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1.
J Hazard Mater ; 476: 135119, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38986405

RESUMEN

Increasing evidence has supported that oxidative potential (OP) serves as a crucial indicator of health risk of exposure to PM2.5 over mass concentration. However, there is a lack of comparative studies across multiple cities, particularly on a fine temporal scale. In this study, we aim to investigate daily variation of ambient PM2.5 OP through simultaneous samplings in six Chinese cities for one year. Results showed that more than 60 % of the sampling days exhibited non-zero ranking difference between volume-normalized oxidative potential (OPv) and mass concentration among the six cities. Key components contributing to OPv inculde Mn, NO3-, and K+, followed by Ca2+, Al, SO42-, Cl-, Fe, and NH4+. Based on these chemical components, we developed a stepwise multivariable linear regression model (R2: 0.71) for OPv prediction. The performance of the model is comparable to both species- and sources-based ones in the literature. These findings suggest that a relatively lower daily-averaged mass concentration of PM2.5 does not necessarily indicate a lower oxidative risk. Future studies and policy developments on health benefits should also consider OPv rather than mass concentration alone. Priority could be given to sources/species that contribute significantly to oxidative potential of ambient PM2.5. SYNOPSIS: This study highlights inclusion of oxidative potential as a complementary metric for air pollution assessment and control.

2.
Alzheimers Dement ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023044

RESUMEN

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38870492

RESUMEN

Background: Implantation is a highly coordinated event involving both embryonic and endometrial participation. The endometrium expresses a complex array of proteins during the menstrual cycle many of which help to define a period of receptivity collectively known as the "window of implantation." Objective: Using high-throughput RNA sequencing technology analysis to find differentially expressed genes before and after the endometrial window, and search for key marker genes of the membrane implantation window. Design: This was a retrospective study. Setting: This study was performed in the Department of Obstetrics and Gynecology, Taizhou People's Hospital. Participants: Fifty patients with repeated implantation failure in in vitro fertilization were selected and were divided into (1) the normal window group (36 cases); (2) the window forward group (8 cases); and (3) the window backward group (6 cases) based on endometrial biopsy findings. Interventions: Using RNA sequencing technology combined with biological information analysis tools to analyze the differentially-expressed genes in 9 samples. Gene Ontology databases were used for the functional annotation of these differentially-expressed genes. Kyoto Encyclopedia of Genes and Genomes analysis was used to draw a signal path diagram. Primary Outcome Measures: (1) Screening of differentially-expressed genes and (2) functional analysis of the differential genes. Results: A total of 22 differentially-expressed genes related to endometrial receptivity were obtained by transcriptome sequencing. Seven of the 22 differentially-expressed genes have been shown to have a close relationship with the endometrial receptive window period. Further, it was proved that the Wnt signaling pathway and mitogen-activated protein kinase signaling pathway were closely related to endometrial receptivity. Conclusions: The present study identified a series of key genes and pathways that may be involved in the endometrial window period, providing an experimental and theoretical basis for exploring the personalized embryo transfer program.

5.
Pharmaceutics ; 16(6)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38931844

RESUMEN

Direct nose-to-brain drug delivery, a promising approach for treating neurological disorders, faces challenges due to anatomical variations between adults and children. This study aims to investigate the spatial particle deposition of micron-sized particles in the nasal cavity among adult and pediatric subjects. This study focuses on the olfactory region considering the effect of intrasubject parameters and particle properties. Two child and two adult nose models were developed based on computed tomography (CT) images, in which the olfactory region of the four nasal cavity models comprises 7% to 10% of the total nasal cavity area. Computational Fluid Dynamics (CFD) coupled with a discrete phase model (DPM) was implemented to simulate the particle transport and deposition. To study the deposition of micrometer-sized drugs in the human nasal cavity during a seated posture, particles with diameters ranging from 1 to 100 µm were considered under a flow rate of 15 LPM. The nasal cavity area of adults is approximately 1.2 to 2 times larger than that of children. The results show that the regional deposition fraction of the olfactory region in all subjects was meager for 1-100 µm particles, with the highest deposition fraction of 5.7%. The deposition fraction of the whole nasal cavity increased with the increasing particle size. Crucially, we identified a correlation between regional deposition distribution and nasal cavity geometry, offering valuable insights for optimizing intranasal drug delivery.

6.
Arch Dermatol Res ; 316(6): 229, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787405

RESUMEN

The disease severity of psoriasis is mainly assessed subjectively via  psoriasis area and severity index (PASI) and body surface area (BSA), while an optimal measure of cutaneous response, may overlook systemic inflammation in psoriasis patients. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), monocyte to high density lipoprotein ratio (MHR), and systemic immune-inflammation index (SII) exhibit notable associations with the inflammation severity in multiple diseases. The aim of this retrospective study was to explore the associations between inflammatory parameters and the skin lesions' severity of psoriasis. After analysis, we found that patients with psoriasis had higher NLR, MLR, PLR, MHR, and SII levels compared to the control group. At baseline, the parameters of NLR (r = 0.124, P = 0.003), MLR (r = 0.153, P < 0.001), MHR (r = 0.217, P < 0.001) and SII (r = 0.141, P = 0.001) had a positive correlation with PASI in psoriasis patients. At the same time, we analyzed the patients who received different systemic therapy. We observed a significant decrease in NLR, PLR, MLR, and SII in psoriasis patients after treatment. Notably, TNF-α inhibitors and IL-17A inhibitors subgroups showed a more significant reduction than IL-23/IL-12/23 inhibitors and MTX medication. Additionally, we found the change of NLR (r = 0.194, P < 0.001), PLR (r = 0.104, P = 0.014), MLR (r = 0.191, P < 0.001), MHR (r = 0.106, P = 0.012), and SII (r = 0.228, P < 0.001) had a positive correlation with the change of PASI in psoriasis patients. In conclusion, this study suggests that NLR, MLR, and SII may serve as useful biomarkers for assessing systemic inflammation extent and disease severity in psoriasis patients.


Asunto(s)
Biomarcadores , Inflamación , Neutrófilos , Psoriasis , Índice de Severidad de la Enfermedad , Humanos , Psoriasis/inmunología , Psoriasis/sangre , Psoriasis/diagnóstico , Femenino , Masculino , Estudios Retrospectivos , Biomarcadores/sangre , Persona de Mediana Edad , Adulto , Neutrófilos/inmunología , Inflamación/inmunología , Inflamación/diagnóstico , Inflamación/sangre , Linfocitos/inmunología , Plaquetas/inmunología , Monocitos/inmunología , Anciano
7.
Mycopathologia ; 189(3): 33, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627263

RESUMEN

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.


Asunto(s)
Dermatomicosis , Humanos , Masculino , Dermatomicosis/patología , Piel/patología , Trichophyton , Microscopía , Escroto/microbiología
9.
Sci Total Environ ; 927: 172338, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608897

RESUMEN

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.


Asunto(s)
Cianobacterias , Eutrofización , Lagos , Temperatura , Lagos/microbiología , Lagos/química , China , Monitoreo del Ambiente , Nitrógeno/análisis , Fitoplancton , Cambio Climático , Estaciones del Año , Fósforo/análisis , Nutrientes/análisis , Calentamiento Global
10.
Protein J ; 43(3): 544-558, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581543

RESUMEN

To solve the large size faultiness of Oryza sativa recombinant human serum albumin nanoparticle (OsrHSA NP), the structural discrepancies between OsrHSA and plasma-derived human serum albumin (pdHSA) were analyzed deeply in this research. It demonstrated that there were some subtle structural discrepancies located in subdomain IA and IIA between OsrHSA and pdHSA, which included peptide backbone, disulphide bridge and some amino acids. Firstly, the structural discrepancies were investigated through literature comparison, it inferred that the structural discrepancies resulted from the fatty acid (FA) binding to OsrHSA at site 2 of subdomain IA and IIA. To form a cavity for accommodation of FA molecule in OsrHSA, the peptide backbone structure of subdomain IA and IIA would change, accompanied by the conformational transition of disulphide bridges and side chain structure change of some amino acids in subdomain IA and IIA. These alterations induced the exposure of tryptophan (Trp) and tyrosine (Tyr) residues in subdomain IA and IIA and the decrease of net negative charges of molecular surface. The former would promote more OsrHSA molecules aggregate, and the latter would weaken the electrostatic repulsion. As a result, the size of OsrHSA NP was more extensive than that of pdHSA NP (175.84 ± 15.63 nm vs. 31.67 ± 1.31 nm) when the concentration of Dimethyl Sulphoxide (DMSO) was 30% (v/v). In this study, the experimental scheme of OsrHSA NP preparation was improved. There were two changes in the enhanced preparation scheme: pH 8.2 PBS buffer and 63% DMSO. It indicated that the improved OsrHSA NP carrier was comparable to the pdHSA NP carrier. The size and drug loading of paclitaxel-loaded improved OsrHSA NP were 53.57 ± 3.63 nm and 7.25 ± 0.46% (w/w), and those of docetaxel-loaded improved OsrHSA NP were 44.75 ± 2.26 nm and 8.43 ± 0.74% (w/w). Moreover, both NPs exhibited good stability for 168 h at 7.4 pH values. It is established that the improved OsrHSA NP is comparable to the pdHSA NP as a taxane delivery system.


Asunto(s)
Nanopartículas , Oryza , Proteínas Recombinantes , Albúmina Sérica Humana , Humanos , Oryza/química , Albúmina Sérica Humana/química , Proteínas Recombinantes/química , Nanopartículas/química , Taxoides/química , Sistemas de Liberación de Medicamentos
11.
Pest Manag Sci ; 80(8): 3997-4005, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38527976

RESUMEN

BACKGROUND: Canonical biocontrol bacteria were considered to inhibit pathogenic bacteria mainly by secreting antibiotic metabolites or enzymes. Recent studies revealed that some biocontrol bacteria can inhibit pathogenic bacteria through contact-dependent killing (CDK) mediated by contact-dependent secretion systems. The CDK was independent of antibiotic metabolites and often ignored in normal biocontrol activity assay. RESULTS: In this study, we aimed to use a pathogen enrichment strategy to isolate non-canonical bacteria with CDK ability. Rhizosphere soil samples from Chinese cabbage showing soft rot symptom were collected and Pectobacterium carotovorum subsp. carotovorum (Pcc), the pathogen of cabbage soft rot, were added into these samples to enrich bacteria which attached on Pcc cells. By co-culture with Pcc, four bacteria strains (named as PcE1, PcE8, PcE12 and PcE13) showing antibacterial activity were isolated from Chinese cabbage rhizosphere. These four bacteria strains showed CDK abilities to different pathogenic bacteria of horticultural plants. Among them, PcE1 was identified as Chryseobacterium cucumeris. Genome sequencing showed that PcE1 genome encoded a type VI secretion system (T6SS) gene cluster. By heterologous expression, four predicted T6SS effectors of PcE1 showed antibacterial activity to Escherichia coli. CONCLUSION: Overall, this study isolated four bacteria strains with CDK activity to various horticultural plant pathogens, and revealed possible involvement of T6SS of Chryseobacterium cucumeris in antibacterial activity. These results provide valuable insight for potential application of CDK activity in biocontrol bacteria. © 2024 Society of Chemical Industry.


Asunto(s)
Antibiosis , Brassica , Pectobacterium carotovorum , Brassica/microbiología , Pectobacterium carotovorum/genética , Microbiología del Suelo , Rizosfera , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Sistemas de Secreción Tipo VI/genética , Sistemas de Secreción Tipo VI/metabolismo
12.
Int J Cardiol ; 405: 131947, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38458390

RESUMEN

BACKGROUND: Remnant cholesterol (RC) promotes cardiovascular disease (CVD) in the general population, but its role among rheumatoid arthritis (RA) patients remains unknown. We aimed to investigate circulating RC levels associated with incident CVD among Chinese patients with RA. METHODS: A total of 1018 RA patients free of baseline CVD were included and followed up in a prospective RA CVD cohort from 2001 to 2022. Fasting serum levels of triglycerides, total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured, while RC and Non-HDL-C levels were calculated. The primary exposure was RC levels. A LASSO Cox model was used to select covariates. The Fine-Gray competing risk model was used to estimate hazard ratios (HRs). RESULTS: RA patients had a mean age of 53.9 years, and 802 (78.8%) were females. After a median follow-up of 5.54 years, 131 patients developed CVD with an incidence rate of 21.6 per 1000 person-years. Continuous and quartile-categorized RC levels were associated with incident CVD before and after multivariate adjustment and Bonferroni correction (all P < 0.001). There were no robust associations of other lipids with incident CVD. The fully adjusted HRs for RC were 2.30 (95% CI 1.58-3.35) per 1 mmol/L increase, and 2.40 (1.36-4.25) and 2.81 (1.60-4.94) for patients in the 3rd and 4th versus the 1st quartile, respectively. CONCLUSIONS: Circulating RC levels are positively associated with incident CVD among Chinese RA patients independent of known risk factors, implying its clinically preferable use for improving the stratification of CVD risk in RA patients.


Asunto(s)
Artritis Reumatoide , Enfermedades Cardiovasculares , Colesterol , Lipoproteínas , Triglicéridos , Humanos , Artritis Reumatoide/sangre , Artritis Reumatoide/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Incidencia , Estudios Prospectivos , Colesterol/sangre , Estudios de Seguimiento , Adulto , China/epidemiología , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Factores de Riesgo
13.
Sci Total Environ ; 926: 171879, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38521271

RESUMEN

Bacteria and fungi are ubiquitous throughout built environments and are suspended in the air, potentially affecting human health. However, the impacts of climate zones on the diversity, structure, and stochastic assembly of indoor airborne microbes remain unknown. This study comprehensively analyzed indoor airborne microbes across five climate zones in China during the summer and winter using high-throughput sequencing. The diversity and structure of indoor airborne communities vary across climatic zones. A random forest model was used to identify biomarkers in different climate zones. The results showed no relationship between the biomarkers and their rankings in mean relative abundance. The Sloan neutral model fitting results indicated that the impact of climate zones on the stochastic process in the assembly of indoor airborne microbes was considerably more important than that of seasons. Additionally, the influence of seasons on the diversity, structure, and stochastic assembly process of indoor airborne microbes differed among different climate zones. The diversity, structure, and stochastic assembly processes of bacteria present distinctive outcomes in climate zones and seasons compared with those of fungi. Overall, these findings indicate that customized strategies are necessary to manage indoor airborne microbial communities in each climate zone, season, and for specific microbial species.


Asunto(s)
Contaminación del Aire Interior , Microbiota , Humanos , Estaciones del Año , Hongos , Bacterias , Microbiología del Aire , Biomarcadores , Contaminación del Aire Interior/análisis
14.
J Clin Nurs ; 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519848

RESUMEN

AIMS: To identify the contaminated areas of the hand collection and analyse the distribution characteristics of bacteria in the hand after swab collection. DESIGN: This study used a cross-sectional design. METHODS: A cross-sectional study sampling 50 pairs of hands (sampling hand and auxiliary hand) of healthcare workers was performed. Ten samples were collected from each participant. The optimal hand hygiene rates and bacterial colony counts of the whole hand and different hand sections without hand hygiene were identified as the primary outcomes. RESULTS: The optimal hand hygiene rates of the sampling hand and auxiliary hand were 88.8% (222/250) and 91.6% (229/250), respectively. The lowest optimal hand hygiene rates for the sampling hand and the auxiliary hand were both on the dorsal side of the finger and the dorsum of the hand (86.0%, 86.0% vs. 90.0%, 86.0%); the optimal hand hygiene rates for both sites of the sampling hand were 86.0% (43/50), and the optimal hand hygiene rates for the auxiliary hand were 90.0% (45/50) and 86.0% (43/50). The bacteria colony counts did not differ between the sampling hands and auxiliary hand. CONCLUSIONS: The dorsal side of the finger and dorsum of the hand were the most likely to be contaminated during oropharyngeal swab collection. Therefore, it is essential to pay extra attention to hand hygiene care of these two sites during the collection process to minimize the risk of cross-contamination. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were adopted in this study.

15.
J Imaging Inform Med ; 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424277

RESUMEN

This study aims to develop an MRI-based radiomics model to assess the likelihood of recurrence in luminal B breast cancer. The study analyzed medical images and clinical data from 244 patients with luminal B breast cancer. Of 244 patients, 35 had experienced recurrence and 209 had not. The patients were randomly divided into the training set (51.5 ± 12.5 years old; n = 171) and the test set (51.7 ± 11.3 years old; n = 73) in a ratio of 7:3. The study employed univariate and multivariate Cox regression along with the least absolute shrinkage and selection operator (LASSO) regression methods to select radiomics features and calculate a risk score. A combined model was constructed by integrating the risk score with the clinical and pathological characteristics. The study identified two radiomics features (GLSZM and GLRLM) from DCE-MRI that were used to calculate a risk score. The AUCs were 0.860 and 0.868 in the training set and 0.816 and 0.714 in the testing set for 3- and 5-year recurrence risk, respectively. The combined model incorporating the risk score, pN, and endocrine therapy showed improved predictive power, with AUCs of 0.857 and 0.912 in the training set and 0.943 and 0.945 in the testing set for 3- and 5-year recurrence risk, respectively. The calibration curve of the combined model showed good consistency between predicted and measured values. Our study developed an MRI-based radiomics model that integrates clinical and radiomics features to assess the likelihood of recurrence in luminal B breast cancer. The model shows promise for improving clinical risk stratification and treatment decision-making.

16.
Alzheimers Dement ; 20(4): 2516-2525, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38329281

RESUMEN

INTRODUCTION: The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aß-PET) in a tertiary memory clinic setting in China. METHODS: A total of 1073 patients were offered Aß-PET using 18F-florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non-AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aß-PET results. RESULTS: After disclosure of the Aß-PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late-onset group, the early-onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence. DISCUSSION: Aß-PET has significant impacts on the changes of diagnoses and management in Chinese population. Early-onset cases are more likely to benefit from Aß-PET than late-onset cases. HIGHLIGHTS: Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients. Amyloid PET leads to a change of treatment plans in Chinese patients. Early-onset cases are more likely to benefit from amyloid PET than late-onset cases.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Amiloide , Enfermedad de Alzheimer/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Proteínas Amiloidogénicas , Compuestos de Anilina , China , Péptidos beta-Amiloides , Disfunción Cognitiva/diagnóstico
17.
Cell Genom ; 4(3): 100501, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38335956

RESUMEN

The precise roles of chromatin organization at osteoporosis risk loci remain largely elusive. Here, we combined chromatin interaction conformation (Hi-C) profiling and self-transcribing active regulatory region sequencing (STARR-seq) to qualify enhancer activities of prioritized osteoporosis-associated single-nucleotide polymorphisms (SNPs). We identified 319 SNPs with biased allelic enhancer activity effect (baaSNPs) that linked to hundreds of candidate target genes through chromatin interactions across 146 loci. Functional characterizations revealed active epigenetic enrichment for baaSNPs and prevailing osteoporosis-relevant regulatory roles for their chromatin interaction genes. Further motif enrichment and network mapping prioritized several putative, key transcription factors (TFs) controlling osteoporosis binding to baaSNPs. Specifically, we selected one top-ranked TF and deciphered that an intronic baaSNP (rs11202530) could allele-preferentially bind to YY2 to augment PAPSS2 expression through chromatin interactions and promote osteoblast differentiation. Our results underline the roles of TF-mediated enhancer-promoter contacts for osteoporosis, which may help to better understand the intricate molecular regulatory mechanisms underlying osteoporosis risk loci.


Asunto(s)
Osteoporosis , Secuencias Reguladoras de Ácidos Nucleicos , Humanos , Factores de Transcripción/genética , Osteoporosis/genética , Cromatina/genética , Regiones Promotoras Genéticas/genética
18.
BMC Med Imaging ; 24(1): 31, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38308230

RESUMEN

PURPOSE: The tumor immune microenvironment is a valuable source of information for predicting prognosis in breast cancer (BRCA) patients. To identify immune cells associated with BRCA patient prognosis from the Cancer Genetic Atlas (TCGA), we established an MRI-based radiomics model for evaluating the degree of immune cell infiltration in breast cancer patients. METHODS: CIBERSORT was utilized to evaluate the degree of infiltration of 22 immune cell types in breast cancer patients from the TCGA database, and both univariate and multivariate Cox regressions were employed to determine the prognostic significance of immune cell infiltration levels in BRCA patients. We identified independent prognostic factors for BRCA patients. Additionally, we obtained imaging features from the Cancer Imaging Archive (TCIA) database for 73 patients who underwent preoperative MRI procedures, and used the Least Absolute Shrinkage and Selection Operator (LASSO) to select the best imaging features for constructing an MRI-based radiomics model for evaluating immune cell infiltration levels in breast cancer patients. RESULTS: According to the results of Cox regression analysis, M2 macrophages were identified as an independent prognostic factor for BRCA patients (HR = 32.288, 95% CI: 3.100-357.478). A total of nine significant features were selected to calculate the radiomics-based score. We established an intratumoral model with AUCs (95% CI) of 0.662 (0.495-0.802) and 0.678 (0.438-0.901) in the training and testing cohorts, respectively. Additionally, a peritumoral model was created with AUCs (95% CI) of 0.826 (0.710-0.924) and 0.752 (0.525-0.957), and a combined model was established with AUCs (95% CI) of 0.843 (0.723-0.938) and 0.744 (0.491-0.965). The peritumoral model demonstrated the highest diagnostic efficacy, with an accuracy, sensitivity, and specificity of 0.773, 0.727, and 0.818, respectively, in its testing cohort. CONCLUSION: The MRI-based radiomics model has the potential to evaluate the degree of immune cell infiltration in breast cancer patients, offering a non-invasive imaging biomarker for assessing the tumor microenvironment in this disease.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Radiómica , Microambiente Tumoral , Pronóstico , Imagen por Resonancia Magnética
19.
Neuroscience ; 540: 27-37, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38218401

RESUMEN

The expression levels of SHANK3 are associated with autism spectrum disorder (ASD). The dynamic changes in SHANK3 expression during different stages of brain development may impact the progression of ASD. However, no studies or detailed analyses exploring the upstream mechanisms that regulate SHANK3 expression have been reported. In this study, we employed immunofluorescence to examine the expression of SHANK3 in brain organoids at various stages. Our results revealed elevated levels of SHANK3 expression in brain-like organoids at Day 60. Additionally, we utilized bioinformatics software to predict and analyze the SHANK3 gene's transcription start site. Through the dual luciferase reporter gene technique, we identified core transcription elements within the SHANK3 promoter. Site-directed mutations were used to identify specific transcription sites of SHANK3. To determine the physical binding of potential transcription factors to the SHANK3 promoter, we employed electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Our findings demonstrated that the transcription factor EGR1 regulates SHANK3 expression by binding to the transcription site of the SHANK3 promoter. Although this study did not investigate the pathological phenotypes of human brain organoids or animal model brains with EGR1 deficiency, which could potentially substantiate the findings observed for SHANK3 mutants, our findings provide valuable insights into the relationship between the transcription factor, EGR1, and SHANK3. This study contributes to the molecular understanding of ASD and offers potential foundations for precise targeted therapy.


Asunto(s)
Trastorno del Espectro Autista , Animales , Humanos , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Regulación de la Expresión Génica , Factores de Transcripción/metabolismo , Regiones Promotoras Genéticas , Encéfalo/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo
20.
Langmuir ; 40(4): 2396-2404, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38237152

RESUMEN

The rate performance of lithium iron phosphate (LiFePO4) is mainly limited by its poor electronic conductivity and slow Li-ion diffusion rate. Graphene-based materials are often compounded with LiFePO4 (LFP) to improve their rate performance, mainly because of their excellent electrical conductivity. Unlike most past composite work focusing on the conductive network between LFP and graphene, in this work, we further developed the functionality of graphene-based materials as nanoparticle carriers, where the nitrogen-doping strategy endows graphene with properties that make it an efficient structural regulation platform during the solvothermal process. Compared to reduced graphene oxide, not only does the nitrogen-doped sites confer more nucleation growth sites for LFP on the graphene surface during the solvothermal process, but also the localized formation of an EG-enriched microenvironment helps to further inhibit the in situ growth of LFP along [010]. The efficient structural regulation platform assisted the synthesis of (010)-oriented LFP with a smaller particle size, which further shortens the Li-ion diffusion paths. The optimized LFP composite electrode materials exhibit a discharge-specific capacity of 133.1 mA·h/g at 10C, which exceeds/is comparable to that of previously reported LFP compounded with graphene-based materials. This work broadens the functionality of graphene-based carriers and provides new ideas for the controllable synthesis of nanoparticles.

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