The renovation and revitalization of vernacular architecture are pivotal in sustainable rural development. In regions like Shangri-La, traditional structures not only safeguard cultural heritage but also provide a foundation for enhancing local communities’ living conditions. However, these villages face growing challenges, including infrastructure decay, cultural erosion, and inadequate adaptation to modern living standards. Addressing these issues requires innovative research approaches that combine heritage preservation with the integration of contemporary functionality. This study employs a research-by-design approach, focusing on the Shanpian House as a case study, to explore how pre-planning and post-evaluation methods can revitalize traditional vernacular architecture. The pre-planning phase utilizes field surveys and archival research to assess spatial, cultural, and environmental conditions, framing a design strategy informed by field theory. In doing so, it evaluates how traditional architectural elements can be preserved while introducing modern construction techniques that meet current living standards. The post-evaluation phase, conducted through questionnaires and semi-structured interviews, assesses user satisfaction, focusing on the impact of architectural esthetics, structural stability, and material choices. Key findings from an OLS regression highlight the strong positive correlation between architectural style, structural choices, and cultural relevance with resident satisfaction. The research emphasizes that design elements such as structural details, materials, and infrastructure upgrades are critical in shaping perceptions of both functionality and cultural identity. Interestingly, the model reveals that improving architectural esthetics, alongside modern indoor features such as network connectivity, has a significant impact on enhancing overall resident satisfaction (significance level: 0.181). This study contributes to the broader discourse on sustainable building renovation by demonstrating how traditional architecture can be thoughtfully adapted for contemporary use and also proposes a paradigm shift in the renovation of historic buildings, advocating for a balance between preservation and modernization. The application of sustainable materials, digital modeling, and innovative construction techniques further ensures that these traditional structures meet the demands of modern civilization while maintaining their cultural integrity.
Abstract Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer and the second leading cause of cancer-related mortality worldwide. The overall prognosis of HCC patients is very poor because it is susceptible to recurrence and metastasis. According to the cancer stem cell (CSC) model, there is a small subset of cancer cells within the tumor bulk that is responsible for tumor relapse and metastasis. CSCs represent cells that can self-renew, initiate tumors, and keep resistant to anti-cancer treatment. However, the fate and signatures of CSCs in HCC remain elusive. Our previous in vitro hepatocyte differentiation model successfully mimicked the liver developmental process from the stage of embryonic stem cells, endoderm, liver progenitor cells, and premature hepatocytes, together with one pair of nontumor and tumor tissue from an HCC patient. We found that the expression of keratin 17 (KRT17) reached its peak at the liver progenitor stage and was down-regulated along with liver development, which shared the same expression pattern with keratin 19 (CK19), a well-known HCC stemness-associated gene. Single-cell RNA sequencing in 9 HCC clinical samples from the GEO dataset revealed that KRT17 was expressed in less than 1% of tumor cells. Moreover, KRT17 shared similar expression patterns among hepatocytes, non-stem like HCC and stem like HCC subpopulations with a panel of hepatic stem cell markers and showed reverse trends with a list of hepatic markers. Clinically, KRT17 was highly expressed in cancer tissues compared to normal counterparts and positively correlated with poor overall survival. Functional assays indicated that KRT17 could considerably facilitate the self-renewal, growth, and metastasis properties of HCC both in vitro and in vivo. Also, KRT17 endowed HCC cells with enhanced resistance to sorafenib treatment. Moreover, the expressions of the CSC marker (CD133) and oncofetal drivers (NANOG and KLF4) were significantly upregulated upon KRT17 overexpression. Bioinformatic analysis using gene expression profiles of patients from the TCGA database revealed that development- and differentiation-related biological processes were dramatically enriched in KRT17-high patients. The underlying molecular mechanism of how KRT17 augments HCC stemness still needs further study. Overall, our study uncovered a new connection between KRT17 and HCC stemness and progression. KRT17 might be a novel marker of CSC and a prognostic biomarker for the treatment of HCC patients. Citation Format: Xiaona Fang, Shan Liu, Liuxian Ban, Jiao Huang, Jie Luo, Lanqi Gong, Baifeng Zhang, Beilei Liu, Jinlin Huang, Yuma Yang, Ching Ngar Wong, Qian Yan, Xin-Yuan Guan. Identification and characterization of the role of KRT17 in the stemness regulation of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2441.
<div>Abstract<p>Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8<sup>+</sup> T-cell cytotoxicity. Mechanistically, FASN inhibition reduced palmitoylation of MHC-I that led to its lysosomal degradation. The palmitoyltransferase DHHC3 directly bound MHC-I and negatively regulated MHC-I protein levels. In an orthotopic HCC mouse model, <i>Fasn</i> deficiency enhanced MHC-I levels and promoted cancer cell killing by tumor-infiltrating CD8<sup>+</sup> T cells. Moreover, the combination of two different FASN inhibitors, orlistat and TVB-2640, with anti–PD-L1 antibody robustly suppressed tumor growth <i>in vivo</i>. Multiplex IHC of human HCC samples and bioinformatic analysis of The Cancer Genome Atlas data further illustrated that lower expression of <i>FASN</i> was correlated with a higher percentage of cytotoxic CD8<sup>+</sup> T cells. The identification of FASN as a negative regulator of MHC-I provides the rationale for combining FASN inhibitors and immunotherapy for treating HCC.</p>Significance:<p>Inhibition of FASN increases MHC-I protein levels by suppressing its palmitoylation and lysosomal degradation, which stimulates immune activity against hepatocellular carcinoma and enhances the efficacy of immune checkpoint inhibition.</p></div>
'/%3e%3cuse xlink:href='%23a' transform='rotate(144 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(216 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(288 450 300)'/%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)