Functional electrolyte is the key to stabilize the highly reductive lithium (Li) metal anode and the high-voltage cathode for longlife, high-energy-density rechargeable Li metal batteries (LMBs). ...However, fundamental mechanisms on the interactions between reactive electrodes and electrolytes are still not well understood. Recently localized high-concentration electrolytes (LHCEs) are emerging as a promising electrolyte design strategy for LMBs. Here, we use LHCEs as an ideal platform to investigate the fundamental correlation between the reactive characteristics of the inner solvation sheath on electrode surfaces due to their unique solvation structures. The effects of a series of LHCEs with model electrolyte solvents (carbonate, sulfone, phosphate, and ether) on the stability of high-voltage LMBs are systematically studied. The stabilities of electrodes in different LHCEs indicate the intrinsic synergistic effects between the salt and the solvent when they coexist on electrode surfaces. Experimental and theoretical analyses reveal an intriguing general rule that the strong interactions between the salt and the solvent in the inner solvation sheath promote their intermolecular proton/charge transfer reactions, which dictates the properties of the electrode/electrolyte interphases and thus the battery performances.
(Dihydro)ceramide synthase 2 (cers2, formerly called lass2) is the most abundantly expressed member of the ceramide synthase gene family, which includes six isoforms in mice. CERS2 activity has been ...reported to be specific toward very long fatty acid residues (C22–C24). In order to study the biological role of CERS2, we have inactivated its coding region in transgenic mice using gene-trapped embryonic stem cells that express lacZ reporter DNA under control of the cers2 promoter. The resulting mice lack ceramide synthase activity toward C24:1 in the brain as well as the liver and show only very low activity toward C18:0–C22:0 in liver and reduced activity toward C22:0 residues in the brain. In addition, these mice exhibit strongly reduced levels of ceramide species with very long fatty acid residues (≥C22) in the liver, kidney, and brain. From early adulthood on, myelin stainability is progressively lost, biochemically accompanied by about 50% loss of compacted myelin and 80% loss of myelin basic protein. Starting around 9 months, both the medullary tree and the internal granular layer of the cerebellum show significant signs of degeneration associated with the formation of microcysts. Predominantly in the peripheral nervous system, we observed vesiculation and multifocal detachment of the inner myelin lamellae in about 20% of the axons. Beyond 7 months, the CERS2-deficient mice developed hepatocarcinomas with local destruction of tissue architecture and discrete gaps in renal parenchyma. Our results indicate that CERS2 activity supports different biological functions: maintenance of myelin, stabilization of the cerebellar as well as renal histological architecture, and protection against hepatocarcinomas.
Electrospinning, as a promising platform in multidisciplinary engineering over the past two decades, has overcome major challenges and has achieved remarkable breakthroughs in a wide variety of ...fields such as energy, environmental, and pharmaceutics. However, as a facile and cost-effective approach, its capability of creating nanofibers is still strongly limited by the numbers of treatable fluids. Most recently, more and more efforts have been spent on the treatments of liquids without electrospinnability using multifluid working processes. These unspinnable liquids, although have no electrospinnability themselves, can be converted into nanofibers when they are electrospun with an electrospinnable fluid. Among all sorts of multifluid electrospinning methods, coaxial electrospinning is the most fundamental one. In this review, the principle of modified coaxial electrospinning, in which unspinnable liquids are explored as the sheath working fluids, is introduced. Meanwhile, several typical examples are summarized, in which electrospun nanofibers aimed for the environment remediation were prepared using the modified coaxial electrospinning. Based on the exploration of unspinnable liquids, the present review opens a way for generating complex functional nanostructures from other kinds of multifluid electrospinning methods.
Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology to understand the biology of myelin ...diseases and to develop treatments for such disorders. Here, we demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor cells is sufficient to rapidly generate O4⁺ OL with an efficiency of up to 70% in 28 d and a global gene-expression profile comparable to primary human OL. We further demonstrate that iPSC-derived OL disperse and myelinate the CNS of Mbpshi/shi
Rag
−/− mice during development and after demyelination, are suitable for in vitro myelination assays, disease modeling, and screening of pharmacological compounds potentially promoting oligodendroglial differentiation. Thus, the strategy presented here to generate OL from iPSC may facilitate the studying of human myelin diseases and the development of high-throughput screening platforms for drug discovery.
For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous lysophospholipid so it may cause ...demyelination in certain diseases. We investigated whether known receptor systems, inflammation or nonspecific lipid disruption mediates LPC‐demyelination in mice. We found that LPC nonspecifically disrupted myelin lipids. LPC integrated into cellular membranes and rapidly induced cell membrane permeability; in mice, LPC injury was phenocopied by other lipid disrupting agents. Interestingly, following its injection into white matter, LPC was cleared within 24 hr but by five days there was an elevation of endogenous LPC that was not associated with damage. This elevation of LPC in the absence of injury raises the possibility that the brain has mechanisms to buffer LPC. In support, LPC injury in culture was significantly ameliorated by albumin buffering. These results shed light on the mechanisms of LPC injury and homeostasis.
Main Points
LPC integrates into cellular membranes causing cell death and demyelination due to its lipid‐disrupting properties.
Opinion statement
Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that represent a profound therapeutic challenge due to their high proclivity for recurrence and ...metastasis and relatively poor response to systemic therapy regimens. While our understanding of the pathophysiology of MPNST is growing, including loss of the tumor suppressor gene neurofibromin and subsequent activation of the Ras pathway, targeted therapy to modify the poor prognosis seen in MPNST patients has thus far been without success. Correspondingly, MPNST patients are treated as per soft tissue sarcoma treatment algorithms with anthracycline-based therapy as the front-line therapy of choice for patients with unresectable, locally advanced, or metastatic MPNST. Beyond first-line anthracycline-based therapy, other standard cytotoxic chemotherapy agents used in advanced MPNST include the alkylating agent ifosfamide and the topoisomerase II inhibitor etoposide. Notably, soft tissue sarcoma regimens are used in MPNST despite distinct systemic therapy sensitivity and prognosis. This is particularly notable for neurofibromatosis type 1 (NF1)-associated MPNST, which is associated with poorer response to systemic therapy and prognosis than sporadic MPNST. As such, NF1-associated MPNST is a particular area in need of novel therapeutic strategies. Given the lack of benefit in the targeting of unique aspects of MPNST disease biology thus far, pre-clinical studies to identify novel rational therapies are critical to inform future clinical trials.
An analytic solution is presented in this paper for the electric potential near a wall in a confined plasma. This is well fitted for both the sheath and pre-sheath regions. In the sheath region, the ...potential is well adapted to the differential equation proposed by Bohm. In the pre-sheath region, the potential is also well suited, decaying to zero electric field in the plasma, which is a physical condition. The potential is also valid for any value of the parameter K measuring the dimensionless Bohm velocity.
Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from ...direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M. leprae but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with M. marinum-expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to M. leprae PGL-1 in initiating nerve damage in leprosy.
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•Mycobacterium leprae infection of zebrafish damages nerves, causing demyelination•Nerve damage requires M. leprae phenolic glycolipid (PGL-1) and host macrophages•PGL-1 induces macrophages to produce excess nitric oxide•Excess nitric oxide damages nerves by damaging their mitochondria
A new model system for leprosy enables the discovery that macrophages, and not the causative bacterium M. leprae, initiate host nerve demyelination and axonal damage.
A hypersonic vehicle is covered by a plasma sheath during flight, which seriously attenuates the power of electromagnetic (EM) waves and generates the so-called "radio blackout" phenomenon when the ...equivalent frequency of plasma is greater than the carrier frequency. However, the parameters of plasma sheath vary randomly with time. The variation produces some random time slots where the equivalent frequency of plasma is lower than the carrier frequency, so the EM waves can penetrate the plasma sheath. Random time slots cause the receiver unable to receive information in the form of a complete frame, resulting in the traditional communication methods being no longer applicable. In order to receive the complete frame in random time slots and maximize the use of temporal resources of the plasma sheath channel, this article constructs a temporal-varying plasma sheath channel, proposes a soft-decision decoding algorithm for short-frame fountain codes (SFFCs), studies the relationship between the encode parameters and the characteristics of the channel, and designs communication experiments based on inductively coupling plasma (ICP). The short-frame fountain code (SFFC) has the characteristics of no-rate and short-frame, which can adapt to the short-time and random of the plasma sheath. In addition, soft-decision decoding algorithm can effectively reduce misjudgment of the receiver, reduce packet error rate, and improve the utilization of limited temporal resources of the plasma sheath channel. Simulation and experiments show that the proposed method achieves higher utilization of temporal resources of plasma sheath channel, and improves the reliability of communication. Even if the plasma equivalent frequency is higher than the carrier frequency, the uninterrupted and correct transmission of information can be realized.
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