Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, ...and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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•CH25H and its enzymatic product, 25HC, inhibit ZIKV entry in vitro•25HC attenuates ZIKV-associated viremia and disease in mice and non-human primates•25HC prevents ZIKV infection in human cortical organoids•25HC protects fetal mice from microcephaly caused by ZIKV infection
Zika virus (ZIKV) presents a major challenge to the global health system. Li et al. find that 25-hydroxycholesterol (25HC) inhibits ZIKV infection in monkeys and human cortical organoids and protects mice from microcephaly. 25HC has potential as a first-line antiviral agent to combat a broad array of pathogenic species, including ZIKV.
Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular ...mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.
Microstructure engineering is an effective strategy to reduce lattice thermal conductivity (κl) and enhance the thermoelectric figure of merit (zT). Through a new process based on melt‐centrifugation ...to squeeze out excess eutectic liquid, microstructure modulation is realized to manipulate the formation of dislocations and clean grain boundaries, resulting in a porous network with a platelet structure. In this way, phonon transport is strongly disrupted by a combination of porosity, pore surfaces/junctions, grain boundaries, and lattice dislocations. These collectively result in a ≈60% reduction of κl compared to zone melted ingot, while the charge carriers remain relatively mobile across the liquid‐fused grains. This porous material displays a zT value of 1.2, which is higher than fully dense conventional zone melted ingots and hot pressed (Bi,Sb)2Te3 alloys. A segmented leg of melt‐centrifuged Bi0.5Sb1.5Te3 and Bi0.3Sb1.7Te3 could produce a high device ZT exceeding 1.0 over the whole temperature range of 323–523 K and an efficiency up to 9%. The present work demonstrates a method for synthesizing high‐efficiency porous thermoelectric materials through an unconventional melt‐centrifugation technique.
The melt‐centrifugation technique is demonstrated to be able to decrease the thermal conductivity while preserving the good electrical properties. By introducing a unique porous structure with microscale dislocation, ≈60% reduction in lattice thermal conductivity compared to conventional zone melted ingots is achieved. Such a method paves a new way for top‐down introduction of large porosity and dense dislocations in bulk materials.
Cancer can invade or spread to almost all parts of the body. The increasing morbidity and high mortality of cancer create a great demand for the development of novel anticancer drugs. Coumarin ...derivatives are ubiquitous in nature and can readily interact with diverse enzymes and receptors in cancer cells via weak bond interactions; hence, coumarin is a highly privileged pharmacophore for the development of novel anticancer agents. This review will focus on the recent development of coumarin hybrids as potential anticancer agents covering articles published from 2019 to 2020.
Coumarin derivatives are ubiquitous in nature and can readily interact with diverse enzymes and receptors in cancer cells via weak bond interactions. This review focuses on the recent development of coumarin derivatives as potential anticancer agents and their mechanisms of action.
Following the first experimental realization of graphene, other ultrathin materials with unprecedented electronic properties have been explored, with particular attention given to the heavy group-IV ...elements Si, Ge and Sn. Two-dimensional buckled Si-based silicene has been recently realized by molecular beam epitaxy growth, whereas Ge-based germanene was obtained by molecular beam epitaxy and mechanical exfoliation. However, the synthesis of Sn-based stanene has proved challenging so far. Here, we report the successful fabrication of 2D stanene by molecular beam epitaxy, confirmed by atomic and electronic characterization using scanning tunnelling microscopy and angle-resolved photoemission spectroscopy, in combination with first-principles calculations. The synthesis of stanene and its derivatives will stimulate further experimental investigation of their theoretically predicted properties, such as a 2D topological insulating behaviour with a very large bandgap, and the capability to support enhanced thermoelectric performance, topological superconductivity and the near-room-temperature quantum anomalous Hall effect.
A dual temperature‐ and light‐responsive C2H2/C2H4 separation switch in a diarylethene metal–organic framework (MOF) is presented. At 195 K and 100 kPa this MOF shows ultrahigh C2H2/C2H4 selectivity ...of 47.1, which is almost 21.4 times larger than the corresponding value of 2.2 at 293 K and 100 kPa, or 15.7 times larger than the value of 3.0 for the material under UV at 195 K and 100 kPa. The origin of this unique control in C2H2/C2H4 selectivity, as unveiled by density functional calculations, is due to a guest discriminatory gate‐opening effect from the diarylethene unit.
Photochromic diarylethene units were used to identify C2H2, leading to ultrahigh C2H2/C2H4 selectivity and promising application in C2H2/C2H4 separation at low temperature. The photochromic material can be further used as a temperature‐ and light‐responsive switch for C2H2/C2H4 separation.
Traumatic brain injury in China Jiang, Ji-Yao; Gao, Guo-Yi; Feng, Jun-Feng ...
Lancet neurology,
March 2019, 2019-03-00, 20190301, Volume:
18, Issue:
3
Journal Article
Peer reviewed
China has more patients with traumatic brain injury (TBI) than most other countries in the world, making this condition a major public health concern. Population-based mortality of TBI in China is ...estimated to be approximately 13 cases per 100 000 people, which is similar to the rates reported in other countries. The implementation of various measures, such as safety legislation for road traffic, establishment of specialised neurosurgical intensive care units, and the development of evidence-based guidelines, have contributed to advancing prevention and care of patients with TBI in China. However, many challenges remain, which are augmented further by regional differences in TBI care. High-level care, such as intracranial pressure monitoring, is not universally available yet. In the past 30 years, the quality of TBI research in China has substantially improved, as evidenced by an increasing number of clinical trials done. The large number of patients with TBI and specialised trauma centres offer unique opportunities for TBI research in China. Furthermore, the formation and development of research collaborations between China and international groups are considered essential to advancing the quality of TBI care and research in China, and to improve quality of life in patients with this condition.
The use of a chiral, emitting skeleton for axially chiral enantiomers showing activity in thermally activated delayed fluorescence (TADF) with circularly polarized electroluminescence (CPEL) is ...proposed. A pair of chiral stable enantiomers, (−)‐(S)‐Cz‐Ax‐CN and (+)‐(R)‐Cz‐Ax‐CN, was designed and synthesized. The enantiomers, both exhibiting intramolecular π‐conjugated charge transfer (CT) and spatial CT, show TADF activities with a small singlet–triplet energy difference (ΔEST) of 0.029 eV and mirror‐image circularly polarized luminescence (CPL) activities with large glum values. Notably, CP‐OLEDs based on the enantiomers feature blue electroluminescence centered at 468 nm with external quantum efficiencies (EQEs) of 12.5 and 12.7 %, and also show intense CPEL with gEL values of −1.2×10−2 and +1.4×10−2, respectively. These are the first CP‐OLEDs based on TADF‐active enantiomers with efficient blue CPEL.
Let's twist again: Axially chiral molecules with thermally activated delayed fluorescence and circularly polarized electroluminescence (CPEL) are presented. CP‐OLEDs based on these molecules display high efficiencies and blue CPEL with large gEL values.
Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot ...correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.
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