RNA m6A methylation regulators in liver cancer.

Liver cancer is one of the most common cancers in the world and a primary cause of cancer-related death. In recent years, despite the great development of diagnostic methods and targeted therapies for liver cancer, the incidence and mortality of liver cancer are still on the rise. As a universal post-transcriptional modification, N6-methyladenosine (m6A) modification accomplishes a dynamic and reversible m6A modification process, which is executed by three types of regulators, methyltransferases (called writers), demethylases (called erasers) and m6A-binding proteins (called readers). Many studies have shown that m6A RNA methylation has an important impact on RNA metabolism, whereas its regulation exception is bound up with the occurrence of human malignant tumors. Aberrant methylation of m6A RNA and the expression of related regulatory factors may be of the essence in the pathogenesis and progression of liver cancer, yet the precise molecular mechanism remains unclear. In this paper, we review the current research situations of m6A methylation in liver cancer. Among the rest, we detail the mechanism by which methyltransferases, demethylases and m6A binding proteins regulate the occurrence and development of liver cancer by modifying mRNA. As well as the potential effect of m6A regulators in hepatocarcinogenesis and progression. New ideas and approaches will be given to the prevention and treatment of liver cancer through the following relevant research results.

High-Performance Thermoelectric Fibers from Metal-Backboned Polymers for Body-Temperature Wearable Power Devices.

Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric composite fiber. It demonstrated a power factor of 719.48 µW ⋅m-1 K-2, which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the composite fiber further showed simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.

Ferroptosis: a new promising target for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is the sixed most common malignant tumor in the world. The study for HCC is mired in the predicament confronted with the difficulty of early diagnosis and high drug resistance, the survival rate of patients with HCC being low. Ferroptosis, an iron-dependent cell death, has been discovered in recent years as a cell death means with tremendous potential to fight against cancer. The in-depth researches for iron metabolism, lipid peroxidation and dysregulation of antioxidant defense have brought about tangible progress in the firmament of ferroptosis with more and more results showing close connections between ferroptosis and HCC. The potential role of ferroptosis has been widely used in chemotherapy, immunotherapy, radiotherapy, and nanotherapy, with the development of various new drugs significantly improving the prognosis of patients. Based on the characteristics and mechanisms of ferroptosis, this article further focuses on the main signaling pathways and promising treatments of HCC, envisioning that existing problems in regard with ferroptosis and HCC could be grappled with in the foreseeable future.

Dynamically Resettable Electrode-Electrolyte Interface through Supramolecular Sol-Gel Transition Electrolyte for Flexible Zinc Batteries.

Flexible batteries based on gel electrolytes with high safety are promising power solutions for wearable electronics but suffer from vulnerable electrode-electrolyte interfaces especially upon complex deformations, leading to irreversible capacity loss or even battery collapse. Here, a supramolecular sol-gel transition electrolyte (SGTE) that can dynamically accommodate deformations and repair electrode-electrolyte interfaces through its controllable rewetting at low temperatures is designed. Mediated by the micellization of polypropylene oxide blocks in Pluronic and host-guest interactions between α-cyclodextrin (α-CD) and polyethylene oxide blocks, the high ionic conductivity and compatibility with various salts of SGTE afford resettable electrode-electrolyte interfaces and thus constructions of a series of highly durable, flexible aqueous zinc batteries. The design of this novel gel electrolyte provides new insights for the development of flexible batteries.

Metal-Backboned Polymers with Well-Defined Lengths.

Constructing the backbones of polymers with metal atoms is an attractive strategy to develop new functional polymeric materials, but it has yet to be studied due to synthetic challenges. Here, metal atoms are interconnected as the backbones of polymers to yield metal-backboned polymers (MBPs). Rational design of multidentate ligands synthesized via an efficient iterative approach leads to the successful construction of a series of nickel-backboned polymers (NBPs) with well-defined lengths and up to 21 nickel atoms, whose structures are systematically confirmed. These NBPs exhibit strong and length-depended absorption with narrow band gaps, offering promising applications in optoelectronic devices and semiconductors. We also demonstrate the high thermal stability and solution processsability of such nickel-backboned polymers. Our results represent a new opportunity to design and synthesize a variety of new metal-backboned polymers for promising applications in the future.

Lithium-Metal Anodes Working at 60†mA cm-2 and 60†mAh cm-2 through Nanoscale Lithium-Ion Adsorbing.

Achieving high-current-density and high-area-capacity operation of Li metal anodes offers promising opportunities for high-performing next-generation batteries. However, high-rate Li deposition suffers from undesired Li-ion depletion especially at the electrolyte-anode interface, which compromises achievable capacity and lifetime. Here, electronegative graphene quantum dots are synthesized and assembled into an ultra-thin overlayer capable of efficient Li-ion adsorbing at the nanoscale on Li-metal to fully relieve Li-ion depletion. The protected Li anode achieves long-term reversible Li plating/stripping over 1000 h at both superior current density of 60 mA cm-2 and areal capacity of 60 mAh cm-2 . Implementation of the protected anode allows for the construction of Li-air full battery with both enhanced rate capability and cycling performance.

Cost-effectiveness of talazoparib for patients with germline BRCA1/2 mutated HER2-negative advanced breast cancer in China and the US.

Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the findings from the Phase III EMBRACE trial (NCT01945775 clinical trial), our analysis reveals that the talazoparib group demonstrated a significant extension in progression-free survival, along with improved response markers and patient-reported outcomes when compared to conventional therapies. This study aims to assess the cost-effectiveness of talazoparib for treating advanced breast cancer with germline BRCA1/2 mutations and HER2 negativity, considering the perspectives of health services in China and the United States. The results obtained will serve as a valuable reference for promoting rational drug utilization and enhancing medical resource efficiency. To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10,223.43 and increasing QALYs by 1.5. The clinical treatment effect of Talazoparib group in BRCA1/2 mutant advanced breast cancer patients is better than that of the standard treatment group, and the progression free survival period is significantly prolonged. From the perspective of medical and health services in China and the United States, the Talazoparib group is more economical than the standard treatment group in treating patients with BRCA1/2 mutant advanced breast cancer.

Role of N6­methyladenosine in the pathogenesis, diagnosis and treatment of prostate cancer (Review).

Prostate cancer (PCa) affects males of all racial and ethnic groups, and leads to higher rates of mortality in those belonging to a lower socioeconomic status due to the late detection of the disease. PCa affects middle­aged males between the ages of 45 and 60 years, and is the highest cause of cancer­associated mortality in Western countries. As the most abundant and common mRNA modification in higher eukaryotes, N6­methyladenosine (m6A) is widely distributed in mammalian cells and influences various aspects of mRNA metabolism. Recent studies have found that abnormal expression levels of various m6A regulators significantly affect the development and progression of various types of cancer, including PCa. The present review discusses the influence of m6A regulatory factors on the pathogenesis and progression of PCa through mRNA modification based on the current state of research on m6A methylation modification in PCa. It is considered that the treatment of PCa with micro­molecular drugs that target the epigenetics of the m6A regulator to correct abnormal m6A modifications is a direction for future research into current diagnostic and therapeutic approaches for PCa.

Economic evaluation of third-line neratinib plus capecitabine versus lapatinib plus capecitabine with HER2+ metastatic breast cancer.

Background: Breast cancer (BC) is one of the most common malignant tumors in women. In addition, human epidermal growth factor receptor 2-positive (HER2+) BC is overexpressed in 25% of BC patients, resulting in the predicament of poor prognosis. Although first- and second-line treatments have been established, optimum third-line treatment is still mired in controversies for HER2+ metastatic BC (mBC). Therefore, this study analyzes the cost-effectiveness of neratinib plus capecitabine (N+C) and lapatinib plus capecitabine (L+C) over a 5-year time horizon from a payer perspective. Methods: A half-cycle corrected four-state Markov model was established to simulate the course of BC events and deaths in N+C and L+C armed patients. The data of this model were derived from NCT01808573 trail and other published literatures. One-way deterministic sensitivity analysis (DSA) was conducted to investigate the impact of variables and probabilistic sensitivity analysis (PSA) was performed based on second-order Monte Carlo simulation. In addition, subgroup analysis was performed to verify its cost-effectiveness in China. Result: The base-case results found that N+C was in dominant position in 82.70% of the generation scenarios, providing an improvement of 0.17 quality-adjusted life-years (QALYs) and a reduction of $1,861.28 compared with L+C. The ICER was $-1,3294.86/QALY, which did not exceed the willingness to pay (WTP) threshold, while in subgroup, the ICER decreased to $-2,448.17/QALY. Conclusion: This analysis indicated that the combination of neratinib plus capecitabine is likely to be cost-effective in comparison with lapatinib plus capecitabine in patients with HER2+ mBC who continues to progress during or after second-line HER2-targeted therapy. So neratinib plus capecitabine can become a third-line treatment option.

A biomass-derived super-flexible hierarchically porous carbon film electrode prepared via environment-friendly ice-microcrystal pore-forming for supercapacitors.

An efficient environmentally friendly purely-physical ice-microcrystal pore-forming strategy, consisting of three steps including the water-swelling biomass process utilizing N-methylmorpholine-N-oxide, freeze-drying and one-step carbonization, was developed to prepare a biomass-derived super-flexible high-performance carbon film electrode capable of being repeatedly folded.

Clinical and Biological Significances of a Ferroptosis-Related Gene Signature in Glioma.

Ferroptosis is a form of cell death characterized by non-apoptosis induced by small molecules in tumors. Studies have demonstrated that ferroptosis regulates the biological behaviors of tumors. Therefore, genes that control ferroptosis can be a promising candidate bioindicator in tumor therapy. Herein, functions of ferroptosis-related genes in glioma were investigated. We systematically assessed the relationship between ferroptosis-related genes expression profiles and prognosis in glioma patients based on The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) RNA sequencing datasets. Using the non-negative matrix factorization (NMF) clustering method, 84 ferroptosis-related genes in the RNA sequencing data were distinctly classified into two subgroups (named cluster 1 and cluster 2) in glioma. The least absolute shrinkage and selection operator (LASSO) was used to develop a 25 gene risk signature. The relationship between the gene risk signature and clinical features in glioma was characterized. Results show that the gene risk signature associated with clinical features can be as an independent prognostic indicator in glioma patients. Collectively, the ferroptosis-related risk signature presented in this study can potentially predict the outcome of glioma patients.