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1.
J Environ Radioact ; 278: 107488, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38968644

RESUMEN

224Ra (t1/2 = 3.6 d) has been widely used as a tracer in environmental water research. Here, we present a new method for measuring 224Ra in natural waters using a pulsed ionization chamber (PIC)-based radon detector. This method is based on the measurement of the 224Ra daughter isotope 220Rn (thoron) after reaching secular equilibrium within 7 min. Radium isotopes are concentrated on ''Mn-fibers'' before measurement of 220Rn, which can be distinguished from 222Rn by the difference in their half-lives. The measurement efficiency of the method is 0.20 ± 0.01 cps/Bq at an optimum airflow rate of 1.0 L/min and a water/Mn-fiber weight ratio of 1.0. Results from natural water samples obtained by this method agree well with analysis via RaDeCC, an established technique for 224Ra assessments. Since the PIC system is lighter compared to RaDeCC, easier to operate, and does not require the usage of helium carrier gas and desiccant, this method is recommended for in-situ 224Ra measurement in long-term fieldwork with limited logistical support.

2.
Nat Plants ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997433

RESUMEN

Rice is one of the most important staple food and model species in plant biology, yet its quantitative proteomes are largely uncharacterized. Here we quantify the relative protein levels of over 15,000 genes across major rice tissues using a tandem mass tag strategy followed by intensive fractionation and mass spectrometry. We identify tissue-specific and tissue-enriched proteins that are linked to the functional specificity of individual tissues. Proteogenomic comparison of rice and Arabidopsis reveals conserved proteome expression, which differs from mammals in that there is a strong separation of species rather than tissues. Notably, profiling of N6-methyladenosine (m6A) across the rice major tissues shows that m6A at untranslated regions is negatively correlated with protein abundance and contributes to the discordance between RNA and protein levels. We also demonstrate that our data are valuable for identifying novel genes required for regulating m6A methylation. Taken together, this study provides a paradigm for further research into rice proteogenome.

3.
Nat Commun ; 15(1): 5221, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890329

RESUMEN

Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.


Asunto(s)
Aminoácidos , Tiorredoxinas , Aminoácidos/metabolismo , Aminoácidos/química , Humanos , Tiorredoxinas/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/química , Reactivos de Enlaces Cruzados/química , Unión Proteica , Péptidos/metabolismo , Péptidos/química , Selenoproteínas/metabolismo , Selenoproteínas/genética , Selenoproteínas/química , Programas Informáticos , Proteínas/metabolismo , Proteínas/química , Células HEK293
4.
iScience ; 27(6): 110055, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38868204

RESUMEN

Humans can quickly adapt to recognize acoustically degraded speech, and here we hypothesize that the quick adaptation is enabled by internal linguistic feedback - Listeners use partially recognized sentences to adapt the mapping between acoustic features and phonetic labels. We test this hypothesis by quantifying how quickly humans adapt to degraded speech and analyzing whether the adaptation process can be simulated by adapting an automatic speech recognition (ASR) system based on its own speech recognition results. We consider three types of acoustic degradation, i.e., noise vocoding, time compression, and local time-reversal. The human speech recognition rate can increase by >20% after exposure to just a few acoustically degraded sentences. Critically, the ASR system with internal linguistic feedback can adapt to degraded speech with human-level speed and accuracy. These results suggest that self-supervised learning based on linguistic feedback is a plausible strategy for human adaptation to acoustically degraded speech.

5.
Int J Med Sci ; 21(7): 1337-1343, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818476

RESUMEN

Background: Interleukin-25 (IL-25) has been proved to play a role in the pathogenesis and metastasis of Hepatocellular carcinoma (HCC), but the relationship between the level of IL-25 and the metastasis and prognosis of HCC is still not clear. This study aimed to investigate the expression of IL-25 and other potential biochemical indicators among healthy people, HBV-associated HCC patients without lung metastasis and HBV-associated HCC patients with lung metastasis. Methods: From September 2019 to November 2021, 33 HCC patients without lung metastasis, 37 HCC patients with lung metastasis and 29 healthy controls were included in the study. IL-25 and other commonly used biochemical markers were measured to establish predictors of overall survival (OS) and progression-free survival (PFS) after treatment. Results: The serum level of IL-25 was increased in HCC patients than healthy controls (p < 0.001) and HCC patients with lung metastasis had higher IL-25 level than HCC patients without metastasis (p = 0.035). Lung metastasis also indicated higher death rate (p < 0.001) by chi-square test, higher GGT level (p = 0.024) and higher AFP level (p = 0.049) by non-parametric test. Kaplan-Meier analysis demonstrated that IL-25 was negatively associated with PFS (p = 0.024). Multivariate Cox-regression analysis indicated IL-25 (p = 0.030) and GGT (p = 0.020) to be independent predictors of poorer PFS, while IL-25 showed no significant association with OS. Conclusion: The level of IL-25 was significantly associated with disease progression and lung metastasis of HBV-associated HCC. The high expression of IL-25 predicted high recurrence rate and death probability of HCC patients after treatment. Therefore, IL-25 may be an effective predictor of prognosis in HCC.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/sangre , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/virología , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Pronóstico , Adulto , China/epidemiología , Hepatitis B/complicaciones , Hepatitis B/virología , Interleucina-17/sangre , Anciano , Pueblos del Este de Asia
6.
Adv Mater ; 36(26): e2400102, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38606728

RESUMEN

Solar-thermal regulation concerning thermal insulation and solar modulation is pivotal for cooling textiles and smart buildings. Nevertheless, a contradiction arises in balancing the demand to prevent external heat infiltration with the efficient dissipation of excess heat from enclosed spaces. Here, a concentration-gradient polymerization strategy is presented for fabricating a gradient porous polymeric film comprising interconnected polymeric microspheres. This method involves establishing an electric field-driven gradient distribution of charged crosslinkers in the precursor solution, followed by subsequent polymerization and freeze-drying processes. The resulting porous film exhibits a significant porosity gradient along its thickness, leading to exceptional unidirectional thermal insulation capabilities with a thermal rectification factor of 21%. The gradient porous film, with its thermal rectification properties, effectively reconciles the conflicting demands of diverse thermal conductivity for cooling unheated and spontaneously heated enclosed spaces. Consequently, the gradient porous film demonstrates remarkable enhancements in solar-thermal management, achieving temperature reductions of 3.0 and 4.1 °C for unheated and spontaneously heated enclosed spaces, respectively, compared to uniform porous films. The developed gradient-structured porous film thus holds promise for the development of thermal-rectified materials tailored to regulate solar-thermal conditions within enclosed environments.

7.
BMJ Open ; 14(3): e082135, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38485177

RESUMEN

INTRODUCTION: The subtransverse process interligamentary (STIL) plane block is an emerging interfascial plane block that has garnered attention for its potential to provide effective postoperative analgesia for breast and thoracic surgeries. However, a direct comparative assessment between the STIL plane block and the paravertebral block is currently lacking. Consequently, our study aims to assess the analgesic efficacy of the STIL block in comparison to paravertebral block for patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS AND ANALYSIS: This study is a randomised, parallel-controlled, double-blind, non-inferiority trial, with the goal of enrolling 114 participants scheduled for uniportal VATS at Shanghai Pulmonary Hospital. Participants will be randomly assigned in a 1:1 ratio through block randomisation to receive either the STIL plane block (n=57) or the paravertebral block (n=57). The primary outcome of the study is the area under the curve of Numerical Rating Scale(NRS) scores recorded over a 48-hour period following the surgical procedure. Secondary outcomes encompass the evaluation of Quality of Recovery-40, cumulative sufentanil consumption, serum inflammatory factors, rescue medication usage, the incidence of adverse events and the patient satisfaction scores. ETHICS AND DISSEMINATION: This study has received approval from the Medical Ethics Committee of Shanghai Pulmonary Hospital (approval no. L22-329). Written informed consent will be obtained from all participants. The findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2200066909.


Asunto(s)
Analgesia , Bloqueo Nervioso , Dolor Postoperatorio , Cirugía Torácica , Humanos , Analgesia/métodos , Analgésicos Opioides/uso terapéutico , China , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Ultrasonografía Intervencional , Estudios de Equivalencia como Asunto
9.
Nanomicro Lett ; 16(1): 131, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38409640

RESUMEN

The demand for highly porous yet transparent aerogels with mechanical flexibility and solar-thermal dual-regulation for energy-saving windows is significant but challenging. Herein, a delaminated aerogel film (DAF) is fabricated through filtration-induced delaminated gelation and ambient drying. The delaminated gelation process involves the assembly of fluorinated cellulose nanofiber (FCNF) at the solid-liquid interface between the filter and the filtrate during filtration, resulting in the formation of lamellar FCNF hydrogels with strong intra-plane and weak interlayer hydrogen bonding. By exchanging the solvents from water to hexane, the hydrogen bonding in the FCNF hydrogel is further enhanced, enabling the formation of the DAF with intra-layer mesopores upon ambient drying. The resulting aerogel film is lightweight and ultra-flexible, which possesses desirable properties of high visible-light transmittance (91.0%), low thermal conductivity (33 mW m-1 K-1), and high atmospheric-window emissivity (90.1%). Furthermore, the DAF exhibits reduced surface energy and exceptional hydrophobicity due to the presence of fluorine-containing groups, enhancing its durability and UV resistance. Consequently, the DAF has demonstrated its potential as solar-thermal regulatory cooling window materials capable of simultaneously providing indoor lighting, thermal insulation, and daytime radiative cooling under direct sunlight. Significantly, the enclosed space protected by the DAF exhibits a temperature reduction of 2.6 °C compared to that shielded by conventional architectural glass.

10.
Sci Total Environ ; 917: 170459, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38290673

RESUMEN

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants ubiquitous in the environment and humans. In-utero PFAS exposure is associated with numerous adverse health impacts. However, little is known about how prenatal PFAS mixture exposure affects offspring's neurobehavioral function. This study aims to determine the causal relationship between in-utero PFAS mixture exposure and neurobehavioral changes in Sprague-Dawley rat offspring. Dams were exposed via drinking water to the vehicle (control), an environmentally relevant PFAS mixture, or a high-dose PFAS mixture. The environmentally relevant mixture was formulated to resemble measured tap water levels in Pittsboro, NC, USA (10 PFAS compounds; sum PFAS =758.6 ng/L). The high-dose PFAS load was 3.8 mg/L (5000×), within the range of exposures in the experimental literature. Exposure occurred seven days before mating until birth. Following exposure to PFAS-laden water or the vehicle during fetal development, neurobehavioral toxicity was assessed in male and female offspring with a battery of motor, cognitive, and affective function tests as juveniles, adolescents, and adults. Just before weaning, the environmentally relevant exposure group had smaller anogenital distances compared to the vehicle and high-dose groups on day 17, and males in the environmentally relevant exposure group demonstrated lower weights than the high-dose group on day 21 (p < 0.05). Reflex development delays were seen in negative geotaxis acquisition for both exposure groups compared to vehicle-exposed controls (p = 0.009). Our post-weaning behavioral measures of anxiety, depression, and memory were not found to be affected by maternal PFAS exposure. In adolescence (week five) and adulthood (week eight), the high PFAS dose significantly attenuated typical sex differences in locomotor activity. Maternal exposure to an environmentally relevant PFAS mixture produced developmental delays in the domains of pup weight, anogenital distance, and reflex acquisition for rat offspring. The high-dose PFAS exposure significantly decreased typical sex differences in locomotor activity.


Asunto(s)
Ácidos Alcanesulfónicos , Agua Potable , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Embarazo , Ratas , Femenino , Animales , Masculino , Humanos , Adolescente , Ratas Sprague-Dawley , Reproducción , Fluorocarburos/toxicidad
11.
Aging (Albany NY) ; 16(2): 1860-1878, 2024 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-38261733

RESUMEN

BACKGROUND: Recent years revealed key molecules in lung cancer research, yet their exact roles in disease onset and progression remain uncertain. Lung cancer's heterogeneity complicates prognosis prediction. This study integrates pivotal molecules to evaluate patient prognosis and immunotherapy efficacy. METHODS: The WGCNA algorithm identified module genes linked to immunity. The Lasso-Cox method built a prognostic model for outcome prediction. GO and KEGG analyses explored gene pathways. ssGSEA quantified immune cell types and functions. The riskScore predicts the effectiveness of immunotherapy based on its correlation with DNA repair and immune checkpoint genes. Single-cell sequencing examined key gene expression across cell types. RESULTS: Using WGCNA, we identified the MEbrown module related to immunity. Lasso-Cox selected "BLK," "ITGB4," "PRKCH," and "SNAI1" for the prognostic model. MF analysis revealed enriched functions including antigen binding, GTPase regulator activity. In terms of BP, processes like immune signaling and mitotic division were enriched. CC enrichment included immunoglobulin complexes and chromosomal regions. Enriched pathways encompassed Cell cycle, Focal adhesion, Cellular senescence, and p53 signaling. ssGSEA evaluated immune cell abundance. RiskScore correlated with CTLA4 and PD1 through MMR and immune checkpoint analysis. Single-cell analysis indicated gene expression across cell types for BLK, ITGB4, PRKCH, and SNAI1. CONCLUSION: In summary, our developed prognostic model utilizing age-related genes effectively predicts lung cancer prognosis and the efficacy of immune therapy.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Pronóstico , Multiómica , Envejecimiento , Inmunoterapia , Aprendizaje Automático , Microambiente Tumoral
12.
Macromol Rapid Commun ; 45(4): e2300568, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37956305

RESUMEN

Fibrous strain sensing materials with both high sensitivity and high linearity are of significant importance for wearable sensors, yet they still face great challenges. Herein, a photo-spun reaction encapsulation strategy is proposed for the continuous fabrication of fibrous strain sensor materials (AMGF) with a core-sheath structure. Metallogels (MOGs) formed by bacterial cellulose (BC) nanofibers and Ag nanoparticles (AgNPs), and thermoplastic elastomers (TPE) are employed as the core and sheath, respectively. The in situ ultraviolet light reduction of Ag+ ensured AgNPs to maintain the interconnections between the BC nanofibers and form electron conductive networks (0.31 S m-1 ). Under applied strain, the BC nanofibers experience separation, bringing AMGF a high sensitivity (gauge factor 4.36). The concentration of free ions in the MOGs uniformly varies with applied deformation, endowing AMGF with high linearity and a goodness-of-fit of 0.98. The sheath TPE provided AMGF sensor with stable working life (>10 000 s). Furthermore, the AMGF sensors are demonstrated to monitor complex deformations of the dummy joints in real-time as a wearable sensor. Therefore, the fibrous hybrid conductive network fibers fabricated via the photo-spun reaction encapsulation strategy provide a new route for addressing the challenge of achieving both high sensitivity and high linearity.


Asunto(s)
Nanopartículas del Metal , Dispositivos Electrónicos Vestibles , Nanopartículas del Metal/química , Electrones , Plata/química , Elastómeros/química
13.
Aging Cell ; 23(3): e14055, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38044578

RESUMEN

The heterogeneity of aging has been investigated at cellular and organic levels in the mouse model and human, but the exploration of aging heterogeneity at whole-organism level is lacking. C. elegans is an ideal model organism for studying this question as they are self-fertilized and cultured in the same chamber. Despite the tremendous progress made in single-cell proteomic analysis, there is few single-worm proteomics studies about aging. Here, we apply single-worm quantitative mass spectrometry to quantify the heterogenous proteomic changes during aging across individuals, a total of 3524 proteins from 157 C. eleagns individuals were quantified. A reconstructed C. elegans aging trajectory and proteomic landscape of fast-aging individuals were used to analyze the heterogeneity of C. elegans aging. We characterized inter-individual proteomic variation during aging and revealed contributing factors that distinguish fast-aging individuals from their siblings.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Ratones , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteómica/métodos , Envejecimiento , Modelos Animales de Enfermedad
15.
Eur Radiol ; 34(7): 4516-4526, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38112763

RESUMEN

OBJECTIVES: To investigate the pathological interplay between immunity and the visual processing system (VPS) in thyroid eye disease (TED). METHODS: A total of 24 active patients (AP), 26 inactive patients (IP) of TED, and 27 healthy controls (HCs) were enrolled. Orbital magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were conducted for each participant. Multiple MRI parameters of the intraorbital optic nerve (ON) were assessed. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated. Correlation analyses were carried out on the above parameters and clinical characteristics. RESULTS: Visual functioning scores differentiated between the AP and IP groups. The ON subarachnoid space and ON sheath diameter were significantly higher in AP than in IP. Six vision-related brain regions were identified in TED patients compared with HCs, including right calcarine (CAL.R), right cuneus (CUN.R), left postcentral gyrus (PoCG.L), right middle temporal gyrus (MTG.R), left superior frontal gyrus (SFG.L), and left caudate (CAU.L). The brain activity of MTG.R, SFG.L, and CAU.L differentiated between the AP and IP groups. The correlation analysis revealed a close association among the vision-related brain regions, MRI parameters of ON, and clinical characteristics in AP and IP, respectively. CONCLUSIONS: Combined orbital and brain neuroimaging revealed abnormalities of the VPS in TED, which had a close correlation with immune statuses. Vision-related brain regions in TED might be possibly altered by peripheral immunity via a direct or indirect approach. CLINICAL RELEVANCE STATEMENT: The discovery of this study explained the disparity of visual dysfunction in TED patients with different immune statuses. With the uncovered neuroimaging markers, early detection and intervention of visual dysfunction could be achieved and potentially benefit TED patients. KEY POINTS: • Patients with different immune statuses of thyroid eye disease varied in the presentation of visual dysfunction. • The combined orbital and brain neuroimaging study identified six altered vision-related brain regions, which had a significant correlation with the MRI parameters of the intraorbital optic nerve and immunological characteristics. • Peripheral immunity might possibly give rise to alterations in the central nervous system part of the visual processing system via a direct or indirect approach.


Asunto(s)
Oftalmopatía de Graves , Imagen por Resonancia Magnética , Neuroimagen , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Oftalmopatía de Graves/diagnóstico por imagen , Oftalmopatía de Graves/complicaciones , Oftalmopatía de Graves/inmunología , Persona de Mediana Edad , Adulto , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Trastornos de la Visión/diagnóstico por imagen , Trastornos de la Visión/etiología , Trastornos de la Visión/fisiopatología , Estudios de Casos y Controles , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Órbita/diagnóstico por imagen
16.
Vasc Endovascular Surg ; 58(5): 535-539, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38158764

RESUMEN

Traumatic iliac arteriovenous fistula is a rare complication of vascular injury. Open surgical repair has an incidence of postoperative complications. In recent years, endovascular treatment has shown better efficacy. We report a 62-year-old female AVF patient with a stab injury history of more than 16 years. Computed tomography angiography (CTA) revealed a large arteriovenous fistula between the right internal iliac artery and the common iliac vein. After considering the patient's relevant conditions, an endovascular approach was satisfactorily performed with the implantation of an Amplatzer Vascular Plug II to interrupt the abnormal vascular communication and maintain arterial and venous patency. The final control images showed closure of the arteriovenous communication.


Asunto(s)
Fístula Arteriovenosa , Angiografía por Tomografía Computarizada , Procedimientos Endovasculares , Arteria Ilíaca , Vena Ilíaca , Lesiones del Sistema Vascular , Heridas Punzantes , Humanos , Femenino , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/lesiones , Arteria Ilíaca/fisiopatología , Arteria Ilíaca/cirugía , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/etiología , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/fisiopatología , Fístula Arteriovenosa/cirugía , Persona de Mediana Edad , Vena Ilíaca/diagnóstico por imagen , Vena Ilíaca/lesiones , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/etiología , Lesiones del Sistema Vascular/cirugía , Lesiones del Sistema Vascular/fisiopatología , Lesiones del Sistema Vascular/terapia , Resultado del Tratamiento , Procedimientos Endovasculares/instrumentación , Heridas Punzantes/diagnóstico por imagen , Heridas Punzantes/cirugía , Heridas Punzantes/complicaciones , Embolización Terapéutica/instrumentación , Flebografía , Grado de Desobstrucción Vascular
17.
J Mol Biol ; 435(24): 168364, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37952770

RESUMEN

Demixing of proteins and nucleic acids into condensed liquid phases is rapidly emerging as a ubiquitous mechanism underlying the complex spatiotemporal organisation of molecules within the cell. Long disordered regions of low sequence complexity (LCRs) are a common feature of proteins that form liquid-like microscopic biomolecular condensates. In particular, RNA-binding proteins with prion-like regions have emerged as key drivers of liquid demixing to form condensates such as nucleoli, paraspeckles and stress granules. Splicing factor proline- and glutamine-rich (SFPQ) is an RNA- and DNA-binding protein essential for DNA repair and paraspeckle formation. SFPQ contains two LCRs of different length and composition. Here, we show that the shorter C-terminal LCR of SFPQ is the main region responsible for the condensation of SFPQ in vitro and in the cell nucleus. In contrast, we find that the longer N-terminal prion-like LCR of SFPQ attenuates condensation of the full-length protein, suggesting a more regulatory role in preventing aberrant condensate formation in the cell. The compositions of these respective LCRs are discussed with reference to current literature. Our data add nuance to the emerging understanding of biomolecular condensation, by providing the first example of a common multifunctional nucleic acid-binding protein with an extensive prion-like region that serves to regulate rather than drive condensate formation.


Asunto(s)
Condensados Biomoleculares , Priones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , ARN , Priones/genética , Priones/metabolismo
18.
Cell Mol Biol (Noisy-le-grand) ; 69(10): 155-159, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37953572

RESUMEN

Insulin-like growth factor 1 (IGF-1) has been reported to potentially link with childhood obesity and obesity-related asthma, although a causal effect has not been illustrated. This study aimed to assess their association via multi-variable Mendelian randomization (MR) analysis with two-sample summary-level data on genetic variants as instrumental variables, thus estimating a causal effect. Genetic variants associated with serum IGF-1 at genome-wide significance (GWS) in the UK Biobank study involving 363,228 individuals of European descent were introduced as instrumental variables. Summary-level data on childhood obesity and obesity-related asthma were obtained from genome-wide association studies (GWAS). Here, MR-Egger, inverse-variance weighted (IVW), simple median, weighted median and penalized weighted median methods were used in the MR study. Results showed that there were strong causal associations of IGF-1 with childhood obesity (OR, 1.27; 95% CI 1.01-1.60; P<0.05) and obesity-related asthma (OR, 1.22; 95% CI 1.07-1.38; P<0.005). In conclusion, A causal association between high IGF-1 levels and high risks of childhood obesity and obesity-related asthma is estimated, which requires further validation in large-scale trials.


Asunto(s)
Asma , Obesidad Infantil , Niño , Humanos , Obesidad Infantil/epidemiología , Obesidad Infantil/genética , Factor I del Crecimiento Similar a la Insulina/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Asma/epidemiología , Asma/genética , Polimorfismo de Nucleótido Simple
19.
Front Immunol ; 14: 1126392, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37033973

RESUMEN

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated lipid nanoparticle (LNP) formulated mRNA vaccines that induce only T cell responses or both T cell and neutralizing antibody responses by using two mRNAs. One mRNA encodes SARS-CoV-2 Omicron Spike protein in prefusion conformation for induction of neutralizing antibodies. The other mRNA encodes over one hundred T cell epitopes (multi-T cell epitope or MTE) derived from non-Spike but conserved regions of the SARS-CoV-2. We show immunization with MTE mRNA alone protected mice from lethal challenge with the SARS-CoV-2 Delta variant or a mouse-adapted virus MA30. Immunization with both mRNAs induced the best protection with the lowest viral titer in the lung. These results demonstrate that induction of T cell responses, in the absence of preexisting antibodies, is sufficient to confer protection against severe disease, and that a vaccine containing mRNAs encoding both the Spike and MTE could be further developed as a universal SARS-CoV-2 vaccine.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Animales , Humanos , Ratones , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Neutralizantes , Epítopos de Linfocito T , ARN Mensajero/genética
20.
Adv Mater ; 35(30): e2301418, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37099393

RESUMEN

The development of a 3D carbon assembly with a combination of extraordinary electrochemical and mechanical properties is desirable yet challenging. Herein, an ultralight and hyperelastic nanofiber-woven hybrid carbon assembly (NWHCA) is fabricated by nanofiber weaving of isotropic porous and mechanical brittle quasi-aerogels. Upon subsequent pyrolysis, metallogel-derived quasi-aerogel hybridization and nitrogen/phosphorus co-doping are integrated into the NWHCA. Finite element simulation indicates that the 3D lamella-bridge architecture of NWHCA with the quasi-aerogel hybridization contributes to resisting plastic deformation and structural damage under high compression, experimentally demonstrated by complete deformation recovery at 80% compression and unprecedented fatigue resistance (>94% retention after 5000 cycles). Due to the superelasticity and quasi-aerogel integration, the zinc-air battery assembled based on NWHCA shows excellent electrochemical performance and flexibility. A proof-of-concept integrated device is presented, in which the flexible battery powers a piezoresistive sensor, using the NWHCA as the air cathode and the elastic conductor respectively, which can detect full-range and sophisticated motions while attached to human skin. The nanofiber weaving strategy allows the construction of lightweight, superelastic, and multifunctional hybrid carbon assemblies with great potential in wearable and integrated electronics.

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