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1.
Discov Oncol ; 15(1): 568, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39417906

RESUMO

OBJECTIVE: This study aims to investigate the causal relationship between cervical carcinoma in situ and antibody-mediated immune responses, providing a scientific basis for the prevention and treatment of cervical carcinoma in situ. METHODS: A bidirectional Mendelian Randomization (MR) approach was utilized, leveraging two Genome-Wide Association Studies (GWAS) related to cervical carcinoma in situ and antibody-mediated immune responses to collect Single Nucleotide Polymorphism (SNP) data. Multiple statistical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, and weighted mode, were utilized. Antibody-mediated immune response-related SNPs were used as instrumental variables (IVs) for a forward MR analysis of cervical carcinoma in situ, while cervical carcinoma in situ-related SNPs served as IVs for a reverse MR analysis of antibody-mediated immune responses. RESULTS: The forward MR analysis revealed significant causal associations between two SNPs, GCST90006901 (P = 0.012, OR (95%CI) = 1.167(1.034-1.317)) and GCST90006909 (P < 0.001, OR (95%CI) = 1.805(1.320-2.467)), within antibody-mediated immune responses and the occurrence of cervical carcinoma in situ. The reverse MR analysis demonstrated that cervical carcinoma in situ exerts influence on multiple SNPs associated with antibody-mediated immune responses. Specifically, GCST90006891 (P = 0.018, OR (95%CI) = 1.164(1.027-1.319)) and GCST90006894 (P = 0.048, OR (95%CI) = 1.074 (1.001-1.153)) showed positive effects, while GCST90006899 (P = 0.022, OR (95%CI) = 0.935(0.882-0.990)) and GCST90006911 (P = 0.0193, OR (95%CI) = 1.226(1.034-1.454)) exhibited distinct trends of influence. CONCLUSION: The Mendelian Randomization analysis indicates a clear causal relationship between antibody-mediated immune responses and the prevalence of cervical carcinoma in situ, with cervical carcinoma in situ also exerting a certain degree of influence on antibody-mediated immune responses. This finding provides important insights into the interaction mechanism between the two and suggests avenues for developing effective prevention and control strategies.

2.
Nucleic Acids Res ; 52(16): 9536-9550, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39106166

RESUMO

Heterochromatin is a key feature of eukaryotic genomes and is crucial for maintaining genomic stability. In fission yeast, heterochromatin nucleation is mainly mediated by DNA-binding proteins or the RNA interference (RNAi) pathway. In the filamentous fungus Neurospora crassa, however, the mechanism that causes the initiation of heterochromatin at the relics of repeat-induced point mutation is unknown and independent of the classical RNAi pathway. Here, we show that casein kinase II (CKII) and its kinase activity are required for heterochromatin formation at the well-defined 5-kb heterochromatin of the 5H-cat-3 region and transcriptional repression of its adjacent cat-3 gene. Similarly, mutation of the histone H3 phosphorylation site T11 also impairs heterochromatin formation at the same locus. The catalytic subunit CKA colocalizes with H3T11 phosphorylation (H3pT11) within the 5H-cat-3 domain and the deletion of cka results in a significant decrease in H3T11 phosphorylation. Furthermore, the loss of kinase activity of CKII results in a significant reduction of H3pT11, H3K9me3 (histone H3 lysine 9 trimethylation) and DNA methylation levels, suggesting that CKII regulates heterochromatin formation by promoting H3T11 phosphorylation. Together, our results establish that histone H3 phosphorylation by CKII is a critical event required for heterochromatin formation.


Assuntos
Caseína Quinase II , Heterocromatina , Histonas , Neurospora crassa , Heterocromatina/metabolismo , Heterocromatina/genética , Fosforilação , Histonas/metabolismo , Caseína Quinase II/metabolismo , Caseína Quinase II/genética , Neurospora crassa/genética , Neurospora crassa/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Metilação de DNA , Regulação Fúngica da Expressão Gênica , Mutação
3.
eNeuro ; 11(8)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39137988

RESUMO

Sensory axons projecting to the central nervous system are organized into topographic maps that represent the locations of sensory stimuli. In some sensory systems, even adjacent sensory axons are arranged topographically, forming "fine-scale" topographic maps. Although several broad molecular gradients are known to instruct coarse topography, we know little about the molecular signaling that regulates fine-scale topography at the level of two adjacent axons. Here, we provide evidence that transsynaptic bone morphogenetic protein (BMP) signaling mediates local interneuronal communication to regulate fine-scale topography in the nociceptive system of Drosophila larvae. We first show that the topographic separation of the axon terminals of adjacent nociceptors requires their common postsynaptic target, the A08n neurons. This phenotype is recapitulated by knockdown of the BMP ligand, Decapentaplegic (Dpp), in these neurons. In addition, removing the Type 2 BMP receptors or their effector (Mad transcription factor) in single nociceptors impairs the fine-scale topography, suggesting the contribution of BMP signaling originated from A08n. This signaling is likely mediated by phospho-Mad in the presynaptic terminals of nociceptors to ensure local interneuronal communication. Finally, reducing Dpp levels in A08n reduces the nociceptor-A08n synaptic contacts. Our data support that transsynaptic BMP signaling establishes the fine-scale topography by facilitating the formation of topographically correct synapses. Local BMP signaling for synapse formation may be a developmental strategy that independently regulates neighboring axon terminals for fine-scale topography.


Assuntos
Proteínas Morfogenéticas Ósseas , Proteínas de Drosophila , Células Receptoras Sensoriais , Transdução de Sinais , Animais , Proteínas de Drosophila/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Transdução de Sinais/fisiologia , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/fisiologia , Drosophila , Larva , Nociceptores/metabolismo , Nociceptores/fisiologia , Animais Geneticamente Modificados , Sinapses/metabolismo , Sinapses/fisiologia , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/fisiologia , Proteínas de Ligação a DNA , Fatores de Transcrição
4.
Curr Med Imaging ; 20: e15734056291283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39150027

RESUMO

BACKGROUND: Chest X-ray image classification for multiple diseases is an important research direction in the field of computer vision and medical image processing. It aims to utilize advanced image processing techniques and deep learning algorithms to automatically analyze and identify X-ray images, determining whether specific pathologies or structural abnormalities exist in the images. OBJECTIVE: We present the MMPDenseNet network designed specifically for chest multi-label disease classification. METHODS: Initially, the network employs the adaptive activation function Meta-ACON to enhance feature representation. Subsequently, the network incorporates a multi-head self-attention mechanism, merging the conventional convolutional neural network with the Transformer, thereby bolstering the ability to extract both local and global features. Ultimately, the network integrates a pyramid squeeze attention module to capture spatial information and enrich the feature space. RESULTS: The concluding experiment yielded an average AUC of 0.898, marking an average accuracy improvement of 0.6% over the baseline model. When compared with the original network, the experimental results highlight that MMPDenseNet considerably elevates the classification accuracy of various chest diseases. CONCLUSION: It can be concluded that the network, thus, holds substantial value for clinical applications.


Assuntos
Redes Neurais de Computação , Radiografia Torácica , Humanos , Radiografia Torácica/métodos , Aprendizado Profundo , Algoritmos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos
5.
Angew Chem Int Ed Engl ; : e202412901, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141415

RESUMO

Electrochemical formic acid oxidation reaction (FAOR) is a pivotal model for understanding organic fuel oxidation and advancing sustainable energy technologies. Here, we present mechanistic insights into a novel molecular-like iridium catalyst (Ir-N4-C) for FAOR. Our studies reveal that isolated sites facilitate a preferential dehydrogenation pathway, circumventing catalyst poisoning and exhibiting high inherent activity. In situ spectroscopic analyses elucidate that weakly adsorbed intermediates mediate the FAOR and are dynamically regulated by potential-dependent redox transitions. Theoretical and experimental investigations demonstrate a parallel mechanism involving two key intermediates with distinct pH and potential sensitivities. The rate-determining step is identified as the adsorption of formate via coupled or sequential proton-electron transfer, which aligns well with the observed kinetic properties, pH dependence, and hydrogen/deuterium isotope effects in experiments. These findings provide valuable insights into the reaction mechanism of FAOR, advancing our understanding at the molecular level and potentially guiding the design of efficient catalysts for fuel cells and electrolyzers.

6.
Cancer Med ; 13(11): e7356, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850125

RESUMO

OBJECTIVE: Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation. The aim of this study was to determine the incidence of mobilization failure and characterize the risk factors associated with poor mobilization (PM) of MM patients in novel therapies era. METHODS: We conducted a retrospective study of 211 MM patients who received their first peripheral blood stem cells (PBSC) mobilization at our single center. The following data were collected: age, gender, clinical stage, disease status, complete blood cell count, induction regimen, CD34+ cell count in peripheral blood (PB), and PBSC collections. RESULTS: In addition to conventional drugs, 22 (10.4%) patients received daratumumab containing induction, and 33 (15.6%) patients used plerixafor for poor mobilization (pre-apheresis PB CD34+ cells <20/µL). Failure of collection occurred in 24 (11.4%) patients and was correlated with low white blood cell (WBC), ≥3 cycles of lenalidomide treatment before mobilization, steady-state mobilization and nouse of plerixafor are associated with mobilization failure. Daratumumab-based induction treatment ≥2 courses, albumin >41 g/L before mobilization, and steady-state mobilization were risk factors for PM in subgroups of patients treated with lenalidomide for <3 courses. In addition, Hepatitis B virus infection at baseline, thalassemia and measurable residual disease positivity were recognized as predictive factors for PM in subset of chemo-mobilization patients. CONCLUSION: In addition to some well-recognized risk factors, baseline WBC count and daratumumab exposure ≥2 courses before mobilization were revealed as the predictive factors of mobilization failure, providing consultation for preemptive use of plerixafor.


Assuntos
Benzilaminas , Ciclamos , Mobilização de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mobilização de Células-Tronco Hematopoéticas/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Ciclamos/uso terapêutico , Ciclamos/farmacologia , Benzilaminas/uso terapêutico , Células-Tronco de Sangue Periférico/metabolismo , Fatores de Risco , Anticorpos Monoclonais/uso terapêutico , Lenalidomida/uso terapêutico , Lenalidomida/administração & dosagem , Compostos Heterocíclicos/administração & dosagem , Compostos Heterocíclicos/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante Autólogo
7.
Lab Chip ; 24(12): 3080-3092, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38747247

RESUMO

Digital PCR is a powerful method for absolute nucleic acid quantification and is widely used in the absolute quantification of viral copy numbers, tumor marker detection, and prenatal diagnosis. However, for most of the existing droplet-based dPCR systems, the droplet generation, PCR reaction, and droplet detection are performed separately using different instruments. Making digital PCR both easy to use and practical by integrating the qPCR workflow into a superior all-in-one walkaway solution is one of the core ideas. A new innovative and integrated digital droplet PCR platform was developed that utilizes cutting-edge microfluidics to integrate dPCR workflows onto a single consumable chip. This makes previously complex workflows fast and simple; the whole process of droplet generation, PCR amplification, and droplet detection is completed on one chip, which meets the clinical requirement of "sample in, result out". It provides high multiplexing capabilities and strong sensitivity while all measurements were within the 95% confidence interval. This study is the first validation of the DropXpert S6 system and focuses primarily on verifying its reliability, repeatability, and consistency. In addition, the accuracy, detection limit, linearity, and precision of the system were evaluated after sample collection. Among them, the accuracy assessment by calculating the absolute bias of each target gene yielded a range from -0.1 to 0.08, all within ±0.5 logarithmic orders of magnitude; the LOB for the assay was set at 0, and the LoD value calculated using probit curves is MR4.7 (0.002%); the linearity evaluation showed that the R2 value of the BCR-ABL was 0.9996, and the R2 value of the ABL metrics calculated using the ERM standard was 0.9999; and the precision evaluation showed that all samples had a CV of less than 4% for intra-day, inter-day, and inter-instrument variation. The CV of inter-batch variation was less than 7%. The total CV was less than 5%. The results of the study demonstrate that dd-PCR can be applied to molecular detection and the clinical evaluation of CML patients and provide more precise personal treatment guidance, and its reproducibility predicts the future development of a wide range of clinical applications.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Dispositivos Lab-On-A-Chip , Proteínas de Fusão bcr-abl/genética , Reação em Cadeia da Polimerase , Técnicas Analíticas Microfluídicas/instrumentação
9.
Science ; 384(6697): adm9190, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38662913

RESUMO

Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins activated by proteolytic removal of the inhibitory domain. In this work, we report two types of cleavage-independent GSDM activation. First, TrichoGSDM, a pore-forming domain-only protein from the basal metazoan Trichoplax adhaerens, is a disulfides-linked autoinhibited dimer activated by reduction of the disulfides. The cryo-electron microscopy (cryo-EM) structure illustrates the assembly mechanism for the 44-mer TrichoGSDM pore. Second, RCD-1-1 and RCD-1-2, encoded by the polymorphic regulator of cell death-1 (rcd-1) gene in filamentous fungus Neurospora crassa, are also pore-forming domain-only GSDMs. RCD-1-1 and RCD-1-2, when encountering each other, form pores and cause pyroptosis, underlying allorecognition in Neurospora. The cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and a heterodimerization-triggered pore assembly mechanism. This study shows mechanistic diversities in GSDM activation and indicates versatile functions of GSDMs.


Assuntos
Proteínas Fúngicas , Gasderminas , Neurospora crassa , Placozoa , Multimerização Proteica , Animais , Microscopia Crioeletrônica , Dissulfetos/química , Proteínas Fúngicas/química , Gasderminas/química , Modelos Moleculares , Domínios Proteicos , Proteólise , Piroptose
10.
Nano Lett ; 24(10): 3249-3256, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477055

RESUMO

The synergistic interaction between the isolated metal sites promoted the electrocatalytic activity of the catalysts. However, the structural heterogeneity of the isolated sites makes it challenging to evaluate this effect accurately. In this work, metal-coordinated polyphthalocyanine molecules (Fe-PPc, Co-PPc, FeCo-PPc) with long-range ordered and precise coordination structures are used as a platform to study the synergies of different isolated metal sites in the electrochemical CO2 reduction reaction. The combination means of experimental and theoretical calculation clearly reveal that the coexistence of Fe and Co sites in PPc significantly enhances the conjugation effect of the macrocycle. This enhancement subsequently causes the metal sites to lose more electrons, thereby improving their adsorption of CO2 and facilitating the formation of intermediate *COOH on them. As a result, FeCo-PPc achieves a CO partial current density of about 57.4 mA/cm2 with a high turnover frequency of over 49000 site-1 h-1 at -0.9 V (vs RHE).

11.
Viruses ; 16(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38399989

RESUMO

The coronavirus disease 2019 (COVID-19) global pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been marked by severe cases demonstrating a "cytokine storm", an upsurge of pro-inflammatory cytokines in the bloodstream. NLRP3 inflammasomes, integral to the innate immune system, are speculated to be activated by SARS-CoV-2 within host cells. This review investigates the potential correlation between NLRP3 inflammasomes and COVID-19, exploring the cellular and molecular mechanisms through which SARS-CoV-2 triggers their activation. Furthermore, promising strategies targeting NLRP3 inflammasomes are proposed to mitigate the excessive inflammatory response provoked by SARS-CoV-2 infection. By synthesizing existing studies, this paper offers insights into NLRP3 as a therapeutic target, elucidating the interplay between COVID-19 and its pathophysiology. It serves as a valuable reference for future clinical approaches in addressing COVID-19 by targeting NLRP3, thus providing potential avenues for therapeutic intervention.


Assuntos
COVID-19 , Humanos , Citocinas , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , SARS-CoV-2/fisiologia
12.
Curr Neurovasc Res ; 21(1): 64-73, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38409728

RESUMO

Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated. METHODS: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment. RESULTS: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation. CONCLUSION: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.


Assuntos
Eletroacupuntura , Proteína 3 que Contém Domínio de Pirina da Família NLR , RNA Longo não Codificante , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Transdução de Sinais , Receptor 4 Toll-Like , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Eletroacupuntura/métodos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/terapia , Ratos , Transdução de Sinais/fisiologia , Masculino , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia , Metilação
13.
Technol Health Care ; 32(4): 2243-2250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38251074

RESUMO

BACKGROUND: During the COVID-19 pandemic, the mobile field hospital, a rapidly deployable healthcare facility for emergency care, was effective in ensuring rapid diagnosis and treatment of patients with mild or asymptomatic SARS-CoV2 infections, effectively preventing the spread of COVID-19. OBJECTIVE: We conducted a survey to gain a thorough understanding of the epidemiological traits among the elderly who contracted the Omicron variant of the SARS-CoV-2 virus at a mobile field hospital set up at the National Exhibition and Convention Center (Shanghai). METHODS: A cross-sectional study approach was employed to examine various factors such as demographic characteristics, clinical features, vaccination status, and nucleic acid testing. We utilized the DezhenTech Integrated Electronic Medical Record Platform (Municipal Isolation Hospital) to collect data and focused on elderly individuals infected with COVID-19 in the fifth isolation zone of the mobile field hospital set up at the National Exhibition and Convention Center (Shanghai). The patients were categorized into different age groups for analysis. RESULTS: Among the 3,183 elderly patients, 54.7% were males and 45.3% were females, with an average age of 65.32 ± 4.41 years. Among them, 47.8% (1523/3183) were 60-64 years old, 34.0% (1082/3183) were 65-69 years old, 14.0% (444/3183) were 70-74 years old, 3.2% (103/3183) were 75-79 years old, and 1.0% (31/3183) were ⩾ 80 years old. The majority (95.7%) of the elderly patients with chronic conditions had hypertension, diabetes, and coronary heart disease. The first viral nucleic acid screening showed a higher positive rate in the community and hospital fever clinics. The cumulative positive rate of the nucleic acid test in the mobile field hospital was 38.7%. The average CT value of the COVID-19 ORF1ab gene was 34.56 ± 5.98, while the average CT value of the N gene was 33.10 ± 6.50. The patients took an average of 3.40 ± 0.45 days to test negative, with a positive rate of 15.4% and an average hospital stay of 7.45 ± 0.53 days. The overall rate of COVID-19 vaccine coverage was 68.0%, with an enhanced coverage rate of 40% and a non-coverage rate of 29.3%. CONCLUSIONS: The overall prognosis for elderly patients who experienced a mild or asymptomatic SARS-CoV-2 Omicron infection at the mobile field hospital was favorable, although the vaccination rate in general was not high. By effectively managing underlying health conditions, the duration of their hospital stay in the mobile field hospital was reduced.


Assuntos
COVID-19 , Unidades Móveis de Saúde , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Feminino , Idoso , Masculino , Estudos Transversais , Pessoa de Meia-Idade , China/epidemiologia , Idoso de 80 Anos ou mais , Pandemias
14.
Eur Radiol ; 34(1): 715-723, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37581653

RESUMO

OBJECTIVES: Microwave ablation (MWA) has achieved excellent long-term efficacy in treating unifocal papillary thyroid microcarcinoma (UPTMC). The therapeutic effect of this treatment on multifocal papillary thyroid microcarcinoma (MPTMC) is unknown. Therefore, we evaluated the long-term efficacy of MWA for low-risk MPTMC and to provide evidence-based medicine for the revision of clinical guidelines. METHODS: This study included 66 MPTMC patients with a total of 158 lesions, all of whom received MWA. We collected and retrospectively analyzed the patients' follow-up data before MWA, at 1, 3, 6, and 12 months posttreatment and every 6 months thereafter until 5 years posttreatment. We evaluated the MWA complication rate, technical success rate (TSR), lesion volume reduction rate (VRR), and complete disappearance rate (CDR) during follow-up and in those patients with tumor progression and delayed surgery. RESULTS: After 60 months of follow-up, all 158 lesions disappeared in 66 patients, and the volume was reduced from 43.82 mm3 to 0.00 mm3. The TSR and VRR were both 100%. The CDRs at 1 year, 2 years, and 3 years were 57.59%, 93.67%, and 100%, respectively. The complication rate was 3.03% (2/66), and the incidence of tumor progression was 3.03% (2/66), including one new intrathyroidal lesion and one cervical lymph node metastasis (LNM). These lesions were retreated with MWA, and the lesions disappeared during the follow-up period. CONCLUSIONS: Ultrasound-guided MWA for low-risk MPTMC is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance (AS). CLINICAL RELEVANCE STATEMENT: This study concludes that ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance. KEY POINTS: • Ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective. • During 5 years of follow-up, multifocal papillary thyroid microcarcinoma patients treated with microwave ablation had a favorable prognosis. • To provide evidence-based medicine for the revision of clinical guidelines.


Assuntos
Carcinoma Papilar , Micro-Ondas , Neoplasias da Glândula Tireoide , Humanos , Seguimentos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Ultrassonografia de Intervenção
15.
Lab Invest ; 104(2): 100298, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38008182

RESUMO

Enterovirus A71 (EV-A71) is one of the major causative agents of hand, foot, and mouth disease (HFMD) that majorly affects children. Most of the time, HFMD is a mild disease but can progress to severe complications, such as meningitis, brain stem encephalitis, acute flaccid paralysis, and even death. HFMD caused by EV-A71 has emerged as an acutely infectious disease of highly pathogenic potential in the Asia-Pacific region. In this review, we introduced the properties and life cycle of EV-A71, and the pathogenesis and the pathophysiology of EV-A71 infection, including tissue tropism and host range of virus infection, the diseases caused by the virus, as well as the genes and host cell immune mechanisms of major diseases caused by enterovirus 71 (EV-A71) infection, such as encephalitis and neurologic pulmonary edema. At the same time, clinicopathologic characteristics of EV-A71 infection were introduced. There is currently no specific medication for EV-A71 infection, highlighting the urgency and significance of developing suitable anti-EV-A71 agents. This overview also summarizes the targets of existing anti-EV-A71 agents, including virus entry, translation, polyprotein processing, replication, assembly and release; interferons; interleukins; the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase B signaling pathways; the oxidative stress pathway; the ubiquitin-proteasome system; and so on. Furthermore, it overviews the effects of natural products, monoclonal antibodies, and RNA interference against EV-A71. It also discusses issues limiting the research of antiviral drugs. This review is a systematic and comprehensive summary of the mechanism and pathological characteristics of EV-A71 infection, the latest progress of existing anti-EV-A71 agents. It would provide better understanding and guidance for the research and application of EV-A71 infection and antiviral inhibitors.


Assuntos
Encefalite , Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Criança , Humanos , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico
16.
Allergy Asthma Proc ; 44(6): 402-412, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37919842

RESUMO

Background: Rhinitis, allergic rhinitis in particular, and urticaria are both common diseases globally. However, there is controversy with regard to the correlation between rhinitis and urticaria. Objective: To examine the accurate association between rhinitis and urticaria. Methods: Three medical literature data bases were searched from data base inception until January 11, 2022. The prevalence and association between rhinitis and urticaria were estimated by meta-analysis. Quality assessment was performed by using the Newcastle-Ottawa Scale. Pooled odds ratios (OR) with 95% confidence intervals (CI) and pooled prevalence were calculated by using random-effects models. Results: Urticaria prevalence in patients with rhinitis was 17.6% (95% CI, 13.2%-21.9%). The pooled prevalence of rhinitis was 31.3% (95% CI, 24.2%-38.4%) in patients with urticaria, and rhinitis prevalence in patients with acute urticaria and chronic urticaria was 31.6% (95% CI, 7.4%-55.8%) and 28.7% (95% CI, 20.4%-36.9%), respectively. Rhinitis occurrence was significantly associated with urticaria (OR 2.67 [95% CI, 2.625-2.715]). Urticaria and rhinitis were diagnosed based on different criteria, possibly resulting in a potential error of misclassification. Conclusion: Rhinitis and urticaria were significantly correlated. Physicians should be cognizant with regard to this relationship and address nasal or skin symptoms in patients.


Assuntos
Rinite Alérgica Perene , Rinite Alérgica , Rinite , Urticária , Humanos , Rinite/epidemiologia , Prevalência , Urticária/epidemiologia , Rinite Alérgica/epidemiologia
17.
PLoS Genet ; 19(10): e1010985, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37844074

RESUMO

UPF-1-UPF-2-UPF-3 complex-orchestrated nonsense-mediated mRNA decay (NMD) is a well-characterized eukaryotic cellular surveillance mechanism that not only degrades aberrant transcripts to protect the integrity of the transcriptome but also eliminates normal transcripts to facilitate appropriate cellular responses to physiological and environmental changes. Here, we describe the multifaceted regulatory roles of the Neurospora crassa UPF complex in catalase-3 (cat-3) gene expression, which is essential for scavenging H2O2-induced oxidative stress. First, losing UPF proteins markedly slowed down the decay rate of cat-3 mRNA. Second, UPF proteins indirectly attenuated the transcriptional activity of cat-3 gene by boosting the decay of cpc-1 and ngf-1 mRNAs, which encode a well-studied transcription factor and a histone acetyltransferase, respectively. Further study showed that under oxidative stress condition, UPF proteins were degraded, followed by increased CPC-1 and NGF-1 activity, finally activating cat-3 expression to resist oxidative stress. Together, our data illustrate a sophisticated regulatory network of the cat-3 gene mediated by the UPF complex under physiological and H2O2-induced oxidative stress conditions.


Assuntos
Peróxido de Hidrogênio , Neurospora , Peróxido de Hidrogênio/farmacologia , Catalase/genética , Degradação do RNAm Mediada por Códon sem Sentido , Estresse Oxidativo/genética
18.
Zhongguo Zhen Jiu ; 43(10): 1099-103, 2023 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-37802512

RESUMO

OBJECTIVE: To observe the effects on neural function, living ability and mental state of the patients with acute intracerebral hemorrhage (ICH), as well as aquaporin 4 (AQP4) in the serum after treated with electroacupuncture (EA) on the base of routine therapy of western medicine. METHODS: Seventy-two acute ICH patients were randomized into an observation group (36 cases, 4 cases dropped off) and a control group (36 cases, 2 cases dropped off). In the control group, the conventional treatment was delivered such as stopping bleeding, preventing re-hemorrhage, controlling blood pressure, mitigating neural edema and reducing intracranial pressure. In the observation group, on the base of the treatment in the control group, EA was supplemented. Acupoints included Shuigou (GV 26), bilateral Neiguan (PC 6) and Sanyinjiao (SP 6) etc. Electric stimulation was operated at Neiguan (PC 6) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave, and 2 Hz/100 Hz in frequency, tolerable current intensity. Electric stimulation was delivered for 30 min in each treatment, once daily and for 6 times per week. The duration of treatment was 2 weeks in the two groups. Before and after treatment, changes of the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and mini-mental state examination (MMSE), as well as AQP4 content in the serum were observed in the two groups; the efficacy and safety were compared between the two groups. RESULTS: The NIHSS scores and the serum AQP4 content decreased after treatment when compared with those before treatment in the two groups (P<0.05), while, MBI and MMSE scores increased (P<0.05). In the observation group, NIHSS score and serum AQP4 content were lower than those of the control group (P<0.05), and MBI and MMSE scores were higher (P<0.05). The total effective rate of the observation group was 93.8% (30/32), higher than that of the control group (73.5%, 25/34, P<0.05). The treatment in the two groups was safe, without adverse reactions and events occurring in the patients. CONCLUSION: Electroacupuncture, on the base of conventional treatment of western medicine, can effectively improve the neural function, living ability, mental state and serum AQP4 content of the patients with acute ICH. It is suggested that the effective treatment by electroacupuncture may be related to the regulation of the serum AQP4 content.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Humanos , Aquaporina 4 , Hemorragia Cerebral/terapia , Resultado do Tratamento , Pontos de Acupuntura
19.
Chem Sci ; 14(41): 11490-11498, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37886099

RESUMO

Development of new second near-infrared (NIR-II, 1000-1700 nm) luminophores is highly desirable, and d8 square-planar metal complexes with NIR-II phosphorescence have been rarely reported. Herein, we explore an asymmetric coordination paradigm to achieve the first creation of NIR-II phosphorescent isocyanorhodium(i) zwitterions. They show a strong tendency for aggregation in solution, arising from close Rh(i)⋯Rh(i) contacts that are further intensified by π-π stacking interactions and the hydrophilic-hydrophobic effect. Based on such supramolecular aggregation, zwitterions 2 and 5 are found to yield NIR-II phosphorescence emissions centered at 1005 and 1120 (1210, shoulder) nm in methanol-water mixed solvents, respectively. These two bands show red shifts to 1070 and 1130 (1230, shoulder) nm in the corresponding polymer nanoparticles in water. The resulting polymer nanoparticles can brighten in vivo tumor issues in the NIR-II region with a long-circulating time. In view of the synthetic diversity established by the asymmetric coordination paradigm, this work provides an extraordinary opportunity to explore NIR-II luminophores.

20.
ACS Macro Lett ; 12(10): 1345-1350, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37722025

RESUMO

Although graphite derivatives, such as graphene, graphene oxide, and reduced graphene oxide, have been widely used as lubricating oil additives to reduce friction and wear, their synthesis either proceeds with complicated procedures in low yield, suffering from high cost, or involves the utilization of highly corrosive chemicals, raising safety and environmental concerns. Therefore, the direct use of pristine graphite as a lubricating oil additive is indispensable for practical tribological applications. However, the realization of this idea has been seriously hampered by the incompatibility of graphite with lubricating base oils. In this work, we report a rational strategy to directly disperse graphite in base oils in the form of oleogels assisted by pyrene functionalized telechelic polymers under mild condition. The resulting oleogels exhibit long-time colloidal stability for more than one year, wherein the graphite has been exfoliated to in situ form graphene through π-π interactions with the pyrene-containing telechelics. Moreover, compared with the base oil, the graphite-based oleogels are found to exhibit remarkable reductions in friction and wear by up to 52% and 97%, respectively. Significantly, such tribological performances are comparable to those of exfoliated graphite derivatives. Taken collectively, directly using pristine graphite as a lubricating oil additive with superior tribological properties represents a revolutionary approach to create low-cost, green, and high-performance lubricants just based on pristine layered materials without involving any pre-exfoliations.

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