The evolution of the SARS‐CoV‐2 new variants reported to be 70% more contagious than the earlier one is now spreading fast worldwide. There is an instant need to discover how the new variants ...interact with the host receptor (ACE2). Among the reported mutations in the Spike glycoprotein of the new variants, three are specific to the receptor‐binding domain (RBD) and required insightful scrutiny for new therapeutic options. These structural evolutions in the RBD domain may impart a critical role to the unique pathogenicity of the SARS‐CoV‐2 new variants. Herein, using structural and biophysical approaches, we explored that the specific mutations in the UK (N501Y), South African (K417N‐E484K‐N501Y), Brazilian (K417T‐E484K‐N501Y), and hypothetical (N501Y‐E484K) variants alter the binding affinity, create new inter‐protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. Our investigation highlighted that the South African (K417N‐E484K‐N501Y), Brazilian (K417T‐E484K‐N501Y) variants are more lethal than the UK variant (N501Y). The behavior of the wild type and N501Y is comparable. Free energy calculations further confirmed that increased binding of the spike RBD to the ACE2 is mainly due to the electrostatic contribution. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection‐driven epistasis in protein evolution. The triple mutants (South African and Brazilian) may pose a serious threat to the efficacy of the already developed vaccine. Our analysis would help to understand the binding and structural dynamics of the new mutations in the RBD domain of the Spike protein and demand further investigation in in vitro and in vivo models to design potential therapeutics against the new variants.
This study precisely explored the mechanism of the interaction of the spike RBD with the host ACE2 and revealed the differences in the binding of the reference and new variants. The systematic investigation revealed that the South African and Brazilian variants are more lethal than the others due to inter‐protein contacts specifically the electrostatic while the N501Y is comparable with the wild type. We hypothesized that the residue at 501Y is continuously subjected to positive selection pressure. We further demonstrated the dynamic behavior is also changed with the protein evolution. Conclusively, this study provides strong basis for structure and rationale‐based drug designing against the new variant by exploring the noticeable differences.
The development of an effective one‐photon excitation pathway to improve the charge‐carrier separation and mobility of semiconductors, which have been proven to be favorable for heterogeneous ...catalysis, is highly desirable but remains a great challenge. Herein, a high‐throughput one‐photon excitation pathway is reported by constructing 0D carbon dots/3D porous carbon nitride nanovesicles (denoted as CDs/PCN NVs) heterostructures for photocatalytic hydrogen evolution. In particular, the optimum CDs/PCN NVs heterostructures exhibit an impressive performance of 14.022 mmol h−1 g−1, which is 56.54 times higher than that of pristine CN. Detailed characterization reveals that the improved performance is primarily attributed to the high‐throughput and one‐photon excitation pathway. The former could be attributed to a great deal of CDs with high charge‐carrier mobility coupled to PCN NVs, which enable more electrons to be photoexcited via the broad absorption response, and the multiple reflection of incident light owing to the porous nanovesicle structure with shortened route of carriers migrating toward the surface; the latter would lead to the photoinduced holes and electrons accumulated at the valence band of PCN NVs and surface of CDs, respectively, achieving an effective spatial separation. The high‐throughput one‐photon excitation pathway demonstrated here may provide insights into the development of nanocomposites for various related applications.
A high‐throughput one‐photon excitation pathway is reported by constructing 0D carbon dots/3D porous carbon nitride nanovesicles (CDs/PCN NVs) heterostructures for visible‐light driven hydrogen evolution. In particular, the covalently bonded CDs on PCN NVs enable a high throughput charge migration in the wide spectrum visible light region and promote effective spatial separation via a one‐photon excitation pathway.
Interface strains and lattice distortion are inevitable issues during perovskite crystallization. Silane as a coupling agent is a popular connector to enhance the compatibility between inorganic and ...organic materials in semiconductor devices. Herein, a protonated amine silane coupling agent (PASCA‐Br) interlayer between TiO2 and perovskite layers is adopted to directionally grasp both of them by forming the structural component of a lattice unit. The pillowy alkyl ammonium bromide terminals at the upper side of the interlayer provide well‐matched growth sites for the perovskite, leading to mitigated interface strain and ensuing lattice distortion; meanwhile, its superior chemical compatibility presents an ideal effect on healing the under‐coordinated Pb atoms and halogen vacancies of bare perovskite crystals. The PASCA‐Br interlayer also serves as a mechanical buffer layer, inducing less cracked perovskite film when bending. The developed molecular‐level flexible interlayer provides a promising interfacial engineering for perovskite solar cells and their flexible application.
A protonated amino silane coupling agent as an interlayer is exploited on rigid and flexible substrates, which not only sets up well‐matched growth underlay but also serves as a structural component of the lattice units, leading to less‐distorted perovskite films, resulting in an obvious advance in device performance, stability, and mechanical tolerance in the corresponding flexible device.
Reported herein is the rhodium‐catalyzed enantioselective CH bond silylation of the cyclopentadiene rings in Fe and Ru metallocenes. Thus, in the presence of (S)‐TMS‐Segphos, the reactions took ...place under very mild conditions to afford metallocene‐fused siloles in good to excellent yields and with ee values of up to 97 %. During this study it was observed that the steric hindrance of chiral ligands had a profound influence on the reactivity and enantioselectivity of the reaction, and might hold the key to accomplishing conventionally challenging asymmetric CH silylations.
New on the (metallo)cene: The title reaction of cyclopentadiene (Cp) rings in Fe and Ru metallocenes is reported. Fine‐tuning the steric hindrance of diphosphine ligands led to the identification of (S)‐TMS‐Segphos (S)‐L, which enabled efficient, enantioselective CH silylation of the Cp rings in metallocenes under mild reaction conditions. cod=1,5‐cyclooctadiene, TMS=trimethylsilyl.
Lung adenocarcinoma (LUAD) is a major subtype of non–small‐cell lung cancer, which is the leading cause of cancer death worldwide. The histone H3K36 methyltransferase SETD2 has been reported to be ...frequently mutated or deleted in types of human cancer. However, the functions of SETD2 in tumor growth and metastasis in LUAD has not been well illustrated. Here, we found that SETD2 was significantly downregulated in human lung cancer and greatly impaired proliferation, migration, and invasion in vitro and in vivo. Furthermore, we found that SETD2 overexpression significantly attenuated the epithelial–mesenchymal transition (EMT) of LUAD cells. RNA‐seq analysis identified differentially expressed transcripts that showed an elevated level of interleukin 8 (IL‐8) in STED2‐knockdown LUAD cells, which was further verified using qPCR, western blot, and promoter luciferase report assay. Mechanically, SETD2‐mediated H3K36me3 prevented assembly of Stat1 on the IL‐8 promoter and contributed to the inhibition of tumorigenesis in LUAD. Our findings highlight the suppressive role of SETD2/H3K36me3 in cell proliferation, migration, invasion, and EMT during LUAD carcinogenesis, via regulation of the STAT1–IL‐8 signaling pathway. Therefore, our studies on the molecular mechanism of SETD2 will advance our understanding of epigenetic dysregulation at LUAD progression.
Our findings highlight the suppressive role of SETD2/H3K36me3 in cell proliferation, migration, invasion, and EMT during LUAD carcinogenesis, via regulation of the STAT1–IL‐8 signaling pathway. Therefore, our studies on the molecular mechanism of SETD2 will advance our understanding of epigenetic dysregulation at LUAD development.
2D amorphous transition metal oxides (a‐TMOs) heterojunctions that have the synergistic effects of interface (efficiently promoting the separation of electron−hole pairs) and amorphous nature ...(abundant defects and dangling bonds) have attracted substantial interest as compelling photocatalysts for solar energy conversion. Strategies to facilely construct a‐TMOs‐based 2D/2D heterojunctions is still a big challenge due to the difficulty of preparing individual amorphous counterparts. A generalized synthesis strategy based on supramolecular self‐assembly for bottom–up growth of a‐TMOs‐based 2D heterojunctions is reported, by taking 2D/2D g‐C3N4 (CN)/a‐TMOs heterojunction as a proof‐of‐concept. This strategy primarily depends on controlling the cooperation of the growth of supramolecular precursor and the coordinated covalent bonds arising from the tendency of metal ions to attain the stable configuration of electrons, which is independent on the intrinsic character of individual metal ion, indicating it is universally applicable. As a demonstration, the structure, physical properties, and photocatalytic water‐splitting performance of CN/a‐ZnO heterojunction are systematically studied. The optimized 2D/2D CN/a‐ZnO exhibits enhanced photocatalytic performance, the hydrogen (432.6 µmol h−1 g−1) and oxygen (532.4 µmol h−1 g−1) evolution rate are 15.5 and 12.2 times than bulk CN, respectively. This synthetic strategy is useful to construct 2D a‐TMOs nanomaterials for applications in energy‐related areas and beyond.
A generalized synthesis strategy for the bottom–up growth of amorphous transition metal oxides (a‐TMOs) 2D/2D heterojunctions with large contact area via covalent interfacial interaction is provided. A number of 2D/2D CN/a‐TMOs heterojunctions, such as CN/a‐FeOx, CN/a‐CuOx, CN/a‐MnOx, CN/a‐CoOx, and CN/a‐ZnO are successfully synthesized, which has a large and perfect order−disorder interface. Particularly, 2D/2D CN/a‐ZnO heterojunction exhibit boosted photocatalytic hydrogen and oxygen evolution.
Abstract
Insufficient access to clean water and resources has emerged as one of the most pressing issues affecting people globally. Membrane‐based ion separation has become a focal point of research ...for the generation of fresh water and the extraction of energy elements. This Review encapsulates recent advancements in the selective ion transport of covalent organic framework (COF) membranes, accomplished by strategically pairing diverse monomers to create membranes with various pore sizes and environments for specific purposes. We first discuss the merits of using COF materials as a basis for fabricating membranes for ion separation. We then explore the development of COF membranes in areas such as desalination, acid recovery, and energy element extraction, with a particular emphasis on the fundamental principles of membrane design. Lastly, we address both theoretical and practical challenges, as well as potential opportunities in the targeted design of ion‐selective membranes. The goal of this Review is to stimulate future investigative efforts in this field, which is of significant scientific and strategic importance.
We report a method to construct chiral tetraorganosilicons by tandem silacyclobutane (SCB) desymmetrization–dehydrogenative silylations. A wide array of dibenzosiloles with stereogenic quaternary ...silicon centers were obtained in good yields and enantioselectivities up to 93 % ee. Chiral TMS‐segphos was found to be a superior ligand in terms of reactivity and enantioselectivity.
Chiral silicon: A Rh‐catalyzed reaction between silacyclobutane and (hetero)arenes in the presence of (R)‐ or (S)‐TMS‐segphos provides access to a wide array of chiral dibenzosiloles in good yields and enantioselectivities (up to 93 % ee). The reaction proceeds through a rarely documented desymmetrization of silacyclobutane, followed by intra‐ and intermolecular dehydrogenative silylation processes.
Tumor‐associated macrophages (TAMs) are crucial components of the tumor microenvironment. They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs ...and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP‐1 cells in vitro to investigate their functions in HCC progression. S100 calcium‐binding protein A9 (S100A9), an inflammatory microenvironment‐related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell‐like properties of HepG2 and MHCC‐97H cells by activating nuclear factor‐kappa B signaling pathway through advanced glycosylation end product‐specific receptor in a Ca2+‐dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC‐97H cells recruited more macrophages via chemokine (CC motif) ligand 2, which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate secreted protein S100A9 and enhance the stem cell‐like properties of HCC cells and provide a potential therapeutic target for combating HCC.
What's new?
Prognosis of hepatocellular carcinoma (HCC) is influenced by tumor‐associated macrophages (TAMs) in the tumor microenvironment. Little is known, however, about how TAMs fuel HCC progression. This comparative analysis of RNA‐sequencing and whole‐genome expression profiling between TAMs and nonactivated M0 macrophages identified three common upregulated genes with potential impact on HCC prognosis. Among them, S100 calcium binding protein A9 (S100A9) was found to enhance stem cell‐like properties in HCC cells, via Ca2+‐dependent signaling along the AGER/NF‐κB axis. Moreover, S100A9 increased TAM infiltration by facilitating CCL2 secretion. The findings warrant further investigation of S100A9 secretion and enhanced HCC cell stemness by TAMs.
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