17 research outputs found
Single-cell spatial profiling of small cell lung cancer suggests clinical outcome related tumor heterogeneity and immune colony niche
No full text<p>High-dimension processed tif images of the publication "<strong>Spatial evolution and colony landscape of small cell lung cancer</strong>". The code used to produce the results of this study is available at <a href="https://github.com/ wangjun-hub/CODEX_SCLC">https://github.com/ wangjun-hub/CODEX_SCLC</a>.</p>
Sensitivity of cultured SGC7901 cells to chemotherapy agents and therapeutic effect of 5-FU in patients with stage IV GC.
No full text<p>(<b>a</b>) Cells exposed to 5-FU showed better viability in the sh-XB130 group than in the scramble group (n = 3–4 at each concentration in each group). (<b>b</b>) Cell viability in the sh-XB130 group is dramatically reduced by exposure to cisplatin (n = 5–10 at each concentration in each group). (<b>c</b>) Irinotecan also reduced cell viability in the sh-XB130 group (n = 3–4 at each concentration in each group). <sup>*</sup><i>p</i><0.05, <sup>†</sup><i>p</i><0.01, <sup>‡</sup><i>p</i><0.001 vs. wild-type cells at the corresponding concentration. (<b>d</b>) XB130-negative patients had a lower survival rate when treated by 5-FU (Fu = 1).</p
Drilling and completion challenges in the deepwater South China Sea – a case study of the Lufeng 22-1 oilfield
No full textMaster's thesis in Offshore technology : Industrial asset managementThe thesis start form the introduction of the background and basic information of the deepwater operations both in the world and in South China Sea, make all the readers have a comprehensive and clear understand on the deepwater oil and gas area, especially in South China Sea; and then fully identify the challenges and problems which the deepwater operation in South China Sea faced, from Three aspects which are environment conditions, facilities, and technologies.
Chapter 2 will introduce the detailed environment factors, which include typhoon, current, temperature, water depth, shallow water flow, shallow gas, and hydrate formation. In the end of chapter 2 the author will emphasize the special marine nature and geological environment conditions.
Chapter 3 will introduce the challenges from the facilities, and primarily introduce the facility selection criteria. Chapter 4 will introduce the technology challenges of offshore deepwater oil and gas development, the author also divide the introduction into two parts, first part is the common technology challenges worldwide, the second part is the special technology challenges in the South China Sea.
The solutions and advices of some of the challenges and problems will list out, and the further study areas also will point out. At last, a case study of the successful development of the first deepwater oilfield in South China Sea, the development of the Lufeng 22-1 oilfield, will be discussed particularly, and some inspirations and experiences will be summarized in the discussions and conclusions as the suggestion for the deepwater operation in South China Sea
Effects of sea buckthorn seeds oil, wild melon seeds oil and ursolic acid on plasma cholesterol and gut microbiota in hypercholesterolemic hamsters
No full textPh.D.Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and hypercholesterolemia is recognized as one of the primary risk factors. Dietary intervention to manage hypercholesterolemia is generally considered to be a safe and effective strategy to prevent the incidence of heart diseases. The gut microbiota has been noted to influence host blood lipids and potentially impact the development of cardiovascular diseases. The purpose of the present study was (i) to evaluate the effects of sea buckthorn seeds oil (SBSO), wild melon seeds oil (CO) and ursolic acids (UA) on plasma cholesterol; (ii) to explore the potency of SBSO, CO and UA in modulating gut microbiota; and (iii) to investigate the related underlying mechanisms in hypercholesterolemic hamsters.Sea buckthorn is one of the most important shrubs grown widely in China. It has been traditionally used as a natural remedy for the prevention of heart diseases, diabetes, and cancer. Recent studies have also indicated that SBSO may possess a variety of health benefits. The first part of the thesis research aimed to examine the effect of SBSO on blood cholesterol in hypercholesterolemic hamsters. Four groups of hamsters (n=8 each) were given one of four diets, namely a non-cholesterol control diet (NCD), a high-cholesterol diet (HCD) containing 0.1% cholesterol, and HCD diet with sea buckthorn seed oil replacing 50% lard (SL) or replacing 100% lard (SH). Feeding SL and SH diets could reduce blood total cholesterol by 20-22%. This was accompanied by downregulation on gene expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA-R), acyl-CoA: cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporter subfamily G member 8 (ABCG8). SBSO supplementation also increased the production of intestinal short-chain fatty acids (SCFAs) and fecal outputs of neutral sterols. The metagenomic analysis demonstrated that feeding SL and SH diets could favorably modulate the relative abundance of Bacteroidales_S24- 7_group, Ruminococcaceae, and Eubacteriaceae. It was therefore concluded that SBSO was effective in reducing blood cholesterol in hypercholesterolemic hamsters via inhibiting hepatic cholesterol synthesis, increasing intestinal cholesterol excretion and promoting the growth of SCFAs-producing bacteria.CO is rich in polyunsaturated fatty acids and phytosterols. The second part of the present study was to investigate the effects of CO on blood cholesterol and gut microbiota in hamsters fed a high cholesterol diet. Hamsters (n=32) were randomly divided into four groups fed one of the four diets namely NCD, HCD, HCD diet containing 4.75% CO, and HCD diet containing 9.5% CO for 6 weeks respectively. Results showed that supplementation of CO at 9.5% reduced plasma cholesterol by 24% and increased the excretion of fecal bile acids by 150%. This was accompanied by up-regulation on the gene expression of hepatic cholesterol 7α-hydroxylase (CYP7A1). In addition, CO supplementation remarkably increased the production of fecal short-chain fatty acids and favorably altered the relative abundance of Eubacteriaceae, Clostridiales_vadinBB60_group, Ruminococcaceae, Streptococcaceae and Desulfovibrionaceae at a family level. It was concluded that CO could favorably reduce plasma cholesterol via promoting the excretion of fecal acidic sterols and modulating gut microbiota.UA, a pentacyclic triterpenoid acid, is abundantly present in fruits and vegetables. Most previous researches have focused on its anti-cancer, anti-inflammatory and antioxidant properties. The third part of the thesis was to examine the effect of UA on cholesterol metabolism and gut microbiota in hamsters. Thirty-two hamsters were assigned into four groups receiving an NCD, an HCD and two HCD diets containing 0.2% and 0.4%, respectively, for 6 weeks. Results suggested that the UA administration significantly reduced plasma TC by 15%-16%, and non-HDL-C by 26%-30%, respectively. This was accompanied by the reduction in liver cholesterol and down-regulation on the gene expression of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA-R). Meanwhile, UA supplementation significantly increased the fecal short chain fatty acids concentration and favorably changed the proportion of Bacteroidales_S24-7_group, Ruminococcaceae and Bifidobacterium. In conclusion, the present study clearly demonstrated UA exhibited the cholesterol lowering activity by regulating cholesterol synthesis in the liver and altering gut microbiota.Taken together, it can be summarized that sea buckthorn seeds oil, wild melon seeds oil and ursolic acid were effective in the prevention of hypercholesterolemia and modulation of gut microbiota in hamsters.心血管疾病（CVDs）是全球死亡的主要原因，而高膽固醇血症被認為是主要的危險因素之一。通過飲食干預來控制高膽固醇血症是預防心血管疾病安全有效的措施。研究表明腸道菌群有助於調節宿主血脂，可能進一步影響心血管疾病的發展。本文以金黃地鼠為模型，研究探討了沙棘籽油（SBSO），野生瓜籽油（CO）和熊果酸（UA）對血漿膽固醇和腸道菌群的影響及其相關潛在機制。沙棘是中國重要的灌木之一。傳統上，沙棘被广泛用于預防心髒病，糖尿病和癌症。最近的研究表明，沙棘籽油可能具有降胆固醇的活性。本論文研究第一部分旨在探索沙棘籽油對高膽固醇倉鼠血膽固醇的影響。将倉鼠（每組n = 8）隨機分為四組并提供四種飲食中的一種，即非膽固醇對照飲食（NCD），含0.1％膽固醇的高膽固醇飲食（HCD），用沙棘籽油替代50％豬油的高膽固醇飲食（SL），或用沙棘籽油更換100％豬油的高膽固醇飲食（SH）。結果表明，飼餵SL和SH飲食可以使血液中的總膽固醇降低20-22％。同時伴隨著對HMG-CoA-R, ACAT2， MTP和ABCG8基因表達的下調。沙棘籽油還增加了腸道短鏈脂肪酸（SCFAs）的產生和糞便中性固醇的輸出。宏基因組學分析表明，飼餵SL和SH飲食可以有利地調節Bacteroidales_S24-7_group, Ruminococcaceae, 和 Eubacteriaceae的相對豐度。綜上所述，沙棘籽油是通過抑制肝脏胆固醇合成，提升腸道膽固醇排泄和促進產生短鏈脂肪酸的細菌的生長來調節高膽固醇血症倉鼠的血液膽固醇。野生瓜籽油（CO）富含多不飽和脂肪酸和植物甾醇。本研究的第二部分旨在研究，在高膽固醇飲食倉鼠中，CO對血液膽固醇和腸道菌群的影響。倉鼠（n = 32）被隨機分為四組，分別餵食NCD，HCD，含4.75％CO的高膽固醇飲食和含9.5％CO的高膽固醇飲食這四種飲食之一。結果顯示，添加9.5％野生瓜籽油可使血漿膽固醇降低24％，並使糞便膽汁酸的排泄增加150％。同時還促進了肝膽CYP7A1基因表達的上調。此外，補充野生瓜籽油可顯著增加糞便短鏈脂肪酸的含量，並有利地改變了Eubacteriaceae, Clostridiales_vadinBB60_group, Ruminococcaceae, Streptococcaceae 和 Desulfovibrionaceae的相對豐度。所以，野生瓜籽油可以通過促進糞便酸性固醇的排泄和調節腸道菌群來降低血漿膽固醇。熊果酸（UA）是一種五環三萜酸，廣泛的分佈於水果和蔬菜中。以前大多數的研究都集中在探索其抗癌，抗炎和抗氧化的特性。本研究的第三部分旨在探索UA對倉鼠膽固醇代謝和腸道菌群的影響。首先將三十二隻倉鼠隨機分為四組，分別用NCD，HCD，含0.2％的高膽固醇飲食和0.4％的高膽固醇飲食餵養。 6週後，結果表明，飼養UA可使血漿總膽固醇分別降低15％-16％，而使非高密度膽固醇降低26％-30％。同時隨著肝膽HMG-CoA-R基因表達的下調。此外，熊果酸顯著增加了糞便短鏈脂肪酸的排除，並有利地改變了Bacteroidales_S24-7_group, Ruminococcaceae 和 Bifidobacterium 的相對含量。總之，本研究表明，熊果酸通過調節肝臟膽固醇合成和改變腸道菌群而表現出降低膽固醇的活性。综上所述，沙棘籽油、野生瓜籽油和熊果酸在預防高膽固醇血症和調節腸道菌群方面是有效的。Hao, Wangjun.Thesis Ph.D. Chinese University of Hong Kong 2020.Includes bibliographical references (leaves 135-153).Abstracts also in Chinese.Title from PDF title page (viewed on January 19, 2022)
Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing
No full textCirculating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC.UICC Fellowship [ICR15-353370]; Wu Jieping Medical Foundation [320.6750.15177]; National Institutes of Health [R01 CA90427, R01 AI084811]SCI(E)[email protected]; [email protected]
An Account of Development of Performance Art in China from 1979-2010
No full textThe research study aims to raise questions about and gain new insights into the development of performance art in China.
The development of performance art in China is set out in a chronological account of the events and art works that illustrate the development of a permissive, open-ended medium with endless variables. The events and works included in this study are executed by Chinese artists impatient with the limitations of traditional or established forms and determined to take their performance art works directly to the public. Following the rapid socio-economic development that started in the late 1970's, soon after the end of the Cultural Revolution and the start of economic reform.
The chronological account of the development of Chinese performance art explains how Chinese artists, in creating their work, draw freely on a number of disciplines and media including literature, poetry, theatre, music, dance, architecture and painting, as well as video, film, slides and narrative. The account also illustrates how Chinese performance art has gradually moved away from the traditions of Chinese performance and how performance art works often promote interpretive individualism.
Research shows that Chinese artists choose performance art to break free from the dominant media and the constraints of working within the evolving social and political environment in China. Research further shows that artists use performance art as a provocation to respond to changes. Finally, performance art is gaining acceptance from the public in recent Chinese socio-economic development
Silencing of XB130 is associated with both the prognosis and chemosensitivity of gastric cancer.
No full textXB130 is a newly characterized adaptor protein that was reported to promote thyroid tumor growth, but its role in the progression of other kinds of cancer such as gastric cancer (GC) remains unknown. Accordingly, we investigated the association between XB130 expression and the prognosis of GC patients. The subjects were 411 patients with GC in stages I to IV. XB130 expression was examined in surgical specimens of GC. Kaplan-Meier analysis and the Cox proportional hazards model were used to assess the prognostic significance of XB130 for survival and recurrence. Moreover, GC cells stably transfected with XB130 short hairpin RNA were established to analyze the effect of XB130 on sensitivity of chemotherapy. The results show that both XB130 mRNA and protein expression were detectable in normal gastric tissues. The overall survival time of stage IV patients and the disease-free period after radical resection of GC in stage I-III patients were significantly shorter when immunohistochemical staining for XB130 was low than when staining was high (both p<0.05). XB130 expression also predicted tumor sensitivity to several chemotherapy agents. Viability of both XB130-silenced SGC7901 cells and wild-type cells was suppressed by 5-fluorouracil (5-FU), cisplatin, and irinotecan in a dose-dependent way, but cisplatin and irinotecan were more sensitive against sXB130-silenced GC cells and 5-FU showed higher sensitivity to wild-type cells. When treated by 5-FU, patients with high expression of XB130 tumors had a higher survival rate than those with low expression tumors. These findings indicate that reduced XB130 protein expression is a prognostic biomarker for shorter survival and a higher recurrence rate in patients with GC, as well as for the response to chemotherapy
Genetic and microenvironmental evolution of colorectal liver metastases under chemotherapy
No full textDrug resistance limits the efficacy of chemotherapy for colorectal cancer liver metastasis (CRLM). However, the evolution of CRLM during drug treatment remains poorly elucidated. Multi-omics and treatment response data from 115 samples of 49 patients with CRLM undergoing bevacizumab (BVZ)-based chemotherapy show little difference in genomic alterations in 92% of cases, while remarkable differences are observed at the transcriptomic level. By decoupling intrinsic and acquired resistance, we find that hepatocyte and myeloid cell infiltration contribute to 38.5% and 23.1% of acquired resistance, respectively. Importantly, SMAD4 mutations and chr20q copy-number gain are associated with intrinsic chemoresistance. Gene interference experiments suggest that SMAD4R361H/C mutations confer BVZ and 5-fluorouracil (5-FU) resistance through STAT3 signaling. Notably, supplementing BVZ and 5-FU with the STAT3 inhibitor GB201 restores therapeutic efficacy in SMAD4R361H/C cancer cells. Our study uncovers the evolutionary dynamics of CRLM and its microenvironment during treatment and offers strategies to overcome drug resistance.</p
Structural Basis for the Immunogenicity of the C-Terminus of VP1 of Echovirus 3 Revealed by the Binding of a Neutralizing Antibody
No full textEchovirus 3 (E3), a serotype of human enterovirus B (HEV-B), causes severe diseases in infants. Here, we determined the structures of E3 with a monoclonal antibody (MAb) 6D10 by cryo-EM to comprehensively understand the specificities and the immunological characteristic of this serotype. The solved cryo-EM structures of the F-, A-, and E-particles of E3 bound with 6D10 revealed the structural features of the virus–antibody interface. Importantly, the structures of E-particles bound with 6D10 revealed for the first time the nature of the C-terminus of VP1 for HEV-Bs at the structural level. The highly immunogenic nature of this region in the E-particles provides new strategies for vaccine development for HEV-Bs
