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1.
Biochem Pharmacol ; 202: 115107, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35643339

RESUMO

Osteoarthritis (OA) is a common and debilitating chronic joint disease, which is characterized by degeneration of articular cartilage and the aging of chondrocytes. Acid-sensitive ion channel 1a (ASIC1a) is a proton-activated cationic channel abundant in chondrocytes, which senses and regulates joint cavity pH. Our previous study demonstrated that ASIC1a was involved in acid-induced rat articular chondrocyte senescence, but the mechanistic basis remained unclear. In this study, we explored the mechanism of ASIC1a in chondrocyte senescence and OA. The results showed that senescence-related-ß-galactosidase, senescence-related markers (p53 and p21) and the autophagy-related protein Beclin-1 were found to be increased, but Lamin B1 was found to be reduced with acid (pH 6.0) treatment. These effects were inhibited by ASIC1a-specific blocker psalmotoxin-1 or ASIC1a-short hairpin RNA respectively in chondrocytes. Moreover, Silencing of Lamin B1 enhanced ASIC1a-mediated chondrocyte senescence, this effect was reversed by overexpression of Lamin B1, indicating that Lamin B1 was involved in ASIC1a-mediated chondrocyte senescence. Further, blockade of ASIC1a inhibits acid-induced autophagosomes and Beclin-1 protein expression, suggesting that ASIC1a is involved in acid-induced chondrocyte autophagy. Blocking autophagy with chloroquine inhibited Beclin-1 and increased Lamin B1 in acid-induced chondrocyte senescence. We further demonstrated that ASIC1a-mediated reduction of Lamin B1 expression was caused by autophagy pathway-dependent protein degradation. Finally, blocking ASIC1a protected cartilage tissue, restored Lamin B1 levels and inhibited chondrocyte senescence in a rat OA model. In summary, these findings suggest that ASIC1a may promote Lamin B1 degradation to mediate osteoarthritis chondrocyte senescence through the autophagy pathway.

2.
Sci Total Environ ; : 156822, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35738372

RESUMO

Conservation agriculture (CA) can be an important strategy for improving soil organic carbon (SOC) and total nitrogen (TN). Numerous studies have examined SOC and TN dynamics in different cropping systems. However, there is some uncertainty regarding the relative impacts of some CA practices, and it is not always clear how other agricultural management, particularly nitrogen addition, interacts with these practices to influence SOC and TN sequestration. Thus, we conducted a global meta-analysis of 752 comparisons from 97 papers to analyze the impacts of nitrogen fertilizers and CA practices (namely crop diversification, minimal soil disturbance (no-tillage) and permanent soil cover), on SOC and TN content worldwide. Overall, our study showed the most significant increase of SOC [21.39 % (CI = 15.16 to 28.64)] and TN [54.34 % (CI = 26.19 to 96.69)] stock with CA practices compared to conventional practices in the 0-15 cm soil depth. It also showed a significant increase in SOC and TN stock with all the individual components of CA compared to conventional practices in the 0-15 cm soil depth. However, the impact of CA on SOC and TN is reduced in 0-60 cm depths compared to surface soil depths due to the limited input of crop residue deeper in the soil profile. Manure and manure mixed with mineral-N led to greater SOC sequestration [20.67 % (CI = 15.23 to 27.10) and 41.67 % (CI = 31.03 to 52.79), respectively] than mineral-N alone [9.08 % (CI = 6.44 to 11.83)]. Cropping systems that included legume residue decreased the C/N ratio. This highlights that adequate mineral-N fertilizer addition may also be required in conjunction with residue retention practices to improve SOC and TN content. Overall, these results show that CA systems that include legume residue and manure mixed with mineral-N have great potential to increase SOC and TN, particularly at 0-15 cm and 0-30 cm soil depth.

3.
Nanoscale ; 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35713601

RESUMO

Photoactivated chemotherapy has attracted widespread attention due to its ability to circumvent the shortcomings of hypoxia in tumor tissues compared with traditional photodynamic therapy. In this work, novel multifunctional nanoplatform (1), Ru-inhibitor@TPPMnCO@N-GQDs, was designed and prepared, which was capable of mitochondria-targeted co-delivery of the cysteine protease inhibitor and carbon monoxide (CO) stimulated with an 808 nm near infrared (NIR) laser. Nanoplatform (1) was prepared by covalent attachment of a mitochondria-targeted CO donor (TPPMnCO) and a Ru(II)-caged cysteine protease inhibitor (Ru-inhibitor) on the surface of fluorescent N-doped graphene quantum dots (N-GQDs). Nanoplatform (1) preferentially accumulated in the mitochondria of cancer cells and instantly delivered CO and the cysteine protease inhibitor upon 808 nm NIR light irradiation, thus damaging mitochondria and leading to significant in vitro and in vivo anticancer efficacy. In addition, nanoplatform (1) has good biocompatibility and did not exert any toxic side effects on mice during the period of treatment. The targeted subcellular mitochondrial co-delivery of CO and the cysteine protease inhibitor may provide new insights into CO and enzyme inhibitor combined therapies for cancer treatment.

4.
5.
Food Chem ; 387: 132924, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429932

RESUMO

To improve the water solubility, stability and bioavailability of quercetin, the quercetin (Que)-quinoa protein (QP)-lotus root amylopectin (LRA) nanomicelles (Que-QP-LRA) were constructed via self-assembly in the present study. Results showed that a uniform and stable Que-QP-LRA nanomicelles was formed when the mass ratio of Que/QP/LRA was 2.5:6:24. Under this condition, the particle size, polydispersity index and zeta potential of the nanomicelles were 157.3 nm, 0.289 and -16.7 mV, respectively. Transmission electron microscopy exhibited that the Que-QP-LRA nanomicelles have a core-shell structure. The analysis of molecular interaction indicated that hydrogen bonding and hydrophobic interaction were the main driving forces to maintain stable structure of Que-QP-LRA nanomicelles. Additionally, the in vitro simulated digestion experiments suggested that Que-QP-LRA nanomicelles can enhance the stability of quercetin in the stomach and enable it to be sustained release in the intestine. These results suggested that Que-QP-LRA nanomicelles were beneficial for improving the bioavailability of quercetin.


Assuntos
Chenopodium quinoa , Quercetina , Amilopectina/química , Disponibilidade Biológica , Micelas , Tamanho da Partícula , Quercetina/química , Solubilidade
6.
Sci Total Environ ; 819: 153089, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35038532

RESUMO

With increasing attention being placed on mitigating global warming and achieving agricultural sustainable intensification, conservation agriculture practices have gradually been implemented in the North China Plain (NCP). However, there are still knowledge gaps on the effects of conservation practices on greenhouse gas (GHG) emissions in this area. In this study, a four-year field experiment was conducted from 2014 to 2018 to assess the effects of tillage and crop residue management practices on the emissions of nitrous oxide (N2O) and methane (CH4). Subsequently, crop yields, area-scaled and yield-scaled total non-carbon dioxide (CO2) GHG emissions were assessed. Our research found that no-till (NT) decreased N2O emissions by 22.6% compared with conventional tillage (CT) in winter wheat (Triticum aestivum L.) seasons, but there was no difference between tillage practices in summer maize (Zea mays L.) seasons. Crop residue retention practice (+R) increased N2O emissions by 28.1% and 26.7% compared with residue removal practice (-R) in winter wheat and summer maize seasons, respectively. The NT soils took up more CH4 compared with the CT soils in summer maize seasons. Area-scaled total non-CO2 GHG emissions showed trends similar to those of N2O emission. Since crop residue retention improved the maize yield compared with the residue removal treatments, yield-scaled total non-CO2 GHGs emission did not differ between residue management practices in summer maize seasons. Our four-year field measurements indicated that no-till practice could be more useful as an option to mitigate non-CO2 GHG emissions in the wheat - maize cropping system.


Assuntos
Gases de Efeito Estufa , Agricultura , China , Fertilizantes/análise , Óxido Nitroso/análise , Solo , Triticum , Zea mays
7.
Free Radic Biol Med ; 178: 111-124, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863875

RESUMO

Inflammation has recently emerged as an important contributor for cardiovascular disease development and participates pivotally in the development of neointimal hyperplasia and abdominal aortic aneurysms (AAA) formation. Kv7.4/KCNQ4, a K+ channel, is one of the important regulators of vascular function but its role in vascular inflammation is unexplored. Here, we showed that the expression of Kv7.4 channel was elevated in the neointima and AAA tissues from mice and humans. Genetic deletion or pharmacological inhibition of Kv7.4 channel in mice alleviated neointimal hyperplasia and AAA formation via downregulation of a set of vascular inflammation-related genes, matrix metalloproteinases (MMP) 2/9, and intercellular adhesion molecule (ICAM-1). Furthermore, genetic deletion or inhibition of Kv7.4 channel suppressed the activation of tumor necrosis factor receptor 1 (TNFR1)-nuclear factor (NF)-κB signaling pathway via blockade of interaction between TNFR1 and TNFR1-associated death domain protein (TRADD) in vascular smooth muscle cells (VSMCs). Knockdown of Kv7.4 in vivo identified VSMC-expressed Kv7.4 as a major factor in vascular inflammation. Collectively, our findings suggest that Kv7.4 channel aggravates vascular inflammatory response, which promotes the neointimal hyperplasia and AAA formation. Inhibition of Kv7.4 channel may be a novel therapeutic strategy for vascular inflammatory diseases.


Assuntos
Aneurisma da Aorta Abdominal , Neointima , Animais , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/patologia , Movimento Celular , Proliferação de Células , Células Cultivadas , Hiperplasia/patologia , Inflamação/genética , Inflamação/patologia , Camundongos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Neointima/patologia , Remodelação Vascular
8.
Glob Chang Biol ; 28(3): 693-710, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726342

RESUMO

Mechanisms of soil organic carbon (SOC) stabilization have been widely studied due to their relevance in the global carbon cycle. No-till (NT) has been frequently adopted to sequester SOC; however, limited information is available regarding whether sequestered SOC will be stabilized for long term. Thus, we reviewed the mechanisms affecting SOC stability in NT systems, including the priming effects (PE), molecular structure of SOC, aggregate protection, association with soil minerals, microbial properties, and environmental effects. Although a more steady-state molecular structure of SOC is observed in NT compared with conventional tillage (CT), SOC stability may depend more on physical and chemical protection. On average, NT improves macro-aggregation by 32.7%, and lowers SOC mineralization in macro-aggregates compared with CT. Chemical protection is also important due to the direct adsorption of organic molecules and the enhancement of aggregation by soil minerals. Higher microbial activity in NT could also produce binding agents to promote aggregation and the formation of metal-oxidant organic complexes. Thus, microbial residues could be stabilized in soils over the long term through their attachment to mineral surfaces and entrapment of aggregates under NT. On average, NT reduces SOC mineralization by 18.8% and PE intensities after fresh carbon inputs by 21.0% compared with CT (p < .05). Although higher temperature sensitivity (Q10 ) is observed in NT due to greater Q10 in macro-aggregates, an increase of soil moisture regime in NT could potentially constrain the improvement of Q10 . This review improves process-based understanding of the physical and chemical mechanism of protection that can act, independently or interactively, to enhance SOC preservation. It is concluded that SOC sequestered in NT systems is likely to be stabilized over the long term.


Assuntos
Carbono , Solo , Carbono/metabolismo , Ciclo do Carbono , Solo/química , Temperatura
9.
J Inorg Biochem ; 226: 111656, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34798307

RESUMO

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.


Assuntos
Monóxido de Carbono , Sistemas de Liberação de Medicamentos , Inibidores de Histona Desacetilases , Raios Infravermelhos , Mitocôndrias/metabolismo , Neoplasias , Fototerapia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Monóxido de Carbono/farmacocinética , Monóxido de Carbono/farmacologia , Células HeLa , Inibidores de Histona Desacetilases/farmacocinética , Inibidores de Histona Desacetilases/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
10.
Glob Chang Biol ; 28(1): 154-166, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34651373

RESUMO

No-till (NT) is a sustainable option because of its benefits in controlling erosion, saving labor, and mitigating climate change. However, a comprehensive assessment of soil pH response to NT is still lacking. Thus, a global meta-analysis was conducted to determine the effects of NT on soil pH and to identify the influential factors and possible consequences based on the analysis of 114 publications. When comparing tillage practices, the results indicated an overall significant decrease by 1.33 ± 0.28% in soil pH under NT than that under conventional tillage (p < .05). Soil texture, NT duration, mean annual temperature (MAT), and initial soil pH are the critical factors affecting soil pH under NT. Specifically, with significant variations among subgroups, when compared to conventional tillage, the soil under NT had lower relative changes in soil pH observed on clay loam soil (-2.44%), long-term implementation (-2.11% for more than 15 years), medium MAT (-1.87% in the range of 8-16℃), neutral soil pH (-2.28% for 6.5 < initial soil pH < 7.5), mean annual precipitation (-1.95% in the range of 600-1200 mm), in topsoil layers (-2.03% for 0-20 cm), with crop rotation (-1.98%), N fertilizer input (the same for NT and conventional tillage) of 100-200 kg N ha-1 (-1.83%), or crop residue retention (-1.52%). Changes in organic matter decomposition under undisturbed soil and with crop residue retention might lead to a higher concentration of H+ and lower of basic cations (i.e., calcium, magnesium, and potassium), which decrease the soil pH, and consequently, impact nutrient dynamics (i.e., soil phosphorus) in the surface layer under NT. Furthermore, soil acidification may be aggravated by NT within site-specific conditions and improper fertilizer and crop residue management and consequently leading to adverse effects on soil nutrient availability. Thus, there is a need to identify strategies to ameliorate soil acidification under NT to minimize the adverse consequences.


Assuntos
Agricultura , Solo , Mudança Climática , Fertilizantes , Concentração de Íons de Hidrogênio
11.
Sci Total Environ ; 806(Pt 4): 150962, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656593

RESUMO

The sensitivity of soil organic carbon (SOC) mineralization to temperature could affect the future atmospheric CO2 levels under global warming. Sieved soils are widely used to assess SOC mineralization and its temperature sensitivity (Q10) via laboratory incubation. However, sieved soils cause a temporary increase in mineralization due to the destruction of soil structure, which can affect estimates of SOC mineralization, especially in soils managed with no-till (NT). To identify the effects of soil sieving on SOC mineralization and Q10, soil was collected from an 11-year field experiment under a wheat-maize cropping system managed with a combination of tillage [NT and plow tillage (PT)] and residue [residue returning (RR) and residue removal (R0)]. Soil was either sieved or left in an undisturbed state and incubated at 15 °C and 25 °C. SOC mineralization in sieved soils at 25 °C was 47.28 g C kg-1 SOC, 160.1% higher than SOC mineralization in undisturbed soils (P < 0.05). Interestingly, Q10 values in sieved soils were 1.29, 77.6% lower than Q10 in undisturbed soils (P < 0.05). Highly significant correlations (P < 0.01) were observed between sieved and undisturbed soils for SOC mineralization (r = 0.85-0.98) and Q10 (r = 0.78-0.87). Soil macro-aggregates had lower SOC mineralization by 6.1-21.9%, but higher Q10 values by 4.7-6.5% compared with micro-aggregates, contributing to lower mineralization and higher Q10 under NT and RR. Furthermore, structure equation and random forest modelling showed that increased SOC contents in NT and RR could not only reduce SOC mineralization, but also constrained the improvement of Q10 in NT and RR. Overall, these results indicated that although sieved soils overestimated SOC mineralization and underestimated Q10 due to the destruction of macro-aggregates, the patterns between treatments were similar and sieving soil for incubation is considered as a suitable approach to evaluate the relative impacts of NT and RR on SOC mineralization and Q10.


Assuntos
Carbono , Solo , Microbiologia do Solo , Temperatura , Triticum
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 839-843, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622602

RESUMO

OBJECTIVE: To compare the clinical manifestations of pertussis in children of different ages and different immunization statuses in Wenzhou, and to explore the limitations of diagnostic criteria for pertussis. METHODS: The clinical data of 288 children diagnosed with pertussis at Yuying Children's Hospital & the Second Affiliated Hospital of Wenzhou Medical University from October 2017 to December 2019 were retrospectively analyzed. The clinical characteristics of children of different ages and different immunization statuses were analyzed. Their clinical data were compared to relevant diagnostic criteria of pertussis in children of different ages according to the Recommendations for Diagnosis and Treatment of Chinese Children with Pertussis and the diagnosis conformity rate was analyzed. RESULTS: Among the 288 children, 124 cases (43.06%) were 3 months old or younger, and 164 cases (288, 56.94%) were >3 months old. Among patients≤3 months of age, cyanosis, three-depression sign, face redness, dyspnea and peripheral blood lymphocyte ratio were significantly higher than those of patients >3 months of age. They also had higher incidence of pneumonia, higher proportion of developing severe pertussis, and longer stay at the hospital. All these findings showed statistically significant difference ( P<0.05). 83 children were fully immunized (receiving the full course of vaccination), and 205 were not fully immunized (not receiving the full course of vaccination or being unvaccinated). The proportion of children presenting cyanosis, shortness of breath, three depression sign and face redness in the incomplete immunization group was higher than that in the complete immunization group. In the incomplete immunization group, the proportion of lymphocytes was higher, the level of C-reactive protein (CRP) was lower, and the length of hospitalization was longer than those of the complete immunization group. All the differences were statistically significant ( P<0.05). Among patients aged ≤3 months, the conformity rate of diagnosis (112/114, 90.32%) upon admission was higher than that among patients aged >3 months (119/164, 72.56%). Among patients aged ≤3 months, 41.94% (52/124, while 54.03% (67/124) of the patients aged ≤3 months had WBC count <20×10 9 L -1. CONCLUSION: Pertussis in children ≤3 months of age in Wenzhou City were more serious, showing higher rate of diagnosis conforming to the recommended clinical diagnostic criteria than that in children >3 months old. The WBC threshold in routine blood test of ≤3 months old could be lowered appropriately and the current diagnostic criteria still needed improvement.


Assuntos
Coqueluche , Criança , Pré-Escolar , Hospitalização , Humanos , Incidência , Lactente , Estudos Retrospectivos , Vacinação , Coqueluche/diagnóstico , Coqueluche/epidemiologia
14.
Sci Total Environ ; 798: 149220, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34315054

RESUMO

Continuous single tillage has the potential to increase greenhouse gas (GHG) emissions and decrease the accumulation of soil organic carbon (SOC), thus increasing carbon footprints (CFs). However, in a wheat-maize cropping system, limited information was available about the effects of strategic tillage on CFs. Thus, a four-year field experiment was conducted, including continuous rotary tillage (RT), continuous no-till (NT), RT + subsoiling (RS), and NT + subsoiling (NS), to investigate the effects of NS (strategic tillage) on the unit area and unit yield. The results showed that CO2 emission was the highest contributor to CFs (73.92%) in a winter wheat-summer maize cropping system, following the order of NS < NT < RS < RT. The direct N2O emissions from fertilizers and residues were 4.43-4.51 t CO2-eq ha-1 yr-1 during the wheat and maize seasons, and indirect N2O emissions from irrigation and fertilizer inputs had a proportion of >80% from total agricultural inputs. The differences in SOC storage significantly affected the CFs. Although the NS treatment increased the amount of GHG emissions from the residues returned and consumption of diesel, the enhancement of SOC storage by deeper SOC increased. Thus, lower area-scaled CFs were observed in the NS treatment. Furthermore, a higher grain yield and an annual change of SOC storage compared with other treatments were observed under the NS system, which helped to reduce the CFs. The yield-scaled CFs followed the order of RT > RS > NT > NS when considering the changes in SOC storage. Therefore, the NS treatment resulted in a higher grain yield and SOC sequestration with lower CFs, and thus, it could be recommended as the best tillage method to achieve sustainable production and environmental balance in a wheat-maize cropping system.


Assuntos
Triticum , Zea mays , Agricultura , Carbono , Pegada de Carbono , China , Óxido Nitroso/análise , Solo
15.
Cell Res ; 31(8): 847-860, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34112954

RESUMO

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.


Assuntos
Antivirais/metabolismo , COVID-19/patologia , Proteínas do Envelope de Coronavírus/metabolismo , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Animais , Antivirais/química , Antivirais/uso terapêutico , Apoptose , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/virologia , Proteínas do Envelope de Coronavírus/antagonistas & inibidores , Proteínas do Envelope de Coronavírus/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Meia-Vida , Humanos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Baço/metabolismo , Baço/patologia , Carga Viral , Virulência
16.
J Mater Chem B ; 9(20): 4241-4248, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34008693

RESUMO

A multifunctional nanoplatform (1), MnCO@TPP@C-TiO2, which consists of a carrier of carbon-doped TiO2 nanoparticles with surface covalent functionalization of manganese carbonyls and a directing group of triphenylphosphine, was prepared for mitochondria-targeted carbon monoxide (CO) delivery combined with photodynamic therapy (PDT). MnCO@TPP@C-TiO2 selectively localized in the mitochondria of HeLa cells where the overexpressed-H2O2 triggered CO release resulting in mitochondrial damage. And singlet oxygen species generated upon 808 nm near infrared light irradiation further destroyed the mitochondria and induced cancer cells apoptosis. Cytotoxicity assays revealed that the nanoplatform with mitochondria-targeted CO delivery and PDT exhibited the highest lethality against cancer cells in comparison with all the other control samples tested, and it showed good dark biocompatibility with normal cells that express low H2O2 levels. This work may provide new insights into combining CO-based gas therapy with traditional PDT for efficient cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Monóxido de Carbono/química , Complexos de Coordenação/farmacologia , Sistemas de Liberação de Medicamentos , Mitocôndrias/efeitos dos fármacos , Fotoquimioterapia , Oxigênio Singlete/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Raios Infravermelhos , Mitocôndrias/metabolismo , Estrutura Molecular , Tamanho da Partícula , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Células Tumorais Cultivadas
17.
Transl Pediatr ; 10(3): 673-678, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33880337

RESUMO

Pseudomembranous laryngotracheobronchitis is rarely reported yet potentially life-threatening infectious cause of airway obstruction in children. The causative organisms of this condition are often considered to promote bacterial superinfection following viral infection. We report a case of pseudomembranous laryngotracheobronchitis in a patient caused by human bocavirus 1 and Mycoplasma pneumoniae (M. pneumoniae). A 2-year-old child was admitted to our hospital presenting with cough, hoarseness, and labored breathing. Computed tomography of the chest revealed atelectasis of the right middle lobe of the lung with bronchostenosis and occlusion. Laryngeal edema, pseudomembrane formation and ulceration of the trachea were found during bronchoscopy. Chronic inflammation of the mucosa and local cellulose exudation with acute and chronic inflammatory cell infiltration were confirmed by hematoxylin-eosin staining. Human bocavirus 1 and M. pneumoniae were detected in the bronchoalveolar lavage fluid by next-generation sequencing. The patient tested positive for IgM antibodies against M. pneumoniae. Bronchoscopy was performed three times to clear the secretions in the airway, and azithromycin, ceftriaxone, methylprednisolone, budesonide inhalation, and ambroxol were administered as treatment. The patient's condition improved and she was discharged 21 days after admission. Clinicians should be aware of the potential involvement of human bocavirus 1 and M. pneumoniae in pseudomembranous laryngotracheobronchitis for accurate diagnosis and timely antibiotic administration, and to lower mortality and morbidity rates.

18.
J Environ Manage ; 289: 112486, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831757

RESUMO

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.


Assuntos
Gases de Efeito Estufa , Oryza , Agricultura , China , Produtos Agrícolas , Aquecimento Global , Efeito Estufa , Gases de Efeito Estufa/análise , Humanos , Metano/análise , Óxido Nitroso/análise , Solo
19.
Science ; 371(6536): 1374-1378, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33602867

RESUMO

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Animais , Antivirais/química , Antivirais/uso terapêutico , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL10/metabolismo , Modelos Animais de Doenças , Desenho de Fármacos , Humanos , Interferon beta/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Oligopeptídeos , Prolina/análogos & derivados , Inibidores de Proteases/química , Inibidores de Proteases/uso terapêutico , Inibidores de Proteases/toxicidade , Ratos , Ratos Sprague-Dawley , Carga Viral/efeitos dos fármacos , Replicação Viral
20.
Mol Ecol Resour ; 21(4): 1243-1255, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33421343

RESUMO

Chinese mahogany (Toona sinensis) is a woody plant that is widely cultivated in China and Malaysia. Toona sinensis is important economically, including as a nutritious food source, as material for traditional Chinese medicine and as a high-quality hardwood. However, the absence of a reference genome has hindered in-depth molecular and evolutionary studies of this plant. In this study, we report a high-quality T. sinensis genome assembly, with scaffolds anchored to 28 chromosomes and a total assembled length of 596 Mb (contig N50 = 1.5 Mb and scaffold N50 = 21.5 Mb). A total of 34,345 genes were predicted in the genome after homology-based and de novo annotation analyses. Evolutionary analysis showed that the genomes of T. sinensis and Populus trichocarpa diverged ~99.1-103.1 million years ago, and the T. sinensis genome underwent a recent genome-wide duplication event at ~7.8 million years and one more ancient whole genome duplication event at ~71.5 million years. These results provide a high-quality chromosome-level reference genome for T. sinensis and confirm its evolutionary position at the genomic level. Such information will offer genomic resources to study the molecular mechanism of terpenoid biosynthesis and the formation of flavour compounds, which will further facilitate its molecular breeding. As the first chromosome-level genome assembled in the family Meliaceae, it will provide unique insights into the evolution of members of the Meliaceae.


Assuntos
Genoma de Planta , Meliaceae , Toona , China , Cromossomos de Plantas , Malásia , Filogenia , Toona/genética
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