N1-methyladenosine (m1A) is an important post-transcriptional modification in RNA; however, the exact biological role of m1A remains to be determined. By employing a quantitative proteomics method, ...we identified multiple putative protein readers of m1A in RNA, including several YTH domain family proteins. We showed that YTHDF1-3 and YTHDC1, but not YTHDC2, could bind directly to m1A in RNA. We also found that Trp432 in YTHDF2, a conserved residue in the hydrophobic pocket of the YTH domain that is necessary for its binding to N 6-methyladenosine (m6A), is required for its recognition of m1A. An analysis of previously published data revealed transcriptome-wide colocalization of YTH domain-containing proteins and m1A sites in HeLa cells, suggesting that YTH domain-containing proteins can bind to m1A in cells. Together, our results uncovered YTH domain-containing proteins as readers for m1A in RNA and provided new insight into the functions of m1A in RNA biology.
Cancer is the most prevalent cause of death globally, and radiotherapy is considered the standard of care for most solid tumors, including lung, breast, esophageal, and colorectal cancers and ...glioblastoma. Resistance to radiation can lead to local treatment failure and even cancer recurrence.
In this review, we have extensively discussed several crucial aspects that cause resistance of cancer to radiation therapy, including radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance of cancer stem cells, modification of cancer cells and their microenvironment, presence of exosomal and non-coding RNA, metabolic reprogramming, and ferroptosis. We aim to focus on the molecular mechanisms of cancer radiotherapy resistance in relation to these aspects and to discuss possible targets to improve treatment outcomes.
Studying the molecular mechanisms responsible for radiotherapy resistance and its interactions with the tumor environment will help improve cancer responses to radiotherapy. Our review provides a foundation to identify and overcome the obstacles to effective radiotherapy.
Metal matrix nanocomposites (MMNCs) are gaining more and more interest because matrices and nanophases with heterogeneous characteristics could combine to provide unprecedented properties. Given the ...high concentration of free electrons in metallic systems, electrical conductivity is one of the most crucial design criteria in selecting suitable MMNCs. However, due to the intrinsic complexity of MMNC systems (e.g., changed interfacial characteristics), reliable and accurate determination of electrical conductivity in MMNCs faces a considerable challenge. Notably, there lacks fundamental guidance with suitable theories and models for MMNCs’ electrical conductivity. To address these issues and provide a clear understanding of electrical properties in MMNCs, this review intends to provide a comprehensive angle to explain, design, and analyze their electrical properties, electronic features, and electron behavior after their 20-year prosperous development. First, the review connects theories, effects of various engineering factors, and electrical conductivity data in the representative systems to provide an omni-spectrum insight into MMNCs’ electrical performance. Following this discussion, the generic trend of electrical conductivity in MMNCs has been clarified for the first time, and the future focus and directions of MMNCs’ electrical behavior study have been proposed. Generally speaking, this review will mitigate the current inconsistencies in MMNCs’ electrical conductivity research and help open up new chances of achieving and extending electrical and other essential functional applications with MMNCs.
Graphical abstract
Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, ...physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1alpha. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications. Keywords: Stem cell, Extracellular matrix, Shear stress, Hydrostatic pressure, Tension, Microgravity, NF-kB, nAChR, PIEZO, HIF-1alpha
To effectively avoid the “dead volume” and improve the utilization ratio of the electrode material, a novel longan-like hybrid structure has been designed and fabricated by controlled growth of ...Ni(OH)2 nanosheets on the surface of yolk–shell PPy nanospheres at a mild reaction temperature. The strategy takes full advantages of the hollow structure and further reduces the charge transport distance, leading to high conductivity and energy storage capacity of longan-like hybrid structures. Furthermore, the assembled asymmetric supercapacitors (ASCs) exhibits a high retention ratio of 91.5% for capacitance after 6000 continuous cycles and an impressive energy density of 34 W h kg−1 at 755 W kg−1. Remarkably, two devices in series have a higher cell-voltage output of 3.0 V compared to a single device. This work will supply a new hollow nanostructure design strategy to enhance the electrochemical performance of electrode materials.
A novel longan-like hybrid architecture takes full advantages of the hollow structure and further reduces the charge transport distance. Herein, a high conductivity and energy storage capacity can be achieved. Display omitted
•An interesting one-step process to synthesize bulk quantities yolk–shell polypyrrole nanospheres.•A novel longan–like hybrid structures been fabricated by controlled growth of Ni(OH)2 nanosheets on the surface of yolk–shell PPy nanospheres.•The hybrid structures not only reserves the advantages of hollow structures but also reduces charge transport distance, herein, a high conductivity and energy storage capacity can be reached.•The assembled ASCs display excellent electrochemical energy storage properties, and two devices in serial have a high output cell voltage.
Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback aids the modulation of neural functions by training self-regulation of brain activity through operant conditioning. This ...technique has been applied to treat several neurodevelopmental and neuropsychiatric disorders, but its effectiveness for stroke rehabilitation has not been examined yet. Here, we systematically review the effectiveness of rt-fMRI neurofeedback training in modulating motor and cognitive processes that are often impaired after stroke. Based on predefined search criteria, we selected and examined 33 rt-fMRI neurofeedback studies, including 651 healthy individuals and 15 stroke patients in total. The results of our systematic review suggest that rt-fMRI neurofeedback training can lead to a learned modulation of brain signals, with associated changes at both the neural and the behavioural level. However, more research is needed to establish how its use can be optimized in the context of stroke rehabilitation.
Metal matrix nanocomposites (MMNCs) become irreplaceable in tribology industries, due to their supreme mechanical properties and satisfactory tribological behavior. However, due to the dual ...complexity of MMNC systems and tribological process, the anti-friction and anti-wear mechanisms are unclear, and the subsequent tribological performance prediction and design of MMNCs are not easily possible: A critical up-to-date review is needed for MMNCs in tribology. This review systematically summarized the fabrication, manufacturing, and processing techniques for high-quality MMNC bulk and surface coating materials in tribology. Then, important factors determining the tribological performance (mainly anti-friction evaluation by the coefficient of friction (CoF) and anti-wear assessment with wear rate) in MMNCs have been investigated thoroughly, and the correlations have been analyzed to reveal their potential coupling/synergetic roles of tuning tribological behavior of MMNCs. Most importantly, this review combined the classical metal/alloy friction and wear theories and adapted them to give a (semi-)quantitative description of the detailed mechanisms of improved anti-friction and anti-wear performance in MMNCs. To guarantee the universal applications of these mechanisms, their links with the analyzed influencing factors (e.g., loading forces) and characteristic features like tribo-film have been clarified. This approach forms a solid basis for understanding, predicting, and engineering MMNCs’ tribological behavior, instead of pure phenomenology and experimental observation. Later, the pathway to achieve a broader application for MMNCs in tribo-related fields like smart materials, biomedical devices, energy storage, and electronics has been concisely discussed, with the focus on the potential development of modeling, experimental, and theoretical techniques in MMNCs’ tribological processes. In general, this review tries to elucidate the complex tribo-performances of MMNCs in a fundamentally universal yet straightforward way, and the discussion and summary in this review for the tribological performance in MMNCs could become a useful supplementary to and an insightful guidance for the current MMNC tribology study, research, and engineering innovations.
Abstract
Microcatheters have enabled diverse minimally invasive endovascular operations and notable health benefits compared with open surgeries. However, with tortuous routes far from the arterial ...puncture site, the distal vascular regions remain challenging for safe catheter access. Therefore, we propose a wireless stent-shaped magnetic soft robot to be deployed, actively navigated, used for medical functions, and retrieved in the example M4 segment of the middle cerebral artery. We investigate shape-adaptively controlled locomotion in phantoms emulating the physiological conditions here, where the lumen diameter shrinks from 1.5 mm to 1 mm, the radius of curvature of the tortuous lumen gets as small as 3 mm, the lumen bifurcation angle goes up to 120
°
, and the pulsatile flow speed reaches up to 26 cm/s. The robot can also withstand the flow when the magnetic actuation is turned off. These locomotion capabilities are confirmed in porcine arteries ex vivo. Furthermore, variants of the robot could release the tissue plasminogen activator on-demand locally for thrombolysis and function as flow diverters, initiating promising therapies towards acute ischemic stroke, aneurysm, arteriovenous malformation, dural arteriovenous fistulas, and brain tumors. These functions should facilitate the robot’s usage in new distal endovascular operations.
Neutrophil elastase (NE), a major protease in the primary granules of neutrophils, is involved in microbicidal activity. NE is an important factor promoting inflammation, has bactericidal effects, ...and shortens the inflammatory process. NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling. However, NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction. Additionally, it plays a complex role in various physiological processes and mediates several diseases. Sivelestat, a specific NE inhibitor, has strong potential for clinical application, particularly in the treatment of coronavirus disease 2019 (COVID-19). This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
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•NE plays a role in several human diseases.•Sivelestat, a selective NE inhibitor, has various clinical applications (particularly in COVID-19).•More studies are needed to identify more diseases associated with NE.•Additional studies to identify more clinical uses of sivelestat are also needed.
Upregulation of long non-coding RNA LINC00963 has been observed in several cancer types. In this study, we analyzed the clinical and biological significance of LINC00963 in breast cancer. The key ...microRNA (miR) mediating the action of LINC00963 was identified. We show that LINC00963 upregulation is correlated with aggressive parameters of breast cancer. Silencing of LINC00963 suppresses the proliferation and tumorigenesis of breast cancer cells, whereas LINC00963 overexpression exerts an opposite effect. Knockdown of LINC00963 enhances DNA damage and oxidative stress and sensitizes breast cancer cells to radiation. Mechanistically, LINC00963 antagonizes the repressive activity of miR-324-3p on ACK1 expression. Clinically, there is a negative correlation between miR-324-3p and LINC00963 expression in breast cancer tissues. Overexpression of LINC00963 or ACK1 rescues the inhibitory effects of miR-324-3p on breast cancer cell proliferation and radiosensitivity. In addition, knockdown of ACK1 attenuates LINC00963-dependent breast cancer growth and tumorigenesis. Taken together, LINC00963 promotes tumorigenesis and radioresistance in breast cancer through interplay with miR-324-3p and derepression of ACK1. LINC00963 may represent a potential target for the treatment of breast cancer.
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