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1.
Proc Natl Acad Sci U S A ; 121(45): e2404173121, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39471229

RESUMEN

The molecular mechanisms underlying the neurodevelopmental disorders (NDDs) caused by DDX3X variants remain poorly understood. In this study, we validated that de novo DDX3X variants are enriched in female developmental delay (DD) patients and mainly affect the evolutionarily conserved amino acids based on a meta-analysis of 46,612 NDD trios. We generated a ddx3x deficient zebrafish allele, which exhibited reduced survival rate, DD, microcephaly, adaptation defects, anxiolytic behaviors, social interaction deficits, and impaired spatial recognitive memory. As revealed by single-nucleus RNA sequencing and biological validations, ddx3x deficiency leads to reduced neural stem cell pool, decreased total neuron number, and imbalanced differentiation of excitatory and inhibitory neurons, which are responsible for the behavioral defects. Indeed, the supplementation of L-glutamate or glutamate receptor agonist ly404039 could partly rescue the adaptation and social deficits. Mechanistically, we reveal that the ddx3x deficiency attenuates the stability of the crebbp mRNA, which in turn causes downregulation of Notch signaling and defects in neurogenesis. Our study sheds light on the molecular pathology underlying the abnormal neurodevelopment and behavior of NDD patients with DDX3X mutations, as well as providing potential therapeutic targets for the precision treatment.


Asunto(s)
ARN Helicasas DEAD-box , Neurogénesis , Receptores Notch , Transducción de Señal , Pez Cebra , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Animales , Humanos , Receptores Notch/metabolismo , Receptores Notch/genética , Femenino , Masculino , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/metabolismo , Trastornos del Neurodesarrollo/patología , Conducta Animal , Mutación
2.
FASEB J ; 38(10): e23661, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38733310

RESUMEN

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.


Asunto(s)
Factores de Crecimiento de Fibroblastos , Ratones Noqueados , Microtúbulos , Prurito , Canales Catiónicos TRPV , Animales , Humanos , Masculino , Ratones , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Ganglios Espinales/metabolismo , Células HEK293 , Ratones Endogámicos C57BL , Microtúbulos/metabolismo , Prurito/metabolismo , Prurito/genética , Canal Catiónico TRPA1/metabolismo , Canal Catiónico TRPA1/genética , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética
3.
Proc Natl Acad Sci U S A ; 119(12): e2114583119, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35290117

RESUMEN

Communication between interacting organisms via bioactive molecules is widespread in nature and plays key roles in diverse biological processes. Small RNAs (sRNAs) can travel between host plants and filamentous pathogens to trigger transkingdom RNA interference (RNAi) in recipient cells and modulate plant defense and pathogen virulence. However, how fungal pathogens counteract transkingdom antifungal RNAi has rarely been reported. Here we show that a secretory protein VdSSR1 (secretory silencing repressor 1) from Verticillium dahliae, a soil-borne phytopathogenic fungus that causes wilt diseases in a wide range of plant hosts, is required for fungal virulence in plants. VdSSR1 can translocate to plant nucleus and serve as a general suppressor of sRNA nucleocytoplasmic shuttling. We further reveal that VdSSR1 sequesters ALY family proteins, adaptors of the TREX complex, to interfere with nuclear export of the AGO1­microRNA (AGO1­miRNA) complex, leading to a great attenuation in cytoplasmic AGO1 protein and sRNA levels. With this mechanism, V. dahliae can suppress the accumulation of mobile plant miRNAs in fungal cells and succedent transkingdom silencing of virulence genes, thereby increasing its virulence in plants. Our findings reveal a mechanism by which phytopathogenic fungi antagonize antifungal RNAi-dependent plant immunity and expand the understanding on the complex interaction between host and filamentous pathogens.


Asunto(s)
MicroARNs , Verticillium , Transporte Activo de Núcleo Celular , Antifúngicos , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades de las Plantas/microbiología , Plantas/genética , ARN de Planta , Verticillium/metabolismo
4.
Funct Integr Genomics ; 24(5): 161, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285026

RESUMEN

Epigenetic regulation plays a role in Parkinson's disease (PD), and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) catalyzes the first step in DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine. We investigated whether TET1 binds to the promoter of the transient receptor potential cation channel subfamily V member 1 (TRPV1) and regulates its expression, thereby controlling oxidative stress in PD. TRPV1 was identified as an oxidative stress-associated gene in the GSE20186 dataset including substantia nigra from 14 patients with PD and 14 healthy controls and the Genecards database. Lentiviral vectors were used to manipulate Trpv1 expression in rats, followed by 6-hydroxydopamine hydrochloride (6-OHDA) injection for modeling. Behavioral tests, immunofluorescence, Nissl staining, western blot assays, DHE fluorescent probe, biochemical analysis, and ELISA were conducted to assess oxidative stress and neurotoxicity. Trpv1 expression was significantly reduced in the brain tissues of 6-OHDA-treated Parkinsonian rats. Trpv1 alleviated behavioral dysfunction, oxidative stress, and dopamine neuron loss in rats. TET1 mediated TRPV1 hydroxymethylation to promote its expression, and Trpv1 inhibition reversed the mitigating effect of Tet1 on oxidative stress and behavioral dysfunction in PD. TRPV1 activated the AMPK signaling by promoting AMPK phosphorylation to alleviate neurotoxicity and oxidative stress in SH-SY5Y cells. Tet1-mediated Trpv1 hydroxymethylation modification promotes the Ampk signaling activation, thereby eliciting neuroprotection in 6-OHDA-treated Parkinsonian rats. These findings provide experimental evidence that targeting the TET1/TRPV1 axis may be neuroprotective for PD by acting on the AMPK signaling.


Asunto(s)
Metilación de ADN , Enfermedad de Parkinson , Transducción de Señal , Canales Catiónicos TRPV , Animales , Humanos , Masculino , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Dioxigenasas , Modelos Animales de Enfermedad , Epigénesis Genética , Oxigenasas de Función Mixta/metabolismo , Oxigenasas de Función Mixta/genética , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxidopamina , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Ratas Sprague-Dawley , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética
5.
Hepatology ; 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37816045

RESUMEN

BACKGROUND AND AIMS: HCC is closely associated with inflammation and immune modulation, and combined chemotherapy with other strategies is under extensive investigation to achieve better efficacy. HCC is accompanied by zinc (Zn) deficiency. This study aims to understand how Zn could affect macrophage function and its application for HCC therapy. APPROACH AND RESULTS: Zn 2+ and the Zn transporter 1 (ZNT1, solute carrier family 30 member 1) were markedly reduced in intrahepatic macrophages from patients with HCC and from mouse liver tumors. Lower ZNT1 expression was associated with higher IL-6 production and shorter survival time in patients with HCC. Critically, ZNT1 regulated endosomal Zn 2+ levels for endocytosis of toll-like receptor 4 and programmed cell death ligand 1, thereby decreasing macrophage-induced inflammation and immunosuppression to protect from liver tumors. Myeloid-specific deletion of ZNT1 in mice increased chronic inflammation, liver fibrosis, tumor numbers, and size. Notably, Zn supplementation could reduce inflammation and surface programmed cell death ligand 1 expression in macrophages with the increased CD8 + T cell cytotoxicity, which synergized the antitumor efficacy of Sorafenib/Lenvatinib. CONCLUSIONS: Our study proposes a new concept that ZNT1 and Zn regulate endosome endocytosis to maintain surface receptors, and Zn supplements might be synergized with chemotherapy to treat inflammation-associated tumors, especially those containing programmed cell death ligand 1 + myeloid cells.

6.
Opt Lett ; 49(10): 2629-2632, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748122

RESUMEN

We propose and experimentally demonstrate a compact and efficient photonic convolution accelerator based on a hybrid integrated multi-wavelength DFB laser array by photonic wire bonding. The photonic convolution accelerator operates at 60.12 GOPS for one 3 × 3 kernel with a convolution window vertical sliding stride of 1 and generates 500 images of real-time image classification. Furthermore, real-time image classification on the MNIST database of handwritten digits with a prediction accuracy of 93.86% is achieved. This work provides a novel, to the best of our knowledge, compact hybrid integration platform to realize the optical convolutional neural networks.

7.
BMC Cancer ; 24(1): 519, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38654216

RESUMEN

BACKGROUND: Uveal melanoma (UVM) is the most common primary intraocular tumor in adults, with a median survival of 4-5 months following metastasis. DNA damage response (DDR) upregulation in UVM, which could be linked to its frequent activation of the PI3K/AKT pathway, contributes to its treatment resistance. We have reported that embryonic stem cell microenvironments (ESCMe) can revert cancer cells to less aggressive states through downregulation of the PI3K signaling, showing promise in modulating the DDR of UVM. METHODS: Since nonhomologous end joining (NHEJ) is the main DNA repair mechanism in UVM, this study utilized gene expression analysis and survival prognosis analysis to investigate the role of NHEJ-related genes in UVM based on public databases. Xenograft mouse models were established to assess the therapeutic potential of ESC transplantation and exposure to ESC-conditioned medium (ESC-CM) on key DNA repair pathways in UVM. Quantitative PCR and immunohistochemistry were used to analyze NHEJ pathway-related gene expression in UVM and surrounding normal tissues. Apoptosis in UVM tissues was evaluated using the TUNEL assay. RESULTS: PRKDC, KU70, XRCC5, LIG4 and PARP1 showed significant correlations with UM progression. High expression of PRKDC and XRCC5 predicted poorer overall survival, while low PARP1 and XRCC6 expression predicted better disease-free survival in UVM patients. ESCMe treatment significantly inhibited the NHEJ pathway transcriptionally and translationally and promoted apoptosis in tumor tissues in mice bearing UVM. Furthermore, ESC transplantation enhanced DDR activities in surrounding normal cells, potentially mitigating the side effects of cancer therapy. Notably, direct cell-to-cell contact with ESCs was more effective than their secreted factors in regulating the NHEJ pathway. CONCLUSIONS: Our results suggest that NHEJ-related genes might serve as prognostic markers and therapeutic targets in UVM. These findings support the therapeutic potential of ESC-based therapy in enhancing UVM sensitivity to radiochemotherapy and improving treatment outcomes while minimizing damage to healthy cells.


Asunto(s)
Daño del ADN , Melanoma , Microambiente Tumoral , Neoplasias de la Úvea , Animales , Humanos , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/mortalidad , Ratones , Melanoma/genética , Melanoma/patología , Melanoma/metabolismo , Melanoma/terapia , Células Madre Embrionarias/metabolismo , Reparación del ADN por Unión de Extremidades , Línea Celular Tumoral , Apoptosis/genética , Regulación Neoplásica de la Expresión Génica , Femenino , Ensayos Antitumor por Modelo de Xenoinjerto , Pronóstico , Masculino , Autoantígeno Ku/metabolismo , Autoantígeno Ku/genética , Transducción de Señal , Reparación del ADN
8.
Langmuir ; 40(14): 7268-7285, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38395626

RESUMEN

It is well-established that interfaces play critical roles in biological and synthetic processes. Aside from significant practical applications, the most accessible and measurable quantity is interfacial tension, which represents a measure of the energy required to create or rejoin two surfaces. Owing to the fact that interfacial processes are critical in polymeric materials, this review outlines recent advances in dynamic interfacial processes involving physics and chemistry targeting self-healing. Entropic interfacial energies stored during damage participate in the recovery, and self-healing depends upon copolymer composition and monomer sequence, monomer molar ratios, molecular weight, and polymer dispersity. These properties ultimately impact chain flexibility, shape-memory recovery, and interfacial interactions. Self-healing is a localized process with global implications on mechanical and other properties. Selected examples driven by interfacial flow and shape memory effects are discussed in the context of covalent and supramolecular rebonding targeting self-healable materials development.

9.
Pharmacol Res ; 207: 107341, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39134188

RESUMEN

Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates.


Asunto(s)
Antineoplásicos , Productos Biológicos , Inmunoconjugados , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Animales , Productos Biológicos/uso terapéutico , Productos Biológicos/química , Productos Biológicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Antineoplásicos/farmacología , Inmunoconjugados/uso terapéutico , Inmunoconjugados/química , Inmunoconjugados/farmacología
10.
Am J Hematol ; 99(4): 523-533, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38247315

RESUMEN

Current standard predictive models of disease risk do not adequately account for the heterogeneity of survival outcomes in patients with new-diagnosed multiple myeloma (NDMM). In this retrospective, multicohort study, we collected clinical and genetic data from 1792 NDMM patients and identified the prognostic impact of all features. Using the top-ranked predictive features, a weighted Myeloma Prognostic Score System (MPSS) risk model was formulated and validated to predict overall survival (OS). In the training cohort, elevated lactate dehydrogenase level (LDH), International Staging System (ISS) Stage III, thrombocytopenia, and cumulative high-risk cytogenetic aberration (HRA) numbers were found to have independent prognostic significance. Each risk factor was defined as its weighted value respectively according to their hazard ratio for OS (thrombocytopenia 2, elevated LDH 1, ISS III 2, one HRA 1, and ≥2 HRA 2, points). Patients were further stratified into four risk groups: MPSS I (22.5%, 0 points), II (17.6%, 1 points), III (38.6%, 2-3 points), and IV (21.3%, 4-7 points). MPSS risk stratification showed optimal discrimination, as well as calibration, of four risk groups with median OS of 91.0, 69.8, 45.0, and 28.0 months, for patients in MPSS I to IV groups (p < .001), respectively. Importantly, the MPSS model retained its prognostic value in the internal validation cohort and an independent external validation cohort, and exhibited significant risk distribution compared with conventional prognostic models (R-ISS, R2-ISS, and MASS). Utilization of the MPSS model in clinical practice could improve risk estimation in NDMM patients, thus prompting individualized treatment strategies.


Asunto(s)
Mieloma Múltiple , Humanos , Pronóstico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Modelos de Riesgos Proporcionales
11.
J Org Chem ; 89(10): 7138-7147, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38695505

RESUMEN

An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.

12.
Fish Shellfish Immunol ; : 109972, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39423905

RESUMEN

The application of artificial micro-diet is an effective way to improve and standardize the quality of aquatic animal larvae. However, the widespread adoption of micro-diet faces a bottleneck due to the limited utilization capacity of the larvae. A 30-day feeding experiment was carried out to investigate the effect of dietary succinic acid (SA) on the growth performance, digestive ability, intestinal development, and immunity of large yellow croaker larvae (initial body weight 11.33 ± 0.57 mg). Four isonitrogenous and isolipidic diets were formulated, incorporating 0.00%, 0.01%, 0.02% and 0.03% SA separately. The results showed that a diet with 0.02% SA significantly increased both the final body weight and the specific growth rate of the larvae. Regarding digestive ability, 0.01% SA supplementation significantly enhanced trypsin activity in both intestinal and pancreatic segments. In addition, 0.01% SA supplementation notably improved amylase activity in the intestinal segment, while diets with 0.01%-0.02% SA significantly improved lipase activity in the pancreatic segment. In terms of intestinal development, 0.01% SA supplementation remarkably boosted the activities of alkaline-phosphatase and leucine-aminopeptidase on brush border membrane in intestine. Furthermore, 0.03% SA supplementation significantly increased the expression of occludin. In terms of immunity, larvae fed diets with 0.01%-0.02% SA exhibited significantly higher lysozyme activity compared to the control group. Supplementation with 0.01% SA also significantly increased both iNOS activity and NO content. In summary, the findings of this study suggested that adding 0.02% SA can improve the growth performance of large yellow croaker larvae by improving digestive enzymes activities, promoting intestinal development, and enhancing nonspecific immunity.

13.
Cell Biol Toxicol ; 40(1): 54, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995476

RESUMEN

BACKGROUND: The neuropathic pain with complex networks of neuroinflammatory activation severely limits clinical therapeutic research. TNF receptor-associated factor 6 (TRAF6) is associated with multiple inflammatory diseases. However, there remains confusion about the effects and mechanisms of TRAF6 in neuropathic pain. METHODS: A chronic constriction injury (CCI) model was developed to simulate neuralgia in vivo. We overexpressed or knocked down TRAF6 in CCI mice, respectively. Activation of microglia by TRAF6, the inflammatory response, and disease progression were inspected using WB, qRT-PCR, immunofluorescence, flow cytometry, and ELISA assays. Moreover, the mechanism of M1/M2 polarization activation of microglia by TRAF6 was elaborated in BV-2 cells. RESULTS: TRAF6 was enhanced in the spinal neurons and microglia of the CCI mice model compared with the sham operation group.. Down-regulation of TRAF6 rescued the expression of Iba-1. In response to mechanical and thermal stimulation, PWT and PWL were improved after the knockdown of TRAF6. Decreased levels of pro-inflammatory factors were observed in TRAF6 knockdown groups. Meanwhile, increased microglial M1 markers induced by CCI were limited in mice with TRAF6 knockdown. In addition, TRAF6 overexpression has the precise opposite effect on CCI mice or microglia polarization. We also identifed that TRAF6 activated the c-JUN/NF-kB pathway signaling; the inhibitor of c-JUN/NF-kB could effectively alleviate the neuropathic pain induced by upregulated TRAF6 in the CCI mice model. CONCLUSION: In summary, this study indicated that TRAF6 was concerned with neuropathic pain, and targeting the TRAF6/c-JUN/NF-kB pathway may be a prospective target for treating neuropathic pain.


Asunto(s)
Microglía , FN-kappa B , Neuralgia , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Animales , Masculino , Ratones , Línea Celular , Polaridad Celular , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Microglía/metabolismo , Neuralgia/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Factor 6 Asociado a Receptor de TNF/metabolismo
14.
J Immunol ; 208(4): 827-838, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35046106

RESUMEN

Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment.


Asunto(s)
Oído Interno/inmunología , Oído Interno/metabolismo , Inmunoglobulina E/inmunología , Lectinas Tipo C/metabolismo , Enfermedad de Meniere/etiología , Enfermedad de Meniere/metabolismo , Receptores de IgE/metabolismo , Adulto , Anciano , Animales , Biomarcadores , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina E/metabolismo , Lectinas Tipo C/genética , Masculino , Enfermedad de Meniere/diagnóstico , Ratones , Persona de Mediana Edad , Imagen Molecular , Fenotipo , Unión Proteica , Transporte de Proteínas , Receptores de IgE/genética , Transcitosis/inmunología , Vestíbulo del Laberinto/inmunología , Vestíbulo del Laberinto/metabolismo , Vestíbulo del Laberinto/patología
15.
Cardiology ; 149(1): 78-92, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37708863

RESUMEN

INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHODS: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59-6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.


Asunto(s)
Enfermedad de la Arteria Coronaria , Humanos , Angiografía Coronaria/métodos , Microcirculación , Enfermedad de la Arteria Coronaria/complicaciones , Pronóstico
16.
Phys Chem Chem Phys ; 26(34): 22798-22810, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39163027

RESUMEN

Here, we employed the nudged elastic band (NEB) method to simulate the diffusion of ferrocene through vanadyl phosphate (VOPO4), with a focus on understanding the diffusion pathways arising from the complex structure of ferrocene. We systematically evaluated a total of 36 potential diffusion paths, categorizing them into three groups based on their directional orientation: 15 paths between V sites along the [110] direction, 15 paths from V to P sites along the [100] direction, and 6 paths between P sites also along the [110] direction. Our analysis revealed that the energy barriers for diffusion along the [110] direction typically ranged between 0.25 and 0.35 eV, which are notably higher than those observed for pathways along the [100] direction, where the energy barriers ranged from 0.11 to 0.20 eV. To further elucidate the complex deformation of ferrocene during diffusion, we established four key measures to characterize the structural conformation: the angle of the axis of the ferrocene molecule relative to the [010] direction within the (001) plane, the dihedral angle between the two cyclopentadienyl rings, the orientation angle of the -CH bonds with respect to the [001] direction, and the angle between two -CH bonds from the two cyclopentadienyl rings.

17.
J Chem Phys ; 161(15)2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39412052

RESUMEN

The current collector, one of the main components in the manufacture of composite electrodes, is mainly used to enhance the mechanical stability and improve the performance and cycle performance of the electrodes. During the electrochemical reaction, the lithium diffusion can induce compressive stress and affect the mechanical performance, lifespan, and performance of batteries. Therefore, this study analyzed the influence of copper foil on the mechanical response and degradation performance of electrodes. In addition, a mathematical model was developed to analyze the effect of copper foil on the stress-strain behavior of the electrodes. The results indicated that the stress and modulus of the graphite electrodes have a non-linear increase with the lithiation process. Based on those findings, utilizing a thinner and more compliant current collector could effectively mitigate the in-plane strain and the stress within electrodes. Thus, developing a thinner and softer copper foil could simultaneously enhance the mechanical properties and specific density of composite electrodes for the next-generation LiBs.

18.
J Chem Phys ; 161(3)2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39007392

RESUMEN

Silicon, renowned for its remarkable energy density, has emerged as a focal point in the pursuit of high-energy storage solutions for the next generation. Nevertheless, silicon electrodes are known to undergo significant volume expansion during the insertion of lithium ions, leading to structural deformation and the development of internal stresses, and causing a rapid decline in battery capacity and overall lifespan. To gain deeper insights into the intricacies of charge rate effects, this study employs a combination of in situ measurements and computational modeling to elucidate the cyclic performance of composite silicon electrodes. The findings derived from the established model and curvature measurement system unveil the substantial alterations in stress and deformation as a consequence of varying charge rates. Notably, the active layer experiences compressive forces that diminish as the charge rate decreases. At a charge rate of 0.2, the active layer endures a maximum stress of 89.145 MPa, providing a comprehensive explanation for the observed deterioration in cycling performance at higher charge rates. This study not only establishes a fundamental basis for subsequent stress analyses of silicon electrodes but also lays a solid foundation for further exploration of the impact of charge rates on composite silicon electrodes.

19.
Appl Opt ; 63(14): 3929-3943, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856357

RESUMEN

In order to extract smooth and accurate strain fields from the noisy displacement fields obtained by digital image correlation (DIC), a point interpolation meshless (PIM) method with a radial basis function (RBF) is introduced for full-field strain calculation, which overcomes the problems of slow calculation speed and unstable matrix inverse calculation of the element-free Galerkin method (EFG). The radial basis point interpolation method (RPIM) with three different radial basis functions and the moving least squares (MLS) and pointwise least squares (PLS) methods are compared by analyzing and validating the strain fields with high-strain gradients in simulation experiments. The results indicate that the RPIM is nearly 80% more computationally efficient than the MLS method when a larger support domain is used, and the efficiency of the RPIM is nearly 26% higher than that of the MLS method when a smaller support domain is used; the strain calculation accuracy is slightly lower than that of the MLS method by 0.3-0.5%, but the stability of the calculation is significantly improved. In contrast with the PLS method, which is easily affected by the noise and the size of the strain calculation window, the RPIM is insensitive to the displacement noise and the size of the support domain and can obtain a similar calculation accuracy. The RPIM with multiquadric (MQ) radial basis functions performs well in balancing the computational accuracy and efficiency and is insensitive to shape parameters. The application cases show that the method can effectively compute the strain field at the crack tip, validating its applicability to the study of the plastic region at the crack tip. In conclusion, the proposed RPIM-based method provides an accurate, practical, and robust approach for full-field strain measurements.

20.
Appl Opt ; 63(10): 2710-2718, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38568556

RESUMEN

Aimed at the regional open-path detection of benzene (C 6 H 6) in the atmosphere, a power-modulated integrated path differential absorption (PM-IPDA) lidar is introduced and demonstrated. Two tunable interband cascade lasers (ICLs) with about 3.2 µm wavelength are utilized to generate the required PM optical signal. These two operation central wavelengths (CWs) of the PM-IPDA lidar are, respectively, 3236.6 and 3187.1 nm, which can mitigate the influence of significant gases such as H 2 O, C H 4, and HCl on the detection performance. In this work, the fast Fourier transform algorithm is used to retrieve the measured values with the time resolution of 0.1 s corresponding to 104 sampling bins at the sampling rate of 100 kSps/s. The modulated frequency of the PM-IPDA lidar is selected as 10 kHz by laboratory experiments. The slow fluctuation characteristic of the benzene absorption spectrum within the vicinity region of 3.2 µm reduces the impact of small wavelength fluctuations on the performance of PM-IPDA lidar, although a scheme modulated only the driving current causes wavelength fluctuations of ∼±0.2n m. These laboratory experiments also indicate the PM-IPDA lidar can reduce the error resulting from 1/f noise. Open-path observation experiments show that the detection limit is about 0.60m g⋅m -3 and that the PM-IPDA lidar can be used for the regional open-path real-time detection of benzene.

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