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1.
Proc Natl Acad Sci U S A ; 119(46): e2207327119, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36343233

RESUMO

Developing peptide-based tools to fine-tune growth signaling pathways, in particular molecules with exquisite selectivity and high affinities, opens up opportunities for cellular reprogramming in tissue regeneration. Here, we present a library based on cystine-knot peptides (CKPs) that incorporate multiple loops for randomization and selection via directed evolution. Resulting binders could be assembled into multimeric structures to fine-tune cellular signaling. An example is presented for the Wnt pathway, which plays a key role in the homeostasis and regeneration of tissues such as lung, skin, and intestine. We discovered picomolar affinity CKP agonists of the human LPR6 receptor by exploring the limits of the topological manipulation of LRP6 dimerization. Structural analyses revealed that the agonists bind at the first ß-propeller domain of LRP6, mimicking the natural Wnt inhibitors DKK1 and SOST. However, the CKP agonists exhibit a different mode of action as they amplify the signaling of natural Wnt ligands but do not activate the pathway by themselves. In an alveolosphere organoid model, the CKP agonists induced alveolar stem cell activity. They also stimulated growth in primary human intestinal organoids. The approach described here advances the important frontier of next-generation agonist design and could be applied to other signaling pathways to discover tunable agonist ligands.


Assuntos
Via de Sinalização Wnt , beta Catenina , Humanos , beta Catenina/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Proteínas Wnt/metabolismo , Cistina , Ligantes , Peptídeos
2.
J Am Chem Soc ; 146(7): 4883-4891, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38326284

RESUMO

Nonprecious transition metal catalysts have emerged as the preferred choice for industrial alkaline water electrolysis due to their cost-effectiveness. However, their overstrong binding energy to adsorbed OH often results in the blockage of active sites, particularly in the cathodic hydrogen evolution reaction. Herein, we found that single-atom sites exhibit a puncture effect to effectively alleviate OH blockades, thereby significantly enhancing the alkaline hydrogen evolution reaction (HER) performance. Typically, after anchoring single Ru atoms onto tungsten carbides, the overpotential at 10 mA·cm-2 is reduced by more than 130 mV (159 vs 21 mV). Also, the mass activity is increased 16-fold over commercial Pt/C (MA100 = 17.3 A·mgRu-1 vs 1.1 A·mgPt-1, Pt/C). More importantly, such electrocatalyst-based alkaline anion-exchange membrane water electrolyzers can exhibit an ultralow potential (1.79 Vcell) and high stability at an industrial current density of 1.0 A·cm-2. Density functional theory (DFT) calculations reveal that the isolated Ru sites could weaken the surrounding local OH binding energy, thus puncturing OH blockage and constructing bifunctional interfaces between Ru atoms and the support to accelerate water dissociation. Our findings exhibit generality to other transition metal catalysts (such as Mo) and contribute to the advancement of industrial-scale alkaline water electrolysis.

3.
Small ; : e2404470, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934337

RESUMO

The uncontrollable growth of lithium dendrites and the flammability of electrolytes are the direct impediments to the commercial application of high-energy-density lithium metal batteries (LMBs). Herein, this study presents a novel approach that combines microencapsulation and electrospinning technologies to develop a multifunctional composite separator (P@AS) for improving the electrochemical performance and safety performance of LMBs. The P@AS separator forms a dense charcoal layer through the condensed-phase flame retardant mechanism causing the internal separator to suffocate from lack of oxygen. Furthermore, it incorporates a triple strategy promoting the uniform flow of lithium ions, facilitating the formation of a highly ion-conducting solid electrolyte interface (SEI), and encouraging flattened lithium deposition with active SiO2 seed points, considerably suppressing lithium dendrites growth. The high Coulombic efficiency of 95.27% is achieved in Li-Cu cells with additive-free carbonate electrolyte. Additionally, stable cycling performance is also maintained with a capacity retention rate of 93.56% after 300 cycles in LFP//Li cells. Importantly, utilizing P@AS separator delays the ignition of pouch batteries under continuous external heating by 138 s, causing a remarkable reduction in peak heat release rate and total heat release by 23.85% and 27.61%, respectively, substantially improving the fire safety of LMBs.

4.
Reprod Biomed Online ; 49(2): 103912, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38810314

RESUMO

RESEARCH QUESTION: What are the metabolic characteristics of follicular fluid in patients with ovarian endometriosis undergoing IVF? DESIGN: This was an exploratory cohort study on endometriosis. In total, 19 infertile patients with ovarian endometriosis diagnosed by laparoscopy, and 23 controls matched in terms of age and body mass index (women with infertility due to male or tubal factors) were enrolled in this study. All patients underwent IVF treatment with a gonadotrophin-releasing hormone antagonist protocol, and follicular fluid was collected at oocyte retrieval. The metabolomics of follicular fluid samples was analysed using an ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). The best combination of biomarkers was selected by performing stepwise logistic regression analysis with backward elimination. RESULTS: Fifteen metabolites were identified as biomarkers associated with endometriosis. A final model containing 8-hydroxy-2-deoxyguanosine, biotin, n-acetyl-L-methionine and n-methylnicotinamide was constructed. Receiver operating characteristic analysis confirmed the value of these parameters in diagnosing endometriosis, with sensitivity of 94.7% and specificity of 95.7%. Enrichment analysis via the Kyoto Encyclopedia of Genes and Genome showed that 15 metabolites were enriched in eight metabolic pathways. CONCLUSION: Metabolomics based on UHPLC-OE-MS effectively characterized the metabolomics analysis of follicular fluid in patients with ovarian endometriosis. These findings may provide a new basis for better understanding of how diseases progress, and for the discovery of new biomarkers.

5.
Eur Radiol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992110

RESUMO

OBJECTIVES: This study aims to evaluate image quality and regional lymph node metastasis (LNM) in patients with rectal cancer (RC) on multi-b-value diffusion-weighted imaging (DWI). METHODS: This retrospective study included 199 patients with RC who had undergone multi-b-value DWI. Subjective (five-point Likert scale) and objective assessments of quality images were performed on DWIb1000, DWIb2000, and DWIb3000. Patients were randomly divided into a training (n = 140) or validation cohort (n = 59). Radiomics features were extracted within the whole volume tumor on ADC maps (b = 0, 1000 s/mm2), DWIb1000, DWIb2000, and DWIb3000, respectively. Five prediction models based on selected features were developed using logistic regression analysis. The performance of radiomics models was evaluated with a receiver operating characteristic curve, calibration, and decision curve analysis (DCA). RESULTS: The mean signal intensity of the tumor (SItumor), signal-to-noise ratio (SNR), and artifact and anatomic differentiability score gradually were decreased as the b-value increased. However, the contrast-to-noise (CNR) on DWIb2000 was superior to those of DWIb1000 and DWIb3000 (4.58 ± 0.86, 3.82 ± 0.77, 4.18 ± 0.84, p < 0.001, respectively). The overall image quality score of DWIb2000 was higher than that of DWIb3000 (p < 0.001) and showed no significant difference between DWIb1000 and DWIb2000 (p = 0.059). The area under curve (AUC) value of the radiomics model based on DWIb2000 (0.728) was higher than conventional ADC maps (0.690), DWIb1000 (0.699), and DWIb3000 (0.707), but inferior to multi-b-value DWI (0.739) in predicting LNM. CONCLUSION: DWIb2000 provides better lesion conspicuity and LNM prediction than DWIb1000 and DWIb3000 in RC. CLINICAL RELEVANCE STATEMENT: DWIb2000 offers satisfactory visualization of lesions. Radiomics features based on DWIb2000 can be applied for preoperatively predicting regional lymph node metastasis in rectal cancer, thereby benefiting the stratified treatment strategy. KEY POINTS: Lymph node staging is required to determine the best treatment plan for rectal cancer. DWIb2000 provides superior contrast-to-noise ratio and lesion conspicuity and its derived radiomics best predict lymph node metastasis. DWIb2000 may be recommended as the optimal b-value in rectal MRI protocol.

6.
Environ Toxicol ; 39(5): 2893-2907, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38299319

RESUMO

BACKGROUND: N6-Methyladenosine (m6A) RNA methylation modulators are implicated in nasopharyngeal carcinoma (NPC). Circular RNAs (circRNAs) stimulate/inhibit the development of NPC by sponging microRNAs (miRNAs). Herein, m6A modifications affecting the circRNA/miRNA axis in NPC were explored. METHODS: Twenty prognostic m6A RNA methylation regulators were identified from 504 head/neck squamous cell carcinoma and 44 normal samples from The Cancer Genome Atlas (TCGA). Differentially expressed miRNAs were screened from the TCGA and Gene Expression Omnibus (GEO) databases. RNA-binding protein (RBP)-circRNA and circRNA-miRNA interactive pairs were verified using RBPmap and RNAhybrid, respectively. The RBP/circRNA/miRNA network was constructed using Cytoscape. Furthermore, CircITCH (hsa_circ_00059948), HNRNPC, and miR-224-3p expressions were detected by western blotting and quantitative polymerase chain reaction. The role of circITCH in NPC was examined using apoptosis, scratch wound healing, transwell invasion, and cell counting kit-8 assays. Finally, CircITCH-miR-224-3p and circITCH-HNRNPC interactions were assessed by dual-luciferase reporter and RNA-immunoprecipitation (RIP) assays, respectively. RESULTS: Bioinformatics analysis revealed that high pathological grade, late-stage tumors, and low survival were associated with increased HNRNPC expression. MiR-224-3p was upregulated in NPC and sequestered by circITCH. Construction of the RBP/circRNA/miRNA network highlighted the HNRNPC/circITCH/miR-224-3p axis. In vitro experiments demonstrated decreased circITCH expression and increased HNRNPC and miR-224-3p expressions in NPC. In NPC cells overexpressing circITCH, HNRNPC and miR-224-3p expressions were significantly decreased. Dual-luciferase assays demonstrated a targeting relationship between circITCH and miR-224-3p, and RIP assays demonstrated interaction of HNRNPC targets with circITCH. CONCLUSION: CircITCH overexpression inhibited NPC progression by sequestering miR-224-3p, and HNRNPC reduced circITCH expression through direct interaction.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Humanos , Regulação para Baixo/genética , Carcinoma Nasofaríngeo/genética , RNA Circular/genética , Carcinogênese/genética , Transformação Celular Neoplásica , Luciferases , MicroRNAs/genética , Linhagem Celular Tumoral , Proliferação de Células , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética
7.
Water Sci Technol ; 90(1): 32-44, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007305

RESUMO

Developing a feasible and low-cost strategy for the recovery of calcium fluoride efficiently from fluoride-containing wastewater is very essential for the recycle of fluoride resources. Herein, a modified lime precipitation method was employed to recover CaF2 from fluorinated wastewater using a special icy lime solution. Intriguingly, the highest F- removal was greater than 95% under the optimal condition, leaving a fluoride concentration from 200 to 8.64 mg/L, while the lime dosage was much lower than that of industry. Importantly, spherical-shaped CaF2 particles with a 93.47% purity and size smaller than 600 nm were recovered, which has a high potential for the production of hydrofluoric acid. Besides, the precipitation was significantly affected by Ca/F molar ratio, stirring time, temperature, and solution pH. Furthermore, the thermodynamics and kinetics were investigated in detail to reveal the crystallization process. As a result, the defluorination reaction followed the pseudo-second order reaction kinetics model. Also, CO2 in the air adversely influenced the CaF2 purity. Based on this facile method, a high lime utilization efficiency was applied to defluorination, which contributed to protecting the environment and saving costs. This study, therefore, provides a feasible approach for the green recovery of fluorine resources and has significance for related research.


Assuntos
Compostos de Cálcio , Fluoreto de Cálcio , Flúor , Óxidos , Águas Residuárias , Fluoreto de Cálcio/química , Águas Residuárias/química , Flúor/química , Compostos de Cálcio/química , Óxidos/química , Poluentes Químicos da Água/química , Eliminação de Resíduos Líquidos/métodos , Fluoretos/química
8.
Int Wound J ; 21(4): e14597, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38124467

RESUMO

Macrophages play a crucial role in aiding all phases of the wound-healing process and has garnered increasing attention recently. Although a substantial body of related studies has been published, there remains a lack of comprehensive bibliometric analysis. In this study, we collected 4296 papers from the Web of Science Core Collection database. Three tools including CiteSpace, VOSviewer and one online analytical platform were employed to conduct bibliometric analysis and data visualization. Our results revealed that the annual number of publications related to macrophage and wound healing has increased exponentially with the year. The United States and China stand as the primary driving forces within this field, collectively constituting 58.2% of the total publication output. The application of biomaterials was one of the most concerned research areas in this field. According to references analysis, the current research focus has shifted to diabetic wound healing and regulating macrophage polarization. Based on the keywords analysis, we identified the following research frontiers in the future: exosomes and other extracellular vesicles; bio-derived materials and drug delivery methods such as nanoparticles, scaffolds and hydrogels; immunomodulation and macrophage polarization in the M2-state; chronic wounds, particularly those associated with diabetes; antimicrobial peptides; and antioxidant. Additionally, TNF, IL-6, IL-10, TGF-ß1 and VEGF ranked as the five genes that have garnered the most research attention in the intersection of macrophage and wound healing. All in all, our findings offered researchers a holistic view of the ongoing progress in the field of macrophages and wound healing, serving as a valuable reference for scholars and policymakers in this domain.


Assuntos
Antioxidantes , Macrófagos , Humanos , Bibliometria , Materiais Biocompatíveis , China
9.
Cereb Cortex ; 32(15): 3224-3242, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34882197

RESUMO

For bilinguals, speaking and listening are assisted by complex control processes including conflict monitoring and inhibition. However, the extent to which these processes adapt to linguistic and situational needs has been examined separately for language production and comprehension. In the present study, we use a dual-EEG to record the carry-over effects of language control on general cognitive control in three language contexts (single-first language [L1], single-second language [L2], and mixed). Chinese learners of English were placed in dyads in which one participant was asked to name pictures while the other listened. Interleaved after each naming/listening trial were flanker trials. The results from picture naming and listening revealed higher delta and theta synchronization in the single-L2 and mixed contexts compared with the single-L1 context and higher theta synchronization in the mixed context compared with the single-L2 and single-L1 contexts. The results from the interleaved flanker trials demonstrated that inhibition was adaptively generalized in the single-L2 and mixed contexts. Altogether, the findings support the natural adaptation of language control to cognitive control and underscore the importance of linguistic context. We argue that these adaptive patterns have the potential to affect corresponding control processes across language and cognitive control tasks.


Assuntos
Compreensão , Multilinguismo , Encéfalo/fisiologia , Compreensão/fisiologia , Eletroencefalografia , Humanos , Idioma
10.
Environ Res ; 236(Pt 1): 116457, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37459944

RESUMO

Over the last several decades, both the academic and therapeutic fields have seen significant progress in the delivery of drugs to the inner ear due to recent delivery methods established for the systemic administration of drugs in inner ear treatment. Novel technologies such as nanoparticles and hydrogels are being investigated, in addition to the traditional treatment methods. Intracochlear devices, which utilize current developments in microsystems technology, are on the horizon of inner ear drug delivery methods and are designed to provide medicine directly into the inner ear. These devices are used for stem cell treatment, RNA interference, and the delivery of neurotrophic factors and steroids during cochlear implantation. An in-depth analysis of artificial neural networks (ANNs) in pharmaceutical research may be found in ANNs for Drug Delivery, Design, and Disposition. This prediction tool has a great deal of promise to assist researchers in more successfully designing, developing, and delivering successful medications because of its capacity to learn and self-correct in a very complicated environment. ANN achieved a high level of accuracy exceeding 0.90, along with a sensitivity of 95% and a specificity of 100%, in accurately distinguishing illness. Additionally, the ANN model provided nearly perfect measures of 0.99%. Nanoparticles exhibit potential as a viable therapeutic approach for bacterial infections that are challenging to manage, such as otitis media. The utilization of ANNs has the potential to enhance the effectiveness of nanoparticle therapy, particularly in the realm of automated identification of otitis media. Polymeric nanoparticles have demonstrated effectiveness in the treatment of prevalent bacterial infections in pediatric patients, suggesting significant potential for forthcoming therapeutic interventions. Finally, this study is based on a research of how inner ear diseases have been treated in the last ten years (2012-2022) using machine learning.


Assuntos
Infecções Bacterianas , Orelha Interna , Doenças do Labirinto , Otite Média , Humanos , Criança , Inteligência Artificial , Doenças do Labirinto/tratamento farmacológico , Preparações Farmacêuticas
11.
Echocardiography ; 40(8): 760-767, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37126423

RESUMO

BACKGROUND: There are relatively few studies investigating cardiac structural and functional abnormalities associated with systemic lupus erythematous (SLE). The long-term prognosis of SLE patients is closely related to the cardiovascular events caused by SLE. Accordingly, it is necessary to assess early myocardial systolic function and synchrony. METHODS: Overall, 90 patients with SLE were randomly selected from our outpatient and inpatient clinics and divided according to SLE Disease Activity Index (SLE-DAI-2000) scores: group A, stable (scores 0-4); group B, mildly active stage (scores 5-9); and group C, moderately active stage (scores ≥10). Each group included 30 patients. Further, 30 sex- and age-matched healthy individuals who were referred for check-ups at the same period were selected as controls (group D). The minimum age for entry into the group was 17 years old. Autostrain LV and three-dimensional quantitative analysis (3DQA) were applied to obtain left ventricular systolic function parameters, information on strain parameters, and correlations between parameters. Simultaneity parameters measured by Autostrain LV and 3DQA were tested for reproducibility. RESULTS: A two-by-two comparison of groups A-C showed that as the disease activity score increased, AP4LS%, AP2LS%, AP3LS%, and the LV mean overall longitudinal strain all gradually decreased, while LV longitudinal strain peak time standard deviation (Tls-SD) gradually increased, with all differences being statistically significant (p < .05). In groups A-C compared with controls, Tmsv-17-SD, Tmsv-17-Dif, Tmsv-17-SD%, and Tmsv-17-Dif% were all significantly prolonged (p < .05). Further, Tls-SD was positively correlated with Tmsv-17-SD and Tmsv-17-Dif, and there was good agreement between Autostrain and 3DQA for the measurement of left ventricular synchrony indexes, with Tmsv-17-Dif having the best repeatability (intraobserver interclass correlation coefficient (ICC) = .979; interobserver ICC = .848, p < .01). CONCLUSION: Autostrain LV can accurately detect changes in left ventricular myocardial strain in patients with SLE early in the disease, with simple operation. The 3DQA technique can quantitatively evaluate left ventricular systolic synchronization in patients with SLE, and Autostrain LV synchronization index measurements correlate significantly with 3DQA. Both methods are reproducible, but 3DQA is more sensitive to left ventricular synchronous motion changes.


Assuntos
Lúpus Eritematoso Sistêmico , Disfunção Ventricular Esquerda , Humanos , Adolescente , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/complicações , Reprodutibilidade dos Testes , Função Ventricular Esquerda , Coração , Lúpus Eritematoso Sistêmico/complicações , Sopros Cardíacos/complicações
12.
Biochemistry ; 61(18): 2007-2013, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36054099

RESUMO

Many disease-causing viruses target sialic acids on the surface of host cells. Some viruses bind preferentially to sialic acids with O-acetyl modification at the hydroxyl group of C7, C8, or C9 on the glycerol-like side chain. Studies of proteins binding to sialosides containing O-acetylated sialic acids are crucial in understanding the related diseases but experimentally difficult due to the lability of the ester group. We recently showed that O-acetyl migration among hydroxyl groups of C7, C8, and C9 in sialic acids occurs in all directions in a pH-dependent manner. In the current study, we elucidate a full mechanistic pathway for the migration of O-acetyl among C7, C8, and C9. We used an ab initio nanoreactor to explore potential reaction pathways and density functional theory, pKa calculations, and umbrella sampling to investigate elementary steps of interest. We found that when a base is present, migration is easy in any direction and involves three key steps: deprotonation of the hydroxyl group, cyclization between the two carbons, and the migration of the O-acetyl group. This dynamic equilibrium may play a defensive role against pathogens that evolve to gain entry to the cell by binding selectively to one acetylation state.


Assuntos
Glicerol , Ácido N-Acetilneuramínico , Acetilação , Ésteres , Ácido N-Acetilneuramínico/metabolismo , Nanotecnologia , Ácidos Siálicos/química
13.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077447

RESUMO

Obesity has become an extensive threat to human health due to associated chronic inflammation and metabolic diseases. Apoptosis-associated speck-like protein (ASC) is a critical link between inflammasome and apoptosis-inducing proteins. In this study, we aimed to clarify the role of ASC in lipid metabolism. With high-fat diet (HFD) and knockout leptin gene mice (ob/ob), we found that ASC expression in subcutaneous adipose tissue (SAT) correlated with obesity. It could also positively regulate the reprogramming of cellular energy metabolism. Stromal vascular fractions (SVF) cells derived from the SAT of Asc-/- mice or SVF from wild-type (WT) mice transfected with ASC siRNA were used to further investigate the underlying molecular mechanisms. We found ASC deficiency could lead to lipogenesis and inhibit lipolysis in SAT, aggravating lipid accumulation and impairing metabolic balance. In addition, our results showed that p53 and AMPKα expression were inhibited in SAT when ASC level was low. p53 and AMP-activated protein kinase α (AMPKα) were then assessed to elucidate whether they were downstream of ASC in regulating lipid metabolism. Our results revealed that ASC deficiency could promote lipid accumulation by increasing lipogenesis and decreasing lipolysis through p53/AMPKα axis. Regulation of ASC on lipid metabolism might be a novel therapeutic target for obesity.


Assuntos
Lipogênese , Lipólise , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Lipídeos , Lipogênese/genética , Lipólise/fisiologia , Camundongos , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
14.
J Gerontol Nurs ; 48(4): 57-64, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35343838

RESUMO

Using a suite of artificial intelligence technologies, the current study sought to determine the prevalence of agitated behaviors in people with dementia in residential aged care facilities (RACFs) in Australia. Computerized natural language processing allowed extraction of agitation instances from the free-text nursing progress notes, a component of electronic health records in RACFs. In total, 59 observable agitated behaviors were found. No difference was found in dementia prevalence between female and male clients (44.1%), across metropolitan and regional facilities (42.1% [SD = 17.9%]), or for agitation prevalence in dementia (76.5% [SD = 18.4%]). The top 10 behaviors were resisting, wandering, speaking in excessively loud voice, pacing, restlessness, pushing, shouting, complaining, frustration, and using profane language. Four to 17 agitated behaviors coexisted in 53% of people with dementia agitation, indicating high caregiver burden in these RACFs. Improving workforce training and redesigning care models are urgent for sustainability of dementia care in RACFs. [Journal of Gerontological Nursing, 48(4), 57-64.].


Assuntos
Demência , Registros Eletrônicos de Saúde , Idoso , Inteligência Artificial , Austrália/epidemiologia , Demência/epidemiologia , Feminino , Humanos , Aprendizado de Máquina , Masculino , Prevalência
15.
Glycobiology ; 30(10): 787-801, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32350512

RESUMO

O-Acetylation of carbohydrates such as sialic acids is common in nature, but its role is not clearly understood due to the lability of O-acetyl groups. We demonstrated previously that 9-acetamido-9-deoxy-N-acetylneuraminic acid (Neu5Ac9NAc) is a chemically and biologically stable mimic of the 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) of the corresponding sialoglycans. Here, a systematic nuclear magnetic resonance (NMR) spectroscopic and molecular dynamics (MD) simulation study was undertaken for Neu5,9Ac2-containing GM3 ganglioside glycan (GM3-glycan) and its Neu5Ac9NAc analog. GM3-glycan with Neu5Ac as the non-O-acetyl form of Neu5,9Ac2 was used as a control. Complete 1H and 13C NMR chemical shift assignments, three-bond 1H-13C trans-glycosidic coupling constants (3JCH), accurate 1H-1H coupling constants (3JHH), nuclear Overhauser effects and hydrogen bonding detection were carried out. Results show that structural modification (O- or N-acetylation) on the C-9 of Neu5Ac in GM3 glycan does not cause significant conformational changes on either its glycosidic dihedral angles or its secondary structure. All structural differences are confined to the Neu5Ac glycerol chain, and minor temperature-dependent changes are seen in the aglycone portion. We also used Density Functional Theory (DFT) quantum mechanical calculations to improve currently used 3JHH Karplus relations. Furthermore, OH chemical shifts were assigned at -10°C and no evidence of an intramolecular hydrogen bond was observed. The results provide additional evidence regarding structural similarities between sialosides containing 9-N-acetylated and 9-O-acetylated Neu5Ac and support the opportunity of using 9-N-acetylated Neu5Ac as a stable mimic to study the biochemical role of 9-O-acetylated Neu5Ac.


Assuntos
Teoria da Densidade Funcional , Gangliosídeo G(M3)/química , Simulação de Dinâmica Molecular , Polissacarídeos/química , Ácidos Siálicos/química , Configuração de Carboidratos , Gangliosídeo G(M3)/biossíntese , Espectroscopia de Ressonância Magnética , Ácido N-Acetilneuramínico/química , Polissacarídeos/biossíntese
16.
Anal Chem ; 92(14): 10129-10137, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32578420

RESUMO

The growing use of fluorochemicals has elevated the need for nontargeted detection of unknown fluorinated compounds and transformation products. Elemental mass spectrometry (MS) coupled to chromatography offers a facile approach for such analyses by using fluorine as an elemental tag. However, efficient ionization of fluorine has been an ongoing challenge. Here, we demonstrate a novel atmospheric-pressure elemental ionization method where fluorinated compounds separated by gas chromatography (GC) are converted to Na2F+ for nontargeted detection. The compounds are first introduced into a helium dielectric barrier discharge (DBD) for breakdown. The plasma products are subsequently ionized by interaction with a nanoelectrospray ionization (nano-ESI) plume of sodium-containing aqueous electrolytes. Our studies point to HF as the main plasma product contributing to Na2F+ formation. Moreover, the results reveal that Na2F+ is largely formed by the ion-neutral reaction between HF and Na2A(NaA)n+, gas-phase reagent ions produced by nano-ESI where A represents the anion of the electrolyte. Near-uniform fluorine response factors are obtained for a wide range of compounds, highlighting good efficiency of HF formation by DBD regardless of the chemical structure of the compounds. Detection limits of 3.5-19.4 pg of fluorine on-column are obtained using the reported GC-DBD-nano-ESI-MS. As an example of nontargeted screening, extractions from oil-and-water-repellent fabrics are analyzed via monitoring Na2F+, resulting in detection of a fluorinated compound on a clothing item. Notably, facile switching of the ion source to atmospheric-pressure chemical ionization with the exact same chromatographic method allows identification of the detected compound at the flagged retention time.

17.
Org Biomol Chem ; 18(4): 738-744, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31912849

RESUMO

5,7-Di-N-acetyllegionaminic acid (Leg5,7Ac2) is a bacterial nonulosonic acid (NulO) analogue of sialic acids, an important class of monosaccharides in mammals and in some bacteria. To develop efficient one-pot multienzyme (OPME) glycosylation systems for synthesizing Leg5,7Ac2-glycosides, Legionella pneumophila cytidine 5'-monophosphate (CMP)-Leg5,7Ac2 synthetase (LpCLS) was cloned and characterized. It was successfully used in producing Leg5,7Ac2-glycosides from chemoenzymatically synthesized Leg5,7Ac2 using a one-pot two-enzyme system or from its chemically synthesized six-carbon monosaccharide precursor 2,4-diacetamido-2,4,6-trideoxymannose (6deoxyMan2,4diNAc) in a one-pot three-enzyme system. In addition, LpCLS was shown to tolerate Neu5Ac7NAc, a C9-hydroxyl analogue of Leg5,7Ac2 and also a stable analogue of 7-O-acetylneuraminic acid (Neu5,7Ac2), to allow OPME synthesis of the corresponding α2-3-linked sialosides, from chemically synthesized six-carbon monosaccharide precursor 4-N-acetyl-4-deoxy-N-acetylmannosamine (ManNAc7NAc).


Assuntos
Proteínas de Bactérias/química , Glicosídeos/síntese química , Legionella pneumophila/enzimologia , Nucleotidiltransferases/química , Ácidos Siálicos/síntese química , Proteínas de Bactérias/genética , Escherichia coli/genética , Nucleotidiltransferases/genética
18.
Environ Sci Technol ; 54(1): 577-585, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31774278

RESUMO

This study investigated catalytic reforming, which is a thermochemical process, as a pioneering method to treat biogas slurry (wastewater from biogas plants) and generate hydrogen. Experimental validation for treating biogas slurries from digested cattle manure, fish intestine, and wheat straw was performed on Ni/α-Al2O3 catalyst. The results showed that the total organic carbon, total nitrogen, and PO43- ion contents in biogas slurry could be reduced by 98.69, 98.01, and 99.32%, respectively. The highest hydrogen yield was obtained in the treatment of biogas slurry from digested cattle manure at 750 °C, in which the hydrogen yield and hydrogen concentration were 13.85 Lhydrogen/LBS and 79.77 vol %, respectively. Changes in the crystalline phase and structure of the catalyst were observed during catalytic reforming of biogas slurry. Active metal oxidization and carbon deposition were likely to be important factors affecting catalytic stability. The mass flow evaluation verified the hydrogen generation potential by the catalytic reforming of biogas slurry, which was close to the methane generation capability of the upstream biogas plant. However, additional effort is required to address the high energy consumption of this method. These findings provide fundamental knowledge about the potential of applying thermochemical techniques to treat and utilize high total organic carbon-containing wastewaters.


Assuntos
Biocombustíveis , Águas Residuárias , Animais , Reatores Biológicos , Bovinos , Esterco , Metano , Nitrogênio
19.
Sensors (Basel) ; 20(23)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297370

RESUMO

Smartphone-sensors-based human activity recognition is attracting increasing interest due to the popularization of smartphones. It is a difficult long-range temporal recognition problem, especially with large intraclass distances such as carrying smartphones at different locations and small interclass distances such as taking a train or subway. To address this problem, we propose a new framework of combining short-term spatial/frequency feature extraction and a long-term independently recurrent neural network (IndRNN) for activity recognition. Considering the periodic characteristics of the sensor data, short-term temporal features are first extracted in the spatial and frequency domains. Then, the IndRNN, which can capture long-term patterns, is used to further obtain the long-term features for classification. Given the large differences when the smartphone is carried at different locations, a group-based location recognition is first developed to pinpoint the location of the smartphone. The Sussex-Huawei Locomotion (SHL) dataset from the SHL Challenge is used for evaluation. An earlier version of the proposed method won the second place award in the SHL Challenge 2020 (first place if not considering the multiple models fusion approach). The proposed method is further improved in this paper and achieves 80.72% accuracy, better than the existing methods using a single model.


Assuntos
Atividades Humanas , Redes Neurais de Computação , Humanos , Reconhecimento Psicológico , Smartphone
20.
Sensors (Basel) ; 20(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532007

RESUMO

The paper presents a novel hybrid network for large-scale action recognition from multiple modalities. The network is built upon the proposed weighted dynamic images. It effectively leverages the strengths of the emerging Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN) based approaches to specifically address the challenges that occur in large-scale action recognition and are not fully dealt with by the state-of-the-art methods. Specifically, the proposed hybrid network consists of a CNN based component and an RNN based component. Features extracted by the two components are fused through canonical correlation analysis and then fed to a linear Support Vector Machine (SVM) for classification. The proposed network achieved state-of-the-art results on the ChaLearn LAP IsoGD, NTU RGB+D and Multi-modal & Multi-view & Interactive ( M 2 I ) datasets and outperformed existing methods by a large margin (over 10 percentage points in some cases).

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