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"Wang, He"
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Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs
Background
As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing.
Results
We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel
COCH
+
fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues.
Conclusions
The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.
Journal Article
أرنوب لا يحب أذنية
تدور أحداث قصة \"أرنوب لا يجب أذنيه حول سوء فهم الأرنوب لولي لنفسه، لأنه أذنيه أصغر من آذان الأرانب الأخرى، فكان دائما يخاف من السخرية والاعتقاد بأنه فأر، لذلك قرر لولي ترك الأرانب، والتنكر في هيئة كلب ثم دب، وتتضمن القصة موضوعا مهما هو : الثقة بالنفس، وسواء أكنا أرانب أو طفلا أو بالغين فيجب أن نتعلم كيف نبني ثقتنا بأنفسنا، وأن ننظر إلأى أنفسنا نظرا صحيحا\"
BOOK
LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment
Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 (
LNMAT1
), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that
LNMAT1
promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. Mechanistically,
LNMAT1
epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter, which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and enhances transcription. Furthermore,
LNMAT1
-induced upregulation of CCL2 recruits macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C excretion. These findings provide a plausible mechanism for
LNMAT1
-modulated tumor microenvironment in lymphatic metastasis and suggest that
LNMAT1
may represent a potential therapeutic target for clinical intervention in LN-metastatic bladder cancer.
Mechanism of lymph node (LN) metastasis induced by tumor associated macrophages (TAMs) remains unclear. Here they demonstrate that a long noncoding RNA LNMAT1 promotes LN metastasis of bladder cancer via recruitment of TAMs through epigenetic regulation of CCL2 expression.
Journal Article
Online Network Revenue Management Using Thompson Sampling
Thompson sampling is a randomized Bayesian machine learning method, whose original motivation was to sequentially evaluate treatments in clinical trials. In recent years, this method has drawn wide attention, as Internet companies have successfully implemented it for online ad display. In “Online network revenue management using Thompson sampling,” K. Ferreira, D. Simchi-Levi, and H. Wang propose using Thompson sampling for a revenue management problem where the demand function is unknown. A main challenge to adopt Thompson sampling for revenue management is that the original method does not incorporate inventory constraints. However, the authors show that Thompson sampling can be naturally combined with a linear program formulation to include inventory constraints. The result is a dynamic pricing algorithm that incorporates domain knowledge and has strong theoretical performance guarantees as well as promising numerical performance results. Interestingly, the authors demonstrate that Thompson sampling achieves poor performance when it does not take into account domain knowledge. Finally, the proposed dynamic pricing algorithm is highly flexible and is applicable in a range of industries, from airlines and internet advertising all the way to online retailing.
We consider a price-based network revenue management problem in which a retailer aims to maximize revenue from multiple products with limited inventory over a finite selling season. As is common in practice, we assume the demand function contains unknown parameters that must be learned from sales data. In the presence of these unknown demand parameters, the retailer faces a trade-off commonly referred to as the “exploration-exploitation trade-off.” Toward the beginning of the selling season, the retailer may offer several different prices to try to learn demand at each price (“exploration” objective). Over time, the retailer can use this knowledge to set a price that maximizes revenue throughout the remainder of the selling season (“exploitation” objective). We propose a class of dynamic pricing algorithms that builds on the simple, yet powerful, machine learning technique known as “Thompson sampling” to address the challenge of balancing the exploration-exploitation trade-off under the presence of inventory constraints. Our algorithms have both strong theoretical performance guarantees and promising numerical performance results when compared with other algorithms developed for similar settings. Moreover, we show how our algorithms can be extended for use in general multiarmed bandit problems with resource constraints as well as in applications in other revenue management settings and beyond.
The online appendix is available at
https://doi.org/10.1287/opre.2018.1755
.
Journal Article
Pharmacokinetics of Anthraquinones from Medicinal Plants
Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.
Journal Article
نهر الرمال
لم يستطع سان تسانغ ومعه وو كونغ وبا جيه إكمال رحلتهم إلى الغرب بسبب نهر الرمال المتحركة الذي اعترض طريقهم، وكان يعيش في النهر شيطان له «عقد» ضخم مكون من تسع جماجم أراد التهام الراهب سان تسانغ فخاض با جيه قتالا عنيفا مع الشيطان ولكنه لم يهزمه وحين هاجمه القرد بعصاه الحديدية فر الشيطان هاربا إلى قاع النهر ولم يجرؤ على الخروج فنزل با جيه في النهر وحاول استدراج الشيطان إلى الشاطئ ليقبض عليه القرد، لكن الشيطان حين رأى القرد غاص في قاع النهر، فلجأ القرد إلى قوان بن طلبا للمساعدة، لكن اتضح أن قوان بن أثارت الشيطان وأمرته باتباع سان تسانغ فأرسلت مساعدها مو تشا لمساعدتهم وبعد أن عرف الشيطان أن سان تسانغ هو راهب تانغ، وافق على أن يصبح تلميذه الثالث، وأطلق عليه سان تسانغ : «الراهب شا» ثم استخدم مو : ثم استخدم مو تشا القرع الأحمر الذي أعطته له قوان ين، ووضعه على عقد الجماجم وحولهما إلى قارب واستطاع سان تسانغ مع تلاميذه الثلاثة عبور النهر ومواصلة رحلتهم.
Book
Depression and anxiety in relation to cancer incidence and mortality: a systematic review and meta-analysis of cohort studies
The link between depression and anxiety status and cancer outcomes has been well-documented but remains unclear. We comprehensively quantified the association between depression and anxiety defined by symptom scales or clinical diagnosis and the risk of cancer incidence, cancer-specific mortality, and all-cause mortality in cancer patients. Pooled estimates of the relative risks (RRs) for cancer incidence and mortality were performed in a meta-analysis by random effects or fixed effects models as appropriate. Associations were tested in subgroups stratified by different study and participant characteristics. Fifty-one eligible cohort studies involving 2,611,907 participants with a mean follow-up period of 10.3 years were identified. Overall, depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted RR: 1.13, 95% CI: 1.06–1.19), cancer-specific mortality (1.21, 1.16–1.26), and all-cause mortality in cancer patients (1.24, 1.13–1.35). The estimated absolute risk increases (ARIs) associated with depression and anxiety were 34.3 events/100,000 person years (15.8–50.2) for cancer incidence and 28.2 events/100,000 person years (21.5–34.9) for cancer-specific mortality. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety were related to higher cancer incidence, poorer cancer survival, and higher cancer-specific mortality. Psychological distress (symptoms of depression and anxiety) was related to higher cancer-specific mortality and poorer cancer survival but not to increased cancer incidence. Site-specific analyses indicated that overall, depression and anxiety were associated with an increased incidence risks for cancers of the lung, oral cavity, prostate and skin, a higher cancer-specific mortality risk for cancers of the lung, bladder, breast, colorectum, hematopoietic system, kidney and prostate, and an increased all-cause mortality risk in lung cancer patients. These analyses suggest that depression and anxiety may have an etiologic role and prognostic impact on cancer, although there is potential reverse causality; Furthermore, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. Early detection and effective intervention of depression and anxiety in cancer patients and the general population have public health and clinical importance.
Journal Article