RESUMEN
Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality, with many patients facing poor prognosis, particularly those with metastatic or drug-resistant tumors. Homologous recombination genes (HRGs) are crucial in tumor progression and therapy resistance, but their clinical significance in LUAD is not well understood. In this study, we systematically characterize key HRGs in LUAD patients, identifying two distinct HR subtypes associated with different outcomes and biological functions. We establish a 5-gene scoring system (XRCC2, RAD51, BRCA1, FANCA, and CHEK1) that reliably predicts patient outcomes and immunotherapy responses in LUAD. Bioinformatics analysis and clinical validation highlight XRCC2 as a crucial biomarker in LUAD. Functional investigations through in vivo and in vitro experiments reveal the role of XRCC2 in promoting lung cancer migration and invasion. Mechanistically, XRCC2 stabilizes vimentin (VIM) protein expression through deubiquitylation. We predict c-MYC as a potential regulator of XRCC2 and demonstrate that inhibiting c-MYC with compound 10058-F4 reduces XRCC2 and VIM expression. Preclinical studies show the synergistic inhibition of metastasis in vivo when combining 10058-F4 with doxorubicin (Dox). Our findings present a potential personalized predictive tool for LUAD prognosis, identifying XRCC2 as a critical biomarker. The c-Myc-XRCC2-VIM axis emerges as a promising therapeutic target for overcoming lung metastasis. This study provides valuable insights into LUAD, proposing a prognostic tool for further clinical validation and unveiling a potential therapeutic strategy for combating lung metastasis by targeting c-Myc-XRCC2-VIM.
RESUMEN
Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80â¯%-90â¯% of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10â¯%. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.
RESUMEN
Malignant tumors constitute a significant category of diseases posing a severe threat to human survival and health, thereby representing one of the most challenging and pressing issues in the field of biomedical research. Due to their malignant nature, which is characterized by a high potential for metastasis, rapid dissemination, and frequent recurrence, the prevailing approach in clinical oncology involves a comprehensive treatment strategy that combines surgery with radiotherapy, chemotherapy, targeted drug therapies, and other interventions. Treatment resistance remains a major obstacle in the comprehensive management of tumors, serving as a primary cause for the failure of integrated tumor therapies and a critical factor contributing to patient relapse and mortality. The Minichromosome Maintenance (MCM) protein family comprises functional proteins closely associated with the development of resistance in tumor therapy.The influence of MCMs manifests through various pathways, encompassing modulation of DNA replication, cell cycle regulation, and DNA damage repair mechanisms. Consequently, this leads to an enhanced tolerance of tumor cells to chemotherapy, targeted drugs, and radiation. Consequently, this review explores the specific roles of the MCM family in various cancer treatment strategies. Its objective is to enhance our comprehension of resistance mechanisms in tumor therapy, thereby presenting novel targets for clinical research aimed at overcoming resistance in cancer treatment. This bears substantial clinical relevance.
Asunto(s)
Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Replicación del ADN , Proteínas de Mantenimiento de Minicromosoma/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismoRESUMEN
Aqueous Zn metal batteries have attracted extensive attention due to their intrinsic advantages. However, zinc ions tend to deposit irregularly, seriously depleting the capacity and stability of the battery. The construction of zincophilic sites can effectively regulate the nucleation and growth of Zn, but there is a defect that these sites will be covered with gradual failure after long-term cycling. Here, in combination with the sustained-compensated strategy, interfacial zincophilic sites are continuously constructed, thus effectively avoiding the threat of dendrites and improving the electrochemical performance. Impressively, at 10 mA cm-2 and 5 mAh cm-2, the protected Zn metal exhibits excellent cycling stability over 2000 cycles in the Zn//Zn battery. Moreover, even the cathode mass loading is considerably high (35 mg cm-2), and the Zn//NVO full cell significantly outperforms with high areal capacity (up to 4 mAh cm-2). This novel strategy provides a direction for the development of high-capacity aqueous batteries.
RESUMEN
Aqueous rechargeable zinc-ion batteries (ZIBs) have recently shined in energy storage and transmission, which are due to high safety and low cost. However, the extremely stubborn by-products in the Zn anode severely inhibited the Zn2+ adsorption/desorption and exacerbated the dendrite formation. Herein, we report a facile strategy to eliminate inert Zn4(OH)6SO4·xH2O for the improvement of ZIBs according to the coordination effect by employing ethylenediaminetetraacetic acid-diamine (EDTA-2Na) as a coordination additive in traditional electrolyte. Zn2+ is coordinated with the carboxyl group of the four acetyl carboxyl groups and the N in C-N bonds, forming a new chelating structure, and thus stubborn deposition will be dissolved in the electrolyte. As a result, the discharge capacity of 102 mAh g-1 in the ZnSO4/Li2SO4 with EDTA-2Na electrolyte at a current density of 4 C and a stable cycle life with a capacity of 90.3% after 150 cycles are achieved. It has been concluded that the coordination effect strategy provides a valuable idea for solving the defects of ZIBs.
RESUMEN
The practical application of aqueous high-rate Zn metal battery (ZMB) is limited due to accelerated dendrite formation at high current densities. It is urgent to find an electrolyte, which could not only be mechanically stiff to clamp down dendrites but also not sacrifice ionic conductivity and interfacial compatibility. Herein, a new type of dynamically "solid-liquid" interconvertible electrolyte based on non-Newtonian fluid (NNFE) is proposed. Liquidity characteristic of NNFE is favorable for electrochemical kinetics and interfacial compatibility. Furthermore, in an area with high current rate NNFE would respond and mechanically stiffen to dissuade localized increase in Zn dendrite growth. Even at a current density of 50 mA cm-2, NNFE enables reversible and stable operation of a Zn symmetrical cell over 20â¯000 cycles. For Zn//Na5V12O32 (NVO) full cell, the NNFE also realizes lengthy cycling for 5000 periods at 5 A g-1. This research opens up new inspirations to high-rate Zn metal even other metal batteries.
RESUMEN
Conversion of solar energy into thermal energy stored in phase change materials (PCMs) can effectively relieve the energy dilemma and improve energy utilization efficiency. However, facile fabrication of form-stable PCMs (FSPCMs) to achieve simultaneously energetic solar-thermal, conversion and storage remains a formidable challenge. Herein, we report a desirable solar-thermal energy conversion and storage system that utilizes paraffin (PW) as energy-storage units, the silver/polypyrrole-functionalized polyurethane (PU) foam as the cage and energy conversion platform to restrain the fluidity of the melting paraffin and achieve high solar-thermal energy conversion efficiency (93.7%) simultaneously. The obtained FSPCMs possess high thermal energy storage density (187.4 J/g) and an excellent leak-proof property. In addition, 200 accelerated solar-thermal energy conversion-cycling tests demonstrated that the resultant FSPCMs had excellent cycling durability and reversible solar-thermal energy conversion ability, which offered a potential possibility in the field of solar energy utilization technology.