Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

N6-Methyladenosine-Modified KREMEN2 Promotes Tumorigenesis and Malignant Progression of High-Grade Serous Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer by far. Herein, clinical HGSOC samples had higher N6-methyladenosine (m6A) modification than normal ovarian tissue, and its dysregulation had been reported to drive aberrant transcription and translation programs. However, Kringle-containing transmembrane protein 2 (KREMEN2) and its m6A modification have not been fully elucidated in HGSOC. In this study, the data from the high-throughput messenger RNA (mRNA) sequencing of clinical samples were processed using the weighted correlation network analysis and functional enrichment analysis. Results revealed that KREMEN2 was a driver gene in the tumorigenesis of HGSOC and a potential target of m6A demethylase fat-mass and obesity-associated protein (FTO). KREMEN2 and FTO levels were upregulated and downregulated, respectively, and correlation analysis showed a significant negative correlation in HGSOC samples. Importantly, upregulated KREMEN2 was remarkably associated with lymph node metastasis, distant metastasis, peritoneal metastasis, and high International Federation of Gynecology and Obstetrics stage (Ⅲ/Ⅳ), independent of the age of patients. KREMEN2 promoted the growth of HGSOC in vitro and in vivo, which was dependent on FTO. The methylated RNA immunoprecipitation qPCR and RNA immunoprecipitation assays were performed to verify the m6A level and sites of KREMEN2. FTO overexpression significantly decreased m6A modification in the 3' and 5' untranslated regions of KREMEN2 mRNA and downregulated its expression. In addition, we found that FTO-mediated m6A modification of KREMEN2 mRNA was recognized and stabilized by the m6A reader IGF2BP1 rather than by IGF2BP2 or IGF2BP3. This study highlights the m6A modification of KREMEN2 and extends the importance of RNA epigenetics in HGSOC.

Deterrence through punishment can resolve collective risk dilemmas in carbon emission games.

Collective risk social dilemmas are at the heart of the most pressing global challenges we are facing today, including climate change mitigation and the overuse of natural resources. Previous research has framed this problem as a public goods game (PGG), where a dilemma arises between short-term interests and long-term sustainability. In the PGG, subjects are placed in groups and asked to choose between cooperation and defection, while keeping in mind their personal interests as well as the commons. Here, we explore how and to what extent the costly punishment of defectors is successful in enforcing cooperation by means of human experiments. We show that an apparent irrational underestimation of the risk of being punished plays an important role, and that for sufficiently high punishment fines, this vanishes and the threat of deterrence suffices to preserve the commons. Interestingly, however, we find that high fines not only avert freeriders, but they also demotivate some of the most generous altruists. As a consequence, the tragedy of the commons is predominantly averted due to cooperators that contribute only their "fair share" to the common pool. We also find that larger groups require larger fines for the deterrence of punishment to have the desired prosocial effect.

Quality evaluation of Huocao based on UPLC fingerprint and multi-component content determination / 中国中药杂志

Huocao(a traditional Chinese herbal medicine) moxibustion is a characteristic technology in Yi medicine suitable for cold-dampness diseases. Huocao, as the moxibustion material, is confusedly used in clinical practice and little is known about its quality control. In this study, UPLC method was used to establish the chemical fingerprint of non-volatile components in Huocao, and the contents of eight phenolic acids such as chlorogenic acid were determined. Multivariate statistical analysis was performed to obtain the indicator components of Huocao for quality evaluation, and thus a comprehensive evaluation system for the quality of Huocao was built. The UPLC fingerprints of 49 batches of Huocao were established, and there were 20 common peaks, of which eight phenolic acids including neochlorogenic acid and chlorogenic acid were identified. Except for three batches of Huocao, the similarity of the other 46 batches was higher than 0.89, suggesting that the established fingerprint method could be used for quality control of the medicinal herb. The correlation coefficient between entropy weight score of the eight phenolic acids and comprehensive fingerprint score in Huocao was 0.875(P<0.01), which indicated that the eight phenolic acids could be used as indicator components for the quality evaluation of Huocao. Furthermore, in multivariate statistical analysis on the common peaks of fingerprint and the contents of the eight phenolic acids, chlorogenic acid, isochlorogenic acid A and isochlorogenic acid C were screened to be the indicator components. The results revealed that the proposed method achieved a simple and accurate quality control of Huocao based on UPLC fingerprint and multi-component content determination, which provided useful data for establishing the quality standard of Huocao.

Study on quality standard of Yi medicine Gynura japonica and quality evaluation of medicinal materials from different producing areas / 中国药房

OBJECTIVE To improve the quality standard of Yi medicine Gynura japonica， and to evaluate its quality. METHODS Using 15 batches of G. japonica from different producing areas as samples， the contents of water， total ash， acid- insoluble ash and water-soluble extract were determined according to the method stated in part Ⅳ of Chinese Pharmacopoeia （2020 edition）. The contents of total alkaloid （calculated by senecionine） was determined by UV spectrophotometry. The contents of senecionine and seneciphylline were determined by HPLC. Using above 7 indexes as evaluation indexes， cluster heat map analysis， principal component analysis （PCA） and entropy weight approximation ideal ranking （TOPSIS） were used to evaluate the quality of medicinal material comprehensively. RESULTS Among 15 batches of G. japonica， the moisture contents were 8.88%-12.60%， the total ash contents were 4.43%-11.02%， the acid-insoluble ash contents were 0.56%-3.45%， the water-soluble extract contents were 21.71%-53.91%， the total alkaloid contents （calculated by senecionine） were 0.15%-0.39%， and the contents of senecionine and seneciphylline were 0.01% -0.05% and 0.01%-0.06% respectively. According to the results of various indicators， it was preliminarily proposed that the water content in the sample of G. japonica should not exceed 13.00%， the total ash content should not exceed 11.50%， the acid-insoluble ash content should not exceed 3.70%， the water-soluble extract should not be less than 20.70%， the total alkaloid content should not be less than 0.15%， the contents of senecionine and seneciphylline should not be less than 0.01% both. The results of cluster heat map analysis showed that the 15 batches of samples could be divided into four categories； the results of PCA and TOPSIS showed that the samples with high-quality ranking were jsq-2， jsq-5， jsq-6 and jsq-10， and the samples with low-quality ranking were jsq-4， jsq-13 and jsq-14. CONCLUSIONS In this study， the quantitative analysis method of total alkaloids （calculated by senecionine）， senecionine and seneciphylline in G. japonica is established， and the limits of each index are preliminarily determined. Among 15 batches of samples， the qualities of medicinal material collected from Linza Village of Ganluo County of Liangshan Yi Autonomous Prefecture， Machangping Village of Luojishan Town of Puge County of Liangshan Yi Autonomous Prefecture and other places are better.

Main components from cultivated and wild Nardostachyos Radix et Rhizoma by LC-MS and GC-MS / 中国中药杂志

In this study, ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography-mass spectrometry(GC-MS) were combined with non-targeted metabonomic analysis based on multivariate statistics analysis, and the content of five indicative components in nardosinone was determined and compared by UPLC. The main chemical components of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma were comprehensively analyzed. The results of multivariate statistical analysis based on liquid chromatography-mass spectrometry(LC-MS) and GC-MS were consistent. G1 and G2 of the imitative wild cultivation group and G8-G19 of the wild group were clustered into category 1, while G7 of the wild group and G3-G6 of the imitative wild cultivation group were clustered into category 2. After removing the outlier data of G1, G2, and G7, G3-G6 of the imitative wild cultivation group were clustered into one category, and G8-G19 of the wild group were clustered into the other category. Twenty-six chemical components were identified according to the positive and negative ion modes detected by LC-MS. The content of five indicative components(VIP>1.5) was determined using UPLC, revealing that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, linarin, nardosinone, and total content in the imitative wild cultivation group were 1.85, 1.52, 1.26, 0.90, 2.93, and 2.56 times those in the wild group, respectively. OPLS-DA based on GC-MS obtained 10 diffe-rential peaks. Among them, the relative content of α-humulene and aristolene in the imitative wild cultivation group were extremely significantly(P<0.01) and significantly(P<0.05) higher than that in the wild group, while the relative content of 7 components such as 5,6-epoxy-3-hydroxy-7-megastigmen-9-one, γ-eudesmol, and juniper camphor and 12-isopropyl-1,5,9-trimethyl-4,8,13-cyclotetrade-catriene-1,3-diol was extremely significantly(P<0.01) and significantly(P<0.05) lower than that in the wild group, respectively. Therefore, the main chemical components of the imitative wild cultivation group and wild group were basically the same. However, the content of non-volatile components in the imitative wild cultivation group was higher than that in the wild group, and the content of some volatile components was opposite. This study provides scientific data for the comprehensive evaluation of the quality of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma.

UPLC fingerprint and indicator components of Boenninghausenia albiflora var. albiflora / 中国中药杂志

The fingerprint of Boenninghausenia albiflora var. albiflora was established by ultra performance liquid chromatography(UPLC), and the content of 12 active components including chlorogenic acid was determined. Multivariate statistical analysis was used to explore the indicator components of B. albiflora var. albiflora and a comprehensive evaluation system was created for the quality of B. albiflora var. albiflora. In this study, 33 batches of B. albiflora var. albiflora with different sources were collected and studied, and the UPLC fingerprint of B. albiflora var. albiflora was developed. There were 37 common peaks, of which 12 components were identified, and the content of these 12 components was measured. In combination of the common peaks and the content of chemical components, multivariate statistical analysis was performed, and the results showed that 6 components [daphnoretin, isoimperatorin, astragalin, imperatorin, neochlorogenic acid, and isoquercitrin(weight coefficient>0.1)] were selected as chemical markers for the quality of B. albiflora var. albiflora. Technique for order of preference by similarity to ideal solution(TOPSIS) analysis and chemometrics revealed that the quality of S32, S28 and S29 were superior, while that of S12, S7 and S16 were inferior. The quality evaluation method of B. albiflora var. albiflora constructed in this study was accurate and reliable, with simpleness and easiness to operate. It is suggested that the 6 above-mentioned active components could be used as indicator components for quality control of B. albiflora var. al-biflora. The samples were harvested during the flowering and fruiting period, which is from the beginning of July to the end of August.

Pre-diagnosis Dairy Product Intake and Ovarian Cancer Mortality: Results From the Ovarian Cancer Follow-Up Study (OOPS).

Background: Dairy product consumption is associated with ovarian cancer (OC) incidence. However, limited evidence is available on its influence on OC mortality. Methods: The association between pre-diagnostic dairy product intake and OC mortality was investigated in the OC follow-up study, which included a hospital-based cohort (n = 853) of women diagnosed with epithelial OC between 2015 and 2020. Pre-diagnosis diet information was collected using a validated food frequency questionnaire. Deaths were ascertained up to March 31, 2021 via death registry linkage. Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for the aforementioned association. Results: A total of 130 women died during the median follow-up of 37.2 months (interquartile: 24.7-50.2 months). Comparisons of highest to lowest tertile intake showed that pre-diagnosis dairy product use was associated with total OC mortality (HR = 2.03, 95% CI = 1.21-3.40, p trend = 0.06). In addition, short survival was separately associated with protein (HR = 2.09, 95% CI = 1.25-3.49, p trend < 0.05), fat (HR = 2.16, 95% CI = 1.30-3.61, p trend < 0.05), and calcium (HR = 2.03, 95% CI = 1.21-3.4, p trend = 0.06) from dairy intake. Similar positive magnitudes were observed for menopausal status, residual lesions, histological type, and body mass index, although not all of these factors showed statistical significance. Conclusion: Pre-diagnosis dairy product consumption, including protein, fat, and calcium from dairy intake, was associated with higher mortality among OC survivors.

LINC00115 promotes stemness and inhibits apoptosis of ovarian cancer stem cells by upregulating SOX9 and inhibiting the Wnt/ß-catenin pathway through competitively binding to microRNA-30a.

OBJECTIVE: Long non-coding RNAs (lncRNAs) and microRNAs (miRs) are differentially expressed in ovarian cancer (OC) cells and influence OC progression. This study intended to explore the underlying roles of LINC00115 and miR-30a in OC. METHODS: Gene Expression Omnibus database was used to find OC microarray datasets and bioinformatics analysis predicted the potential molecular mechanism of OC. OC stem cells (OCSCs) surface marker was isolated from human OC cell line and identified. CD133+ OCSCs were transfected with LINC00115, miR-30a and SOX9 alone or together to detect sphere-forming ability and apoptosis of OCSCs. Caspase-3 activity and DNA damage in cell supernatant were detected. The levels of CD44, NANOG, POU5F1, LINC00115, CD133, miR-30a and SOX9 were measured. Then sh-LNC00115-treated OCSCs were added with Wnt/ß-catenin activator SKL2001 to observe the changes of cell stemness and activity. Finally, animal models were established to evaluate the effect of LINC00115 on OCSC in vivo. RESULTS: LINC00115 and SOX9 were highly expressed in OC, while miR-30a was lowly expressed. After silencing LINC00115 or overexpressing miR-30a, the sphere-forming rate of CD133+ OCSC and levels of CD133, CD44, NANOG and POU5F1 decreased, while apoptotic rate, Caspase-3 activity and histone-related DNA damage increased. SOX9 reversed these trends. Additionally, LINC00115 could bind to miR-30a and miR-30a could target SOX9. SKL2001 partially reversed cell stemness and activity in sh-LNC00115-treated OCSCs. Finally, silencing LINC00115 could inhibit OCSCs growth in vivo. CONCLUSION: LINC00115 promoted stemness and inhibited apoptosis of OCSCs by upregulating SOX9 and in activating the Wnt/ß-catenin pathway through competitively binding to miR-30a.

Using machine learning to examine street green space types at a high spatial resolution: Application in Los Angeles County on socioeconomic disparities in exposure.

Background: Compared to commonly-used green space indicators from downward-facing satellite imagery, street view-based green space may capture different types of green space and represent how environments are perceived and experienced by people on the ground, which is important to elucidate the underlying mechanisms linking green space and health. Objectives: This study aimed to evaluate machine learning models that can classify the type of vegetation (i.e., tree, low-lying vegetation, grass) from street view images; and to investigate the associations between street green space and socioeconomic (SES) factors, in Los Angeles County, California. Methods: SES variables were obtained from the CalEnviroScreen3.0 dataset. Microsoft Bing Maps images in conjunction with deep learning were used to measure total and types of street view green space, which were compared to normalized difference vegetation index (NDVI) as commonly-used satellite-based green space measure. Generalized linear mixed model was used to examine associations between green space and census tract SES, adjusting for population density and rural/urban status. Results: The accuracy of the deep learning model was high with 92.5% mean intersection over union. NDVI were moderately correlated with total street view-based green space and tree, and weakly correlated with low-lying vegetation and grass. Total and three types of green space showed significant negative associations with neighborhood SES. The percentage of total green space decreased by 2.62 [95% confidence interval (CI): -3.02, -2.21, p < 0.001] with each interquartile range increase in CalEnviroScreen3.0 score. Disadvantaged communities contained approximately 5% less average street green space than other communities. Conclusion: Street view imagery coupled with deep learning approach can accurately and efficiently measure eye-level street green space and distinguish vegetation types. In Los Angeles County, disadvantaged communities had substantively less street green space. Governments and urban planners need to consider the type and visibility of street green space from pedestrian's perspective.

Associations between green space and preterm birth: Windows of susceptibility and interaction with air pollution.

BACKGROUND: Recent studies have reported inconsistent associations between maternal residential green space and preterm birth (PTB, born < 37 completed gestational weeks). In addition, windows of susceptibility during pregnancy have not been explored and potential interactions of green space with air pollution exposures during pregnancy are still unclear. OBJECTIVES: To evaluate the relationships between green space and PTB, identify windows of susceptibility, and explore potential interactions between green space and air pollution. METHODS: Birth certificate records for all births in California (2001-2008) were obtained. The Normalized Difference Vegetation Index (NDVI) was used to characterized green space exposure. Gestational age was treated as a time-to-event outcome; Cox proportional hazard models were applied to estimate the association between green space exposure and PTB, moderately PTB (MPTB, gestational age < 35 weeks), and very PTB (VPTB, gestational age < 30 weeks), after controlling for maternal age, race/ethnicity, education, and median household income. Month-specific green space exposure was used to identify potential windows of susceptibility. Potential interactions between green space and air pollution [fine particulate matter < 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3)] were examined on both additive and multiplicative scales. RESULTS: In total, 3,753,799 eligible births were identified, including 341,123 (9.09%) PTBs, 124,631 (3.32%) MPTBs, and 22,313 (0.59%) VPTBs. A reduced risk of PTB was associated with increases in residential NDVI exposure in 250 m, 500 m, 1000 m, and 2000 m buffers. In the 2000 m buffer, the association was strongest for VPTB [adjusted hazard ratio (HR) per interquartile range increase in NDVI: 0.959, 95% confidence interval (CI): 0.942-0.976)], followed by MPTB (HR = 0.970, 95% CI: 0.962-0.978) and overall PTB (HR = 0.972, 95% CI: 0.966-0.978). For PTB, green space during the 3rd - 5th gestational months had stronger associations than those in the other time periods, especially during the 4th gestational month (NDVI 2000 m: HR = 0.970, 95% CI: 0.965-0.975). We identified consistent positive additive and multiplicative interactions between decreasing green space and higher air pollution. CONCLUSION: This large study found that maternal exposure to residential green space was associated with decreased risk of PTB, MPTB, and VPTB, especially in the second trimester. There is a synergistic effect between low green space and high air pollution levels on PTB, indicating that increasing exposure to green space may be more beneficial for women with higher air pollution exposures during pregnancy.

Tetrandrine Reverses Paclitaxel Resistance in Human Ovarian Cancer via Inducing Apoptosis, Cell Cycle Arrest Through ß-Catenin Pathway.

BACKGROUND: Paclitaxel (PTX) resistance is a great obstacle for the treatment of ovarian cancer. A previous study indicated that tetrandrine (TET) could induce the apoptosis of ovarian cancer cells. This study aimed to explore the effect of TET in combination with PTX on PTX resistance in ovarian cancer cells. MATERIALS AND METHODS: CCK-8 assay, flow cytometry and wound healing assays were used to detect the proliferation, apoptosis and migration of PTX-resistant SKOV3 cells (SKOV3/PTX). The expressions of Bax, Bcl-2, cleaved caspase 3, ß-catenin, c-Myc, cyclin D1 and p21 in SKOV3/PTX cells were detected with Western blot. In vivo animal study was performed finally. RESULTS: In this study, the inhibitory effects of PTX on the proliferation and migration of SKOV3/PTX cells were markedly enhanced by TET. In addition, PTX-induced apoptosis in SKOV3/PTX cells was significantly enhanced by the treatment of TET via upregulating the levels of Bax and cleaved caspase 3, and downregulating the expression of Bcl-2. Moreover, combination of TET and PTX obviously induced cell cycle arrest in SKOV3/PTX cells via increasing the level of p21 and decreasing the levels of c-Myc and Cyclin D1. Meanwhile, combination of TET with PTX significantly decreased the expression of ß-catenin in SKOV3/PTX cells. In vivo experiments further confirmed that TET enhanced the anti-tumor effect of PTX in SKOV3/PTX xenograft model. CONCLUSION: We found that TET could enhance the sensitivity of SKOV3/PTX cells to PTX via inhibiting the ß-catenin/c-Myc/Cyclin D1 signaling pathway. Therefore, PTX combined with TET might be considered as a potential approach for the treatment of PTX-resistant ovarian cancer.

Ultrasonographic Imaging Features of Female Urethral and Peri-urethral Masses: A Retrospective Study of 95 Patients.

The aim of this study was to assess the imaging features of urethral and peri-urethral masses on transvaginal or transperineal ultrasound (US) in a cohort of 95 women. In this retrospective study, medical records of 95 female patients with 98 asymptomatic or symptomatic urethral and peri-urethral masses were retrospectively reviewed. Data regarding patient demographic characteristics, symptoms, signs, imaging features on 2-D and 3-D transvaginal or transperineal US, diagnostic tests and physical and intra-operative findings were extracted. The US imaging features and clinicopathologic characteristics of each urethral or peri-urethral mass were compared. On ultrasound, 39 masses (in 39 patients) were diagnosed as urethral diverticula, which manifested mostly as complex cystic masses (24/39, 61.5%); 35 masses (in 33 patients) were diagnosed as para-urethral cysts, which manifested mostly as simple cystic masses (19/35, 54.3%); 13 hypo-echoic solid masses (in 12 patients) exhibiting blood flow signals on color Doppler imaging were diagnosed as urethral leiomyomas; hypo-echoic or heterogeneous solid masses (in 8 patients) exhibiting blood flow signals on color Doppler imaging were diagnosed as urethral caruncles, including one complicated by malignant transformation; solid masses with mixed echogenicity (in 2 patients) exhibiting blood flow signals on color Doppler imaging were diagnosed as urethral squamous cell carcinoma or adenocarcinoma, and a hypoechoic solid mass (in one patient) with blood-flow signals on color Doppler imaging was diagnosed as urethral condyloma associated with human papillomavirus infection. This study confirmed transvaginal or transperineal 2-D and 3-D ultrasonography to be a valid, non-invasive, cost-effective diagnostic modality for the differential diagnosis of urethral and periurethral masses.

Robust RGB-D Face Recognition Using Attribute-Aware Loss.

Existing convolutional neural network (CNN) based face recognition algorithms typically learn a discriminative feature mapping, using a loss function that enforces separation of features from different classes and/or aggregation of features within the same class. However, they may suffer from bias in the training data such as uneven sampling density, because they optimize the adjacency relationship of the learned features without considering the proximity of the underlying faces. Moreover, since they only use facial images for training, the learned feature mapping may not correctly indicate the relationship of other attributes such as gender and ethnicity, which can be important for some face recognition applications. In this paper, we propose a new CNN-based face recognition approach that incorporates such attributes into the training process. Using an attribute-aware loss function that regularizes the feature mapping using attribute proximity, our approach learns more discriminative features that are correlated with the attributes. We train our face recognition model on a large-scale RGB-D data set with over 100K identities captured under real application conditions. By comparing our approach with other methods on a variety of experiments, we demonstrate that depth channel and attribute-aware loss greatly improve the accuracy and robustness of face recognition.

Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways / 中华医学杂志(英文版)

BACKGROUND@#Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms.@*METHODS@#Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogen-activated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests.@*RESULTS@#The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways.@*CONCLUSIONS@#KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.

3D Face Reconstruction with Geometry Details from a Single Image.

3D face reconstruction from a single image is a classical and challenging problem, with wide applications in many areas. Inspired by recent works in face animation from RGBD or monocular video inputs, we develop a novel method for reconstructing 3D faces from unconstrained 2D images, using a coarse-to-fine optimization strategy. First, a smooth coarse 3D face is generated from an example-based bilinear face model, by aligning the projection of 3D face landmarks with 2D landmarks detected from the input image. Afterwards, using local corrective deformation fields, the coarse 3D face is refined using photometric consistency constraints, resulting in a medium face shape. Finally, a shape-from-shading method is applied on the medium face to recover fine geometric details. Our method outperforms stateof- the-art approaches in terms of accuracy and detail recovery, which is demonstrated in extensive experiments using real world models and publicly available datasets.

Association of Dietary Carotenoids Intake with Skeletal Fluorosis in the Coal-burning Fluorosis Area of Guizhou Province / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore whether the intake of dietary carotenoids could protect against skeletal fluorosis in Guizhou province in which coal-burning fluorosis is endemic.</p><p><b>METHODS</b>A case-control study of 196 patients with skeletal fluorosis and 196 age and gender-matched controls was conducted in Zhijin, Guizhou Province. Face-to-face interviews were conducted to assess habitual dietary intake using a 75-item food frequency questionnaire and various covariates with structured questionnaires. Urinary fluoride was measured using an ion-selective electrode method. The genotype of superoxide dismutase 2 (SOD2) rs11968525 was detected by TaqMan method.</p><p><b>RESULTS</b>We observed significant dose-dependent inverse associations of skeletal fluorosis with intake of β-carotene, lutein/zeaxanthin, lycopene, and total carotenoids (P-trend = 0.002 to 0.018), whereas α-carotene and β-cryptoxanthin intakes were not found to be related to skeletal fluorosis, after adjustment for potential confounders. The adjusted ORs and 95% CI of skeletal fluorosis for the highest versus lowest quartile were 0.30 (0.10, 0.86) for β-carotene, 0.23 (0.08, 0.66) for lycopene, 0.26 (0.10, 0.75) for lutein/zeaxanthin and 0.34 (0.14, 0.74) for total carotenoids (all P-trend < 0.05). Stratified analyses showed that the protective effects of lutein/zeaxanthin and total carotenoids on skeletal fluorosis were more evident for individuals with the AG+AA genotypes of SOD2 (rs11968525).</p><p><b>CONCLUSION</b>Increased intakes of β-carotene, lutein/zeaxanthin, lycopene, and total carotenoids are independently associated with a lower risk of coal-burning skeletal fluorosis. SOD2 (rs11968525) polymorphisms might modify the inverse associations between dietary carotenoids and skeletal fluorosis.</p>

Correlation between platelet-to-lymphocyte ratio and the prognosis of diabetes ketoacidosis / 中华内分泌外科杂志

Objective To investigate the relationship between platelet-to-lymphocyte ratio(PLR) and the prognosis of diabetes ketoacidosis (DKA).Methods 120 patients with DKA were divided into two groups:the DKA survived group (n=86) and the DKA died group (n=34).80 patients with type 2 diabetes (T2DM)were also enrolled in our study as the control group.Their clinical and biochemical parameters were determined.PLR was calculated by blood routine examination.Results Patients in the DKA died group had higher PLR than patients in the DKA survived group and the control group.According to logistic regression analysis,age [OR=2.119(95％CI 1.506-3.994),P=0.032],infection [OR=2.047(95％ CI 1.421-3.885),P=0.021],Glasgow coma score [OR=0.523(95％ CI 0.394-0.693),P=O.O11],simultaneous other organ dysfunction [OR=3.642 (95％ CI 2.287-5.442),P=0.006],PLR[OR=3.073 (95％ CI 1.951-5.142),P＜0.001],mechanical ventilation [OR=3.846 (95％ CI 2.623-5.113),P＜0.001] and lactic acid [0R=2.854 (95％ CI 1.514-4.216,P=0.008] were all significantly correlated with the prognosis of DKA.The optimal cutoff value of PLR for predicting the prognosis of DKA was 192.26.Its sensitivity and specificity were 82.40％ and 67.60％,respectively.Conclusion PLR can be used as a sensitive indicator to predict the prognosis of DKA.

Dietary n-3 polyunsaturated fatty acids, fish consumption, and endometrial cancer risk: a meta-analysis of epidemiological studies.

The relationship between intake of fish and n-3 fatty acids and endometrial cancer risk has not been consistent across epidemiological studies. We quantitatively assessed the aforementioned association through a systematic review and meta-analysis. PubMed and Embase were searched through March 2017 for eligible epidemiological studies. Fixed or random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). The dose-response relationship was also evaluated. Based on the literature search, five prospective studies and 11 case-control studies were identified. All 16 studies were categorized as high-quality studies. After pooling available risk estimates, no significant association was detected between overall fish intake and endometrial cancer risk. In subgroup analyses, every one additional serving/week of fish intake was significantly associated with inversed endometrial cancer risk in studies adjusted for smoking (RR (95% CI): 0.95 (0.91-1.00)), or studies performed in Europe (RR (95% CI): 0.90 (0.84-0.97)), but not in other tested subgroups. In studies conducted in Asia, there was significant positive association (RR (95% CI): 1.15 (1.10-1.21)). Regarding n-3 PUFA intake, marginally inverse associations of high EPA or DHA intake were detected (EPA: RR (95% CI) = 0.79 (0.61-1.04); DHA: RR (95% CI) = 0.85 (0.64-1.11)). Dose-response analyses suggested a significant nonlinear relationship between DHA intake and endometrial cancer risk (p: 0.04). Overall, this meta-analysis suggests that intake of n-3 PUFA may be inversely associated with endometrial cancer risk at some level of evidence, although the exact relationship, especially for fish intake, needs further characterization. Further well-designed studies are warranted.

Lewis(y) antigen promotes the progression of epithelial ovarian cancer by stimulating MUC1 expression.

MUC1 is a type I transmembrane glycoprotein and is overexpressed in various epithelial tumor tissues. Some researchers have demonstrated that the glycosylation status of MUC1 can affect MUC1-mediated tumor growth and cell differentiation. In our previous study, we proved that the abilities of cell proliferation, adhesion, invasion and metastasis, and drug resistance were enhanced in ovarian cancer cells stably expressing Lewis(y). Therefore, we hypothesized that Lewis(y) antigen may play a central role in regulating MUC1 expression, and MUC1-mediated cell growth and differentiation may be closely associated with Lewis(y) antigen. This study aimed to examine the correlation between MUC1 expression and Lewis(y) antigen levels in ovarian cancer cell lines and tissue samples. A series of techniques, including RT-qPCR, western blot anlaysis, immunoprecipitation, immunohistochemistry and double-labeling immunofluorescence were applied to detect the expression of Lewis(y) and MUC1. In malignant epithelial ovarian tumors, the positive expression rates of Lewis(y) antigen and MUC1 were 88.33 and 86.67%, respectively, which were markedly higher than those in borderline (60.00 and 53.33%, P<0.05), benign (33.33 and 30%, P<0.01) and normal (0 and 25%, P<0.01) ovarian samples. There was no correlation between the positive expression rates of Lewis(y) or MUC1 and clinicopathological parameters in ovarian cancers (P>0.05). The expression levels of Lewis(y) and MUC1 correlated with the clinical FIGO stage (P<0.05). Both MUC1 and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P<0.01). In α1,2-fucosyltransferase (α1,2-FT)-transfected cells, the gene and protein expression levels of MUC1 were significantly upregulated compared with the cells that did not overexpress α1,2-FT (P<0.05). The ratio of Lewis(y) immunoprecipitated with MUC1 to total MUC1 increased 1.55-fold in α1,2-FT-overexpressing cells (P<0.05). The overexpression of Lewis(y) resulted in the upregulation of MUC1. On the whole, our data indicate that both MUC1 and Lewis(y) are associated with the occurrence and development of ovarian cancers.