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1.
Mol Ecol Resour ; : e14002, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39092596

RESUMEN

Populus tomentosa, an indigenous tree species, is widely distributed and cultivated over 1,000,000 km2 in China, contributing significantly to forest production, ecological conservation and urban-rural greening. Although a reference genome is available for P. tomentosa, the intricate interspecific hybrid origins, chromosome structural variations (SVs) and sex determination mechanisms remain confusion and unclear due to its broad and even overlapping geographical distribution, extensive morphological variations and cross infiltration among white poplar species. We conducted a haplotype-resolved de novo assembly of P. tomentosa elite individual GM107, which comprises subgenomes a and b with a total genome size of 714.9 Mb. We then analysed the formation of hybrid species and the phylogenetic evolution and sex differentiation across the entire genus. Phylogenomic analyses suggested that GM107 likely originated from a hybridisation event between P. alba (♀) and P. davidiana (♂) approximately 3.8 Mya. A total of 1551 chromosome SVs were identified between the two subgenomes. More noteworthily, a distinctive inversion structure spanning 2.15-2.95 Mb was unveiled among Populus, Tacamahaca, Turaga, Aigeiros poplar species and Salix, highlighting a unique evolutionary feature. Intriguingly, a novel sex genotype of the ZY type, which represents a crossover between XY and ZW systems, was identified and confirmed through both natural and artificial hybrids populations. These novel insights offer significant theoretical value for the study of the species' evolutionary origins and serve as a valuable resource for ecological genetics and forest biotechnology.

2.
Fitoterapia ; : 106109, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39043502

RESUMEN

Chrysosplenium axillare Maxim. is used in traditional Tibetan medicine for the treatment of various human diseases, such as fever, headache, cholecystitis, acute icterohepatitis and acute liver necrosis. In this study, five new cucurbitane triterpenoid derivatives, chrysosaxillins A-E (1-5), along with three known structurally related compounds (6-8) have been isolated from whole herb of C. axillare. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR, HRESIMS, UV, IR, ECD and single-crystal X-ray diffraction. All isolates were evaluated for cytotoxic activities against four tumor cell lines including PC-3, A549, MCF-7, and HepG2. The results discovered that compound 1 possessed the most potent cytotoxicity against A549 cells with IC50 value of 0.05 µM, while compounds 2 and 4 have mild cytotoxicities against cells tested with IC50 values ranging from 8.78 to 41.72 µM. Our study suggests that C. axillare might serve as a valuable source of cucurbitane triterpenoids potentially useful for the development of new anti-tumor agents and support its use as a crop benefits to local economic.

3.
Front Oncol ; 14: 1415225, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38983923

RESUMEN

Epidermoid cyst of the spleen is a rare disease, and relatively few cases were reported by literatures. Most published case reports provided inadequate information on the impact of splenic epidermoid cyst on tumor markers. A 32-year-old woman with a giant splenic epidermoid cyst was reported, for whom the serum concentration of a collection of tumor markers (CA19-9, CEA, CA125, CA242, and CA50) increased abruptly accompanied by left upper abdominal pain for 5 days. After comprehensive preoperative examination and multidisciplinary team discussion, we ruled out any concurrent malignancy and a laparoscopic total splenectomy was performed, during which the splenic cyst spontaneously ruptured unexpectedly. After surgery, the elevated serum tumor marker levels decreased sharply until reaching normal range 3 months later. Learning from the case, we conclude that interval monitoring of serum tumor markers is of critical value for patients with splenic epidermoid cyst. Abrupt elevation of tumor marker levels and abdominal pain may serve as signs of cyst rupture, which is strongly indicative of surgical intervention as soon as possible. Total removal of the splenic cyst is strongly suggested considering the recurrence and malignant potential of the splenic epidermoid cyst.

4.
Structure ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38968938

RESUMEN

Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (KD ∼200 nM). Cryo-EM structures of full-length CNTN2 and CNTN2_Ig1-Ig6 reveal a T-shaped homodimer formed by intertwined, parallel monomers. Unexpectedly, the horseshoe-shaped Ig1-Ig4 headpieces extend their Ig2-Ig3 tips outwards on either side of the homodimer, while Ig4, Ig5, Ig6, and the FN domains form a central stalk. Cross-linking mass spectrometry and cell-based binding assays confirm the 3D assembly of the CNTN2 homodimer. The interface mediating homodimer formation differs between CNTNs, as do the homophilic versus heterophilic interaction mechanisms. The CNTN family thus encodes a versatile molecular platform that supports a very diverse portfolio of protein interactions and that can be leveraged to strategically guide neural circuit development.

5.
Am Surg ; : 31348241266631, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031071

RESUMEN

OBJECTIVES: Patients with peripheral artery disease (PAD) often require treatment with open lower extremity revascularization (LER). Patients with PAD often have other comorbidities and associated conditions that affect procedural outcomes, including abdominal stomas. The aim of this work is to investigate the impact that stomas may have on postoperative outcomes and complications. METHODS: We performed a 5-year (2016-2020) analysis of the Nationwide Readmission Database. We identified all adult patients undergoing open LER. These patients were categorized into 2 groups: stoma and no-stoma. Propensity score matching (1:1) was used to control for demographics and comorbidities. Index admission outcomes and readmission rate were examined. RESULTS: 212,275 open LER patients were identified. A matched cohort of 3088 patients (1:1 stoma vs no-stoma) was obtained. Patients with stomas had higher rates of several postoperative complications: acute posthemorrhagic anemia (29.1%, P < 0.01), acute kidney injury (21.4%, P < 0.001), index sepsis (10.3%, P < 0.001), and index SSI (2.8%, P < 0.001). There were no significant statistical differences between the 2 groups for acute myocardial infarction. Those with stomas had worse outcomes: greater in-hospital mortality (4.7%, P < 0.05), length of stays (median 7 days, P < 0.001), total charges (median 108,037 dollars, P < 0.001), discharges to long-term care facilities (30.8%, P < 0.001), discharges to their own homes needing home health care (30.1%, P < 0.001), 30-day readmission rates (23.2%, P < 0.01), and 30-day readmission mortality (6.1%, P < 0.01). CONCLUSIONS: Concurrent abdominal stoma is associated with increased postoperative morbidity and mortality after open LER. Further prospective studies are needed to validate these results.

6.
Nat Commun ; 15(1): 4395, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782894

RESUMEN

The conformational dynamics of nucleosome arrays generate a diverse spectrum of microscopic states, posing challenges to their structural determination. Leveraging cryogenic electron tomography (cryo-ET), we determine the three-dimensional (3D) structures of individual mononucleosomes and arrays comprising di-, tri-, and tetranucleosomes. By slowing the rate of condensation through a reduction in ionic strength, we probe the intra-array structural transitions that precede inter-array interactions and liquid droplet formation. Under these conditions, the arrays exhibite irregular zig-zag conformations with loose packing. Increasing the ionic strength promoted intra-array compaction, yet we do not observe the previously reported regular 30-nanometer fibers. Interestingly, the presence of H1 do not induce array compaction; instead, one-third of the arrays display nucleosomes invaded by foreign DNA, suggesting an alternative role for H1 in chromatin network construction. We also find that the crucial parameter determining the structure adopted by chromatin arrays is the angle between the entry and exit of the DNA and the corresponding tangents to the nucleosomal disc. Our results provide insights into the initial stages of intra-array compaction, a critical precursor to condensation in the regulation of chromatin organization.


Asunto(s)
ADN , Tomografía con Microscopio Electrónico , Nucleosomas , Nucleosomas/metabolismo , Nucleosomas/ultraestructura , Nucleosomas/química , Tomografía con Microscopio Electrónico/métodos , ADN/química , ADN/metabolismo , Microscopía por Crioelectrón/métodos , Conformación de Ácido Nucleico , Cromatina/química , Cromatina/ultraestructura , Cromatina/metabolismo , Histonas/metabolismo , Histonas/química , Concentración Osmolar , Animales
7.
Nat Commun ; 15(1): 4561, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811575

RESUMEN

The mammalian SWI/SNF-like BAF complexes play critical roles during animal development and pathological conditions. Previous gene deletion studies and characterization of human gene mutations implicate that the complexes both repress and activate a large number of genes. However, the direct function of the complexes in cells remains largely unclear due to the relatively long-term nature of gene deletion or natural mutation. Here we generate a mouse line by knocking in the auxin-inducible degron tag (AID) to the Smarca4 gene, which encodes BRG1, the essential ATPase subunit of the BAF complexes. We show that the tagged BRG1 can be efficiently depleted by osTIR1 expression and auxin treatment for 6 to 10 h in CD4 + T cells, hepatocytes, and fibroblasts isolated from the knock-in mice. The acute depletion of BRG1 leads to decreases in nascent RNAs and RNA polymerase II binding at a large number of genes, which are positively correlated with the loss of BRG1. Further, these changes are correlated with diminished accessibility at DNase I Hypersensitive Sites (DHSs) and p300 binding. The acute BRG1 depletion results in three major patterns of nucleosome shifts leading to narrower nucleosome spacing surrounding transcription factor motifs and at enhancers and transcription start sites (TSSs), which are correlated with loss of BRG1, decreased chromatin accessibility and decreased nascent RNAs. Acute depletion of BRG1 severely compromises the Trichostatin A (TSA) -induced histone acetylation, suggesting a substantial interplay between the chromatin remodeling activity of BRG1 and histone acetylation. Our data suggest BRG1 mainly plays a direct positive role in chromatin accessibility, RNAPII binding, and nascent RNA production by regulating nucleosome positioning and facilitating transcription factor binding to their target sites.


Asunto(s)
ADN Helicasas , Proteínas Nucleares , Factores de Transcripción , Animales , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , ADN Helicasas/metabolismo , ADN Helicasas/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Ratones , Nucleosomas/metabolismo , Nucleosomas/genética , Ácidos Indolacéticos/metabolismo , ARN Polimerasa II/metabolismo , Fibroblastos/metabolismo , Técnicas de Sustitución del Gen , Hepatocitos/metabolismo , Proteína p300 Asociada a E1A/metabolismo , Proteína p300 Asociada a E1A/genética , Activación Transcripcional , Transcripción Genética , Histonas/metabolismo , Desoxirribonucleasa I/metabolismo , Cromatina/metabolismo , Humanos
8.
J Vasc Surg Venous Lymphat Disord ; : 101908, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38759751

RESUMEN

BACKGROUND: Venous thromboembolism (VTE) stands as the leading cause of preventable death within hospitals in the United States. Although there have been some studies investigating the incidence rates of VTE, there has yet to be a large-scale study elucidating disparities in sex, race, income, region, and seasons in patients with VTE. The goal of this study was to report the disparities in race, sex, income, region, and seasons in patients with VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT), in hospitalized patients from 2016 to 2019. METHODS: We used the United States National Inpatients Sample database to identify inpatients diagnosed with PE, DVT, and PE and DVT from 2016 to 2019. The inpatient incidence per thousand was calculated for sex and race using the weighted sample model. The regional and monthly incidence of DVT and PE per thousand inpatients and risk of incidence were calculated. Patients' characteristics including hospital type, bed size, median length of stay, median total charges, and mortality were also collected. RESULTS: We examined 455,111 cases of VTE, 177,410 cases of DVT, 189,271 cases of PE, and 88,430 cases of both DVT and PE combined. Over the study period, we observed a statistically significant trend among PE hospitalization incidences. There was a strong and positive correlation between DVT and PE inpatients. Black inpatients had the highest cumulative incidence of hospitalizations in all cohorts with 10.36 per 1000 in PE and 9.1 per 1000 in DVT. Asian and Pacific Islander inpatients had the lowest cumulative incidence with 4.42 per 1000 in PE and 4.28 per 1000 in DVT. Females showed the lowest cumulative incidence with 7.47 per 1000 in PE and 6.53 per 1000 in DVT. The Mountain region was the highest among PE hospitalizations with 9.62 per 1000. For DVT, the Middle Atlantic region was the highest at 8.65 per 1000. The in-hospital mortality rate was the highest among the PE hospitalizations at 7.3%. Also, the trend analysis showed significant increases among all groups. CONCLUSIONS: Over the study period (2016-2019), we report the racial, biological sex, and geographical disparities from the National Inpatient Sample database, highlighting that Black inpatients had the highest incidence of PE and DVT, whereas Asian/Pacific Islander inpatients had the lowest incidences of PE and DVT. Moreover, women had a lower incidence compared with men. The observed regional variations indicated that the incidence of PE was highest in the Mountain region, whereas the incidence of DVT was lowest in the Middle Atlantic region. There was an increase in the mortality of inpatients diagnosed with VTE reflecting the growing burden of this condition in the US health care system.

9.
Bioconjug Chem ; 35(6): 843-854, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38775802

RESUMEN

The prevalence and fatality rates of gastric cancer (GC) remain elevated, with advanced stages presenting a grim prognosis. Noninvasive diagnosis of GC cancer often proves challenging until the disease has progressed to an advanced stage or metastasized. Initially, the level of fibronectin (FN) in cancer-associated fibroblasts (CAFs) of GC was at least 3.7 times higher than that in normal fibroblasts. Herein, two FN-targeting magnetic resonance/near-infrared fluorescence (MR/NIRF) imaging contrast agents were developed to detect GC and peritoneal metastasis noninvasively. The probes CREKA-Cy7-(Gd-DOTA) and CREKA-Cy7-(Gd-DOTA)3 demonstrated significant FN-targeting capability (with dissociation constants of 1.0 and 2.1 mM) and effective MR imaging performance (with proton relaxivity values of 9.66 and 27.44 mM-1 s-1 at 9.4 T, 37 °C). In vivo imaging revealed a high signal-to-noise ratio and successful visualization of GC metastasis using NIRF imaging as well as successful tumor detection in MR imaging. Therefore, this study highlights the potential of FN-targeting probes for GC diagnosis and aids in the advancement of new diagnostic strategies for the clinical detection of GC.


Asunto(s)
Medios de Contraste , Fibronectinas , Imagen por Resonancia Magnética , Neoplasias Peritoneales , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Fibronectinas/metabolismo , Imagen por Resonancia Magnética/métodos , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/diagnóstico , Humanos , Medios de Contraste/química , Animales , Ratones , Imagen Óptica/métodos , Compuestos Organometálicos/química , Línea Celular Tumoral , Compuestos Heterocíclicos
10.
Front Surg ; 11: 1370702, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742149

RESUMEN

Background and objective: Surgery is the primary therapy that crucially affects the survival of patients with kidney cancer (KC). However, pertinent surgical decision criteria for individuals with stage T2-3 KC are lacking. This study aimed to display the practical choices and evolving trends of surgical procedures and elucidate their implied value. Methods: Through the Surveillance, Epidemiology, and End Results (SEER) dataset, the levels and evolving trends of different surgical methods were examined to determine cancer-specific risk of death (CSRD). Additionally, stratification analysis and survival rate analysis were performed to explore the effectiveness of partial nephrectomy (PN). Results: In this study, 9.27% of patients opted for PN. Interestingly, an upward trend was observed in its decision, with an average annual percentage change (AAPC) of 7.0 (95% CI: 4.8-9.3, P < 0.05). Patients who underwent PN and were in a relatively less severe condition exhibited more favorable CSRD levels (0.17-0.36 vs. 0.50-0.67) and an improvement trend compared with those who underwent radical nephrectomy (RN) (AAPC: -1.9 vs. -0.8). Further analysis showed that the levels of CSRD and survival rates for patients opting for different surgical methods followed a similar pattern. Conclusions: This study showed that RN was still the most common surgical method. Patients with stage T2-3 KC had an increasing preference for PN and exhibited more favorable cancer-related survival outcomes, which underscores the need for further investigation and validation.

11.
New Phytol ; 242(6): 2872-2887, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581199

RESUMEN

In the Vetrix clade of Salix, a genus of woody flowering plants, sex determination involves chromosome 15, but an XY system has changed to a ZW system. We studied the detailed genetic changes involved. We used genome sequencing, with chromosome conformation capture (Hi-C) and PacBio HiFi reads to assemble chromosome level gap-free X and Y of Salix arbutifolia, and distinguished the haplotypes in the 15X- and 15Y-linked regions, to study the evolutionary history of the sex-linked regions (SLRs). Our sequencing revealed heteromorphism of the X and Y haplotypes of the SLR, with the X-linked region being considerably larger than the corresponding Y region, mainly due to accumulated repetitive sequences and gene duplications. The phylogenies of single-copy orthogroups within the SLRs indicate that S. arbutifolia and Salix purpurea share an ancestral SLR within a repeat-rich region near the chromosome 15 centromere. During the change in heterogamety, the X-linked region changed to a W-linked one, while the Z was derived from the Y.


Asunto(s)
Cromosomas de las Plantas , Filogenia , Salix , Cromosomas de las Plantas/genética , Salix/genética , Haplotipos/genética , Evolución Biológica , Evolución Molecular , Sitios Genéticos , Procesos de Determinación del Sexo/genética
12.
Immunity ; 57(5): 987-1004.e5, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38614090

RESUMEN

The development and function of the immune system are controlled by temporospatial gene expression programs, which are regulated by cis-regulatory elements, chromatin structure, and trans-acting factors. In this study, we cataloged the dynamic histone modifications and chromatin interactions at regulatory regions during T helper (Th) cell differentiation. Our data revealed that the H3K4me1 landscape established by MLL4 in naive CD4+ T cells is critical for restructuring the regulatory interaction network and orchestrating gene expression during the early phase of Th differentiation. GATA3 plays a crucial role in further configuring H3K4me1 modification and the chromatin interaction network during Th2 differentiation. Furthermore, we demonstrated that HSS3-anchored chromatin loops function to restrict the activity of the Th2 locus control region (LCR), thus coordinating the expression of Th2 cytokines. Our results provide insights into the mechanisms of how the interplay between histone modifications, chromatin looping, and trans-acting factors contributes to the differentiation of Th cells.


Asunto(s)
Diferenciación Celular , Cromatina , Código de Histonas , Histonas , Células Th2 , Diferenciación Celular/inmunología , Animales , Cromatina/metabolismo , Ratones , Células Th2/inmunología , Histonas/metabolismo , Factor de Transcripción GATA3/metabolismo , Regulación de la Expresión Génica , Ratones Endogámicos C57BL , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Región de Control de Posición , Citocinas/metabolismo
13.
Clin Neurol Neurosurg ; 238: 108168, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38382131

RESUMEN

INTRODUCTION: Elevated intracranial pressure (ICP) can cause progressive neurological deterioration following traumatic brain injury (TBI). ICP can be monitored to guide subsequent treatment decisions. However, there is conflicting data in the literature regarding the utility of ICP monitoring. We aim to describe patterns and outcomes of ICP monitoring in the United States with the use of a nationwide healthcare database. METHODS: We performed a 5-year analysis of the Nationwide Inpatient Sample database. We identified all adult TBI patients with a Glasgow Coma Scale (GCS) measuring 3-8 using International Classification of Diseases diagnostic codes. Propensity score matching (1:2 ratio) was performed to control for demographics, injury parameters and comorbidities. Outcome measures included inpatient mortality, length of stay (LOS), cost of care, and discharge disposition. RESULTS: After propensity score matching, a cohort of 1664 patients was obtained (monitored, 555; non-monitored, 1109). Index outcomes with respect to monitor and no-monitor are as follows: inpatient mortality (35.1%, 42.4%, P <0.01), median LOS (15 days, 6 days, P<0.001), median total charge (289,797 USD, 154,223 USD, P <0.001), discharge home (7.9%, 19.3%, P <0.001) and discharge to another facility (53.9%, 35.4%, P <0.001). DISCUSSION: ICP monitoring in TBI patients is associated with decreased inpatient mortality and discharge to home, and it is associated with an increased hospital LOS, total charge, and chance of discharge to another facility. CONCLUSION: The risks and benefits of ICP monitoring should be seriously considered when managing adults with severe TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Adulto , Humanos , Estados Unidos/epidemiología , Presión Intracraneal , Pacientes Internos , Monitoreo Fisiológico/métodos , Escala de Coma de Glasgow
14.
Plant Physiol ; 195(1): 652-670, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38412470

RESUMEN

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.


Asunto(s)
Alelos , Genoma de Planta , Populus , Populus/genética , Genoma de Planta/genética , Regulación de la Expresión Génica de las Plantas , Haplotipos/genética , Hibridación Genética , Aprendizaje Automático
15.
bioRxiv ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38405796

RESUMEN

Background: Biomarkers of early pathogenesis of type 1 diabetes (T1D) are crucial to enable effective prevention measures in at-risk populations before significant damage occurs to their insulin producing beta-cell mass. We recently introduced the concept of integrated parallel multi-omics and employed a novel data augmentation approach which identified promising candidate biomarkers from a small cohort of high-risk T1D subjects. We now validate selected biomarkers to generate a potential composite signature of T1D risk. Methods: Twelve candidate biomarkers, which were identified in the augmented data and selected based on their fold-change relative to healthy controls and cross-reference to proteomics data previously obtained in the expansive TEDDY and DAISY cohorts, were measured in the original samples by ELISA. Results: All 12 biomarkers had established connections with lipid/lipoprotein metabolism, immune function, inflammation, and diabetes, but only 7 were found to be markedly changed in the high-risk subjects compared to the healthy controls: ApoC1 and PON1 were reduced while CETP, CD36, FGFR1, IGHM, PCSK9, SOD1, and VCAM1 were elevated. Conclusions: Results further highlight the promise of our data augmentation approach in unmasking important patterns and pathologically significant features in parallel multi-omics datasets obtained from small sample cohorts to facilitate the identification of promising candidate T1D biomarkers for downstream validation. They also support the potential utility of a composite biomarker signature of T1D risk characterized by the changes in the above markers.

16.
J Cell Physiol ; 239(2): e31159, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38212939

RESUMEN

Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.


Asunto(s)
MicroARNs , ARN Circular , Animales , Bovinos , Diferenciación Celular/genética , Proliferación Celular/genética , Mamíferos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Desarrollo de Músculos/genética , Mioblastos/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , ARN Interferente Pequeño/metabolismo , Células Cultivadas , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
17.
Heliyon ; 10(1): e23755, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38223708

RESUMEN

Objective: To report and analyze the clinical characteristics of 15 patients with Listeria meningitis in adult. Methods: We reviewed the medical records of 15 patients with Listeria meningitis who were admitted to Shanxi Bethune Hospital between January 2017 and January 2023. Results: The clinical manifestations was primarily characterized by fever, altered mental status, headache, neck stiffness, and vomiting. Blood or cerebrospinal fluid (CSF) cultures were performed in 15 cases, and pathogens were detected in 11 of them. Metagenomic next-generation sequencing (mNGS) detected pathogens in 10 cases, with four being negative by conventional methods and six being positive through traditional tests. The laboratory blood results presented leukocytosis. The CSF analysis upon admission showed elevated levels of white blood cells and proteins, as well as decreased chloride and glucose concentration. The brain computed tomography (CT) revealed ventricular enlargement in 3 patients. The brain magnetic resonance imaging (MRI) showed abnormalities in multiple areas of the brain. Despite 3 patients with decompensated hydrocephalus underwent lateral ventricle puncture and drainage,their neurological deterioration were increasingly deteriorating.7 patients were treated by mechanical ventilation due to respiratory insufficiency. After 3 months, there were 9 cases with excellent outcomes(modified Rankin Scale score of 0-2),2 cases with favorable outcomes(score of 3-5), and 4 deaths(score of 6). Conclusions: This thesis found that the detection rate of Listeria monocytogenes has been on a rise over the past six years in our department, ranking second only to Streptococcus pneumoniae. Additionally, the detection rate achieved by mNGS surpasses that of other conventional methods. Among the patient cohort, 11 had underlying diseases such as systemic lupus erythematosus, tuberculosis, diabetes mellitus, pituitary neoplasms, leukemia and other related illnesses. Once listeriosis is early identified, the adequate antibiotic therapy should be promptly introduced in the course of empirical treatment.

18.
Accid Anal Prev ; 195: 107403, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38007877

RESUMEN

Jaywalker-vehicle (J-V) conflicts at mid-blocks without crossing facilities in China are frequent and hazardous. Due to the unexpected and sudden nature of jaywalking activity, it is crucial to develop predictive models for J-V conflicts to offer pre-conflict warnings for road users. This study introduces a novel encoder-decoder framework that utilizes multi-source data to predict J-V conflict severity. We define three encoders to represent three types of input data, (1) J-V interaction encoder (Bi-LSTM), (2) jaywalker motion encoder (Bi-LSTM) and (3) background information encoder (MLP). Subsequently, features extracted by these three encoders are concatenated and transferred to the conflict severity decoder (MLP) to obtain the predicted severity level. We further conduct a case study using the surveyed video data at three mid-blocks without crossing facilities in Nanjing, China. The experimental results indicate that, compared to classical models, our proposed encoder-decoder (Proposed ED) model exhibits the best and stable predictive metrics. Furthermore, the results of the ablation study suggest that the incorporation of background information significantly enhances the four evaluative metrics of the Proposed ED model, with an average improvement of 24.291%. Additionally, the results of transferability analysis suggest that, when the ratio of added samples from the new mid-block reaches 40% to 50%, the predictive metrics of the updated models could stabilize at around 80% to 95%, indicating a notably good performance. Eventually, we derive several practical suggestions from the above findings, in order to help with J-V conflict prediction and jaywalking safety improvement.


Asunto(s)
Accidentes de Tránsito , Humanos , China , Movimiento (Física)
19.
Radiol Case Rep ; 19(2): 825-830, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38111550

RESUMEN

This study presents a rare case of an older woman with an intracranial mesenchymal tumor in the right frontal and parietal lobes. Despite prompt surgical intervention, her condition rapidly deteriorated because of tumor dissemination, leading to her demise. We highlight the tumor's marked invasiveness and heterogeneity, coupled with a propensity for distant systemic metastasis, which negatively impacted the patient's prognosis. This particular clinical behavior had not been previously reported, making this a novel observation. Thus, through a comprehensive review of relevant literature, we aim to provide valuable insights for further understanding, diagnosing, and treating such tumors.

20.
Front Oncol ; 13: 1194120, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37909021

RESUMEN

Objective: To investigate the value of a clinical-MRI radiomics model based on clinical characteristics and T2-weighted imaging (T2WI) for preoperatively evaluating lymph node (LN) metastasis in patients with MRI-predicted low tumor (T) staging rectal cancer (mrT1, mrT2, and mrT3a with extramural spread ≤ 5 mm). Methods: This retrospective study enrolled 303 patients with low T-staging rectal cancer (training cohort, n = 213, testing cohort n = 90). A total of 960 radiomics features were extracted from T2WI. Minimum redundancy and maximum relevance (mRMR) and support vector machine were performed to select the best performed radiomics features for predicting LN metastasis. Multivariate logistic regression analysis was then used to construct the clinical and clinical-radiomics combined models. The model performance for predicting LN metastasis was assessed by receiver operator characteristic curve (ROC) and clinical utility implementing a nomogram and decision curve analysis (DCA). The predictive performance for LN metastasis was also compared between the combined model and human readers (2 seniors). Results: Fourteen radiomics features and 2 clinical characteristics were selected for predicting LN metastasis. In the testing cohort, a higher positive predictive value of 75.9% for the combined model was achieved than those of the clinical model (44.8%) and two readers (reader 1: 54.9%, reader 2: 56.3%) in identifying LN metastasis. The interobserver agreement between 2 readers was moderate with a kappa value of 0.416. A clinical-radiomics nomogram and decision curve analysis demonstrated that the combined model was clinically useful. Conclusion: T2WI-based radiomics combined with clinical data could improve the efficacy in noninvasively evaluating LN metastasis for the low T-staging rectal cancer and aid in tailoring treatment strategies.

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