Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
12,015
result(s) for
"Tian, Lin"
Sort by:
Collaborative Consumption: Strategic and Economic Implications of Product Sharing
Recent technological advances in online and mobile communications have enabled collaborative consumption or product sharing among consumers on a massive scale. Collaborative consumption has emerged as a major trend as the global economic recession and social concerns about consumption sustainability lead consumers and society as a whole to explore more efficient use of resources and products. We develop an analytical framework to examine the strategic and economic impact of product sharing among consumers. A consumer who purchased a firm’s product can derive different usage values across different usage periods. In a period with low self-use value, the consumer may generate some income by renting out her purchased product through a third-party sharing platform as long as the rental fee net of transaction costs exceeds her own self-use value. Our analysis shows that transaction costs in the sharing market have a nonmonotonic effect on the firm’s profits, consumer surplus, and social welfare. We find that when the firm strategically chooses its retail price, consumers’ sharing of products with high marginal costs is a win-win situation for the firm and the consumers, whereas their sharing of products with low marginal costs can be a lose-lose situation. Furthermore, in the presence of the sharing market, the firm will find it optimal to strategically increase its quality, leading to higher profits but lower consumer surplus.
This paper was accepted by J. Miguel Villas-Boas, marketing
.
Journal Article
Analysis of the Artistic Effect of Garden Plant Landscaping in Urban Greening
At present, China is at an essential stage in the progress of social civilisation. At the same time, China's current economic level is developing rapidly and the level of urbanisation is also increasing. However, the uncontrolled development of urban space and excessive consumption of land resources have led to many urban ecological and environmental problems. As a result, there is an urgent need to improve the urban habitat. Plant landscaping is an important part of the urban environment. In addition, plant landscaping is also a crucial part of the visual arts and plays a key role in the shaping of urban spaces. In the context of the urban construction boom, people are increasingly demanding quality in the urban environment. Spatial scale, as a vital factor influencing the visual effect of planting, is gradually becoming a focus of landscape design. Urban greening based on plant landscape can not only improve the urban ecological environment and enhance people’s quality of life but also resolve the contradiction between the demand for urban green space and the continuous reduction of urban greening land. Therefore, plant landscaping is recognised as a key step towards global sustainable development. However, according to current research and application practice, the development of urban greenery is limited and hindered by the value of plant landscaping and its applications. In addition, no comprehensive theoretical system has yet been established at the plant scale. In other words, there are still problems of scale in plant landscaping, such as unreasonable density, disproportion, and unclear hierarchy. Therefore, this paper begins with the definition of plant spatial scale in the city and analyses plant spatial types and scale characteristics from multiple perspectives, so as to establish an overall knowledge of plant landscaping. After that, through a study of the current situation of plant landscaping in cities, a quantitative analysis of the visual scale of plant space in urban squares is carried out to address the issues of plant scale design in this research. The focus of the analysis is on the scale of plants in relation to related elements. Furthermore, this study explores the influence of visual aesthetic scale and psychological scale on planting based on the functional scale of plant elements. Finally, the above quantitative analyses are applied to derive some relative data criteria and to summarise the design strategies for the spatial scale of planting in the city. The findings of this study can provide some guiding suggestions and references for the future construction of urban greenery, thus promoting the orderly development of plant landscaping in cities.
Journal Article
Expanding C–T base editing toolkit with diversified cytidine deaminases
Base editing tools for cytosine to thymine (C–T) conversion enable genome manipulation at single base-pair resolution with high efficiency. Available base editors (BEs) for C–T conversion (CBEs) have restricted editing scopes and nonnegligible off-target effects, which limit their applications. Here, by screening diversified lamprey cytidine deaminases, we establish various CBEs with expanded and diversified editing scopes, which could be further refined by various fusing strategies, fusing at either N-terminus or C–terminus of nCas9. Furthermore, off-target analysis reveals that several CBEs display improved fidelity. Our study expands the toolkits for C–T conversion, serves as guidance for appropriate choice and offers a framework for benchmarking future improvement of base editing tools.
Cytosine base editors are limited by editing scope and potential off-target effects. Here the authors screen diversified lamprey cytidine deaminases along with different protein fusion architectures and present base editors with improved fidelity.
Journal Article
Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials
p53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53–MDM2 negative feedback loop. Abnormal p53 can be observed in almost all tumors, mainly including p53 mutation and functional inactivation. Blocking MDM2 to restore p53 function is a hotspot in the development of anticancer candidates. Till now, nine MDM2 inhibitors with different structural types have entered clinical trials. However, no MDM2 inhibitor has been approved for clinical application. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53–MDM2 interaction.
Journal Article
m6A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1
Background
Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified.
Methods
lncRNA expression profiles in matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138 J23.1 (RP11), in development of CRC were checked both in vitro and in vivo. Its association with clinical progression of CRC was further analyzed.
Results
RP11 was highly expressed in CRC tissues, and its expression increased with CRC stage in patients. RP11 positively regulated the migration, invasion and epithelial mesenchymal transition (EMT) of CRC cells in vitro and enhanced liver metastasis in vivo. Post-translational upregulation of Zeb1, an EMT-related transcription factor, was essential for RP11-induced cell dissemination. Mechanistically, the RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m
6
A methylation was involved in the upregulation of RP11 by increasing its nuclear accumulation. Clinical analysis showed that m
6
A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC.
Conclusions
m
6
A-induced lncRNA RP11 can trigger the dissemination of CRC cells via post-translational upregulation of Zeb1. Considering the high and specific levels of RP11 in CRC tissues, our present study paves the way for further investigations of RP11 as a predictive biomarker or therapeutic target for CRC.
Journal Article
UGI relocation inside Cas9 reduces Cas9 dependent off target effects in cytosine base editors
Cytosine base editors (CBEs) achieve precise C-to-T conversions by addition of uracil DNA glycosylase inhibitor (UGI) with Cas9 nickase (nCas9) and cytidine deaminase, and the conventional fusion at the nCas9 carboxyl terminus effectively inhibits uracil excision repair to enhance editing efficiency. However, despite potent on-target activity, classical CBEs exhibit significant Cas9-dependent DNA off-target effects that necessitate optimization for future applications. Here we present a strategic UGI relocation through internal fusion within the nCas9 architecture. This spatial reorganization maintains comparable on-target editing efficiency while substantially reducing Cas9-dependent DNA off-target activity. Our findings establish an alternative engineering paradigm to develop high-fidelity CBEs, offering an improved platform for widespread genome editing applications.
Journal Article
TRADABILITY AND THE LABOR-MARKET IMPACT OF IMMIGRATION
In this paper, we study how occupation (or industry) tradability shapes local labor-market adjustment to immigration. Theoretically, we derive a simple condition under which the arrival of foreign-born labor into a region crowds native-born workers out of (or into) immigrant-intensive jobs, thus lowering (or raising) relative wages in these occupations, and we explain why this process differs within tradable versus within non-tradable activities. Using data for U.S. commuting zones over the period 1980–2012, we find—consistent with our theory—that a local influx of immigrants crowds out employment of native-born workers in more relative to less immigrant-intensive nontradable jobs, but has no such effect across tradable occupations. Further analysis of occupation labor payments is consistent with adjustment to immigration within tradables occurring more through changes in output (versus changes in prices) when compared to adjustment within nontradables, thereby confirming our model’s theoretical mechanism. We then use the model to explore the quantitative consequences of counterfactual changes in U.S. immigration on real wages at the occupation and region level.
Journal Article
KDM5A silencing transcriptionally suppresses the FXYD3‐PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR‐433 up‐regulation
Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP‐qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR‐433, while dual luciferase assay was carried out to confirm the targeting relationship between miR‐433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo‐tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A‐miR‐433‐FXYD3‐PI3K‐AKT axis in the progression of HCC after loss‐ and gain‐function assays. KDM5A p‐p85 and p‐AKT were highly expressed but miR‐433 was down‐regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR‐433 by demethylating H3K4me3 on its promoterregion. miR‐433 negatively targeted FXYD3. Depleting miR‐433 or re‐expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down‐regulated miR‐433 and up‐regulated FXYD3‐PI3K‐AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3‐PI3K‐AKT axis to enhance angiogenesis in HCC by suppressing miR‐433.
Journal Article
Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions
The Chimera antigen receptor (CAR)-T cell therapy has gained great success in the clinic. However, there are still major challenges for its wider applications in a variety of cancer types including lack of effectiveness due to the highly complex tumor microenvironment, and the forbiddingly high cost due to the personalized manufacturing procedures. In order to overcome these hurdles, numerous efforts have been spent focusing on optimizing Chimera antigen receptors, engineering and improving T cell capacity, exploiting features of subsets of T cell or NK cells, or making off-the-shelf universal cells. Here, we developed induced pluripotent stem cells (iPSCs)-derived, CAR-expressing macrophage cells (CAR-iMac). CAR expression confers antigen-dependent macrophage functions such as expression and secretion of cytokines, polarization toward the pro-inflammatory/anti-tumor state, enhanced phagocytosis of tumor cells, and in vivo anticancer cell activity. This technology platform for the first time provides an unlimited source of iPSC-derived engineered CAR-macrophage cells which could be utilized to eliminate cancer cells.
Journal Article