Recent advances in various adeno-associated viruses (AAVs) as gene therapy agents in hepatocellular carcinoma.

Primary liver cancer, which is scientifically referred to as hepatocellular carcinoma (HCC), is a significant concern in the field of global health. It has been demonstrated that conventional chemotherapy, chemo-hormonal therapy, and conformal radiotherapy are ineffective against HCC. New therapeutic approaches are thus urgently required. Identifying single or multiple mutations in genes associated with invasion, metastasis, apoptosis, and growth regulation has resulted in a more comprehensive comprehension of the molecular genetic underpinnings of malignant transformation, tumor advancement, and host interaction. This enhanced comprehension has notably propelled the development of novel therapeutic agents. Therefore, gene therapy (GT) holds great promise for addressing the urgent need for innovative treatments in HCC. However, the complexity of HCC demands precise and effective therapeutic approaches. The adeno-associated virus (AAV) distinctive life cycle and ability to persistently infect dividing and nondividing cells have rendered it an alluring vector. Another appealing characteristic of the wild-type virus is its evident absence of pathogenicity. As a result, AAV, a vector that lacks an envelope and can be modified to transport DNA to specific cells, has garnered considerable interest in the scientific community, particularly in experimental therapeutic strategies that are still in the clinical stage. AAV vectors emerge as promising tools for HCC therapy due to their non-immunogenic nature, efficient cell entry, and prolonged gene expression. While AAV-mediated GT demonstrates promise across diverse diseases, the current absence of ongoing clinical trials targeting HCC underscores untapped potential in this context. Furthermore, gene transfer through hepatic AAV vectors is frequently facilitated by GT research, which has been propelled by several congenital anomalies affecting the liver. Notwithstanding the enthusiasm associated with this notion, recent discoveries that expose the integration of the AAV vector genome at double-strand breaks give rise to apprehensions regarding their enduring safety and effectiveness. This review explores the potential of AAV vectors as versatile tools for targeted GT in HCC. In summation, we encapsulate the multifaceted exploration of AAV vectors in HCC GT, underlining their transformative potential within the landscape of oncology and human health.

A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer.

According to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV. Video Abstract.

Bandgap of two-dimensional materials: Thorough assessment of modern exchange-correlation functionals.

The density-functional theory (DFT) approximations that are the most accurate for the calculation of bandgap of bulk materials are hybrid functionals, such as HSE06, the modified Becke-Johnson (MBJ) potential, and the GLLB-SC potential. More recently, generalized gradient approximations (GGAs), such as HLE16, or meta-GGAs, such as (m)TASK, have also proven to be quite accurate for the bandgap. Here, the focus is on two-dimensional (2D) materials and the goal is to provide a broad overview of the performance of DFT functionals by considering a large test set of 298 2D systems. The present work is an extension of our recent studies [T. Rauch, M. A. L. Marques, and S. Botti, Phys. Rev. B 101, 245163 (2020); Patra et al., J. Phys. Chem. C 125, 11206 (2021)]. Due to the lack of experimental results for the bandgap of 2D systems, G0W0 results were taken as reference. It is shown that the GLLB-SC potential and mTASK functional provide the bandgaps that are the closest to G0W0. Following closely, the local MBJ potential has a pretty good accuracy that is similar to the accuracy of the more expensive hybrid functional HSE06.

Orbital-free approximations to the kinetic-energy density in exchange-correlation MGGA functionals: Tests on solids.

A recent study of Mejia-Rodriguez and Trickey [Phys. Rev. A 96, 052512 (2017)] showed that the deorbitalization procedure (replacing the exact Kohn-Sham kinetic-energy density by an approximate orbital-free expression) applied to exchange-correlation functionals of the meta-generalized gradient approximation (MGGA) can lead to important changes in the results for molecular properties. For the present work, the deorbitalization of MGGA functionals is further investigated by considering various properties of solids. It is shown that depending on the MGGA, common orbital-free approximations to the kinetic-energy density can be sufficiently accurate for the lattice constant, bulk modulus, and cohesive energy. For the bandgap, calculated with the modified Becke-Johnson MGGA potential, the deorbitalization has a larger impact on the results.

Unveiling the potential effects of resveratrol in lung cancer treatment: Mechanisms and nanoparticle-based drug delivery strategies.

Lung cancer ranks among the most prevalent forms of cancer and remains a significant factor in cancer-related mortality across the world. It poses significant challenges to healthcare systems and society as a whole due to its high incidence, mortality rates, and late-stage diagnosis. Resveratrol (RV), a natural compound found in various plants, has shown potential as a nanomedicine for lung cancer treatment. RV has varied effects on cancer cells, including promoting apoptosis by increasing pro-apoptotic proteins (Bax and Bak) and decreasing anti-apoptotic proteins (Bcl-2). It also hinders cell proliferation by influencing important signaling pathways (MAPK, mTOR, PI3K/Akt, and Wnt/ß-catenin) that govern cancer progression. In addition, RV acts as a potent antioxidant, diminishing oxidative stress and safeguarding cells against DNA damage. However, using RV alone in cancer treatment has drawbacks, such as low bioavailability, lack of targeting ability, and susceptibility to degradation. In contrast, nanoparticle-based delivery systems address these limitations and hold promise for improving treatment outcomes in lung cancer; nanoparticle formulations of RV offer advantages such as improved drug delivery, increased stability, controlled release, and targeted delivery to lung cancer cells. This article will provide an overview of lung cancer, explore the potential of RV as a therapeutic agent, discuss the benefits and challenges of nanoparticle-based drug delivery, and highlight the promise of RV nanoparticles for cancer treatment, including lung cancer. By optimizing these systems for clinical application, future studies aim to enhance overall treatment outcomes and improve the prognosis for lung cancer patients.

Role of non-coding RNAs in neuroblastoma.

Neuroblastoma is known as the most prevalent extracranial malignancy in childhood with a neural crest origin. It has been widely accepted that non-coding RNAs (ncRNAs) play important roles in many types of cancer, including glioma and gastrointestinal cancers. They may regulate the cancer gene network. According to recent sequencing and profiling studies, ncRNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation. Disturbances in the expression of ncRNAs may act either as oncogenes or as anti-tumor suppressor genes, and can lead to the induction of cancer hallmarks. ncRNAs can be secreted from tumor cells inside exosomes, where they can be transferred to other cells to affect their function. However, these topics still need more study to clarify their exact roles, so the present review addresses different roles and functions of ncRNAs in neuroblastoma.

Efficient Band Structure Calculation of Two-Dimensional Materials from Semilocal Density Functionals.

The experimental and theoretical realization of two-dimensional (2D) materials is of utmost importance in semiconducting applications. Computational modeling of these systems with satisfactory accuracy and computational efficiency is only feasible with semilocal density functional theory methods. In the search for the most useful method in predicting the band gap of 2D materials, we assess the accuracy of recently developed semilocal exchange-correlation (XC) energy functionals and potentials. Though the explicit forms of exchange-correlation (XC) potentials are very effective against XC energy functionals for the band gap of bulk solids, their performance needs to be investigated for 2D materials. In particular, the LMBJ [J. Chem. Theory Comput.2020, 16, 2654] and GLLB-SC [Phys. Rev. B82, 2010, 115106] potentials are considered for their dominance in bulk band gap calculation. The performance of recently developed meta generalized gradient approximations, like TASK [Phys. Rev. Res.1, 2019, 033082] and MGGAC [Phys. Rev. B. 100, 2019, 155140], is also assessed. We find that the LMBJ potential constructed for 2D materials is not as successful as its parent functional, i.e., MBJ [Phys. Rev. Lett.102, 2009, 226401] in bulk solids. Due to a contribution from the derivative discontinuity, the band gaps obtained with GLLB-SC are in a certain number of cases, albeit not systematically, larger than those obtained with other methods, which leads to better agreement with the quasi-particle band gap obtained from the GW method. The band gaps obtained with TASK and MGGAC can also be quite accurate.

Elucidating the formation and active state of Cu co-catalysts for photocatalytic hydrogen evolution.

The design of active and selective co-catalysts constitutes one of the major challenges in developing heterogeneous photocatalysts for energy conversion applications. This work provides a comprehensive insight into thermally induced bottom-up generation and transformation of a series of promising Cu-based co-catalysts. We demonstrate that the volcano-type HER profile as a function of calcination temperature is independent of the type of the Cu precursor but is affected by changes in oxidation state and location of the copper species. Supported by DFT modeling, our data suggest that low temperature (<200 °C) treatments facilitate electronic communication between the Cu species and TiO2, which allows for a more efficient charge utilization and maximum HER rates. In contrast, higher temperatures (>200 °C) do not affect the Cu oxidation state, but induce a gradual, temperature-dependent surface-to-bulk diffusion of Cu, which results in interstitial, tetra-coordinated Cu+ species. The disappearance of Cu from the surface and the introduction of new defect states is associated with a drop in HER performance. This work examines electronic and structural effects that are in control of the photocatalytic activity and can be transferred to other systems for further advancing photocatalysis.