Oncogenic Role of Skp2 and p27^(Kip1) in Intraductal Proliferative Lesions of the Breast

Objective To investigate whether the connection of p27 Kip1 to S-phase kinase-associated protein 2 (Skp2) plays an oncogenic role in intraductal proliferative lesions of the breast. Methods Here we investigated the mechanism involved in association of Skp2's degradation of p27 Kip1 with the breast carcinogenesis by immunohistochemical method through detection of Skp2 and p27 Kip1 protein levels in 120 paraffin-embedded tissues of intraductal proliferative lesions including usual ductal hyperplasia (UDH, n=30), atypical ductal hyperplasia (n=30), flat epithelial atypia (FEA, n=30), and ductal carcinoma in situ (DCIS, n=30). Moreover, the expression status of Skp2 and p27 Kip1 in 30 cases of the normal breast paraffin-embedded tissues were explored. Results The DCIS group was with the highest Skp2 level and the lowest p27 Kip1 level, and the UDH group was with the lowest Skp2 level and the highest p27 Kip1 level. Both Skp2 and p27 Kip1 levels in the DCIS group were significantly different from those in the UDH group (all P<0.01). The levels of Skp2 and p27 Kip1 in the FEA group were significantly different from both the DCIS and UDH groups (all P<0.05). p27 Kip1 was negatively correlated with Skp2 in both the UDH group (r=-0.629, P=0.026) and DCIS group (r=-0.893, P=0.000). Conclusion Overexpression of Skp2 might be the mechanism underlying p27 Kip1 over degradation.

Triple negative breast cancer: special histological types and emerging therapeutic methods

Triple negative breast cancer(TN BC)is a complex and malignant breast cancer subtype that lacks expression of the estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(H ER2),thereby making therapeutic targeting difficult.TNBC is generally considered to have high malignancy and poor prognosis.However,patients diagnosed with certain rare histomorphologic subtypes of TNBC have better prognosis than those diagnosed with typical triple negative breast cancer.In addition,with the discovery and development of novel treatment targets such as the androgen receptor(AR),PI3K/AKT/mTOR and AMPK signaling pathways,as well as emerging immunotherapies,the therapeutic options for TNBC are increasing.In this paper,we review the literature on various histological types of TNBC and focus on newly developed therapeutic strategies that target and potentially affect molecular pathways or emerging oncogenes,thus providing a basis for future tailored therapies focused on the mutational aspects of TNBC.

Response Relationship between the Seasonal Freezing-Thawing Process of Soil and Spatial Factor Changes in the Dayekou Basin of the Qilian Mountains

Objective: In this study, the influence and response relationship between the seasonal freezing-thawing process of soil and the spatial factor changes in the management and utilization of water resource processes were explored. Methods: The monitoring equipment in this study was arranged at different altitudes, gradients, and slope directions, such as the typical forest sample area in the Dayekou Basin of the Qilian Mountains. The spatial variation characteristics of the seasonal freezing-thawing process of the soil were analyzed, and a regression model was established. Results: 1) The results of this study determined that the rate of the soil’s freezing increased with the altitude in a trend of volatility. However, the rate of the thawing of the frozen soil was found to have an opposite trend. The variation degree of the freezing-thawing process increased with the altitude in a trend of volatility. The end time of the approximate soil freezing with altitude increased in a volatility trend ahead of schedule. However, the opposite was observed in the thawing rate of the frozen soil;2) The rate of the soil’s freezing under the mosses of the spruce forest at an altitude of 3028 m was found to be the lowest. However, in the sub-alpine scrub forest at an altitude of 3300 m, a maximum in the spatial ordering was observed, with an average of 1.9 cm·d-1. The thawing rate of the frozen soil in scrub-spruce forest at an altitude of 3300 m was found to be minimal. However, in the sunny slope grassland at an altitude of 2946 m, a maximum in the spatial ordering was observed, with an average of 1.5 cm·d-1. In the spatial ordering of the variation degree of the process of freezing-thawing with an average of 1.2, the scrub-grassland at an altitude of 2518 m was found to be the lowest, and the scrub-spruce forest at an altitude of 3195 m was also low;3) The soil freezing began on approximately October 20th, and the rate of soil freezing gradually became reduced. The arrival time of the frozen soil of up to 150 cm in depth in sub-alpine scrub forest was first observed at an altitude of 3028 m. However, the scrub-spruce forest at an altitude of 3100 m did not become frozen until approximately January 12th on average. Then, the thawing rate of the frozen soil increased gradually. The end time of the thawing was earliest observed in the sunny slope grassland at an altitude of 2946 m. However, the scrub-spruce forest at an altitude of 3100 m was found to be the last to thaw, and averaged approximately July 27th. The average durations of the freezing and thawing of the soil were 77 and 121 days, respectively, and the average duration of the entire process of freezing-thawing was 199 days;4) This study’s established regression models of the duration time of frozen soil’s thaw, and the rate of frozen soil’s thaw, all passed the R test of goodness of fit, F test of variance, and t test. Conclusions: The characteristics of the seasonal freezing-thawing process of the soil with the spatial changes were seasonal. However, the characteristics under the different spatial factor influences were not the same.

Natural products:Regulating glucose metabolism and improving insulin resistance

Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus.These compounds isolated from natural plants can be classified seven categories:terpenoids,alkaloids,quinones,flavonoids,phenols,phenyl propanoids,steroids,and other types of compounds.They exert biological effects by different ways and mechanisms.This review illustrated the potential natural products as a rich resource in regulation of glucose metabolism and IR,as well as their mechanisms.

Relationship between sand-dust weather and water dynamics of desert areas in the middle reaches of Heihe River

Sand-dust weather has become an international social-environmental issue of common concern, and constitutes a serious threat to human lives and economic development. In order to explore the responses of natural desert sand and dust to the dynamics of water in desertification, we extracted long-term monitoring data related to precipitation, soil water, groundwater, and sand-dust weather. These data originated from the test stations for desertification control in desert areas of the middle reaches of the Heihe River. We used an algorithm of characteristic parameters, correlations, and multiple regression analysis to establish a regression model for the duration of sand-dust weather. The response char-acteristics of the natural desert sand and dust and changes of the water inter-annual and annual variance were also examined. Our results showed： （1） From 2006 to 2014 the frequency, duration, and volatility trends of sand-dust weather obviously increased, but the change amplitudes of precipitation, soil water, and groundwater level grew smaller. （2） In the vegetative growth seasons from March to November, the annual variance rates of the soil moisture content in each of four studied layers of soil samples were similar, and the changes in the frequency and duration of sand-dust weather were similar. （3） Our new regression equation for the duration of sand-dust weather passed the R test, F test, and t test. By this regression model we could predict the duration of sand-dust weather with an accuracy of 42.9%. This study can thus provide technological support and reference data for water resource management and re-search regarding sand-dust weather mechanisms.

Expression of E2F-1, Rb and ER in Peripheral Papil-loma and Ductal Carcinoma in Situ of the Breast and its Significance

OBJECTIVE To investigate the correlation of E2F-1, Rb and ER expression with peripheral papilloma (Peri-PM) and ductal carcinoma in situ of the breast (DCIS), and further explore some molecular mechanisms of the canceration of Peri-PM. METHODS Imunohistochemistry was used to examine the expression of E2F-1, Rb and ER in 60 Peri-PM, 60 Peri-PM with atypical ductal hyperplasia (Peri-PM with ADH) and 60 DCIS. Normal breast tissues were selected as a control group. RESULTS Based on immunohistochemical staining, the positive rate of E2F-1 expression in Peri-PM, Peri-PM with ADH and DCIS was 21.7%, 46.7% and 78.3% respectively. The positive rate of Rb expression was 83.3 %, 53.9% and 21.7% and the ER expression was 86.7%,61.7% and 55.0%. Significant differences were found among the 3 groups (Peri-PM, Peri-PM with ADH and DCIS) (P<0.05). Significant differences existed between any 2 groups (P<0.05) except for the rate of ER positive expression comparing Peri-PM with ADH verus DCIS (P>0.05). The expression of E2F-1 was nega- tively correlated with ER and Rb, and at the same time the expression of ER was positively correlated with Rb. Following the degree of breast epithelial hyperplasia involved and its development into carcinoma, the positive rate of E2F-1 expression displayed an elevating tendency, but that of Rb and ER expression showed a tendency to decline. CONCLUSION The interaction of the 3 indexes studied may play an im- portant role in the conversion of precancerous lesions to early in situ breast carcinoma, and the evaluation of these indexes might provide a valuable basis for screening high-risk cases of Peri-PM.

Clonal Analysis of Peripheral Papilloma and Cancerous Cells of the Breast

OBJECTIVE Because almost al malignancies represent monoclonal proliferations,we have studied the clonal status of peripheral papil omas (peri-PM),ductal carcinomas in situ(DCIS),and normal breast tissues to explore a reliable way to distinguish benign and malignant(or pre-malignant) cases previously diagnosed morphologically. METHODS Twenty-six cases of peri-PM,25 cases of peri-PM with atypical ductal hyperplasia(ADH),27 cases of DCIS,16 cases of developed canceration and 20 specimens of normal tissue were examined in the study.The clonal status of these tissues was studied using an assay based on inactivation mosaicism of the lenth-polymorphic X-chromosomes at the androgen receptor(AR)locus. RESULTS Loss of polymorphism at the AR locus was found in all DCIS cases and 10 cases(10/25,40.0%)of peri-PM with ADH,indicating the monoclonality of the tumors.Twenty-four out of 26(92.3%)cases with peri-PM and 19 specimens of normal tissue were shown to be polyclonal.In 16 cases of developed canceration,identical X chromosome inactivation(monoclonal alterations)was observed from both the peri-PM with ADH part,and the DCIS part in each case. CONCLUSION These results contribute to the understanding of the genetic changes of peri-PM,and confirm the peri-PM withADH as a precancerous lesion of the breast.Clonal analysis might be a useful modality to screen high-risk cases from precancerous lesions or to distinguish between benign hyperplasia and early carcinoma.

Clinically applicable Gleason grading(GD)system for prostate cancer based on deep learning

To the Editor:Prostate cancer is one of the most common malignant tumors of the male genital system,with approximately 1.1 million new cases in 2012.[1]The accurate diagnosis of prostate cancer leads to a better chance of successful treatment when it is still confined to the prostate gland.The Gleason grading(GD)system was first established by Donald Gleason during 1966 to 1974.[2,3]The Gleason pattern ranges from 1 to 5.A higher score corresponds to poorer differentiation,which indicates a worse prognosis and higher metastasis possibility.The total score is calculated with the first half of the dominant Gleason pattern and the second half based on the non-dominant one.

A 10 Gbps in-line network security processor based on configurable hetero-multi-cores

This paper deals with an in-line network security processor (NSP) design that implements the Internet Protocol Security (IPSec) protocol processing for the 10 Gbps Ethernet. The 10 Gbps high speed data transfer, the IPSec processing including the crypto-operation, the database query, and IPSec header processing are integrated in the design. The in-line NSP is implemented using 65 nm CMOS technology and the layout area is 2.5 mm×3 mm with 360 million gates. A configurable crossbar data transfer skeleton implementing an iSLIP scheduling algorithm is proposed, which enables simultaneous data transfer between the heterogeneous multiple cores. There are, in addition, a high speed input/output data buffering mechanism and design of high performance hardware structures for modules, wherein the transfer efficiency and the resource utilization are maximized and the IPSec protocol processing achieves 10 Gbps line speed. A high speed and low power hardware look-up method is proposed, which effectively reduces the area and power dissipation. The post simulation results demonstrate that the design gives a peak throughput for the Authentication Header (AH) transport mode of 10.06 Gbps with the average test packet length of 512 bytes under the clock rate of 250 MHz, and power dissipation less than 1 W is obtained. An FPGA prototype is constructed to verify the function of the design. A test bench is being set up for performance and function verification.

Analysis of the contributions of human factors and natural factors affecting the vegetation pattern in coastal wetlands

Introduction:Accurate identification of the dominant factors affecting coastal wetlands can provide a reference for vegetation rehabilitation.In this study,quantitative analysis was performed on the Yancheng coastal wetland using ANOVA and geostatistical methods.Outcomes/other:The results indicated that in the directions perpendicular and parallel to the coastline,the soil moisture and salinity in the study area exhibited relatively significant(p<0.05)spatial variability.Vegetation in the southern experimental zone was in a low-moisture,low-salinity ecological niche,whereas vegetation in the northern experimental zone was in a high-moisture,high-salinity ecological niche.Soil salinity exhibited higher spatial variability than soil moisture,and it was most correlated with unvegetated mudflats,followed by areas with Spartina alterniflora,Suaeda glauca,and Phragmites australis.Discussion:The fitting of the semivariogram showed that the nugget and sill of the ratio were relatively low(<25%)for soil moisture and salinity in the northern experimental zone and northern buffer zone,whereas these values were relatively high(>75%)for soil moisture and salinity in the southern experimental zone and southern buffer zone.Conclusion:Compared with the northern study area,the contribution of human disturbance to the spatial heterogeneity of soil moisture and salinity in the southern study area is higher.