BackgroundThe phosphatidylinositol 3-kinase (PI3K) is frequently hyperactivated in cancer and plays important roles in both malignant and immune cells. The effect of PI3Kα inhibitors on the tumor microenvironment (TME) remains largely unknown. Here, we investigated the modulation of the TME by a clinical PI3Kα-specific inhibitor CYH33.MethodsThe activity of CYH33 against a panel of murine tumors in the immune-competent context or athymic mice was detected. Single-cell RNA sequencing and multi-parameter flow cytometry were performed to determine the immune profiling of TME. The effect of CYH33 on immune cells was conducted with primary murine cells.ResultsCYH33 exhibited more potent antitumor activity in immune-competent context. CYH33 enhanced the infiltration and activation of CD8+T and CD4+T cells, while attenuating M2-like macrophages and regulatory CD4+T cells. Increase in memory T cells was confirmed by the induction of long-term immune memory on CYH33 treatment. Mechanistically, CYH33 relieved the suppressed expansion of CD8+T cells via preferential polarization of the macrophages to the M1 phenotype. CYH33 promoted fatty acid (FA) metabolism in the TME, while FA enhanced the activity of CD8+T cells in vitro. The combination of CYH33 with the FA synthase (FASN) inhibitor C75 synergistically inhibited tumor growth with enhanced host immunity.ConclusionsCYH33 induces immune activation and synergizes with FASN inhibitor to further promote the antitumor immunity, which gains novel insights into how PI3K inhibitors exert their activity by modulating TME and provides a rationale for the concurrent targeting of PI3K and FASN in breast cancer treatment.

The green building certification system of Taiwan, EEWH (Ecology, Energy Saving, Waste Reduction and Health), has been in operation for more than 20 years (since 1999). In order to understand the relationship between green building certification and the construction costs of residential buildings, this study obtained 37 green building-certified residential cases and 36 general residential cases available from public information and conducted a comparative analysis. The results of this study showed that the average construction cost of a green building certification residential building was only 1.58% higher than a general residential building, indicating that green building certification does not require a large increase in costs. However, for residential buildings, achieving a high-grade (gold-grade or diamond-grade) green building certification means an increase of 6.7% to 9.3% in construction costs. This shows that the pursuit of higher levels of green building certification does require higher construction costs. In addition, the results of this study can not only provide important references for the government in making green building policies, but also offer a practical strategy for developers for decision-making.

The COVID-19 pandemic broke out in early 2020, and the infection rate of COVID-19 variants is considerably higher than that of the original virus. The pandemic is still spreading globally. In June 2021, two families living on different floors of a building in Fongshan, Kaohsiung, were simultaneously infected with COVID-19. Investigation results suggested that an elevator in buildings was the most likely place where the virus transmission occurred. Building elevators are a necessary vertical transportation facility for residents or workers in high-rise buildings, and people touch elevator buttons while operating elevators. When a passenger carrying the virus touches elevator buttons, subsequent passengers may be easily infected if they touch those buttons and then touch their mouth, eyes, or nose by accident before sanitizing or washing their hands. In this study, we developed a contact-free elevator ride system by applying smart speech recognition, contact-free perceptual buttons, gesture recognition sensors, and a web page browser activated by quick response codes to operate an elevator. This system reduces the risk of virus infection caused by contact during an elevator ride, effectively enhancing pandemic prevention and protecting people’s health.

This study experimentally investigated the seismic behavior of Ultra-High-Performance Concrete (UHPC) columns after fire exposure. The experimental program included six concrete column specimens reinforced with high-strength reinforcing bars, comprising of two normal-strength concrete (NSC) columns, two high-strength concrete (HSC) columns, and two UHPC columns containing steel and polypropylene fibers at volume fractions of 1.5% and 1.0%, respectively. One column of each type was subjected to a 2-hour fire exposure according to standard heating conditions, while the remaining columns were used as control specimens and not exposed to fire.To assess the fire effect on the seismic performance, all column specimens were subjected to lateral displacement reversals with a constant axial load. The results showed that the lateral strengths of NSC, HSC, and UHPC columns were reduced by 8.0%, 12.0%, and 6.9%, respectively, after fire exposure. Moreover, the effective stiffnesses degraded by 48%, 55%, and 52%, respectively. While the 2-hour fire exposure had a relatively minor effect on the lateral strength of the concrete columns, it considerably reduced the stiffness of the columns irrespective of the concrete material. The use of steel and polypropylene fibers in UHPC was found to be effective in restraining spalling due to fire exposure.