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Electric vehicle (EV) purchasing decisions are significantly influenced by costs. Focusing on China, this research comprehensively examines the levelized costs of EV recharging (including charging and swapping) at the provincial level considering various factors, including charging locations, time of charging, and power levels. Results indicate that the national average EV charging costs, with and without home chargers, amount to 0.973 RMB/kWh and 1.148 RMB/kWh, respectively. Remarkable variations are observed among provinces, with Xinjiang and Shanghai experiencing the lowest and highest levelized cost of EV charging (LCOC), respectively, with disparities of up to 147.26%, primarily attributed to regional discrepancies in electricity prices and vehicle usage intensity. Despite generous capital subsidies, swapping costs remain considerably higher than charging, ranging from 3.780 RMB/kWh to 4.082 RMB/kWh. Additionally, the sensitivity analysis of major parameters, including infrastructure utilization, suggests that levelized EV recharging costs are already more cost-attractive than the fuel costs of comparable gasoline cars at today's utilization rates.
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How dysregulated liquid-liquid phase separation (LLPS) contributes to the oncogenesis of female triple-negative breast cancer (TNBC) remains unknown. Here we demonstrate that phosphorylated histone deacetylase 6 (phospho-HDAC6) forms LLPS condensates in the nuclei of TNBC cells that are essential for establishing aberrant chromatin architecture. The disordered N-terminal domain and phosphorylated residue of HDAC6 facilitate effective LLPS, whereas nuclear export regions exert a negative dominant effect. Through phase-separation-based screening, we identified Nexturastat A as a specific disruptor of phospho-HDAC6 condensates, which effectively suppresses tumor growth. Mechanistically, importin-ß interacts with phospho-HDAC6, promoting its translocation to the nucleus, where 14-3-3θ mediates the condensate formation. Disruption of phospho-HDAC6 LLPS re-established chromatin compartments and topologically associating domain boundaries, leading to disturbed chromatin loops. The phospho-HDAC6-induced aberrant chromatin architecture affects chromatin accessibility, histone acetylation, RNA polymerase II elongation and transcriptional profiles in TNBC. This study demonstrates phospho-HDAC6 LLPS as an emerging mechanism underlying the dysregulation of chromatin architecture in TNBC.
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Electric vehicles (EVs) are a promising pathway to providing cleaner personal mobility. China provides substantial supports to increase EV market share. This study provides an extensive analysis of the currently unclear environmental and health benefits of these incentives at the provincial level. EVs in China have modest cradle-to-gate CO2 benefits (on average 29%) compared to conventional internal combustion engine vehicles (ICEVs), but have similar carbon emissions relative to hybrid electric vehicles. Well-to-wheel air pollutant emissions assessment shows that emissions associated with ICEVs are mainly from gasoline production, not the tailpipe, suggesting tighter emissions controls on refineries are needed to combat air pollution problems effectively. By integrating a vehicle fleet model into policy scenario analysis, we quantify the policy impacts associated with the passenger vehicles in the major Chinese provinces: broader EV penetration, especially combined with cleaner power generation, could deliver greater air quality and health benefits, but not necessarily significant climate change mitigation. The total value to society of the climate and mortality benefits in 2030 is found to be comparable to a prior estimate of the EV policy's economic costs.
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The promotion of plug-in electric vehicles (PEVs) is pivotal to China's carbon neutrality strategy. Therefore, it is important to understand the vehicle market evolution and its impacts in terms of costs, sales, industry fuel economy, and PEV's battery material demand. By examining vehicle technologies, cost, policy incentives, infrastructure, and driver behavior, this study quantitatively projects the dynamics of China's passenger vehicle market from 2020 to 2050 under multiple technology evolution scenarios. By 2050, battery electric vehicles could gain significant market share-as much as 30.4%-64.6%; and the industry's sales-weighted average fuel consumption could reach 1.81-3.11 L/100 km. Cumulative battery demand from PEVs could soar to over 700 GWh by 2050, whereas battery recycling alone could satisfy about 60% of the demand by 2050. The key metal supplies-lithium, cobalt, and nickel-for China's PEV market are projected, and nickel should be concerned more over the coming decades.
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BACKGROUND: Anaplastic thyroid cancer is the most aggressive thyroid cancer and has a poor prognosis. At present, there is no effective treatment for it. METHODS: Here, we used different concentrations of GSK-J4 or a combination of GSK-J4 and doxorubicin to treat human Cal-62, 8505C, and 8305C anaplastic thyroid cancer (ATC) cell lines. The in vitro experiments were performed using cell viability assays, cell cycle assays, annexin-V/PI binding assays, Transwell migration assays, and wound-healing assays. Tumor xenograft models were used to observe effects in vivo. RESULTS: The half maximal inhibitory concentration (IC50) of GSK-J4 in Cal-62 cells was 1.502 µM, and as the dose of GSK-J4 increased, more ATC cells were blocked in the G2-M and S stage. The combination of GSK-J4 and doxorubicin significantly increased the inhibitory effect on proliferation, especially in KRAS-mutant ATC cells in vivo (inhibition rate 38.0%) and in vitro (suppresses rate Fa value 0.624, CI value 0.673). The invasion and migration abilities of the KRAS-mutant cell line were inhibited at a low concentration (p < 0.05). CONCLUSIONS: The combination of GSK-J4 with doxorubicin in KRAS-mutant ATC achieved tumor-suppressive effects at a low dose. The synergy of the combination of GSK-J4 and doxorubicin may make it an effective chemotherapy regimen for KRAS-mutant ATC.
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BACKGROUND: H3K27me3 modification inactivates gene transcription by resulting in condensed chromatin. However, the landscape and biological functions of H3K27me3 in breast cancer remain unclear. METHODS: Fluorescence enzyme assay was used to analyze the cell proliferation. Transwell assay was used to test the ability of migration and invasion in MDA-MB-231 cells with designed treatment. Transfection of exogenous plasmid was used to intervene specific gene expression. Nude mouse tumor xenograft model was employed to detect the effect of GSKJ-4 in vivo. ChIP-Seq analyzed the modification state of H3K27me3 around the TSS of the gene CEMIP. RNA-Seq was used to analyze the mRNA levels after treating with GSKJ-4 in MDA-MB-231 cells. RESULTS: Loss of H3K27me3 is specific for aggressive subtypes of breast cancer and may be a useful diagnostic marker. Epigenetic chemical screening identified histone H3K27me3 demethylation inhibition as a therapeutic strategy for triple-negative breast cancer (TNBC). Functional studies and RNA-seq/ChIP-seq data revealed that inactivation of the protein CEMIP (which is translated by oncogene KIAA1199) by increasing H3K27me3 leads to decreased tumor cell growth and migration. Moreover, survival analysis showed that CEMIP was associated with poor outcome in TNBC. CONCLUSIONS: Our data suggest H3K27me3 loss as an important event in CEMIP mediated breast cancer carcinogenesis and progression. Loss of H3K27me3 is specific for aggressive subtypes of breast cancer and may be a useful diagnostic marker.
Asunto(s)
Benzazepinas/farmacología , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Histonas/metabolismo , Hialuronoglucosaminidasa/metabolismo , Pirimidinas/farmacología , Animales , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Carcinogénesis , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Estudio de Asociación del Genoma Completo , Histonas/genética , Humanos , Hialuronoglucosaminidasa/genética , Ratones , Ratones Desnudos , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Thyroid carcinoma is the most common malignant endocrine tumor; the anaplastic thyroid cancer subtype is aggressive and has a poor prognosis. However, there is no effective treatment for this disease. METHODS: This study was analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Joinpoint regression models, linear regression models, Kaplan-Meier survival curves and Cox regression models were used to study the trends in incidence, survival rate and median survival time and to detect the risk factors affecting prognosis in patients with anaplastic thyroid cancer. RESULTS: While the incidence rate and truncated incidence rate fluctuated slightly over the past 30 years, they were relatively stable and had no obvious upward trend (APC = -0.22 and 0.24, respectively, P>0.05). The median survival was 3.16 months, and the survival rate did not improve significantly (the APC values of the 3-, 6-, 9-, and 12-month survival rates were 0.44, 0.35, -0.23 and -0.86, respectively, P>0.05). After subgroup analysis and survival analysis, it was concluded that the prognosis of the patients might be related to their metastatic stage, surgical status, chemotherapy treatment, age and socioeconomic status at the time of diagnosis (P<0.05). Total thyroidectomy is superior to other methods and is beneficial in prolonging the life of patients and improving the overall survival rate (the median survival was 10 months, and the 6-month survival rate was 59.26%). CONCLUSION: The incidence trend for anaplastic thyroid cancer over the last 30 years was stable, and the survival rate and median survival time were not significantly improved. The prognosis of the patients may be related to their metastatic stage, age, socioeconomic status, surgical status and chemotherapy treatment.
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Glioblastoma multiforme (GBM), grade IV astrocytoma, is the most fatal malignant primary brain tumor. GBM contains functional subsets of cells called glioblastoma stem-like cells (GSCs), which are radioresistant and chemoresistant and eventually lead to tumor recurrence. Recent studies showed that GSCs reside in particular tumor niches that are necessary to support their behavior. To successfully eradicate GBM growth and recurrence, new strategies selectively targeting GSCs and/or their microenvironmental niche should be designed. In this regard, here we focus on elucidating the molecular mechanisms that govern these GSC properties and on understanding the mechanism of the microenvironmental signals within the tumor mass. Moreover, to overcome the blood-brain barrier, which represents a critical limitation of GBM treatments, a new drug delivery system should be developed. Nanoparticles can be easily modified by different methods to facilitate delivery efficiency of chemotherapeutics, to enhance the accumulation within the tumors, and to promote the capacity for targeting the GSCs. Therefore, nanotechnology has become the most promising approach to GSC-targeting therapy. Additionally, we discussed the future of nanotechnology-based targeted therapy and point out the disadvantages that should be overcome.