Extracellular vesicles (EVs) contain specific proteins, lipids, and nucleic acids that can be passed to other cells as signal molecules to alter their function. However, there are many problems and ...challenges in the conversion and clinical application of EVs. Storage and protection of EVs is one of the issues that need further research. To adapt to potential clinical applications, this type of problem must be solved. This review summarizes the storage practices of EVs in recent years, and explains the impact of temperature on the quality and stability of EVs during storage based on current research, and explains the potential mechanisms involved in this effect as much as possible.
Extracellular vesicles (EVs) contain specific proteins, lipids, and nucleic acids that can be passed to other cells as signal molecules to alter their function. However, there are many problems and challenges in the conversion and clinical application of EVs. Storage and protection of EVs is one of the issues that need further research. To adapt to potential clinical applications, this type of problem must be solved. Here, we briefly review EVs' biogenesis, contents, subtypes and effect of storage temperature on its quality and stability, as well as application of cryoprotectants in EVs cryopreservation, and specifically focus on the mechanism by which storage temperature affects the quality and stability of EVs.
Reported is a highly enantioselective copper‐catalyzed Markovnikov protoboration of unactivated terminal alkenes. A variety of simple and abundant feedstock α‐olefins bearing a diverse array of ...functional groups and heterocyclic substituents can be used as substrates, and the reaction proceeds under mild reaction conditions at ambient temperature to provide expedient access to enantioenriched alkylboronic esters in good regioselectivity and with excellent enantiocontrol. Critical to the success of the protocol was the development and application of a novel, sterically hindered N‐heterocyclic carbene, (R,R,R,R)‐ANIPE, as the ligand for copper.
By design: A highly enantioselective copper‐catalyzed Markovnikov protoboration of α‐olefins is described. This mild and general process effectively converts simple and abundant feedstock α‐olefins into a diverse array of chiral alkylboronic esters with excellent enantiocontrol. Key to the success of the protocol was the use of a newly developed, sterically hindered N‐heterocyclic carbene, (R,R,R,R)‐ANIPE, as the ligand.
In contrast to solid parts fabricated through conventional injection molding (CIM), foamed parts manufactured via foam injection molding (FIM) exhibit substantial variations in mechanical properties, ...which are attributed to differences in the cellular structure. In this study, parts with different cellular structures are fabricated via FIM, during which the gas dissolution and desorption processes are controlled by subjecting the gas‐laden melt to reciprocating compression and expansion operations. The results suggest that the cell density can be drastically improved by rapidly decreasing the pressure caused by the mold opening and that the cell orientation obviously occurs in the direction perpendicular to the mold‐opening direction. Moreover, the cell density and cellular orientation can be adjusted by utilizing appropriate mold opening and closing operations, leading to improvements in the resultant ultimate mechanical properties. In particular, the foamed samples fabricated with controlled mold opening‐closing operations exhibit excellent tensile strength and strain‐at‐break, indicating that samples containing a high density of cells oriented along the tensile test direction facilitate the formation of superductility and an increase in tensile strength. Hence, a method that combines FIM with batch foaming has been proposed for improving the cellular structure and controlling the cellular orientation.
The blood-brain barrier (BBB) plays a vital role in regulating the trafficking of fluid, solutes and cells at the blood-brain interface and maintaining the homeostatic microenvironment of the CNS. ...Under pathological conditions, such as ischemic stroke, the BBB can be disrupted, followed by the extravasation of blood components into the brain and compromise of normal neuronal function. This article reviews recent advances in our knowledge of the mechanisms underlying BBB dysfunction and recovery after ischemic stroke. CNS cells in the neurovascular unit, as well as blood-borne peripheral cells constantly modulate the BBB and influence its breakdown and repair after ischemic stroke. The involvement of stroke risk factors and comorbid conditions further complicate the pathogenesis of neurovascular injury by predisposing the BBB to anatomical and functional changes that can exacerbate BBB dysfunction. Emphasis is also given to the process of long-term structural and functional restoration of the BBB after ischemic injury. With the development of novel research tools, future research on the BBB is likely to reveal promising potential therapeutic targets for protecting the BBB and improving patient outcome after ischemic stroke.
Brain perivascular macrophages (PVMs) belong to a distinct population of brain‐resident myeloid cells located within the perivascular space surrounding arterioles and venules. Their characterization ...depends on the combination of anatomical localization, phagocytic capacity, and molecular markers. Under physiological status, they provide structural and functional support for maintaining brain homeostasis, including facilitation of blood‐brain barrier integrity and lymphatic drainage, and exertion of immune functions such as phagocytosis and antigen presentation. Increasing evidence also implicates their specific roles in diseased brain, ranging from cerebrovascular diseases, Aβ pathologies, infections, and autoimmunity. Collectively, PVMs are key components of the brain‐resident immune system, actively participate in a broad‐spectrum of processes in normal and diseased status. Details of the processes are largely underexplored. Targeting PVMs would lead to new insights and be a promising strategy for a broad array of human diseases.
Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of the SCI lesion, the glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in ...spinal cord regeneration. In recent years, it has become increasingly accepted that the glial scar plays a dual role in SCI recovery. However, the underlying mechanisms of this dual role are complex and need further clarification. This dual role also makes it difficult to manipulate the glial scar for therapeutic purposes. Here, we briefly discuss glial scar formation and some representative components associated with scar-forming astrocytes. Then, we analyze the dual role of the glial scar in a dynamic perspective with special attention to scar-forming astrocytes to explore the underlying mechanisms of this dual role. Finally, taking the dual role of the glial scar into account, we provide several pieces of advice on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.
The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic ...drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange.
Stroke is the number one cause of neurological dysfunction in adults and has a heavy socioeconomic burden worldwide. The etiological origins of ischemic stroke and resulting pathological processes ...are mediated by a multifaceted cascade of molecular mechanisms that are in part modulated by posttranscriptional activity. Accumulating evidence has revealed a role for microRNAs (miRNAs) as essential mediators of posttranscriptional gene silencing in both the physiology of brain development and pathology of ischemic stroke. In this review, we compile miRNAs that have been reported to regulate various stroke risk factors and pre-disease mechanisms, including hypertension, atherosclerosis, and diabetes, followed by an in-depth analysis of miRNAs in ischemic stroke pathogenesis, such as excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis and neurogenesis. Since promoting or suppressing expression of miRNAs by specific pharmaceutical and non-pharmaceutical therapies may be beneficial to post-stroke recovery, we also highlight the potential therapeutic value of miRNAs in clinical settings.
In the central nervous system (CNS), astrocytes form networks interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. When unopposed by an adjoining hemichannel, astrocytic ...connexins can act as hemichannels to control the release of small molecules such as ATP and glutamate into the extracellular space. Accruing evidence indicates that astrocytic connexins are crucial for the coordination and maintenance of physiologic CNS activity. Here we provide an update on the role of astrocytic connexins in neurodegenerative disorders, glioma, and ischemia. In addition, we address the regulation of Cx43 in chronic pain.
Highlights • Cognitive impairment and dementia are age-related health burden. • Neurovascular aging predisposes the brain to reduced blood flow and long-term ischemic injuries, leading to VCID. • ...Diverse pathology underlies VCID, including neuronal loss and white matter injury. Microinfarcts and leukoaraiosis are common. • Age-related VCID can be classified into ischemic, hemorrhagic and post-stroke subtypes.
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