Upregulation of NUAK2: A novel prognostic marker in breast cancer

Background. Breast cancer is the most commonly diagnosed neoplasm in women worldwide. New molecular biomarkers and effective prognostic models are being developed. This study aimed to investigate the clinical and prognostic significance of NUAK2 expression in patients with breast cancer. Methods. The expression of NUAK 2 was examined in breast cancer cells and tissues by real-time PCR, western blotting, and immunohistochemical staining. CCK-8 and colony formation assays were performed to verify the effect of NUAK2 on the proliferation and tumor progression of breast cancer cells. A tumor formation assay in nude mice was performed to analyze the effect of NUAK2 on the tumorigenicity of breast cancer cells. Results. The expression of NUAK2 in breast cancer tissues was higher than that in paracarcinoma and normal breast tissues. The overall survival of patients with high NUAK2 expression was significantly lower than that of patients with low NUAK2 expression. Multivariate analyses indicated that NUAK2 was an independent prognostic indicator of survival in breast cancer. In vitro experiments demonstrated that knocking down NUAK2 in breast cancer cells inhibited cell proliferation and tumor-forming ability, and overexpression of NUAK2 showed the opposite effects. NUAK2 overexpression promoted the tumorigenicity of breast cancer cells in vivo. Conclusion. These findings suggest that NUAK2 is involved in breast cancer development and progression. NUAK2 may be a valuable prognostic indicator in patients with breast cancer

Genetic Analysis of PICK1 Gene in Alzheimer's Disease: A Study for Finding a New Gene Target

Background: Alzheimer's disease (AD) is a neurodegenerative disease with no effective treatment. Researchers have focused on exploring biomarkers for its early diagnosis, especially on finding a new gene target. Recent studies have shown that protein interacting with C-kinase-1(PICK1) is related to AD through regulating hippocampal synaptic plasticity. PICK1 gene polymorphisms have been identified in psychological and other related disorders.Methods: This study included 133 sporadic AD patients and 173 healthy controls. All coding exons and intron-exon boundaries of the PICK1 gene were amplified by polymerase chain reaction (PCR), which were subsequently sequenced and analyzed.Results: This is the first genetic association study to investigate the association between PICK1 gene and AD risk in Chinese Han population. Seven single nucleotide polymorphisms (SNPs) were found in our research (rs397780637, rs713729, rs2076369, rs58230476, rs7289911, rs149474436; and rs146770324 for patient M1659 only). Frequencies of the T allele (p = 0.002; OR, 0.083; 95%CI, 0.011–0.634) and TT/TC genotypes (p = 0.001) of rs149474436 were lower in AD patients than in the controls. The GG homozygotes of rs397780637 were found to be associated with an increased risk of AD (p = 0.018) in APOEε4 allele carriers, while the frequency of the T allele of rs149474436 was significantly lower among AD patients in APOEε4 non-carriers (p = 0.005).Conclusions: Our results suggest that PICK1 gene SNPs are associated with AD susceptibility in East Asian population, T allele of rs149474436 may play as a protective factor while the rs397780637 GG homozygotes may be associated with an increased risk of AD. Further studies should be considered in a larger cohort of patients with diverse demographics

Analysis of the non-volatile components and volatile compounds of hydrolysates derived from unmatured cheese curd hydrolysis by different enzymes

peer reviewedFifteen cheese protein hydrolysates were produced by using four different proteases. Then, the free amino acids (FAAs), molecular weight distribution (MWD), electronic tongue evaluation, and 45 volatile compounds of the corresponding products were evaluated, respectively. The results 46 suggested that 2SD had the strongest hydrolysis characteristic, followed by 6SD and FN. Samples 47 hydrolyzed for less than 6 h or more than 18 h contained great defects of taste. Peptides with 150 48 Da – 450 Da were mainly responsible for bitterness, saltiness, umami, and aftertaste in some enzyme 49 hydrolysis. Under the same total enzyme concentration condition, the sample hydrolyzed by 50 Flavourzyme and Neutrase for 18 h released more richness and less bitterness than the other systems, 51 which were characterized by butter and cream odor. Notably, it was found for the first time that 52 tetramethylpyrazine (TMP) was detected in cheese proteolysis with the highest content of 17.59 53 µg/g in Protease 2SD for 30 h. 2-Undecanone and acetoin played a key role in the flavor formation 54 of the tested samples. Regarding the different chemical families of volatiles, acids were more 55 abundant in the samples hydrolyzed by Protease 2SD and 6SD, while FN systems can achieve high 56 ketone content

Microstructural alterations of the hypothalamus in Parkinson's disease and probable REM sleep behavior disorder

Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial. We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels. This study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4. PD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I. Our study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Virus-Free and Live-Cell Visualizing SARS-CoV-2 Cell Entry for Studies of Neutralizing Antibodies and Compound Inhibitors

新型冠状病毒SARS-CoV-2在全球蔓延，给全球公共卫生带来严重威胁。快速研制疫苗、抗体和治疗药物成为科学界面临的重大挑战。由于SARS-CoV-2的高度传染性，采用病毒感染模型进行中和抗体及小分子抑制剂的药效评估需要在高等级生物安全实验室中进行，且常需要数天时间才能完成检测，限制了抗体和药物筛选的效率。发展快速、可视、不依赖于活病毒的新冠病毒入胞检测探针和细胞模型，对于加速新冠病毒抗体和药物的研究有重要意义。夏宁邵教授团队通过CHO真核表达系统高效表达制备出C端融合抗酸荧光蛋白Gamillus的重组新冠病毒spike蛋白STG。STG经SEC分子筛和冷冻电镜确认呈现与天然病毒刺突高度相似的三聚体结构，且与ACE2有很高的亲和力（18.2nM）。STG具备良好的细胞相容性和荧光性质，研究者进一步开发了可定量测定感染恢复期血清、疫苗免疫血清中和抗体（入胞阻断抗体）水平的CSBT检测方法。除了抗体检测评估方面的应用外，该研究发展的探针和模型还可用于筛选分析抑制新冠病毒入胞及胞内转运的小分子化合物。 我校博士后张雅丽，博士生王邵娟、巫洋涛，博士后侯汪衡、袁伦志和深圳市第三人民医院沈晨光博士为共同第一作者。厦门大学夏宁邵教授、袁权教授、程通教授为该论文共同通讯作者。The ongoing corona virus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system,a genetically engineered sensor of fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process is developed.In ACE2-expressing cells, it is found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.This study was supported by National Natural Science Foundation of China (81993149041 for N.X.; 81902057 for Y.Z.; 81871316 and U1905205 for Q.Y.), the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402‐002‐003 for T.C. and No. 2017ZX10202203‐009 for Q.Y.), the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2018ZX09711003‐005‐003 for T.C.), the Science and Technology Major Project of Fujian (2020YZ014001), the Science and Technology Major Project of Xiamen (3502Z2020YJ01), and the Guangdong Basic and Applied Basic Research Foundation (2020A1515010368 for C.S.). 该研究得到了国家自然科学基金、传染病防治国家科技重大专项、福建省应急科技攻关项目和厦门应急科技攻关项目的支持

Establishment of a predictive model for early virologic response in previously untreated chronic hepatitis B patients treated with telbivudine

Objective To investigate the establishment of a predictive model for early virologic response in previously untreated chronic hepatitis B (CHB) patients treated with telbivudine, since early virologic response can predict the long-term efficacy of nucleotide analogues. MethodsA total of 135 CHB patients who visited Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2007 to August 2014 were enrolled and treated with telbivudine (600 mg qd) for at least 24 weeks. Follow-up was performed once every 2 weeks, and the patients′ baseline data and data measured during treatment were recorded. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Cox proportional hazards regression model was used to analyze the influencing factors for early virologic response and establish the predictive model. ResultsThe patients without a family history of hepatitis B virus (HBV) infection (P=0.000 3) and with high baseline levels of total bilirubin (TBil) (P=0.002 6) and aspartate aminotransferase (AST) (P=0.007 4) and a low HBV DNA load (P=0.002 3) tended to show early virologic response. The predictive model was established based on these variables, and the risk score (R) of CHB patients was calculated. The CHB patients with R＞0.85 were more likely to achieve early virologic response. ConclusionThe model established based on the four variables of family history, baseline TBil level, baseline AST level, and HBV DNA level can well predict early virologic response in previously untreated CHB patients treated with telbivudine

Corrosion Behavior of Pipeline Steel X65 in Oilfield

The inner- and outer- surface corrosion behavior of X65 pipeline steel used in Shengli Chengdao oilfield was studied in this paper. The inner surface corrosion behavior of X65 pipeline steel in oil-water mixtures with different flow rate and oil content was examined by means of mass loss method and electrochemical technique. The corrosion resistance of the outer surface of X65 pipeline steel in soil extracts was also examined by means of polarization curves and electrochemical impedance spectroscopy (EIS). The phase constituents and surface morphology of corrosion products were characterized by using X-ray diffraction techniques (XRD) and scanning electron microscopy (SEM), respectively. The results indicated that the corrosion rate of X65 steel increased with the increasing flow rate of oil-water mixture, which could reach the maximum value when the oil content was 0.5% (mass fraction). The corrosion current density of X65 steel increased with immersion time in soil extracts. A loose corrosion product film formed on the steel surface, which can accelerate the cathodic depolarization reaction

Decreased risk of Parkinson's disease in diabetic patients with thiazolidinediones therapy: An exploratory meta-analysis.

BACKGROUND:It has been found that thiazolidinediones (TZDs) may play a protective role in animal models of Parkinson's disease (PD), while the results remain controversial whether TZDs protect against Parkinson's disease in humans. The purpose of this meta-analysis is to explore the association between TZDs use and the incidence of PD in diabetic patients. METHODS:A systematic online search was conducted to find studies published up to 31 December 2018. In our exploratory meta-analysis, studies comparing incidence of PD between TZD-treated and non-TZD-treated groups of diabetic patients were included. Data analysis was performed using a random or fixed effects model and expressed as odds ratios (OR) with 95% confidence interval (95% CI). We used the Cochrane Collaboration's Review Manager 5.3 software to analyze data. RESULTS:In total, 5 retrospective observational cohort studies were identified which met the inclusion criteria. The pooled odds ratio (OR) was 0.70 [95% CI, 0.51 to 0.96; p = 0.03] in a random-effects model, indicating a 30% lower risk of developing PD in diabetic patients treated with TZDs compared with non-TZD-treated patients. CONCLUSION:In this exploratory meta-analysis, we found that TZDs use was associated with reduced risk of PD in diabetic patients. However, this meta-analysis was not registered online although we followed a protocol designed for it. Further prospective observational studies with larger sample size and more strict inclusion criteria including controlling for diabetes complication severity index, hypoglycemic drugs combination, sex ratio, and comorbidity are needed to guide whether RCTs are warranted. And RCTs can better determine whether TZDs use could lower incidence of PD in diabetic patients