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1.
Int J Biol Macromol ; 279(Pt 3): 135367, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39244117

RESUMEN

Chitosan, as a biological macromolecule with excellent biocompatibility, has great potential for application in immobilized metal affinity chromatography (IMAC) strategies. In-depth analysis of low-abundance phosphopeptides in organisms can help reveal the pathological mechanisms of diseases. Here, we developed an IMAC material based on a biomimetic honeycomb chitosan membrane. The material demonstrates excellent biocompatibility, good hydrophilicity, and strong metal chelating capacity, which collectively confer outstanding enrichment properties. The material has high sensitivity (0.05 fmol), great selectivity (1:2000), excellent cycling stability (at least 10 cycles) and acid-base stability. In addition, the material was employed in human serum, successfully enriching 129 phosphopeptides from the serum of gastric cancer patients and 146 phosphopeptides from healthy controls. Sequence logo suggests a potential association between gastric cancer and glutamine. Ultimately, an in-depth gene ontology analysis was carried out on the phosphopeptides that were enriched in the serum samples. Compared to normal controls, our results demonstrated dysregulated expression of biological process, cellular component, and molecular function in gastric cancer patients. This suggests that the disease involves, such as blood coagulation pathways, cholesterol metabolism, and heparin binding. All experimental outcomes converge to demonstrate the substantial promise of the material for applications within proteomics research.

2.
J Alzheimers Dis ; 101(1): 75-89, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39177597

RESUMEN

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is not easily detected in the early stage. Handwriting and walking have been shown to be potential indicators of cognitive decline and are often affected by AD. Objective: This study proposes an assisted screening framework for AD based on multimodal analysis of handwriting and gait and explores whether using a combination of multiple modalities can improve the accuracy of single modality classification. Methods: We recruited 90 participants (38 AD patients and 52 healthy controls). The handwriting data was collected under four handwriting tasks using dot-matrix digital pens, and the gait data was collected using an electronic trail. The two kinds of features were fused as inputs for several different machine learning models (Logistic Regression, SVM, XGBoost, Adaboost, LightGBM), and the model performance was compared. Results: The accuracy of each model ranged from 71.95% to 96.17%. Among them, the model constructed by LightGBM had the best performance, with an accuracy of 96.17%, sensitivity of 95.32%, specificity of 96.78%, PPV of 95.94%, NPV of 96.74%, and AUC of 0.991. However, the highest accuracy of a single modality was 93.53%, which was achieved by XGBoost in gait features. Conclusions: The research results show that the combination of handwriting features and gait features can achieve better classification results than a single modality. In addition, the assisted screening model proposed in this study can achieve effective classification of AD, which has development and application prospects.


Asunto(s)
Enfermedad de Alzheimer , Análisis de la Marcha , Escritura Manual , Aprendizaje Automático , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Masculino , Femenino , Anciano , Análisis de la Marcha/métodos , Anciano de 80 o más Años , Sensibilidad y Especificidad
3.
Org Biomol Chem ; 22(36): 7321-7326, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39171619

RESUMEN

A novel process has been developed for the selective synthesis of ß-sulfonyl-enamines and 2,3-diarylthiopyrroles. This process utilizes the decarboxylative coupling and ß-C(sp3)-H functionalization of α-amino acids. In this reaction, iodine functions dually as a tandem catalyst to initiate the decarboxylation of α-amino acids and as an oxidant to facilitate the formation of organic sulfides. This innovative approach not only simplifies the synthesis but also enhances the yield and selectivity of the desired products.

4.
Heliyon ; 10(15): e35115, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39165928

RESUMEN

Problem: Previous studies had confirmed that some deep learning models had high diagnostic performance in staging liver fibrosis. However, training efficiency of models predicting liver fibrosis need to be improved to achieve rapid diagnosis and precision medicine. Aim: The deep learning framework of EfficientNetV2-S was noted because of its faster training speed and better parameter efficiency compared with other models. Our study sought to develop noninvasive predictive models based on EfficientNetV2-S framework for staging liver fibrosis. Methods: Patients with chronic liver disease who underwent multi-parametric abdominal MRI were included in the retrospective study. Data augmentation methods including horizontal flip, vertical flip, perspective transformation and edge enhancement were applied to multi-parametric MR images to solve the data imbalance between different liver fibrosis groups. The EfficientNetV2-S models were used for the prediction of liver fibrosis stages F1-2, F1-3, F3, F4 and F3-4. We evaluated the diagnostic performance of our models in training, validation, and test sets by using receiver operating characteristic curve (ROC) analysis. Results: The total training time of EfficientNetV2-S was about 6 h. For differentiating of F1-2 vs F3, the accuracy, sensitivity and specificity of EfficientNetV2-S model were 96.2 %, 96.4 % and 96.0 % in the test set. The AUC in test set was 0.559. The accuracy, sensitivity and specificity were 82.1 %, 74.5 % and 89.6 % in the test set by using EfficientNetV2-S model to differentiate F1-2 vs F3-4, and the AUC in test set were 0.763. For differentiating F1-3 vs F4, the accuracy, sensitivity and specificity of EfficientNetV2-S model were 71.5 %, 73.4 % and 69.5 % in the test set. The AUC was 0.553 in test set. For differentiating F1-2 vs F4, the accuracy, sensitivity and specificity of our model were 84.3 %, 80.2 % and 88.3 % in the test set, and the AUC was 0.715, respectively. For differentiating F3 vs F4, the accuracy, sensitivity and specificity of EfficientNetV2-S model were 92.5 %, 89.1 % and 95.6 % in the test set, and the AUC was 0.696 in the test set. Conclusions: The EfficientNetV2-S models based on multi-parametric MRI had the feasibility for staging of liver fibrosis because they showed high training speed and diagnostic performance in our study.

5.
J Econ Entomol ; 117(4): 1315-1323, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38856713

RESUMEN

Sitobion miscanthi and Schizaphis graminum (Rondani) are the 2 main aphid species that occur simultaneously, causing significant loss to wheat production. Acetamiprid has been used to control a variety of pests, including aphids. In this study, the sublethal effect of acetamiprid on S. miscanthi and S. graminum was evaluated using life-table analyses. The results showed that acetamiprid has a high toxicity to S. miscanthi and S. graminum with a LC50 of 1.90 and 3.58 mg/L at 24 h, respectively. The adult longevity and fecundity of S. miscanthi and S. graminum F0 generation were significantly reduced after being exposed to a sublethal concentration of acetamiprid. Additionally, the sublethal concentration of acetamiprid had negative transgenerational effects on S. miscanthi and S. graminum, which showed a significant decrease in fecundity and population life-table parameters involving age-stage-specific survival rate (sxj), age-specific survival rate (lx), and intrinsic rate of increase (r). Furthermore, the population projections showed that the total population size of S. miscanthi and S. graminum was significantly lower in the aphid group exposed to sublethal concentration of acetamiprid compared to the control group. These results suggest that sublethal concentration of acetamiprid suppresses the population growth of S. miscanthi and S. graminum. This finding is beneficial to the control of wheat aphids, and is important to fully understand the role of acetamiprid in integrated pest management.


Asunto(s)
Áfidos , Insecticidas , Neonicotinoides , Crecimiento Demográfico , Animales , Áfidos/efectos de los fármacos , Insecticidas/farmacología , Fertilidad/efectos de los fármacos , Longevidad/efectos de los fármacos , Femenino , Ninfa/crecimiento & desarrollo , Ninfa/efectos de los fármacos , Triticum
6.
J Genet Genomics ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38849111

RESUMEN

Histone citrullination, an important post-translational modification mediated by peptidyl arginine deiminases, is essential for many physiological processes and epigenetic regulation. However, the causal relationship between histone citrullination and specific gene regulation remains unresolved. In this study, we develop a programmable epigenetic editor by fusing the peptidyl arginine deiminase PPAD from Porphyromonas gingivalis with dCas9. With the assistance of gRNA, PPAD-dCas9 can recruit peptidyl arginine deiminases to specific genomic loci, enabling direct manipulation of the epigenetic landscape and regulation of gene expression. Our citrullination editor allows for site-specific manipulation of histone H3R2,8,17 and 26 at target human gene loci, resulting in the activation or suppression of different genes in a locus-specific manner. Moreover, the epigenetic effects of the citrullination editor are specific and sustained. This epigenetic editor offers an accurate and efficient tool for exploring gene regulation of histone citrullination.

7.
J Fam Psychol ; 38(5): 732-742, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38753378

RESUMEN

Prior research has established that parents who are in a relationship, yet unmarried at the time of their child's birth, are at an increased risk of relationship instability. However, the processes that may lead to the dissolution of these unmarried parents' couple relationships are less clear. Guided by the vulnerability-stress-adaptation model, the present study examined data from a sample of 1,575 mother and father dyads who participated in the Future of Families and Child Wellbeing Study over a 9-year period. A mixed effects Cox regression model was used to investigate how unmarried parents' reports of enduring vulnerability (depressive symptoms) over time influenced the onset of relationship dissolution between the time their focal child was 1- and 9-years old. Further, the potential mediating effect of mothers' and fathers' reports of stressful events (parenting stress) and adaptive processes (couple relationship interactions and coparenting behaviors) on the association between depressive symptoms and relationship dissolution by the 9-year follow-up were also examined. Results indicated that mothers' and fathers' reports of experiencing depressive symptoms over time were associated with relationship dissolution. Further, perceptions of couple interactions emerged as a significant mediator at the 3- (mothers) and 5- (mothers and fathers) year follow-up. Coparenting behaviors were a significant mediator for mothers and fathers at the 3- and 5-year follow-up. These results highlight how experiencing depressive symptoms over time, as well as perceptions of couple interactions and coparenting behaviors throughout the early years of parenting, are salient factors in the instability of unmarried parents' relationships. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Adaptación Psicológica , Depresión , Estrés Psicológico , Humanos , Femenino , Masculino , Adulto , Estrés Psicológico/psicología , Depresión/psicología , Adaptación Psicológica/fisiología , Niño , Padres/psicología , Divorcio/psicología , Divorcio/estadística & datos numéricos , Responsabilidad Parental/psicología , Lactante , Preescolar , Relaciones Interpersonales , Ilegitimidad/psicología , Ilegitimidad/estadística & datos numéricos , Madres/psicología , Madres/estadística & datos numéricos
8.
J Adolesc ; 96(5): 1137-1152, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38584575

RESUMEN

INTRODUCTION: Witnessing violence and violent victimization have detrimental effects on adolescents' emotional functioning and ability to envision and plan for their futures. However, research is limited on the impact of violence that occurs in adolescents' communities-whether or not it was witnessed or experienced firsthand. This paper investigated the associations between community exposure to gun homicide and adolescents' high school and college graduation aspirations. METHODS: We analyzed data from the Future of Families and Child Wellbeing Study (N = 3031), a cohort study of children born 1998-2000 in 20 large US cities, merged with incident-level data on deadly gun violence from the Gun Violence Archive (2014-2017). Outcomes were reported by adolescents (girls and boys) during wave 6 (2014-2017) of the study, conducted when the children were 15 years of age. We employed ordinary least squares regression, ordered logistic regression, and multilevel stratification to examine the average and heterogeneous impacts of community exposure to gun homicide on adolescents' educational aspirations. RESULTS: Community exposure to gun homicide was associated with reduced high school graduation aspirations, particularly among adolescents with the lowest risk of exposure to gun homicide. Gun homicide exposure was also associated with increased college graduation aspirations; this association was concentrated among adolescents with moderate-high risk of exposure. CONCLUSIONS: Given the importance of education for job opportunities and the better health that accompanies education and occupational attainment, preventing early exposure to gun violence and providing institutional supports to help adolescents facing adversity realize their goals is essential to their long-term health and success.


Asunto(s)
Homicidio , Humanos , Adolescente , Masculino , Femenino , Homicidio/estadística & datos numéricos , Homicidio/psicología , Estados Unidos/epidemiología , Violencia con Armas/estadística & datos numéricos , Violencia con Armas/psicología , Escolaridad , Aspiraciones Psicológicas , Exposición a la Violencia/estadística & datos numéricos , Exposición a la Violencia/psicología , Armas de Fuego/estadística & datos numéricos
9.
Anal Bioanal Chem ; 416(14): 3361-3371, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38607383

RESUMEN

The elucidation of disease pathogenesis can be achieved by analyzing the low-abundance phosphopeptides in organisms. Herein, we developed a novel and easy-to-prepare polymer-coated nanomaterial. By improving the hydrophilicity and spatial conformation of the material, we effectively enhanced the adsorption of phosphopeptides and demonstrated excellent enrichment properties. The material was able to successfully enrich the phosphopeptides in only 1 min. Meanwhile, the material has high selectivity (1:2000), good loading capacity (100 µg/mg), excellent sensitivity (0.5 fmol), and great acid and alkali resistance. In addition, the material was applied to real samples, and 70 phosphopeptides were enriched from the serum of Parkinson's disease (PD) patients and 67 phosphopeptides were enriched from the serum of normal controls. Sequences Logo showed that PD is probably associated with threonine, glutamate, serine, and glutamine. Finally, gene ontology (GO) analysis was performed on phosphopeptides enriched in PD patients' serum. The results showed that PD patients expressed abnormal expression of the cholesterol metabolic process and cell-matrix adhesion in the biological process (BP), endoplasmic reticulum and lipoprotein in the cellular component (CC), and heparin-binding, lipid-binding, and receptor-binding in the molecular function (MF) as compared with normal individuals. All the experiments indicate that the nanomaterials have great potential in proteomics studies.


Asunto(s)
Nanoestructuras , Enfermedad de Parkinson , Fosfopéptidos , Polímeros , Enfermedad de Parkinson/sangre , Humanos , Fosfopéptidos/sangre , Polímeros/química , Nanoestructuras/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
10.
Sci Adv ; 10(17): eadk3852, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38657063

RESUMEN

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.


Asunto(s)
Migración Animal , Genómica , Viento , Animales , Genómica/métodos , Hemípteros/genética , Genoma de los Insectos , Genética de Población
11.
Anal Methods ; 16(17): 2751-2759, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38634398

RESUMEN

Exosomes have gained recognition as valuable reservoirs of biomarkers, holding immense potential for early cancer detection. Consequently, there is a pressing need for the development of an economical and highly sensitive exosome detection methodology. In this work, we present a fluorescence method for breast cancer-derived exosome detection based on Cu-triggered click reaction of azide-modified CD63 aptamer and alkyne functionalized Pdots. The detection threshold for the exosomes obtained from the breast cancer serum was determined to be 6.09 × 107 particles per µL, while the measurable range spanned from 6.50 × 107 to 1.30 × 109 particles per µL. The employed methodology achieved notable success in accurately distinguishing breast cancer patients from healthy individuals through serum analysis. The application of this method showcases the significant potential for early exosome analysis in the clinical diagnosis of breast cancer patients.


Asunto(s)
Alquinos , Aptámeros de Nucleótidos , Azidas , Técnicas Biosensibles , Neoplasias de la Mama , Química Clic , Exosomas , Tetraspanina 30 , Humanos , Neoplasias de la Mama/sangre , Femenino , Exosomas/química , Tetraspanina 30/metabolismo , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Azidas/química , Alquinos/química , Colorantes Fluorescentes/química , Polímeros/química
12.
Small ; 20(33): e2401379, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38522026

RESUMEN

Phase transitions of Mn-based cathode materials associated with the charge and discharge process play a crucial role on the rate capability and cycle life of zinc ion batteries. Herein, a microscopic electrochemical failure mechanism of Zn-MnO2 batteries during the phase transitions from δ-MnO2 to λ-ZnMn2O4 is presented via systematic first-principle investigation. The initial insertion of Zn2+ intensifies the rearrangement of Mn. This is completed by the electrostatic repulsion and co-migration between guest and host ions, leading to the formation of λ-ZnMn2O4. The Mn relocation barrier for the λ-ZnMn2O4 formation path with 1.09 eV is significantly lower than the δ-MnO2 re-formation path with 2.14 eV, indicating the irreversibility of the layered-to-spinel transition. Together with the phase transition, the rearrangement of Mn elevates the Zn2+ migration barrier from 0.31 to 2.28 eV, resulting in poor rate performance. With the increase of charge-discharge cycles, irreversible and inactive λ-ZnMn2O4 products accumulate on the electrode, causing continuous capacity decay of the Zn-MnO2 battery.

13.
Sheng Wu Gong Cheng Xue Bao ; 40(2): 517-528, 2024 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-38369838

RESUMEN

The α-1 antitrypsin Z-mutant protein (ATZ) is the primary cause of α-1 antitrypsin deficiency (AATD). Studying the ubiquitination modification and degradation of ATZ protein is importance for developing treatments for AATD. STUB1 is an important E3 ubiquitin ligase that regulates ubiquitination modification of various proteins. However, whether STUB1 in involved in the ubiquitination modification of ATZ has not been fully elucidated. In this study, the ATZ and STUB1 coding genes were first cloned into the pET28a plasmid, constructing 2 protein expression plasmids. The recombinant plasmids were then transferred into the Escherichia coli for expression. With the optimization of induction temperature and IPTG dosage, the recombinant proteins were successfully expressed. The target proteins were then efficiently purified from cell lysates using metal-chelating affinity chromatography, and the accuracy of the amino acid sequence was verified through protein mass spectrometry analysis. Using the purified ATZ and STUB1, we established an in vitro ubiquitination reaction system. Experimental results showed that, in the presence of ATP, E1 ubiquitin-activating enzyme, and E2 ubiquitin-conjugating enzyme, STUB1 catalyzed the ubiquitination modification of ATZ. This study provides a method for obtaining the ATZ protein in vitro, elucidates the mechanism of STUB1 mediating ATZ ubiquitination, thereby advancing our understanding of the intracellular degradation mechanism of the α-1 antitrypsin Z-mutant.


Asunto(s)
Ubiquitina-Proteína Ligasas , Ubiquitinación , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
14.
Anal Methods ; 16(5): 695-703, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38214200

RESUMEN

The comprehensive investigation of protein phosphorylation and glycosylation aids in the discovery of novel biomarkers as well as the understanding of the pathophysiology of illness. In this work, a nitrogen/titanium-rich porous organic polymer was developed by copolymerizing carbohydrazide (CH) and 2,3-dihydroxyterephthalaldehyde (2,3-Dha) and modifying with Ti4+ (CH-Dha-Ti4+). The adequate nitrogen contributes to the enrichment of glycopeptides via HILIC, while titanium benefits from capturing phosphopeptides through IMAC. The proposed method exhibits excellent selectivity (1 : 1000, both for glycopeptides and phosphopeptides), LOD (for glycopeptides: 0.05 fmol µL-1, for phosphopeptides: 0.2 fmol), loading capacity (for glycopeptides: 100 mg g-1, for phosphopeptides: 125 mg g-1) and size-exclusion effect (1 : 10 000, both for glycopeptides and phosphopeptides). Furthermore, CH-Dha-Ti4+ was applied to capture glycopeptides and phosphopeptides from human serum; 205 glycopeptides and 45 phosphopeptides were detected in the serum of normal controls; and 294 glycopeptides and 63 phosphopeptides were found in the serum of uremia patients after being analyzed by nano LC-MS/MS. The discovered glycopeptides and phosphopeptides were involved in several molecular biological processes and activities, according to a gene ontology study.


Asunto(s)
Fosfopéptidos , Polímeros , Humanos , Fosfopéptidos/química , Fosfopéptidos/metabolismo , Titanio/química , Glicopéptidos/química , Porosidad , Espectrometría de Masas en Tándem
15.
ACS Med Chem Lett ; 15(1): 99-106, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38229745

RESUMEN

A series of spiropiperidines was designed and synthesized by structural modifications based on our previous lead compound 1 and evaluated with cellular signaling assays for the discovery of 5-HT2C receptor (5-HT2CR) selective agonists with a Gq bias. Structure-activity relationship (SAR) studies of spiropiperidines uncovered spiro[chromene-2,4'-piperidine]s as a novel chemotype of 5-HT2CR selective agonists. Among this new series, the 7-chloro analogue 8 was identified as the most potent and selective 5-HT2CR partial agonist (Emax = 71.09%) with an EC50 value of 121.5 nM and no observed activity toward 5-HT2AR or 5-HT2BR. Moreover, compound 8 exhibited no recruitment activity for ß-arrestin and showed low inhibition of hERG at 10 µM. These findings may pave the way to develop more potent Gq-biased 5-HT2CR partial agonists as useful pharmacological tool compounds or potential drug candidates.

16.
Appl Biochem Biotechnol ; 196(8): 5616-5630, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38103122

RESUMEN

Gene knockout is a widely used technique for engineering bacterial genomes, investigating the roles of genes in metabolism, and conferring biological characteristics. Herein, we developed a rapid, efficient, and simple method for the knockout of long gene cassettes in Pseudomonas spp., based on a traditional allelic exchange strategy. The upstream and downstream sequences of the target gene cluster to be deleted were amplified using primers with 5'-end sequences identical to the multiple cloning sites of a suicide plasmid (mutant allele insert vector). The sequences were then fused with the linearized suicide plasmid in one step via seamless cloning. The resulting allelic exchange vector (recombinant plasmid) was introduced from the donor strain (Escherichia coli SM 10) into recipient cells (Pseudomonas putida, P. composti, and P. khazarica) via conjugation. Single-crossover merodiploids (integrates the vector into host chromosome by homologous recombination) were screened based on antibiotic resistance conferred by the plasmid, and double-crossover haploids (deleting the target gene clusters and inserted alien plasmid backbone) were selected using sucrose-mediated counterselection. Unlike other approaches, the method described herein introduces no selective marker genes into the genomes of the knockout mutants. Using our method, we successfully deleted polysaccharide-encoding gene clusters in P. putida, P. composti, and P. khazarica and generated four mutants with single-gene cassette deletions up to 18 kbp and one mutant with double-gene cassette deletion of approximately 34 kbp. Collectively, our results indicate that this method is ideal for the deletion of long genetic sequences, yielding seamless mutants of various Pseudomonas spp.


Asunto(s)
Técnicas de Inactivación de Genes , Plásmidos , Pseudomonas , Pseudomonas/genética , Técnicas de Inactivación de Genes/métodos , Plásmidos/genética , Alelos , Familia de Multigenes , Vectores Genéticos/genética
17.
Mikrochim Acta ; 191(1): 26, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38091130

RESUMEN

A surface-initiated atom transfer radical polymerization method combining click chemistry was employed to prepare a novel porphyrin-based covalent organic framework composite grafted with polymer brushes (TAPBB@GMA@AMA@Cys) for the specific enrichment of N-glycopeptides. The material successfully realized the high efficiency enrichment of N-glycopeptides with good selectivity (1:1000), low detection limit (0.2 fmol/µL), and high loading capacity (133.3 mg·g-1). The TAPBB@GMA@AMA@Cys was successfully applied to actual sample analysis; 235 N-glycopeptides related to 125 glycoproteins and 210 N-glycopeptides related to 121 glycoproteins were recognized from the serum of normal individuals and Alzheimer's disease patients, respectively. Gene ontology studies of molecular functions, cellular components, and biological processes have revealed that identified glycoproteins are strongly associated with neurodegenerative diseases involving innate immune responses, basement membranes, calcium binding, and receptor binding. The above results confirm the surprising potential of materials in glycoproteomics research and practical sample applications.


Asunto(s)
Estructuras Metalorgánicas , Humanos , Estructuras Metalorgánicas/química , Polímeros/química , Glicopéptidos/análisis , Interacciones Hidrofóbicas e Hidrofílicas , Glicoproteínas
18.
Cardiovasc Eng Technol ; 14(6): 827-839, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37973699

RESUMEN

PURPOSE: Pulmonary valve (PV) monocusp reconstruction in transannular patch (TAP) right ventricular outflow tract (RVOT) repair for Tetralogy of Fallot has variable clinical outcomes across different surgical approaches. The study purpose was to systematically evaluate how monocusp leaflet design parameters affect valve function in-vitro. METHODS: A 3D-printed, disease-specific RVOT model was tested under three infant physiological conditions. Monocusps were sewn into models with the native main pulmonary artery (MPA) forming backwalls that constituted 40% and 50% of the reconstructed circumference for z-score zero PV annulus and MPA diameters (native PV z-score - 3.52 and - 2.99 for BSA 0.32m2). Various leaflet free edge lengths (FEL) (relative to backwall), positions (relative to PV STJ), and scallop depths were investigated across both models. Pressure gradient, regurgitation, and coaptation were analyzed with descriptive statistics and regression models. RESULTS: Increasing FEL beyond 100% of the MPA backwall decreased gradient but mildly increased regurgitation to a peak of 25%. Positioning the free edge 2 mm past the STJ mildly increased gradient for each FEL without significantly changing regurgitation compared to STJ placement. Scalloping leaflets trivially affected performance. Pre-folding leaflets improved mobility and slightly reduced gradient. CONCLUSIONS: Balancing gradient, regurgitation, and oversizing for growth, a set of leaflet designs have been selected for pre-clinical evaluation. Designs with leaflet widths 140-160% in the 40% backwall model (110-120% in the 50% backwall), positioned at or 2 mm past the STJ, demonstrated the best results. The next stage of ex-vivo testing will additionally consider native RVOT distensibility, native leaflet interactions, and TAP characteristics.


Asunto(s)
Insuficiencia de la Válvula Pulmonar , Válvula Pulmonar , Tetralogía de Fallot , Lactante , Humanos , Tetralogía de Fallot/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Ventrículos Cardíacos , Politetrafluoroetileno , Resultado del Tratamiento , Estudios Retrospectivos
19.
Sci Adv ; 9(46): eadf3980, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37976354

RESUMEN

Embryonic stem cells (ESCs) have transcriptionally permissive chromatin enriched for gene activation-associated histone modifications. A striking exception is DOT1L-mediated H3K79 dimethylation (H3K79me2) that is considered a positive regulator of transcription. We find that ESCs are depleted for H3K79me2 at shared locations of enrichment with somatic cells, which are highly and ubiquitously expressed housekeeping genes, and have lower RNA polymerase II (RNAPII) at the transcription start site (TSS) despite greater nascent transcription. Inhibiting DOT1L increases the efficiency of reprogramming of somatic to induced pluripotent stem cells, enables an ESC-like RNAPII pattern at the TSS, and functionally compensates for enforced RNAPII pausing. DOT1L inhibition increases H3K27 methylation and RNAPII elongation-enhancing histone acetylation without changing the expression of the causal histone-modifying enzymes. Only the maintenance of elevated histone acetylation is essential for enhanced reprogramming and occurs at loci that are depleted for H3K79me2. Thus, DOT1L inhibition promotes the hyperacetylation and hypertranscription pluripotent properties.


Asunto(s)
Cromatina , Histonas , Histonas/metabolismo , Acetilación , Diferenciación Celular , Cromatina/genética , Transcripción Genética , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo
20.
Front Public Health ; 11: 1155225, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38035307

RESUMEN

Purpose: Chronic low back pain (CLBP) is an aging and public health issue that is a leading cause of disability worldwide and has a significant economic impact on a global scale. Treatments for CLBP are varied, and there is currently no study with high-quality evidence to show which treatment works best. Exercise therapy has the characteristics of minor harm, low cost, and convenient implementation. It has become a mainstream treatment method in clinics for chronic low back pain. However, there is insufficient evidence on which specific exercise regimen is more effective for chronic non-specific low back pain. This network meta-analysis aimed to evaluate the effects of different exercise therapies on chronic low back pain and provide a reference for exercise regimens in CLBP patients. Methods: We searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to 10 May 2022. Inclusion and exclusion criteria were used for selection. We collected information from studies to compare the effects of 20 exercise interventions on patients with chronic low back pain. Results: This study included 75 randomized controlled trials (RCTs) with 5,254 participants. Network meta-analysis results showed that tai chi [standardized mean difference (SMD), -2.11; 95% CI, -3.62 to -0.61], yoga (SMD, -1.76; 95% CI -2.72 to -0.81), Pilates exercise (SMD, -1.52; 95% CI, -2.68, to -0.36), and sling exercise (SMD, -1.19; 95% CI, -2.07 to -0.30) showed a better pain improvement than conventional rehabilitation. Tai chi (SMD, -2.42; 95% CI, -3.81 to -1.03) and yoga (SMD, -2.07; 95% CI, -2.80 to -1.34) showed a better pain improvement than no intervention provided. Yoga (SMD, -1.72; 95% CI, -2.91 to -0.53) and core or stabilization exercises (SMD, -1.04; 95% CI, -1.80 to -0.28) showed a better physical function improvement than conventional rehabilitation. Yoga (SMD, -1.81; 95% CI, -2.78 to -0.83) and core or stabilization exercises (SMD, -1.13; 95% CI, -1.66 to -0.59) showed a better physical function improvement than no intervention provided. Conclusion: Compared with conventional rehabilitation and no intervention provided, tai chi, toga, Pilates exercise, sling exercise, motor control exercise, and core or stabilization exercises significantly improved CLBP in patients. Compared with conventional rehabilitation and no intervention provided, yoga and core or stabilization exercises were statistically significant in improving physical function in patients with CLBP. Due to the limitations of the quality and quantity of the included studies, it is difficult to make a definitive recommendation before more large-scale and high-quality RCTs are conducted.


Asunto(s)
Dolor de la Región Lumbar , Yoga , Humanos , Dolor de la Región Lumbar/terapia , Metaanálisis en Red , Calidad de Vida , Terapia por Ejercicio/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
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