HIV/HBV coinfection: understanding the complex interactions and their impact on spontaneous HBV clearance, chronic liver damage, cirrhosis, and hepatocellular carcinoma.

Compared to either HIV or hepatitis B virus (HBV) monoinfected individuals, HIV/HBV-coinfected individuals have a decreased probability of spontaneous HBV clearance and a greater risk of developing chronic liver damage and a faster progression to cirrhosis and hepatocellular carcinoma. This manuscript attempts to provide a comprehensive review of the landscape of current HIV/HBV coinfection research with a focus on the intricate interactions between these two viruses. Our review will help understand the disease dynamics of HIV/HBV coinfection and has important implications for designing public health strategies.

Design of molybdenum phosphide @ nitrogen-doped nickel-cobalt phosphide heterostructures for boosting electrocatalytic overall water splitting.

Transition metal phosphides (TMPs) are one of the most promising alternatives to noble metal electrocatalysts, but so far their activity and stability still fall short of expectations. Here, we prepare nitrogen-doped nickel-cobalt phosphide (N-NiCoP) and molybdenum phosphide (MoP) heterostructures engineered on nickel foam (NF) with nanosheet structure by high-temperature annealing and low-temperature phosphorylation. Notably, heteroatomic N doping and heterostructures construction are achieved together through a simple co-pyrolysis method. The distinctive composition can synergistically promote the electron transfer, lower the reaction barriers, thus improving the catalytic performance. Therefore, the modified MoP@N-NiCoP requires low overpotentials of 43 mV and 232 mV to reach 10 mA cm-2 current density for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) accompanied by satisfactory stability in 1 M KOH. Density functional theory (DFT) calculations reveal the electron coupling and synergistic interfacial effects at the heterogeneous interface. This study provides a new strategy for heterogeneous electrocatalysts with elemental doping to promote hydrogen applications.

Corrigendum: Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis.

[This corrects the article DOI: 10.3389/fimmu.2022.1032819.].

Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis.

The number of new cases of hepatocellular carcinoma (HCC) worldwide reached 910,000, ranking the sixth, 80% HCC is associated with viruses, so exploring the molecular mechanism of viral carcinogenicity is imperative. The study showed that both HBV and HCV associated HCC and non-viral HCC have the same molecular phenotype (low gene expression and inhibition of immune pathways), but in the tumor immune micro-environment, there is excessive M2-type macrophage polarization in virus-associated hepatocellular carcinoma. To address this phenomenon, the data sets were analyzed and identified five hub genes (POLR2A, POLR2B, RPL5, RPS6, RPL23A) involved in viral gene expression and associated with PI3K-Akt-mTOR pathway activation by six algorithms. In addition, numerous studies have reported that M2-type macrophages participate in the hepatic fibro-pathological process of the development of HCC and are regulated by the PI3K-Akt-mTOR pathway. On this basis, the study showed that hepatitis virus causes abnormal expression of hub genes, leading to the activation of the pathway, which in turn promote the differentiation of M2-type macrophages and eventually promote the formation of liver fibrosis, leading to the occurrence of HCC. In addition, these hub genes are regulated by transcription factors and m6A enzyme, and have good prognosis and diagnostic value. With regard to drug reuse, the results suggest that patients with virus-related HCC for whom Cytidine triphosphate disodium salt and Guanosine-5'-Triphosphate are used as supplementary therapy, and may have a better prognosis. In conclusion, the study has identified novel molecules that are carcinogenic to hepatitis viruses and are expected to serve as molecular markers and targets for diagnosis and treatment.

The In Vitro Effect of Psoralen on Glioma Based on Network Pharmacology and Potential Target Research.

Glioma is an aggressive tumor, currently there is no satisfactory management available. Psoralen, as a natural product, has been found to have an effect of treating cancer in recent years, but its effect on glioma has not been explored. In this study, we investigated the in vitro inhibition effect and potential targets of psoralen on glioma through network pharmacology and in vitro glioma treatment experiments. First, we used network pharmacology to preliminarily predict the 21 core genes of psoralen in the treatment of glioma, including PIK3CA, PIK3CB, PIK3CG, and JAK2. The CCK-8 method was used to detect the effect of psoralen on the proliferation of glioma U87 and U251 cells, and the results showed that psoralen could significantly inhibit the proliferation of U87 and U251 cells. The flow cytometry was used to detect the apoptosis and cell cycle changes, and it was found that psoralen could significantly promote the early apoptosis of U87 and U251 cells and had a significant cycle arrest effect on the two cells. The cell scratch test showed that psoralen could significantly inhibit the migration of U87 and U251 cells. The relative expression levels of PIK3CA, PIK3CB, PIK3CG, and JAK2 were analyzed by Real-time Quantitative polymerase chain reaction (QT-PCR), and the results showed that psoralen could inhibit the gene expression of PIK3CA, PIK3CB, PIK3CG, and JAK2. Later, Western blotting (WB) experiments showed that psoralen could inhibit the protein expressions of PI3K and JAK2. This study has preliminarily explored and verified the antiglioma effect of psoralen in the form of inhibiting cell proliferation and migration, promoting cell apoptosis and organizing cell cycle in vitro. And may play a role by inhibiting the expression of PIK3CA, PIK3CB, PIK3CG, JAK2 gene and PI3K, JAK2 protein, psoralen has become a potential antiglioma drug.

Trace removal of benzene vapour using double-walled metal-dipyrazolate frameworks.

In principle, porous physisorbents are attractive candidates for the removal of volatile organic compounds such as benzene by virtue of their low energy for the capture and release of this pollutant. Unfortunately, many physisorbents exhibit weak sorbate-sorbent interactions, resulting in poor selectivity and low uptake when volatile organic compounds are present at trace concentrations. Herein, we report that a family of double-walled metal-dipyrazolate frameworks, BUT-53 to BUT-58, exhibit benzene uptakes at 298 K of 2.47-3.28 mmol g-1 at <10 Pa. Breakthrough experiments revealed that BUT-55, a supramolecular isomer of the metal-organic framework Co(BDP) (H2BDP = 1,4-di(1H-pyrazol-4-yl)benzene), captures trace levels of benzene, producing an air stream with benzene content below acceptable limits. Furthermore, BUT-55 can be regenerated with mild heating. Insight into the performance of BUT-55 comes from the crystal structure of the benzene-loaded phase (C6H6@BUT-55) and density functional theory calculations, which reveal that C-H···X interactions drive the tight binding of benzene. Our results demonstrate that BUT-55 is a recyclable physisorbent that exhibits high affinity and adsorption capacity towards benzene, making it a candidate for environmental remediation of benzene-contaminated gas mixtures.

A Green-Emission Metal-Organic Framework-Based Nanoprobe for Imaging Dual Tumor Biomarkers in Living Cells.

The modular nature of metal-organic frameworks (MOFs) permits their tunable structure and function for target application, such as in biomedicine. Herein, a green-emission Zr(IV)-MOF (BUT-88) was constructed from a customized luminescent carbazolyl ligand. BUT-88 represents the first bcu-type MOF with both organic linker and metal node in eight connections and shows medium-sized pores, rich accessible linking sites, and good water stability and biocompatibility. In virtue of these merits, BUT-88 was then fabricated into a MOF-based fluorescent nanoprobe, drDNA-BUT-88. Using it, the live-cell imaging of dual tumor biomarkers was achieved for the first time upon a MOF-based probe, offering enhanced detection precision in early cancer diagnosis. Particularly, the probe showed efficient ratiometric fluorescent sensing toward the cytoplasmic biomarker microRNA-21, further improving the detection accuracy at the cellular level. In this work, the elaborate combination of MOF engineering and the fluorescent detection technique has contributed a facile biosensing platform, unlocking more possibilities of MOF chemistry.

Nanocage-Based Porous Metal-Organic Frameworks Constructed from Icosahedrons and Tetrahedrons for Selective Gas Adsorption.

Two isostructural nanocage-based porous Ni/Co(II)-MOFs have been hydrothermally synthesized, which were interestingly composed of icosahedron and tetrahedron cages with a new (3,8)-connected 3D topology. Moreover, the stable Ni-MOF exhibits good selective CO2/CH4 and CO2/N2 adsorption owing to its exposed nitrogen active sites.

Nanoporous Nickel Composite Catalyst for the Dry Reforming of Methane.

The development of efficient catalysts with high activities and durabilities for use in the dry reforming of methane (DRM) is desirable but challenging. We report the development of a nanoporous nickel composite (nanoporous Ni/Y2O3) via a facile one-step dealloying technique, for use in the DRM. Focusing on the low-temperature DRM, our composite possessed remarkable activity and durability against coking compared with conventional particle-based Ni catalysts. This was attributed to the aluminum oxides present on the Ni surface, which suppress pore coarsening. In addition, the inert bundled Y2O3 nanowires are suitable for use as substrates for nanoporous Ni.

Functionalized Base-Stable Metal-Organic Frameworks for Selective CO2 Adsorption and Proton Conduction.

Metal-organic frameworks (MOFs) have shown great potential for application in various fields, including CO2 capture and proton conduction. For promoting their practical applications, both optimization of a given property and enhancement of chemical stability are crucial. In this work, three base-stable isostructural MOFs, [Ni8 (OH)4 (H2 O)2 (BDP-X)6 ] (Ni-BDP-X; H2 BDP=1,4-bis(4-pyrazolyl)benzene, X=CHO, CN, COOH) with different functional groups, are designed, synthesized, and used in CO2 capture and proton conduction experiments. They possess face-centered cubic topological structures with functional nanoscale cavities. Importantly, these MOFs are fairly stable to maintain their structures in boiling water and 4 M sodium hydroxide solution at room temperature. Functionalization endows them with tunable properties. In gas adsorption studies, these MOFs exhibit selective adsorption of CO2 over CH4 and N2 , and in particular the introduction of COOH groups provides the highest selectivity. In addition, the COOH-functionalized Ni-BDP exhibits a high proton conductivity of 2.22×10-3  S cm-1 at 80 °C and approximately 97 % relative humidity.

A Base-Resistant ZnII -Based Metal-Organic Framework: Synthesis, Structure, Postsynthetic Modification, and Gas Adsorption.

A ZnII -based metal-organic framework (MOF), [Zn2 (bdp-CHO)2 ]⋅(DMF)(CH3 CN)(H2 O)2 (BUT-31) is reported that was synthesized by the reaction between a newly designed aldehyde-tagged polypyrazole ligand 2,5-di(1H-pyrazol-4-yl)benzaldehyde (H2 bdp-CHO) and a zinc salt. BUT-31 has a unique pillared layered framework structure with 3D intersecting channels approximately 3.4-5.4 Šin size. Powder X-ray diffraction and N2 adsorption experiments revealed that BUT-31 is rigid and permanently porous with the Brunauer-Emmett-Teller surface area of 926 m2 g-1 . Notably, this MOF tolerates boiling water and even highly basic aqueous solution (4 m sodium hydroxide), although dilute acid gradually decomposes its framework. Owing the permanent porosity and chemical stability of BUT-31, covalent post-modification of the free aldehyde group exposed on the pore surface was accomplished by treating the MOF in a concentrated ammonia solution (25 %) at near room temperature, giving rise to an imine-functionalized analogue of BUT-31. Gas adsorption results show that the aldehyde- and imine-functionalized MOFs have high CO2 adsorption capacities, as well as CO2 /N2 and CO2 /CH4 adsorption selectivities.

A hydrothermally stable Zn(ii)-based metal-organic framework: structural modulation and gas adsorption.

By the solvothermal reaction of a triangular ligand, 2,4,6-tris-(4-carboxyphenoxy)-1,3,5-triazine (H3tcpt) with Zn(NO3)2·6H2O in N,N'-dimethylacetamide/acetonitrile/H2O (v/v/v = 1 : 1 : 1) mixed solvents, a two-fold, interpenetrated, three-dimensional (3D), porous metal-organic framework, [Zn2(tcpt)OH]·solvents (1·solvents), with a rare, paddlewheel secondary building unit (SBU), Zn2(COO)3, was synthesized and characterized. It was found that a single 3D structure of 1 forms when two-dimensional layers, which are constructed by tcpt(3-) bonding with the paddlewheel SBUs, are linked by -OH groups along the axial sites of the SBUs. Compared with the reported Zn(ii)-based partners with this ligand, synthesis conditions, particularly the solvents used, clearly played a key role in the formation of different SBUs, thereby resulting in distinct MOFs with the same ligand. In particular, 1 features good water and thermal stability and can withstand acidic aqueous solutions with pH values ranging from 5 to 12. In addition, 1 displays good adsorption ability towards H2 (2.21 wt% at 77 K and 1 atm) and can selectively adsorb CO2 from CH4 and N2, in spite of its relatively low void volume (36.8%), suggesting potential applications in gas storage and separation.

Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinase inhibitor (BMS-540215).

A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The l-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials.

Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor.

A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo[2,1-f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure-activity relationship studies revealed that a methyl group at the 5-position and a substituted alkoxy group at the 6-position of the pyrrolo[2,1-f][1,2,4]triazine core gave potent compounds. Biochemical potency, kinase selectivity, and pharmacokinetics of the series were optimized and in vitro safety liabilities were minimized to afford BMS-540215 (12), which demonstrated robust preclinical in vivo activity in human tumor xenograft models. The l-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in clinical trials for the treatment of solid tumors.