Chiral chromophores and their ordered assemblies are intriguing for yielding circularly polarized luminescence (CPL) and exploring intrinsic structure–light emission relationships. With the ...extensively studied chiral organic molecules and inorganic nanoparticle assemblies for the amplified CPL, the assemblies of copper halide hybrid clusters have attracted intensive attention due to their potential efficient CPL. Here, we report robust chiral phosphine–copper iodide hybrid clusters and their layered assemblies in crystalline states for amplified CPL. We reveal that the intermolecular interactions endow the clusters with the capability of assembling into chiral crystalline CPL materials, including hexagonal platelet-shaped microcrystals (g lum ≈ 9.5 × 10–3) and highly oriented crystalline films (g lum ≈ 5 × 10–3). Owing to the high crystalline feature of the thin film, we demonstrate an electroluminescent device with bright electroluminescence (1200 cd m–2).
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IJS, KILJ, NUK, PNG, UL, UM
Dextran sulfate sodium (DSS) replicates ulcerative colitis (UC)-like colitis in murine models. However, the microbial characteristics of DSS-triggered colitis require further clarification. To ...analyze the changes in gut microbiota associated with DSS-induced acute and chronic colitis.
Acute colitis was induced in mice by administering 3% DSS for 1 week in the drinking water, and chronic colitis was induced by supplementing drinking water with 2.5% DSS every other week for 5 weeks. Control groups received the same drinking water without DSS supplementation. The histopathological score and length of the colons, and disease activity index (DAI) were evaluated to confirm the presence of experimental colitis. Intestinal microbiota was profiled by 16S rDNA sequencing of cecal content.
Mice with both acute and chronic DSS-triggered colitis had significantly higher DAI and colon histopathological scores in contrast to the control groups (P < 0.0001, P < 0.0001), and the colon was remarkably shortened (P < 0.0001, P < 0.0001). The gut microbiota α-diversity was partly downregulated in both acute and chronic colitis groups in contrast to their respective control groups (Pielou index P = 0.0022, P = 0.0649; Shannon index P = 0.0022, P = 0.0931). The reduction in the Pielou and Shannon indices were more obvious in mice with acute colitis (P = 0.0022, P = 0.0043). The relative abundance of Bacteroides and Turicibacter was increased (all P < 0.05), while that of Lachnospiraceae, Ruminococcaceae, Ruminiclostridium, Rikenella, Alistipes, Alloprevotella, and Butyricicoccus was significantly decreased after acute DSS induction (all P < 0.05). The relative abundance of Bacteroides, Akkermansia, Helicobacter, Parabacteroides, Erysipelatoclostridium, Turicibacter and Romboutsia was also markedly increased (all P < 0.05), and that of Lachnospiraceae_NK4A136_group, Alistipes, Enterorhabdus, Prevotellaceae_UCG-001, Butyricicoccus, Ruminiclostridium_6, Muribaculum, Ruminococcaceae_NK4A214_group, Family_XIII_UCG-001 and Flavonifractor was significantly decreased after chronic DSS induction (all P < 0.05).
DSS-induced acute and chronic colitis demonstrated similar symptoms and histopathological changes. The changes in the gut microbiota of the acute colitis model were closer to that observed in UC. The acute colitis model had greater abundance of SCFAs-producing bacteria and lower α-diversity compared to the chronic colitis model.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vascular stenosis caused by atherosclerosis instigates activation and aggregation of platelets, eventually resulting in thrombus formation. Although antiplatelet drugs are commonly used to inhibit ...platelet activation and aggregation, they unfortunately cannot prevent recurrent thrombotic events in patients with atherosclerosis. This is partially due to the limited understanding of the efficacy of antiplatelet drugs in the complex hemodynamic environment of vascular stenosis. Conventional methods for evaluating the efficacy of antiplatelet drugs under stenosis either fail to simulate the hemodynamic environment of vascular stenosis characterized by high shear stress and recirculatory flow or lack spatial resolution in their analytical techniques to statistically identify and characterize platelet aggregates. Here we propose and experimentally demonstrate a method comprising an
in vitro
3D stenosis microfluidic chip and an optical time-stretch quantitative phase imaging system for studying the efficacy of antiplatelet drugs under stenosis. Our method simulates the atherogenic flow environment of vascular stenosis while enabling high-resolution and statistical analysis of platelet aggregates. Using our method, we distinguished the efficacy of three antiplatelet drugs, acetylsalicylic acid (ASA), cangrelor, and eptifibatide, for inhibiting platelet aggregation induced by stenosis. Specifically, ASA failed to inhibit stenosis-induced platelet aggregation, while eptifibatide and cangrelor showed high and moderate efficacy, respectively. Furthermore, we demonstrated that the drugs tested also differed in their efficacy for inhibiting platelet aggregation synergistically induced by stenosis and agonists (
e.g.
, adenosine diphosphate, and collagen). Taken together, our method is an effective tool for investigating the efficacy of antiplatelet drugs under vascular stenosis, which could assist the development of optimal pharmacologic strategies for patients with atherosclerosis.
Optofluidic imaging on a chip is developed for studying the efficacy of antiplatelet drugs on atherosclerosis.
A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized ...by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis of the big image data shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, respiratory condition, and vascular endothelial dysfunction level of COVID-19 patients.
Abstract
Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the ...dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis. The highly optimized HNP has high capacity and long-term circulation capability for the selective sequestration and neutralization of histones. Intravenous injection of the HNP protects mice against a lethal dose of histones through the inhibition of platelet aggregation and migration into the lungs. In vivo administration in murine sepsis model mice results in near complete survival. These results establish the potential for synthetic, nonbiological polymer hydrogel sequestrants as a new intervention strategy for sepsis therapy and adds to our understanding of the importance of histones to this condition.
The previous study has indicated that the interplanetary magnetic field (IMF) By and solar wind flow speed (Vsw) have crucial effects on the cusp auroral intensity in the Northern Hemisphere. ...However, it is not clear how these factors influence the cusp aurora in the Southern Hemisphere. Using DMSP/SUSSI observations from 2004 to 2017 during non‐storm periods, we compared the factors affecting the intensity of cusp aurora between the Northern and Southern Hemispheres by dividing the observations into weak‐ and intense‐emission events. We found that the auroral intensity in the southern cusp: (a) has a positive correlation with solar wind power input, (b) is statistically weak under southward IMF conditions, and (c) is critically controlled by the IMF By and Vsw. These results are essentially consistent with those obtained in the Northern Hemisphere. However, the IMF By effect shows apparent interhemispheric asymmetry, that is, the IMF By effect reaches the maximum at 2 nT in the Northern Hemisphere, but at −2 nT in the Southern Hemisphere. Further analysis shows that the 2‐nT deviations disappear after dividing all events by season and the IMF By distributions of intense‐emission events show clear seasonal difference. Based on these results, we suggest that the dependence of the cusp auroral intensity on the IMF By is not only controlled by −Vsw × By field, but also affected by season.
Plain Language Summary
As one of the most important regions in the magnetosphere, the polar cusp is the direct entry of the solar wind particles entering the Earth. The cusp aurora is produced by the interaction of the solar wind particles and the neutral particles in the upper atmosphere. Therefore, the intensity of the cusp aurora is significantly influenced by solar wind power input. According to previous research, solar wind power input can be well measured by the solar wind speed, the interplanetary field magnitude, and the IMF direction together, and the dependence of the cusp auroral intensity on these factors has also been widely investigated. A recent work statistically analyzed the occurrence conditions, that is, the solar wind and IMF conditions, for “auroral midday gap” observed above the Northern Hemisphere. It revealed that the IMF By component is vital in enhancing the auroral emissions near the cusp. However, whether these factors have the same effects in the Southern Hemisphere is still unclear. In this study, we made an interhemispheric comparison of the interplanetary factors affecting the cusp auroral intensity. Some new results were obtained, and they are important for fully understanding the cusp aurora.
Key Points
Among factors deciding solar wind power input, the IMF By is confirmed to critically control cusp auroral intensity in both hemispheres
The dependence of the cusp aurora on the IMF By shows clear interhemispheric asymmetry and seasonal difference
The interhemispheric asymmetry of the IMF By effect is affected by both the −Vsw × By electric field and the season
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Technological advances in image-based platelet analysis or platelet morphometry are critical for a better understanding of the structure and function of platelets in biological research as well as ...for the development of better clinical strategies in medical practice. Recently, the advent of high-throughput optical imaging and deep learning has boosted platelet morphometry to the next level by providing a new set of capabilities beyond what is achievable with traditional platelet morphometry, shedding light on the unexplored domain of platelet analysis. This Opinion article introduces emerging opportunities in ‘intelligent’ platelet morphometry, which are expected to pave the way for a new class of diagnostics, pharmacometrics, and therapeutics.
Technological advances in platelet analysis are critical for a better understanding of platelets, which are highly complex, dynamic, and multifunctional in nature.The advent of high-throughput imaging and deep learning has boosted traditional image-based platelet analysis or platelet morphometry to the next level, shedding light on the unexplored domain of platelet biology.Key methods for this ‘intelligent’ platelet morphometry include, but are not limited to, intelligent platelet aggregate classification and intelligent image-activated cell sorting.Intelligent platelet morphometry is expected to pave the way for a new class of diagnostics, pharmacometrics, and therapeutics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse ...pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions.
Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE−/− mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration.
TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.
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•TRIM65 expression positively correlated with AS lesions in human atherosclerotic tissues, indicating TRIM65 could be implicated in atherogenesis.•Overexpression of TRIM65 promoted progression of atherosclerosis by increasing AS plaque formation, loss of VSMCs contractile phenotype, cell proliferation, and activation of PI3K/Akt/mTOR signaling in WD-fed ApoE−/− mice.•TRIM65 was upregulated in PDGF-BB-induced VSMCs phenotype transformation model.•Overexpression of TRIM65 promoted PDGF-BB-dependent or independent VSMCs phenotype transformation, and PDGF-BB-induced cell proliferation and migration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
9.
An Auroral Signature of the Duskside Boundary of the Cusp Feng, Hui‐Ting; Han, De‐Sheng; Teng, Shang‐Chun ...
Journal of geophysical research. Space physics,
August 2022, 2022-08-00, 20220801, Volume:
127, Issue:
8
Journal Article
Peer reviewed
The cusp is a region in which the solar wind plasma can directly penetrate into the ionosphere. Most previous studies mainly focused on the low‐ and high‐latitude boundaries of the cusps, the ...identification of the dawnside and duskside boundaries of them appears to be questionable. The auroras are the ionospheric manifestations of solar‐terrestrial energy coupling. This paper presents a new approach to diagnose the duskside boundary of the cusp with the observation of a particular polar cap arc (PCA) located near the ∼1500 magnetic local time sector (15MLT‐PCA). Using measurements from Defense Meteorological Satellite Program satellite, we selected several 15MLT‐PCA examples where the satellite flew over different regions and analyze the particle characteristics. We identified the precipitating particles in dawnside and duskside regions next to 15MLT‐PCA are from the low latitude boundary layer/cusp and boundary plasma sheet/central plasma sheet respectively. The statistical result further confirms our findings. Therefore, we proposed that 15MLT‐PCA can be used as an identifiable optical signature of the duskside boundary of the cusp. This paper provides a valuable approach to identify the cusp boundaries, and the results are critical for understanding the generation mechanism of 15MLT‐PCA.
Plain Language Summary
The polar cusps are important regions in which the particles originating from the solar wind can directly enter the upper atmosphere. Those precipitating particles can produce auroras in the ionosphere. The polar cusps have been studied in great detail for several decades and their properties have been characterized under different interplanetary magnetic field conditions. Until now, how to determine the cusp boundaries is still a topic of investigation. This study emphasizes one special auroral phenomenon called 1500 magnetic local time‐polar cap arc (15MLT‐PCA), and we check the particle distributions around 15MLT‐PCA using the observations provided by the Defence Meteorological Satellite Program satellite. We found that the 15MLT‐PCA occurs at the duskside boundary of the cusp, thus allowing the possibility that 15MLT‐PCA can be regarded as an optical signature of duskside boundary of the cusp.
Key Points
The 1500 magnetic local time‐polar cap arc (15MLT‐PCA) is suggested to be an auroral indicator of the duskside boundary of the cusp
At the dawnside (duskside) auroral oval of 15MLT‐PCA, the precipitating particles appear as low latitude boundary layer (LLBL)/cusp (boundary plasma sheet/central plasma sheet BPS/CPS) characteristics
The 15MLT‐PCA can be viewed as a separator between dayside LLBL/cusp and duskside CPS/BPS auroras
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal ...GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. Overall, this study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.
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