The influence of virtual environment on thermal perception: physical reaction and subjective thermal perception on outdoor scenarios in virtual reality.

Positive thermal perception can affect users' climate-controlling behavior, indirectly reducing a building's operational carbon emissions. Studies show that some visual elements, such as window sizes and light colors, can influence thermal perception. However, until recently there has been little interest in the interaction of thermal perception and outdoor visual scenarios or natural elements like water or trees, and little quantitative evidence has been found associating visual natural elements and thermal comfort. This experiment explores and quantifies the extent to which visual scenarios outdoors affect thermal perception. The experiment used a double-blind clinical trial. All tests were done in a stable laboratory environment to eliminate temperature changes, and scenarios were shown through a virtual reality (VR) headset. Forty-three participants were divided into three groups randomly, separately watched VR-outdoor scenarios with natural elements, VR-indoor scenarios, and a control scenario of the real laboratory, then finished a subjective questionnaire conducted to evaluate their thermal, environmental, and overall perceptions while their physical data (heart rate, blood pressure, pulse) was real-time recorded. Results show that visual scenarios could significantly influence thermal perception (Cohen's d between groups > 0.8). Significant positive correlations were found between key thermal perception index, thermal comfort, and visual perception indexes including visual comfort, pleasantness, and relaxation (all PCCs ≤ 0.01). Outdoor scenarios, with better visual perception, rank higher average scores (M ± SD = 1.0 ± 0.7) in thermal comfort than indoor groups (average M ± SD = 0.3 ± 1.0) while the physical environment remains unchanged. This connection between thermal and environmental perception can be used in building design. By being visually exposed to pleasing outdoor environments, the positive thermal perception will increase, and thus reduce building energy consumption. Designing positive visual environments with outdoor natural elements is not only a requirement for health but also a feasible path toward a sustainable net-zero future.

SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression.

BACKGROUND: This investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures. METHODS: LncRNASNP database was firstly adopted to predict SNPs that possibly affected binding of UCA1 with miRNAs and then the interactive effect of SNPs and environmental exposure on CRC risk was evaluated by recurring to type 2 gene-environment interactions (GEI) model. Besides, MTT assay, colony formation assay, transwell assay and wound healing assay were performed to assess the activity of CRC cell lines which carried distinct genotypes of specific SNPs. The impact of nicotine on activity of CRC cells was also appraised. RESULTS: SNP rs12982687 of UCA1 intervened in the binding capacity of UCA1 with several miRNAs, especially miR-873-5p. MiRNAs regulated by UCA1, as predicted by mirPath software, shared genes that were enriched in HIF1 signaling pathway. Moreover, homozygote TT of rs12982687 reduced CRC risk among smokers, and CRC cells that carried rs12982687 (CC) displayed strong migration and invasion. By contrast, miR-873-5p mimic, which reduced UCA1 expression, delayed metastasis of CRC cells (all P < 0.05). Additionally, nicotine not merely elevated UCA1 and HIF-1α expressions in CRC cells, but also facilitated proliferation and metastasis of CRC cells (P < 0.05). CONCLUSIONS: SNP rs12982687 was involved in smoking-triggered CRC progression, given its influence on UCA1's binding with miR-873-5p and HIF-1 signaling.

Functional extracellular vesicles engineered with lipid-grafted hyaluronic acid effectively reverse cancer drug resistance.

Multidrug resistance (MDR) is a key issue accounting for ineffectiveness of cancer chemotherapy. Numerous multifunctional nanocarriers have been developed to increase drug delivery efficacy and inhibit drug efflux for overcoming cancer drug resistance. However, limited success has been achieved in clinic because of nanocarriers' complicated multi-step fabrication procedures and their undesired side toxicity as well as potential immunogenicity. Here, hyaluronic acid (HA) functionalized extracellular vesicles (EVs) are generated as natural vehicles to efficiently deliver doxorubicin (DOX) and reverse MDR. The EVs isolated from noncancerous HEK293T cells (hEVs) reduce P-glycoprotein (P-gp) expression in drug resistant MCF7/ADR cells. To acquire tumor-targeting capability, hEVs are modified with lipidomimetic chains-grafted HA (lipHA) by a simple incubation. Owing to CD44-mediated cancer-specific targeting and P-gp suppressive capability, the HA-functionalized hEVs (lipHA-hEVs) remarkably promote the intracellular DOX accumulation in drug resistant breast cancer cells. In preclinical MDR tumor models, lipHA-hEVs deeply penetrate into tumor tissue and effectively transport DOX into tumor local, while eliminating DOX's systemic toxicity. Importantly, DOX@lipHA-hEVs inhibited MDR tumor growth by 89% and extend animal survival time by approximately 50%. Thus, our engineered tumor-targeting hEVs are promising natural carriers for overcoming cancer MDR.

Alginate Enhances Memory Properties of Antitumor CD8+ T Cells by Promoting Cellular Antioxidation.

Alginate, an FDA-approved natural biomaterial usually used as a therapeutic adjuvant, drug carrier, and biological scaffold, reportedly assists the immune system to activate cytotoxic T cells in antitumor assays. In this study, we investigated the direct effect of alginate on cytotoxic T cell function. By incubating sorted cytotoxic CD8+ T cells with alginate, we found that this material facilitated the antitumor cytotoxic activities of T cells. Alginate incubation significantly promoted memory properties of CD8+ T cells and elevated the proportion of CD62L+CD44+ central memory T cell (TCM), a less differentiated T cell subset with high immune activity. Mechanistically, alginate reduced reactive oxide species in CD8+ T cells by increasing intracellular glutathione generation, which was critical for conferring T cells with memory properties. Further, we found that guluronic acid, a constituent component (G unit) of alginate, is responsible for inducing glutathione and promoting TCM. Collectively, we reported new biological activities of alginate on scavenging reactive oxide species and regulating the function of cytotoxic T cells, which suggests that alginate and guluronic acid may be used for improving cytotoxic T cell functions in immunotherapy.

TRIM28 protects CARM1 from proteasome-mediated degradation to prevent colorectal cancer metastasis.

TRIM28 (Tripartite motif-containing protein 28), a member of TRIM family, is aberrantly expressed and reportedly has different functions in many types of human cancer. However, the biological roles of TRIM28 and related mechanism in colorectal cancer (CRC) remain unclear. Here, we showed that TRIM28 was downregulated in colorectal cancer compared with normal mucosa, especially at advanced stages, and acted as an independent prognostic factor of favorable outcome. Functional studies demonstrated that TRIM28 restrained CRC migration and invasion in vitro and in vivo. Mechanistically, we reported that CARM1 (co-activator-associated arginine methyltransferase1) was a critical player downstream of TRIM28. TRIM28 interacted with CARM1, and protected CARM1 from proteasome-mediated degradation through physical protein-protein interaction to suppress CRC metastasis. Further, TRIM28 suppressed the migration and invasion of CRC cells through inhibiting WNT/ß-catenin signaling in a CARM1-dependent manner, but independent of CARM1's methyltransferase activity. The protein expression of CARM1 was positively correlated with TRIM28 in CRC tissues. Patients with high levels of TRIM28 and CARM1 had improved prognosis, whereas patients with low TRIM28 and CARM1 expression had the poor outcomes. Thus, our study reveals an inhibitory role of TRIM28 in CRC metastasis, which was achieved through a TRIM28-CARM1-WNT/ß-catenin axis. This work provides potential prognostic and therapeutic targets for CRC treatment.

The prognostic value of AGR2 expression in solid tumours: a systematic review and meta-analysis.

The prognostic value of anterior gradient-2 (AGR2) in tumours remains inconclusive. Here, we systematically reviewed the literature evidence and assessed the association between AGR2 expression and prognosis in solid tumours. The primary outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS). All analyses were performed by STATA 12.0, with the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) as the effect size estimate. A total of 20 studies containing 3285 cases were included. Pooled analyses revealed that AGR2 overexpression had an unfavourable impact on OS (HR 1.93, 95% CI 1.32-2.81) and time to tumour progression (TTP) (DFS/RFS/PFS) (HR 1.60 95% CI 1.06-2.40) in solid tumour patients. Subgroup analyses indicated that AGR2 overexpression in breast cancer patients was significantly associated with poor OS (HR 3.02, 95% CI 1.03-8.81) and TTP (HR 1.93, 95% CI 1.17-3.20). Excluding breast cancer, AGR2 overexpression was also found to have a significant correlation with poor OS in the remaining solid tumour patients (HR 1.51, 95% CI 1.04-2.19). Overall, AGR2 might be a potential biomarker to predict prognosis in solid tumour patients.

Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway.

Alcohol abuse is an important cause of gastric mucosal epithelial cell injury and gastric ulcers. A number of studies have demonstrated that autophagy, an evolutionarily conserved cellular mechanism, has a protective effect on cell survival. However, it is not known whether autophagy can protect gastric mucosal epithelial cells against the toxic effects of ethanol. In the present study, gastric mucosal epithelial cells (GES-1 cells) and Wistar rats were treated with ethanol to detect the adaptive response of autophagy. Our results demonstrated that ethanol exposure induced gastric mucosal epithelial cell damage, which was accompanied by the downregulation of mTOR signaling pathway and activation of autophagy. Suppression of autophagy with pharmacological agents resulted in a significant increase of GES-1 cell apoptosis and gastric mucosa injury, suggesting that autophagy could protect cells from ethanol toxicity. Furthermore, we evaluated the cellular oxidative stress response following ethanol treatment and found that autophagy induced by ethanol inhibited generation of reactive oxygen species and degradation of antioxidant and lipid peroxidation. In conclusion, these findings provide evidence that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate oxidative damage induced by ethanol in gastric mucosal epithelial cells. Therefore, modifying autophagy may provide a therapeutic strategy against alcoholic gastric mucosa injury. Impact statement The effect and mechanism of autophagy on ethanol-induced cell damage remain controversial. In this manuscript, we report the results of our study demonstrating that autophagy can protect gastric mucosal epithelial cells against ethanol toxicity in vitro and in vivo. We have shown that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate ethanol-induced oxidative damage in gastric mucosal epithelial cells. This study brings new and important insights into the mechanism of alcoholic gastric mucosal injury and may provide an avenue for future therapeutic strategies.