 45.8% for NF-κB nuclear expression, 41.7% for ER, and 29.2% for PR. NF-κB nuclear expression was positively correlated with the 4th edition WHO grade (P=0.045) and tumor stage (P=0.001). NF-κB cytoplasmic expression was associated with preoperative serum CA125 level (P=0.015) and ascites (P=0.042). Neither cytoplasmic nor nuclear staining of NF-κB showed any association with survival. PR expression was correlated with tumor stage (P=0.023) and omental metastasis (P=0.022). Omental metastasis occurred more frequently in ER-/PR- tumors (P=0.009). No correlation between NF-κB expression and ER, PR expression was observed. In conclusion, in ovarian serous carcinoma, NF-κB nuclear expression correlated with the 4th edition WHO grade and PR was a favorable prognostic factor for ovarian serous carcinoma.

G protein plays an important role in signaling pathways and is involved in various signal transduction systems in plant. A full-length cDNA encoding a putative G protein γ subunit (Gγ), designated as BnGG2, was isolated from Brassica napus L. BnGG2 is predicted to encode a precursor protein of 100 amino acid residues. The expression of BnGG2 in different B. napus tissues and developmental stages was analyzed by using real-time PCR. The results showed that BnGG2 expression level was high at the 7-day-old seedling stage, the bolting stage, and the fruiting stage. Moreover, BnGG2 was analyzed under four different plant hormones. All of the four tested hormones, abscisic acid (ABA), gibberellins acid 3 (GA3), brassinosteroid (BR) and indole-3-acetic acid (IAA), triggered an induction of BnGG2 expression at different hormone concentrations. The expression of BnGG2 was significantly induced by the high concentrations of ABA, BR, and IAA. The expression of BnGG2 was also induced by low GA3 concentrations and inhibited by high GA3 concentrations. In addition, BnGG2 was responsive to different abiotic stresses. The BnGG2 was up-regulated in salt and drought stress and down-regulated in heat and cold stress. These results suggested that BnGG2 plays an important role in plant hormone signaling pathways and may be also involved in plant defense systems against environmental stresses in B. napus.

G protein plays an important role in signaling pathways and is involved in various signal transduction systems in plant. A full-length cDNA encoding a putative G protein γ subunit (Gγ), designated as BnGG2, was isolated from Brassica napus L. BnGG2 is predicted to encode a precursor protein of 100 amino acid residues. The expression of BnGG2 in different B. napus tissues and developmental stages was analyzed by using real-time PCR. The results showed that BnGG2 expression level was high at the 7-day-old seedling stage, the bolting stage, and the fruiting stage. Moreover, BnGG2 was analyzed under four different plant hormones. All of the four tested hormones, abscisic acid (ABA), gibberellins acid 3 (GA3), brassinosteroid (BR) and indole-3-acetic acid (IAA), triggered an induction of BnGG2 expression at different hormone concentrations. The expression of BnGG2 was significantly induced by the high concentrations of ABA, BR, and IAA. The expression of BnGG2 was also induced by low GA3 concentrations and inhibited by high GA3 concentrations. In addition, BnGG2 was responsive to different abiotic stresses. The BnGG2 was up-regulated in salt and drought stress and down-regulated in heat and cold stress. These results suggested that BnGG2 plays an important role in plant hormone signaling pathways and may be also involved in plant defense systems against environmental stresses in B. napus.

Aim Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that preferentially induces apoptosis in cancer cells while exhibiting little or no toxicity in normal cells. In this study, we evaluated the clinicopathological significance of TRAIL signalling members’ expression profiles in cervical squamous cell carcinoma (CSCC). Methods TRAIL, DR5, caspase-8 and cellular FLICE-inhibitory protein (c-FLIP) protein expression was investigated in 72 stage IA2-IIIA CSCC patients using immunohistochemistry. Correlation between protein expression and clinicopathological features, radiotherapy response and survival was statistically analysed. Results Positive c-FLIP expression was an independent negative indicator for disease-free survival (DFS) (p=0.015) in multivariate Cox regression analysis. The DR5 nuclear positive group (p=0.069 by log rank test) showed some advantage of radiotherapy for overall survival (OS) compared with the DR5 nuclear negative cohort (p=0.568 by log rank test). In addition, loss of TRAIL expression was associated with worse differentiation (p=0.004), while absence of caspase-8 staining was more frequently observed in cases with lymphovascular invasion (p=0.035). Conclusions High c-FLIP expression is shown to be an independent prognostic variable, DR5 nuclear expression may serve as a predictive biomarker for radiotherapy, and TRAIL as well as caspase-8 loss may be associated with malignant progression.

Kindlin-2 has been known to promote most cancer progression through regulation of multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2 was identified in serous epithelial ovarian cancer progression, which sharply contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic low expression of Kindlin-2 was found in the tumor tissues of serous epithelial ovarian cancer, especially in the high-grade serous epithelial ovarian cancer. Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression correlated with higher tumor grade and older patients. Intriguingly, decreased Kindlin-2 expression predicts poor overall and progression-free survivals in serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a mesenchymal to epithelial transition in serous epithelial ovarian cancer cells, at least in part, by up-regulation of estrogen receptor α which was recruited to the promoter of E-cadherin and thereby enhanced the transcription of E-cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients.

Hyperandrogenemia is the leading defect in patients with polycystic ovary syndrome (PCOS) and considered to be involved in the ovulation dysfunction of PCOS. During the process of ovulation, granulosa cells (GCs) undergo epithelial–mesenchymal transition (EMT), and integrin-interacting protein kindlin 2 is a well-known regulator in EMT. Therefore, our objective here was to compare the expression levels of kindlin 2 in luteinized GCs between patients with PCOS and control women and the relationship between kindlin 2 and PCOS pathogenesis. In this study, kindlin 2 expression was significantly increased in luteinized GCs from patients with PCOS, and kindlin 2 could be induced by testosterone both in vitro and in vivo. Meanwhile, kindlin 2 was positively correlated with androgen receptor (AR) in PCOS GCs. Taken together, kindlin 2 may play a role in luteinized GCs, especially in the case of excess androgen. Further studies are required to assess the specific role of kindlin 2 in follicular development and PCOS pathogenesis.

The stress singularity near the Mode Ⅲ interface end of isotropic and orthotropic bi-material was studied. Based on arbitrary angle boundary conditions, by solving a class of harmonic equations we discussed the root of the characteristic equation with the help of complex function method of material fracture. The expression and variation of the singularity index of the tip of interfacial crack and the symmetric interface end is obtained as well. The analytical expressions of the stress and displacements fields and the stress intensity factor around the interfacial crack are derived.

G protein plays an important role in signal pathways and involved in various signal transduction systems in plant. A full-length cDNA encoding a putative G protein α subunit (Gα), designated as BnGA1, was isolated from Brassica napus. The expression of BnGA1 in different B. napus tissues and developmental stags was analyzed using real-time PCR. The results showed that BnGA1 expressed was high in root, cotyledon and shoot apex. Stage expression pattern analysis revealed that BnGA1 expressed strongly at the 7th day, the bolting stage and fruiting stage. In addition, the expression of BnGA1 was analyzed under different concentrations of four plant hormones. The expression of BnGA1 was significantly induced by the high concentrations of abscisic acid (ABA) and brassinosteroid (BR). The expression of BnGA1 was also induced by low gibberellins acid 3 (GA(3)) concentrations and higher GA(3) concentrations inhibit the expression of BnGA1. However, the expression of BnGA1 did not significantly regulated by exogenous indole-3-acetic acid (IAA). Moreover, the expression of BnGA1 under different abiotic stresses was analyzed at different time points. The BnGA1 was up-regulated in salt and drought stress and down-regulated in heat and cold stress. These expression results suggested that BnGA1 play an important role in plant hormones signal pathways and BnGA1 may be involved in plant defense system against environmental stresses in B. napus.