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1.
Genes Dev ; 37(19-20): 883-900, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890975

RESUMO

Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance and its DNA binding, and G118E mice manifest RTT-like symptoms seen in the patient, affirming the pathogenicity of this mutation. Using live-cell and single-molecule imaging, we found that G118E mutation alters MeCP2's chromatin interaction properties in live neurons independently of its effect on protein levels. Here we report the generation and characterization of RTT models of a male hypomorphic variant and reveal new insight into the mechanism by which this pathological mutation affects MeCP2's chromatin dynamics. Our ability to quantify protein dynamics in disease models lays the foundation for harnessing high-resolution single-molecule imaging as the next frontier for developing innovative therapies for RTT and other diseases.


Assuntos
Cromatina , Síndrome de Rett , Feminino , Humanos , Masculino , Camundongos , Animais , Cromatina/metabolismo , Encéfalo/metabolismo , Proteína 2 de Ligação a Metil-CpG/genética , Síndrome de Rett/genética , Mutação , Neurônios/metabolismo
2.
Nucleic Acids Res ; 51(11): e65, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37194709

RESUMO

Despite the need in various applications, accurate quantification of nucleic acids still remains a challenge. The widely-used qPCR has reduced accuracy at ultralow template concentration and is susceptible to nonspecific amplifications. The more recently developed dPCR is costly and cannot handle high-concentration samples. We combine the strengths of qPCR and dPCR by performing PCR in silicon-based microfluidic chips and demonstrate high quantification accuracy in a large concentration range. Importantly, at low template concentration, we observe on-site PCR (osPCR), where only certain sites of the channel show amplification. The sites have almost identical ct values, showing osPCR is a quasi-single molecule phenomenon. Using osPCR, we can measure both the ct values and the absolute concentration of templates in the same reaction. Additionally, osPCR enables identification of each template molecule, allowing removal of nonspecific amplification during quantification and greatly improving quantification accuracy. We develop sectioning algorithm that improves the signal amplitude and demonstrate improved detection of COVID in patient samples.


Assuntos
Teste para COVID-19 , Reação em Cadeia da Polimerase , Humanos , COVID-19 , DNA/genética , Microfluídica
3.
PLoS Genet ; 18(3): e1010130, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35353808

RESUMO

SARS-CoV-2 is a positive-sense, single-stranded RNA virus responsible for the COVID-19 pandemic. It remains unclear whether and to what extent the virus in human host cells undergoes RNA editing, a major RNA modification mechanism. Here we perform a robust bioinformatic analysis of metatranscriptomic data from multiple bronchoalveolar lavage fluid samples of COVID-19 patients, revealing an appreciable number of A-to-I RNA editing candidate sites in SARS-CoV-2. We confirm the enrichment of A-to-I RNA editing signals at these candidate sites through evaluating four characteristics specific to RNA editing: the inferred RNA editing sites exhibit (i) stronger ADAR1 binding affinity predicted by a deep-learning model built from ADAR1 CLIP-seq data, (ii) decreased editing levels in ADAR1-inhibited human lung cells, (iii) local clustering patterns, and (iv) higher RNA secondary structure propensity. Our results have critical implications in understanding the evolution of SARS-CoV-2 as well as in COVID-19 research, such as phylogenetic analysis and vaccine development.


Assuntos
COVID-19 , SARS-CoV-2 , Adenosina Desaminase/metabolismo , COVID-19/genética , Humanos , Nucleotídeos/metabolismo , Pandemias , Filogenia , RNA/metabolismo , Edição de RNA/genética , SARS-CoV-2/genética
4.
PLoS Genet ; 18(9): e1010424, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36129930

RESUMO

In most plants, sucrose, a major storage sugar, is transported into sink organs to support their growth. This key physiological process is dependent on the function of sucrose transporters. Sucrose export from source tissues is predominantly controlled through the activity of SUCROSE TRANSPORTER 2 (SUC2), required for the loading of sucrose into the phloem of Arabidopsis plants. However, how SUC2 activity is controlled to support root growth remains unclear. Glucose is perceived via the function of HEXOKINASE 1 (HXK1), the only known nuclear glucose sensor. HXK1 negatively regulates the stability of ETHYLENE-INSENSITIVE3 (EIN3), a key ethylene/glucose interaction component. Here we show that HXK1 functions upstream of EIN3 in the regulation of root sink growth mediated by glucose signaling. Furthermore, the transcription factor EIN3 directly inhibits SUC2 activity by binding to the SUC2 promoter, regulating glucose signaling linked to root sink growth. We demonstrate that these molecular components form a HXK1-EIN3-SUC2 module integral to the control of root sink growth. Also, we demonstrate that with increasing age, the HXK1-EIN3-SUC2 module promotes sucrose phloem loading in source tissues thereby elevating sucrose levels in sink roots. As a result, glucose signaling mediated-sink root growth is facilitated. Our findings thus establish a direct molecular link between the HXK1-EIN3-SUC2 module, the source-to sink transport of sucrose and root growth.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a DNA/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Glucose/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Folhas de Planta , Plantas/metabolismo , Sacarose/metabolismo , Fatores de Transcrição/genética
5.
Carcinogenesis ; 45(6): 387-398, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38693810

RESUMO

Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc., P < 0.05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells, etc., P < 0.001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (P < 0.0001). Additionally, NECTIN4 (P < 0.05) and LILRB4 were linked to improved disease-free survival in the MPLC. In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Transcriptoma , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Masculino , Feminino , Microambiente Tumoral/genética , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Idoso , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Prognóstico , Genômica/métodos , Perfilação da Expressão Gênica , Nectinas/genética , Células Matadoras Naturais/imunologia
6.
BMC Plant Biol ; 24(1): 941, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39385111

RESUMO

Rapeseed (Brassica napus L.) is a major oilseed crop in the middle and lower reaches of the Yangtze River in China. However, it is susceptible to waterlogging stress. This study aimed to investigate the physiological characteristics, cellular changes, and gene expression patterns of rapeseed under waterlogging stress, with the goal of providing a foundation for breeding waterlogging-tolerant rapeseed. The results revealed that waterlogging-tolerant rapeseed exhibited higher levels of soluble sugars and antioxidant enzyme activity, particularly in the roots. Conversely, waterlogging-sensitive rapeseed displayed greater changes in malondialdehyde, proline, and hydrogen peroxide levels. Cellular observations showed that after experiencing waterlogging stress, the intercellular space of rapeseed leaf cells expanded, leading to disintegration of mitochondria and chloroplasts. Moreover, the area of the root xylem increased, the number of vessels grew, and there were signs of mitochondrial disintegration and vacuole shrinkage, with more pronounced changes observed in waterlogging-sensitive rapeseed. Furthermore, significant differences were found in the transcription levels of genes related to anaerobic respiration and flavonoid biosynthesis, and different varieties demonstrated varied responses to waterlogging stress. In conclusion, there are differences in the response of different varieties to waterlogging stress at the levels of morphology, physiological characteristics, cell structure, and gene transcription. Waterlogging-tolerant rapeseed responds to waterlogging stress by regulating its antioxidant defense system. This study provides valuable insights for the development of waterlogging-tolerant rapeseed varieties.


Assuntos
Brassica napus , Estresse Fisiológico , Brassica napus/fisiologia , Brassica napus/genética , Brassica napus/metabolismo , Estresse Fisiológico/fisiologia , Água/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/fisiologia , Raízes de Plantas/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/metabolismo , China , Antioxidantes/metabolismo
7.
Appl Environ Microbiol ; 90(4): e0153723, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38445862

RESUMO

Many insect taxa cultivate fungi for food. Compared to well-known fungus cultivation in social insects, our knowledge on fungus cultivation in nonsocial insects is still limited. Here, we studied the nutritional potentials of the fungal cultivar, Penicillium herquei, for the larvae of its nonsocial insect farmer, Euops chinensis, a specialist on Japanese knotweed Reynoutria japonica. Overall, fungal hyphae and leaf rolls contained significantly higher carbon (C), stable isotopes of C (δ13C), and nitrogen (δ15N) but significantly lower C/N ratios compared to unrolled leaves, whereas insect bodies contained significantly higher N contents but lower C and C/N ratios compared to other types of samples. The MixSIAR model indicated that fungal hyphae contributed a larger proportion (0.626-0.797) to the diet of E. chinensis larvae than leaf materials. The levels of ergosterol, six essential amino acids, seven nonessential amino acids, and three B vitamins tested in fungal hyphae and/or leaf rolls were significantly higher than in unrolled leaves and/or larvae. The P. herquei genome contains the complete set of genes required for the biosynthesis of ergosterol, the essential amino acids valine and threonine, nine nonessential amino acids, and vitamins B2 and B3, whereas some genes associated with five essential and one nonessential amino acid were lost in the P. herquei genome. These suggest that P. herquei is capable of providing the E. chinensis larvae food with ergosterol, amino acids, and B vitamins. P. herquei appears to be able to synthesize or concentrate these nutrients considering that they were specifically concentrated in fungal hyphae. IMPORTANCE: The cultivation of fungi for food has occurred across divergent insect lineages such as social ants, termites, and ambrosia beetles, as well as some seldom-reported solitary insects. Although the fungal cultivars of these insects have been studied for decades, the dietary potential of fungal cultivars for their hosts (especially for those nonsocial insects) is largely unknown. Our research on the mutualistic system Euops chinensis-Penicillium herquei represents an example of the diverse nutritional potentials of the fungal cultivar P. herquei in the diet of the larvae of its solitary host, E. chinensis. These results demonstrate that P. herquei has the potential to synthesize or concentrate ergosterol, amino acids, and B vitamins and benefits the larvae of E. chinensis. Our findings would shed light on poorly understood fungal cultivation mutualisms in nonsocial insects and underscore the nutritional importance of fungal cultivars in fungal cultivation mutualisms.


Assuntos
Besouros , Penicillium , Complexo Vitamínico B , Gorgulhos , Animais , Gorgulhos/microbiologia , Larva/microbiologia , Besouros/microbiologia , Insetos/microbiologia , Aminoácidos Essenciais , Simbiose/genética , Dieta , Ergosterol
8.
Appl Environ Microbiol ; 90(10): e0098624, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39324818

RESUMO

High-throughput metagenomic sequence technology was employed to evaluate changes in microbial community composition and carbohydrate-active enzymes encoding gene enrichment status in Elymus nutans silages to altitudinal gradients in the world's highest alpine region of Qinghai-Tibetan Plateau (QTP). E. nutans were collected from three different altitudes in QTP: 2,600 m (low altitude), 3600 m (moderate altitude), and 4,600 m [high (H) altitude], and ensiled for 7, 14, 30, and 60 d. Results indicated an improvement in silage quality with the increasing altitude, although the acetic acid concentration and dry matter loss were greater in H altitude silages after 30 d of ensiling. Harmful bacteria or potential pathogens predominated in the microbial community on d 7 and 14 of fermentation, while genera belonging to lactic acid bacteria gradually became the main microorganisms with the increasing altitude on d 30 and 60 of ensiling. The abundance of carbohydrate-active enzymes genes responsible for macromolecular carbohydrate degradation in silage increased with increasing altitude, and those genes were mainly carried by Lactiplantibacillus and Pediococcus at 30 and 60 d of ensiling. The abundance of key enzymatic genes associated with glycolysis and organic acid production in carbohydrate metabolism pathway was higher in H altitude silages, and Lactiplantibacillus and Pediococcus were also the main hosts after 30 d of silage fermentation, except for the fact that acetic acid production was also related to genera Leuconostoc, Latilactobacillus, and Levilactobacillus. IMPORTANCE: The fermentation quality of Elymus nutans silage was getting better with the increase of altitude in the Qinghai-Tibetan Plateau. The abundance of hosts carrying carbohydrate-active enzymes genes and key enzyme genes related to organic acid production increased with increasing altitude during the later stages of fermentation. Lactiplantibacillus and Pediococcus were the core microorganisms responsible for both polysaccharide hydrolysis and silage fermentation in the late stage of ensiling. This study provided insights on the influence of different altitudes on the composition and function of silage microbiome in the Qinghai-Tibetan Plateau, and provided a reference approach for improving the quality and controllability of silage production in high altitude areas of the Qinghai-Tibetan Plateau.


Assuntos
Altitude , Bactérias , Elymus , Microbiota , Silagem , Silagem/microbiologia , Silagem/análise , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Elymus/microbiologia , Elymus/genética , Fermentação , Tibet , Ácido Acético/metabolismo
9.
Phys Rev Lett ; 132(24): 240801, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38949366

RESUMO

Quantum networks promise unprecedented advantages in information processing and open up intriguing new opportunities in fundamental research, where network topology and network nonlocality fundamentally underlie these applications. Hence, the detections of network topology and nonlocality are crucial, which, however, remain an open problem. Here, we conceive and experimentally demonstrate to determine the network topology and network nonlocality hosted by a triangle quantum network comprising three parties, within and beyond Bell theorem, with a general witness operator for the first time. We anticipate that this unique approach may stimulate further studies toward the efficient characterization of large complex quantum networks so as to better harness the advantage of quantum networks for quantum information applications.

10.
Phys Rev Lett ; 132(20): 203801, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829094

RESUMO

Non-Hermitian systems can exhibit unique quantum phases without any Hermitian counterparts. For example, the latest theoretical studies predict a new surprising phenomenon that bulk bands can localize and dissipate prominently at the system boundary, which is dubbed the non-Hermitian edge burst effect. Here we realize a one-dimensional non-Hermitian Su-Schrieffer-Heeger lattice with bulk translation symmetry implemented with a photonic quantum walk. Employing time-resolved single-photon detection to characterize the chiral motion and boundary localization of bulk bands, we determine experimentally that the dynamics underlying the non-Hermitian edge burst effect is due to the interplay of non-Hermitian skin effect and imaginary band gap closing. This new non-Hermitian physical effect deepens our understanding of quantum dynamics in open quantum systems.

11.
Mol Psychiatry ; 28(10): 4215-4224, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37537282

RESUMO

We previously discovered using transcriptomics that rats undergoing withdrawal after chronic ethanol exposure had increased expression of several genes encoding RNA splicing factors in the hippocampus. Here, we examined RNA splicing in the rat hippocampus during withdrawal from chronic ethanol exposure and in postmortem hippocampus of human subjects diagnosed with alcohol use disorder (AUD). We found that expression of the gene encoding the splicing factor, poly r(C) binding protein 1 (PCBP1), was elevated in the hippocampus of rats during withdrawal after chronic ethanol exposure and AUD subjects. We next analyzed the rat RNA-Seq data for differentially expressed (DE) exon junctions. One gene, Hapln2, had increased usage of a novel 3' splice site in exon 4 during withdrawal. This splice site was conserved in human HAPLN2 and was used more frequently in the hippocampus of AUD compared to control subjects. To establish a functional role for PCBP1 in HAPLN2 splicing, we performed RNA immunoprecipitation (RIP) with a PCBP1 antibody in rat and human hippocampus, which showed enriched PCBP1 association near the HAPLN2 exon 4 3' splice site in the hippocampus of rats during ethanol withdrawal and AUD subjects. Our results indicate a conserved role for the splicing factor PCBP1 in aberrant splicing of HAPLN2 after chronic ethanol exposure. As the HAPLN2 gene encodes an extracellular matrix protein involved in nerve conduction velocity, use of this alternative splice site is predicted to result in loss of protein function that could negatively impact hippocampal function in AUD.


Assuntos
Alcoolismo , Sítios de Splice de RNA , Humanos , Ratos , Animais , Splicing de RNA/genética , Etanol/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Alcoolismo/genética , Alcoolismo/metabolismo , Hipocampo/metabolismo , Processamento Alternativo/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
12.
PLoS Biol ; 19(2): e3001113, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33626035

RESUMO

Transforming growth factor-ß (TGF-ß) signaling plays a critical role in promoting epithelial-to-mesenchymal transition (EMT), cell migration, invasion, and tumor metastasis. ΔNp63α, the major isoform of p63 protein expressed in epithelial cells, is a key transcriptional regulator of cell adhesion program and functions as a critical metastasis suppressor. It has been documented that the expression of ΔNp63α is tightly controlled by oncogenic signaling and is frequently reduced in advanced cancers. However, whether TGF-ß signaling regulates ΔNp63α expression in promoting metastasis is largely unclear. In this study, we demonstrate that activation of TGF-ß signaling leads to stabilization of E3 ubiquitin ligase FBXO3, which, in turn, targets ΔNp63α for proteasomal degradation in a Smad-independent but Erk-dependent manner. Knockdown of FBXO3 or restoration of ΔNp63α expression effectively rescues TGF-ß-induced EMT, cell motility, and tumor metastasis in vitro and in vivo. Furthermore, clinical analyses reveal a significant correlation among TGF-ß receptor I (TßRI), FBXO3, and p63 protein expression and that high expression of TßRI/FBXO3 and low expression of p63 are associated with poor recurrence-free survival (RFS). Together, these results demonstrate that FBXO3 facilitates ΔNp63α degradation to empower TGF-ß signaling in promoting tumor metastasis and that the TßRI-FBXO3-ΔNp63α axis is critically important in breast cancer development and clinical prognosis. This study suggests that FBXO3 may be a potential therapeutic target for advanced breast cancer treatment.


Assuntos
Neoplasias da Mama/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Células HEK293 , Células HaCaT , Humanos , Metástase Neoplásica/patologia , Isoformas de Proteínas , Proteínas Supressoras de Tumor/metabolismo
13.
Soft Matter ; 20(18): 3780-3786, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38639061

RESUMO

Acylphosphatase (AcP) is an enzyme which catalyses the hydrolysis of acylphosphate. The binding with the phosphate ion (Pi) assumes significance in preserving both the stability and enzymatic activity of AcP. While previous studies using single molecule force spectroscopy explored the mechanical properties of AcP, the influence of Pi on its folding and unfolding dynamic behaviors remains unexplored. In this work, using stable magnetic tweezers, we measured and compared the force-dependent folding and unfolding rates of AcP in the Tris buffer and phosphate buffer within a force range from 2 pN to 40 pN. We found that Pi exerts no discernible effect on the folding dynamics but consistently decreases the force-dependent unfolding rate of AcP by a constant ratio across the entire force spectrum. The free energy landscapes of AcP in the absence and presence of Pi are constructed. Our results reveal that Pi selectively binds to the native state of AcP, stabilizing it and suggesting the general properties of specific ligand-receptor interactions.


Assuntos
Acilfosfatase , Dobramento de Proteína , Desdobramento de Proteína , Termodinâmica , Ligantes , Fosfatos/química , Fosfatos/metabolismo
14.
Int J Legal Med ; 138(2): 487-498, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37940721

RESUMO

The medial clavicle epiphysis is a crucial indicator for bone age estimation (BAE) after hand maturation. This study aimed to develop machine learning (ML) and deep learning (DL) models for BAE based on medial clavicle CT images and evaluate the performance on normal and variant clavicles. This study retrospectively collected 1049 patients (mean± SD: 22.50±4.34 years) and split them into normal training and test sets, and variant training and test sets. An additional 53 variant clavicles were incorporated into the variant test set. The development stages of normal MCE were used to build a linear model and support vector machine (SVM) for BAE. The CT slices of MCE were automatically segmented and used to train DL models for automated BAE. Comparisons were performed by linear versus ML versus DL, and normal versus variant clavicles. Mean absolute error (MAE) and classification accuracy was the primary parameter of comparison. For BAE, the SVM had the best MAE of 1.73 years, followed by the commonly-used CNNs (1.77-1.93 years), the linear model (1.94 years), and the hybrid neural network CoAt Net (2.01 years). In DL models, SE Net 18 was the best-performing DL model with similar results to SVM in the normal test set and achieved an MAE of 2.08 years in the external variant test. For age classification, all the models exhibit superior performance in the classification of 18-, 20-, 21-, and 22-year thresholds with limited value in the 16-year threshold. Both ML and DL models produce desirable performance in BAE based on medial clavicle CT.


Assuntos
Aprendizado Profundo , Humanos , Clavícula/diagnóstico por imagem , Estudos Retrospectivos , Determinação da Idade pelo Esqueleto/métodos , Aprendizado de Máquina , Tomografia Computadorizada por Raios X/métodos
15.
Int J Legal Med ; 138(3): 927-938, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38129687

RESUMO

Bone age assessment (BAA) is a crucial task in clinical, forensic, and athletic fields. Since traditional age estimation methods are suffered from potential radiation damage, this study aimed to develop and evaluate a deep learning radiomics method based on multiparametric knee MRI for noninvasive and automatic BAA. This retrospective study enrolled 598 patients (age range,10.00-29.99 years) who underwent MR examinations of the knee joint (T1/T2*/PD-weighted imaging). Three-dimensional convolutional neural networks (3D CNNs) were trained to extract and fuse multimodal and multiscale MRI radiomic features for age estimation and compared to traditional machine learning models based on hand-crafted features. The age estimation error was greater in individuals aged 25-30 years; thus, this method may not be suitable for individuals over 25 years old. In the test set aged 10-25 years (n = 95), the 3D CNN (a fusion of T1WI, T2*WI, and PDWI) demonstrated the lowest mean absolute error of 1.32 ± 1.01 years, which is higher than that of other MRI modalities and the hand-crafted models. In the classification for 12-, 14-, 16-, and 18- year thresholds, accuracies and the areas under the ROC curves were all over 0.91 and 0.96, which is similar to the manual methods. Visualization of important features showed that 3D CNN estimated age by focusing on the epiphyseal plates. The deep learning radiomics method enables non-invasive and automated BAA from multimodal knee MR images. The use of 3D CNN and MRI-based radiomics has the potential to assist radiologists or medicolegists in age estimation.


Assuntos
Aprendizado Profundo , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Radiômica , Imageamento por Ressonância Magnética/métodos , Articulação do Joelho/diagnóstico por imagem
16.
J Nanobiotechnology ; 22(1): 607, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379937

RESUMO

Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.


Assuntos
Colite , Sulfato de Dextrana , Exossomos , Sophora , Animais , Camundongos , Exossomos/metabolismo , Administração Oral , Sophora/química , Colite/tratamento farmacológico , Colite/induzido quimicamente , Masculino , Células RAW 264.7 , Camundongos Endogâmicos C57BL , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Nanopartículas/química , Humanos , Sophora flavescens
17.
Med Sci Monit ; 30: e943666, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850016

RESUMO

BACKGROUND Helicobacter pylori has a high infection rate worldwide, and epidemiological study of H. pylori is important. Artificial intelligence has been widely used in the field of medical research and has become a hotspot in recent years. This paper proposed a prediction model for H. pylori infection based on machine learning in adults. MATERIAL AND METHODS Adult patients were selected as research participants, and information on 30 factors was collected. The chi-square test, mutual information, ReliefF, and information gain were used to screen the feature factors and establish 2 subsets. We constructed an H. pylori infection prediction model based on XGBoost and optimized the model using a grid search by analyzing the correlation between features. The performance of the model was assessed by comparing its accuracy, recall, precision, F1 score, and AUC with those of 4 other classical machine learning methods. RESULTS The model performed better on the part B subset than on the part A subset. Compared with the other 4 machine learning methods, the model had the highest accuracy, recall, F1 score, and AUC. SHAP was used to evaluate the importance of features in the model. It was found that H. pylori infection of family members, living in rural areas, poor washing hands before meals and after using the toilet were risk factors for H. pylori infection. CONCLUSIONS The model proposed in this paper is superior to other models in predicting H. pylori infection and can provide a scientific basis for identifying the population susceptible to H. pylori and preventing H. pylori infection.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Aprendizado de Máquina , Humanos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco
18.
BMC Public Health ; 24(1): 236, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38243163

RESUMO

BACKGROUND: Although years have passed since the implementation of China's universal two-child policy, the effectiveness of this policy remains unclear. To address this knowledge gap, we, here, assessed the impact of the two-child policy on total live births, preterm births, and multiple live births. METHODS: Data identifying pregnancies resulting in at least one live birth between April 1 2013 and December 31 2018 were collected from the Hospital Quality Monitoring System database. Using an interrupted time-series analysis, we estimated immediate level changes and long-term trends in total, preterm (birth before 37 weeks' gestation), and multiple live births that had occurred after July 2016, when the universal two-child policy had taken effect. RESULTS: A total of 8,273,622 live births were reported during the study time frame. The number of live births (p = 0.277), preterm births (p = 0.052), and multiple births (p = 0.856) per month slightly increased immediately after July 2016, but these increases did not meet statistical significance. Further, all three outcomes showed a significant downward trend that lasted until the end of 2018 (p < 0.0001 for all). Among all live births, the percentage of preterm births remained stable (p = 0.101), while the percentage of multiple live births that were preterm significantly increased (trend change = 0.21% per month, 95% CI 0.14 to 0.28, p < 0.0001). The percentage of live multiple births among all live births significantly decreased (p for trend = 0.0039). CONCLUSIONS: Overall, our data reveal a transient baby boom, as well as an increase in the proportion of live multiple births that were preterm, after China's two-child policy took effect. The latter should be noted by healthcare professionals due to the high risk of complications and special medical care required by preterm babies.


Assuntos
Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Nascimento Prematuro/epidemiologia , Recém-Nascido Prematuro , Prole de Múltiplos Nascimentos , Políticas , China/epidemiologia
19.
BMC Public Health ; 24(1): 1850, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992612

RESUMO

BACKGROUND: Myopia is a major health issue around the world. Myopia in children has increased significantly during the COVID-19 pandemic in China, but reports are scarce on the prevalence of myopia following the pandemic. This study collected vision screening data of school children in China for five consecutive years to observe the changes in myopia after the pandemic and compare the observed prevalence of myopia before and after the pandemic. METHODS: A school-based vision screening study used stratified samplings to collect the vision screening data in school children aged 6-13 from 45 primary schools in Hangzhou. Vision screening data including uncorrected visual acuity(UCVA) and spherical equivalent refraction(SER). Calculating the mean of SER and the prevalence of myopia and hyperopia from 2019 to 2023. RESULTS: A total of 79,068 screening results (158,136 eyes) were included in the analysis. A substantial myopic shift (approximately -0.30 diopters [D] on average) was found in 2020 and 2021 compared with 2019 in all age groups and a substantial myopic shift (approximately 0.4 D on average) was found in 2022 compared with 2021. A slight myopic shift (approximately -0.14 D on average) was found in 2023 compared with 2022. The prevalence of myopia in all age groups was the highest for five years in 2020 or 2021, which was 31.3% for 6-year-olds, 43.0% for 7-year-olds, and 53.7% for 8-year-olds. A positive change in the prevalence rate of myopia was found at 6 years old (0.59%, 0.12%, 0.36%, 0.25%, p < 0.001). The change in prevalence rate in myopia was shifted slightly in children aged 10-13 years. Children aged 8 to 13 years had a slight increase in myopia prevalence from 2022 to 2023. The prevalence of hyperopia was low and stable in all grade groups, ranging from 0.7% to 2.2% over five years. CONCLUSION: Myopia in children has increased rapidly during the COVID-19 pandemic. After the pandemic, the prevalence of myopia in children gradually decreased temporarily and then rebounded. Myopic shift was more apparent in younger children. Myopic shift in children may be related to the reduction of outdoor time, less light, and near work habits, and further research is needed.


Assuntos
COVID-19 , Miopia , Seleção Visual , Humanos , COVID-19/epidemiologia , Criança , Miopia/epidemiologia , China/epidemiologia , Masculino , Adolescente , Feminino , Prevalência , Instituições Acadêmicas , Pandemias
20.
Artigo em Inglês | MEDLINE | ID: mdl-38007175

RESUMO

The physiological response to feeding is important for production aspects that include feed utilization and growth, and the responses require the action of numerous secretory factors. However, as an important aquaculture animal, the secretory response of Pacific White Shrimp (Litopenaeus vannamei) after feeding has not been comprehensively characterized. In this study, transcriptome analysis showed that 3172 differentially expressed genes were involved in the post-feeding response, including 289 new genes not annotated in the L. vannamei reference genome. Subsequently, 715 differentially expressed secretory reference genes and 18 new differentially expressed secretory genes were obtained through the identification of signal peptides in secreted proteins. Functional classification revealed that differentially expressed secretory genes were enriched in pathways pertaining to lipid metabolism (20 genes), carbohydrate metabolism (21 genes), glycan biosynthesis and metabolism (27 genes), digestive system (40 genes), and transport and metabolism (43 genes). The 14 pathways most enriched by differentially expressed secretory genes involved 83 genes, 71 of which encoded enzymes involved in food digestion and metabolism. Specific enzymes such as lipase 3-like and NPC intracellular cholesterol transporter 1-like in lipid metabolism, alpha-amylase-like and glucosylceramidase-like in carbohydrate metabolism, and cysteine proteinase 4-like and trypsin-1-like in the digestive system were found to be differentially expressed. Furthermore, we discovered a new gene, MSTRG.2504, that participates in the digestive system and carbohydrate metabolism. The study provides valuable insights into the secretory response (especially metabolism-related enzymes) to feeding in L. vannamei, uncovering the significant roles of both known and new genes. Furthermore, this study will improve our understanding of the feeding physiology of L. vannamei and provide a reference basis for further feeding endocrine research in the future.


Assuntos
Perfilação da Expressão Gênica , Penaeidae , Animais , Expressão Gênica , Penaeidae/metabolismo , Alimentos , Transcriptoma
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