The mitochondrial permeability transition pore is a nonspecific transmembrane channel. Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial ...swelling, calcium overload, and axonal degeneration. Cyclophilin D is an important component of the mitochondrial permeability transition pore. Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear. In this study, we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice, in which pyramidal neurons and axons express yellow fluorescent protein. We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin. We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening. We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage. We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury. In addition, inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage. Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage; inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage. Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.
The formation of disordered solid solution in the hexagonal close-packed (hcp) structure in the GdHoLaTbY alloy and its mechanical properties were investigated in this study. The single hcp phase of ...the alloy in the as-cast state was confirmed by X-ray diffraction and scanning electron microscopy analyses. The compressive yield strength, fracture strength, and plastic strain of the alloy are 108MPa, 880MPa, and 21.8%, respectively, and the Vickers hardness is 96HV. The results show that the yield strength, fracture strength, and hardness of the alloy obey the rule of mixture, which indicates that there is no hardening effect from entropy. Although the high entropy of mixing stabilizes the solid solution against intermetallic compounds, lack of severe lattice distortion from elastic strain or electronic interactions between principal elements impacts little on the mechanical properties.
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•The GdHoLaTbY high-entropy alloy forms a hexagonal close-packed solid solution.•The strengthening effect from the configurational entropy is not found in the alloy.•The mechanical properties and Vickers hardness of the alloy obey the rule of mixture.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Solid oxide cells (SOCs) have the potential to be the most efficient energy storage and conversion systems. To minimize energy loss due to charge and mass transport associated with the operation of ...SOC systems at intermediate temperatures, electrodes and electrolytes containing different types of heterointerfaces have been designed, fabricated, and tested under various conditions. While heterointerfaces can significantly enhance not only the ionic and/or electronic conductivity but also the electrocatalytic activity and stability of SOC components, as predicted by theoretical calculations and demonstrated by experimental results, the mechanisms of these enhancements are yet to be fully understood. In this review, we start with an overview of the techniques for fabrication of heterointerfaces with controlled composition, structure, and morphology. Then, the latest developments in performance enhancement of SOCs with heterointerfaces are summarized, including boosting the ionic conductivity of heterostructured electrolytes (oxygen ion conductors and proton conductors) and increasing the electrocatalytic activity and durability of heterostructured electrodes (oxygen electrodes and fuel electrodes). Subsequently, we will highlight the unique attributes of heterointerfaces in the enhancement of the SOC performance and provide important insights into the mechanisms of performance enhancement in order to establish the scientific basis for rational design of better electrolyte and electrode materials. Finally, the remaining challenges in design and fabrication of novel materials for advanced solid-state electrochemical systems will be discussed, together with possible strategies to overcome these critical issues, new research directions, and future perspectives.
This article overviews the latest developments in enhancing the conductivity, electro-catalytic activity, and stability of SOC materials through heterointerface engineering.
Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration ...of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by
spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by
spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as
and
spp.
Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota.
spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of
spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula.
A functional material with coexisting energetically equivalent phases often exhibits extraordinary properties such as piezoelectricity, ferromagnetism, and ferroelasticity, which is simultaneously ...accompanied by field-driven reversible phase transformation. The study on the interplay between such phase transformation and the performance is of great importance. Here, we have experimentally revealed the important role of field-driven reversible phase transformation in achieving enhanced electromechanical properties using in situ high-energy synchrotron x-ray diffraction combined with 2D geometry scattering technology, which can establish a comprehensive picture of piezoelectric-related microstructural evolution. High-throughput experiments on various Pb/Bi-based perovskite piezoelectric systems suggest that reversible phase transformation can be triggered by an electric field at the morphotropic phase boundary and the piezoelectric performance is highly related to the tendency of electric-field-driven phase transformation. A strong tendency of phase transformation driven by an electric field generates peak piezoelectric response. Further, phase-field modeling reveals that the polarization alignment and the piezoelectric response can be much enhanced by the electric-field-driven phase transformation. The proposed mechanism will be helpful to design and optimize the new piezoelectrics, ferromagnetics, or other related functional materials.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Blue light extensively regulates multiple physiological processes and secondary metabolism of plants. Although blue light quantity (fluence rate) is important for plant life, few studies have focused ...on the effects of different blue light intensity on plant secondary metabolism regulation, including tea plants. Here, we performed transcriptomic and metabolomic analyses of young tea shoots (one bud and two leaves) under three levels of supplemental blue light, including low-intensity blue light (LBL, 50 μmol m
s
), medium-intensity blue light (MBL, 100 μmol m
s
), and high-intensity blue light (HBL, 200 μmol m
s
). The total number of differentially expressed genes (DEGs) in LBL, MBL and HBL was 1, 7 and 1097, respectively, indicating that high-intensity blue light comprehensively affects the transcription of tea plants. These DEGs were primarily annotated to the pathways of photosynthesis, lipid metabolism and flavonoid synthesis. In addition, the most abundant transcription factor (TF) families in DEGs were bHLH and MYB, which have been shown to be widely involved in the regulation of plant flavonoids. The significantly changed metabolites that we detected contained 15 lipids and 6 flavonoid components. Further weighted gene co-expression network analysis (WGCNA) indicated that
(TEA001045) may be a hub gene for the regulation of lipid and flavonoid metabolism by blue light. Our results may help to establish a foundation for future research investigating the regulation of woody plants by blue light.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A novel photocatalytic hydrazonyl radical-mediated radical cyclization/allylation cascade reaction of β,γ-unsaturated hydrazones is developed using allyl sulfones and Morita–Baylis–Hillman adduct as ...allyl sources, which provides an efficient and practical access to various diversely functionalized dihydropyrazoles and tetrahydropyridazines. The reaction is enabled by controllable generation of hydrazonyl radicals via an oxidative deprotonation electron transfer strategy and selective trapping of the resultant C-centered radicals under visible light irradiation.
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IJS, KILJ, NUK, PNG, UL, UM
The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear.
MR uniformity ratio estimates (URE) can ...detect LVMD and assess STEMI prognosis.
Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453).
Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls.
3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging.
MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared.
The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant.
CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF.
CURE and RURE may be useful to evaluate long-term prognosis after STEMI.
4 TECHNICAL EFFICACY: Stage 2.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
To reveal detailed histopathological changes, virus distributions, immunologic properties and multi‐omic features caused by SARS‐CoV‐2 in the explanted lungs from the world's first ...successful lung transplantation of a COVID‐19 patient.
Materials and methods
A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID‐19‐associated pulmonary fibrosis.
Results
The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+CD4− T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL‐1β and IL‐6 were in the area of mild fibrosis. Multi‐omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation.
Conclusions
Our results provide novel insight that the significant neutrophil/ CD3+CD4− T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID‐19 patient and may contribute to a better understanding of COVID‐19 pathogenesis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
A concave-shaped photonic crystal fiber (PCF) combined with square-channel using indium tin oxide (ITO) for surface plasmon resonance (SPR) sensing is proposed. By means of finite element method ...(FEM) to multiple parameter optimization of structure, the operation wavelength spans from 1270 nm to 1692 nm covering low-loss communication band when a dynamic refractive index (RI) in a range of 1.19 to 1.29, and meanwhile the sensor displays the maximum wavelength sensitivity of 1700–10700 nm/RIU. This is so far the minimum RI detection sensor in the known reported D-shaped PCF-SPR sensors. It reveals the remarkable ability of our sensor to detect the 10−6 scaled smallest RI changes in solutions of medical oxygen, liquid CO2, and fluorine-containing organics, which extremely expands the application of existing PCF-SPR sensors for medical testing, unknown biomolecules and organic chemistry detections.
•The SPR effect is excited by coating indium tin oxide on the rectangle slot.•Detecting the 10−6- 10−5 scaled small RI changes of medical oxygen, liquid CO2 , and fluorine-containing organics.•Low plasmonic material consumption and minute sample detection contribute to high cost-effectiveness.•Uniformly coating film on the flat surface of rectangle open-ring.•Variable side-polished depth of D-shaped fiber make fabrication easier.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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