Traumatic brain injury (TBI) is recognized as a global health problem due to its increasing occurrence, challenging treatment, and persistent impacts on brain pathophysiology. Neural cell death in ...patients with TBI swiftly causes inflammation in the injured brain areas, which is recognized as focal brain inflammation. Focal brain inflammation causes secondary brain injury by exacerbating brain edema and neuronal death, while also exerting divergent beneficial effects, such as sealing the damaged limitans and removing cellular debris. Recent evidence from patients with TBI and studies on animal models suggest that brain inflammation after TBI is not only restricted to the focal lesion but also disseminates to remote areas of the brain. The dissemination of inflammation has been detected within days after the primary injury and persists chronically. This state of inflammation may be related to remote complications of TBI in patients, such as hyperthermia and hypopituitarism, and may lead to progressive neurodegeneration, such as chronic traumatic encephalopathy. Future studies should focus on understanding the mechanisms that govern the initiation and propagation of brain inflammation after TBI and its impacts on post-trauma brain pathology.
Stroke, including acute ischaemic stroke and intracerebral haemorrhage, results in neuronal cell death and the release of factors such as damage-associated molecular patterns (DAMPs) that elicit ...localised inflammation in the injured brain region. Such focal brain inflammation aggravates secondary brain injury by exacerbating blood–brain barrier damage, microvascular failure, brain oedema, oxidative stress, and by directly inducing neuronal cell death. In addition to inflammation localised to the injured brain region, a growing body of evidence suggests that inflammatory responses after a stroke occur and persist throughout the entire brain. Global brain inflammation might continuously shape the evolving pathology after a stroke and affect the patients' long-term neurological outcome. Future efforts towards understanding the mechanisms governing the emergence of so-called global brain inflammation would facilitate modulation of this inflammation as a potential therapeutic strategy for stroke.
Remote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote ...difunctionalization of alkenes with CO2. This visible‐light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine‐ or phosphorus‐containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional‐group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5‐hydrogen atom‐transfer process, the rate‐limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an IrII species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO2 to generate carboxylates.
Reported is the first remote difunctionalization of unactivated alkenes with CO2 by visible‐light photoredox catalysis. Mechanistic studies indicate that a 1,5‐hydrogen atom‐transfer process is the rate‐limiting step and reduction of radical intermediates generates the corresponding carbanions. Other electrophiles, including aldehydes, ketones, and benzylic bromides, are also applicable in this process, demonstrating a general strategy for redox‐neutral remote difunctionalization of unactivated alkenes.
Chiral catalysts tolerating photochemical reactions are in great demand for the vast development of visible‐light‐induced asymmetric synthesis. Now, chiral octahedral complexes based on ...earth‐abundant metal and chiral N4 ligands are reported. One well‐defined chiral CoII‐complex is shown to be an efficient catalyst in the visible‐light‐induced conjugated addition of enones by alkyl and acyl radicals, providing synthetically valued chiral ketones and 1,4‐dicarbonyls in 47–>99 % yields with up to 97:3 e.r.
Chiral octahedral complexes were prepared from earth‐abundant cobalt and chiral N4 ligands. One structurally well‐defined cobalt complex was an efficient chiral catalyst in visible‐light‐induced radical conjugated additions. Synthetically valued chiral ketones and 1,4‐dicarbonyls were afforded in 47–>99 % yields (46 examples) with up to 97:3 e.r.
Approaches for the effective management of acute stroke are sparse, and many measures for brain protection fail. However, our ability to modulate the immune system and modify the progression of ...multiple sclerosis is increasing. As a result, immune interventions are currently being explored as therapeutic interventions in acute stroke. In this Review, we compare the immunological features of acute stroke with those of multiple sclerosis, identify unique immunological features of stroke, and consider the evidence for immune interventions. In patients with acute stroke, microglial activation and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the ischaemia or haemorrhage. Immune interventions that restrict brain inflammation, vascular permeability and tissue oedema must be administered rapidly to reduce acute immune-mediated destruction and to avoid subsequent immunosuppression. Preliminary results suggest that the use of drugs that modify disease in multiple sclerosis might accomplish these goals in ischaemic and haemorrhagic stroke. Further elucidation of the immune mechanisms involved in stroke is likely to lead to successful immune interventions.
Genomic sequencing reveals similar but limited numbers of protein-coding genes in different genomes, which begs the question of how organismal diversities are generated. Alternative pre-mRNA ...splicing, a widespread phenomenon in higher eukaryotic genomes, is thought to provide a mechanism to increase the complexity of the proteome and introduce additional layers for regulating gene expression in different cell types and during development. Among a large number of factors implicated in the splicing regulation are the SR protein family of splicing factors and SR protein-specific kinases. Here, we summarize the rules for SR proteins to function as splicing regulators, which depend on where they bind in exons versus intronic regions, on alternative exons versus flanking competing exons, and on cooperative as well as competitive binding between different SR protein family members on many of those locations. We review the importance of cycles of SR protein phosphorylation/dephosphorylation in the splicing reaction with emphasis on the recent molecular insight into the role of SR protein phosphorylation in early steps of spliceosome assembly. Finally, we highlight recent discoveries of SR protein-specific kinases in transducing growth signals to regulate alternative splicing in the nucleus and the connection of both SR proteins and SR protein kinases to human diseases, particularly cancer.
Amyotrophic lateral sclerosis (ALS) was initially thought to be associated with oxidative stress when it was first linked to mutant superoxide dismutase 1 (SOD1). The subsequent discovery of ...ALS-linked genes functioning in RNA processing and proteostasis raised the question of how different biological pathways converge to cause the disease. Both familial and sporadic ALS are characterized by the aggregation of the essential DNA- and RNA-binding protein TDP-43, suggesting a central role in ALS etiology. Here we report that TDP-43 aggregation in neuronal cells of mouse and human origin causes sensitivity to oxidative stress. Aggregated TDP-43 sequesters specific microRNAs (miRNAs) and proteins, leading to increased levels of some proteins while functionally depleting others. Many of those functionally perturbed gene products are nuclear-genome-encoded mitochondrial proteins, and their dysregulation causes a global mitochondrial imbalance that augments oxidative stress. We propose that this stress-aggregation cycle may underlie ALS onset and progression.
Dong, F., 2020. Influence factors of aerobic exercise on the constitution of ocean going seafarers based on the exercise intervention and regulation. In: Bai, X. and Zhou, H. (eds.), Advances in ...Water Resources, Environmental Protection, and Sustainable Development. Journal of Coastal Research, Special Issue No. 115, pp. 566-569. Coconut Creek (Florida), ISSN 0749-0208. As an important group of long-distance marine workers, ocean seamen live far away from land for a long time, with single diet, high work intensity and heavy psychological burden. The impact of marine living environment on crew's health is mainly reflected in the chronic diseases caused by the maladjustment to the marine environment, which has been confirmed in relevant research. As the most common cardiovascular disease in China, hypertension is also the most common chronic disease of crew, which has become a major problem affecting the health of ocean going crew. In this paper, the high blood pressure symptoms of the crew were statistically analyzed. The crew with high blood pressure were divided into the control group and the experimental group, and the control experiment of aerobic exercise was carried out. It was concluded that the appropriate aerobic exercise of the crew with high blood pressure could help to reduce the blood pressure of the crew with high blood pressure, but it had little effect on sugar and lipid.
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