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.
AIM To determine the role of G0/G1 switch gene 2(G0 S2) and its transcriptional regulation in palmitate-induced hepatic lipid accumulation.METHODS Hep G2 cells were treated with palmitate,or ...palmitate in combination with CCAAT/enhancer binding protein(C/EBP)β si RNA or G0 S2 si RNA. The m RNA expression of C/EBPβ,peroxisome proliferator-activated receptor(PPAR)γ and PPARγ target genes(G0 S2,GPR81,GPR109 A and Adipoq) was examined by q PCR. The protein expression of C/EBPβ,PPARγ,and G0 S2 was determined by Western blotting. Lipid accumulation was detected with Oil Red O staining and quantified by absorbance value of the extracted Oil Red O dye. Lipolysis was evaluated by measuring the amount of glycerol released into the medium. RESULTS Palmitate caused a dose-dependent increase in lipid accumulation and a dose-dependent decrease in lipolysis in Hep G2 cells. In addition,palmitate increased the m RNA expression of C/EBPβ,PPARγ,and PPARγ target genes(G0 S2,GPR81,GPR109 A,and Adipoq) and the protein expression of C/EBPβ,PPARγ,and G0 S2 in a dose-dependent manner. Knockdown of C/EBPβ decreased palmitate-induced PPARγ and its target genes(G0 S2,GPR81,GPR109 A,and Adipoq) m RNA expression and palmitate-induced PPARγ and G0 S2 protein expression in Hep G2 cells. Knockdown of C/EBPβ also attenuated lipid accumulation and augmented lipolysis in palmitate-treated Hep G2 cells. G0 S2 knockdown attenuated lipid accumulation and augmented lipolysis,while G0 S2 knockdown had no effects on the m RNA expression of C/EBPβ,PPARγ,and PPARγ target genes(GPR81,GPR109 A and Adipoq) in palmitate-treated Hep G2 cells. CONCLUSION Palmitate can induce lipid accumulation in Hep G2 cells by activating C/EBPβ-mediated G0 S2 expression.
Parkinson's disease (PD) can be classified into three motor-based subtypes: postural instability/gait difficulty (PIGD), tremor dominant (TD), and indeterminate. The neuropathophysiological ...mechanisms of the three motor subtypes are different, which may lead to different responses to therapy. Sixty-nine patients with idiopathic Parkinson's disease (Hoehn-Yahr stage ≤ 3) were screened from 436 patients with Parkinsonism recruited through outpatient services and the internet. According to the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) TD/PIGD ratio, the patients were divided into PIGD (TD/PIGD ≤ 0.09; n = 36), TD (TD/PIGD ≥1.15; n = 19), and indeterminate (TD/PIGD = 0.90-1.15; n = 14) groups. All patients received 2 weeks of multidisciplinary intensive rehabilitation treatment (MIRT) during hospitalization, as well as a remote home rehabilitation health education class. Compared with the scores at admission, all patients showed significant improvements in their MDS-UPDRS III score, walking ability, balance, and posture control at discharge. Moreover, the MDS-UPDRS III score improvement was greater in the PIGD group than in the TD group. The follow-up data, collected for 3 months after discharge, showed that overall symptom improvement in each group was maintained for 1-3 months. Furthermore, there were no significant differences in the duration or grade effects of symptom improvement among the three groups. These findings suggest that 2 weeks of MIRT is effective for improving motor performance in all three motor subtypes. Patients in the PIGD group had a better response after hospitalization than those in the TD group. This study was approved by the Institutional Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University of China (approval No. 2018bkky022) on May 7, 2018 and registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900020771) on January 19, 2019.
The dried vine stems of
are commonly used in traditional Chinese medicine for treating gynecological and cardiovascular diseases. In this study, five new compounds named spasuberol A (
), ...homovanillyl-4-oxo-nonanoate (
), spasuberol C (
), spasuberoside A (
), and spasuberoside B (
), together with ten known compounds (
,
,
,
-
), were isolated from the dried vine stems of
. Their chemical structures were analyzed using spectroscopic assays. This is the first study interpreting the detailed structural information of
. The anti-inflammatory activity of these compounds was evaluated by reducing nitric oxide overproduction in RAW264.7 macrophages stimulated by lipopolysaccharide. Compounds
and
-
showed strong inhibitory activity with half maximal inhibitory concentration (IC
) values of 5.69, 16.34, 16.87, and 6.78 μM, respectively, exhibiting higher activity than the positive drug l-
-(1-iminoethyl)-lysine (l-NIL) with an IC
value of 19.08 μM. The IC
values of inhibitory activity of compounds
and
-
were 46.26, 40.05, 45.87, and 28.29 μM respectively, which were lower than l-NIL, but better than that of positive drug indomethacin with an IC
value of 55.44 μM. Quantitative real-time polymerase chain reaction analysis revealed that assayed compounds with good anti-inflammatory activity, such as
,
,
, and
at different concentrations, can reduce the messenger RNA (mRNA) expression of some pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). The anti-inflammatory activity and the possible mechanism of the compounds mentioned in this paper were studied preliminarily.
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•A novel N/O functional reticulated TAPT-DMTA-COF was prepared.•PBDEs are captured by electronegative N/O atoms of TAPT-DMTA-COF by halogen bond.•An in-depth understanding of ...adsorption mechanism was elucidated by DFT study.•This d-SPE technique was used to quantify PBEDs in environmental and food samples.
Food and environmental safety issues attributable to the polybrominated diphenyl ethers (PBDEs) are gaining increasing attention, and these urge us to establish a high-performance sample-handling technique. In this study, an outstanding adsorption performance with short adsorption time (10 min) was achieved for PBDEs using a novel synthesized dispersive solid-phase extraction adsorbent, a reticulated covalent organic framework with N/O functional groups (i.e., imine linkage, triazine, and methoxy) (TAPT–DMTA–COF). By conducting sufficient experimentation and theoretical simulation on adsorption mechanism, the halogen bond between electronegative N/O atoms of TAPT–DMTA–COF and the electropositive Br atoms of PBDEs were observed to play a more pivotal role than π–π, C–H…π interactions, and hydrophobic effects. Furthermore, the positive linear relation between calculated adsorption energy and Br content directly clarified that enrichment behavior of PBDEs can be attributed to halogen bonding. These data implied that integrated nanostructure (i.e., N/O functional groups and reticulated architecture) effectively enhanced adsorption capacity. In case of PBDE analysis, this approach achieved excellent results with low limits of detection (0.03−0.13 ng L–1). Finally, the promising potential applications of aforementioned method were verified by spiking water, fish, and milk samples with PBDEs; good PBDEs recoveries were obtained.
Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ...ethanolic extract; (2) to study the in vitro and in vivo antifungal activity of isoxanthohumol, an isoprene flavonoid from H. lupulus, against Botrytis cinerea; and (3) to explore the antifungal mechanism of isoxanthohumol on B. cinerea. The present data revealed that the ethanolic extract of H. lupulus exhibited moderate antifungal activity against the five tested phytopathogenic fungi in vitro, and isoxanthohumol showed highly significant antifungal activity against B. cinerea, with an EC50 value of 4.32 µg/mL. Meanwhile, it exhibited moderate to excellent protective and curative efficacies in vivo. The results of morphologic observation, RNA-seq, and physiological indicators revealed that the antifungal mechanism of isoxanthohumol is mainly related to metabolism; it affected the carbohydrate metabolic process, destroyed the tricarboxylic acid (TCA) cycle, and hindered the generation of ATP by inhibiting respiration. Further studies indicated that isoxanthohumol caused membrane lipid peroxidation, thus accelerating the death of B. cinerea. This study demonstrates that isoxanthohumol can be used as a potential botanical fungicide for the management of phytopathogenic fungi.
Summary
Endothelial progenitor cells (EPCs), which can be cultured in vitro from mononuclear cells in peripheral blood or bone marrow, express both hematopoietic stem cell and endothelial cell ...markers on their surface. They are believed to participate in endothelial repair and postnatal angiogenesis due to their abilities of differentiating into endothelial cells and secreting protective cytokines and growth factors. Mounting evidence suggests that circulating EPCs are reduced and dysfunctional in various diseases including hypertension, diabetes, coronary heart disease, and ischemic stroke. Therefore, EPCs have been documented to be a potential biomarker for vascular diseases and a hopeful candidate for regenerative medicine. Ischemic stroke, as the major cause of disability and death, still has limited therapeutics based on the approaches of vascular recanalization or neuronal protection. Emerging evidence indicates that transplantation of EPCs is beneficial for the recovery of ischemic cerebral injury. EPC‐based therapy could open a new avenue for ischemic cerebrovascular disease. Currently, clinical trials for evaluating EPC transfusion in treating ischemic stroke are underway. In this review, we summarize the general conceptions and the characteristics of EPCs, and highlight the recent research developments on EPCs. More importantly, the rationale, perspectives, and strategies for using them to treat ischemic stroke will be discussed.
Pulmonary embolism (PE) remains largely underdiagnosed due to nonspecific symptoms. This study aims to evaluate typical symptoms of PE patients, their related predictors, and to differentiate typical ...clusters of patients and principal components of PE symptoms. Clinical data from a total of 551 PE patients between January 2012 and April 2016 were retrospectively reviewed. PE was diagnosed according to the European Society of Cardiology Guidelines. Logistic regression models, system clustering method, and principal component analysis were used to identify potential risk factors, different clusters of the patients, and principal components of PE symptoms. The most common symptoms of PE were dyspnea, cough, and tachypnea in more than 60% of patients. Some combined chronic conditions, laboratory and clinical indicators were found to be related to these clinical symptoms. Our study also suggested that PE is associated with a broad list of symptoms and some PE patients might share similar symptoms, and some PE symptoms were usually cooccurrence. Based on ten symptoms generated from our sample, we classified the patients into five clusters which represent five groups of PE patients during clinical practice, and identified four principal components of PE symptoms. These findings will improve our understanding of clinical symptoms and their potential combinations which are helpful for clinical diagnosis of PE.
The purpose of this study was to analyse the clinical characteristics of patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) PCR re-positivity after recovering from coronavirus ...disease 2019 (COVID-19). Patients (n = 1391) from Guangzhou, China, who had recovered from COVID-19 were recruited between 7 September 2021 and 11 March 2022. Data on epidemiology, symptoms, laboratory test results and treatment were analysed. In this study, 42.7% of recovered patients had re-positive result. Most re-positive patients were asymptomatic, did not have severe comorbidities, and were not contagious. The re-positivity rate was 39%, 46%, 11% and 25% in patients who had received inactivated, mRNA, adenovirus vector and recombinant subunit vaccines, respectively. Seven independent risk factors for testing re-positive were identified, and a predictive model was constructed using these variables. The predictors of re-positivity were COVID-19 vaccination status, previous SARs-CoV-12 infection prior to the most recent episode, renal function, SARS-CoV-2 IgG and IgM antibody levels and white blood cell count. The predictive model could benefit the control of the spread of COVID-19.
•18 wheat field experiments were conducted in two provinces of China.•Relation of wheat response to NH4+ and NO3− with soil nitrate N at different depths.•Soil ammonium and nitrate N were measured ...from 0 to 100cm.•NO3− was better to wheat than NH4+ when soil accumulated low nitrate N at root depth.
Eleven field experiments were conducted in Yongshou County, Shanxi Province and seven in Luoyang, Henan Province, and five layers of soil were sampled in 20-cm increments to 100cm depth for each experimental field to study the difference of wheat (Triticum aestivum) responses to nitrate and ammonium nitrogen (N) and the relation of its responses to nitrate N cumulative amount in different soil layers. In Yongshou, each experimental site included seven treatments (control, two varieties of nitrate N, two varieties of ammonium N, and two combinations of ammonium to nitrate N in a ratio of 1:2) while in Luoyang, six treatments (only one variety of nitrate N). Total 150kgha−1 N was added as basal for N fertilization treatments at wheat seeding time. Results showed that differences in two varieties of each N form or combinations were much less than those of N forms. As a whole, wheat responses to nitrate N were better in most cases and in few cases, there was no significant difference between nitrate N and ammonium N on wheat yield. Using averages of yield, yield increase amount (kgha−1) and percentage (%) of different N forms for comparison, nitrate N was highest in yield and yield increase, followed by the combination, while the ammonium N was lowest. The lower the amount of accumulated nitrate N in the soil profile, the better the nitrate N superiority. Our finding was that the superiority of nitrate N over ammonium N on wheat yield depended on the accumulative nitrate amounts in soil, and only in soil having low cumulative nitrate N amount at the rooting depth, did the nitrate N show its superiority over the ammonium N. In contrast, if the accumulative nitrate N amount was high, the two N forms had no significant difference on wheat yield.
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