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1.
IEEE Trans Cybern ; PP2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533159

RESUMO

Falling down is a serious problem for health and has become one of the major etiologies of accidental death for the elderly living alone. In recent years, many efforts have been paid to fall recognition based on wearable sensors or standard vision sensors. However, the prior methods have the risk of privacy leaks, and almost all these methods are based on video clips, which cannot localize where the falls occurred in long videos. For these reasons, in this article, the bioinspired vision sensor-based falls temporal localization framework is proposed. The bioinspired vision sensors, such as dynamic and active-pixel vision sensor (DAVIS) camera applied in this work responds to pixels' brightness change, and each pixel works independently and asynchronously compared to the standard vision sensors. This property makes it have a very high dynamic range and privacy preserving. First, to better represent event data, compared with the typical constant temporal window mechanism, an adaptive temporal window conversion mechanism is developed. The temporal localization framework follows a proven proposal and classification paradigm. Second, for the high-efficient and recall proposal generation, different from the traditional sliding window scheme, the event temporal density as the actionness score is set and the 1D-watershed algorithm to generate proposals is applied. In addition, we combine the temporal and spatial attention mechanism with our feature extraction network to temporally model the falls. Finally, to evaluate the performance of our framework, 30 volunteers are recruited to join the simulated fall experiments. According to the results of experiments, our framework can realize precise falls temporal localization and achieve the state-of-the-art performance.

2.
J Environ Manage ; 315: 115147, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35490485

RESUMO

Large quantities of landfill sludge (LS) with higher water content (WC) were stored underground, and excavation and re-dewatering of LS is a sustainable and economic strategy to save landfill space and reduce the leaching of contaminants. In this study, polyferric silicate sulfate (PFSS) was first applied in the conditioning of excavated LS, and the effects of the Si/Fe mass ratio and PFSS dosage on physicochemical properties, dewaterability and rheological properties were investigated. At the best Si/Fe of 0.18, PFSS conditioning obtained compact aggregates with the strongest internal structure, thus achieving the lowest WC. Large sludge flocs were formed, and slime and loosely-bound extracellular polymeric substances were effectively removed with the PFSS dosage above 100 mg/g dried solids, which made the WC to be lower than 51.4%. The whole mechanical compression process of conditioned LS can be described by the modified Terzaghi-Voigt model, and increasing the PFSS dosage induced the release of bound water and migration of the consolidation stage from ternary to secondary. PFSS is an economically sustainable conditioner for LS, integrating multiple functions such as charge neutralization, particle aggregation, interparticle bridging and skeleton building in one chemical.


Assuntos
Esgotos , Instalações de Eliminação de Resíduos , Esgotos/química , Silicatos , Sulfatos , Eliminação de Resíduos Líquidos , Água/química
3.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2491-2499, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35531696

RESUMO

The present study investigated the therapeutic effect and mechanism of Di'ao Xinxuekang(DXXK) on non-alcoholic steatohepatitis(NASH) in mice. Sixty-five C57 BL/6 J mice were randomly divided into a normal group and an experimental group for model induction with the high-fat diet for 16 weeks. Then the mice in the experimental group were randomly divided into a model group, an atorvastatin group(4 mg·kg~(-1)·d~(-1)), and high-(200 mg·kg~(-1)·d~(-1)), medium-(60 mg·kg~(-1)·d~(-1)), and low-dose(20 mg·kg~(-1)·d~(-1)) DXXK groups, with 10 mice in each group. Drugs were administered by gavage for eight weeks. Serum lipid, liver lipid, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione reductase(GSH-Px) were determined. Interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). The liver index was calculated. The liver pathological change and lipid accumulation were observed by HE and oil red O staining. The liver ultrastructure was observed by the transmission electron microscope. The mRNA and protein expression of nuclear factor-erythroid 2 related factor 2(Nrf2) and heme oxygenase-1(HO-1) was detected by real-time fluorescence-based quantitative PCR and Western blot, respectively. The results showed that compared with the normal group, the model group displayed serum lipid and liver lipid metabolism disorders, elevated transaminase, lipid deposition, steatosis, and inflammation, suggesting that the NASH model in mice was properly induced. Compared with the model group, the DXXK groups showed decreased serum lipid, liver lipid, ALT, AST, MDA, IL-1ß, and TNF-α, increased SOD and GSH-Px, alleviated hepatic steatosis, ballooning, and inflammation, and up-regulated Nrf2 and HO-1 gene and protein expression. In conclusion, DXXK can significantly alleviate NASH in mice, which is related to the inhibition of oxidative stress and inflammatory damage by up-regulating the Nrf2/HO-1 signaling pathway.


Assuntos
Fator 2 Relacionado a NF-E2 , Hepatopatia Gordurosa não Alcoólica , Animais , Medicamentos de Ervas Chinesas , Inflamação/metabolismo , Lipídeos , Fígado , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Brief Bioinform ; 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35511110

RESUMO

BACKGROUND: The long reads of the third-generation sequencing significantly benefit the quality of the de novo genome assembly. However, its relatively high single-base error rate has been criticized. Currently, sequencing accuracy and throughput continue to improve, and many advanced tools are constantly emerging. PacBio HiFi sequencing and Oxford Nanopore Technologies (ONT) PromethION are two up-to-date platforms with low error rates and ultralong high-throughput reads. Therefore, it is urgently needed to select the appropriate sequencing platforms, depths and genome assembly tools for high-quality genomes in the era of explosive data production. METHODS: We performed 455 (7 assemblers with 4 polishing pipelines or without polishing on 13 subsets with different depths) and 88 (4 assemblers with or without polishing on 11 subsets with different depths) de novo assemblies of Yeast S288C on high-coverage ONT and HiFi datasets, respectively. The assembly quality was evaluated by Quality Assessment Tool (QUAST), Benchmarking Universal Single-Copy Orthologs (BUSCO) and the newly proposed Comprehensive_score (C_score). In addition, we applied four preferable pipelines to assemble the genome of nonreference yeast strains. RESULTS: The assembler plays an essential role in genome construction, especially for low-depth datasets. For ONT datasets, Flye is superior to other tools through C_score evaluation. Polishing by Pilon and Medaka improve accuracy and continuity of the preassemblies, respectively, and their combination pipeline worked well in most quality metrics. For HiFi datasets, Flye and NextDenovo performed better than other tools, and polishing is also necessary. Enough data depth is required for high-quality genome construction by ONT (>80X) and HiFi (>20X) datasets.

6.
Macromol Rapid Commun ; : e2200140, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578395

RESUMO

Providing access to diverse polymer structures is highly desirable, which helps to explore new polymer materials. Poly(thioester sulfonamide)s, combining both the advantages of thioesters and amides, however, have been rarely available in polymer chemistry. Here, we report the ring-opening copolymerization (ROCOP) of cyclic thioanhydride with N-sulfonyl aziridine using mild phosphazene base, resulting in well-defined poly(thioester sulfonamide)s with highly alternative structures, high yields, and controlled molecular weights. Additionally, benefiting from the mild catalytic process, this ROCOP can be combined with ROCOP of N-sulfonyl aziridines with cyclic anhydrides to produce novel block copolymers. This article is protected by copyright. All rights reserved.

7.
Front Psychiatry ; 13: 788677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35546939

RESUMO

Preclinical and clinical studies have suggested that fibroblast growth factor (FGF) system contributed to the onset and development of schizophrenia (SCZ). However, there was no strong clinical evidence to link an individual FGF with SCZ. In this study, we aim to measure blood FGF9 levels in the patients with SCZ with and/or without medication, and test whether FGF9 has a potential to be a biomarker for SCZ. We recruited 130 patients with SCZ and 111 healthy individuals, and the ELISA and qRT-PCR assays were used to measure serum FGF9 levels in the participants. ELISA assay demonstrated that serum FGF9 protein levels were dramatically reduced in first-episode, drug-free patients, but not in chronically medicated patients when compared to healthy control subjects. Further analysis showed that treatment of the first-episode, drug-free SCZ patients with antipsychotics for 8 weeks significantly increased the serum FGF9 levels. In addition, we found that blood FGF9 mRNA levels were significantly lower in first-onset SCZ patients than controls. Under the receiver operating characteristic curve, the optimal cutoff values for FGF9 protein level as an indicator for diagnosis of drug-free SCZ patients was projected to be 166.4 pg/ml, which yielded a sensitivity of 0.955 and specificity of 0.86, and the area under the curve was 0.973 (95% CI, 0.954-0.993). Furthermore, FGF9 had good performance to discriminate between drug-free SCZ patients and chronically medicated patients, the optimal cutoff value for FGF9 concentration was projected to be 165.035 pg/ml with a sensitivity of 0.86 and specificity of 0.919, and the AUC was 0.968 (95% CI, 0.944, 0.991). Taken together, our results for the first time demonstrated the dysregulation of FGF9 in SCZ, and FGF9 has the potential to be served as a biomarker for SCZ.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35570478

RESUMO

BACKGROUND: Kinesio tape (KT) has been in extensive use for the rehabilitation of injuries related to sports, however, only a handful of studies have focused on the efficacy of KT following extraction of a third molar tooth. OBJECTIVE: The study aims to assess whether pain and edema following surgical extraction of the third molar can be reduced by KT. METHOD: This research was carried out following the principles of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Web of Science, Embase, PubMed, The Cochrane Library, CNKI, VIP, and WanFang Data databases were searched for trials published from their inception to eighth October 2021. They included published randomized controlled trials in Chinese or English languages. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database scale. Mean differences (MDs) with 95% confidence intervals (CIs) were used for the analysis of continuous data. The heterogeneity was measured using the I2 statistics. Then, Revman 5.4 software was employed for performing the meta-analysis. RESULTS: Eight studies comprising 453 participants in total were included. In comparison to the no kinesio tape group, KT did not furnish improved results on mouth opening ([MD = 0.36, 95% CI (-0.67, 1.40), p= 0.49]), and swelling ([MD =-1.24, 95% CI (-3.43, 0.95), p= 0.79]). However, KT manifested a reduction in operation time ([MD =-1.00, 95% CI (-1.93, -0.07), P= 0.04]), edema ([MD =-0.53, 95% CI (-0.88, -0.19), P= 0.003]), and pain intensity ([MD =-1.29, 95% CI (-1.86, -0.73), P< 0.00001]), favouring the kinesio tape group. Overall, the size of the effect was found in the small to moderate range. CONCLUSION: Despite the fact that KT can reduce pain and has been shown to have positive effects in several studies, there is no convincing evidence that it can reduce the swelling after surgical extraction of the third molar.

9.
Appl Environ Microbiol ; 88(9): e0239821, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35465724

RESUMO

Zymomonas mobilis metabolizes sugar anaerobically through the Entner-Doudoroff pathway with less ATP generated for lower biomass accumulation to direct more sugar for product formation with improved yield, making it a suitable host to be engineered as microbial cell factories for producing bulk commodities with major costs from feedstock consumption. Self-flocculation of the bacterial cells presents many advantages, such as enhanced tolerance to environmental stresses, a prerequisite for achieving high product titers by using concentrated substrates. ZM401, a self-flocculating mutant developed from ZM4, the unicellular model strain of Z. mobilis, was employed in this work to explore the molecular mechanism underlying this self-flocculating phenotype. Comparative studies between ZM401 and ZM4 indicate that a frameshift caused by a single nucleotide deletion in the poly-T tract of ZMO1082 fused the putative gene with the open reading frame of ZMO1083, encoding the catalytic subunit BcsA of the bacterial cellulose synthase to catalyze cellulose biosynthesis. Furthermore, the single nucleotide polymorphism mutation in the open reading frame of ZMO1055, encoding a bifunctional GGDEF-EAL protein with apparent diguanylate cyclase/phosphodiesterase activities, resulted in the Ala526Val substitution, which consequently compromised in vivo specific phosphodiesterase activity for the degradation of cyclic diguanylic acid, leading to intracellular accumulation of the signaling molecule to activate cellulose biosynthesis. These discoveries are significant for engineering other unicellular strains from Z. mobilis with the self-flocculating phenotype for robust production. IMPORTANCE Stress tolerance is a prerequisite for microbial cell factories to be robust in production, particularly for biorefinery of lignocellulosic biomass to produce biofuels, bioenergy, and bio-based chemicals for sustainable socioeconomic development, since various inhibitors are released during the pretreatment to destroy the recalcitrant lignin-carbohydrate complex for sugar production through enzymatic hydrolysis of the cellulose component, and their detoxification is too costly for producing bulk commodities. Although tolerance to individual stress has been intensively studied, the progress seems less significant since microbial cells are inevitably suffering from multiple stresses simultaneously under production conditions. When self-flocculating, microbial cells are more tolerant to multiple stresses through the general stress response due to enhanced quorum sensing associated with the morphological change for physiological and metabolic advantages. Therefore, elucidation of the molecular mechanism underlying such a self-flocculating phenotype is significant for engineering microbial cells with the unique multicellular morphology through rational design to boost their production performance.


Assuntos
Zymomonas , Celulose/metabolismo , Floculação , Diester Fosfórico Hidrolases/metabolismo , Açúcares/metabolismo , Zymomonas/genética , Zymomonas/metabolismo
10.
Br J Pharmacol ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428974

RESUMO

BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) is a global public health problem and one of the leading causes of all-cause mortality. However, the pathogenic mechanisms and intervention methods for CKD progression are not fully understood. EXPERIMENTAL APPROACH: Plasma from patients with uraemia and from healthy controls (n = 30 per group) was analysed with LC-MS/MS-based non-targeted metabolomics to identify potential markers of uraemia. These potential markers were validated in the same cohort and a second cohort (n = 195) by quantitative analysis of the markers, using LC-MS/MS. The most promising marker was identified by correlation analysis and further validated using HK-2 cells and mouse models. KEY RESULTS: Trimethylamine N-oxide (TMAO) was identified as a promising marker among the 18 potential markers found in the first cohort, and it was optimally correlated with renal function of CKD patients in the second cohort. Treatment of HK-2 cells with TMAO decreased cell viability and up-regulated expression of α-smooth muscle actin. In mice, a TMAO-containing diet decreased kidney mass and increased protein expression of α-smooth muscle actin. Also, control of TMAO production by inhibiting its biosynthetic pathway with 3,3-dimethyl-1-butanol or disrupting gut microbiota function with an antibiotic cocktail, attenuated renal injury in a murine model of CKD. CONCLUSION AND IMPLICATIONS: Our data show that decreased TMAO production could be a new strategy to attenuate the progression of renal injury in CKD.

11.
Chin J Traumatol ; 25(3): 181-183, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35440401

RESUMO

Arthroscopic superior capsular reconstruction is an innovative technique for the irreparable rotator cuff tears, but spontaneous pneumothorax after surgery is very rare. The present case was a 66-year-old female with irreparable rotator cuff tears of the right shoulder, treated with the arthroscopic shoulder superior capsular reconstruction. The general anesthesia and operation went smoothly, but the patient experienced stuffiness in the chest and shortness of breath after recovery from anesthesia. Thoracic CT scans showed spontaneous pneumothorax in the right side, which was successfully treated by the conservative treatments (oxygen therapy) according to multidisciplinary team. Prompt and accurate early-stage diagnosis is necessary in controlling postoperative complications and standardized treatment is the key to relieve the suffering. Spontaneous pneumothorax after arthroscopic shoulder surgery has been rarely reported in previous literatures.


Assuntos
Pneumotórax , Lesões do Manguito Rotador , Articulação do Ombro , Idoso , Artroscopia/efeitos adversos , Artroscopia/métodos , Feminino , Humanos , Pneumotórax/etiologia , Pneumotórax/cirurgia , Amplitude de Movimento Articular , Lesões do Manguito Rotador/cirurgia , Ombro , Resultado do Tratamento
12.
Int J Biol Macromol ; 209(Pt A): 315-329, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35405151

RESUMO

In this study, we used a combination of chemical and biological pretreatment methods to extract cellulose from corn straw with a relative content of 92.40%. The adsorption performance and mechanism of the prepared porous carbon were investigated using synthetic dye malachite green (MG) and antibiotic tetracycline hydrochloride (TC) as adsorption models. The kinetic studies suggested that the adsorption followed the pseudo-second-order model and Bangham model. The Freundlich isotherm model fitted the adsorption data best for both MG and TC. The thermodynamic studies showed that the adsorption of MG and TC by adsorbents were spontaneous and endothermic in nature. In addition, the adsorption performance was maintained at 50% of the original value after five cycles. More importantly, this method not only improved the adsorption performance of prepared porous carbon materials but also provides a reference for the application of other lignocellulosic materials for cellulose extraction.

13.
Mol Diagn Ther ; 26(3): 345-352, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35430704

RESUMO

BACKGROUND: Mycoplasma pneumoniae (MP) is the most common pathogen of atypical pneumonia and the main cause of community-acquired pneumonia (CAP) in infants and older adults. This study aimed at investigating a method based on the cross-priming amplification (CPA) technique for the rapid detection of MP in clinical specimens collected from patients with CAP. METHODS: The sensitivity and specificity of the EasyNAT MP assay were determined. Oropharyngeal swab specimens were collected from 162 in-patients of Hangzhou First People's Hospitals from January 2018 to December 2020. The patients were aged between 1 and 15 years with symptoms, signs, and chest radiographs consistent with CAP. This study evaluated the presence of MP in the clinical specimens using the EasyNAT method and the conventional fluorescence quantitative PCR technique. RESULTS: The limit of detection using the EasyNAT MP assay was 500 copies/mL, while the test results of the other 13 common pathogens causing CAP or colonizing in the upper respiratory tract showed no cross-reactivity. Of 162 specimens, EasyNAT MP gave a positive indication in 82 specimens. Compared with conventional fluorescence quantitative PCR, the positive coincidence rate and the negative coincidence rate of EasyNAT MP was found to be 100.00% and 97.56%, respectively. Of the 82 specimens, two specimens were determined to be negative by the conventional fluorescence quantitative PCR, but were positive for EasyNAT MP. The two samples were re-extracted and confirmed to be positive by conventional fluorescence quantitative PCR. CONCLUSION: EasyNAT MP is suitable as an initial test for MP diagnosis due to its simplicity, low turnaround time, and high sensitivity and specificity.

14.
ACS Omega ; 7(15): 12617-12623, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35474839

RESUMO

In this study, magnesium aluminate spinel (MgAl2O4) was synthesized by a self-propagating high-temperature synthesis method using Mg-Al alloy with a Mg/Al mass ratio of 50:50 as raw material. Synthesized MgAl2O4 was characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, UV-vis diffused reflectance spectroscopy, photoluminescence, and thermogravimetric differential scanning calorimetry techniques. The results show that synthesized products are of high purity and excellent crystallinity. However, the particle size is not uniform and there is obvious agglomeration. The crystallite size of spinel phase is calculated to be 37.78 nm. In the UV band, the synthesized MgAl2O4 has a certain absorption capacity, and the extrapolated band gap is 4.02 eV. The synthesis mechanism was studied, and continued rupture and growth of the oxidation layer is thought to be responsible for grain refinement.

15.
Front Bioeng Biotechnol ; 10: 837813, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402407

RESUMO

Robust yeast strains that are tolerant to multiple stress environments are desired for an efficient biorefinery. Our previous studies revealed that zinc sulfate serves as an important nutrient for stress tolerance of budding yeast Saccharomyces cerevisiae. Acetic acid is a common inhibitor in cellulosic hydrolysate, and the development of acetic acid-tolerant strains is beneficial for lignocellulosic biorefineries. In this study, comparative proteomic studies were performed using S. cerevisiae cultured under acetic acid stress with or without zinc sulfate addition, and novel zinc-responsive proteins were identified. Among the differentially expressed proteins, the protein kinase Kic1p and the small rho-like GTPase Cdc42p, which is required for cell integrity and regulation of cell polarity, respectively, were selected for further studies. Overexpression of KIC1 and CDC42 endowed S. cerevisiae with faster growth and ethanol fermentation under the stresses of acetic acid and mixed inhibitors, as well as in corncob hydrolysate. Notably, the engineered yeast strains showed a 12 h shorter lag phase under the three tested conditions, leading to up to 52.99% higher ethanol productivity than that of the control strain. Further studies showed that the transcription of genes related to stress response was significantly upregulated in the engineered strains under the stress condition. Our results in this study provide novel insights in exploring zinc-responsive proteins for applications of synthetic biology in developing a robust industrial yeast.

16.
Dalton Trans ; 51(16): 6162-6165, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35383809

RESUMO

We herein report the discovery of inorganic toroidal and capsule titanium oxysulfate clusters by ionothermal synthesis. The ratio between geometrically different anions (tetrahedral SO42-vs. pseudo-tetrahedral PO33-) shows an interesting influence on cluster structure formation.

17.
Microbiol Spectr ; 10(2): e0015022, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35404079

RESUMO

Gametogenesis is essential for malaria parasite transmission, but the molecular mechanism of this process remains to be refined. Here, we identified a G-protein-coupled receptor 180 (GPR180) that plays a critical role in signal transduction during gametogenesis in Plasmodium. The P. berghei GPR180 was predominantly expressed in gametocytes and ookinetes and associated with the plasma membrane in female gametes and ookinetes. Knockout of pbgpr180 (Δpbgpr180) had no noticeable effect on blood-stage development but impaired gamete formation and reduced transmission of the parasites to mosquitoes. Transcriptome analysis revealed that a large proportion of the dysregulated genes in the Δpbgpr180 gametocytes had assigned functions in cyclic nucleotide signal transduction. In the Δpbgpr180 gametocytes, the intracellular cGMP level was significantly reduced, and the cytosolic Ca2+ mobilization showed a delay and a reduction in the magnitude during gametocyte activation. These results suggest that PbGPR180 functions upstream of the cGMP-protein kinase G-Ca2+ signaling pathway. In line with this functional prediction, the PbGPR180 protein was found to interact with several transmembrane transporter proteins and the small GTPase Rab6 in activated gametocytes. Allele replacement of pbgpr180 with the P. vivax ortholog pvgpr180 showed equal competence of the transgenic parasite in sexual development, suggesting functional conservation of this gene in Plasmodium spp. Furthermore, an anti-PbGPR180 monoclonal antibody and the anti-PvGPR180 serum possessed robust transmission-blocking activities. These results indicate that GPR180 is involved in signal transduction during gametogenesis in malaria parasites and is a promising target for blocking parasite transmission. IMPORTANCE Environmental changes from humans to mosquitoes activate gametogenesis of the malaria parasite, an obligative process for parasite transmission, but how the signals are relayed remains poorly understood. Here, we show the identification of a Plasmodium G-protein-coupled receptor, GPR180, and the characterization of its function in gametogenesis. In P. berghei, GPR180 is dispensable for asexual development and gametocytogenesis, but its deletion impairs gametogenesis and reduces transmission to mosquitoes. GPR180 appears to function upstream of the cGMP-protein kinase G-Ca2+ signaling pathway and is required for the maximum activity of this pathway. Genetic complementation shows that the GPR180 ortholog from the human malaria parasite P. vivax was fully functional in P. berghei, indicating functional conservation of GPR180 in Plasmodium spp. With predominant expression and membrane association of GPR180 in sexual stages, GPR180 is a promising target for blocking transmission, and antibodies against GPR180 possess robust transmission-blocking activities.


Assuntos
Culicidae , Malária , Parasitos , Animais , Proteínas Quinases Dependentes de GMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Feminino , Gametogênese/genética , Humanos , Malária/parasitologia , Plasmodium berghei/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais
18.
Sci Rep ; 12(1): 6590, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449379

RESUMO

Acinetobacter baumannii is a nosocomial bacterial pathogen and is responsible for a wide range of diseases including pneumonia, necrotizing fasciitis, meningitis, and sepsis. The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (encoded by aroA gene) in ESKAPE pathogens catalyzes the sixth step of shikimate pathway. The shikimate pathway is an attractive drug targets pathway as it is present in bacteria but absent in humans. As EPSP is essential for the A. baumannii growth and needed during the infection process, therefore it was used as a drug target herein for high-throughput screening of a comprehensive marine natural products database (CMNPD). The objective was to identify natural molecules that fit best at the substrate binding pocket of the enzyme and interact with functionally critical residues. Comparative assessment of the docking scores allowed selection of three compounds namely CMNPD31561, CMNPD28986, and CMNPD28985 as best binding molecules. The molecules established a balanced network of hydrophobic and hydrophilic interactions, and the binding pose remained in equilibrium throughout the length of molecular simulation time. Radial distribution function (RDF) analysis projected key residues from enzyme active pocket which actively engaged the inhibitors. Further validation is performed through binding free energies estimation that affirms very low delta energy of <-22 kcal/mol in MM-GBSA method and <-12 kcal/mol in MM-PBSA method. Lastly, the most important active site residues were mutated and their ligand binding potential was re-investigated. The molecules also possess good druglike properties and better pharmacokinetics. Together, these findings suggest the potential biological potency of the leads and thus can be used by experimentalists in vivo and in vitro studies.


Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Antibacterianos/química , Simulação por Computador , Desenho de Fármacos , Humanos , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular
19.
Autophagy ; : 1-3, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35380918

RESUMO

High levels of reactive oxygen species (ROS) result in oxidative stress, which damages cells and leads to the development of many diseases. Macroautophagy/autophagy plays an important role in protecting cells from diverse stress stimuli including oxidative stress. However, the molecular mechanisms of autophagy activation in response to oxidative stress remain largely unclear. In this study, we showed that TRAF6 mediates oxidative stress-induced ATG9A ubiquitination at two C-terminal lysine residues (K581 and K838). ATG9A ubiquitination promotes its association with BECN1, BECN1-PIK3C3/VPS34-UVRAG complex assembly and PIK3C3/VPS34 activation, thereby activating autophagy and endocytic trafficking. We also identified TNFAIP3/A20 as a negative regulator of oxidative-induced autophagy by counteracting TRAF6-mediated ATG9A ubiquitination. Moreover, ATG9A depletion attenuates LPS-induced autophagy and causes aberrant TLR4 signaling and inflammatory responses. Our findings revealed a critical role of ATG9A ubiquitination in oxidative stress-induced autophagy, endocytic trafficking and innate immunity.

20.
ACS Omega ; 7(12): 10469-10475, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35382280

RESUMO

The energetic performance of hexanitrohexaazaisowurtzitane (CL-20) was modulated with two energetic coordination polymers (ECPs), [Cu(ANQ)2(NO3)2] and [Ni(CHZ)3](ClO4)2, in this study by a two-step method. First, tannic acid polymerized in situ on the surface of CL-20 crystals. Then, [Cu(ANQ)2(NO3)2] and [Ni(CHZ)3](ClO4)2 were hydrothermally formed on the surface of CL-20/TA, respectively. Explosion performance tests show that the impact sensitivity of the coated structure CL-20/TA/[Cu(ANQ)2(NO3)2] is 58% less than that of CL-20 with no energy decrease. On the other hand, CL-20/TA/[Ni(CHZ)3](ClO4)2 can be initiated by a low laser energy of 107.3 mJ (Nd:YAG, 1064 nm, 6.5 ns pulse width), whereas CL-20 cannot be initiated by even 4000 mJ laser energy. This study shows that it is feasible to modify the performance of CL-20 by introducing energetic CPs with certain properties, like high energy insensitive, laser-sensitive, etc., which could be a prospective method for designing high energy insensitive energetic materials in the future.

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