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1.
J Immunother Cancer ; 12(7)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004437

RESUMEN

BACKGROUND: Vorinostat (SAHA) is a histone deacetylase inhibitor that has shown clinical efficacy against advanced cutaneous T-cell lymphoma (CTCL). However, only a subset of patients with CTCL (30-35%) respond to SAHA and the response is not always sustainable. Thus, understanding the mechanisms underlying evasive resistance in this cancer is an unmet medical need to improve the efficacy of current therapies. PURPOSE: This study aims to identify factors contributing to resistance against SAHA in CTCL and ways to mitigate it. METHODS AND RESULTS: In this study, we demonstrated that attenuated reactive oxygen species (ROS) induces the expression of interleukin (IL)-2Rα, one of the IL-2 receptors, which drives resistance to SAHA in CTCL. We also determined that cantharidin could overcome SAHA resistance to CTCL by blocking IL-2Rα-related signaling via ROS-dependent manner. Mechanistically, accelerated translation of IL-2Rα contributes to excessive IL-2Rα protein formation as a result of reduced ROS levels in SAHA-resistant CTCL. At the same time, amplified IL-2R signals are evidenced by strengthened interaction of IL-2Rß with IL-2Rγ and Janus kinase/signal transducer and activator of transcription molecules, and by increased expression of protein kinase B (AKT)/mTOR and mitogen-activated protein kinase signaling. Moreover, cantharidin, an active constituent of Mylabris used in traditional Chinese medicine, markedly increased ROS levels, and thereby restrained IL-2Rα translation, resulting in suppression of downstream pathways in SAHA-resistant cells. Cantharidin is also found to synergize with SAHA and triggers SAHA-resistant cell death via IL-2R signaling both in vitro and in vivo. CONCLUSION: Our study uncovers a novel molecular mechanism of acquired SAHA resistance and also suggests that using cantharidin is a potential approach to overcome CTCL therapy resistance. Our findings underlie the therapeutic potential of cantharidin in treating CTCL.


Asunto(s)
Cantaridina , Resistencia a Antineoplásicos , Linfoma Cutáneo de Células T , Especies Reactivas de Oxígeno , Transducción de Señal , Vorinostat , Humanos , Cantaridina/farmacología , Cantaridina/uso terapéutico , Vorinostat/farmacología , Vorinostat/uso terapéutico , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Ratones , Línea Celular Tumoral , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología
2.
mLife ; 3(2): 307-316, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38948141

RESUMEN

The microbial synthesis of sulfonolipids within the human body is likely involved in maintaining human health or causing diseases. However, the enzymes responsible for their biosynthesis remain largely unknown. In this study, we identified and verified the role of 3-ketocapnine reductase, the third-step enzyme, in the four-step conversion of l-phosphoserine into sulfobacin B both in vivo and in vitro. This finding builds upon our previous research into sulfonolipid biosynthesis, which focused on the vaginal bacterium Chryseobacterium gleum DSM 16776 and the gut bacterium Alistipes finegoldii DSM 17242. Through comprehensive gene mapping, we demonstrate the widespread presence of potential sulfonolipid biosynthetic genes across diverse bacterial species inhabiting various regions of the human body. These findings shed light on the prevalence of sulfonolipid-like metabolites within the human microbiota, suggesting a potential role for these lipid molecules in influencing the intricate biointeractions within the complex microbial ecosystem of the human body.

3.
Opt Express ; 32(10): 17464-17478, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858929

RESUMEN

Microwave-induced thermoacoustic (TA) imaging (MTAI) combines pulsed microwave excitation and ultrasound detection to provide high contrast and spatial resolution images through dielectric contrast, which holds great promise for clinical applications. However, artifacts caused by microwave dielectric effect will seriously affect the accuracy of MTAI images that will hinder the clinical translation of MTAI. In this work, we propose a deep learning-based method fully dense generative adversarial network (FD-GAN) for removing artifacts caused by microwave dielectric effect in MTAI. FD-GAN adds the fully dense block to the generative adversarial network (GAN) based on the mutual confrontation between generator and discriminator, which enables it to learn both local and global features related to the removal of artifacts and generate high-quality images. The practical feasibility was tested in simulated, experimental data. The results demonstrate that FD-GAN can effectively remove the artifacts caused by the microwave dielectric effect, and shows superiority in denoising, background suppression, and improvement of image distortion. Our approach is expected to significantly improve the accuracy and quality of MTAI images, thereby enhancing the diagnostic accuracy of this innovative imaging technique.

4.
Nat Commun ; 15(1): 4901, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851779

RESUMEN

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.


Asunto(s)
Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Animales , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/química , Humanos , Familia de Multigenes , Ratones , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana/efectos de los fármacos , Genoma Bacteriano/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Biología Computacional/métodos , Cisteína/metabolismo , Cisteína/química
5.
Invest Ophthalmol Vis Sci ; 65(6): 34, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38913005

RESUMEN

Purpose: The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms. Methods: In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected. Results: We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice. Conclusions: Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.


Asunto(s)
Neovascularización Coroidal , Modelos Animales de Enfermedad , Macrófagos , Ratones Endogámicos C57BL , Ratones Noqueados , Semaforinas , Transducción de Señal , Quinasas Asociadas a rho , Proteína de Unión al GTP rhoA , Animales , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/genética , Neovascularización Coroidal/patología , Ratones , Macrófagos/metabolismo , Quinasas Asociadas a rho/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Transducción de Señal/fisiología , Proteína de Unión al GTP rhoA/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Western Blotting , Masculino , Angiografía con Fluoresceína
6.
Nat Commun ; 15(1): 5375, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918392

RESUMEN

Coupling the Si-based anodes with nickel-rich LiNixMnyCo1-x-yO2 cathodes (x ≥ 0.8) in the energy-dense cell prototype suffers from the mechanical instability of the Li-Si alloys, cathode collapse upon the high-voltage cycling, as well as the severe leakage current at elevated temperatures. More seriously, the cathode-to-anode cross-talk effect of transitional metal aggravates the depletion of the active Li reservoir. To reconcile the cation utilization degree, stress dissipation, and extreme temperature tolerance of the Si-based anode||NMC prototype, we propose a gel polymer electrolyte to reinforce the mechanical integrity of Si anode and chelate with the transitional cations towards the stabilized interfacial property. As coupling the conformal gel polymer electrolyte encapsulation with the spatial arranged Si anode and NMC811 cathode, the 2.7 Ah pouch-format cell could achieve the high energy density of 325.9 Wh kg-1 (based on the whole pouch cell), 88.7% capacity retention for 2000 cycles, self-extinguish property as well as a wide temperature tolerance. Therefore, this proposed polymerization strategy provides a leap toward the secured Li batteries.

7.
Neuropsychologia ; 201: 108941, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38908477

RESUMEN

Utilizing the high temporal resolution of event-related potentials (ERPs), we compared the time course of processing incongruent color versus 3D-depth information. Participants were asked to judge whether the food color (color condition) or 3D structure (3D-depth condition) was congruent or incongruent with their previous knowledge and experience. The behavioral results showed that the reaction times in the congruent 3D-depth condition were slower than those in the congruent color condition. The reaction times in the incongruent 3D-depth condition were slower than those in the incongruent color condition. The ERP results showed that incongruent color stimuli induced a larger N270, larger P300, and smaller N400 components in the fronto-central region than the congruent color stimuli. Incongruent 3D-depth stimuli induced a smaller N1 in the occipital region, larger P300 and smaller N400 in the parietal-occipital region than congruent 3D-depth stimuli. The time-frequency analysis found that incongruent color stimuli induced a larger theta band (360-580 ms) activation in the fronto-central region than congruent color stimuli. Incongruent 3D-depth stimuli induced larger alpha and beta bands (240-350 ms) activation in the parietal region than congruent 3D-depth stimuli. Our results suggest that the human brain deals with violating general color or depth knowledge in different time courses. We speculate that the depth perception conflict was dominated by solving the problem with visual processing, whereas the color perception conflict was dominated by solving the problem with semantic violation.


Asunto(s)
Encéfalo , Percepción de Color , Percepción de Profundidad , Electroencefalografía , Potenciales Evocados , Tiempo de Reacción , Humanos , Masculino , Femenino , Percepción de Color/fisiología , Adulto Joven , Tiempo de Reacción/fisiología , Encéfalo/fisiología , Potenciales Evocados/fisiología , Percepción de Profundidad/fisiología , Adulto , Estimulación Luminosa , Factores de Tiempo , Mapeo Encefálico
8.
Cell Death Dis ; 15(6): 389, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830896

RESUMEN

Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo-/-) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo-/- Apoe-/- and Apoo-/- Ldlr-/- mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.


Asunto(s)
Colesterol , Factor 2 Relacionado con NF-E2 , Receptores de LDL , Animales , Receptores de LDL/metabolismo , Colesterol/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Ratones Noqueados , Ratones Endogámicos C57BL , Metabolismo de los Lípidos , Masculino , Aterosclerosis/metabolismo , Apolipoproteínas/metabolismo , Apolipoproteínas/genética , Humanos , Hígado/metabolismo , Apolipoproteínas E/metabolismo , Hiperlipidemias/metabolismo
9.
Small ; : e2400069, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38634246

RESUMEN

The normal operation of organelles is critical for tumor growth and metastasis. Herein, an intelligent nanoplatform (BMAEF) is fabricated to perform on-demand destruction of mitochondria and golgi apparatus, which also generates the enhanced photothermal-immunotherapy, resulting in the effective inhibition of primary and metastasis tumor. The BMAEF has a core of mesoporous silica nanoparticles loaded with brefeldin A (BM), which is connected to ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and folic acid co-modified gold nanoparticles (AEF). During therapy, the BMAEF first accumulates in tumor cells via folic acid-induced targeting. Subsequently, the schiff base/ester bond cleaves in lysosome to release brefeldin A and AEF with exposed EGTA. The EGTA further captures Ca2+ to block ion transfer among mitochondria, endoplasmic reticulum, and golgi apparatus, which not only induced dysfunction of mitochondria and golgi apparatus assisted by brefeldin A to suppress both energy and material metabolism against tumor growth and metastasis, but causes AEF aggregation for tumor-specific photothermal therapy and photothermal assisted immunotherapy. Moreover, the dysfunction of these organelles also stops the production of BMI1 and heat shock protein 70 to further enhance the metastasis inhibition and photothermal therapy, which meanwhile triggers the escape of cytochrome C to cytoplasm, leading to additional apoptosis of tumor cells.

10.
Ital J Pediatr ; 50(1): 84, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38650007

RESUMEN

BACKGROUND: The COVID-19 pandemic have impacts on the prevalence of other pathogens and people's social lifestyle. This study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China. METHODS: Patients with pneumonia admitted to the Department of Pediatric Pulmonology of Xinhua Hospital between March-August 2019 and March-August 2020 were recruited. And clinical characteristics of the patients in 2019 were compared with those in 2020. RESULTS: Hospitalizations for pneumonia decreased by 74% after the COVID-19 pandemic. For pathogens, virus, mycoplasma pneumoniae (MP) and mixed infection rates were all much lower in 2020 than those in 2019 (P < 0.01). Regarding allergens, compared with 2019, the positive rates of house dust mite, shrimp and crab were significantly higher in 2020 (P < 0.01). And for micronutrients, the levels of vitamin B2, B6, C and 25-hydroxyvitamin D (25(OH)D) in 2020 were observed to be significantly lower than those in 2019 (P < 0.05). For all the study participants, longer hospital stay (OR = 1.521, P = 0.000), milk allergy (OR = 6.552, P = 0.033) and calcium (Ca) insufficiency (OR = 12.048, P = 0.019) were identified as high-risk factors for severe pneumonia by multivariate analysis. CONCLUSIONS: The number of children hospitalized with pneumonia and incidence of common pathogen infections were both reduced, and that allergy and micronutrient status in children were also changed after the outbreak of the COVID-19 pandemic.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Niño , China/epidemiología , Preescolar , Hospitalización/estadística & datos numéricos , Lactante , SARS-CoV-2 , Neumonía/epidemiología , Adolescente
11.
Nat Metab ; 6(5): 933-946, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38609677

RESUMEN

Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we proposed that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the 'coenzyme' category have been examined, including a gene cluster encoding for the cofactor pyrroloquinoline quinone. When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides an innovative engineering strategy for improving polyketide production and finding previously unidentified BGCs.


Asunto(s)
Productos Biológicos , Familia de Multigenes , Streptomyces , Productos Biológicos/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Policétidos/metabolismo , Evolución Molecular , Vías Biosintéticas/genética , Filogenia , Ingeniería Metabólica/métodos
12.
ACS Appl Mater Interfaces ; 16(13): 16962-16972, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38520330

RESUMEN

Typical methods for stable immobilization of proteins often involve time-consuming surface modification of silicon-based materials to enable specific binding, while the nonspecific adsorption method is faster but usually unstable. Herein, we fused a silica-binding protein, Si-tag, to target proteins so that the target proteins could attach directly to silica substrates in a single step, markedly streamlining the immobilization process. The adhesion force between the Si-tag and glass substrates was determined to be approximately 400-600 pN at the single-molecule level by atomic force microscopy, which is greater than the unfolding force of most proteins. The adhesion force of the Si-tag exhibits a slight increase when pulled from the C-terminus compared to that from the N-terminus. Furthermore, the Si-tag's adhesion force on a glass surface is marginally higher than that on a silicon nitride probe. The binding properties of the Si-tag are not obviously affected by environmental factors, including pH, salt concentration, and temperature. In addition, the macroscopic adhesion force between the Si-tag-coated hydrogel and glass substrates was ∼40 times higher than that of unmodified hydrogels. Therefore, the Si-tag, with its strong silica substrate binding ability, provides a useful tool as an excellent fusion tag for the rapid and mechanically robust immobilization of proteins on silica and for the surface coating of silica-binding materials.


Asunto(s)
Proteínas Portadoras , Dióxido de Silicio , Dióxido de Silicio/química , Análisis Espectral , Microscopía de Fuerza Atómica , Propiedades de Superficie
13.
Urolithiasis ; 52(1): 44, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38451326

RESUMEN

Urolithiasis is closely linked to lifestyle factors. However, the causal relationship and underlying mechanisms remain unclear. This study aims to investigate the relationship between lifestyle factors and the onset of urolithiasis and explore potential blood metabolite mediators and their role in mediating this relationship. In this study, we selected single nucleotide polymorphisms (SNPs) as instrumental variables if they exhibited significant associations with our exposures in genome-wide association studies (GWAS) (p < 5.0 × 10-8). Summary data for urolithiasis came from the FinnGen database, including 8597 cases and 333,128 controls. We employed multiple MR analysis methods to assess causal links between genetically predicted lifestyle factors and urolithiasis, as well as the mediating role of blood metabolites. A series of sensitivity and pleiotropy analyses were also conducted. Our results show that cigarettes smoked per day (odds ratio [OR] = 1.159, 95% confidence interval [CI] = 1.004-1.338, p = 0.044) and alcohol intake frequency (OR = 1.286, 95% CI = 1.056-1.565, p = 0.012) were positively associated with increased risk of urolithiasis, while tea intake (OR = 0.473, 95% CI = 0.299-0.784, p = 0.001) was positively associated with reduced risk of urolithiasis. Mediation analysis identifies blood metabolites capable of mediating the causal relationship between cigarettes smoked per day, tea intake and urolithiasis. We have come to the conclusion that blood metabolites serve as potential causal mediators of urolithiasis, underscoring the importance of early lifestyle interventions and metabolite monitoring in the prevention of urolithiasis.


Asunto(s)
Estudio de Asociación del Genoma Completo , Urolitiasis , Humanos , Análisis de la Aleatorización Mendeliana , Estilo de Vida , Urolitiasis/etiología , Urolitiasis/genética ,
14.
Cereb Cortex ; 34(3)2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38436464

RESUMEN

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.


Asunto(s)
Neoplasias Encefálicas , Neoplasias de la Mama , Conectoma , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Miedo
15.
ACS Nano ; 18(10): 7596-7609, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38415583

RESUMEN

The compact design of an environmentally adaptive battery and effectors forms the foundation for wearable electronics capable of time-resolved, long-term signal monitoring. Herein, we present a one-body strategy that utilizes a hydrogel as the ionic conductive medium for both flexible aqueous zinc-ion batteries and wearable strain sensors. The poly(vinyl alcohol) hydrogel network incorporates nano-SiO2 and cellulose nanofibers (referred to as PSC) in an ethylene glycol/water mixed solvent, balancing the mechanical properties (tensile strength of 6 MPa) and ionic diffusivity at -20 °C (2 orders of magnitude higher than 2 M ZnCl2 electrolyte). Meanwhile, cathode lattice breathing during the solvated Zn2+ intercalation and dendritic Zn protrusion at the anode interface are mitigated. Besides the robust cyclability of the Zn∥PSC∥V2O5 prototype within a wide temperature range (from -20 to 80 °C), this microdevice seamlessly integrates a zinc-ion battery with a strain sensor, enabling precise monitoring of the muscle response during dynamic body movement. By employing transmission-mode operando XRD, the self-powered sensor accurately documents the real-time phasic evolution of the layered cathode and synchronized strain change induced by Zn deposition, which presents a feasible solution of health monitoring by the miniaturized electronics.

16.
Exp Brain Res ; 242(4): 809-817, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38400993

RESUMEN

It is well known that information on stimulus orientation plays an important role in sensory processing. However, the neural mechanisms underlying somatosensory orientation perception are poorly understood. Adaptation has been widely used as a tool for examining sensitivity to specific features of sensory stimuli. Using the adaptation paradigm, we measured event-related potentials (ERPs) in response to tactile orientation stimuli presented pseudo-randomly to the right-hand palm in trials with all the same or different orientations. Twenty participants were asked to count the tactile orientation stimuli. The results showed that the adaptation-related N60 component was observed around contralateral central-parietal areas, possibly indicating orientation processing in the somatosensory regions. Conversely, the adaptation-related N120 component was identified bilaterally across hemispheres, suggesting the involvement of the frontoparietal circuitry in further tactile orientation processing. P300 component was found across the whole brain in all conditions and was associated with task demands, such as attention and stimulus counting. These findings help provide an understanding of the mechanisms of tactile orientation processing in the human brain.


Asunto(s)
Electroencefalografía , Percepción del Tacto , Humanos , Potenciales Evocados/fisiología , Tacto/fisiología , Encéfalo/fisiología , Atención/fisiología , Percepción del Tacto/fisiología
17.
Neuroscience ; 544: 28-38, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38423162

RESUMEN

Our previous study revealed that acupuncture may exhibit therapeutic effects on Alzheimer's disease (AD) through the activation of metabolism in memory-related brain regions. However, the underlying functional mechanism remains poorly understood and warrants further investigation. In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) to explore the potential effect of electroacupuncture (EA) on the 5xFAD mouse model of AD. We found that the EA group exhibited significant improvements in the number of platforms crossed and the time spent in the target quadrant when compared with the Model group (p < 0.05). The functional connectivity (FC) of left hippocampus (Hip) was enhanced significantly among 12 regions of interest (ROIs) in the EA group (p < 0.05). Based on the left Hip as the seed point, the rsfMRI analysis of the entire brain revealed increased FC between the limbic system and the neocortex in the 5xFAD mice after EA treatment. Additionally, the expression of amyloid-ß(Aß) protein and deposition in the Hip showed a downward trend in the EA group compared to the Model group (p < 0.05). In conclusion, our findings indicate that EA treatment can improve the learning and memory abilities and inhibit the expression of Aß protein and deposition of 5xFAD mice. This improvement may be attributed to the enhancement of the resting-state functional activity and connectivity within the limbic-neocortical neural circuit, which are crucial for cognition, motor function, as well as spatial learning and memory abilities in AD mice.


Asunto(s)
Enfermedad de Alzheimer , Electroacupuntura , Neocórtex , Ratones , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Electroacupuntura/métodos , Péptidos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Neocórtex/diagnóstico por imagen , Neocórtex/metabolismo , Aprendizaje Espacial , Modelos Animales de Enfermedad , Ratones Transgénicos
18.
Environ Res ; 250: 118469, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38354884

RESUMEN

Global warming reportedly poses a critical risk to coral reef ecosystems. Bacteria and archaea are crucial components of the coral holobiont. The response of archaea associated with warming is less well understood than that of the bacterial community in corals. Also, there have been few studies on the dynamics of the microbial community in the coral holobiont under long-term heat stress. In order to track the dynamic alternations in the microbial communities within the heat-stressed coral holobiont, three-week heat-stress monitoring was carried out on the coral Pocillopora damicornis. The findings demonstrate that the corals were stressed at 32 °C, and showed a gradual decrease in Symbiodiniaceae density with increasing duration of heat stress. The archaeal community in the coral holobiont remained relatively unaltered by the increasing temperature, whereas the bacterial community was considerably altered. Sustained heat stress exacerbated the dissimilarities among parallel samples of the bacterial community, confirming the Anna Karenina Principle in animal microbiomes. Heat stress leads to more complex and unstable microbial networks, characterized by an increased average degree and decreased modularity, respectively. With the extension of heat stress duration, the relative abundances of the gene (nifH) and genus (Tistlia) associated with nitrogen fixation increased in coral samples, as well as the potential pathogenic bacteria (Flavobacteriales) and opportunistic bacteria (Bacteroides). Hence, our findings suggest that coral hosts might recruit nitrogen-fixing bacteria during the initial stages of suffering heat stress. An environment that is conducive to the colonization and development of opportunistic and pathogenic bacteria when the coral host becomes more susceptible as heat stress duration increases.


Asunto(s)
Antozoos , Archaea , Bacterias , Antozoos/microbiología , Antozoos/fisiología , Animales , Archaea/genética , Archaea/fisiología , Bacterias/genética , Bacterias/clasificación , Respuesta al Choque Térmico , Microbiota , Calor , Arrecifes de Coral
19.
Front Neurol ; 15: 1309691, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38414554

RESUMEN

Background: Preoperative imaging for some unusual lesions in the sellar region can pose challenges in establishing a definitive diagnosis, impacting treatment strategies. Methods: This study is a retrospective analysis of eight cases involving unusual sellar region lesions, all treated with endoscopic endonasal transsphenoidal surgery (EETS). We present the clinical, endocrine, and radiological characteristics, along with the outcomes of these cases. Results: Among the eight cases, the lesions were identified as follows: Solitary fibrous tumor (SFT) in one case, Lymphocytic hypophysitis (LYH) in one case, Cavernous sinus hemangiomas (CSH) in one case, Ossifying fibroma (OF) in two cases; Sphenoid sinus mucocele (SSM) in one case, Pituitary abscess (PA) in two cases. All patients underwent successful EETS, and their diagnoses were confirmed through pathological examination. Postoperatively, all patients had uneventful recoveries without occurrences of diabetes insipidus or visual impairment. Conclusion: Our study retrospectively analyzed eight unusual lesions of the sellar region. Some lesions exhibit specific imaging characteristics and clinical details that can aid in preoperative diagnosis and inform treatment strategies for these unusual sellar diseases.

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