N4-acetylcytidine (ac4C) is an ancient and conserved RNA modification. Previously, ac4C mRNA modification has been reported promoting proliferation and metastasis of tumor cells. However, it remains unclear whether and how ac4C-related mRNA modification patterns influencing the prognosis of hepatocellular carcinoma (HCC) patients. Hereby, we constructed an ac4Cscore model and classified patients into two groups and investigated the potential intrinsic and extrinsic characteristics of tumor. The ac4Cscore model, including COL15A1, G6PD and TP53I3, represented ac4C-related mRNA modification patterns in HCC. According to ac4Cscore, patients were stratified to high and low groups with distinct prognosis. Patients subject to high group was related to advanced tumor stage, higher TP53 mutation rate, higher tumor stemness, more activated pathways in DNA-repair system, lower stromal score, higher immune score and higher infiltrating of T cells regulatory. While patients attributed to low group were correlated with abundance of T cells CD4 memory, less aggressive immune subtype and durable therapy benefit. We also found ac4Cscore as a novel marker to predict patients' prognosis with anti-PD1 immunotherapy and/or mTOR inhibitor treatment. Our study for the first time showed the association between ac4C-related mRNA modification patterns and tumor intrinsic and extrinsic characteristics, thus influencing the prognosis of patients.
NOP56 is a highly conserved nucleolar protein. Amplification of the intron GGCCTG hexanucleotide repeat sequence of the NOP56 gene results in spinal cerebellar ataxia type 36 (SCA36). NOP56 contains an N-terminal domain, a coiled-coil domain, and a C-terminal domain. Nucleolar protein NOP56 is significantly abnormally expressed in a number of malignant tumors, and its mechanism is different in different tumors, but its regulatory mechanism in most tumors has not been fully explored. NOP56 promotes tumorigenesis in some cancers and inhibits tumorigenesis in others. In addition, NOP56 is associated with methylation in some tumors, suggesting that NOP56 has the potential to become a tumor-specific marker. This review focuses on the structure, function, related signaling pathways, and role of NOP56 in the progression of various malignancies, and discusses the progression of NOP56 in neurodegenerative and other diseases.
4H-SiC floating junction Schottky barrier diodes (FJ-SBDs) are excellent SiC devices with high Baliga's figure of merit (BFOM). However, the p-type buried layers in epilayers partially obstruct the current paths, and increase the on-resistance, while the buried layers of dot patterns can reduce the obstruction. In this paper, a three-dimensional (3D) simulation of 4H-SiC FJ-SBDs with dot patterns is reported for the first time. By comparing the results obtained from stripe, square, octagon, and circle patterns, dot patterns are proved to be good choices for buried layers in 4H-SiC FJ-SBDs, and the FJ-SBD with the circle pattern has the highest BFOM of 12.09 GW/cm2, which is 22.62% greater than that of the FJ-SBD with the stripe pattern.
Cl, Br, and I are elements in the halogen family, and are often used as dopants in semiconductors. When employed as dopants, these halogens can significantly modify the optoelectronic properties of materials. From the perspective of halogen doping, we have successfully achieved the stabilization of crystal structures in CH3NH3PbX3, CH3NH3PbI3-xClx, CH3NH3PbI3-xBrx, and CH3NH3PbBr3-xClx, which are organic-inorganic hybrid perovskites. Utilizing first-principles density functional theory calculations with the CASTEP module, we investigated the optoelectronic properties of these structures by simulations. According to the calculations, a smaller difference in electronegativity between different halogens in doped structures can result in smoother energy bands, especially in CH3NH3PbI3-xBrx and CH3NH3PbBr3-xClx. The PDOS of the Cl-3p orbitals undergoes a shift along the energy axis as a result of variances in electronegativity levels. The optoelectronic performance, carrier mobility, and structural stability of the CH3NH3PbBr3-xClx system are superior to other systems like CH3NH3PbX3. Among many materials considered, CH3NH3PbBr2Cl exhibits higher carrier mobility and a relatively narrower bandgap, making it a more suitable material for the absorption layer in solar cells. This study provides valuable insights into the methodology employed for the selection of specific types, quantities, and positions of halogens for further research on halogen doping.
Abstract Analysis of human cancer genome sequences has revealed specific mutational signatures associated with BRCA1 -deficient tumors, but the underlying mechanisms remain poorly understood. Here, we show that one-ended DNA double strand breaks (DSBs) converted from CRISPR/Cas9-induced nicks by DNA replication, not two-ended DSBs, cause more characteristic chromosomal aberrations and micronuclei in Brca1 -deficient cells than in wild-type cells. BRCA1 is required for efficient homologous recombination of these nick-converted DSBs and suppresses bias towards long tract gene conversion and tandem duplication (TD) mediated by two-round strand invasion in a replication strand asymmetry. However, aberrant repair of these nick-converted one-ended DSBs, not that of two-ended DSBs in Brca1 -deficient cells, generates mutational signatures such as small indels with microhomology (MH) at the junctions, unbalanced translocations and small MH-mediated TDs, resembling those in BRCA1 -deficient tumors. These results suggest a major contribution of DNA nicks to mutational signatures associated with BRCA1 deficiency in cancer and the underlying mechanisms.
Objective: To explore the relationship between NAD(P)H:quinine oxidoreductase 1 (NQO1) gene polymorphism and susceptibility of lung cancer. Methods: CNKI, Chongqing VIP database, Wanfang database, Medline, PubMed, Embase, Science Online and other databases were used to search a large number of case control studies associated with NQO1 gene cDNA609 polymorphism and susceptibility of lung cancer. Quality assessments were done for every included research study. The systematic analysis was conducted by meta-analysis software Review Manager 5.0. Results: The meta-analysis included 26 research studies finally. In both the TT and CT+TT genotype frequencies of NQO1 gene cDNA609, there were no statistical significances between cases and
Abstract Weight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival ( P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.
The COVID-19 pandemic has created a very difficult time for the whole world with utmost challenge and responsibility on the public health sector to provide symptomatic relief and timely treatment. This condition has stimulated immediate research on the mode of transmission and pathogenesis of the viral variants. As the composition of SARS CoV-2 is similar to SARS-CoV by more than 50%, therefore the management of COVID-19 can possibly be done by repurposing the existing drugs used to treat SARS-CoV infection. The management of SARS CoV-2 infection can be performed at the level of control, prophylaxis and treatment. Many bioactive compounds isolated from medicinal plants have been studied for efficacy in controlling COVID-19 infection by either repression of viral host cell adjunction and subsequent penetration or by repression of viral genomic replication. The bioactive compounds target specific viral or host cell molecules in order to control the spread of virus. Another prominent approach is the development of plant-based vaccines to control the COVID-19 infection and associated complications. The literature also provides evidence of some phytonutrients present in the food supplements which are responsible for increasing the antioxidant, anti-inflammatory, immuno-stimulatory and anti-viral activities in the host cells. For the purpose of COVID prophylaxis and treatment, these phytonutrients can be administered in appropriate functional doses. The chapter is a compilation of research on SARS CoV-2 with its life cycle, pathogenesis, currently used drugs for treatment, including the synthetic ones and the medical herbs and the specific bioactive compounds found efficacious against COVID-19.
The dual-carbon structure maximizes the material's electronic conductivity, improves electron transmission at high current densities, enhances rate performance, and boosts cycle stability at elevated rates.
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