ABSTRACT
During a long‐duration manned spaceflight mission, such as flying to Mars and beyond, all crew members will spend a long period in an independent spacecraft with closed‐loop bioregenerative ...life‐support systems. Saving resources and reducing medical risks, particularly in mental heath, are key technology gaps hampering human expedition into deep space. In the 1960s, several scientists proposed that an induced state of suppressed metabolism in humans, which mimics ‘hibernation’, could be an ideal solution to cope with many issues during spaceflight. In recent years, with the introduction of specific methods, it is becoming more feasible to induce an artificial hibernation‐like state (synthetic torpor) in non‐hibernating species. Natural torpor is a fascinating, yet enigmatic, physiological process in which metabolic rate (MR), body core temperature (Tb) and behavioural activity are reduced to save energy during harsh seasonal conditions. It employs a complex central neural network to orchestrate a homeostatic state of hypometabolism, hypothermia and hypoactivity in response to environmental challenges. The anatomical and functional connections within the central nervous system (CNS) lie at the heart of controlling synthetic torpor. Although progress has been made, the precise mechanisms underlying the active regulation of the torpor–arousal transition, and their profound influence on neural function and behaviour, which are critical concerns for safe and reversible human torpor, remain poorly understood. In this review, we place particular emphasis on elaborating the central nervous mechanism orchestrating the torpor–arousal transition in both non‐flying hibernating mammals and non‐hibernating species, and aim to provide translational insights into long‐duration manned spaceflight. In addition, identifying difficulties and challenges ahead will underscore important concerns in engineering synthetic torpor in humans. We believe that synthetic torpor may not be the only option for manned long‐duration spaceflight, but it is the most achievable solution in the foreseeable future. Translating the available knowledge from natural torpor research will not only benefit manned spaceflight, but also many clinical settings attempting to manipulate energy metabolism and neurobehavioural functions.
Mesoporous hybrid shells of carbonized polyaniline (CPANI)/Mn2O3 with well-controlled diameter and high surface area have been synthesized through surface protected calcination processes. Originating ...from polystyrene template, PANI, MnO2, and SiO2 were sequentially loaded, followed by template removal and calcination, resulting in the desired CPANI/Mn2O3 hybrid shells. The introduction of SiO2 shell was established to play the determining role in maintaining the configuration during calcination process under high temperature. The CPANI/Mn2O3 hybrid shells showed outstanding electrocatalytic activity toward oxygen reduction reaction (ORR), with the onset potential at +0.974 V (versus RHE), the specific current at 60.8 mA/mg, and an overall quasi 4-electron transfer, which are comparable to those of the benchmark Pt/C. The remarkable ORR performance was attributed to the high specific surface area, the surface oxidation state of Mn, and composition-codependent behavior.
Objective
To investigate the efficacy and safety of His‐bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady‐arrhythmias, who suffer from permanent ...atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF).
Methods
All patients with brady‐arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end‐diastolic diameter (LVEDD), and left atrial size were compared.
Results
A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow‐up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his‐bundle and the threshold of the left ventricular lead remained stable during follow‐up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow‐up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP.
Conclusion
HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady‐arrhythmias, permanent AF and HFrEF compared with BVP.
Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was ...limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers.
Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined ...with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre- to post-onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5-HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5-HT levels, in which both restrained inhibitory inputs by excessive 5-HT
R signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5-HT
R contribute to aberrant neuronal hyperactivity. Downregulation of these two 5-HT receptors simultaneously enables neurons to resist β-amyloid peptides (Aβ) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5-HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline.
The concentrations, profiles, sources and spatial distribution of polycyclic aromatic hydrocarbons (PAHs) were determined in 40 surface soil samples collected from Beijing, Tianjin and surrounding ...areas, North China in 2007, and all sampling sites were far from industrial areas, roadsides and other pollution sources, and across a range of soil types in remote, rural villages and urban areas. The total concentrations of 16 PAHs ranged from 31.6 to 1475.0 ng/g, with an arithmetic average of 336.4 ng/g. The highest PAH concentrations were measured in urban soils, followed by rural village soils and soils from remote locations. The remote–rural village–urban PAH concentration gradient was related to population density, gross domestic product (GDP), long-range atmospheric transport and different types of land use. In addition, the PAH concentration was well correlated with the total organic carbon (TOC) concentration of the soil. The PAH profile suggested that coal combustion and biomass burning were primary PAH sources.
The concentration, profiles and possible sources of PAHs in Beijing, Tianjin and surrounding area soils were studied and related to population density and gross domestic product (GDP).
Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a ...critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid.
Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α.
The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice.
Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice.
In this work, it is reported that zirconium oxide (ZrO
) doped organosilica nanodots (OSiNDs: ZrO
) with light- and charge-management properties serve as efficient cathode interlayers for ...high-efficiency inverted organic solar cells (i-OSCs). ZrO
doping effectively improves the light harvesting of the active layer, the physical contact between the active layer, as well as the electron collection property by habiting charge recombination loss. Consequently, all devices utilizing the OSiNDs: ZrO
cathode interlayer exhibit enhanced power conversion efficiency (PCE). Specifically, i-OSCs based on PM6:Y6 and PM6:BTP-eC9 achieve remarkable PCEs of 17.16% and 18.43%, respectively. Furthermore, the PCE of device based on PM6:Y6 maintains over 97.2% of its original value following AM 1.5G illumination (including UV light) at 100 mW cm
for 600 min.
The aim of this study was to investigate the protective role of intranasally administered substance P-loaded gelatin nanoparticles (SP-GNPs) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in ...vitro and in vivo, and to provide a new strategy for treating brain pathology, such as Parkinson's disease.
SP-GNPs were prepared by a water-in-water emulsion method, and their stability, encapsulating efficiency, and loading capacity were evaluated. PC-12 cells were used to examine the enhancement of growth and inhibition of apoptosis by SP-GNPs in vitro using MTT assays. In the in vivo study, hemiparkinsonian rats were created by intracerebroventricular injection of 6-OHDA. The rats then received intranasal SP-GNPs daily for 2 weeks. Functional improvement was assessed by quantifying rotational behavior, and the degree of apoptosis was assessed by immunohistochemical staining for caspase-3 in the substantia nigra region.
PC-12 cells with 6-OHDA-induced disease treated with SP-GNPs showed higher cell viability than their untreated counterparts, and cell viability increased as the concentration of substance P (SP) increased, indicating that SP could enhance cell growth and inhibit the cell apoptosis induced by 6-OHDA. Rats with 6-OHDA-induced hemiparkinsonism treated with SP-GNPs made fewer rotations and showed less staining for caspase-3 than their counterparts not treated with SP, indicating that SP protects rats with 6-OHDA-induced hemiparkinsonism from apoptosis and therefore demonstrates their functional improvement.
Intranasal delivery of SP-GNPs protects against 6-OHDA-induced apoptosis both in vitro and in vivo.
Cardiovascular diseases (CVDs) are the leading cause of hospitalization and death worldwide, especially in developing countries. The increased prevalence rate and mortality due to CVDs, despite the ...development of several approaches for prevention and treatment, are alarming trends in global health. Chronic inflammation and macrophage infiltration are key regulators of the initiation and progression of CVDs. Recent data suggest that epigenetic modifications, such as DNA methylation, posttranslational histone modifications, and RNA modifications, regulate cell development, DNA damage repair, apoptosis, immunity, calcium signaling, and aging in cardiomyocytes; and are involved in macrophage polarization and contribute significantly to cardiac disease development. Cardiac macrophages not only trigger damaging inflammatory responses during atherosclerotic plaque formation, myocardial injury, and heart failure but are also involved in tissue repair, remodeling, and regeneration. In this review, we summarize the key epigenetic modifications that influence macrophage polarization and contribute to the pathophysiology of CVDs, and highlight their potential for the development of advanced epigenetic therapies.
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