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1.
Phytochem Rev ; : 1-35, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35035319

RESUMO

Tsaoko Fructus, the dried ripe fruit of Amomum tsao-ko Crevost & Lemarié, is used as both medicinal material and food additive. This review summarized the traditional uses, botany, phytochemistry, and pharmacological progress on Tsaoko Fructus. One classical prescription and the other 11 representative prescriptions containing Tsaoko Fructus were reviewed. The indications of these prescriptions are major in treating spleen and stomach disorders and epidemic febrile diseases including malaria. At least 209 compounds have been isolated and identified from Tsaoko Fructus, most of which belong to terpenoids, phenylpropanoids, and organic acids. Essential oil, crude extract, and some compounds were observed to have pharmacological activities such as anti-biotics, anti-inflammation, antioxidant, mostly via in vitro experiments. However, the mechanism of its medicinal uses remains unclear. This review provides a comprehensive understanding of Tsaoko Fructus, which will be beneficial to exploring the mechanism and potential medicinal applications of Tsaoko Fructus, as well as developing a rational quality control system for Tsaoko Fructus as a medicinal material in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s11101-021-09793-x.

2.
BMC Infect Dis ; 22(1): 59, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039000

RESUMO

BACKGROUND: In March 2020, the WHO declared the novel coronavirus outbreak a global pandemic. While great success in coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategies in Beijing, China. METHODS: This retrospective study included all imported cases transferred to Beijing Ditan Hospital from 29 February to 20 March 2020 who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at the initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging, were collected and analysed. RESULTS: In total, 2545 cases were included, among which 71 (2.8%) were finally diagnosed with laboratory-confirmed COVID-19. The majority 63 (88.7%) were from Europe. The most common initial symptoms were cough and fever, which accounted for 49.3% and 42.3%, respectively. Only four cases (5.6%) had lymphocytopenia, and thirteen cases (18.3%) demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin (PCT). At initial presentation, among the 71 confirmed cases, 59 (83.1%) had a positive RT-PCR assay, and 35 (49.3%) had a positive chest CT. Twelve (16.9%) had a negative RT-PCR assay but a positive chest CT. CONCLUSIONS: A combination of RT-PCR and chest CT is an effective strategy for the screening of imported COVID-19 cases. Our findings provide important information and clinical evidence about the infection control of imported COVID-19 cases.


Assuntos
COVID-19 , Pequim/epidemiologia , China/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2
3.
Chemosphere ; 286(Pt 2): 131806, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426137

RESUMO

Microplastics, as defined here as plastics with a diameter of <5 mm, can impose severely detrimental impacts on the environment and can now be commonly found in different water bodies. To date, the status of microplastics in limnic systems, which have different hydrologic systems compared to other water bodies such as oceans or rivers, has rarely been reviewed. In the present study, the microplastic pollutants in different countries and regions were comparatively investigated in terms of their abundances, morphologies, and polymer types in the water and sediments of lakes. The concentration and characteristics of microplastics were found to be largely different across countries and regions, which was related to the local development level and economic structure. The migration paths of microplastics in the inner and external limnic ecosystems further revealed the causes for the regional divergence in microplastics. Policy developments in different countries and regions were also discussed to highlight the urgency of better controlling microplastic pollution in lake systems. The characteristics of microplastics vary across countries and regions, depending on the local development level and economic structure.


Assuntos
Microplásticos , Poluentes Químicos da Água , Ecossistema , Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Plásticos , Poluentes Químicos da Água/análise
4.
Infect Drug Resist ; 14: 5501-5510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955644

RESUMO

Purpose: Human brucellosis is the most common bacterial zoonosis globally that poses a severe health threat. Despite the availability of antibiotic therapy for human brucellosis, its tendencies of chronicity and persistence may lead to severe debilitating and disabling conditions in patients. Comprehensive understanding of the immune response in brucellosis will be helpful in improving the treatment strategies. In this study, we measured serum levels of T helper cell type 1 (Th1), Th2, and Th17 cytokines in patients with acute brucellosis before and after treatment. Patients and Methods: Overall, 30 patients with acute brucellosis from the Beijing Di Tan Hospital and 26 healthy controls were enrolled in this study. All the patients received a 6-week therapy regimen comprising ceftriaxone, doxycycline, and rifampicin. Serum samples were collected from patients with acute Brucella infection and healthy controls before and after treatment. Serum seven cytokine levels of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were measured using cytometric bead array. Results: In patients with acute infection, the IL-2, IFN-γ, and IL-10 levels were significantly increased compared with those in healthy controls (P < 0.001). After treatment, IL-2, IFN-γ, and IL-10 levels significantly decreased (P < 0.05) and the TNF-α level significantly increased compared with the corresponding baseline levels and those in healthy controls (P < 0.05). Furthermore, the IFN-γ, IL-4, and IL-10 levels were higher in patients after treatment than in healthy controls (P < 0.05). IL-2 and IL-6 levels exhibited a positive correlation with the C-reactive protein (CRP) level in acute brucellosis (P < 0.05). Conclusion: Levels of most serum Th1 and Th2 cytokines were simultaneously increased in acute infection, followed by reduction in the corresponding cytokine levels and residual cytokine response during treatment. This residual immune response could represent a therapeutic opportunity that may improve the long-term clinical outcomes in patients with acute brucellosis after treatment.

5.
Small Methods ; 5(11): e2100878, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34927978

RESUMO

The rational design and construction of cost-effective nickel-based phosphide or sulfide (photo)electrocatalysts for hydrogen production from water splitting has sparked a huge investigation surge in recent years. Whereas, nickel phosphides (Nix Py ) possess more than ten stoichiometric compositions with different crystalline. Constructing Nix Py with well crystalline and revealing their intrinsic catalytic mechanism at atomic/molecular levels remains a great challenge. Herein, an easy-to-follow phase-controllable phosphating strategy is first proposed to prepare well crystalline Nix Py (Ni3 P and Ni12 P5 ) modified CdS@Ni3 S2 heterojunction electrocatalysts. It is found that Ni3 P modified CdS@Ni3 S2 (CdS@Ni3 S2 /Ni3 P) exhibits remarkable stability and bifunctional electrocatalytic activities in both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Density functional theory results suggest that P-Ni sites and P sites in CdS@Ni3 S2 /Ni3 P, respectively, serve as OER and HER active sites during electrocatalytic water splitting processes. Moreover, benefiting from the advantageous photocatalyst@electrocatalyst core@shell structure, CdS@Ni3 S2 /Ni3 P delivers an advantaged photoassisted electrocatalytic water splitting property. The champion electrical to hydrogen and solar to hydrogen energy conversion efficiencies of CdS@Ni3 S2 /Ni3 P, respectively, reach 93.35% and 4.65%. This work will provide a general guidance for synergistically using solar energy and electric energy for large-scale H2 production from water splitting.

6.
Eur Neurol ; : 1-10, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34818658

RESUMO

INTRODUCTION: The combination of mechanical thrombectomy (MT) and intravenous thrombolysis (IVT) is more effective than IVT alone in patients with large vessel occlusion, which has been proven in recent studies. However, there are still debates over whether IVT benefits patients treated with only direct mechanical thrombectomy (dMT). METHODS: PubMed, Embase, and Cochrane Library were searched on June 15, 2021, for randomized controlled trials (RCTs). Seven RCTs with 2,143 patients were enrolled in our study. RESULTS: MT combined with IVT had comparable efficacy and safety outcome compared with dMT in proximal anterior circulation occlusion at 90 days. For the primary outcome, pooled data showed no significant difference in the modified Rankin Scale (mRS) 0-2 at 90 days between the dMT and MT+IVT groups (pooled odds ratio 0.96, 95% confidence interval, 0.79, 1.17, p = 0.39). As for the mRS score 0-1 at 90 days, the degree of benefit conferred by dMT was substantial: for every 100 patients treated, the number of patients which had an excellent outcome in the dMT group was 10 higher than that of the MT+IVT group. CONCLUSION: In this meta-analysis including 7 RCTs, MT had comparable consequences to bridging treatment in efficacy and safety outcomes for patients with ischemic stroke caused by the occlusion of proximal anterior circulation, irrespective of geographical location. These findings support the adoption of dMT in acute ischemic stroke treatments and have higher cost-effectiveness in global applications.

7.
Hum Psychopharmacol ; : e2825, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739739

RESUMO

OBJECTIVE: In recent years, interest in using lysergic acid diethylamide (LSD) in psychiatric research and corresponding therapy has increased rapidly. In this meta-analysis, we explored the effects of LSD on healthy subjects with respect to subjective drug effects, blood pressure, heart rate, body temperature and side effects. METHOD: PubMed, Embase, and the Cochrane Library were searched from January 2010 to December 2020 for randomized controlled trials (RCTs) on the effects of LSD in healthy people. Subsequently, 5 RCTs with 132 healthy people which focused on the effects of LSD were enrolled in our study. RESULT: We found that taking 50, 100 and 200 mcg LSD doses were associated with a significant increase in the maximal difference from the baseline compared to the placebo group among the outcomes of AMRS (Adjective Mood Rating Scale) score. Significant differences existed between the LSD and placebo groups when taking 100 and 200 mcg LSD in acute adverse effects (100 mcg: SMD = .97, 95% confidence interval [CI], .50, 1.44, Z = 4.04, p < .001; 200 mcg: SMD = 1.18, 95% CI, 0.65, 1.72, Z = 4.32, p < .001). CONCLUSIONS: Meta-analysis of the subjective effects of LSD in healthy people revealed moderate significant effect sizes in favor of LSD with no significant adverse effects. A 100 mcg dose of LSD has potential for use in psychological-assisted therapy and may improve the mental fitness of patients with disease-related psychiatric distress. Additional clinical trials are necessary to explore the efficacy and safety of LSD as a psychological-assisted therapy.

9.
J Virol ; : JVI0171721, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787451

RESUMO

A 2-year surveillance study of influenza A viruses in migratory birds was conducted to understand the subsequent risk during the migratory seasons in Dandong Yalu River Estuary Coastal Wetland National Nature Reserve, Liaoning Province, China, a major stopover site on the East Asian-Australasian flyway. Overall, we isolated 27 influenza A viruses with multiple subtypes, including H3N8 (n=2), H4N6 (n=2), H4N7 (n=2), H7N4 (n=9), H7N7 (n=1), H10N7 (n=7), and H13N6 (n=4). Particularly, a novel reassortant influenza A(H7N4) virus was first identified in a woman and her backyard poultry flock in Jiangsu Province, China, posing a serious threat to public health. Here, we describe the genetic characterization and pathogenicity of the nine influenza A(H7N4) isolates. Phylogenetic analysis indicated that complex viral gene flow occurred among Asian countries. We also demonstrated a similar evolutionary trajectory of the surface genes of the A(H7N4) isolates and Jiangsu human-related A(H7N4) viruses. Our A(H7N4) isolates exhibited differing degrees of virulence in mice, suggesting a potential risk to other mammalian species, including humans. We revealed multiple mutations that might affect viral virulence in mice. Our report highlights the importance and needs for the long-term surveillance of avian influenza virus in migratory birds, combined with domestic poultry surveillance along migratory routes and flyways, and thereby develop measures to manage potential health threats. Importance The H7 subtype avian influenza viruses, such as H7N2, H7N3, H7N4, H7N7, and H7N9, were documented being capable of infecting humans, and the H7 subtype low pathogenic avian influenza viruses are capable of mutating into highly pathogenic avian influenza; therefore, they pose a serious threat to public health. Here, we investigated the evolutionary history, molecular characteristics, and pathogenicity of shorebird-origin influenza A(H7N4) viruses, showing a similar evolutionary trajectory with Jiangsu human A(H7N4) viruses in HA and NA genes. Moreover, our isolates exhibited variable virulence (including moderate virulence) in mice, suggesting a potential risk to other mammalian species, including humans.

10.
Brain Res Bull ; 177: 340-351, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34717966

RESUMO

Damage to the blood-brain barrier (BBB) is an important factor leading to intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Krüppel-like transcription factor 2 (KLF2) plays an important role in the maintenance of the BBB. This study aims to detect the changes of KLF2 after ICH and evaluate the potential effects of fraxinellone on ICH-induced SBI and its correlation with KLF2. An ICH model was established by injecting autologous blood into the right basal ganglia of Sprague-Dawley (SD) rats. First, after ICH induction, the protein levels of KLF2 were reduced. Then, we found that the decrease of KLF2 protein levels induced by ICH could be effectively reversed with the treatment of fraxinellone in vascular endothelial cells. Furthermore, fraxinellone treatment effectively alleviated brain edema, decreased the levels of TNF-α and IL-1ß, and improved neuronal cell degeneration induced by ICH. Meanwhile, fraxinellone ameliorated neurobehavioral disorders, motor and sensory impairments, and neurobehavioral disorders and memory loss caused by ICH. Collectively, these findings reveal that KLF2 may be a potential target for fraxinellone to exert neuroprotective effects after ICH, and fraxinellone could be a potential therapeutic agent for SBI after ICH.

11.
BMC Infect Dis ; 21(1): 1025, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592958

RESUMO

BACKGROUND: The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. METHODS: Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People's Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-ß1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. RESULTS: The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-ß1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-ß1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). CONCLUSIONS: Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-ß1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.


Assuntos
Brucelose , Linfócitos T Reguladores , Citocinas , Fatores de Transcrição Forkhead , Humanos , Proteínas de Checkpoint Imunológico , Leucócitos Mononucleares
13.
Front Microbiol ; 12: 712081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707577

RESUMO

COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut-lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman's correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34300142

RESUMO

In the urban drainage system, the formation of sewer sediments is inevitable, and the removal of sewer sediments is necessary for system maintenance. Disposal of arisings from sewer sediment removal is becoming a serious environmental issue. The current knowledge of sewer sediments is limited, which is restrained to sewer sediments management. To better understand this municipal waste, the sewer sediments of a combined sewer system in Longgang District, Shenzhen were collected and characterized, and the spatial distribution characteristics of contaminants were analyzed. Based on the bivariate correlation analysis, it is found that many contaminants in sewer sediments have a strong relationship with spatial variables. Compared to the sewer sediments in industrial areas, those in residential areas contain higher concentrations of Hg and phosphorus. The sediments in the sewage conduit also contain more organic matter (OM), phosphorus, Cu, and Ni, and the sediments in the rainwater conduit contain a higher concentration of Cd. Moreover, the sediments produced in different catchments also show huge differences in the content of contaminants. These spatial distribution characteristics may provide help for the further classification of sewer sediments, thereby making the disposal of sediments more targeted. According to the local standards of sludge disposal, land application and incineration are not suitable for managing sewer sediments due to the low OM content and poor lower heating value (LHV). Although sanitary landfill is feasible for sewer sediments disposal, the complicated composition of sewer sediments still poses the risk of polluting the surrounding environment. The management of sewer sediments via the production of building materials is a promising technical route that can avoid the migration of hazardous contaminants and produce valuable products. This study may improve our understanding of sewer sediments and provide a reliable recommendation for sewer sediment management.


Assuntos
Sedimentos Geológicos , Esgotos , Fósforo
15.
Mol Neurobiol ; 58(10): 4999-5013, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34232477

RESUMO

Mitochondrial damage has been reported to be a critical factor for secondary brain injury (SBI) induced by intracerebral hemorrhage (ICH). MIC60 is a key element of the mitochondrial contact site and cristae junction organizing system (MICOS), which takes a principal part in maintaining mitochondrial structure and function. The role of MIC60 and its underlying mechanisms in ICH-induced SBI are not clear, which will be investigated in this present study. To establish and emulate ICH model in vivo and in vitro, autologous blood was injected into the right basal ganglia of Sprague-Dawley (SD) rats; and primary-cultured cortical neurons were treated by oxygen hemoglobin (OxyHb). First, after ICH induction, mitochondria were damaged and exhibited mitochondrial crista-structure remodeling, and MIC60 protein levels were reduced. Furthermore, MIC60 overexpression reduced ICH-induced neuronal death both in vivo and in vitro. In addition, MIC60 upregulation reduced ICH-induced cerebral edema, neurobehavioral impairment, and cognitive dysfunction; by contrast, MIC60 knockdown had the opposite effect. Additionally, in primary-cultured neurons, MIC60 overexpression could reverse ICH-induced neuronal cell death and apoptosis, mitochondrial membrane potential collapse, and decrease of mitophagy, indicating that MIC60 overexpression can maintain the integrity of mitochondrial structures. Moreover, loss of MIC60 is after ICH-induced reduction in PINK1 levels and mislocalization of Parkin in primary-cultured neurons. Taken together, our findings suggest that MIC60 plays an important role in ICH-induced SBI and may represent a promising target for ICH therapy.

16.
ACS Appl Mater Interfaces ; 13(31): 37299-37307, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34324293

RESUMO

A copper (Cu) material is catalytically active for formaldehyde (HCHO) dehydrogenation to produce H2, but the unsatisfactory efficiency and easy corrosion hinder its practical application. Alloying with other metals and coating a carbon layer outside are recognized as effective strategies to improve the catalytic activity and the long-term durability of nonprecious metal catalysts. Here, highly dispersed CuNi alloy-carbon layer core-shell nanoparticles (CuNi@C) have been developed as a robust catalyst for efficient H2 generation from HCHO aqueous solution at room temperature. Under the optimized reaction conditions, the CuNi@C catalyst exhibits a H2 evolution rate of 110.98 mmol·h-1·g-1, which is 1.5 and 4.9 times higher than those of Cu@C and Ni@C, respectively, which ranks top among the reported nonprecious metal catalysts for catalytic HCHO reforming at room temperature to date. Furthermore, CuNi@C also displays excellent stability toward the catalytic HCHO reforming into H2 in tap water owing to the well-constructed carbon sheath protecting CuNi nanocrystals from oxidation in an alkaline medium. Combined with density functional theory calculations, the superior catalytic efficiency of CuNi@C for H2 generation results from the synergistic contribution between the massive active species from HCHO decomposition on the Cu sites and the remarkable H2 evolution activity on Ni sites. The improved performance of CuNi@C highlights the enormous potential of advancing noble-metal-free nanoalloys as cost-effective and recyclable catalysts for energy recovery from industrial HCHO wastewater.

18.
Nat Metab ; 3(7): 909-922, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34158670

RESUMO

Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane1. Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes2,3, investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19.


Assuntos
COVID-19/metabolismo , COVID-19/virologia , Vesículas Extracelulares/metabolismo , Lipidômica , Metabolômica , SARS-CoV-2 , Transporte Biológico , COVID-19/epidemiologia , Fracionamento Celular , Membrana Celular/metabolismo , Fracionamento Químico , Análise por Conglomerados , Biologia Computacional/métodos , Exossomos/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Lipidômica/métodos , Metaboloma , Metabolômica/métodos , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/imunologia
19.
J Exp Biol ; 224(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34018551

RESUMO

Ghost crabs are the fastest and most aerobically fit of the land crabs. The exceptional locomotory capacity of these invertebrate athletes seemingly depends upon effective coupling between the cardiovascular system and skeletal muscles, but how these systems are integrated has not been well defined. In the present study, we investigated the relationship between aerobic muscle fibers within the skeletal muscles used to power running and the blood vessels supplying these muscles. We used histochemical staining techniques to identify aerobic versus glycolytic fibers and to characterize membrane invaginations within the aerobic fibers. We also determined how the diameters of these two fiber types scale as a function of body size, across two orders of magnitude. Vascular casts were made of the blood vessels perfusing these muscles, and special attention was given to small, capillary-like vessels supplying the fibers. Finally, we injected fluorescent microspheres into the hearts of living crabs and tracked their deposition into different muscle regions to quantify relative hemolymph flow to metabolic fiber types. Collectively, these analyses demonstrate that ghost crab muscles are endowed with an extensive arterial hemolymph supply. Moreover, the hemolymph flow to aerobic fibers is significantly greater than to glycolytic fibers within the same muscles. Aerobic fibers are increasingly subdivided by membrane invaginations as crabs increase in size, keeping the diffusive distances relatively constant. These findings support a functional coupling between a well-developed circulatory system and metabolically active muscle fibers in these invertebrates.


Assuntos
Braquiúros , Animais , Artérias , Hemolinfa , Humanos , Fibras Musculares Esqueléticas , Músculo Esquelético
20.
Sci China Life Sci ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33945069

RESUMO

Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase activity. However, detailed mechanism underlying LATS1 stability and activation remains elusive. Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4. Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation. Mechanistically, LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation, leading to increased YAP nucleus translocation and promoted target gene expression. Functionally, LATS1-K751Q, the acetylation mimic mutant potentiated lung cancer cell migration, invasion and tumor growth, whereas LATS1-K751R, the acetylation deficient mutant inhibited these functions. Taken together, we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1.

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