GLUT1 promotes cell proliferation via binds and stabilizes phosphorylated EGFR in lung adenocarcinoma.

BACKGROUND: While previous studies have primarily focused on Glucose transporter type 1 (GLUT1) related glucose metabolism signaling, we aim to discover if GLUT1 promotes tumor progression through a non-metabolic pathway. METHODS: The RNA-seq and microarray data were comprehensively analyzed to evaluate the significance of GLUT1 expression in lung adenocarcinoma (LUAD). The cell proliferation, colony formation, invasion, and migration were used to test GLUT1 's oncogenic function. Co-immunoprecipitation and mass spectrum (MS) were used to uncover potential GLUT1 interacting proteins. RNA-seq, DIA-MS, western blot, and qRT-PCR to probe the change of gene and cell signaling pathways. RESULTS: We found that GLUT1 is highly expressed in LUAD, and higher expression is related to poor patient survival. GLUT1 knockdown caused a decrease in cell proliferation, colony formation, migration, invasion, and induced apoptosis in LUAD cells. Mechanistically, GLUT1 directly interacted with phosphor-epidermal growth factor receptor (p-EGFR) and prevented EGFR protein degradation via ubiquitin-mediated proteolysis. The GLUT1 inhibitor WZB117 can increase the sensitivity of LUAD cells to EGFR-tyrosine kinase inhibitors (TKIs) Gefitinib. CONCLUSIONS: GLUT1 expression is higher in LUAD and plays an oncogenic role in lung cancer progression. Combining GLUT1 inhibitors and EGFR-TKIs could be a potential therapeutic option for LUAD treatment.

Distribution characteristics and influencing factors of household consumption carbon emissions in China from a spatial perspective.

Household consumption carbon emissions (HCCEs) have become the main growth point of China's carbon emissions in the future. It is important to investigate the factors affecting the demand-side carbon emissions in order to find the accurate entry point of emission reduction and achieve carbon peaking and carbon neutrality goals. Different from previous studies, this study analyzed the spatial and temporal evolution characteristics of provincial HCCEs in China from a spatial perspective by using the Theil index and spatial auto-correlation and explored the key influencing factors and spatial spillover effects of HCCEs in different regions by using an econometric model. The results of the study showed that: (1) Per capita HCCEs increased by 11.90% annually, and the eastern region > northeastern region > western region > central region. (2) There were regional differences in per capita HCCEs, but the decrease was significant at 40.32%. (3) The spatial agglomeration effect of per capita HCCEs was significant, and the hot spots were mainly concentrated in the eastern coastal areas. (4) From the national level, every 1% increase in residents' consumption power would increase HCCEs by 2.489%. Which was the main factor for the growth of HCCEs, while the increase in fixed asset investment would restrain HCCEs. At the regional level, the change in population size significantly increased the HCCEs in the eastern and central regions. While for the western region, a 1% increase in population would reduce the HCCEs by 0.542%. For the eastern and central regions, the degree of aging and the consumption structure of residents could suppress regional HCCEs. However, the consumption structure of residents drove the growth of HCCEs in the western region. For the Northeast region, residents' consumption capacity and cooling degree days were the main factors for the growth of residents' consumption, while fixed asset investment could inhibit the growth of HCCEs.

Advances of Protein Palmitoylation in Tumor Cell Deaths.

In this comprehensive survey, we delve into the multifaceted role of palmitoylation across various cell death modalities in the oncological context, from its intricate correlations with tumorigenesis, steered by the Asp-His-His-Cys tetrapeptide motif (DHHC) family, to the counter-process of depalmitoylation mediated by enzymes like Palmitoyl protein thioesterase-1 (PPT1). Innovations in detection methodologies have paralleled our growing understanding, transitioning from rudimentary techniques to sophisticated modern methods. Central to our discourse are agents like Ezurpimtrostat (GNS561) and dimeric chloroquine (DC661), promising heralds in palmitoylation-targeted cancer therapy. Collectively, this review accentuates palmitoylation's transformative potential in oncology, foreshadowing groundbreaking therapeutic strategies and deepening our molecular comprehension of cancer dynamics.

Empirical research on household consumption carbon emissions and key impact factors in urban and rural China.

The analysis of household consumption carbon emissions (HCCEs), a significant source of CO2 emissions, is essential to achieving China's carbon peak before 2030 and carbon neutrality before 2060. Based on the calculation of urban and rural HCCEs during 2005-2019, the differences between urban and rural areas, spatial-temporal pattern and agglomeration characteristics of HCCEs were analyzed, and the panel quantile STIRPAT model was constructed to empirically test the influence of socioeconomic factors on urban and rural HCCEs at different quantile levels. The results indicate that, first, China's HCCEs are generally growing, indirect HCCEs are more than direct HCCEs, urban HCCEs are far more than rural, and the gap has a growing trend. Second, the urban and rural HCCEs have significant disequilibrium and agglomeration characteristics in space, and high-high and low-low agglomerations dominated the local region. Third, household size and the number of patent application authorizations increase the urban and rural HCCEs, while the consumption capacity and consumption structure inhibit the urban and rural HCCEs. In addition, the level of education also has an inhibitory effect on the rural HCCEs, while the aging degree of the population has a significant positive impact on the rural HCCEs when it is only at the 90th percentile. Finally, it is suggested to formulate differentiated emission reduction policies.

Evaluation of the Social Effects of Enterprise Carbon Accounts Based on Variable Weight CFPR Fuzzy VIKOR.

The carbon account is a digital path for an enterprise to achieve low-carbon transformation and high-quality sustainable development under the 'dual carbon' strategy. The carbon account has a good social effect while generating economic benefits. An evaluation index system of the social effects of enterprise carbon accounts has been established, including the concepts of energy conservation and carbon reduction, contributions, technological innovation, and customer trust. In view of the difficulty of quantifying the evaluation indicators of the social effects of enterprise carbon accounts and the requirement of effect equalization, a variable-weight CFPR fuzzy VIKOR evaluation model was constructed. Compared with the traditional fuzzy VIKOR model, the variable-weight CFPR fuzzy VIKOR model can solve the problem of quantifying indicators and realize the balance between indicators. This method can better compare and analyze the social effects of each enterprise's carbon accounts and provides a basis for overall carbon account construction and digging improvement space.

In-vitro antiviral activity of doxepin hydrochloride against group B coxsackievirus.

Group B coxsackievirus is an enterovirus that can cause a variety of diseases, including myocarditis, aseptic meningitis, and hand, foot, and mouth disease. Currently, there is no effective antiviral drug against this virus. In this study, we used a cytopathic effect-based viral inhibition assay to screen an FDA-approved drug library and found that doxepin hydrochloride had potential antiviral activity. Doxepin hydrochloride exhibited strong antiviral activity against coxsackievirus B types 1-3 with a 50% inhibitory concentration of 10.12 ± 0.85 µM. Moreover, doxepin hydrochloride did not exert antiviral activity against other enteroviruses, including enterovirus A71 (subtypes BrCr/C4) and coxsackievirus A (subtypes 6/10/16). Furthermore, doxepin hydrochloride inhibited virus replication in the early stage of the infection cycle rather than affecting the entry or assembly process. In addition, a few mechanism-related pharmacophores were discovered through gene association network analysis. These findings identify a possible lead compound for treating coxsackievirus B infection and simultaneously offer valuable clues for drug repositioning.

Two Sets of Compound Complex Driving for High Efficiency of Nonintegration Reprogramming of Human Fibroblasts.

Currently, plentiful chemical-assisted methods have been applied for mouse induced pluripotent stem cells (iPSCs). It has been reported that small-molecule compounds can only reprogram mouse embryonic fibroblasts into mouse chemically induced pluripotent stem cells (mouse CiPSCs). However, human CiPSCs have not been reported. Therefore, it is still necessary to search for safer chemically assisted human pluripotent stem cells, which might realize the potential of human iPSCs. Here, we developed two sets of chemical cocktails to greatly improve the induction efficiency of human nonintegrated iPSCs, including the 4 compound mixture (4M) and the 5 compound mixture (4MI). These two sets of complex driving strategies might greatly improve the reprogramming efficiency to generate integration-free iPSCs.

Modeling Cystic Fibrosis Using Pluripotent Stem Cell-Derived Human Pancreatic Ductal Epithelial Cells.

UNLABELLED: We established an efficient strategy to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell (iPSC) line derived from patients with cystic fibrosis, to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-derived PDECs expressed functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. In addition, iPSC lines were derived from a patient with CF carrying compound frameshift and mRNA splicing mutations and were differentiated to PDECs. PDECs derived from Weill Cornell cystic fibrosis (WCCF)-iPSCs showed defective expression of mature CFTR protein and impaired chloride ion channel activity, recapitulating functional defects of patients with CF at the cellular level. These studies provide a new methodology to derive pure PDECs expressing CFTR and establish a "disease in a dish" platform to identify drug candidates to rescue the pancreatic defects of patients with CF. SIGNIFICANCE: An efficient strategy was established to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell line derived from patients with cystic fibrosis (CF-iPSCs), to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-PDECs derived from CF-iPSCs showed defective expression of mature cystic fibrosis transmembrane conductance regulator (CFTR) protein and impaired chloride ion channel activity, recapitulating functional pancreatic defects of patients with CF at the cellular level. These studies provide a new methodology for deriving pure PDECs expressing CFTR, and they establish a "disease-in-a-dish" platform for identifying drug candidates to rescue the pancreatic defects of these patients.

A chemical platform for improved induction of human iPSCs.

The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (200-fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, nonviral methods for reprogramming human somatic cells.