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1.
J Colloid Interface Sci ; 674: 1037-1047, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39002292

RESUMO

Cobalt-free, high-nickel cathode materials are essential for the sustainable evolution of energy storage technologies, reducing the dependence on resources with significant environmental and social implications and simultaneously improving the efficiency and cost effectiveness of batteries. This paper introduces a cobalt-free, high-nickel cathode material called 0.01B-LiNi0.98Mg0.01Zr0.01O2 (NMZB) developed using a novel blend of elements to enhance mechanical and surface chemical stability. Detailed evaluations confirmed the successful integration of Mg, Zr, and B into the particles, with Mg and Zr primarily located within the particle interior and B predominantly on the surface. This unique elemental configuration significantly improves the stability of the bulk phase and surface structure of the material. In addition, the refinement of primary particles within NMZB further enhances its mechanical stability. As a result, NMZB exhibits exceptional electrochemical stability, achieving 90.5 % capacity retention after 200 cycles at a 1C rate. This compositional strategy incorporates a high nickel content into layered materials while eliminating cobalt, which is crucial for advancing the development of cost effective and high-performance lithium-ion battery technology.

2.
Comput Biol Med ; 177: 108637, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38824789

RESUMO

Radiotherapy is a preferred treatment for brain metastases, which kills cancer cells via high doses of radiation meanwhile hardly avoiding damage to surrounding healthy cells. Therefore, the delineation of organs-at-risk (OARs) is vital in treatment planning to minimize radiation-induced toxicity. However, the following aspects make OAR delineation a challenging task: extremely imbalanced organ sizes, ambiguous boundaries, and complex anatomical structures. To alleviate these challenges, we imitate how specialized clinicians delineate OARs and present a novel cascaded multi-OAR segmentation framework, called OAR-SegNet. OAR-SegNet comprises two distinct levels of segmentation networks: an Anatomical-Prior-Guided network (APG-Net) and a Point-Cloud-Guided network (PCG-Net). Specifically, APG-Net handles segmentation for all organs, where multi-view segmentation modules and a deep prior loss are designed under the guidance of prior knowledge. After APG-Net, PCG-Net refines small organs through the mini-segmentation and the point-cloud alignment heads. The mini-segmentation head is further equipped with the deep prior feature. Extensive experiments were conducted to demonstrate the superior performance of the proposed method compared to other state-of-the-art medical segmentation methods.


Assuntos
Neoplasias Encefálicas , Planejamento da Radioterapia Assistida por Computador , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em Risco , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Processamento de Imagem Assistida por Computador/métodos
3.
Front Genet ; 15: 1296533, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919951

RESUMO

Small RNAs (sRNAs) are important non-coding RNA regulators that play key roles in the development and pathogenesis of plant pathogens, as well as in other biological processes. However, whether these abundant and varying sRNAs are involved in Phytophthora development or infection remains enigmatic. In this study, sRNA sequencing of 4 asexual stages of Phytophthora capsici (P. capsici), namely, as mycelia (HY), sporangia (SP), zoospores (ZO), cysts (CY), and pepper infected with P. capsici (IN), were performed, followed by sRNA analysis, microRNA (miRNA) identification, and miRNA target prediction. sRNAs were mainly distributed at 25-26 nt in HY, SP, and ZO but distributed at 18-34 nt in CY and IN. 92, 42, 176, 39, and 148 known miRNAs and 15, 19, 54, 13, and 1 novel miRNA were identified in HY, SP, ZO, CY, and IN, respectively. It was found that the expression profiles of known miRNAs vary greatly at different stages and could be divided into 4 categories. Novel miRNAs mostly belong to part I. Gene ontology (GO) analysis of known miRNA-targeting genes showed that they are involved in the catalytic activity pathway, binding function, and other biological processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis of novel miRNA-targeting genes showed that they are involved in the lysine degradation pathway. The expression of candidate miRNAs was validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and miRNAs were downregulated in PcDCL1 or PcAGO1 mutants. To further explore the function of the detected miRNAs, the precursor of a novel miRNA, miR91, was knockout by CRISPR-Cas9, the mutants displayed decreased mycelial growth, sporangia production, and zoospore production. It was found that 503142 (Inositol polyphosphate 5-phosphatase and related proteins) can be predicted as a target of miR91, and the interaction between miR91 and 503142 was verified using the tobacco transient expression system. Overall, our results indicate that the diverse and differentially expressed sRNAs are involved in the development and pathogenesis of P. capsici.

4.
J Cancer Res Clin Oncol ; 150(6): 317, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914670

RESUMO

INTRODUCTION: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. METHODOLOGY: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.


Assuntos
Neoplasias da Mama , Antígeno CD24 , Proliferação de Células , Progressão da Doença , MicroRNAs , RNA Longo não Codificante , Humanos , Antígeno CD24/genética , Antígeno CD24/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , MicroRNAs/genética , Animais , Camundongos , RNA Longo não Codificante/genética , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Movimento Celular/genética , Camundongos Endogâmicos BALB C , Prognóstico
5.
Nat Commun ; 15(1): 4641, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821955

RESUMO

Adsorption and activation of C-H bonds by photocatalysts are crucial for the efficient conversion of C-H bonds to produce high-value chemicals. Nevertheless, the delivery of surface-active oxygen species for C-H bond oxygenation inevitably needs to overcome obstacles due to the separated active centers, which suppresses the catalytic efficiency. Herein, Ni dopants are introduced into a monolayer Bi2WO6 to create cascaded active units consisting of unsaturated W atoms and Bi/O frustrated Lewis pairs. Experimental characterizations and density functional theory calculations reveal that these special sites can establish an efficient and controllable C-H bond oxidation process. The activated oxygen species on unsaturated W are readily transferred to the Bi/O sites for C-H bond oxygenation. The catalyst with a Ni mass fraction of 1.8% exhibits excellent toluene conversion rates and high selectivity towards benzaldehyde. This study presents a fascinating strategy for toluene oxidation through the design of efficient cascaded active units.

6.
Enzyme Microb Technol ; 178: 110446, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38626535

RESUMO

Formaldehyde (FALD) has gained prominence as an essential C1 building block in the synthesis of valuable chemicals. However, there are still challenges in converting FALD into commodities. Recently, cell-free biocatalysis has emerged as a popular approach for producing such commodities. Acetoin, also known as 3-hydroxy-2-butanone, has been widely used in food, cosmetic, agricultural and the chemical industry. It is valuable to develop a process to produce acetoin from FALD. In this study, a cell-free multi-enzyme catalytic system for the production of acetoin using FALD as the substrate was designed and constructed. It included three scales: FALD utilization pathway, glycolysis pathway and acetoin synthesis pathway. After the optimization of the reaction system, 20.17 mM acetoin was produced from 122 mM FALD, with a yield of 0.165 mol/mol, reaching 99.0% of the theoretical yield. The pathway provides a new approach for high-yield acetoin production from FALD, which consolidates the foundation for the production of high value-added chemicals using cheap one-carbon compounds.


Assuntos
Acetoína , Biocatálise , Formaldeído , Acetoína/metabolismo , Formaldeído/metabolismo , Sistema Livre de Células
7.
Int J Stem Cells ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658195

RESUMO

Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated- (p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4. IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.

8.
Cardiology ; : 1-14, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38643761

RESUMO

BACKGROUND: Ventricular septal rupture (VSR) is a mechanical issue that can occur following an acute myocardial infarction (AMI) and has a high mortality rate. It requires a comprehensive, team-based approach for prompt diagnosis and maintaining stable blood flow. While the occurrence of VSR has lessened over the past hundred years and advancements have been made in treatment techniques, the mortality rate within 30 days can still surpass 40 percent. Surgery is the primary treatment method. For patients with stable blood flow, it is generally considered safer to perform surgery 4-6 weeks after the AMI to repair the VSR. However, the timing of surgery for patients with early instability in their blood flow is still a topic of debate. SUMMARY: There is a lack of set criteria and standards to determine the best time for surgery in patients with VSR following an infarction who have unstable blood flow, especially when considering the use of blood circulation support devices and other techniques for maintaining blood flow that are used in clinical settings. KEY MESSAGES: This review outlines the features of different mechanical circulatory support devices utilized in treating VSR, along with the current scoring system designed to direct the treatment approach for VSR patients.

9.
PLoS One ; 19(4): e0298589, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38557643

RESUMO

BACKGROUND: Previous studies have found that psychological interventions have a positive effect on improving physical and psychological problems in colorectal cancer survivors. However, there is still a lack of high-quality evidence reviews that summarize and compare the impact of different psychological interventions. The aim of this study was to synthesize existing psychological interventions and use network meta-analysis to explore whether psychological interventions improve anxiety, depression, fatigue and quality of life in colorectal cancer (CRC) survivors. METHODS: We will extract relevant randomized controlled trials of psychological interventions for CRC survivors from eight electronic databases, including PubMed, Embase, The Cochrane Library, Web of Science, CINAHL, PsycInFO, CNKI, and Wanfang database. Two reviewers will independently screen the literature and extract data. The risk of bias of the included studies will be assessed using the RoB2: Revised Cochrane Risk of Bias Tool. We will then conduct paired meta-analyses and network meta-analyses of the extracted data, using a frequency-based framework and random effects models. DISCUSSION: To the best of our knowledge, this study is the first proposed qualitative and quantitative integration of existing evidence using systematic evaluation and network meta-analysis. This study will inform health policy makers, healthcare providers' clinical intervention choices and guideline revisions, and will help to reduce depression and anxiety in CRC survivors, reduce fatigue, improve quality of life.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Humanos , Metanálise em Rede , Intervenção Psicossocial , Depressão/terapia , Ansiedade/terapia , Sobreviventes/psicologia , Fadiga/terapia , Neoplasias Colorretais/terapia , Metanálise como Assunto , Revisões Sistemáticas como Assunto
10.
Cancer Nurs ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527098

RESUMO

BACKGROUND: Benefit finding is gaining attention as a strong predictor of quality of life, but few studies have addressed the mechanisms of its development. OBJECTIVE: The purpose of this study was to determine the relationship between illness perception and benefit finding in female thyroid cancer survivors and to further elucidate the mechanisms by which illness perception contributes to benefit finding through sense of coherence and self-disclosure. METHODS: A total of 280 female thyroid cancer survivors completed the questionnaire between January and August 2023. The study investigated participants' baseline information, illness perception, sense of coherence, self-disclosure, and benefit finding. The bootstrap method was used to test the chain mediation effect. RESULTS: The findings showed that in the chain-mediated model, illness perception negatively predicted sense of coherence (ß = -.475, P < .001) and self-disclosure (ß = -.335, P < .001). Sense of coherence positively predicted self-disclosure (ß = .272, P < .001) and benefit finding (ß = .251, P < .001). Self-disclosure positively predicted benefit finding (ß = .213, P < .001). The separate mediating roles of sense of coherence and self-disclosure between illness perception and benefit finding were both significant, as were the chained mediating roles of sense of coherence, and self-disclosure. CONCLUSION: This study provides a theoretical basis for elucidating the mechanisms of benefit finding and provides precise targets for clinical intervention. IMPLICATIONS FOR PRACTICE: Healthcare professionals can improve mental health outcomes by improving cancer survivors' disease awareness, fostering their sense of coherence, and encouraging moderate self-disclosure to achieve benefit finding.

11.
Diabetes ; 73(6): 879-895, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506804

RESUMO

Defective fatty acid oxidation (FAO) has been implicated in diabetic kidney disease (DKD), yet little is known about the role of carnitine palmitoyltransferase-1A (CPT1A), a pivotal rate-limiting enzyme of FAO, in the progression of DKD. Here, we investigate whether CPT1A is a reliable therapeutic target for DKD. We first confirmed the downregulation expression of CPT1A in glomeruli from patients with diabetes. We further evaluated the function of CPT1A in diabetic models. Overexpression of CPT1A exhibited protective effects in diabetic conditions, improving albuminuria and glomerular sclerosis as well as mitigating glomerular lipid deposits and podocyte injury in streptozotocin-induced diabetic mice. Mechanistically, CPT1A not only fostered lipid consumption via fatty acid metabolism pathways, thereby reducing lipotoxicity, but also anchored Bcl2 to the mitochondrial membrane, thence preventing cytochrome C release and inhibiting the mitochondrial apoptotic process. Furthermore, a novel transcription factor of CPT1A, FOXA1, was identified. We elucidate the crucial role of CPT1A in mitigating podocyte injury and the progression of DKD, indicating that targeting CPT1A may be a promising avenue for DKD treatment.


Assuntos
Apoptose , Carnitina O-Palmitoiltransferase , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Podócitos , Animais , Humanos , Masculino , Camundongos , Albuminúria/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/genética , Ácidos Graxos/metabolismo , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Podócitos/metabolismo , Podócitos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética
12.
Acta Pharm Sin B ; 14(3): 953-1008, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38487001

RESUMO

Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves as a significant indicator of malignant tumor transformation. The Warburg effect primarily impacts cancer occurrence by influencing the aerobic glycolysis pathway in cancer cells. Key enzymes involved in this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, and PKM2. Moreover, the expression of transcriptional regulatory factors and proteins, such as FOXM1, p53, NF-κB, HIF1α, and c-Myc, can also influence cancer progression. Furthermore, lncRNAs, miRNAs, and circular RNAs play a vital role in directly regulating the Warburg effect. Additionally, gene mutations, tumor microenvironment remodeling, and immune system interactions are closely associated with the Warburg effect. Notably, the development of drugs targeting the Warburg effect has exhibited promising potential in tumor treatment. This comprehensive review presents novel directions and approaches for the early diagnosis and treatment of cancer patients by conducting in-depth research and summarizing the bright prospects of targeting the Warburg effect in cancer.

13.
J Pediatr Nurs ; 77: e38-e53, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523049

RESUMO

PROBLEM: The phenomenon of emergence delirium in pediatric patients undergoing general anesthesia has garnered increasing attention in the academic community. While formal non-pharmaceutical interventions have demonstrated efficacy in mitigating this phenomenon, the diversity of intervention types and their varying degrees of effectiveness necessitate further discussion. A scoping review was conducted to identify and explicate the categorization, content elements, and outcomes measures of non-pharmacological interventions utilized to forestall the onset of emergence delirium in children undergoing general anesthesia. ELIGIBILITY CRITERIA: This review was conducted in accordance with the Arksey and O'Malley's methodology framework and PRISMA-ScR. It encompassed experimental and quasi-experimental studies that involved any non-pharmacological interventions during the perioperative period to prevent emergence delirium in children aged 0 to 18 years undergoing general anesthesia for elective surgery. SAMPLE: Thirty-two articles met the inclusion criteria, of which 29 were randomized controlled trials. The total sample size of the population was 4633. RESULTS: The scoping review revealed 10 non-pharmacological interventions, that included distraction intervention, visual preconditioning, virtual reality, parental participation, maternal voice, light drinking, acupuncture, auditory stimulation, monochromic light and breathing training. Emergence delirium, preoperative anxiety, and postoperative pain were the primary outcomes, and four assessment instruments were employed to measure the extent and incidence of emergence delirium. CONCLUSION: Numerous non-pharmacological interventions have been employed to prevent emergence delirium. Nevertheless, the effectiveness of some interventions is not yet evident. IMPLICATIONS: The utilization of visual preconditioning and distraction interventions appears to be an emerging area of interest.


Assuntos
Anestesia Geral , Delírio do Despertar , Humanos , Anestesia Geral/efeitos adversos , Delírio do Despertar/prevenção & controle , Criança , Adolescente , Pré-Escolar , Feminino , Lactente , Masculino
14.
Angew Chem Int Ed Engl ; 63(14): e202318897, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38326236

RESUMO

Mirror-image proteins (D-proteins) are useful in biomedical research for purposes such as mirror-image screening for D-peptide drug discovery, but the chemical synthesis of many D-proteins is often low yielding due to the poor solubility or aggregation of their constituent peptide segments. Here, we report a Lys-C protease-cleavable solubilizing tag and its use to synthesize difficult-to-obtain D-proteins. Our tag is easily installed onto multiple amino acids such as DLys, DSer, DThr, and/or the N-terminal amino acid of hydrophobic D-peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal-mediated deprotection, and yet can be completely removed by Lys-C protease under denaturing conditions to give the desired D-protein. The efficacy and practicality of the new method were exemplified in the synthesis of two challenging D-proteins: D-enantiomers of programmed cell death protein 1 IgV domain and SARS-CoV-2 envelope protein, in high yield. This work demonstrates that the enzymatic cleavage of solubilizing tags under denaturing conditions is feasible, thus paving the way for the production of more D-proteins.


Assuntos
Peptídeos , Proteínas , Proteínas/química , Peptídeos/química , Aminoácidos/química , Técnicas de Química Sintética/métodos , Peptídeo Hidrolases , Endopeptidases
15.
J Wound Care ; 33(2): 143-152, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38329830

RESUMO

OBJECTIVE: To identify the most important risk factors for predicting pressure injury (PI) occurrence in adult orthopaedic surgical patients based on investigation data, thereby identifying at-risk patients and facilitating formulation of an effective patient care strategy. METHOD: Patients were assessed with an instrument designed by the authors specifically for this study in a cross-sectional investigation following the STROBE checklist. The random forest method was adopted to select the most important risk factors and predict occurrence of PIs. RESULTS: A dataset of 27 risk factors from 1701 patients was obtained. A subset of the 15 most important risk factors was identified. The random forest method had a high prediction accuracy of 0.9733 compared with 0.9281 calculated with a logistic model. CONCLUSION: Results indicated that the selected 15 risk factors, such as activity ability, friction/shear force, skin type and anaesthesia score, performed very well in predicting the occurrence of PIs in adult orthopaedic surgical patients.


Assuntos
Ortopedia , Úlcera por Pressão , Adulto , Humanos , Estudos Transversais , Algoritmo Florestas Aleatórias , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Cicatrização , Fatores de Risco
16.
Aging (Albany NY) ; 16(1): 285-298, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38180746

RESUMO

Gastric cancer poses a serious threat to human health and affects the digestive system. The lack of early symptoms and a dearth of effective identification methods make diagnosis difficult, with many patients only receiving a definitive diagnosis at a malignant stage, causing them to miss out on optimal therapeutic interventions. Melanoma-associated antigen-A (MAGE-A) is part of the MAGE family and falls under the cancer/testis antigen (CTA) category. The MAGE-A subfamily plays a significant role in tumorigenesis, proliferation and migration. The expression, prognosis and function of MAGE-A family members in GC, however, remain unclear. Our research and screening have shown that MAGE-A11 was highly expressed in GC tissues and was associated with poor patient prognosis. Additionally, MAGE-A11 functioned as an independent prognostic factor in GC through Cox regression analysis, and its expression showed significant correlation with both tumour immune cell infiltration and responsiveness to immunotherapy. Our data further indicated that MAGE-A11 regulated GC cell proliferation and migration. Subsequently, our findings propose that MAGE-A11 may operate as a prognostic factor, having potential as an immunotherapy target for GC.


Assuntos
Proteínas de Neoplasias , Neoplasias Gástricas , Masculino , Humanos , Proteínas de Neoplasias/metabolismo , Antígenos de Neoplasias/metabolismo , Prognóstico , Neoplasias Gástricas/patologia , Imunoterapia , Biomarcadores
17.
iScience ; 27(1): 108608, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38174317

RESUMO

Magnetic resonance imaging (MRI) is a widely used imaging modality in clinics for medical disease diagnosis, staging, and follow-up. Deep learning has been extensively used to accelerate k-space data acquisition, enhance MR image reconstruction, and automate tissue segmentation. However, these three tasks are usually treated as independent tasks and optimized for evaluation by radiologists, thus ignoring the strong dependencies among them; this may be suboptimal for downstream intelligent processing. Here, we present a novel paradigm, full-stack learning (FSL), which can simultaneously solve these three tasks by considering the overall imaging process and leverage the strong dependence among them to further improve each task, significantly boosting the efficiency and efficacy of practical MRI workflows. Experimental results obtained on multiple open MR datasets validate the superiority of FSL over existing state-of-the-art methods on each task. FSL has great potential to optimize the practical workflow of MRI for medical diagnosis and radiotherapy.

18.
J Agric Food Chem ; 72(3): 1527-1538, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38193425

RESUMO

An estimated 240 fungicides are presently in use, but the direct targets for the majority remain elusive, constraining fungicide development and efficient resistance monitoring. In this study, we found that Pcα-actinin knockout did not influence the sensitivity of Phytophthora capsici to fluopicolide, which is a notable oomycete inhibitor. Using a combination of Bulk Segregant Analysis Sequencing and Drug Affinity Responsive Target Stability (DARTS) assays, the vacuolar H+-ATPase subunit a (PcVHA-a) was pinpointed as the target protein of fluopicolide. We also confirmed four distinct point mutations in PcVHA-a responsible for fluopicolide resistance in P. capsici through site-directed mutagenesis. Molecular docking, ATPase activity assays, and a DARTS assay suggested a fluopicolide-PcVHA-a interaction. Sequence analysis and further molecular docking validated the specificity of fluopicolide for oomycetes or fish. These findings support the claim that PcVHA-a is the target of fluopicolide, proposing vacuolar H+-ATPase as a promising target for novel fungicide development.


Assuntos
Fungicidas Industriais , Phytophthora , Fungicidas Industriais/farmacologia , Simulação de Acoplamento Molecular , Benzamidas/metabolismo , Phytophthora/genética , ATPases Translocadoras de Prótons/metabolismo , Doenças das Plantas
19.
Fish Shellfish Immunol ; 146: 109360, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38184181

RESUMO

As a lymphocyte-specific surface receptor belonging to the cysteine-rich superfamily of scavenger receptors, CD6 acts as a pattern recognition receptor for microbial components and is involved in the regulation of inflammatory responses. However, the characteristics and functions of CD6 molecules in lower vertebrates represented by teleost fish are unknown. In this study, a CD6 homolog (designated OnCD6) was characterized from Nile tilapia (Oreochromis niloticus), and establishing its role as a PRRs that participates in immune recognition. OnCD6 contains an open reading frame of 1872 bp that encodes a peptide of 623 amino acids, and contains two conserved SR domain. Multiple sequence alignment revealed that OnCD6 shares a relatively high level of identity with those of other species. Transcriptional expression analysis revealed that OnCD6 was constitutively expressed in immunes tissues such as head kidney and thymus. The expression level of OnCD6 in mainly immune tissues were found significantly upregulated after the injection of Streptococcus agalactiae (S. agalactiae). Moreover, OnCD6 protein was located in the head kidney and brain, mainly over the plasma membrane of lymphocytes in these immune tissues. In vitro experiments showed that CD6 extracellular protein bound to and aggregated several Gram-positive and -negative bacterial strains through the recognition of bacterial surface conserved components LPS and LTA etc. In vivo experiments demonstrated that overexpression OnCD6 before S. agalactiae challenge significantly improved tilapia survival, and this was concomitant with reduced bacterial load and pro-inflammatory cytokines (IL-1ß and TNF-α). Taken together, our results illustrated the function of CD6 molecular pattern recognition receptors (PRRs) is conserved and plays an important role in antibacterial infection.


Assuntos
Ciclídeos , Doenças dos Peixes , Infecções Estreptocócicas , Animais , Streptococcus agalactiae/fisiologia , Sequência de Aminoácidos , Citocinas/metabolismo , Inflamação , Proteínas de Peixes/química , Infecções Estreptocócicas/veterinária , Regulação da Expressão Gênica
20.
Photodiagnosis Photodyn Ther ; 45: 103918, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070632

RESUMO

Epidermodysplasia verruciformis (EV) is a rare inherited immune disease characterized by pityriasis versicolor-like macules, hyperpigmented or hypopigmented warty papules and irregular reddish-brown plaques, mainly on the face, neck and extremities. Some therapeutic options include medications, lifestyle changes, ALA-PDT, surgery and so on. But there is no cure for EV and thus the clinical management is challenging. We report a case of EV that was refractory to multiple therapies and achieved an encouraging result with a combination therapy of surgery and 5-aminolevulinic acid photodynamic therapy (ALA-PDT).


Assuntos
Epidermodisplasia Verruciforme , Fotoquimioterapia , Verrugas , Humanos , Epidermodisplasia Verruciforme/tratamento farmacológico , Ácido Aminolevulínico/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico
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