Damaged mitochondria need to be cleared to maintain the quality of the mitochondrial pool. Here, we report mitocytosis, a migrasome-mediated mitochondrial quality-control process. We found that, upon ...exposure to mild mitochondrial stresses, damaged mitochondria are transported into migrasomes and subsequently disposed of from migrating cells. Mechanistically, mitocytosis requires positioning of damaged mitochondria at the cell periphery, which occurs because damaged mitochondria avoid binding to inward motor proteins. Functionally, mitocytosis plays an important role in maintaining mitochondrial quality. Enhanced mitocytosis protects cells from mitochondrial stressor-induced loss of mitochondrial membrane potential (MMP) and mitochondrial respiration; conversely, blocking mitocytosis causes loss of MMP and mitochondrial respiration under normal conditions. Physiologically, we demonstrate that mitocytosis is required for maintaining MMP and viability in neutrophils in vivo. We propose that mitocytosis is an important mitochondrial quality-control process in migrating cells, which couples mitochondrial homeostasis with cell migration.
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•Mild mitochondrial stress triggers disposal of damaged mitochondria by migrasomes•In this process (mitocytosis), motor proteins selectively bind damaged mitochondria•Damaged mitochondria become localized at the cell periphery to facilitate mitocytosis•Mitocytosis maintains mitochondrial quality and viability in neutrophils in vivo
Migrating cells selectively remove damaged mitochondria to maintain homeostasis in a process called mitocytosis.
Efficient low-grade heat recovery can help to reduce greenhouse gas emission as over 70% of primary energy input is wasted as heat, but current technologies to fulfill the heat-to-electricity ...conversion are still far from optimum. Here we report a direct thermal charging cell, using asymmetric electrodes of a graphene oxide/platinum nanoparticles cathode and a polyaniline anode in Fe
/Fe
redox electrolyte via isothermal heating operation. When heated, the cell generates voltage via a temperature-induced pseudocapacitive effect of graphene oxide and a thermogalvanic effect of Fe
/Fe
, and then discharges continuously by oxidizing polyaniline and reducing Fe
under isothermal heating till Fe
depletion. The cell can be self-regenerated when cooled down. Direct thermal charging cells attain a temperature coefficient of 5.0 mV K
and heat-to-electricity conversion efficiency of 2.8% at 70 °C (21.4% of Carnot efficiency) and 3.52% at 90 °C (19.7% of Carnot efficiency), outperforming other thermoelectrochemical and thermoelectric systems.
Efficient production of chemicals from cellulose provides sustainable routes for the utilization of natural renewable resources to meet the requirements of human society. Herein, we reported a highly ...efficient and simple metal salt catalyst, Al 2 (SO 4 ) 3 , for cellulose conversion to methyl levulinate (ML) under microwave conditions. A highest ML yield of 70.6% was obtained at 180 °C within a very short time of 40 min. The introduction of water could reduce humin/coke formation and solvent consumption, and could also switch the reaction pathway via the more reactive intermediate glucose. Kinetic and mechanistic studies of the subreactions showed that both cellulose hydrolysis and alcoholysis pathways were involved in the cellulose conversion to ML, with the former as the main route in the presence of water. The Lewis acid species Al(OH) x (H 2 O) y n+ and the Brønsted acid species H + , generated by in situ hydrolysis of Al 2 (SO 4 ) 3 , were responsible for the reaction conversions. The reaction with microwave heating showed accelerated reaction rates of 25 times the reaction with conventional oil heating, and even more times for the rates of glucose and methyl glucoside (MG) dehydration, resulting in higher reaction selectivity toward ML production. The catalyst was also successfully recycled and applied to the conversion of cellulose to other alkyl levulinates, as well as the conversion of raw biomass to ML with high yields. The homogeneous nature of Al 2 (SO 4 ) 3 , together with its high efficiency and excellent recyclability, make it a potential catalyst for the large-scale production of ML in industry.
Laser speckle contrast imaging (LSCI) is a powerful tool to monitor blood flow distribution and has been widely used in studies of microcirculation, both for animal and clinical applications. ...Conventionally, LSCI usually works on reflective-detected mode. However, it could provide promising temporal and spatial resolution for in vivo applications only with the assistance of various tissue windows, otherwise, the overlarge superficial static speckle would extremely limit its contrast and resolution. Here, we systematically investigated the capability of transmissive-detected LSCI (TR-LSCI) for blood flow monitoring in thick tissue. Using Monte Carlo simulation, we theoretically compared the performance of transmissive and reflective detection. It was found that the reflective-detected mode was better when the target layer was at the very surface, but the imaging quality would rapidly decrease with imaging depth, while the transmissive-detected mode could obtain a much stronger signal-to-background ratio (SBR) for thick tissue. We further proved by tissue phantom, animal, and human experiments that in a certain thickness of tissue, TR-LSCI showed remarkably better performance for thick-tissue imaging, and the imaging quality would be further improved if the use of longer wavelengths of near-infrared light. Therefore, both theoretical and experimental results demonstrate that TR-LSCI is capable of obtaining thick-tissue blood flow information and holds great potential in the field of microcirculation research.
The purpose of this study was to investigate the effects of secreted protein acidic and rich in cysteine (SPARC) on the maintenance of limbal epithelial stem cell (LESC) stemness and restoration of ...ocular surface. To determine the suitable concentration of SPARC for LESC culture, the marker expression, mitogenic effect, and holoclone‐forming capacity of LESCs treated with different concentrations of SPARC were analyzed. To investigate the mechanism of SPARC's action on the preservation of LESCs stemness, the phosphorylation of related signaling pathways was evaluated by Western blotting. A corneal wound model was established to verify the function of SPARC in ocular surface repair. Consecutive subculturing, colony‐forming efficiency, immunofluorescence, and 5‐ethynyl‐2‐deoxyuridine incorporation assays indicated that 1 μg/mL SPARC was a suitable concentration to stimulate LESC proliferation and preserve their proliferative potential. Compared with a control group, 1 μg/mL SPARC effectively increased the expression of ABCG‐2, Bmi‐1, and Ki67, while decreasing that of CK3/12. The mitogenic effect of SPARC on LESCs was found to be mediated by the phosphorylation of c‐Jun N‐terminal kinase (JNK) and p38‐MAPK signaling pathways, whereas the inhibitors of JNK and p38 MAPK reduced the marker expression and mitogenic capacity of LESCs. In a corneal injury model, SPARC facilitated corneal epithelial wound healing and promoted the proliferation of p63α‐positive cells both in the limbus and in the epithelial healing front. SPARC promotes proliferation while suppressing spontaneous differentiation of LESCs through JNK and p38‐MAPK signaling pathways, suggesting that SPARC is a promising factor for the improvement of LESCs culture in vitro and in vivo.
When cultured in medium containing1μg/mL secreted protein acidic and rich in cysteine (SPARC) in vitro, limbal epithelial stem cells (LESCs) showed a greater proliferative and clonogenic capacity and a higher expression of LESCs marker through c‐Jun N‐terminal kinase/p38 MAPK signal pathway. In corneal wounding model, exogenous SPARC accelerated corneal epithelial wound healing and promoted the proliferation of p63α‐positive cells both in limbus and in epithelial healing front.
Nonalcoholic fermentation could improve the organoleptic quality and functionality of fruit juice, and lactic acid bacteria (LAB)-fermented fruit juice has been proven to be beneficial to human ...health. However, LAB exhibit strain specificity with different food matrices. In the present study, the effects of L. plantarum and L. acidophilus on the physicochemical characteristics, antioxidant activity and metabolomics of loquat juices were investigated. Both LAB strains fermentation could significantly enhance the antioxidant activity of loquat juice. L. acidophilus grows faster than L. plantarum in loquat juice, but L. plantarum fermentation more effectively increased the total flavonoid content. Nontargeted metabolomics analysis based on UHPLC-Q Exactive HF-X/MS were performed to reveal the different metabolic profiles between LAB fermentation. A total of 776 metabolites were identified and annotated. The significant differentially regulated metabolites were concentrated mainly in lipids and lipid-like molecules; organic acids and derivatives; amino acids, peptides, and analogs; phenolic compounds and terpenoids. The regulation of metabolites plays a very important role in the flavor reconstruction and functional improvement of loquat juices. In addition, the metabolic profiles between L. plantarum- and L. acidophilus-fermented loquat juices were different, and the application of cofermentation of these two strains may be considered in future studies.
•L. plantarum and L. acidophilus were selected to prepared functional loquat juice.•Both strains fermentation could enhance the antioxidant activity of loquat juice.•L. acidophilus grows faster than L. plantarum in loquat juice fermentation.•L. plantarum fermentation more effectively increased the total flavonoid content.•Nontargeted metabolomics were used to reveal the differences of metabolic profiles.
Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled ...prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.
Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the ...effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.
In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of ...2019-nCoV pneumonia.
In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020.
Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 83% patients), cough (81 82% patients), shortness of breath (31 31% patients), muscle ache (11 11% patients), confusion (nine 9% patients), headache (eight 8% patients), sore throat (five 5% patients), rhinorrhoea (four 4% patients), chest pain (two 2% patients), diarrhoea (two 2% patients), and nausea and vomiting (one 1% patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure.
The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection.
National Key R&D Program of China.
Agricultural lands adjacent to industrial activities are vulnerable due to the risk of trace elements (TEs) being accumulated into crops and subsequently humans. One such case concerns the industrial ...area of Volos, Greece, a suspected contaminated area which has never been studied. We measured Ag, Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Se, Sn, Tl, V, and Zn in soil and maize (leaves and grains) and assessed health risk of human exposure via soil ingestion and grain consumption. We found that the most highly enriched elements in soils were Tl (enrichment factor = 19), Se (17.68), Sb (14.81), As (7.89), Ni (6.91), Mo (5.22) and Cr (4.33); they all likely derived from anthropogenic activities and in particular from a nearby major steel factory, except for Ni which is known to be lithogenically elevated in that area. Synchrotron XANES spectra analysis revealed that As species were associated with ferrihydrite, and predominant species were As(V) (at ca. 85%) and As(III) (at ca. 15%). Although the total content of the studied elements was high, the ammonium bicarbonate-DTPA extractions recovered very low element concentrations, probably due to the fact that soil conditions decelerated solubility (i.e., soils were alkaline, clayey, and with high Fe oxides content). This was confirmed by the soil-to-grain transfer index, which was particularly low for all studied elements. In 5% of sampled grains concerning Cd, and in 40% concerning Pb, the European food-related regulation limits were surpassed. Health risk assessment showed a dramatically elevated risk for Tl via soil ingestion (hazard quotient, HQ = 2.399), a value that contributed 74% of the total risk. Similarly, concerning the grain consumption-related health risk, Tl was the predominant contributor (HQ = 0.128, contributing 40% of the total risk). Such elevated Tl risk which has rarely been reported previously, led to a considerably high hazard index (HI) well above the threshold of HI = 1. Cancer risk was below the 1 × 10−4 risk threshold for As and Pb. Our findings indicate that this study should be pivotal concerning similar industrially-affected agricultural soils of suspected contamination, since less-expected toxic elements such as Tl here may be primary contributors to health risk.
•Studied soils were highly enriched with Tl, a highly toxic metal.•Se, Sb, and Mo were also found severely enriched, as well as As, Ni and Cr.•Health risk assessment via soil ingestion indicated a significant risk.•Carcinogenic risk was below the 1 × 10−4 threshold for both As and Pb.•There is an urgent future need for monitoring other similar areas in Greece.
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