Vpr driving DNA methylation variation of CD4 + T cells in HIV-1 infection.

BACKGROUND: Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted. METHODS: In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection. RESULTS: We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes. CONCLUSIONS: These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Construction of Buertai Coal Macromolecular Model and GCMC Simulation of Methane Adsorption in Micropores.

With the increase in high gas mines in the low coal rank mining area in the northwestern part of China, high gas mines in the low-rank coal mining area have caused many gas emission accidents. Coal is a porous material, containing a large number of micropores (<2 nm), which can absorb large amounts of methane, so it is necessary to explore methane adsorption in micropores of low-rank coal. In this work, FTIR, HRTEM, and 13C-NMR were used to test the macromolecular structural parameters of Buertai coal, which was a kind of low-rank Jurassic coal in northwestern China. The results showed that the aromatic structural units in the Buertai coal structure mainly consist of naphthalene, anthracene, and phenanthrene. The fat structure mainly occurs in the form of aliphatic side chains, cycloalkanes, and other compounds. The oxygen atoms are present in the form of carbonyl groups, ether bonds, and phenol groups with a ratio of about 6:4:9. The nitrogen atoms are present in the form of pyrrole and pyridine compounds. Finally, the macromolecular structure model of Buertai coal was built, and the calculated NMR spectrum from the model was very consistent with the experimental NMR spectrum of Buertai coal. The relationship between the macromolecular density and energy of Buertai coal was explored using the Amorphous Cell module in the simulation software, Materials Studios 8.0 (MS 8.0), and the density value at the lowest energy was determined to be about 1.23 g/cm3. The pore structure parameters of Buertai coal were also calculated. It was found that both pore volume and void fraction decreased evenly as the diameter of the probe molecule increased, but the surface area decreased rapidly when the diameter of the probe molecule was 3.46 Å. All pore sizes were found to be smaller than 10 Å from the pore size distribution (PSD) curve of Buertai coal, which provided a lot of adsorption sites for methane (CH4). The results of the CH4 adsorption simulation from Grand Canonical Monte Carlo (GCMC) showed that CH4 is adsorbed inside the micropores of coal, and the adsorption capacity of CH4 depends on the diameters of micropores when the micropores are less than 8.5 Å. There are many micropores where CH4 did not appear because these micropores are closed and did not provide a channel for CH4 to enter. The results of experimental methane adsorption indicate that the excess adsorption capacity from the GCMC simulation was very close to the experimental results of Buertai coal. This work provides a new perspective to study the methane adsorption behavior in micropores of coal.

Insight into the rapid sodium storage mechanism of the fiber-like oxygen-doped hierarchical porous biomass derived hard carbon.

Biomass, as a continuously available raw material, is widely used to produce hard carbon. However, many researchers have ignored the natural special morphology of biomass and the influence of oxygen on the sodium storage performance. Here, we use the cilia of the setaria viridis as the precursor to obtain a fiber-like oxygen-doped hierarchical porous hard carbon (SVC). The sodium storage mechanism of SVC is studied by controlling the pyrolysis temperature. Studies have shown that the natural fibrous structure and vertical holes of SVC can provide channels for the rapid penetration of electrolyte. The appropriate nanocrystal size affords commodious circumstances for the insertion of Na+. More importantly, the increase in carbonization temperature will change the bonding mode of carbon and oxygen, promote the rupture of single bonds and retain the existence of double bonds, which is beneficial to the improvement of coulombic efficiency and reversible capacity. The hybrid sodium storage mechanism composed of insertion behavior and capacitance behavior promotes SVC to have higher reversible capacity (285.4 mAh g-1 at 0.05 A g-1) and excellent rate performance (90.7 mAh g-1 at 5 A g-1). This research provides some new ideas for the study of hard carbon.

Preparation of Activated Carbon Doped with Graphene Oxide Porous Materials and Their High Gas Adsorption Performance.

It is still a great challenge to develop a new porous carbon adsorbent with excellent separation performance and to recover low-concentration CH4 in coal mine gas. This work provides a new idea for the study of CH4 adsorption on activated carbon (AC) composites. Composite materials with microporous structures were prepared from coconut-shell activated carbon (CAC) doped with graphene oxide (GO) by a chemical activation process in this paper. The expansion and dissociation of GO at high temperatures indirectly improve the specific surface area (SSA) of the composite. The interlayer aggregation is reduced, the activation effect is improved, and a new low-cost adsorption material is prepared. The SSA of CAC-50 is more than 3000 m2·g-1. A high SSA and a narrow pore size distribution lead to a higher total adsorption capacity of CH4. The breakthrough test also confirmed that AC/GOs had a better adsorption capacity for CH4. The separation performance of the CH4/N2 mixture is not good at room temperature, which is due to the influence of a high SSA and average pore size. As a low-cost and rich material, CAC has a wide range of application prospects. The composite is a potential material for recovering low-concentration CH4 from the coal mine, which is worthy of attention. In the future, the selectivity of AC/GOs to CH4 can be increased by loading functional groups or modification.

A Novel Strategy to Enhance the Performance of CO2 Adsorption Separation: Grafting Hyper-cross-linked Polyimide onto Composites of UiO-66-NH2 and GO.

Graphene oxide (GO) is widely used to improve the pore structure, dispersion capacity, adsorption selectivity, resistance to acids and bases, and thermal stability of metal-organic frameworks (MOFs). However, it remains a daunting challenge to enhance selectivity simply by modifying the pore surface polarity and producing a suitable pore structure for CO2 molecules through a combination of GO with MOFs. Herein, we demonstrate a novel porous hyper-cross-linked polyimide-UiO-graphene composite adsorbent for CO2 capture via in situ chemical knitting and condensation reactions. Specifically, a network of polyimides rich in carbonyl and nitrogen atoms with amino terminations was synthesized via the reaction of 4,4'-oxydiphthalic anhydride (ODPA) and 2,4,6-trimethyl-1,3-phenylenediamine (DAM). The product plays a crucial role in the separation of CO2 from N2. As expected, the resulting composite (PI-UiO/GO-1) exhibited a 3-fold higher CO2 capacity (8.24 vs 2.8 mmol·g-1 at 298 K and 30 bar), 4.2 times higher CO2/N2 selectivity (64.71 vs 15.43), and significantly improved acid-base resistance stability compared with those values of pristine UiO-66-NH2. Furthermore, breakthrough experiments verified that the porous composites can effectively separate CO2 from simulated fuel gas (CO2/N2 = 15/85 vol %) with great potential in industrial applications. More importantly, this strategy can be extended to prepare other MOF-based composites. This clearly advances the development of MOF-polymer materials for gas capture.

Transforming Metal-Organic Frameworks into Porous Liquids via a Covalent Linkage Strategy for CO2 Capture.

Porous liquids (PLs), an emerging kind of liquid materials with permanent porosity, have attracted increasing attention in gas capture. However, directly turning metal-organic frameworks (MOFs) into PLs via a covalent linkage surface engineering strategy has not been reported. Additionally, challenges including reducing the cost and simplifying the preparation process are daunting. Herein, we proposed a general method to transform Universitetet i Oslo (UiO)-66-OH MOFs into PLs by surface engineering with organosilane (OS) and oligomer species via covalent bonding linkage. The oligomer species endow UiO-66-OH with superior fluidity at room temperature. Meanwhile, the resulting PLs showed great potential in both CO2 adsorption and CO2/N2 selective separation. The residual porosity of PLs was verified by diverse characterizations and molecular simulations. Besides, CO2 selective capture sites were determined by grand canonical Monte Carlo (GCMC) simulation. Furthermore, the universality of the covalent linkage surface engineering strategy was confirmed using different classes of oligomer species and another MOF (ZIF-8-bearing amino groups). Notably, this strategy can be extended to construct other PLs by taking advantages of the rich library of oligomer species, thus making PLs promising candidates for further applications in energy and environment-related fields, such as gas capture, separation, and catalysis.