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1.
PLoS Genet ; 19(12): e1011098, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38134213

RESUMEN

Cell death resistance is a hallmark of tumor cells that drives tumorigenesis and drug resistance. Targeting cell death resistance-related genes to sensitize tumor cells and decrease their cell death threshold has attracted attention as a potential antitumor therapeutic strategy. However, the underlying mechanism is not fully understood. Recent studies have reported that NeuroD1, first discovered as a neurodifferentiation factor, is upregulated in various tumor cells and plays a crucial role in tumorigenesis. However, its involvement in tumor cell death resistance remains unknown. Here, we found that NeuroD1 was highly expressed in hepatocellular carcinoma (HCC) cells and was associated with tumor cell death resistance. We revealed that NeuroD1 enhanced HCC cell resistance to ferroptosis, a type of cell death caused by aberrant redox homeostasis that induces lipid peroxide accumulation, leading to increased HCC cell viability. NeuroD1 binds to the promoter of glutathione peroxidase 4 (GPX4), a key reductant that suppresses ferroptosis by reducing lipid peroxide, and activates its transcriptional activity, resulting in decreased lipid peroxide and ferroptosis. Subsequently, we showed that NeuroD1/GPX4-mediated ferroptosis resistance was crucial for HCC cell tumorigenic potential. These findings not only identify NeuroD1 as a regulator of tumor cell ferroptosis resistance but also reveal a novel molecular mechanism underlying the oncogenic function of NeuroD1. Furthermore, our findings suggest the potential of targeting NeuroD1 in antitumor therapy.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Peróxidos Lipídicos , Ferroptosis/genética , Neoplasias Hepáticas/genética , Peróxidos , Carcinogénesis , Línea Celular Tumoral
2.
J Physiol ; 602(2): 317-332, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38152023

RESUMEN

It has been documented that increased sympathetic activity contributes to the development of cardiovascular diseases, such as hypertension. We previously reported that ß-arrestin-1, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)-22-3p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR-22-3p in ß-arrestin-1-mediated central cardiovascular regulation in hypertension. It was observed that miR-22-3p was upregulated in the RVLM of SHRs compared with normotensive Wistar-Kyoto (WKY) rats, and it was subsequently confirmed to target the ß-arrestin-1 gene using a dual-luciferase reporter assay. miR-22-3p was downregulated in the RVLM using adeno-associated virus with 'tough decoys', which caused a significant increase of ß-arrestin-1 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR-22-3p using lentivirus in the RVLM of WKY rats significantly increased BP. In in vitro PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR-22-3p inhibitor, and this effect could be abolished by ß-arrestin-1 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR-22-3p expression, and enhanced ß-arrestin-1 expression in the RVLM of SHRs. Activation of BV2 cells in vitro evoked a significant increase of miR-22-3p expression, and this BV2 cell culture medium was also able to facilitate miR-22-3p expression in PC12 cells. Collectively, our findings support a critical role for microglia-derived miR-22-3p in inhibiting ß-arrestin-1 in the RVLM, which is involved in central cardiovascular regulation in hypertension. KEY POINTS: Impairment of ß-arrestin-1 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of ß-arrestin-1 dysfunction in hypertension. miR-22-3p is implicated in multiple biological processes, but the role of miR-22-3p in central regulation of cardiovascular activity in hypertension remains unknown. We predicted that miR-22-3p could directly bind to the ß-arrestin-1 gene (Arrb1), and this hypothesis was confirmed by using a dual-luciferase reporter assay. Inhibition of ß-arrestin-1 by miR-22-3p was further verified in both in vivo and in vitro experiments. Furthermore, our results suggested miR-22-3p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho-excitation and hypertension. Our present study provides evidence that microglia-derived miR-22-3p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting ß-arrestin-1 in the RVLM.


Asunto(s)
Hipertensión , MicroARNs , Animales , Ratas , beta-Arrestina 1/genética , beta-Arrestina 1/metabolismo , Presión Sanguínea/fisiología , Luciferasas/metabolismo , Bulbo Raquídeo/fisiología , MicroARNs/genética , MicroARNs/metabolismo , Ratas Endogámicas SHR , Ratas Endogámicas WKY
3.
BMC Plant Biol ; 24(1): 189, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38486149

RESUMEN

BACKGROUND: Growing evidence demonstrates that the synergistic interaction of far-red light with shorter wavelength lights could evidently improve the photosynthesis efficiency of multiple species. However, whether/how far-red light affects sink organs and consequently modulates the source‒sink relationships are largely unknown. RESULTS: Here, equal intensities of white and far-red lights were added to natural light for grape plantlets to investigate the effects of far-red light supplementation on grapevine growth and carbon assimilate allocation, as well as to reveal the underlying mechanisms, through physiological and transcriptomic analysis. The results showed that additional far-red light increased stem length and carbohydrate contents in multiple organs and decreased leaf area, specific leaf weight and dry weight of leaves in comparison with their counterparts grown under white light. Compared to white light, the maximum net photosynthetic rate of the leaves was increased by 31.72% by far-red light supplementation, indicating that far-red light indeed elevated the photosynthesis efficiency of grapes. Transcriptome analysis revealed that leaves were most responsive to far-red light, followed by sink organs, including stems and roots. Genes related to light signaling and carbon metabolites were tightly correlated with variations in the aforementioned physiological traits. In particular, VvLHCB1 is involved in light harvesting and restoring the balance of photosystem I and photosystem II excitation, and VvCOP1 and VvPIF3, which regulate light signal transduction, were upregulated under far-red conditions. In addition, the transcript abundances of the sugar transporter-encoding genes VvSWEET1 and VvSWEET3 and the carbon metabolite-encoding genes VvG6PD, VvSUS7 and VvPGAM varied in line with the change in sugar content. CONCLUSIONS: This study showed that far-red light synergistically functioning with white light has a beneficial effect on grape photosystem activity and is able to differentially affect the growth of sink organs, providing evidence for the possible addition of far-red light to the wavelength range of photosynthetically active radiation (PAR).


Asunto(s)
Clorofila , Luz Roja , Clorofila/metabolismo , Transcriptoma , Fotosíntesis , Azúcares , Carbono
4.
Planta ; 260(3): 69, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127837

RESUMEN

MAIN CONCLUSION: Supplying monochromatic blue LED light during the day, but not at night, promotes early coloration and improves anthocyanin accumulation in the skin of grape berries. Specific light spectra, such as blue light, are known to promote the biosynthesis and accumulation of anthocyanins in fruit skins. However, research is scarce on whether supplement of blue light during different periods of one day can differ in their effect. Here, we compared the consequences of supplying blue light during the day and night on the accumulation of anthocyanins in pigmented grapevine (Vitis vinifera) berries. Two treatments of supplemented monochromatic blue light were tested, with light emitting diodes (LED) disposed close to the fruit zone, irradiating between 8:00 and 18:00 (Dayblue) or between 20:00 and 6:00 (Nightblue). Under the Dayblue treatment, berry coloration was accelerated and total anthocyanins in berry skins increased faster than the control (CK) and also when compared to the Nightblue condition. In fact, total anthocyanin content was similar between CK and Nightblue. qRT-PCR analysis indicated that Dayblue slightly improved the relative expression of the anthocyanin-structural gene UFGT and its regulator MYBA1. Instead, the expression of the light-reception and -signaling related genes CRY, HY5, HYH, and COP1 rapidly increased under Dayblue. This study provides insights into the effect of supplementing monochromatic LED blue light during the different periods of one day, on anthocyanins accumulation in the berry skin.


Asunto(s)
Antocianinas , Frutas , Luz , Vitis , Vitis/efectos de la radiación , Vitis/metabolismo , Vitis/genética , Antocianinas/metabolismo , Frutas/efectos de la radiación , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Pigmentación/efectos de la radiación
5.
Med Sci Monit ; 30: e943181, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38366581

RESUMEN

The number of patients with malignant tumors is increasing in China, and venous access ports have unique advantages for chemotherapy. Currently, China's research on venous access port-mediated kinesiophobia is still in the developing stage. Using the combination of subjective words and freedom words, and based on literature traceability methods, China National Knowledge Infrastructure (CNKI), Wanfang, Vipp, Chinese Biomedical Database (CBM), Web of Science, The COCHRANE LIBRARY, Embase, and PubMed were searched. Relevant articles published from the construction of the database to October 30, 2023, were identified. Based on the many articles and analyses, the methods of assessing kinesiophobia in malignant tumors patients using venous access port, the related influencing factors and the preventive and intervention strategies were collated. We found 33 articles examining kinesiophobia in oncology patients, of which 4 were specifically conducted on patients with malignant tumors using VAPs or PICCs. The relevant preventive and therapeutic experiences regarding kinesiophobia in cancer patients with VAP still need improvement. Nursing staff can use assessment tools such as the Tampa Rating Scale for Kinesiophobia, the Fear Avoidance Beliefs Questionnaire, and the Cancer Fatigue Scale to reasonably and effectively assess kinesiophobia among patients with malignant tumors who use VAPs. Attention should be paid to the mechanisms and roles of demographic factors, pain and foreign body sensation, cancer fatigue, pain management strategies, and other factors influencing kinesiophobia. This study provides advice to nursing staff for the management of VAP. Such considerations may reduce the complications of kinesiophobia and improve the quality of life of patients.


Asunto(s)
Cateterismo Venoso Central , Neoplasias , Humanos , Kinesiofobia , Calidad de Vida , Neoplasias/complicaciones , Fatiga
6.
Sci Technol Adv Mater ; 25(1): 2345041, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742153

RESUMEN

Exosomes, a type of extracellular vesicles, have attracted considerable attention due to their ability to provide valuable insights into the pathophysiological microenvironment of the cells from which they originate. This characteristic implicates their potential use as diagnostic disease biomarkers clinically, including cancer, infectious diseases, neurodegenerative disorders, and cardiovascular diseases. Aptasensors, which are electrochemical aptamers based biosensing devices, have emerged as a new class of powerful detection technology to conventional methods like ELISA and Western analysis, primarily because of their capability for high-performance bioanalysis. This review covers the current research landscape on the detection of exosomes utilizing nanoarchitectonics strategy for the development of electrochemical aptasensors. Strategies involving signal amplification and biofouling prevention are discussed, with an emphasis on nanoarchitectonics-based bio-interfaces, showcasing their potential to enhance sensitivity and selectivity through optimal conduction and mass transport properties. The ongoing challenges to broaden the clinical applications of these biosensors are also highlighted.


This review emphasizes the significant impact of integrating nanoarchitectonics into aptamer-based electrochemical biosensors for exosome detection, thereby enhancing early disease detection and monitoring disease progression in clinical settings.

7.
Sensors (Basel) ; 24(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38894213

RESUMEN

In this study, we investigated reconfigurable intelligent surface (RIS)-assisted device-to-device (D2D) communication systems over Nakagami-m fading channels. To enhance the reliability of RIS-assisted D2D communications, we utilized the rate-splitting multiple access (RSMA) technique to maximize the achievable ergodic rate for our considered systems. Specifically, both devices decoded the common symbol by treating private symbols as interference, and then each private symbol was decoded by treating the other as interference. In order to maximize the achievable ergodic rate at the destination, we analyzed the achievable ergodic rate of the RIS link and the D2D link, and the destination jointly decoded both symbols transmitted from the source and device by involving the maximum ratio combination (MRC). We obtained a closed-form expression for the achievable ergodic rate of the proposed RIS-assisted D2D communication system. Finally, we investigated the influence of power allocation factors and the number of reflective elements on the achievable ergodic rate. As seen by the numerical results, there was a good match between the analysis and simulation results, as well as significant superiority compared with existing works.

8.
Methods Mol Biol ; 2783: 137-156, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38478230

RESUMEN

Cats are among the most popular household pets. However, compared to other species, there is little information specific to feline adult mesenchymal stromal/stem cells. Despite the phylogenetic distance between domesticated cats, Felis silvestris catus, and humans, they share some similar health challenges like kidney disease, asthma, and diabetes. Investigative efforts have been focused on adult adipose-derived stromal/stem cell (ASC) therapies to address feline illnesses, including de novo pancreatic tissue generation for diabetes treatment. Given the relatively small size of domestic cats, optimized cell isolation from small quantities of adipose tissue is important in the development of feline ASC-based therapies. Additionally, there are unique features of feline ASC culture conditions and characterization. This chapter contains a few of the novel aspects of feline ASC isolation, culture, preservation, and differentiation.


Asunto(s)
Tejido Adiposo , Diabetes Mellitus , Humanos , Adulto , Gatos , Animales , Filogenia , Diferenciación Celular , Separación Celular/veterinaria
9.
J Affect Disord ; 351: 387-391, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38281594

RESUMEN

OBJECTIVES: With the development of online technology and the increase in real-world needs, conducting psychotherapy on online platforms has become a popular trend. The present study followed the schedule and content of Mindfulness-based Cognitive Therapy (MBCT), and only changed the treatment format (from offline to online) to investigate the effectiveness of online group MBCT for Chinese outpatients with depression. METHODS: The study used before-and-after controlled design, and included 88 depressed outpatients, of which 75 formally underwent a 10-week online group MBCT. The 24-item Hamilton Depression Scale (HAMD-24), Hamilton Anxiety Scale (HAMA), Self-Depression Rating Scale (SDS), Mindful Attention Awareness Scale (MAAS), and Self-Acceptance Questionnaire (SAQ) were administered to patients one week prior to treatment, the fifth week of treatment, and the tenth week of treatment. Repeated-measures data were processed using linear mixed-effects models. RESULTS: 75 patients (85.23 %) attended >4 sessions, 44 of whom were taking psychotropic medication during treatment. HAMD-24 and HAMA scores decreased significantly in both medicated and unmedicated patients (w10 < w1, p < 0.05). HAMD-24 and HAMA scores declined more rapidly in patients taking medication, with significant decreases in the fifth week (w5 < w1, p < 0.05). The remarkable effectiveness of treatment (HAMD-24 score reduction >50 %) was >30 %, but there were no significant changes in patients' SDS, MAAS, or SAQ scores. CONCLUSIONS: This study supports the effectiveness of online group MBCT for outpatients with depression and the adherence of depressed patients to participate in online group MBCT was high.


Asunto(s)
Terapia Cognitivo-Conductual , Atención Plena , Humanos , Depresión/terapia , Depresión/psicología , Pacientes Ambulatorios , Resultado del Tratamiento
10.
PLoS One ; 19(6): e0304973, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38838022

RESUMEN

Cities are commonly recognized as the immediate hinterland of ports and play a crucial role in fostering the sustainable development of ports. Therefore, it is imperative to investigate the influence of cities on ports. By employing panel data from 2001 to 2021 for both ports and cities in the Bohai Rim region, this study examines the spatial spillover effect of urban economy on port efficiency using the spatial error model (SEM). The findings show that urban economies have a significant spatial spillover effect on port efficiency, but this effect diminishes across different spatial matrices. In particular, the geographical matrix demonstrates a stronger spatial spillover effect of the urban economy on port efficiency. These research findings help to establish a collaborative mechanism for port-city development and provide useful insights for government management decision-making.


Asunto(s)
Ciudades , Humanos , China , Desarrollo Sostenible/economía
11.
Sci Rep ; 14(1): 12040, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802498

RESUMEN

This paper presents a frequency selective surface (FSS) with a wideband second-order bandpass response in the dual-band of microwave and millimeter wave. The overall structure consists of three layers of metal pattern and two layers of thin dielectric substrate. The top and bottom metal layers have capacitive patches with integrated curled Jerusalem cross slot resonators, while the intermediate metal layer has an inductive grid structure with cross-shaped slot resonators. The incorporated slot resonators play a pivotal role in achieving the desired transmission poles or zeros, which enable a wideband second-order filtering response in the dual-band and a quick roll-off at the passband edges, increasing the efficacy of electromagnetic shielding. To fully investigate the structure's frequency response, an equivalent circuit model of the structure is created, spanning the complete frequency range of 5-50 GHz. Physical samples are created and measured to confirm the suggested approach's efficacy. The passband center frequencies of the FSS are found at f1 = 19.42 GHz and f2 = 42.78 GHz, and the - 3 dB bandwidth is 4.34 GHz (17.25-21.59 GHz) and 8.54 GHz (38.51-47.05 GHz), respectively. The simulation results align well with the experimental data. The transmission response rapidly transitions from the passband to the stopband at the passband boundaries.

12.
J Hazard Mater ; 472: 134481, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38723483

RESUMEN

The membrane interface probe (MIP) is an efficient and economical in-situ tool for chlorinated hydrocarbon (CH) contaminated site investigation. Given that the interpretation of MIP test is currently limited to a qualitative level, a theoretical model considering multiphase flow and multifield coupling is firstly proposed to simulate MIP test process. This model can consider phase change, membrane effect, adsorption and dissolution of the CH liquid, gas diffusion, and evaporation. Then, the model is used to study the changes in soil temperature and soil CH concentration during MIP test, as well as the influences of soil CH concentration and soil properties (initial water saturation, soil intrinsic permeability, and thermal properties) on MIP response. Finally, a simplified MIP interpretation model is developed based on parametric analysis results and verified against field and laboratory test data. It is found that the soil CH concentration, rather than soil properties, dominates the MIP response. The simplified interpretation model can deliver practical prediction of the CH concentration through the detected results by MIP, which may improve the applicability of MIP.

13.
Sci Rep ; 14(1): 9415, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658637

RESUMEN

This work presents a novel tri-band bandpass frequency selective surface (FSS) that achieves high-order filtering responses in different frequency bands by means of a complementary structure. The proposed FSS is composed of three metal periodic arrays, which are separated by multilayer dielectric substrates. The gridded-double convoluted loop (G-DCL) structure, which is the middle layer structure, is a hybrid resonator that generates different resonant frequencies. The top and bottom layer structures are designed as complementary structures to the middle layer. To accurately describe the frequency responses, an equivalent circuit model (ECM) has been constructed over the entire band from 0 to 16 GHz. The results of the simulation indicate that the developed FSS can generate three pass-bands operating at 3.79 GHz, 8.34 GHz, and 12.52 GHz, respectively, and - 3 dB fractional bandwidths are 52.8%, 13.7%, and 19.7%. The transmission responses at the edges of each passband show a quick roll-off from the passband to the stopband, and there is significant out-of-band suppression between adjacent passbands. Moreover, the FSS maintains excellent angular and polarization stability within a 50° range. For verification, the tri-band FSS has been fabricated and tested. The experimental results match the simulation results, validating the accuracy of the FSS design.

14.
Small Methods ; : e2301644, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38593356

RESUMEN

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry imaging (MSI) holds great value in spatial metabolomics and tumor diagnosis. Tissue imprinting on the SALDI target can avoid laser-induced tissue ablation and simplifies the sample preparation. However, the tissue imprinting process always causes lateral diffusion of biomolecules, thereby losing the fidelity of metabolite distribution on tissue. Herein, a membrane-mediated imprinting mass spectrometry imaging (MMI-MSI) strategy is proposed using isoporous nuclepore track-etched membrane as a mediating imprinting layer to selectively transport metabolites through uniform and vertical pores onto silicon nanowires (SiNWs) array. Compared with conventional direct imprinting technique, MMI-MSI can not only exclude the adsorption of large biomolecules but also avoid the lateral diffusion of metabolites. The whole time for MMI-based sample preparation can be reduced to 2 min, and the lipid peak number can increase from 46 to 113 in kidney tissue detection. Meanwhile, higher resolution of MSI can be achieved due to the confinement effect of the pore channel in the diffusion of metabolites. Based on MMI-MSI, the tumor margins of liver cancer can be clearly discriminated and their different subtypes can be precisely classified. This work demonstrates MMI-MSI is a rapid, highly sensitive, robust and high-resolution technique for spatially-resolved metabolomics and pathological diagnosis.

15.
Biosens Bioelectron ; 248: 115973, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38150797

RESUMEN

Hybridization chain reaction (HCR) based enzyme-free amplification techniques have recently been developed for the visualization of intracellular messenger RNA (mRNA). However, the slow kinetics and potential interference with the intricate biological environments hinder its application in the clinic and in vivo. Herein, we designed a nanofirecracker probe-based strategy using intramolecular hybridization chain reaction (IHCR) amplifier for rapid, efficient, sensitive, specific detection and imaging of survivin mRNA both in vitro and vivo. Two probes, HP1 and HP2, in IHCR were simultaneously incorporated into a DNA nanowire scaffolds to bring HP1 and HP2 to close proximity on the assembled nanowire scaffolds. Empowered by the DNA nanowire scaffolds and spatial confinement effect, the nanofirecracker probe-based IHCR sensing system exhibited improved biostability, accelerated reaction kinetics, and enhanced signal amplification. This new strategy has been successfully applied to imaging mRNA in both cultured cells and in mice. Importantly, this novel sensing method was capable of detecting survivin mRNA in clinical blood samples from subjects with colorectal cancer. Thus, this novel nanofirecracker probe-based IHCR strategy holds great potential in advancing both biomedical research and in molecular diagnostics.


Asunto(s)
Técnicas Biosensibles , Humanos , Animales , Ratones , ARN Mensajero/genética , Survivin/genética , Técnicas Biosensibles/métodos , Hibridación de Ácido Nucleico/métodos , ADN/genética , Proteínas Cromosómicas no Histona/genética
16.
Orphanet J Rare Dis ; 19(1): 19, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243274

RESUMEN

BACKGROUND: Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy. METHODS: We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded. RESULTS: Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066-2.975; p = 0.028). All the adverse events were transient and tolerable. CONCLUSION: Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.


Asunto(s)
Metilprednisolona , Miastenia Gravis , Humanos , Prednisona/uso terapéutico , Estudios Retrospectivos , Metilprednisolona/uso terapéutico , Tacrolimus/uso terapéutico , Miastenia Gravis/tratamiento farmacológico , Resultado del Tratamiento
17.
Mar Environ Res ; 196: 106393, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38367293

RESUMEN

Understanding the metal concentrations in oysters is important because of its relevance to human health and biomonitoring. However, metal concentrations in oysters are highly variable in nature and not well explained by metal exposure. This study examined the metal contamination in farm oysters Crassostrea hongkongensis grown in Qinzhou Bay, south China. Cadmium (Cd), zinc (Zn), nickel (Ni), and copper (Cu) concentrations in the oysters varied between 7.9 and 72.2, 282-17003, 0.37-47.7 and 37-4012 µg g-1, respectively, showing large metal variability among different individuals. Oyster metal concentrations decreased with increasing body size and significantly higher levels were observed in wet season. Low salinity and slower oyster growth due to inferior growth conditions could be responsible for the elevated metal concentrations in the wet season. Biokinetic modeling showed that the coupling of ingestion rate and growth can cause 2.8-4.2 folds differences in the oyster Cd and Zn concentrations, respectively, suggesting the significant role of oyster bioenergetics in contributing to the metal variability. Modeling data revealed that Cd and Zn concentrations in oyster tissues reach maximum levels when oysters have their lowest growth efficiency. This suggests that any factors influencing the energy budget in oysters could simultaneously alter their metal concentrations, which might be the reason why oyster metal concentrations are so variable in the natural environment.


Asunto(s)
Crassostrea , Contaminantes Químicos del Agua , Animales , Humanos , Cadmio/toxicidad , Cadmio/análisis , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Metales/toxicidad , Metales/análisis , Zinc/toxicidad , Zinc/análisis , Monitoreo del Ambiente
18.
Open Forum Infect Dis ; 11(4): ofae163, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38585185

RESUMEN

Background: The aim of this study was to investigate the changes of epidemic characteristics of influenza activity pre- and post-coronavirus disease 2019 (COVID-19) in Beijing, China. Methods: Epidemiologic data were collected from the influenza surveillance system in Beijing. We compared epidemic intensity, epidemic onset and duration, and influenza transmissibility during the 2022-2023 season with pre-COVID-19 seasons from 2014 to 2020. Results: The overall incidence rate of influenza in the 2022-2023 season was significantly higher than that of the pre-COVID-19 period, with the record-high level of epidemic intensity in Beijing. The onset and duration of the influenza epidemic period in 2022-2023 season was notably later and shorter than that of the 2014-2020 seasons. Maximum daily instantaneous reproduction number (Rt) of the 2022-2023 season (Rt = 2.31) was much higher than that of the pre-COVID-19 period (Rt = 1.49). The incidence of influenza A(H1N1) and A(H3N2) were the highest among children aged 0-4 years and 5-14 years, respectively, in the 2022-2023 season. Conclusions: A late, intense, and short-term peak influenza activity was observed in the 2022-2023 season in Beijing. Children <15 years old were impacted the most by the interruption of influenza circulation during the COVID-19 pandemic. Maintaining continuous surveillance and developing targeted public health strategies of influenza is necessary.

19.
J Control Release ; 371: 530-554, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38857787

RESUMEN

Wound management remains a great challenge for clinicians due to the complex physiological process of wound healing. Porous silicon (PSi) with controlled pore morphology, abundant surface chemistry, unique photonic properties, good biocompatibility, easy biodegradation and potential bioactivity represent an exciting class of materials for various biomedical applications. In this review, we focus on the recent progress of PSi in the design of advanced sensing and delivery systems for wound management applications. Firstly, we comprehensively introduce the common type, normal healing process, delaying factors and therapeutic drugs of wound healing. Subsequently, the typical fabrication, functionalization and key characteristics of PSi have been summarized because they provide the basis for further use as biosensing and delivery materials in wound management. Depending on these properties, the rise of PSi materials is evidenced by the examples in literature in recent years, which has emphasized the robust potential of PSi for wound monitoring, treatment and theranostics. Finally, challenges and opportunities for the future development of PSi-based sensors and delivery systems for wound management applications are proposed and summarized. We hope that this review will help readers to better understand current achievements and future prospects on PSi-based sensing and delivery systems for advanced wound management.


Asunto(s)
Sistemas de Liberación de Medicamentos , Silicio , Cicatrización de Heridas , Silicio/química , Humanos , Porosidad , Cicatrización de Heridas/efectos de los fármacos , Animales , Sistemas de Liberación de Medicamentos/métodos , Técnicas Biosensibles/métodos
20.
Adv Sci (Weinh) ; 11(26): e2308690, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38682484

RESUMEN

Spindle assembly checkpoint (SAC) is a crucial safeguard mechanism of mitosis fidelity that ensures equal division of duplicated chromosomes to the two progeny cells. Impaired SAC can lead to chromosomal instability (CIN), a well-recognized hallmark of cancer that facilitates tumor progression; paradoxically, high CIN levels are associated with better therapeutic response and prognosis. However, the mechanism by which CIN determines tumor cell survival and therapeutic response remains poorly understood. Here, using a cross-omics approach, YY2 is identified as a mitotic regulator that promotes SAC activity by activating the transcription of budding uninhibited by benzimidazole 3 (BUB3), a component of SAC. While both conditions induce CIN, a defect in YY2/SAC activity enhances mitosis and tumor growth. Meanwhile, hyperactivation of SAC mediated by YY2/BUB3 triggers a delay in mitosis and suppresses growth. Furthermore, it is revealed that YY2/BUB3-mediated excessive CIN causes higher cell death rates and drug sensitivity, whereas residual tumor cells that survived DNA damage-based therapy have moderate CIN and increased drug resistance. These results provide insights into the role of SAC activity and CIN levels in influencing tumor cell survival and drug response, as well as suggest a novel anti-tumor therapeutic strategy that combines SAC activity modulators and DNA-damage agents.


Asunto(s)
Inestabilidad Cromosómica , Neoplasias Colorrectales , Progresión de la Enfermedad , Inestabilidad Cromosómica/genética , Humanos , Ratones , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Animales , Línea Celular Tumoral , Puntos de Control de la Fase M del Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Modelos Animales de Enfermedad
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