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1.
medRxiv ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38699361

RESUMEN

Insertion of active retroelements-L1s, Alus, and SVAs-can disrupt proper genome function and lead to various disorders including cancer. However, the role of de novo retroelements (DNRTs) in birth defects and childhood cancers has not been well characterized due to the lack of adequate data and efficient computational tools. Here, we examine whole-genome sequencing data of 3,244 trios from 12 birth defect and childhood cancer cohorts in the Gabriella Miller Kids First Pediatric Research Program. Using an improved version of our tool xTea (x-Transposable element analyzer) that incorporates a deep-learning module, we identified 162 DNRTs, as well as 2 pseudogene insertions. Several variants are likely to be causal, such as a de novo Alu insertion that led to the ablation of a whole exon in the NF1 gene in a proband with brain tumor. We observe a high de novo SVA insertion burden in both high-intolerance loss-of-function genes and exons as well as more frequent de novo Alu insertions of paternal origin. We also identify potential mosaic DNRTs from embryonic stages. Our study reveals the important roles of DNRTs in causing birth defects and predisposition to childhood cancers.

2.
Cell ; 187(8): 1955-1970.e23, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38503282

RESUMEN

Characterizing somatic mutations in the brain is important for disentangling the complex mechanisms of aging, yet little is known about mutational patterns in different brain cell types. Here, we performed whole-genome sequencing (WGS) of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals spanning 0.4-104 years of age and identified >92,000 somatic single-nucleotide variants (sSNVs) and small insertions/deletions (indels). Although both cell types accumulate somatic mutations linearly with age, oligodendrocytes accumulated sSNVs 81% faster than neurons and indels 28% slower than neurons. Correlation of mutations with single-nucleus RNA profiles and chromatin accessibility from the same brains revealed that oligodendrocyte mutations are enriched in inactive genomic regions and are distributed across the genome similarly to mutations in brain cancers. In contrast, neuronal mutations are enriched in open, transcriptionally active chromatin. These stark differences suggest an assortment of active mutagenic processes in oligodendrocytes and neurons.


Asunto(s)
Envejecimiento , Encéfalo , Neuronas , Oligodendroglía , Humanos , Envejecimiento/genética , Envejecimiento/patología , Cromatina/genética , Cromatina/metabolismo , Mutación , Neuronas/metabolismo , Neuronas/patología , Oligodendroglía/metabolismo , Oligodendroglía/patología , Análisis de Expresión Génica de una Sola Célula , Secuenciación Completa del Genoma , Encéfalo/metabolismo , Encéfalo/patología , Polimorfismo de Nucleótido Simple , Mutación INDEL , Bancos de Muestras Biológicas , Células Precursoras de Oligodendrocitos/metabolismo , Células Precursoras de Oligodendrocitos/patología
3.
Plant Commun ; : 100856, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38431772

RESUMEN

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(2): 202-204, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38442939

RESUMEN

The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.


Asunto(s)
Antiinfecciosos , Drenaje , Humanos , Cánula , Consenso , Hospitales
5.
Nat Genet ; 56(3): 541-552, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38361034

RESUMEN

Mutational signature analysis is a recent computational approach for interpreting somatic mutations in the genome. Its application to cancer data has enhanced our understanding of mutational forces driving tumorigenesis and demonstrated its potential to inform prognosis and treatment decisions. However, methodological challenges remain for discovering new signatures and assigning proper weights to existing signatures, thereby hindering broader clinical applications. Here we present Mutational Signature Calculator (MuSiCal), a rigorous analytical framework with algorithms that solve major problems in the standard workflow. Our simulation studies demonstrate that MuSiCal outperforms state-of-the-art algorithms for both signature discovery and assignment. By reanalyzing more than 2,700 cancer genomes, we provide an improved catalog of signatures and their assignments, discover nine indel signatures absent in the current catalog, resolve long-standing issues with the ambiguous 'flat' signatures and give insights into signatures with unknown etiologies. We expect MuSiCal and the improved catalog to be a step towards establishing best practices for mutational signature analysis.


Asunto(s)
Música , Neoplasias , Humanos , Neoplasias/genética , Mutación , Carcinogénesis/genética , Mutación INDEL
6.
medRxiv ; 2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-38293061

RESUMEN

Despite the overall efficacy of immune checkpoint blockade (ICB) for mismatch repair deficiency (MMRD) across tumor types, a sizable fraction of patients with MMRD still do not respond to ICB. We performed mutational signature analysis of panel sequencing data (n = 95) from MMRD cases treated with ICB. We discover that T>C-rich single base substitution (SBS) signatures-SBS26 and SBS54 from the COSMIC Mutational Signatures catalog-identify MMRD patients with significantly shorter overall survival. Tumors with a high burden of SBS26 show over-expression and enriched mutations of genes involved in double-strand break repair and other DNA repair pathways. They also display chromosomal instability (CIN), likely related to replication fork instability, leading to copy number losses that trigger immune evasion. SBS54 is associated with transcriptional activity and not with CIN, defining a distinct subtype. Consistently, cancer cell lines with a high burden of SBS26 and SBS54 are sensitive to treatments targeting pathways related to their proposed etiology. Together, our analysis offers an explanation for the heterogeneous responses to ICB among MMRD patients and supports an SBS signature-based predictor as a prognostic biomarker for differential ICB response.

7.
Aging (Albany NY) ; 16(1): 538-549, 2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-38214606

RESUMEN

RBCK1 is an important E3 ubiquitin ligase, which plays an important role in many major diseases. However, the function and mechanism of RBCK1 in pan-cancer and its association with immune cell infiltration have not been reported. The purpose of this study is to find out the expression of RBCK1 in cancer, and to explore the relationship between RBCK1 and the prognosis of patients. Our results show that the expression of RBCK1 is up-regulated in a variety of malignant tumors, and is closely related to the prognosis of patients. Further studies have shown that RBCK1 regulates protein expression in the nucleus and plays an important role in ribosome and valine, leucine, and isoleucine degradation. Genetic variation analysis showed that RBCK1 was mainly involved in missense mutations in multiple tumors, and mutated patients showed poor prognoses. Further studies showed that RBCK1 may be interacted with proteins such as RNRPB, MCRS1, TRIB3, MKKS and ARPC3. Through protein interaction analysis, we found 43 proteins interacting with RBCK1 in liver cancer. We also analyzed immune cell infiltration and found that RBCK1 expression was positively correlated with T cells and macrophages, while it was negatively correlated with neutrophils, NK cells, and DCs in liver cancer. Finally, we confirmed experimentally that RBCK1 can significantly inhibit the apoptosis and invasion of HCC. Therefore, we speculate that RBCK1 plays an important regulatory role in the occurrence and development of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Chlorocebus aethiops , Neoplasias Hepáticas/genética , Pronóstico , Proteínas de Unión al ARN , Factores de Transcripción/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
8.
Biomimetics (Basel) ; 9(1)2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38248612

RESUMEN

Inspired by the natural skeletal muscles, this paper presents a novel shape memory alloy-based artificial muscle matrix (AMM) with advantages of a large output force and displacement, flexibility, and compactness. According to the composition of the AMM, we propose a matrix control strategy to achieve independent control of the output force and displacement of the AMM. Based on the kinematics simulation and experiments, we obtained the output displacement and bearing capacity of the smart digital structure (SDS) and confirmed the effectiveness of the matrix control strategy to achieve force and displacement output independently and controllably. A bionic mechanical ankle actuated by AMM was proposed to demonstrate the actuating capability of the AMM. Experimental results show that the angle and force of the bionic mechanical ankle are output independently and have a significant gradient. In addition, by using a self-sensing method (resistance self-feedback) and PD control strategy, the output angle and force of the bionic mechanical ankle can be maintained for a long time without overheating of the AMM.

9.
Life Sci ; 339: 122414, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38216121

RESUMEN

Contamination by pathogens, such as bacteria, can irritate a wound and prevent its healing, which may affect the physical fitness of the infected person. As such, the development of more novel nano-biomaterials able to cope with the inflammatory reaction to bacterial infection during the wound healing process to accelerate wound healing is required. Herein, a halofuginone­silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. HTPM&AgNPs-gel was characterized based on thermogravimetric analysis, differential scanning calorimetry, morphology, injectability, and rheological mechanics that reflected its exemplary nature. Moreover, HTPM&AgNPs-gel was further tested for its ability to facilitate healing of skin fibroblasts and exert antibacterial activity. Finally, HTPM&AgNPs-gel was tested for its capacity to accelerate general wound healing and treat bacterially induced wound damage. HTPM&AgNPs-gel appeared spherical under a transmission electron microscope and showed a grid structure under a scanning electron microscope. Additionally, HTPM&AgNPs-gel demonstrated excellent properties, including injectability, temperature-dependent swelling behavior, low loss at high temperatures, and appropriate rheological properties. Further, HTPM&AgNPs-gel was found to effectively promote healing of skin fibroblasts and inhibit the proliferation of Escherichia coli and Staphylococcus aureus. An evaluation of the wound healing efficacy demonstrated that HTPM&AgNPs-gel had a more pronounced ability to facilitate wound repair and antibacterial effects than HTPM-gel or AgNPs-gel alone, and exhibited ideal biocompatibility. Notably, HTPM&AgNPs-gel also inhibited inflammatory responses in the healing process. HTPM&AgNPs-gel exhibited antibacterial, anti-inflammatory, and scar repair features, which remarkably promoted wound healing. These findings indicated that HTPM&AgNPs-gel holds great clinical potential as a promising and valuable wound healing treatment.


Asunto(s)
Nanopartículas del Metal , Piperidinas , Quinazolinonas , Plata , Humanos , Plata/farmacología , Plata/química , Staphylococcus aureus , Cicatrización de Heridas , Nanopartículas del Metal/química , Antibacterianos/farmacología , Hidrogeles/química , Antiinflamatorios/farmacología
10.
World J Pediatr ; 20(3): 250-258, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38070095

RESUMEN

BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).


Asunto(s)
Neuroblastoma , Niño , Humanos , Estudios Retrospectivos , Incidencia , Metástasis Linfática , Neuroblastoma/epidemiología , Neuroblastoma/cirugía , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Estadificación de Neoplasias
11.
New Phytol ; 241(4): 1543-1558, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38031462

RESUMEN

Lysophosphatidic acid acyltransferases (LPAATs) catalyze the formation of phosphatidic acid (PA), a central metabolite in both prokaryotic and eukaryotic organisms for glycerolipid biosynthesis. Phaeodactylum tricornutum contains at least two plastid-localized LPAATs (ptATS2a and ptATS2b), but their roles in lipid synthesis remain unknown. Both ptATS2a and ptATS2b could complement the high temperature sensitivity of the bacterial plsC mutant deficient in LPAAT. In vitro enzyme assays showed that they prefer lysophosphatidic acid over other lysophospholipids. ptATS2a is localized in the plastid inner envelope membrane and CRISPR/Cas9-generated ptATS2a mutants showed compromised cell growth, significantly changed plastid and extra-plastidial membrane lipids at nitrogen-replete condition and reduced triacylglycerols (TAGs) under nitrogen-depleted condition. ptATS2b is localized in thylakoid membranes and its knockout led to reduced growth rate and TAG content but slightly altered molecular composition of membrane lipids. The changes in glycerolipid profiles are consistent with the role of both LPAATs in the sn-2 acylation of sn-1-acyl-glycerol-3-phosphate substrates harboring 20:5 at the sn-1 position. Our findings suggest that both LPAATs are important for membrane lipids and TAG biosynthesis in P. tricornutum and further highlight that 20:5-Lyso-PA is likely involved in the massive import of 20:5 back to the plastid to feed plastid glycerolipid syntheses.


Asunto(s)
Aciltransferasas , Lípidos de la Membrana , Triglicéridos , Aciltransferasas/metabolismo , Plastidios/metabolismo , Ácidos Fosfatidicos , Nitrógeno
12.
Zool Res ; 45(1): 79-94, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38114435

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is associated with mutations in lipopolysaccharide-binding protein ( LBP), but the underlying epigenetic mechanisms remain understudied. Herein, LBP -/- rats with NAFLD were established and used to conduct integrative targeting-active enhancer histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency. Notably, LBP -/- reduced the inflammatory response but markedly aggravated high-fat diet (HFD)-induced NAFLD in rats, with pronounced alterations in the histone acetylome and regulatory transcriptome. In total, 1 128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type (WT) and LBP -/- NAFLD rats. Based on integrative analysis, CCAAT/enhancer-binding protein ß (C/EBPß) was identified as a pivotal transcription factor (TF) and contributor to dysregulated histone acetylome H3K27ac, and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD. This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPß and functional gene SCD as potential regulators and therapeutic targets.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Ratas , Acetilación , Histonas/metabolismo , Lípidos , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/veterinaria , Estearoil-CoA Desaturasa/metabolismo
13.
World J Gastroenterol ; 29(42): 5699-5715, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38075847

RESUMEN

Esophageal cancer (EC) has a high incidence and mortality rate and is emerging as one of the most common health problems globally. Owing to the lack of sensitive detection methods, uncontrollable rapid metastasis, and pervasive treatment resistance, EC is often diagnosed in advanced stages and is susceptible to local recurrence. Exosomes are important components of intercellular communication and the exosome-mediated crosstalk between the cancer and surrounding cells within the tumor microenvironment plays a crucial role in the metastasis, progression, and therapeutic resistance of EC. Considering the critical role of exosomes in tumor pathogenesis, this review focused on elucidating the impact of exosomes on EC metastasis and therapeutic resistance. Here, we summarized the relevant signaling pathways involved in these processes. In addition, we discussed the potential clinical applications of exosomes for the early diagnosis, prognosis, and treatment of EC.


Asunto(s)
Neoplasias Esofágicas , Exosomas , Humanos , Resistencia a Antineoplásicos , Exosomas/metabolismo , Neoplasias Esofágicas/patología , Transducción de Señal , Comunicación Celular , Microambiente Tumoral
14.
Heliyon ; 9(11): e22186, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38045189

RESUMEN

Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, ß-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.

15.
Cell Mol Biol (Noisy-le-grand) ; 69(11): 207-212, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38015520

RESUMEN

The present study aimed to investigate the effect of Apelin-13 on nicotine-induced injuries of cardiomyocytes. To establish an H9c2 cell model of nicotine-induced apoptosis, H9c2 cells were divided into the control group, nicotine group, and Apelin-13+nicotine group. The apoptosis rate of H9c2 cells was then detected by flow cytometry. Later, the expressions of indicators related to apoptosis, oxidative stress, and inflammatory responses were measured via Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The results revealed that the expression of B-cell lymphoma-2 (Bcl-2) was remarkably down-regulated (P<0.01), while the apoptosis rate and the expressions of apoptosis-related proteins (Bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase-3 (Caspase-3)) were significantly up-regulated (P<0.01) in the nicotine group. However, the variation trends of Bcl-2, Bax, and Caspase-3 in the Apelin-13+nicotine group were contrary to those in the nicotine group (P<0.01). Additionally, the expressions of interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) obviously declined (P<0.01), while those of superoxide dismutase 1 (SOD1) and SOD2 dramatically rose in the Apelin-13+nicotine group (P<0.01). Furthermore, Apelin-13 treatment evidently elevated the expressions of phosphorylated protein kinase B (p-AKT) and phosphorylated phosphatidylinositol 3-kinase (PI3K). In conclusion, Apelin-13 inhibits nicotine-induced apoptosis and oxidative stress in H9c2 cells via the PI3K/AKT signaling pathway.


Asunto(s)
Miocitos Cardíacos , Proteínas Proto-Oncogénicas c-akt , Caspasa 3 , Ligandos , Nicotina/farmacología , Fosfatidilinositol 3-Quinasas , Proteína X Asociada a bcl-2 , Apoptosis , Estrés Oxidativo
16.
Artículo en Inglés | MEDLINE | ID: mdl-37934640

RESUMEN

Graph anomaly detection (GAD) has gained increasing attention in various attribute graph applications, i.e., social communication and financial fraud transaction networks. Recently, graph contrastive learning (GCL)-based methods have been widely adopted as the mainstream for GAD with remarkable success. However, existing GCL strategies in GAD mainly focus on node-node and node-subgraph contrast and fail to explore subgraph-subgraph level comparison. Furthermore, the different sizes or component node indices of the sampled subgraph pairs may cause the "nonaligned" issue, making it difficult to accurately measure the similarity of subgraph pairs. In this article, we propose a novel subgraph-aligned multiview contrastive approach for graph anomaly detection, named SAMCL, which fills the subgraph-subgraph contrastive-level blank for GAD tasks. Specifically, we first generate the multiview augmented subgraphs by capturing different neighbors of target nodes forming contrasting subgraph pairs. Then, to fulfill the nonaligned subgraph pair contrast, we propose a subgraph-aligned strategy that estimates similarities with the Earth mover's distance (EMD) of both considering the node embedding distributions and typology awareness. With the newly established similarity measure for subgraphs, we conduct the interview subgraph-aligned contrastive learning module to better detect changes for nodes with different local subgraphs. Moreover, we conduct intraview node-subgraph contrastive learning to supplement richer information on abnormalities. Finally, we also employ the node reconstruction task for the masked subgraph to measure the local change of the target node. Finally, the anomaly score for each node is jointly calculated by these three modules. Extensive experiments conducted on benchmark datasets verify the effectiveness of our approach compared to existing state-of-the-art (SOTA) methods with significant performance gains (up to 6.36% improvement on ACM). Our code can be verified at https://github.com/hujingtao/SAMCL.

17.
Nucleic Acids Res ; 51(21): 11453-11465, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-37823611

RESUMEN

SINE-VNTR-Alu (SVA) retrotransposons are evolutionarily young and still-active transposable elements (TEs) in the human genome. Several pathogenic SVA insertions have been identified that directly mutate host genes to cause neurodegenerative and other types of diseases. However, due to their sequence heterogeneity and complex structures as well as limitations in sequencing techniques and analysis, SVA insertions have been less well studied compared to other mobile element insertions. Here, we identified polymorphic SVA insertions from 3646 whole-genome sequencing (WGS) samples of >150 diverse populations and constructed a polymorphic SVA insertion reference catalog. Using 20 long-read samples, we also assembled reference and polymorphic SVA sequences and characterized the internal hexamer/variable-number-tandem-repeat (VNTR) expansions as well as differing SVA activity for SVA subfamilies and human populations. In addition, we developed a module to annotate both reference and polymorphic SVA copies. By characterizing the landscape of both reference and polymorphic SVA retrotransposons, our study enables more accurate genotyping of these elements and facilitate the discovery of pathogenic SVA insertions.


Asunto(s)
Genoma Humano , Retroelementos , Humanos , Elementos Alu , Genoma Humano/genética , Repeticiones de Minisatélite/genética , Retroelementos/genética , Elementos de Nucleótido Esparcido Corto
18.
Theriogenology ; 209: 243-250, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37480702

RESUMEN

The survival, motility and capacitation of sperm in the female reproductive tract are important prerequisites for fertilization. The uterus is the main location for sperm capacitation. One of the most important physiological functions of the endometrial epithelium is to create a suitable uterine environment under the regulation of ovarian hormones, to ensure sperm capacitation. The composition of uterine fluid directly affects sperm capacitation. Fructose is an important component of semen that supports sperm viability and motility. Aldose reductase, a rate-limiting enzyme in the polyol pathway, metabolizes sorbitol and fructose, thereby supplying cells with necessary energy for functional activities. Existing studies have reported the presence aldose reductase in the endometrium, leading us to hypothesize that its expression in endometrial epithelium might promote sperm capacitation by maintaining the uterine environment. Yet, the mechanism of regulation has not been clarified. In this study, we investigated the expression of aldose reductase in mouse endometrial epithelium and its potential role in sperm capacitation. We initially investigated the periodic characteristics of glucose, fructose and sorbitol in uterine fluid. We then studied the temporal and spatial characteristics of aldose reductase in the endometrial epithelium. Next, we examined the effect of aldose reductase on glucose, fructose and sorbitol in uterine fluid. Finally, we explored the effect of aldose reductase on sperm capacitation and fertilization. The results showed that glucose and fructose content in uterine fluid and the expression of aldose reductase fluctuated periodically during physiological periods. Inhibition of aldose reductase in the endometrial epithelium interfered with sperm capacitation and fertilization by reducing the fructose levels in the uterine fluid. To conclude, the aldose reductase-mediated polyol pathway in endometrial epithelial cells is essential to maintain an appropriate fructose environment in the uterine fluid for sperm capacitation and fertilization.


Asunto(s)
Enfermedades Uterinas , Femenino , Masculino , Animales , Ratones , Aldehído Reductasa/genética , Capacitación Espermática , Semen , Células Epiteliales , Enfermedades Uterinas/veterinaria , Fructosa/farmacología , Glucosa/farmacología
19.
Sensors (Basel) ; 23(11)2023 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-37299792

RESUMEN

This paper considers the problem of estimating the parameters of a frequency-hopping signal under non-cooperative conditions. To make the estimation of different parameters independently of each other, a compressed domain frequency-hopping signal parameter estimation algorithm based on the improved atomic dictionary is proposed. By segmenting and compressive sampling the received signal, the center frequency of each signal segment is estimated using the maximum dot product. The signal segments are processed with central frequency variation using the improved atomic dictionary to accurately estimate the hopping time. We highlight that one superiority of the proposed algorithm is that high-resolution center frequency estimation can be directly obtained without reconstructing the frequency-hopping signal. Additionally, another superiority of the proposed algorithm is that hopping time estimation has nothing to do with center frequency estimation. Numerical results show that the proposed algorithm can achieve superior performance compared with the competing method.


Asunto(s)
Algoritmos , Compresión de Datos
20.
Infect Drug Resist ; 16: 3981-3988, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37366502

RESUMEN

Objective: To evaluate the effect of sleep duration on blood pressure in patients with hypertension urgencies combined with SARS-CoV-2 infection in a Fangcang shelter hospital. Methods: From April 10, 2020 to May 20, 2022, we statistically analyzed the blood pressure and sleep conditions of 52 patients with combined hypertension urgencies and SARS-CoV-2 infection admitted in Shanghai National Convention and Exhibition Center Fangcang shelter hospital. They were divided into the short-term (daily sleep duration: <7 h) and normal sleep group (7-9 h). We performed a comparison of the control effects of basic antihypertensive drugs. Additionally, patients in the short-term sleep group underwent drug therapy for sleep regulation and continuous monitoring of blood pressure. Results: Among these patients, the blood pressure was higher in the short-term sleep group than that of the normal sleep group, and also more difficult to control (p <0.05). Furthermore, the blood pressure of the patients in the short-term sleep group was more easily controlled after treatment with drugs for sleep regulation and basic antihypertensive drugs (p <0.05). Conclusion: The blood pressure level in patients with combined SARS-CoV-2 infection and hypertension urgencies was higher in those with a shorter duration of daily sleep, and also more difficult to control in Fangcang shelter hospital. Drug therapy for sleep regulation should be administered early to obtain sufficient blood pressure control effects.

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