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Distal myopathies are a group of rare heterogeneous diseases that are mostly caused by genetic factors. At least 20 genes have been associated with distal myopathies. We performed whole-exome sequencing to identify the genetic cause of disease in a family with distal myopathy. Following the American College of Medical Genetics and Genomics (ACMG) guidelines, we analyzed the sequencing results and screened suspicious mutations based on mutation frequency, functional impact, and disease inheritance pattern. The harmfulness of the mutations was predicted using bioinformatics methods, and the pathogenic mutations were determined. We identified a novel amino acid mutation (NP_005467.1:p.S663L) on the GNE gene that may cause familial distal myopathy. This mutation is the result of the simultaneous mutation of two adjacent nucleotides (c.1988C > T, c.1989C > A) in the codon. First, we measured the mRNA and protein expression of the GNE gene in the lymphoblastoid cell lines (LCLs) of the probands and their family members. Second, GNE vectors carrying the novel mutation, two other known pathogenic mutations, and the wild-type gene were constructed and transfected into HEK293T cells. The enzymatic activity of these GNE variants was investigated and showed that the p.S663L mutation significantly reduced the activity of the bifunctional GNE enzyme without altering the expression level of the GNE protein. Furthermore, the mutation may also alter the immunogenicity of the 3' end of the GNE protein, potentially affecting its oligomer formation. In this study, a novel GNE gene mutation that may cause distal myopathy was identified, expanding the spectrum of genetic mutations associated with this disease.
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Miopatías Distales , Complejos Multienzimáticos , Linaje , Humanos , Masculino , Femenino , Células HEK293 , Miopatías Distales/genética , Complejos Multienzimáticos/genética , Mutación , Adulto , Secuenciación del Exoma/métodos , Persona de Mediana EdadRESUMEN
The conventional Hall effect is linearly proportional to the field component or magnetization component perpendicular to a film. Despite the increasing theoretical proposals on the Hall effect to the in-plane field or magnetization in various special systems induced by the Berry curvature, such an unconventional Hall effect has only been experimentally reported in Weyl semimetals and in a heterodimensional superlattice. Here, we report an unambiguous experimental observation of the antisymmetric planar Hall effect (APHE) with respect to the in-plane magnetic field in centrosymmetric rutile RuO2 and IrO2 single-crystal films. The measured Hall resistivity is found to be linearly proportional to the component of the applied in-plane magnetic field along a particular crystal axis and to be independent of the current direction or temperature. Both the experimental observations and theoretical calculations confirm that the APHE in rutile oxide films is induced by the Lorentz force. Our findings can be generalized to ferromagnetic materials for the discovery of anomalous Hall effects and quantum anomalous Hall effects induced by in-plane magnetization. In addition to significantly expanding knowledge of the Hall effect, this work opens the door to explore new members in the Hall effect family.
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Doxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.
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Cardiotoxicidad , Doxorrubicina , Microbioma Gastrointestinal , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Doxorrubicina/efectos adversos , Cardiotoxicidad/etiología , Animales , Disbiosis , Trasplante de Microbiota FecalRESUMEN
Background: Increasing evidence indicating that coronavirus disease 2019 (COVID-19) increased the incidence and related risks of pericarditis and whether COVID-19 vaccine is related to pericarditis has triggered research and discussion. However, mechanisms behind the link between COVID-19 and pericarditis are still unknown. The objective of this study was to further elucidate the molecular mechanisms of COVID-19 with pericarditis at the gene level using bioinformatics analysis. Methods: Genes associated with COVID-19 and pericarditis were collected from databases using limited screening criteria and intersected to identify the common genes of COVID-19 and pericarditis. Subsequently, gene ontology, pathway enrichment, protein-protein interaction, and immune infiltration analyses were conducted. Finally, TF-gene, gene-miRNA, gene-disease, protein-chemical, and protein-drug interaction networks were constructed based on hub gene identification. Results: A total of 313 common genes were selected, and enrichment analyses were performed to determine their biological functions and signaling pathways. Eight hub genes (IL-1ß, CD8A, IL-10, CD4, IL-6, TLR4, CCL2, and PTPRC) were identified using the protein-protein interaction network, and immune infiltration analysis was then carried out to examine the functional relationship between the eight hub genes and immune cells as well as changes in immune cells in disease. Transcription factors, miRNAs, diseases, chemicals, and drugs with high correlation with hub genes were predicted using bioinformatics analysis. Conclusions: This study revealed a common gene interaction network between COVID-19 and pericarditis. The screened functional pathways, hub genes, potential compounds, and drugs provided new insights for further research on COVID-19 associated with pericarditis.
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COVID-19 , Pericarditis , Humanos , Vacunas contra la COVID-19 , COVID-19/genética , Biología Computacional , Biología de Sistemas , Pericarditis/genéticaRESUMEN
Purpose: Doxorubicin-induced cardiotoxicity (DIC) is a severe side reaction in cancer chemotherapy that greatly impacts the well-being of cancer patients. Currently, there is still an insufficiency of effective and reliable biomarkers in the field of clinical practice for the early detection of DIC. This study aimed to determine and validate the potential diagnostic and predictive values of critical signatures in DIC. Methods: We obtained high-throughput sequencing data from the GEO database and performed data analysis and visualization using R software, GO, KEGG and Cytoscape. Machine learning methods and weighted gene coexpression network (WGCNA) were used to identify key genes for diagnostic model construction. Receiver operating characteristic (ROC) analysis and a nomogram were used to assess their diagnostic values. A multiregulatory network was built to reveal the possible regulatory relationships of critical signatures. Cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) analysis was used to investigate differential immune cell infiltration. Additionally, a cell and animal model were constructed to investigate the relationship between the identified genes and DIC. Results: Among the 3713 differentially expressed genes, three key genes (CSGALNACT1, ZNF296 and FANCB) were identified. A nomogram and ROC curves based on three key genes showed excellent diagnostic predictive performance. The regulatory network analysis showed that the TFs CREB1, EP300, FLI1, FOXA1, MAX, and MAZ modulated three key genes. An analysis of immune cell infiltration indicated that many immune cells (activated NK cells, M0 macrophages, activated dendritic cells and neutrophils) might be related to the progression of DIC. Furthermore, there may be various degrees of correlation between the three critical signatures and immune cells. RTâqPCR demonstrated that the mRNA expression of CSGALNACT1 and ZNF296 was significantly upregulated, while FANCB was significantly downregulated in DOX-treated cardiomyocytes in vitro and in vivo. Conclusion: Our study suggested that the differential expression of CSGALNACT1, ZNF296 and FANCB is associated with cardiotoxicity and is also involved in immune cell infiltration in DIC. They might be potential biomarkers for the early occurrence of DIC.
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Recently, research into the link between thyroid dysfunction and Alzheimer's disease (AD) remains a current topic of interest. Previous research has primarily concentrated on examining the impact of thyroid dysfunction on the risk of developing AD, or solely explored the mechanisms of interaction between hypothyroidism and AD, a comprehensive analysis of the mechanisms linking thyroid dysfunction, including hyperthyroidism and hypothyroidism, to Alzheimer's disease (AD) still require further elucidation. Therefore, the aim of this review is to offer a thorough and comprehensive explanation of the potential mechanisms underlying the causal relationship between thyroid dysfunction and AD, highlighting the existence of a vicious circle. The effect of thyroid dysfunction on AD includes neuron death, impaired synaptic plasticity and memory, misfolded protein deposition, oxidative stress, and diffuse and global neurochemical disturbances. Conversely, AD can also contribute to thyroid dysfunction by affecting the stress repair response and disrupting pathways involved in thyroid hormone (TH) production, transport, and activation. Furthermore, this review briefly discusses the role and significance of utilizing the thyroid as a therapeutic target for cognitive recovery in AD. By exploring potential mechanisms and therapeutic avenues, this research contributes to our understanding and management of this devastating neurodegenerative disease.
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Enfermedad de Alzheimer , Hipertiroidismo , Hipotiroidismo , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/metabolismo , Hipotiroidismo/psicología , Hipertiroidismo/complicacionesRESUMEN
Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing's syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients' circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.
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Síndrome de Cushing , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Estados Unidos , Humanos , Mitotano/uso terapéutico , Hidrocortisona , Síndrome de Cushing/tratamiento farmacológico , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/tratamiento farmacológico , Hormona AdrenocorticotrópicaRESUMEN
BACKGROUND: This study investigated the effects of early-onset type 2 diabetes (EOD) vs late-onset type 2 diabetes (LOD) on nonfatal cardiovascular diseases (CVD) in China. METHODS: We conducted a cross-sectional survey of 46 239 participants from 14 provinces in China from 2007 to 2008, selecting 4949 participants with type 2 diabetes for analysis. Participants were categorized as EOD (<40 years) or LOD (≥40 years) based on age at diabetes diagnosis. Sociodemographic and nonfatal CVD information was collected through an interviewer-assisted questionnaire and clinical examination. Logistic regression analysis was used to investigate the nonfatal CVD risk. RESULTS: Out of 4949 participants with type 2 diabetes, 390 (7.88%) had nonfatal CVD. Participants with EOD had a higher age-standardized prevalence of nonfatal CVD than those with LOD (11.4% vs 4.4%). Compared to LOD patients, EOD patients tended to be males and had a higher family history of diabetes, unhealthy lifestyle behaviors, and lower blood pressure levels. After adjustment for age and sex, EOD patients had a higher risk of nonfatal CVD than LOD patients (odds ratio [OR] 2.3, 95% CI 1.5-3.5). After further adjustment for diabetes duration, use of drugs, and other risk factors, the OR of nonfatal CVD was reduced but significant (OR 1.8, 95% CI 1.1-2.9). Sensitivity analysis revealed that EOD patients with metabolic syndrome had an increased nonfatal CVD risk compared to LOD patients (OR 2.0, 95% CI 1.2-3.5). CONCLUSIONS: EOD patients are at increased risk of nonfatal CVD. Individualized intervention and management measures for EOD patients are necessary.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Masculino , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios Transversales , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Edad de Inicio , Factores de Riesgo , China/epidemiologíaRESUMEN
Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is an important subtype of myocardial infarction. Although comprising less than 50% stenosis in the main epicardial coronary arteries, it constitutes a severe health risk. A variety of approaches have been recommended, but definitive diagnosis remains elusive. In addition, the lack of a comprehensive understanding of underlying pathophysiology makes clinical management difficult and unpredictable. This review highlights ongoing efforts to identify relevant biomarkers in MINOCA to improve diagnosis, individualize treatment and better predict outcomes.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Humanos , MINOCA , Angiografía Coronaria , Factores de Riesgo , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Infarto del Miocardio/diagnóstico , Biomarcadores , Vasos CoronariosRESUMEN
Following the publication of the above article, an interested reader drew to the authors' attention that, in Figs. 7A and 8A. apparently the same mouse had been featured to represent two different experimental groups, albeit displaying distinct fluorescence values. Moreover, following an independent investigation in the Editorial Office, an additional instance of probable data duplication was also noted, comparing between the 'SCC15 / siNC' cell migration image in Fig. 2D and the 'SCC15EV' migration assay image in Fig. 1C. After having consulted their original data, the authors realized that these errors arose during the process of assembling the images for Figs. 2 and 8. First, the image for the DZNep (42d) experiment in Fig. 7A had inadvertently been used for the mimic NC (7d) experiment in Fig. 8A; moreover, the 'SCC15 / siNC' cell migration image in Fig. 2D had been selected incorrectly. The revised versions of Figs. 2 and 8, showing the correct data for the the 'SCC15 / siNC' cell migration image in Fig. 2D and the mimic NC (7d) experiment in Fig. 8A, are shown on the next two pages. The authors regret that these errors went unnoticed prior to publication, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 52: 11491164, 2018; DOI: 10.3892/ijo.2018.4293].
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High-temperature laser bed powder fusion (HT-LPBF) technology is an ideal method for processing poly-ether-ether-ketone (PEEK) implants with personalized bionic structures, but the biological inertia of PEEK limits its medical applications. In this study, we evaluated the mechanical and biological properties of a novel akermanite (AKM)/PEEK composite for HT-LPBF. The results showed that tiny AKM particles are evenly attached to the surface of the PEEK particle. The delayed peak crystallization temperature and stable sintering window ensure the processing feasibility of the AKM/PEEK composites. The tensile strength and Young's modulus are in the range of 30.83-98.73 MPa and 2.27-3.71 GPa, respectively, which can match the properties of cancellous bones and meet their implanting requirement. The CCK-8 experiments demonstrated the biocompatibility of the composites and the good proliferation of bone marrow stromal cells. The dense hydroxyapatite network layer and petal-like hydroxyapatite demonstrates biological activity, indicating that the composite has a good potential in the orthopedics fields.
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PURPOSE: Pathological complete response(pCR) during neoadjuvant chemotherapy(NAC) has been proposed as a predictor for better prognosis in breast cancer. However, few studies compare the outcomes of patients receiving NAC and adjuvant chemotherapy(AC). METHODS: We retrospectively matched the patients who received NAC(N = 462) and AC(N = 462) by age, time of diagnosis, and primary clinical stage using the propensity score match in breast cancer patients treated in Sir Run Run Shaw Hospital with the median follow up of 67 months. Death from breast cancer and recurrence were used as endpoints. A multivariable Cox models were used to estimate the hazard ratios for breast-cancer specific survival (BCSS) and DFS. A multivariable logistic regression model was simulated to predict pCR. RESULTS: In patients who received NAC, 18.0%(83/462) patients achieved pCR, while the rest of the patients did not. pCR subgroup demonstrated significant better BCSS and DFS than patients receiving AC(BCSS: HR = 0.39, 95% CI:0.12-0.93, P = 0.03; DFS: HR = 0.16, 95%CI 0.009-0.73, P = 0.013) and non-pCR patients(BCSS: HR = 0.32, 95%CI 0.10-0.77, P = 0.008; DFS: HR = 0.12, 95%CI 0.007-0.55, P = 0.002). Patients who received AC demonstrated insignificant survival compared to non-pCR patients(BCSS: HR= 0.82, 95%CI 0.62-1.10, P = 0.19; DFS: HR = 0.75, 95%CI 0.53-1.07, P = 0.12). Patients with AC had significant better DFS than non-pCR patients(HR = 0.33, 95% CI 0.10-0.94, P = 0.04) in luminal B Her2+ patients. More NAC cycles(>2), TNBC, lower cT stage, and mixed histology indicate higher possibility of pCR(AUC = 0.89). CONCLUSION: pCR patients with NAC indicated better prognosis than patients receiving AC or non-pCR patients from NAC. The timing of chemotherapy may need carefully pondering in luminal B Her2+ patients.
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Neoplasias de la Mama , Humanos , Preescolar , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Terapia Neoadyuvante , Estudios Retrospectivos , Pronóstico , Quimioterapia AdyuvanteRESUMEN
BACKGROUND: Diffusion tensor imaging (DTI) has found clinical applications in the evaluation of the central nervous system and has been extensively used to image peripheral neuropathy. However, few studies have focused on lumbosacral nerve root fiber damage in diabetic peripheral neuropathy (DPN). The aim of the study was to evaluate whether DTI of the lumbosacral nerve roots can be used to detect DPN. METHODS: Thirty-two type 2 diabetic patients with DPN and thirty healthy controls (HCs) were investigated with a 3T MRI scanner. DTI with tractography of the L4, L5, and S1 nerve roots was performed. Anatomical fusion with the axial T2 sequences was used to provide correlating anatomical information. Mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured from tractography images and compared between groups. Diagnostic value was assessed using receiver operating characteristic (ROC) analysis. The Pearson correlation coefficient was used to explore the correlation between DTI parameters and clinical data and the nerve conduction study (NCS) in the DPN group. RESULTS: In the DPN group, FA was decreased (p < 0.001) and ADC was increased (p < 0.001) compared with the values of the HC group. FA displayed the best diagnostic accuracy, with an area under the ROC curve of 0.716. ADC was positively correlated with HbA1c level (r = 0.379, p = 0.024) in the DPN group. CONCLUSIONS: DTI of lumbosacral nerve roots demonstrates appreciable diagnostic accuracy in patients with DPN.
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BACKGROUND: Water exchange across blood-brain barrier (BBB) (WEXBBB ) is an emerging biomarker of BBB dysfunction with potential applications in many brain diseases. Several MRI methods have been proposed to measure WEXBBB , but evidence remains scarce whether different methods can produce comparable WEXBBB . PURPOSE: To explore whether dynamic contrast-enhanced (DCE)-MRI and vascular water exchange imaging (VEXI) could produce comparable WEXBBB in high-grade glioma (HGG) patients. STUDY TYPE: Prospective cross-sectional. SUBJECTS: 13 HGG patients (58.4 ± 9.4 years, 9 females, 4 WHO III and 9 WHO IV). FIELD STRENGTH/SEQUENCE: A 3 T, spoiled gradient-recalled-echo DCE-MRI and VEXI containing two pulsed-gradient spin-echo blocks separated by a mixing block. ASSESSMENTS: The enhanced tumor and contralateral normal-appearing white matter (cNAWM) volume-of-interests (VOIs) were drew by two neuroradiologists. And whole-brain NAWM and normal-appearing gray matter (NAGM) without tumor-affected regions were segmented by automated segmentation algorithm in FSL. STATISTICAL TESTS: Student's t-test was used to evaluate parameters difference between cNAWM and tumor, NAGM and NAWM, respectively. The correlation between vascular water efflux rate constant (kbo ) from DCE-MRI and apparent exchange rate across BBB (AXRBBB ) from VEXI was evaluated by Pearson correlation. P < 0.05 was considered statistically significant. RESULTS: Compared with cNAWM, both kbo and AXRBBB were significantly reduced in tumor (kbo = 3.50 ± 1.18 sec-1 vs. 1.03 ± 0.75 sec-1 ; AXRBBB = 3.54 ± 1.11 sec-1 vs. 1.94 ± 1.04 sec-1 ). Both kbo and AXRBBB showed significantly higher values in NAWM than NAGM (kbo = 3.50 ± 0.59 sec-1 vs. 2.10 ± 0.56 sec-1 ; AXRBBB = 3.35 ± 0.77 sec-1 vs. 2.07 ± 0.52 sec-1 ). The VOI-averaged kbo and AXRBBB were also linearly correlated in tumor, NAWM, and NAGM (r = 0.59). DATA CONCLUSION: DCE-MRI and VEXI showed comparable and correlated WEXBBB in HGG patients, suggesting that the consistence and reliability of these two MRI methods in measuring WEXBBB . EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.
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Neoplasias Encefálicas , Glioma , Femenino , Humanos , Barrera Hematoencefálica/diagnóstico por imagen , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Reproducibilidad de los Resultados , Estudios Transversales , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Glioma/diagnóstico por imagen , Glioma/patología , Medios de ContrasteRESUMEN
Blood-brain barrier (BBB) impairment is an important pathophysiological process in Alzheimer's disease (AD) and a potential biomarker for early diagnosis of AD. However, most current neuroimaging methods assessing BBB function need the injection of exogenous contrast agents (or tracers), which limits the application of these methods in a large population. In this study, we aim to explore the feasibility of vascular water exchange MRI (VEXI), a diffusion-MRI-based method proposed to assess the BBB permeability to water molecules without using a contrast agent, in the detection of the BBB breakdown in AD. We tested VEXI on a 3T MRI scanner on three groups: AD patients (AD group), mild cognitive impairment (MCI) patients due to AD (MCI group), and the age-matched normal cognition subjects (NC group). Interestingly, we find that the apparent water exchange across the BBB (AXRBBB) measured by VEXI shows higher values in MCI compared with NC, and this higher AXRBBB happens specifically in the hippocampus. This increase in AXRBBB value gets larger and extends to more brain regions (medial orbital frontal cortex and thalamus) from MCI group to the AD group. Furthermore, we find that the AXRBBB values of these three regions is correlated significantly with the impairment of respective cognitive domains independent of age, sex and education. These results suggest VEXI is a promising method to assess the BBB breakdown in AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Barrera Hematoencefálica/diagnóstico por imagen , Medios de Contraste , Agua , Imagen por Resonancia Magnética/métodos , Disfunción Cognitiva/diagnóstico por imagenRESUMEN
In semiconductor and data storage device manufacturing, it is desirable to produce feature sizes less than 30 nm with a high depth-to-width aspect ratio on the target material rapidly at a low cost. However, optical diffraction limits the smallest focused laser beam diameter to around half of the laser wavelength (λ/2). The existing approach to achieving nanoscale fabrication is mainly based on costly extreme ultraviolet (EUV) technology operating within the diffraction limit. In this paper, a new method is shown to achieve materials processing resolution down to 10 nm (λ/80) at an infrared laser wavelength of around 800 nm in the far-field, in air, well beyond the optical diffraction limit. A high-quality longitudinal field with a purity of 94.7% is generated to realise this super-resolution. Both experiments and theoretical modelling have been carried out to verify and understand the findings. The ablation craters induced on polished silicon, copper, and sapphire are compared for different types of light fields. Holes of 10-30 nm in diameter are produced on sapphire with a depth-to-width aspect ratio of over 16 and a zero taper with a single pulse at 100-120 nJ pulse energy. Such high aspect ratio sub-50 nm holes produced with single pulse laser irradiation are rarely seen in laser processing, indicating a new material removal mechanism with the longitudinal field. The working distance (lens to target) is around 170 µm, thus the material processing is in the far field. Tapered nano-holes can also be produced by adjusting the lens to the target distance.
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BACKGROUND: Triple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer. METHODS: We measured the levels of PLAC8 in breast cancer cell lines and found that PLAC8 is post-translationally modified by ubiquitin-fold modifier 1 (UFM1). Then, we revealed a new regulatory system of PD-L1 by PLAC8 in triple-negative breast cancer. We also tested the molecular functions of PLAC8 in triple-negative breast cancer cell lines and measured the expression of PLAC8 and PD-L1 in breast cancer tissues. RESULTS: PLAC8 was generally highly expressed in triple-negative breast cancer and could be modified by UFM1, which maintains PLAC8 protein stability. Moreover, PLAC8 could promote cancer cell proliferation and affect the immune response by regulating the level of PD-L1 ubiquitination. Additionally, among patients with breast cancer, the expression of PLAC8 was higher in triple-negative breast cancer than in non-triple-negative breast cancer and positively correlated with the level of PD-L1. CONCLUSIONS: Our current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.
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Antígeno B7-H1 , Neoplasias de la Mama Triple Negativas , Humanos , Antígeno B7-H1/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Inmunoterapia , Inmunidad , Proliferación Celular , Proteínas/uso terapéuticoRESUMEN
BACKGROUND: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and rapidly progressive intestinal T-cell non-Hodgkin lymphoma associated with a very poor prognosis and a median survival of 7 mo. Advances in the identification of MEITL over the last two decades have led to its recognition as a separate entity. MEITL patients, predominantly male, typically present with vague and nonspecific symptoms and diagnosis is predominantly confirmed at laparotomy. Currently, there are no standardized treatment protocols, and the optimal therapy remains unclear. CASE SUMMARY: We report a case of MEITL that was initially considered to be gastrointestinal stromal tumor (GIST) and Imatinib was administered for one cycle. The 62-year-old man presented with abdominal pain, abdominal distension, and weight loss of 20 pounds. Within 2 wk, the size of the mass considerably increased on computed tomography scans. The patient underwent surgery followed by chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and stem-cell transplant. A correct diagnosis of MEITL was established based on postoperative pathology. Immunophenotypically, the neoplastic cells fulfilled the diagnostic criteria for MEITL as they were CD3+, CD4+, CD8+, CD56+, and TIA-1+. CONCLUSION: Given that MEITL has no predisposing factor and presents with vague symptoms with rapid progression, the concomitant presence of abdominal symptoms and B symptoms (weight loss, fever, and night sweats) with hypoalbuminemia, anemia, low lymphocytic count and endoscopic findings of diffuse infiltrating type lesions should alert physicians to this rare disease, especially when it comes to Asian patients. Immediate laparotomy should then be carried out followed by chemotherapy and stem-cell transplant.
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Neurologic autoimmune disorders affect people's physical and mental health seriously. Glial cells, as an important part of the nervous system, play a vital role in the occurrence of neurologic autoimmune disorders. Glial cells can be hyperactivated in the presence of autoantibodies or pathological changes, to influence neurologic autoimmune disorders. This review is mainly focused on the roles of glial cells in neurologic autoimmune disorders and the influence of autoantibodies produced by autoimmune disorders on glial cells. We speculate that the possibility of glial cells might be a novel way for the investigation and therapy of neurologic autoimmune disorders.
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Background and aims: Evidence regarding associations of circulating saturated fatty acids (SFAs) with chronic diseases is mixed. The objective of this study was to determine the associations between total or individual SFA biomarkers and the risk of cardiometabolic diseases. Methods: Four electronic databases were searched from inception to March 2022. Three investigators independently assessed for inclusion and extracted data. Random-effects or fixed-effects models was used to estimate the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association of total or individual SFA biomarkers, including even-chain SFAs (e.g., 14:0, myristic acid; 16:0, palmitic acid; 18:0, stearic acid), odd-chain SFAs (e.g., 15:0, pentadecanoic acid; 17:0, margaric acid) and very-long-chain SFAs (VLCSFAs; e.g., 20:0, arachidic acid; 22:0, behenic acid; 24:0, lignoceric acid), with risk of incident type 2 diabetes (T2D), cardiovascular disease [CVD; coronary heart disease (CHD) inclusive of stroke], CHD and stroke. Results: A total of 49 prospective studies reported in 45 articles were included. Higher concentration of circulating total SFAs was associated with an increasing risk of cardiometabolic diseases, the risk increased significantly by 50% for CVD (95%CI:1.31-1.71), 63% for CHD (95%CI:1.38-1.94), 38% for stroke (95%CI:1.05-1.82), respectively. Similarly, levels of even-chain SFAs were positively associated with higher risk of chronic diseases, with RRs ranging from 1.15 to 1.43. In contrast, the risk of cardiometabolic diseases was reduced with increasing odd-chain SFA levels, with RRs ranging from 0.62 to 0.91. A higher level of VLCSFAs corresponded to 19% reduction in CVD. Further dose-response analysis indicated that each 50% increment in percentage of total SFAs in circulating was associated with an 8% higher risk of T2D (RR: 1.08, 95%CI: 1.02-1.14) and trends toward higher risk of CVD (RR: 1.15, 95%CI: 0.98-1.34). Inverse linear relationships were observed between 17:0 biomarker and T2D or CVD risk. Conclusion: Our findings support the current recommendations of reducing intake of saturated fat as part of healthy dietary patterns. Further studies are needed to confirm our findings on these SFAs in relation to cardiometabolic outcomes and to elucidate underlying mechanisms. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022329182], identifier [CRD42022329182].