Semiconductor polymeric graphitic carbon nitride (g-C
3
N
4
) photocatalysts have attracted dramatically growing attention in the field of the visible-light-induced hydrogen evolution reaction (HER) ...because of their facile synthesis, easy functionalization, attractive electronic band structure, high physicochemical stability and photocatalytic activity. This review article presents a panorama of the latest advancements in the rational design and development of g-C
3
N
4
and g-C
3
N
4
-based composite photocatalysts for HER application. Concretely, the review starts with the development history, synthetic strategy, electronic structure and physicochemical characteristics of g-C
3
N
4
materials, followed by the rational design and engineering of various nanostructured g-C
3
N
4
(
e.g.
thinner, highly crystalline, doped, and porous g-C
3
N
4
) photocatalysts for HER application. Then a series of highly efficient g-C
3
N
4
(
e.g.
, metal/g-C
3
N
4
, semiconductor/g-C
3
N
4
, metal organic framework/g-C
3
N
4
, carbon/g-C
3
N
4
, conducting polymer/g-C
3
N
4
, sensitizer/g-C
3
N
4
) composite photocatalysts are exemplified. Lastly, this review provides a comprehensive summary and outlook on the major challenges, opportunities, and inspiring perspectives for future research in this hot area on the basis of pioneering works. It is believed that the emerging g-C
3
N
4
-based photocatalysts will act as the "holy grail" for highly efficient photocatalytic HER under visible-light irradiation.
Graphitic carbon nitrides and their composites with various morphologies and bandgaps engineered for the hydrogen evolution reaction under visible light are reviewed.
Impaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a ...as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL-HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.
Abstract
The recently discovered non-Hermitian skin effect (NHSE) manifests the breakdown of current classification of topological phases in energy-nonconservative systems, and necessitates the ...introduction of non-Hermitian band topology. So far, all NHSE observations are based on one type of non-Hermitian band topology, in which the complex energy spectrum winds along a closed loop. As recently characterized along a synthetic dimension on a photonic platform, non-Hermitian band topology can exhibit almost arbitrary windings in momentum space, but their actual phenomena in real physical systems remain unclear. Here, we report the experimental realization of NHSE in a one-dimensional (1D) non-reciprocal acoustic crystal. With direct acoustic measurement, we demonstrate that a twisted winding, whose topology consists of two oppositely oriented loops in contact rather than a single loop, will dramatically change the NHSE, following previous predictions of unique features such as the bipolar localization and the Bloch point for a Bloch-wave-like extended state. This work reveals previously unnoticed features of NHSE, and provides the observation of physical phenomena originating from complex non-Hermitian winding topology.
Thermally sprayed coatings are essentially layered materials and contain large numbers of lamellar pores. It is thus quite necessary to clarify the formation mechanism of lamellar pores which ...significantly influence coating performances. In the present study, to elaborate the formation mechanism of lamellar pores, the yttria-stabilized zirconia (ZrO
2
–7 wt% Y
2
O
3
, 7YSZ) splats, which have high fracture toughness and tetragonal phase stability, were employed. Interestingly, anomalous epitaxial growth occurred for all deposition temperatures in spite of the extremely high cooling rate, which clearly indicated chemical bonding and complete contact at splat/substrate interface before splat cooling. However, transverse spallation substantially occurred for all deposition temperatures in spite of the high fracture toughness of 7YSZ, which revealed that the lamellar pores were from transverse cracking/spallation due to the large stress during splat cooling. Additionally, fracture mechanics analysis was carried out, and it was found that the stress arose from the constraint effect of the shrinkage of the splat by locally heated substrate with the value about 1.97 GPa. This clearly demonstrated that the stress was indeed large enough to drive transverse cracking/spallation forming lamellar pores during splat cooling. All of these contribute to understanding the essential features of lamellar bonding and further tailoring the coating structures and performance.
Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it ...impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.
Lysine‐specific demethylase 5A (KDM5A) has recently become a promising target for epigenetic therapy. In this study, we designed and synthesized metal complexes bearing ligands with reported ...demethylase and p27 modulating activities. The Rh(III) complex 1 was identified as a direct, selective and potent inhibitor of KDM5A that directly abrogate KDM5A demethylase activity via antagonizing the KDM5A‐tri‐/di‐methylated histone 3 protein–protein interaction (PPI) in vitro and in cellulo. Complex 1 induced accumulation of H3K4me3 and H3K4me2 levels in cells, causing growth arrest at G1 phase in the triple‐negative breast cancer (TNBC) cell lines, MDA‐MB‐231 and 4T1. Finally, 1 exhibited potent anti‐tumor activity against TNBC xenografts in an in vivo mouse model, presumably via targeting of KDM5A and hence upregulating p27. Moreover, complex 1 was less toxic compared with two clinical drugs, cisplatin and doxorubicin. To our knowledge, complex 1 is the first metal‐based KDM5A inhibitor reported in the literature. We anticipate that complex 1 may be used as a novel scaffold for the further development of more potent epigenetic agents against cancers, including TNBC.
A rhodium(III)‐based complex has been discovered as an inhibitor of KDM5A, an epigenetic target for triple‐negative breast cancer. The complex inhibited the KDM5A–H3K4me3 interaction and suppressed proliferation of triple‐negative breast cancer (TNBC) tumors in mice and may be used as a novel scaffold for further development of more potent epigenetic agents against cancers, including TNBC.
The emerging role of KDM5A in human cancer Yang, Guan-Jun; Zhu, Ming-Hui; Lu, Xin-Jiang ...
Journal of hematology and oncology,
02/2021, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, ...transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.
Lymphatic malformation (LM) is a vascular anomaly from lymphatic endothelial cells (ECs), and a fraction of the patients could progress to the deadly malignant lymphangiosarcoma (LAS). Using genetic ...tools to delete an essential autophagy gene Rb1cc1/FIP200 or its mutation specifically blocking its autophagy function, we demonstrated that autophagy inhibition abrogated LM progression to LAS although not affecting LM formation in our recently developed mouse model of LAS. Analysis of the mouse models in vivo and vascular tumor cells in vitro showed that autophagy inhibition reduced vascular tumor cell proliferation in vitro and tumorigenicity in vivo without affecting mTORC1 signaling as an oncogenic driver directly. Transcriptional profiling of autophagy-deficient tumor cells and further mechanistic studies revealed a role for osteopontin (OPN) and its downstream Jak/Stat3 signaling in mediating regulation of vascular tumor cells by autophagy. Together, these results support potential new prophylactic strategies to targeting autophagy and/or its downstream OPN expression to prevent progression of the benign LM to the malignant and deadly LAS.
Abbreviations: LM: lymphatic malformation; EC: endothelial cell; LAS: lymphangiosarcoma; OPN: osteopontin; RB1CC1: RB1 Inducible Coiled-Coil 1; FIP200: FAK family-interacting protein of 200 kDa.
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Histone demethylation is a kind of epigenetic modification mediated by a variety of enzymes and participates in regulating multiple physiological and pathological events. ...Lysine-specific demethylase 7A is a kind of α-ketoglutarate- and Fe(II)-dependent demethylase belonging to the PHF2/8 subfamily of the JmjC demethylases. KDM7A is mainly localized in the nucleus and contributes to transcriptional activation via removing mono- and di-methyl groups from the lysine residues 9 and 27 of Histone H3. Mounting studies support that KDM7A is not only necessary for normal embryonic, neural, and skeletal development, but also associated with cancer, inflammation, osteoporosis, and other diseases. Herein, the structure of KDM7A is described by comparing the similarities and differences of its amino acid sequences of KDM7A and other Histone demethylases; the functions of KDM7A in homeostasis and dyshomeostasis are summarized via documenting its content and related signaling; the currently known KDM7A-specific inhibitors and their structural relationship are listed based on their structure optimization and pharmacological activities; and the challenges and opportunities in exploring functions and developing targeted agents of KDM7A are also prospected via presenting encountered problems and potential solutions, which will provide an insight in functional exploration and drug discovery for KDM7A-related diseases.
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