Histone deacetylases (HDACs) are essential for maintaining homeostasis by catalyzing histone deacetylation. Aberrant expression of HDACs is associated with various human diseases. Although HDAC ...inhibitors are used as effective chemotherapeutic agents in clinical practice, their applications remain limited due to associated side effects induced by weak isoform selectivity. HDAC6 displays unique structure and cellular localization as well as diverse substrates and exhibits a wider range of biological functions than other isoforms. HDAC6 inhibitors have been effectively used to treat cancers, neurodegenerative diseases, and autoimmune disorders without exerting significant toxic effects. Progress has been made in defining the crystal structures of HDAC6 catalytic domains which has influenced the structure-based drug design of HDAC6 inhibitors. This review summarizes recent literature on HDAC6 inhibitors with particular reference to structural specificity and functional diversity. It may provide up-to-date guidance for the development of HDAC6 inhibitors and perspectives for optimization of therapeutic applications.
Abstract
Architected materials that actively respond to external stimuli hold tantalizing prospects for applications in energy storage, wearable electronics, and bioengineering. Molybdenum disulfide, ...an excellent two-dimensional building block, is a promising candidate for lithium-ion battery anode. However, the stacked and brittle two-dimensional layered structure limits its rate capability and electrochemical stability. Here we report the dewetting-induced manufacturing of two-dimensional molybdenum disulfide nanosheets into a three-dimensional foam with a structural hierarchy across seven orders of magnitude. Our molybdenum disulfide foam provides an interpenetrating network for efficient charge transport, rapid ion diffusion, and mechanically resilient and chemically stable support for electrochemical reactions. These features induce a pseudocapacitive energy storage mechanism involving molybdenum redox reactions, confirmed by in-situ X-ray absorption near edge structure. The extraordinary electrochemical performance of molybdenum disulfide foam outperforms most reported molybdenum disulfide-based Lithium-ion battery anodes and state-of-the-art materials. This work opens promising inroads for various applications where special properties arise from hierarchical architecture.
Traumatic brain injury (TBI) is a major public health challenge that is also the third leading cause of death worldwide. It is also the leading cause of long-term disability in children and young ...adults worldwide. Despite a large body of research using predominantly
and
rodent models of brain injury, there is no medication that can reduce brain damage or promote brain repair mainly due to our lack of understanding in the mechanisms and pathophysiology of the TBI. The aim of this review is to examine
TBI studies conducted from 2008-2018 to better understand the TBI
model available in the literature. Specifically, our focus was to perform a detailed analysis of the
experimental protocols used and their subsequent biological findings. Our review showed that the uniaxial stretch is the most frequently used way of load application, accounting for more than two-thirds of the studies reviewed. The rate and magnitude of the loading were varied significantly from study to study but can generally be categorized into mild, moderate, and severe injuries. The
studies reviewed here examined key processes in TBI pathophysiology such as membrane disruptions leading to ionic dysregulation, inflammation, and the subsequent damages to the microtubules and axons, as well as cell death. Overall, the studies examined in this review contributed to the betterment of our understanding of TBI as a disease process. Yet, our review also revealed the areas where more work needs to be done such as: 1) diversification of load application methods that will include complex loading that mimics
head impacts; 2) more widespread use of human brain cells, especially patient-matched human cells in the experimental set-up; and 3) need for building a more high-throughput system to be able to discover effective therapeutic targets for TBI.
Backgrounds
Periodontitis is an oral‐bacteria‐directed disease that occurs worldwide. Currently, periodontal pathogens are mostly determined using traditional culture techniques, next‐generation ...sequencing, and microbiological screening system. In addition to the well‐known and cultivatable periodontal bacteria, we aimed to discover a novel periodontal pathogen by using DNA sequencing and investigate its role in the progression of periodontitis.
Objective
This study identified pathogens from subgingival dental plaque in patients with periodontitis by using the Oxford Nanopore Technology (ONT) third‐generation sequencing system and validated the impact of selected pathogen in periodontitis progression by ligature‐implanted mice.
Methods
Twenty‐five patients with periodontitis and 25 healthy controls were recruited in this study. Subgingival plaque samples were collected for metagenomic analysis. The ONT third‐generation sequencing system was used to confirm the dominant bacteria. A mouse model with ligature implantation and bacterial injection verified the pathogenesis of periodontitis. Neutrophil infiltration and osteoclast activity were evaluated using immunohistochemistry and tartrate‐resistant acid phosphatase assays in periodontal tissue. Gingival inflammation was evaluated using pro‐inflammatory cytokines in gingival crevicular fluids. Alveolar bone destruction in the mice was evaluated using micro‐computed tomography and hematoxylin and eosin staining.
Results
Scardovia wiggsiae (S. wiggsiae) was dominant in the subgingival plaque of the patients with periodontitis. S. wiggsiae significantly deteriorated ligature‐induced neutrophil infiltration, osteoclast activation, alveolar bone destruction, and the secretion of interleukin‐6, monocyte chemoattractant protein‐1, and tumor necrosis factor‐α in the mouse model.
Conclusion
Our metagenome results suggested that S. wiggsiae is a dominant flora in patients with periodontitis. In mice, the induction of neutrophil infiltration, proinflammatory cytokine secretion, osteoclast activation, and alveolar bone destruction further verified the pathogenic role of S. wiggsiae in the progress of periodontitis. Future studies investigating the metabolic interactions between S. wiggsiae and other periodontopathic bacteria are warranted.
The as-prepared binder-free Co1−xS/MCF anode exhibits the desirable electrochemical performance for LIBs and SIBs, which can be attributed to the unique hierarchical nanostructure which provides ...enough active sites and internal space for volume expansion.
Display omitted
•The flexible Co1−xS/MCF electrode is prepared via the electrospinning technique.•The Co1−xS/MCF presents hierarchically hollow and multichannel structures.•The Co1−xS/MCF electrode can effectively ease the huge volume expansion.•The Co1−xS/MCF electrode shows high electrochemical performance for LIBs and SIBs.
The exploration of prospective electrode materials represents great challenges for remarkable lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). Herein, we report a reliable synthetic approach for the in-situ growth of the Co-based zeolitic imidazolate framework (ZIF-67) on electrospun nanofibers, followed by carbonization and sulfurization with the formation of free-standing Co1−xS hollow polyhedrons anchored on multichannel carbon nanofibers (Co1−xS/MCF) for LIBs and SIBs. The Co1−xS/MCF electrode displays a high reversible capacity (813 mAh g−1 over 180 cycles at 0.1 A g−1), and stable cycle performance (559 mAh g−1 for 300 cycles at 1 A g−1) in LIBs. For SIBs, Co1−xS/MCF electrode exhibits a favorable Na-storage capacity (433 mAh g−1 over 120 cycles at 0.1 A g−1). The as-prepared binder-free Co1−xS/MCF anode demonstrates the advanced electrochemical properties for LIBs and SIBs. It is attributed to the particular multichannel nanostructure and the Co1−xS hollow polyhedrons (Co1−xS HPs), which provide enough active sites, and the internal void space effectively reduces the structural strain and eases the volume expansion to maintain structural integrity. This work gives insights to design a unique structure for promising LIBs and SIBs.
Abstract
Exploring a simple, fast, solvent-free synthetic method for large-scale preparation of cheap, highly active electrocatalysts for industrial hydrogen evolution reaction is one of the most ...promising work today. In this work, a simple, fast and solvent-free microwave pyrolysis method is used to synthesize ultra-small (3.5 nm) Ru-Mo
2
C@CNT catalyst with heterogeneous structure and strong metal-support interaction in one step. The Ru-Mo
2
C@CNT catalyst only exhibits an overpotential of 15 mV at a current density of 10 mA cm
−2
, and exhibits a large turnover frequency value up to 21.9 s
−1
under an overpotential of 100 mV in 1.0 M KOH. In addition, this catalyst can reach high current densities of 500 mA cm
−2
and 1000 mA cm
−2
at low overpotentials of 56 mV and 78 mV respectively, and it displays high stability of 1000 h. This work provides a feasible way for the reasonable design of other large-scale production catalysts.
Twisted carbon nanobelts could display persistent chirality, which is desirable for material applications, but their synthesis is very challenging. Herein, we report the successful synthesis and ...chiral resolution of such a kind of molecules (1-H and 1) with a figure-eight configuration. 1-H was synthesized first by macrocyclization through Suzuki coupling reaction followed by benzannulation via Bi(OTf)3-mediated cyclization reaction of vinyl ether. Oxidative dehydrogenation of 1-H gave the fully π-conjugated 1. Their twisted structures were confirmed by X-ray crystallographic analysis and calculations, and they can be resolved by chiral high-performance liquid chromatography. The isolated enantiomers showed persistent chiroptical properties according to the circular dichroism measurements, with moderate |g abs| values (0.0016 for 1-H and 0.005–0.007 for 1). Their photophysical properties were also briefly studied.
Active control of metasurfaces can be achieved using the magnetic effect, which is, however, quite weak. Here, a different method for realizing the magnetic tuning is proposed. For this purpose, a ...simple two-dimensional array of split-ring resonators (SRRs), consisting of ultrathin flexible metals bonded with Mn-Zn ferrite patches, has been designed. With the external magnetic field, a magnetic force will be exerted on the ferrite patches, leading to the deformation of the meta-atoms (i.e., the flexible SRRs). Consequently, the gap size of the SRRs can be altered continuously by varying the magnetic field, which modifies the electromagnetic properties of the metasurface. The active tuning of resonance frequency and transmission efficiency has been demonstrated with theory and experiments in the microwave band. The result may be useful for constructing magnetically- controllable switches and modulators as well as the magnetic sensors operating in the microwave or THz regime.
Electrolyte additive is an effective strategy to inhibit the uncontrolled growth of Li dendrites for lithium metal batteries (LMBs). However, most of the additives are complex synthesis and prone to ...decompose in cycling. Herein, in order to guide the homogeneous deposition of Li+, carbonized polymer dots (CPDs) as electrolyte additives are successfully designed and synthesized by microwave (M‐CPDs) and hydrothermal (H‐CPDs) approaches. The controllable functional groups containing N or O (especially pyridinic‐N, pyrrolic‐N, and carboxyl group) enable CPDs to keep stable in electrolytes for at least 3 months. Meanwhile, the clusters formed between CPDs and Li+ through electrostatic interaction effectively guide the uniform Li dispersion and limit the “tip effect” and dendrite formation. Moreover, as lithiophilic groups increase, the strong electrostatic interference for the solvation effect of Li+ in the electrolyte is formed, which induces faster Li+ diffusion/transfer. As expected, H‐CPDs achieve the ultra‐even Li+ transfer. The corresponding Li//LiFePO4 full cell delivers a high capacity retention rate of 93.8% after 200 cycles, which is much higher than that of the cells without additives (61.2%) and with M‐CPDs (83.7%) as additives. The strategy in this work provides a theoretical direction for CPDs as electrolyte additives used in energy storage devices.
Two kinds of carbonized polymer dots (CPDs) (M‐CPDs and H‐CPDs) as electrolyte additives are successfully designed and synthesized. H‐CPDs with more pyridinic‐N, pyrrolic‐N, and COOH deliver more even Li+ flux through abundant H‐CPDs‐Li clusters bound by strong electrostatic interaction. The symmetrical cell exhibits enhanced cycling stability of 3700 h.
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