Molecular Detection of Mutations within the Quinolone Resistance-Determining Regions in Non Typhoidal Salmonella Isolates from Malaysia

Introduction: The efficacy of chemotherapy in bacteraemia caused by non-typhoidal Salmonella (NTS) is compromised by antibiotic resistance. Objective: This study was undertaken to describe the mechanism of resistance among clinical NTS isolates. Materials & Methodology: Thirty of NTS were isolated from blood (n = 19), stool (n = 10) and bronchioalveolar lavage (BAL;n = 1) respectively. These isolates were tested for susceptibility testing by disc diffusion method against ampicillin, gentamicin, tetracycline, co-trimoxazole, nalidixic acid, ciprofloxacin and ceftriaxone. Epsilometer tests (E-test) for nalidixic acid and ciprofloxacin were performed for nalidixic acid resistant isolates by disc diffusion method. DNA sequencing was carried out on six of the nalidixic acid resistant Salmonella Enteritidis isolates to identify mutations within quinolones resistance determining regions (QRDR) of gyrA, gyrB, parC and parE genes. Results: Resistance rates of NTS isolates from blood, stool, and BAL were respectively 37%, 20% and 0% for ampicillin, 79%, 40% and 0% for tetracycline, 32%, 40% and 0% for co-trimoxazole, 37%, 10% and 100% for nalidixic acid. Eight isolates were resistant to nalidixic acid and had exhibited reduced susceptibility towards ciprofloxacin by E-test. Mutation within QRDR was detected in gyrA gene (n = 6;Asp 47 → His [3], Asp 51 → Asn [1], Asp 73 → Gly [1], and Gly 48 → Asp [1]) and double mutation was detected in parE gene (n = 3;Gly 48 → Asp [3], Glu 82 → Ser [3]). Out of six isolates, three isolates were found to have both gyrA and parE gene mutations. Conclusions: There was no mutation observed in gyrB and parC gene. Mutation in gyrA gene was sufficient to induce decreased susceptibility to ciprofloxacin. Variation in amino acid sequences are novel, while detection of other gene mutation was uncommon.

Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial cancer.In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels.Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers.An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.

Prognostic significance of sex determining region Y-box 2,Ecadherin,and vimentin in esophageal squamous cell carcinoma

BACKGROUND Sex determining region Y-box 2(SOX2) can promote squamous cell carcinoma(SSC) because it regulates the migration and invasion of several different types of squamous carcinoma cells.However,few studies have examined the prognostic value of SOX2 and its effect on the epithelial-mesenchymal transition(EMT) in esophageal SSC(ESCC),a cancer characterized by high invasion and rapid metastasis.AIM To verify the relationship of SOX2 and the EMT in ESCC and determine the prognostic value and significance of SOX2 and protein markers of the EMT in ESCC.METHODS One hundred and eighty-five postsurgical ESCC patients were retrospectively examined.Immunohistochemistry was used to detect SOX2,E-cadherin,and vimentin in ESCC tissues.The chi-square test was used to determine the relationships of the expression of these proteins with clinical data.Kaplan-Meier survival curves were used to evaluate factors associated with overall survival(OS).RESULTS SOX2 and vimentin had high expression in ESCC tissues and correlated with the depth of local carcinoma invasion.SOX2 expression had positive correlations with tumor size,vimentin expression,and the EMT,and a negative correlation with Ecadherin expression.Expression of SOX2 and vimentin had negative correlations with OS.SOX2 expression was an independent prognostic risk factor for poor OS in patients with ESCC.CONCLUSION SOX2 expression was an independent risk factor for OS in patients with ESCC and its expression had a positive correlation with the expression of vimentin,a classic marker of the EMT.SOX2 promoted the migration and invasion of ESCC,and this may related to its effect on vimentin in promoting the EMT.

An Innovative Land Approach for Spatially Determining SDGs-Sustainably Governing German Spree Forest and Lusatia Region

In times of highest necessities for United Nations Sustainable Development Goals(SDGs)and acknowledging planetary boundaries,the need for understanding general global goals and regional to local strategic governing structures has to be supported while combining assessment,monitoring,governance approaches,together with landscape planning,land use based approaches,land system and sustainability science.The initial research embeds an incrementally worked out theoretical framework followed by applied research parts.The case studies and field data in the German Lusatia Region and inner part Spree Forest Region inhabit intrinsic drivers of finding ways over bridging deficiencies of theoretical and applied adjusted objectives and in this small excerpt mainly about the scale and planning level,instrumental flexibility deficiencies while transmitting global transformation needs to the regional,local planning level and backward(counter-current principle).Innovative instrumental assessment structures were created with a new approach of spatially determining SDGs for accelerated Climate Smart Planning(CSP)and Integrated Drought and Water Management(IDWM).This research supports processes around acceleration and assessment of climate change-,crises-related and sustainable development options while enhancing interdisciplinary sustainability science for gaining more regional land resilience.

A Localization Algorithm Using a Mobile Anchor Node Based on Region Determination in Underwater Wireless Sensor Networks

At present, most underwater positioning algorithms improve the positioning accuracy by increasing the number of anchor nodes which resulting in the increasing energy consumption. To solve this problem, the paper proposes a localization algorithm assisted by mobile anchor node and based on region determination(LMRD), which not only improves the positioning accuracy of nodes positioning but also reduces the energy consumption. This algorithm is divided into two stages: region determination stage and location positioning stage. In the region determination stage, the target region is divided into several sub-regions by the region division strategy with the smallest overlap rate which can reduce the number of virtual anchor nodes and lock the target node to a sub-region, and then through the planning of mobile nodes to optimize the travel path, reduce the moving distance, and reduce system energy consumption. In the location positioning stage, the target node location can be calculated using the HILBERT path planning and trilateration. The simulation results show that the proposed algorithm can improve the positioning accuracy when the energy consumption is reduced.

Determinants of Farmers’ Perception of Climate Change: A Case Study from the Coastal Region of Bangladesh

Socio-economic conditions of farmers, especially in the coastal region in Bangladesh, have been severely affected because of climate change. This study was focused on analyzing the farmers’ perception of climate change by examining three vital issues: (1) description of the socioeconomic characteristics of farmers;(2) reporting on the perception of farmers experiences with climatic change;and (3) identification of the socio-economic factors associated with farmers’ perception of climate change. The study area encompasses three villages within the coastal region (Sathkhira district) of Bangladesh, a geographic region where climate change literature has highlighted as prone to accelerated degradation. A logit model, along with weighted indexes for ranking and descriptive statistics, was used to analyze the result of 100 farmers surveyed by questionnaire. We found that the majority of the farmers (88%) perceived changes in climatic conditions. Almost all farmers indicated increases in temperature, droughts, floods, cyclones, salinity level and decreasing rainfall over the last 20 years. The logit model explained that out of the nine factors surveyed;education, family size, farm size, family income, farming experiences and training received were significantly related and influential factors to perception of climate change. Therefore, government and non-governmental organizations are recommended to push forward with interventions, especially focusing on identified factors, in order to strengthen the farmers’ capacity to battle against climate change effects.

Determinants of Regional Obesity (Visceral and Subcutaneous Obesity) within Cardiovascular Risk Factors in the Cardiology Department of the University Clinics of Kinshasa

Objective: This study aimed to determine searching for the determinants of regional obesity (visceral and subcutaneous obesity) within the cardiovascular risk factors (CVRF) in patients followed in cardiology at the University Clinics of Kinshasa (UCK) in the Democratic Republic of Congo (DRC). Material and Methods: Cross-sectional and analytical study had sought the determinants of regional obesity (visceral and subcutaneous obesity) by bio-impedance inside the CVRF during the period from July 1 to September 31, 2014. The multivariate analysis (logistic regression) has established the levels of association between regional obesity and CVRF. The statistical significance threshold was set at p Results: A total of 642 patients participated in the present study. The frequencies of visceral and subcutaneous obesity were respectively 45.5% (without significant distinction between the two sexes: Men 48% n = 92/188 vs. Women 44.1 n = 200/454;p = 0.148) and 60.7% with a predominance in women (36.2 n = 68/188 vs. 70.9% n = 322/454;p that alongside regional obesity was: advanced age, tobacco use, alcohol use, physical inactivity, high blood pressure (HBP), diabetes mellitus (DM) and Chronic renal failure (CRF) in the respective proportions of 50.8%, 13.4%, 44.2%, 86.3%, 10.7%, 13.4% and 0.3%. The determinants of regional obesity were advanced age, smoking and obesity on body mass index (BMI) for visceral obesity;advanced age, female gender, alcohol intake and obesity on BMI and waist circumference (WC) as well as hypertriglyceridemia for subcutaneous obesity. Conclusion: This study showed a significant frequency of regional obesity with the following determinants: advanced age, female gender, smoking, alcohol, BMI/WC obesity and hypertriglyceridemia.

Factors and Determinants of Interregional Unemployment Rate Differences in Rural Russia

This study involves an econometric assessment of the impact that macroeconomic, institutional, structural, demographic and social variables produce on the rate of and interregional differences in rural unemployment. We classify the regions of Russia by the rate of overall and rural unemployment and characterize the groups of regions we have selected according to key parameters of the labor market and features of regional development. Employing a regression analysis, this paper focuses on the factors of regional unemployment in the subjects of Russian Federation. When making our regression models, stepwise regression methods were used. Evaluating the regression models that include demographic, economic and social factors, we identify the determinants of rural unemployment. The regression analysis was carried out for both the Russian Federation as a whole and each of the typological groups individually. We find that such factors like a big share of young people in the structure of the rural population and a low level of education of rural residents do contribute to the growth of rural unemployment. At the same time, higher employment, diversification of the rural economy through promoting non-agricultural employment, and higher levels of vocational education among rural residents cause the rate of rural unemployment to fall.

A Dynamic Analysis on Determining of Housing Demand： A Comparison for Turkey, Hungary, and UK

Housing is both good and investment assets so that it plays an important role in the economy. Housing also can be characterized the most complex economic good because of its durability, heterogeneity, locational fixity, the possibility to raise loans against housing collateral, and the effect on well-developed secondary markets. On the other hand, income distribution, socio-economic justice, and regional disparities imply that housing market is an important concept for social and cultural transformation. In this study, the determinants of housing demand were compared for countries. These countries are selected according to economic situation： Turkey, Hungary, and United Kingdom. As a scope of this, the dynamic relationship between the housing demand and variables determining the housing demand in Turkey, Hungary, and UK has been analyzed. The model estimated uses quarterly data from January 2002 to January 2014. Building permits has been considered as housing demand. The other variables used for determining the housing demand are GDP, monetary aggregate, interest rate, and share prices. The long term relationship among variables has been analyzed with Vector Autoregressive Model （VAR） as impulse response and variance decomposition. The findings indicate that determining of housing demand changes according to economic and financial components such as government policies, mortgage system, consumer choice, tax, and subsidy in selected countries. All variables play an important role in housing demand, although the level of their impacts varies.

Male sex determination： insights into molecular mechanisms

Disorders of sex development often arise from anomalies in the molecular or cellular networks that guide the differentiation of the embryonic gonad into either a testis or an ovary, two functionally distinct organs. The activation of the Y-linked gene Sry （sex- determining region Y） and its downstream target Sox9 （Sry box-containing gene 9） triggers testis differentiation by stimulating the differentiation of Sertoli cells, which then direct testis morphogenesis. Once engaged, a genetic pathway promotes the testis development while actively suppressing genes involved in ovarian development. This review focuses on the events of testis determination and the struggle to maintain male fate in the face of antagonistic pressure from the underlying female programme.

Climate Warming Mitigation from Nationally Determined Contributions

Individual countries are requested to submit nationally determined contributions(NDCs)to alleviate global warming in the Paris Agreement.However,the global climate effects and regional contributions are not explicitly considered in the countries’decision-making process.In this study,we evaluate the global temperature slowdown of the NDC scenario(ΔT=0.6°C)and attribute the global temperature slowdown to certain regions of the world with a compact earth system model.Considering reductions in CO_(2),CH_(4),N_(2)O,BC,and SO_(2),the R5OECD(the Organization for Economic Co-operation and Development in 1990)and R5ASIA(Asian countries)are the top two contributors to global warming mitigation,accounting for 39.3%and 36.8%,respectively.R5LAM(Latin America and the Caribbean)and R5MAF(the Middle East and Africa)followed behind,with contributions of 11.5%and 8.9%,respectively.The remaining 3.5%is attributed to R5REF(the Reforming Economies).Carbon Dioxide emission reduction is the decisive factor of regional contributions,but not the only one.Other greenhouse gases are also important,especially for R5MAF.The contribution of short-lived aerosols is small but significant,notably SO_(2)reduction in R5ASIA.We argue that additional species beyond CO_(2)need to be considered,including short-lived pollutants,when planning a route to mitigate climate change.It needs to be emphasized that there is still a gap to achieve the Paris Agreement 2-degree target with current NDC efforts,let alone the ambitious 1.5-degree target.All countries need to pursue stricter reduction policies for a more sustainable world.

Estimation of Global Solar Radiation Using Clearness Index and Cloud Transmittance Factor at Trans-Himalayan Region in Nepal

This paper presents the global solar radiation (GSR) and cloud transmittance factor (cf) measured at the horizontal surface over a period of one year from 2009 to 2010 using CMP6 Pyranometer and NILUUV Irradiance Meter at Lukla (Latitude 26.69oN,Longitude 86.73?E and Altitude 2850 m) in the foothills of the Mt Everest (8850 m high). Monthly and seasonal variations of global solar radiation as well as correlation between clearness index and cloud transmittance factor at Lukla are presented. The annual average daily global solar radiation is about 3.83 kWh/sq·m/day which is sufficient to promote solar active and passive energy technology at high mountain terrain where there is no other viable alternative sources of energy. The maximum and minimum global solar radiation of 5.33 and 2.08 kWh/sq·m/day is recorded in April and September 2010 respectively. The seasonal variation of solar energy is about 2.87 kWh/sq·m/day and 4.83 kWh/sq·m/day in summer and spring respectively which is not in line with the general trend. The coefficient of determination (R2) between cloud transmittance factor (cf) and clearness factor (K) is found to be 0.97. This novel result can be utilized to estimate the global solar radiation at the horizontal surface where K and cf are available.

Regional VS. Global Patterns of Democratization： A Comparative Study

This study analyzes the comparative patterns of democratization between geographic regions and the world. It addresses the question that how some determinants of democracy have different effects among geographical regions. Further, by comparing the similarities and differences in the patterns of democratic diffusion across regions, this study seeks to delineate what changes scholars should adopt in our epistemological approaches and methodological tools, such as the indices of democracy, in an attempt to better understand the policy implications of disparate findings from various empirical studies. As part of a larger research project, this paper focuses its attention on two of the geographical regions Asia and the Middle East.

阿达木单抗还原肽指纹图谱鉴别方法的建立与验证

目的 建立阿达木单抗基于高分辨质谱的肽指纹图谱表征分析方法及用于质控放行的肽指纹图谱液相鉴别方法。方法 阿达木单抗经变性、还原、烷基化和酶解后,应用高分辨质谱测定阿达木单抗氨基酸序列覆盖率,并确证互补决定区(complementarity determining region, CDR)特征肽段。建立能够有效鉴别阿达木单抗肽指纹图谱的液相色谱分析方法,并进行方法学验证和应用评价。结果 阿达木单抗经胰蛋白酶(Trypsin)和胞内蛋白酶(Lys-C)酶解后,CDR肽段均由高分辨质谱完成确证。贝伐珠单抗和利妥昔单抗用于评估方法专属性,结果表明该方法专属性强。选择Fc段保守氨基酸序列作为参比峰,以CDR特征肽段的相对保留时间(RRT)和相对峰面积(RPA)考察方法的变异程度。Trypsin酶解的样品连续5次进样各特征肽段RRT的RSD在0.008%~1.097%之间,RPA的RSD在1.212%~7.951%之间;中间精密度考察各特征肽段RRT的RSD在0.010%~0.985%之间,RPA的RSD在2.306%~10.939%之间;酶切比例为1∶35~1∶45,酶切时间为3.5~4.5 h时,RRT和RPA的RSD均符合方法耐用性要求。Lys-C酶解的样品方法学验证结果也表明其精密度、耐用性均表现良好。不同色谱柱对肽段的选择性、保留强弱、分离效果以及峰强度等具有一定差异。结论 建立的基于Trypsin/Lys-C酶切、鉴定CDR特征肽段的高效液相肽指纹图谱鉴别方法可用于阿达木单抗的质量控制及批检验放行,同时可为企业建立单抗肽指纹图谱鉴别方法提供参考。

先天性巨结肠患儿术后肠道组织中CAD、SOX2的表达水平及其临床意义

目的探讨先天性巨结肠(HD)患儿术后肠道组织蛋白酶D(CAD)、性别决定区Y框蛋白2(SOX2)的表达水平及其临床意义。方法选取2015年5月至2019年3月郑州大学第一附属医院收治的56例HD患儿结肠组织(HD组)和23例因肠道梗阻或穿孔实施造瘘手术获取的结肠组织标本(对照组)。采用免疫组化、Western-blot技术检测结肠组织中CAD、SOX2的表达水平,并采用Pearson线性相关分析法分析CAD、SOX2表达与病变肠段肌间神经丛直径、神经节细胞数的关系。结果HD患儿的狭窄段组织中CAD蛋白、SOX2蛋白阳性表达率分别为7.14%、12.50%,移行段肠组织中CAD蛋白、SOX2蛋白阳性表达率分别为32.14%、35.71%,明显低于对照组的78.26%、82.61%,而狭窄段组织中CAD蛋白、SOX2蛋白阳性表达率明显低于移行段,差异均有统计学意义(P<0.05);HD患儿的狭窄段肠组织中肌间神经丛直径、神经节细胞数目分别为(30.66±5.14)μm、(0.83±0.24)个/视野,移行段肠组织中肌间神经丛直径、神经节细胞数目分别为(31.20±5.83)μm、(1.94±0.56)个/视野,明显短(少)于对照组的(54.29±8.50)μm、(5.40±1.84)个/视野,狭窄段肠组织中肌间神经丛直径、神经节细胞数目明显短(少)于移行段,差异均有统计学意义(P<0.05);Pearson相关分析结果显示,HD患儿狭窄段、移行段肠组织中肌间神经丛直径、神经节细胞数目与CAD蛋白、SOX2蛋白表达强度均呈显著正相关(P<0.05)。结论HD患儿病变结肠组织中CAD蛋白、SOX2蛋白的表达强度下调,可能与肌间神经丛直径、神经节细胞数目的减少有关。

基于改进Faster R-CNN与U-Net算法的桥梁病害识别与量化方法

为实现桥梁病害检测的自动化,对基于图像处理技术的混凝土桥梁表观病害的智能识别和尺寸确定方法展开研究.提出基于改进Faster R-CNN算法的病害识别方法,利用K均值聚类和遗传算法对区域候选网络锚框进行优化设计;以裂缝预测区域为基础,提出ResNet34结合U-Net的裂缝形态提取方法,并结合裂缝形态学研究了裂缝像素宽度和长度的确定方法.结果表明:锚框优化设计可改进Faster R-CNN算法的表观病害识别效果,5类常见病害的预测准确率、召回率、平均精确率分别由68.40%、69.87%、74.64%提升到85.40%、83.59%、83.72%;利用病害预测框,结合改进U-Net算法的裂缝像素尺寸计算,可实现裂缝病害尺寸的自动测量;基于改进Faster R-CNN和改进U-Net的方法可实现混凝土桥梁常见病害的智能识别和尺寸量化,从而提高桥梁病害检测效率并促进桥梁技术状况评定的智能化.

非小细胞肺癌组织中miR-363-3p、SOX4 mRNA表达及对上皮间质转化进程的影响

目的探讨非小细胞肺癌组织中微小RNA-363-3p(miR-363-3p)、性别决定区Y框蛋白4(SOX4)表达及对上皮间质转化(EMT)进程的影响。方法收集行手术切除的84例非小细胞肺癌患者的癌及其癌旁组织。采用实时荧光定量聚合酶链反应检测癌及癌旁组织miR-363-3p、SOX4 mRNA表达,免疫组化SP法检测癌及癌旁组织中E-cadherin、Vimentin表达。比较不同病理特征患者癌组织中miR-363-3p、SOX4 mRNA表达,采用Spearman秩相关分析癌组织miR-363-3p、SOX4 mRNA表达与E-cadherin、Vimentin相关性。使用相对超危险度比(RERI)、归因比(AP)、交互作用指数(SI)分析miR-363-3p、SOX4参与EMT进程的交互作用。结果癌组织中miR-363-3p表达低于癌旁组织,SOX4 mRNA表达高于癌旁组织(P均<0.05);癌组织中miR-363-3p、SOX4 mRNA表达与性别、年龄、吸烟史、肿瘤最大径无关(P均>0.05),与分化程度、TNM分期有关(P均<0.05);癌组织E-cadherin阳性表达率低于癌旁组织,Vimentin阳性表达率高于癌旁组织(P均<0.05);癌组织miR-363-3p与E-cadherin表达呈正相关(r=0.491,P<0.05),与Vimentin表达呈负相关(r=-0.506,P<0.05);癌组织SOX4 mRNA与E-cadherin表达呈负相关(r=-0.527,P<0.05),与Vimentin表达呈正相关(r=0.463,P<0.05)。癌组织miR-363-3p、SOX4对EMT进程存在负向交互作用(RERI=29.639,AP=70.91,SI=3.656)。结论非小细胞肺癌组织中miR-363-3p、SOX4异常表达与EMT有关,且二者对EMT进程存在负向交互作用。

血清金属蛋白酶组织抑制剂3和性别决定区Y框蛋白2在2型糖尿病肾损伤早期诊断中的临床应用

目的探究血清金属蛋白酶组织抑制剂3(tissue inhibitors of metalloproteinases 3,TIMP3)和性别决定区Y框蛋白2(transcription factor determining region Y box protein 2,SOX2)对2型糖尿病(type 2 diabetes mellitus,T2DM)肾损伤的早期诊断。方法选取2022年4月至2023年4月在华北石油管理局总医院就诊的102例T2DM患者为研究对象,根据24 h尿蛋白排泄率(uri-nary albumin excretion rate,UAER)将T2DM患者分为肾损伤组(n=40)和无肾损伤组(n=62),另选取同期在华北石油管理局总医院行体检的健康者50名为对照组。酶联免疫吸附法测定所有受试者血清TIMP3、SOX2水平;比较3组受试者一般资料、糖化血红蛋白(hemoglobin A1c,HbA1c)、UAER、血肌酐(serum creatinine,Scr)、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)、血清TIMP3、SOX2水平;Pearson相关性分析血清TIMP3与SOX2及两者与HbA1c、UAER、Scr、eGFR之间的关系;受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清TIMP3、SOX2对T2DM患者肾损伤的诊断价值。结果T2DM患者血清TIMP3[(0.68±0.17)μg/L比(1.35±0.35)μg/L]及eGFR[(105.99±20.56)mL·min^(-1)·(1.73 m^(2))比(133.15±26.18)mL·min^(-1)·(1.73 m^(2))^(-1)]显著低于对照组(P<0.05),且肾损伤患者血清TIMP3[(0.47±0.11)μg/L比(0.82±0.21)^(-1)μg/L]及eGFR[(74.69±10.22)mL·min^(-1)·(1.73 m^(2))比(126.18±27.23)mL·min^(-1)·(1.73 m^(2))^(-1)]显著低于无肾损伤患者(P<0.05);血清SOX2[(8.91±1.82)kU/L比(5.15±1.31)kU/L]及HbA1c[(8.80±1.55)%比(5.52±0.83)%]、UAER[(70.13±18.06)mg/24 h比(13.22±3.61)mg/24 h]、Scr[(82.14±15.23)µmol/L比(53.19±5.62)µmol/L]显著高于对照组(P<0.05),且肾损伤患者血清SOX2[(10.81±2.13)kU/L比(5.15±1.31)kU/L]及UAER[(156.83±40.29)mg/24 h比(13.22±3.61)mg/24 h]、Scr[(113.77±13.58)µmol/L比(53.19±5.62)µmol/L]显著高于无肾损伤患者(P<0.05)。Pearson相关性分析结果显示,TIMP3与UAER、Scr、HbA1c呈显著负相关(P<0.05),与eGFR呈显著正相关(P<0.05);SOX2与UAER、Scr、HbA1c呈显著正相关(P<0.05),与eGFR呈显著负相关(P<0.05);血清TIMP3与SOX2呈显著负相关(r=-0.590,P<0.05)。ROC结果显示,血清TIMP3联合SOX2诊断T2DM患者肾损伤的敏感度和特异度分别为95.0%、85.3%,显著高于TIMP3、SOX2单独测定。结论T2DM肾损伤患者血清TIMP3水平显著降低,SOX2水平显著升高,且两者与T2DM患者肾损伤密切相关,可用于T2DM患者肾损伤早期诊断。

SOX7靶向ERK1/2/PD-L1通路抑制结直肠癌血管生成

目的探讨性别决定区Y框蛋白7(SOX7)对结直肠癌血管生成的影响及潜在作用机制。方法应用免疫荧光检测结直肠癌患者组织样本中SOX7表达水平,之后通过裸鼠、转染SOX7 mimic的人结直肠癌细胞系SW480细胞和人脐静脉内皮细胞(HUVEC)共培养进一步研究。用Western-blot验证SOX7与ERK1/2/PD-L1对结直肠癌细胞的相关蛋白表达的影响。用CCK8检测SOX7与ERK1/2/PD-L1对HUVEC增殖的影响。通过体外内皮细胞成管实验测定SOX7与ERK1/2/PD-L1对肿瘤血管生成的影响。结果SOX7在人结直肠癌组织中表达被抑制(P<0.01),同时SOX7的过表达抑制了小鼠体内肿瘤生长(P<0.01)。SW480细胞中SOX7的过表达抑制了ERK1/2、c-Jun的表达,并在ERK1/2的激动剂Senkyunolide I的作用下上调了SW480细胞的ERK1/2、c-Jun蛋白表达(P<0.01),逆转了SOX7对SW480细胞中ERK1/2、c-Jun蛋白表达的影响(P<0.01)。HUVEC中SOX7抑制了PD-L1、V-EGFR2、p-PI3K、HIF-1α的蛋白表达,Senkyunolide I上调了HUVEC的PD-L1、V-EGFR2、p-PI3K、HIF-1α的蛋白表达,并逆转了SOX7对HUVEC中上述相关蛋白表达的影响(P<0.01)。PD-1/PD-L1 Inhibitor 3抑制了PD-L1、V-EGFR2、p-PI3K、HIF-1α的蛋白表达,SOX7过表达在PD-1/PD-L1 Inhibitor 3的影响下并没有表现出抑制作用。CCK8实验结果显示SOX7过表达显著抑制了HUVEC的增殖能力,Senkyunolide I作用下的两组HUVEC增殖能力较SOX7 NC组与SOX7 mimic组明显上升,PD-1/PD-L1 Inhibitor 3作用下的两组HUVEC增殖能力较SOX7 NC组与SOX7 mimic组明显下降,以上均有明显统计学差异(P<0.01)。成管实验结果显示SOX7过表达抑制了HUVEC的血管生成,Senkyunolide I强烈加速了血管生成,而PD-1/PD-L1 Inhibitor 3血管生成则被显著抑制,以上均有明显统计学差异(P<0.01)。结论SOX7通过ERK1/2/PD-L1通路抑制结直肠肿瘤的增殖和血管生成,SOX7可能是晚期CRC患者临床治疗中潜在的抗血管生成靶点。

SOX9及其增强子在哺乳动物性别决定中的研究进展

性别决定指的是胚胎发育早期,在转录因子的精确调控下,具有双重分化潜能的性腺向睾丸(雄性)或卵巢(雌性)方向转变的过程。SOX9(SRY-boxtranscription factor9)是哺乳动物发育过程中的多功能转录因子,在性别决定及随后的雄性生殖器官发育中发挥关键作用。近年来相关研究表明,SOX9上游的多个增强子也在性别决定过程中扮演着重要的角色。本文主要对SOX9及其与性腺发育相关的增强子在性别决定中的研究进展进行了综述,以期加深人们对SOX9在性别决定中调控作用机制的认识,为加快动物性别控制技术研究提供理论参考。