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1.
Mol Cell Proteomics ; 23(5): 100766, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608841

RESUMO

The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical (IHC), and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging-based shotgun proteomics to characterize proteomes of formalin-fixed, paraffin-embedded tumor samples of PAIM (n = 22) and lmCRC (n = 17).Then three machine learning algorithms, namely support vector machine (SVM), random forest, and the Least Absolute Shrinkage and Selection Operator, were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by IHC to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection. The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of ten candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: CK7 (an established marker), NARR, MLPH, S100A14) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.


Assuntos
Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Neoplasias Colorretais , Neoplasias Pulmonares , Proteômica , Humanos , Biomarcadores Tumorais/metabolismo , Proteômica/métodos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Masculino , Feminino , Diagnóstico Diferencial , Diferenciação Celular , Pessoa de Meia-Idade , Idoso , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia
2.
Exp Cell Res ; 435(2): 113929, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38272106

RESUMO

Early repolarization syndrome (ERS) is defined as occurring in patients with early repolarization pattern who have survived idiopathic ventricular fibrillation with clinical evaluation unrevealing for other explanations. The pathophysiologic basis of the ERS is currently uncertain. The objective of the present study was to examine the electrophysiological mechanism of ERS utilizing induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing. Whole genome sequencing was used to identify the DPP6 (c.2561T > C/p.L854P) variant in four families with sudden cardiac arrest induced by ERS. Cardiomyocytes were generated from iPSCs from a 14-year-old boy in the four families with ERS and an unrelated healthy control subject. Patch clamp recordings revealed more significant prolongation of the action potential duration (APD) and increased transient outward potassium current (Ito) (103.97 ± 18.73 pA/pF vs 44.36 ± 16.54 pA/pF at +70 mV, P < 0.05) in ERS cardiomyocytes compared with control cardiomyocytes. Of note, the selective correction of the causal variant in iPSC-derived cardiomyocytes using CRISPR/Cas9 gene editing normalized the Ito, whereas prolongation of the APD remained unchanged. ERS cardiomyocytes carrying DPP6 mutation increased Ito and lengthen APD, which maybe lay the electrophysiological foundation of ERS.

3.
J Mol Cell Cardiol ; 194: 3-15, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38844061

RESUMO

Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.


Assuntos
DNA Glicosilases , Cardiomiopatias Diabéticas , Resistência à Insulina , Animais , DNA Glicosilases/metabolismo , DNA Glicosilases/genética , DNA Glicosilases/deficiência , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Camundongos , Masculino , PPAR gama/metabolismo , Glucose/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Modelos Animais de Doenças , Glicólise , Humanos , Camundongos Endogâmicos C57BL
4.
J Proteome Res ; 23(7): 2518-2531, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38810119

RESUMO

Phosphorylation is the most studied post-translational modification, and has multiple biological functions. In this study, we have reanalyzed publicly available mass spectrometry proteomics data sets enriched for phosphopeptides from Asian rice (Oryza sativa). In total we identified 15,565 phosphosites on serine, threonine, and tyrosine residues on rice proteins. We identified sequence motifs for phosphosites, and link motifs to enrichment of different biological processes, indicating different downstream regulation likely caused by different kinase groups. We cross-referenced phosphosites against the rice 3,000 genomes, to identify single amino acid variations (SAAVs) within or proximal to phosphosites that could cause loss of a site in a given rice variety and clustered the data to identify groups of sites with similar patterns across rice family groups. The data has been loaded into UniProt Knowledge-Base─enabling researchers to visualize sites alongside other data on rice proteins, e.g., structural models from AlphaFold2, PeptideAtlas, and the PRIDE database─enabling visualization of source evidence, including scores and supporting mass spectra.


Assuntos
Genoma de Planta , Oryza , Fosfoproteínas , Proteínas de Plantas , Proteômica , Transdução de Sinais , Oryza/genética , Oryza/metabolismo , Oryza/química , Proteômica/métodos , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/química , Fosfoproteínas/análise , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Fosfopeptídeos/metabolismo , Fosfopeptídeos/análise , Bases de Dados de Proteínas , Motivos de Aminoácidos , Espectrometria de Massas
5.
J Cell Mol Med ; 28(11): e18408, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837585

RESUMO

We employed single-cell analysis techniques, specifically the inferCNV method, to dissect the complex progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) through minimally invasive adenocarcinoma (MIA) to invasive adenocarcinoma (IAC). This approach enabled the identification of Cluster 6, which was significantly associated with LUAD progression. Our comprehensive analysis included intercellular interaction, transcription factor regulatory networks, trajectory analysis, and gene set variation analysis (GSVA), leading to the development of the lung progression associated signature (LPAS). Interestingly, we discovered that the LPAS not only accurately predicts the prognosis of LUAD patients but also forecasts genomic alterations, distinguishes between 'cold' and 'hot' tumours, and identifies potential candidates suitable for immunotherapy. PSMB1, identified within Cluster 6, was experimentally shown to significantly enhance cancer cell invasion and migration, highlighting the clinical relevance of LPAS in predicting LUAD progression and providing a potential target for therapeutic intervention. Our findings suggest that LPAS offers a novel biomarker for LUAD patient stratification, with significant implications for improving prognostic accuracy and guiding treatment decisions.


Assuntos
Adenocarcinoma de Pulmão , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Genômica , Neoplasias Pulmonares , Análise de Célula Única , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Prognóstico , Análise de Célula Única/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Genômica/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Redes Reguladoras de Genes , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Invasividade Neoplásica
6.
J Cell Mol Med ; 28(13): e18520, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38958523

RESUMO

Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi-omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs-associated machine learning model (MOCM) based on eight MOCs-specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability.


Assuntos
Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Imunoterapia , Neoplasias Pulmonares , Aprendizado de Máquina , Humanos , Imunoterapia/métodos , Prognóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Perfilação da Expressão Gênica , MicroRNAs/genética , Multiômica
7.
BMC Genomics ; 25(1): 280, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493091

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Fatores de Risco , Magnésio , Análise da Randomização Mendeliana , Cálcio , Potássio , Fosfatos , Eletrólitos , Estudo de Associação Genômica Ampla/métodos
8.
J Am Chem Soc ; 146(29): 20458-20467, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38980827

RESUMO

The unprecedented silylene-supported dibenzodiboraoxepin 2 and 9,10-diboraphenanthrene complexes 6 and 8 were synthesized. The (NHSi)2B2(xanthene) [NHSi = PhC(NtBu)2(Me2N)Si:] 2 results from debromination of the bis(NHSi)-stabilized bis(dibromoboryl)xanthene 1 with potassium graphite (KC8); 2 is capable of activating white phosphorus and ammonia to form the B2P4 cage compound 3 and H2N-B-B-H diborane species 4, respectively. The thermal rearrangement of 2 affords the 9,10-dihydro-9,10-diboraphenanthrene 5 through a bis(NHSi)-assisted intramolecular reductive C-O-C deoxygenation process. Notably, the 9,10-diboraphenanthrene derivatives 6 and 8 could be generated by deoxygenation of 2 with KC8 and 1,3,4,5-tetramethylimidazol-2-ylidene, respectively. The aromaticity of 6 and 8 was confirmed by computational studies. Strikingly, the NHSi ligand in 8 engenders the monodeoxygenation of carbon dioxide in toluene at room temperature to form the CO-stabilized 9,10-diboraphenanthrene derivative 9 via the silaoxadiborinanone intermediate 10.

9.
J Am Chem Soc ; 146(9): 6025-6036, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38408197

RESUMO

The formation of isolable monatomic BiI complexes and BiII radical species is challenging due to the pronounced reducing nature of metallic bismuth. Here, we report a convenient strategy to tame BiI and BiII atoms by taking advantage of the redox noninnocent character of a new chelating bis(germylene) ligand. The remarkably stable novel BiI cation complex 4, supported by the new bis(iminophosphonamido-germylene)xanthene ligand [(P)GeII(Xant)GeII(P)] 1, [(P)GeII(Xant)GeII(P) = Ph2P(NtBu)2GeII(Xant)GeII(NtBu)2PPh2, Xant = 9,9-dimethyl-xanthene-4,5-diyl], was synthesized by a two-electron reduction of the cationic BiIIII2 precursor complex 3 with cobaltocene (Cp2Co) in a molar ratio of 1:2. Notably, owing to the redox noninnocent character of the germylene moieties, the positive charge of BiI cation 4 migrates to one of the Ge atoms in the bis(germylene) ligand, giving rise to a germylium(germylene) BiI complex as suggested by DFT calculations and X-ray photoelectron spectroscopy (XPS). Likewise, migration of the positive charge of the BiIIII2 cation of 3 results in a bis(germylium)BiIIII2 complex. The delocalization of the positive charge in the ligand engenders a much higher stability of the BiI cation 4 in comparison to an isoelectronic two-coordinate Pb0 analogue (plumbylone; decomposition below -30 °C). Interestingly, 4[BArF] undergoes a reversible single-electron transfer (SET) reaction (oxidation) to afford the isolable BiII radical complex 5 in 5[BArF]2. According to electron paramagnetic resonance (EPR) spectroscopy, the unpaired electron predominantly resides at the BiII atom. Extending the redox reactivity of 4[OTf] employing AgOTf and MeOTf affords BiIII(OTf)2 complex 7 and BiIIIMe complex 8, respectively, demonstrating the high nucleophilic character of BiI cation 4.

10.
Antimicrob Agents Chemother ; : e0005424, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687016

RESUMO

Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol, and impaired the polymerase activity of 3D pol, hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our findings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.

11.
Biochem Biophys Res Commun ; 693: 149375, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38128243

RESUMO

BACKGROUND: Myocardial fibrosis (MF) is a common pathological condition in cardiovascular diseases that often causes severe cardiac dysfunction. MF is characterized by changes in cardiomyocytes, cardiac fibroblasts (CFs), levels of collagen (Col) -1, -3, and overdeposition of the extracellular matrix. Our previous research showed that leonurine (LE) effectively inhibits collagen synthesis and differentiation of CFs, but the mechanism is not fully elucidated. Recent evidence indicates that fat mass and obesity-associated proteins (FTO) regulates the occurrence and development of MF. This study aimed to explore the role of FTO in the antifibrotic effects of LE. METHODS: Neonatal rat CFs were isolated, and induced using angiotensin II (Ang II) to establish a cell model of MF. Cell viability, wound healing and transwell assays were used to detect cell activity and migration ability. The protein and mRNA levels of MF-related factors were measured following stimulation with Ang II and LE under normal conditions or after FTO knockdown. The RNA methylation level was measured by dot blot assay. RESULTS: The results showed that LE (20, 40 µM) was not toxic to normal CFs. LE reduced the proliferation, migration and collagen synthesis of Ang II-induced CFs. Further investigation showed that FTO was downregulated by Ang II stimulation, whereas LE reversed this effect. FTO knockdown facilitated the migration of CFs, upregulated the protein levels of Col-3, α-SMA and Col-1 in Ang II and LE-stimulated CFs, and enhanced the fluorescence intensity of α-SMA. Furthermore, LE reduced N6-methyladenosine (m6A) RNA methylation, which was partially blocked by FTO knockdown. FTO knockdown also reduced the expression levels of p53 protein in Ang II and LE-stimulated CFs. CONCLUSIONS: Our findings suggest that the inhibition of FTO may attenuate the antifibrotic effect of LE in CFs, suggesting that FTO may serve as a key protein for anti-MF of LE.


Assuntos
Cardiomiopatias , Fibroblastos , Ratos , Animais , Fibroblastos/metabolismo , Proliferação de Células , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Miócitos Cardíacos/metabolismo , Cardiomiopatias/patologia , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Miocárdio/metabolismo , Fibrose , Células Cultivadas
12.
BMC Plant Biol ; 24(1): 10, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163896

RESUMO

BACKGROUND: Understanding the genetic mechanisms underlying gray leaf spot (GLS) resistance in maize is crucial for breeding GLS-resistant inbred lines and commercial hybrids. Genome-wide association studies (GWAS) and gene functional annotation are valuable methods for identifying potential SNPs (single nucleotide polymorphism) and candidate genes associated with GLS resistance in maize. RESULTS: In this study, a total of 757 lines from five recombinant inbred line (RIL) populations of maize at the F7 generation were used to construct an association mapping panel. SNPs obtained through genotyping-by-sequencing (GBS) were used to perform GWAS for GLS resistance using a linear mixture model in GEMMA. Candidate gene screening was performed by analyzing the 10 kb region upstream and downstream of the significantly associated SNPs linked to GLS resistance. Through GWAS analysis of multi-location phenotypic data, we identified ten candidate genes that were consistently detected in two locations or from one location along with best linear unbiased estimates (BLUE). One of these candidate genes, Zm00001d003257 that might impact GLS resistance by regulating gibberellin content, was further identified through haplotype-based association analysis, candidate gene expression analysis, and previous reports. CONCLUSIONS: The discovery of the novel candidate gene provides valuable genomic resources for elucidating the genetic mechanisms underlying GLS resistance in maize. Additionally, these findings will contribute to the development of new genetic resources by utilizing molecular markers to facilitate the genetic improvement and breeding of maize for GLS resistance.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Zea mays/genética , Doenças das Plantas/genética , Resistência à Doença/genética , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética , Fenótipo
13.
Chemistry ; 30(14): e202303781, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38196025

RESUMO

Tuning the topology of two-dimensional (2D) covalent organic frameworks (COFs) is of paramount scientific interest but remains largely unexplored. Herein, we present a site-selective synthetic strategy that enables the tuning of 2D COF topology by simply adjusting the molar ratio of an amine-functionalized dihydrazide monomer (NH2 -Ah) and 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (Tz). This approach resulted in the formation of two distinct COFs: a clover-like 2D COF with free amine groups (NH2 -Ah-Tz) and a honeycomb-like COF without amine groups (Ah-Tz). Both COFs exhibited good crystallinity and moderate porosity. Remarkably, the clover-shaped NH2 -Ah-Tz COF, with abundant free amine groups, displayed significantly enhanced adsorption capacities toward crystal violet (CV, 261 mg/g) and congo red (CR, 1560 mg/g) compared to the non-functionalized honeycomb-like Ah-Tz COF (123 mg/g for CV and 1340 mg/g for CR), underscoring the pivotal role of free amine functional groups in enhancing adsorption capacities for organic dyes. This work highlights that the site-selective synthetic strategy paves a new avenue for manipulating 2D COF topology by adjusting the monomer feeding ratio, thereby modulating their adsorption performances toward organic dyes.

14.
Neural Comput ; 36(4): 718-743, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38457767

RESUMO

Combining information-theoretic learning with deep learning has gained significant attention in recent years, as it offers a promising approach to tackle the challenges posed by big data. However, the theoretical understanding of convolutional structures, which are vital to many structured deep learning models, remains incomplete. To partially bridge this gap, this letter aims to develop generalization analysis for deep convolutional neural network (CNN) algorithms using learning theory. Specifically, we focus on investigating robust regression using correntropy-induced loss functions derived from information-theoretic learning. Our analysis demonstrates an explicit convergence rate for deep CNN-based robust regression algorithms when the target function resides in the Korobov space. This study sheds light on the theoretical underpinnings of CNNs and provides a framework for understanding their performance and limitations.

15.
Protein Expr Purif ; 218: 106447, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38369031

RESUMO

Diaminopropionate ammonia-lyase transforms D and L isomers of 2,3-diaminopropionate to pyruvate and ammonia. It catalyzes D- and l-serine less effectively. L-2,3-diaminopropionate is a precursor in the biosynthesis of oxalyl diaminopropionate as a neurotoxin in certain legume species. In this work, we cyclized the diaminopropionate ammonia-lyase from Salmonella typhimurium in vitro using the redox-responsive split intein, and identified that backbone cyclization afforded the enzyme with the improved activity, thermal stability and resistance to the exopeptidase proteolysis, different from effects of the incorporated sequence recognized by tobacco vein mottling virus protease at C-terminus. Using analyses of three fluorescent dyes including 8-anilino-1-naphthalenesulfonic acid, N-phenyl-1-naphthylamine, and thioflavin T, the same amounts of the cyclic protein displayed less fluorescence than those of the linear protein upon the heat treatment. The cyclic enzyme displayed the enhanced activity in Escherichia coli cells using the designed novel reporter. In this system, d-serine was added to the culture and transported into the cytoplasm. It was transformed by pre-overexpression of the diaminopropionate ammonia-lyase, and untransformed d-serine was oxidized by the coproduced human d-amino acid oxidase to generate hydrogen peroxide. This oxidant is monitored by the HyPer indicator. The current results presented that the cyclized enzyme could be applied as a better candidate to block the neurotoxin biosynthesis in certain plant species.


Assuntos
Amônia-Liases , Neurotoxinas , Salmonella typhimurium , Humanos , Ciclização , Escherichia coli/genética , Serina
16.
Inorg Chem ; 63(9): 4185-4195, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38364251

RESUMO

Posttreatment of pristine metal-organic frameworks (MOFs) with suitable vapor may be an effective way to regulate their structures and properties but has been less explored. Herein, we report an interesting example in which a crystalline nonporous Eu(III)-MOF was transferred to a porous amorphous MOF (aMOF) via iodine vapor adsorption-desorption posttreatment, and the resulting aMOF showed improved turn-on sensing properties with respect to Ag+ ions. The crystalline Eu-MOF, namely, Eu-IPDA, was assembled from Eu(III) and 4,4'-{4-[4-(1H-imidazol-1-yl)phenyl]pyridine-2,6-diyl}dibenzoic acid (H2IPDA) and exhibited a two-dimensional (2D) coordination network based on one-dimensional secondary building blocks. The close packing of the 2D networks gives rise to a three-dimensional supramolecular framework without any significant pores. Interestingly, the nonporous Eu-IPDA could absorb iodine molecules when Eu-IPDA crystals were placed in iodine vapor at 85 °C, and the adsorption capacity was 1.90 g/g, which is comparable to those of many MOFs with large BET surfaces. The adsorption of iodine is attributed to the strong interactions among the iodine molecule, the carboxy group, and the N-containing group and leads to the amorphization of the framework. After immersion of the iodine-loaded Eu-IPDA in EtOH, approximately 89.7% of the iodine was removed, resulting in a porous amorphous MOF, denoted as a-Eu-IPDA. In addition, the remaining iodine in the a-Eu-IPDA framework causes strong luminescent quenching in the fluorescence emission region of the Eu(III) center when compared with that in Eu-IPDA. The luminescence intensity of a-Eu-IPDA in water suspensions was significantly enhanced when Ag+ ions were added, with a detection limit of 4.76 × 10-6 M, which is 1000 times that of pristine Eu-IPDA. It also showed strong anti-interference ability over many common competitive metal ions and has the potential to sense Ag+ in natural water bodies and traditional Chinese medicine preparations. A mechanistic study showed that the interactions between Ag+ and the absorbed iodine, the carboxylate group, and the N atoms all contribute to the sensing performance of a-Eu-IPDA.

17.
BMC Infect Dis ; 24(1): 50, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182990

RESUMO

BACKGROUND: Linezolid exhibits antibacterial activity against sensitive and drug-resistant strains of Mycobacterium tuberculosis. Knowledge on the distribution of linezolid in different types of bones in patients with spinal tuberculosis (TB) is lacking, which limits the pharmacokinetic and pharmacodynamic studies of linezolid. This study aimed to evaluate the distribution of linezolid in diseased and nondiseased bones in patients with spinal TB. METHODS: Spinal TB patients treated with linezolid-containing regimens and whose diseased and nondiseased bones were collected during surgery were enrolled retrospectively from January 2017 to February 2022. Blood, nondiseased bones, and diseased bones were collected simultaneously during the operation. Linezolid concentrations in the plasma, nondiseased bones, and diseased bones were subjected to high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Seven eligible spinal TB patients, including one rifampicin-resistant case, were enrolled. Following a 600 mg oral administration of linezolid before surgery, the median concentrations of linezolid in plasma, nondiseased bone, and diseased bone of the seven patients were 8.23, 1.01, and 2.13 mg/L, respectively. The mean ratios of linezolid concentration in nondiseased bones/plasma, diseased bones/plasma and diseased bones/nondiseased bones reached 0.26, 0.49, and 2.27, respectively. The diseased bones/plasma presented a higher mean ratio of linezolid concentration than nondiseased bones/plasma, and the difference was statistically significant (t = 2.55, p = 0.025). Pearson's correlation analysis showed the positively correlation of linezolid concentrations in diseased and nondiseased bones (r = 0.810, p = 0.027). CONCLUSIONS: Linezolid exhibits a higher concentration distribution in diseased bones than in nondiseased bones.


Assuntos
Mycobacterium tuberculosis , Tuberculose da Coluna Vertebral , Humanos , Linezolida/uso terapêutico , Tuberculose da Coluna Vertebral/tratamento farmacológico , Estudos Retrospectivos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
18.
BMC Geriatr ; 24(1): 189, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409011

RESUMO

BACKGROUND: There are a variety of determinants that are key to functional disability of older adults. However, little is known regarding the relationship between cognitive frailty and disability among older people. The aims of this study were to examine the associations between cognitive frailty and its six components with instrumental activities of daily living (IADL) functioning in community-dwelling older adults. METHODS: A total of 313 community-dwelling older adults (aged ≥ 65 years) were recruited from eight community centers in central China. Cognitive frailty was operationalized using the Mini-Mental State Examination for the evaluation of cognitive status and the Fried criteria for the evaluation of physical frailty. The outcome was functional disability assessed by the IADL scale. The association between cognitive frailty, as well as its components, and IADL limitations was identified by conducting binary logistic regression analysis. RESULTS: The prevalence of cognitive frailty was 8.9% in this study. The results showed that cognitive frailty (OR = 22.86) and frailty without cognitive impairment (OR = 8.15) were associated with IADL limitations. Subdimensions of cognitive frailty, exhaustion, weakness, low physical activity and cognitive impairment components were independently associated with IADL limitations. CONCLUSION: Cognitive frailty was associated with a higher prevalence of disability. Interventions for improving cognitive frailty should be developed to prevent IADL disability among community-dwelling older adults in China.


Assuntos
Fragilidade , Idoso , Humanos , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Idoso Fragilizado/psicologia , Vida Independente/psicologia , Estudos Transversais , Atividades Cotidianas , China/epidemiologia , Cognição , Avaliação Geriátrica/métodos
19.
BMC Musculoskelet Disord ; 25(1): 429, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824539

RESUMO

This article reports a case of a female patient admitted with swelling and subcutaneous mass in the right forearm, initially suspected to be multiple nerve fibroma. However, through preoperative imaging and surgery, the final diagnosis confirmed superficial thrombophlebitis. This condition resulted in entrapment of the radial nerve branch, leading to noticeable nerve entrapment and radiating pain. The surgery involved the excision of inflammatory tissue and thrombus, ligation of the cephalic vein, and complete release of the radial nerve branch. Postoperative pathology confirmed the presence of Superficial Thrombophlebitis. Through this case, we emphasize the importance of comprehensive utilization of clinical, imaging, and surgical interventions for more accurate diagnosis and treatment. This is the first clinical report of radial nerve branch entrapment due to superficial thrombophlebitis.


Assuntos
Antebraço , Síndromes de Compressão Nervosa , Nervo Radial , Tromboflebite , Humanos , Feminino , Tromboflebite/cirurgia , Tromboflebite/etiologia , Tromboflebite/diagnóstico , Síndromes de Compressão Nervosa/etiologia , Síndromes de Compressão Nervosa/cirurgia , Antebraço/inervação , Antebraço/irrigação sanguínea , Antebraço/cirurgia , Nervo Radial/cirurgia , Neuropatia Radial/etiologia , Neuropatia Radial/cirurgia , Pessoa de Meia-Idade
20.
Risk Anal ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622068

RESUMO

Climate change presents challenges to policy and economic stability, necessitating effective trading strategies to reduce environmental risks. This article addresses gaps in existing studies by using a Markov-switching model to consider climate risk. Backward stochastic differential equations are used to optimize utility with three hedging strategies based on the concept of risk aversion. Numerical scenarios confirm the model's superiority in incorporating exogenous events, with our risk-averse strategy outperforming classical approaches. Our strategy outperforms classical strategies by taking a flexible risk trading when investors face risk-averse behavior due to climate risk events. The findings presented in this article have important implications for the development of more resilient investment portfolios and can contribute to climate policy.

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