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1.
Dent Mater ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39322445

RESUMO

OBJECTIVES: This study was to investigate the effects of optimized microstructured surfaces on bond strength and bond durability of the latest nanoparticle jetting (NPJ)-printed zirconia. METHODS: Zirconia microstructured surfaces with different geometries and void volume were analyzed through three-dimensional finite element analysis for surface micromorphology optimization. Zirconia disks and cylinders were additively manufactured by an NPJ 3D printer (N = 128). They were randomly divided into four groups based on surface micromorphology optimization and airborne-particle abrasion (APA) treatment before they were bonded using 10-methacryloloxydecyl dihydrogen phosphate (MDP) containing resin cement (Clearfil SA luting cement). The shear bond strengths (SBSs) were tested before and after 10,000 thermocycles and were analyzed by one-way ANOVA analysis. Failure modes were determined by optical microscopy. Zirconia surfaces were analyzed with X-ray diffraction, scanning electron microscopy, and three-dimensional interference microscopy. RESULTS: The optimized microstructured surface was characterized by circular microstructures with 60 % void volume, about 20 µm of depths, about 10 µm of undercuts, and consistent beam widths. The optimized microstructured surface combined with APA treatment and MDP-containing resin cement possessed the highest SBSs both before and after thermocycling aging (P<0.05). The greater reductions of zirconia bond strengths occurred when the zirconia were not treated with APA (P<0.05). SIGNIFICANCE: The optimized microstructured zirconia surface with circular microstructures and 60 % void volume fabricated by the latest NPJ printing technology could greatly enhance the zirconia bond strength and durability in combination with APA treatment and application of MDP-containing resin cement, which might be promising for adhesively bonded indirect restorations of NPJ-printed zirconia.

2.
Int J Mol Sci ; 25(17)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39273167

RESUMO

Selenium is a vital trace mineral that is crucial for maintaining regular biological processes in aquatic animals. In this study, a four-week dietary trial was carried out to assess the impact of bio-fermented selenium (Bio-Se) on the growth and immune response of Chinese mitten crabs, Eriocheir sinensis. The crabs were randomly allocated to five dietary treatment groups, each receiving a different dose of Bio-Se. The doses included 0, 0.3, 0.6, 1.5, and 3.0 mg/kg and were accurately measured in basal diet formulations. The results showed the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) in the 1.5 mg/kg Bio-Se group were the highest, and 3.0 mg/kg of Bio-Se has an inhibitory effect on the WGR, SGR, and SR. The activities of the immune enzymes, including glutathione peroxidase (GPX), superoxide dismutase (SOD), and acid phosphatase (ACP), of the hepatopancreas were significantly (p < 0.05) increased in the 1.5 mg/kg Bio-Se group, while they decreased (p < 0.05) in the 3.0 mg/kg feeding group compared to the 0 mg/kg feeding group. The concentration of maleic dialdehyde (MDA) exhibited the opposite pattern. Similarly, the mRNA expression levels of antimicrobial peptides (ALF-1, Crus-1, and LYS), ERK, and Relish genes were also observed to be the highest in the 1.5 mg/kg Bio-Se group compared with the other groups. Furthermore, the administration of 1.5 mg/kg of Bio-Se resulted in an increase in the thickness of the intestinal plica and mucosal layer, as well as in alterations in the intestinal microbial profile and bacterial diversity compared to the dose of 0 mg/kg of Bio-Se. Notably, the population of the beneficial bacterial phylum Fusobacteria was increased after crabs were fed the 1.5 mg/kg Bio-Se diet. In conclusion, the oral administration of 1.5 mg/kg of Bio-Se improved the growth efficiency, antioxidant capabilities, immunity, and intestinal health of E. sinensis. Through a broken-line analysis of the WGR against dietary Bio-Se levels, optimal dietary Bio-Se levels were determined to be 1.1 mg/kg. These findings contribute valuable insights to the understanding of crab cultivation and nutrition.


Assuntos
Braquiúros , Suplementos Nutricionais , Microbioma Gastrointestinal , Selênio , Animais , Selênio/farmacologia , Braquiúros/crescimento & desenvolvimento , Braquiúros/microbiologia , Braquiúros/imunologia , Braquiúros/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Fermentação , Ração Animal , Glutationa Peroxidase/metabolismo , Superóxido Dismutase/metabolismo , Hepatopâncreas/metabolismo , Hepatopâncreas/efeitos dos fármacos
3.
Pediatr Infect Dis J ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39259854

RESUMO

BACKGROUND: Severity of illness determination for children with acute hematogenous osteomyelitis should be accomplished during the earliest stages of evaluation to guide treatment and establish prognosis. This study objectively defines an outcome of complicated osteomyelitis and explores an illness severity-based model with an improved ability to predict this outcome as soon and accurately as possible, comparing it to existing models. METHODS: Children with Staphylococcus aureus acute hematogenous osteomyelitis (n = 438) were retrospectively studied to identify adverse events and predictors of severity. The outcome of complicated osteomyelitis was ultimately defined as the occurrence of any major or at least 3 minor adverse events, which occurred in 52 children. Twenty-four clinical and laboratory predictors were evaluated through univariate and stacked multivariable regression analyses of chronologically distinct groups of variables. Receiver operating characteristic curve analyses were conducted to compare models. RESULTS: Accelerated Severity of Illness Score included: triage tachycardia [odds ratio: 10.2 (95% confidence interval: 3.48-32.3], triage tachypnea [6.0 (2.4-15.2)], C-reactive proteininitial ≥17.2 mg/dL [4.5 (1.8-11.8)], white blood cell count band percentageinitial >3.8% [4.6 (2.0-11.0)], hemoglobininitial ≤10.4 g/dL [6.0 (2.6-14.7)], methicillin-resistant S. aureus [3.0 (1.2-8.5)], septic arthritis [4.5 (1.8-12.3)] and platelet nadir [7.2 (2.7-20.4)]. The receiver operating characteristic curve of Accelerated Severity of Illness Score [area under the curve = 0.96 (0.941-0.980)] were superior to those of Modified Severity of Illness Score = 0.903 (0.859-0.947), Acute Score for Complications of Osteomyelitis Risk Evaluation = 0.878 (0.830-0.926) and Chronic Score for Complications of Osteomyelitis Risk Evaluation = 0.858 (0.811-0.904). Successive receiver operating characteristic curve analyses established an exponentially increasing risk of complicated osteomyelitis for children with mild (0/285 or 0%), moderate (4/63 or 6.3%), severe (15/50 or 30.0%) and hyper-severe (33/40 or 82.5%) acute hematogenous osteomyelitis (P<0.0001). CONCLUSIONS: This study improves upon previous severity of illness models by identifying early predictors of a rigorously defined outcome of complicated osteomyelitis.

4.
BMC Cancer ; 24(1): 1140, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266997

RESUMO

In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.


Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsênio , Recidiva Local de Neoplasia , Neuroblastoma , Terapia de Salvação , Humanos , Trióxido de Arsênio/administração & dosagem , Trióxido de Arsênio/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Feminino , Masculino , Pré-Escolar , Criança , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Topotecan/administração & dosagem , Topotecan/uso terapêutico , Topotecan/efeitos adversos , Lactente , Resultado do Tratamento , Adolescente , Resistencia a Medicamentos Antineoplásicos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos
5.
Dev Comp Immunol ; 161: 105242, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39128619

RESUMO

Molting is a key biological process of crustaceans, which is mainly regulated by 20-hydroxyecdyone (20E). The molting cycle could be divided into three main stages including pre-molt, post-molt and inter-molt stages. The mechanism of immune regulation during molting process still requires further exploration. Yorkie (Yki) is a pivotal transcription factor in the Hippo signaling pathway, and it plays an essential role in regulating cell growth and immune response. In the present study, a Yki gene was identified from Eriocheir sinensis (designed as EsYki), and the regulatory role of EsYki in controlling the expression of antimicrobial peptide genes throughout the molting process was investigated. The mRNA expression level of EsYki was higher at the pre-molt stage compared to the post-molt stage and inter-molt stage. Following the injection of 20E, there was a notable and consistent rise in the EsYki mRNA expression in haemocytes. The increase was observed from 3 h to 48 h with the maximum level at 12 h. And the phosphorylation of Yki in the haemocytes was also significantly up-regulated at 3 h post 20E injection. Moreover, the levels of EsYki mRNA expression at three molting stages were significantly increased post Aeromonas hydrophila stimulation. The maximum level was detected at post-molt stage following A. hydrophila stimulation, while the lowest level was observed at inter-molt stage. The expression pattern of EsCrus was in contrast to EsCrus. After EsYki mRNA transcripts were inhibited by Yki inhibitor (CA3), the mRNA expression levels of EsCrus1 and EsCrus2 following A. hydrophila stimulation were significantly elevated. Furthermore, the phosphorylation level of NF-κB was also increased following the inhibition of Yki. Collectively, our findings indicated that EsYki could be induced by 20E and has a suppressive effect on the expression of EsCrus via inhibiting NF-κB during molting process. This research contributes to the understanding of the immunological regulation mechanism during molting process in crustaceans.


Assuntos
Aeromonas hydrophila , Proteínas de Artrópodes , Braquiúros , Hemócitos , Muda , Animais , Braquiúros/imunologia , Braquiúros/genética , Proteínas de Artrópodes/metabolismo , Proteínas de Artrópodes/genética , Hemócitos/metabolismo , Hemócitos/imunologia , Aeromonas hydrophila/fisiologia , Aeromonas hydrophila/imunologia , Proteínas de Sinalização YAP/metabolismo , Transdução de Sinais , Transativadores/metabolismo , Transativadores/genética , Peptídeos Antimicrobianos/metabolismo , Peptídeos Antimicrobianos/genética , Ecdisterona/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Imunidade Inata
6.
Sensors (Basel) ; 24(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39124117

RESUMO

Wireless Power Transfer (WPT) has become a key technology to extend network lifetime in Wireless Rechargeable Sensor Networks (WRSNs). The traditional omnidirectional recharging method has a wider range of energy radiation, but it inevitably results in more energy waste. By contrast, the directional recharging mode enables most of the energy to be focused in a predetermined direction that achieves higher recharging efficiency. However, the MC (Mobile Charger) in this mode can only supply energy to a few nodes in each direction. Thus, how to set the location of staying points of the MC, its service sequence and its charging orientation are all important issues related to the benefit of energy replenishment. To address these problems, we propose a Fuzzy Logic-based Directional Charging (FLDC) scheme for Wireless Rechargeable Sensor Networks. Firstly, the network is divided into adjacent regular hexagonal grids which are exactly the charging regions for the MC. Then, with the help of a double-layer fuzzy logic system, a priority of nodes and grids is obtained that dynamically determines the trajectory of the MC during each round of service, i.e., the charging sequence. Next, the location of the MC's staying points is optimized to minimize the sum of charging distances between MC and nodes in the same grid. Finally, the discretized charging directions of the MC at each staying point are adjusted to further improve the charging efficiency. Simulation results show that FLDC performs well in both the charging benefit of nodes and the energy efficiency of the MC.

7.
BDJ Open ; 10(1): 65, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138157

RESUMO

BACKGROUND: The treatment strategy for patients with severe tooth wear associated with Class II Division 2 malocclusion remains a major challenge for dental practitioners. OBJECTIVES: To systematically review and summarize the literature on treatment strategies, restoration procedures and clinical outcomes for Class II Division 2 malocclusion patients with severe tooth wear. METHODS: A literature review was conducted using Pubmed, Embase, the Cochrane Library, and Web of Science to identify eligible articles. Publications until October 16th, 2023 were searched independently and cross-checked by two researchers. RESULTS: Of 1513 articles screened, 10 reports detailed treatment processes, including six males and four females aged 34-68 years old. Four articles recorded pre-treatment freeway space (FWS) values ranging from 5 to 9 mm. All ten cases had significant occlusal vertical dimension (OVD) loss and the increase in OVD after treatment ranged from 1 to 7 mm. Pre-prosthetic orthodontic treatment was performed in two cases, in one of which only the maxillary region was orthodontically treated. The most common restorations provided were full coverage restorations. In most cases, temporary restorations were applied before the permanent restorations for eight weeks to six months. Four different sequences of final restoration were proposed. Follow-up ranged from four months to six years and included seven patients, one of them showed symptoms of temporomandibular disorder (TMD). CONCLUSIONS: A multidisciplinary team (MDT) approach to treatment is recommended. Consideration of pre-prosthetic orthodontic treatment is essential. Commonly used cephalometric measurements for anterior teeth include the interincisal angle and collum angle. The increases in OVD ranging from 1 to 7 mm can be effectively accommodated. Temporary restorations are recommended to accommodate the OVD, and the transition periods of 8 weeks to 6 months help the patients adapted well. Four different sequences for final rehabilitation have demonstrated positive clinical outcomes. Full crown restorations have emerged as the preferred choice for the ultimate restoration of these patients.

8.
Food Sci Nutr ; 12(8): 5587-5604, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39139959

RESUMO

This study aims to elucidate the detailed metabolic implications of varying monacolin K levels and sterilization methods on Monascus-fermented rice products (MFRPs), acclaimed for their health benefits and monacolin K content. Advanced metabolite profiling of various MFRP variants was conducted using ultrahigh-performance liquid chromatography coupled with tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS). Statistical analysis encompassed t-tests, ANOVA, and multivariate techniques including PCA, PLS-DA, and OPLS-DA. Notable variations in metabolites were observed across MFRPs with differing monacolin K levels, particularly in variants such as MR1-S, MR1.5-S, MR2-S, and MR3-S. Among the 524 identified metabolites, significant shifts were noted in organic acids, derivatives, lipids, nucleosides, and organic oxygen compounds. The study also uncovered distinct metabolic changes resulting from different sterilization methods and the use of highland barley as a fermentation substitute for rice. Pathway analysis shed light on affected metabolic pathways, including those involved in longevity regulation, cGMP-PKG signaling, and the biosynthesis of unsaturated fatty acids. The research provides critical insights into the complex metabolic networks of MFRPs, underscoring the impact of fermentation substrates and conditions on monacolin K levels and their health implications. This study not only guides the nutritional optimization of MFRPs but also emphasizes the strategic importance of substrate choice and sterilization techniques in enhancing the nutritional and medicinal value of these functional foods.

9.
Front Immunol ; 15: 1439367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206203

RESUMO

Leukocyte cell-derived chemotaxin 2 (LECT2) is linked to various immune diseases. Previously, we reported that serum LECT2 levels correlate with disease severity in atopic dermatitis (AD) patients. To investigate the role of LECT2 in AD and elucidate its potential mechanisms, we used LECT2 to treat an AD mouse model induced by 1-Chloro-2,4-dinitrobenzene (DNCB) in LECT2 knockout (KO) and wild-type (WT) mice, and an AD cell model using TNF-α/IFN-γ-induced HaCaT cells. Inflammatory factors and barrier proteins were analyzed by histology, immunohistochemistry, RT-qPCR, ELISA, and Western Blot. Activation of the NF-κB signaling pathway was evaluated by Western Blot and immunofluorescence. In the AD mouse model, LECT2 treatment increased epidermal and dermal thickness, mast cell infiltration, and downregulated barrier proteins. Inflammatory factors were increased in skin lesions and serum. In the AD cell model, LECT2 decreased barrier protein levels and increased inflammatory factor levels, enhancing NF-κB P65 nuclear translocation. These results indicate that LECT2 exacerbates AD-like responses by dysregulating the NF-κB signaling pathway, highlighting its potential as a therapeutic target for AD management.


Assuntos
Dermatite Atópica , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos Knockout , NF-kappa B , Transdução de Sinais , Animais , Humanos , Camundongos , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Dinitroclorobenzeno , Células HaCaT , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Pele/patologia , Pele/metabolismo , Pele/imunologia , Masculino
10.
Fish Shellfish Immunol ; 153: 109842, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39153580

RESUMO

Molting is a crucial biological process of crustaceans. Crustaceans go through three separate stages throughout their molting process, including pre-molt, post-molt and inter-molt. However, the exact mechanism of immunological modulation during molting remains unclear. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been extensively documented to participate in immune defense. In the present study, a TRAF6 gene with two TRAF-type zinc finger domains was identified from Eriocheir sinensis (designed as EsTRAF6), and its role in regulating immune response during molting process was explored. The mRNA expression level of EsTRAF6 at pre-molt stage was higher than that at post-molt stage and inter-molt stage. After Aeromonas hydrophila stimulation, the expression levels of EsTRAF6, EsRelish and anti-lipopolysaccharide factors (ALFs) genes exhibited a considerable increase at three molting stages. Subsequently, the expression patterns of EsTRAF6 and EsRelish in response to the treatment with 20-hydroxyecdysone (20E) were examined. The mRNA expression of EsTRAF6 and EsRelish were significantly increased at 12 h after 20E injection. Additionally, the protein expression level of TRAF6 was also up-regulated in 20E group compared to control group. Furthermore, the role of EsTRAF6 in regulating the anti- ALFs expression at pre-molt stage post A. hydrophila stimulation was investigated. Following the inhibition of the EsTRAF6 transcript using RNAi or the injection of inhibitor (TMBPS), there was a notable decrease of the EsALF1, EsALF2 and EsALF3 transcripts. Moreover, a significant reduction in the phosphorylation level of NF-κB at pre-molt stage was observed after A. hydrophila stimulation in TRAF6-inhibited crabs. Collectively, our results suggest that EsTRAF6 could be induced by 20E and promoted the EsALFs expression by activating NF-κB at pre-molt stage, which provides a novel insight into the research of immune regulatory mechanism during the process of molting of crustaceans.


Assuntos
Proteínas de Artrópodes , Decápodes , NF-kappa B , Fator 6 Associado a Receptor de TNF , Animais , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Muda/imunologia , Muda/genética , NF-kappa B/genética , NF-kappa B/metabolismo , NF-kappa B/imunologia , Filogenia , Alinhamento de Sequência/veterinária , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/imunologia
11.
Mater Today Bio ; 27: 101138, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39027677

RESUMO

In contrast to conventional therapies that require repeated dosing, gene therapy can treat diseases by correcting defective genes after a single transfection and achieving cascade amplification, and has been widely studied in clinical settings. However, nucleic acid drugs are prone to catabolism and inactivation. A variety of nucleic acid drug vectors have been developed to protect the target gene against nuclease degradation and increase the transformation efficiency and safety of gene therapy. In addition, gene therapy is often combined with chemotherapy, phototherapy, magnetic therapy, ultrasound, and other therapeutic modalities to improve the therapeutic effect. This review systematically introduces ribonucleic acid (RNA) interference technology, antisense oligonucleotides, and clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) genome editing. It also introduces the commonly used nucleic acid drug vectors, including viral vectors (adenovirus, retrovirus, etc.), organic vectors (lipids, polymers, etc.), and inorganic vectors (MOFs, carbon nanotubes, mesoporous silica, etc.). Then, we describe the combined gene therapy modalities and the pathways of action and report the recent applications in solid tumors of the combined gene therapy. Finally, the challenges of gene therapy in solid tumor treatment are introduced, and the prospect of application in this field is presented.

12.
Front Oncol ; 14: 1336106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962268

RESUMO

Objective: The escape from T cell-mediated immune surveillance is an important cause of death for patients with acute myeloid leukemia (AML). This study aims to identify clonal heterogeneity in leukemia progenitor cells and explore molecular or signaling pathways associated with AML immune escape. Methods: Single-cell RNA sequencing (scRNA-seq) was performed to identified AML-related cellular subsets, and intercellular communication was analyzed to investigate molecular mechanisms associated with AML immune escape. Bulk RNA sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs) related to hematopoietic stem cell progenitors (HSC-Prog) in AML, and critical ore signaling pathways and hub genes were found by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The mRNA level of the hub gene was verified using quantitative real-time PCR (qRT-PCR) and the protein level of human leukocyte antigen A (HLA-A) using enzyme-linked immuno sorbent assay (ELISA). Results: scRNA-seq analysis revealed a large heterogeneity of HSC-Prog across samples, and the intercellular communication analysis indicated a strong association between HSC-Prog and CD8+-T cells, and HSC-Prog also had an association with HLA-A. Transcriptome analysis identified 1748 DEGs, enrichment analysis results showed that non-classical wnt signaling pathway was associated with AML, and 4 pathway-related genes (RHOA, RYK, CSNK1D, NLK) were obtained. After qRT-PCR and ELISA validation, hub genes and HLA-A were found to be down-regulated in AML and up-regulated after activation of the non-classical Wnt signaling pathway. Conclusion: In this study, clonal heterogeneity of HSC-Prog cells in AML was identified, non-classical wnt signaling pathways associated with AML were identified, and it was verified that HLA-A could be upregulated by activation of non-classical wnt signaling, thereby increasing antigen presentation.

13.
Acta Biomater ; 184: 383-396, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936753

RESUMO

Triple-negative breast cancer (TNBC) is a relatively "cold" tumour with low immunogenicity compared to other tumour types. Especially, the immune checkpoint inhibitors to treat metastatic TNBC only shows the modest immune response rates. Here, we used Chlorella vulgaris as a bioreactor to synthesize an efficient nanobomb (Bio-MnSe) aimed at eliciting systemic anti-tumour immune response. Despite possessing extremely low Mn content, Bio-MnSe effectively produced more ROS and activated stronger cGAS-STING signal pathway compared to pure Se nanoparticles and free Mn2+ ions, promoting the infiltration of natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) in tumour, effectively turning "cold" tumour into "hot" tumour, and achieving strong antitumour immunotherapy. Additionally, the use of αPD-L1 as an immune checkpoint antagonist further increased the anti-tumour immune response of Bio-MnSe, resulting in enhanced anti-tumour effects. Doxorubicin (Dox), an immunogenic cell death (ICD) inducer, was combined with Bio-MnSe to form Bio-MnSe@Dox. This Bio-MnSe@Dox not only directly damaged tumour cells and induced tumour ICD but also promoted dendritic cell maturation, cytotoxic T lymphocyte infiltration, and NK cell recruitment, synergistically intensifying anti-tumour immune responses and suppressing tumour relapse and lung metastasis. Collectively, our findings propose an effective strategy for transforming 'cold' tumours to 'hot' ones, thereby advancing the development of anti-tumour immune drugs. STATEMENT OF SIGNIFICANCE: A biogenic MnSe (Bio-MnSe) nanocomposite was synthesized using Chlorella vulgaris as a bioreactor for enhanced immunotherapy of TNBC. Bio-MnSe demonstrated a stronger ability to activate the cGAS-STING signalling pathway and generate more ROS compared to pure Se nanoparticles and free Mn2+ ions. Apoptotic cells induced by Bio-MnSe released a significant amount of interferon, leading to the activation of T and natural killer (NK) cells, ultimately transforming immunologically 'cold' breast tumours to 'hot' tumours and enhancing the tumour's response to immune checkpoint inhibitors. The combination of Bio-MnSe with Dox or αPD-L1 further enhanced the anti-tumour immune response, fostering dendritic cell maturation, infiltration of cytotoxic T lymphocytes, and recruitment of NK cells, thereby enhancing the anti-tumour immunotherapy of TNBC.


Assuntos
Morte Celular Imunogênica , Manganês , Proteínas de Membrana , Nucleotidiltransferases , Transdução de Sinais , Animais , Feminino , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos , Humanos , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Nucleotidiltransferases/metabolismo , Proteínas de Membrana/metabolismo , Manganês/química , Manganês/farmacologia , Doxorrubicina/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Selênio/química , Selênio/farmacologia , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Antígeno B7-H1/metabolismo , Camundongos Endogâmicos BALB C , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos
14.
Cancer Lett ; 597: 217072, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38885807

RESUMO

CD39 is a pivotal enzyme in cancer, regulating immune response and tumor progression via extracellular ATP and adenosine in the tumor microenvironment (TME). Beyond its established immunoregulatory function, CD39 influences cancer cell angiogenesis and metabolism, opening new frontiers for therapeutic interventions. Current research faces gaps in understanding CD39's full impact across cancer types, with ongoing debates about its potential beyond modulating immune evasion. This review distills CD39's multifaceted roles, examining its dual actions and implications for cancer prognosis and treatment. We analyze the latest therapeutic strategies, highlighting the need for an integrated approach that combines molecular insights with TME dynamics to innovate cancer care. This synthesis underscores CD39's integral role, charting a course for precision oncology that seeks to unravel controversies and harness CD39's therapeutic promise for improved cancer outcomes.


Assuntos
Apirase , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/patologia , Neoplasias/terapia , Neoplasias/metabolismo , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Apirase/metabolismo , Animais , Antígenos CD/metabolismo , Neovascularização Patológica
15.
BMC Womens Health ; 24(1): 307, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783362

RESUMO

BACKGROUND: This study aimed to analyze the relationship between physical activity and the risk of premenstrual syndrome among college students. METHODS: Eligible studies were searched from the PubMed, Web of Science, and Embase databases. The link between physical activity and the risk of premenstrual syndrome was evaluated using odds ratio (OR) and 95% confidence interval (CI). The heterogeneity of the included studies was tested and their sources were explored by subgroup analysis. A sensitivity analysis was performed to assess the effect of a single study on the pooled results. The included studies were evaluated for publication bias. Five moderate-quality studies were included in this meta-analysis. RESULTS: Physical activity levels were negatively associated with risk of premenstrual syndrome among college students (OR [95%CI] = 1.46 [1.09, 1.96], P = .011). The pooled results were not influenced after being stratified by the study region and whether multi-factor correction was performed or not. Publication bias was not observed in the included studies. CONCLUSION: A high level of physical activity is dramatically associated with a reduced risk of premenstrual syndrome among female college students.


Assuntos
Exercício Físico , Síndrome Pré-Menstrual , Estudantes , Humanos , Síndrome Pré-Menstrual/epidemiologia , Feminino , Estudantes/estatística & dados numéricos , Exercício Físico/fisiologia , Universidades , Adulto Jovem , Fatores de Risco , Adulto
16.
Front Pharmacol ; 15: 1393409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774213

RESUMO

Recent research on traditional Chinese medicine (TCM) saponin pharmacokinetics has revealed transformative breakthroughs and challenges. The multicomponent nature of TCM makes it difficult to select representative indicators for pharmacokinetic studies. The clinical application of saponins is limited by their low bioavailability and short half-life, resulting in fluctuating plasma concentrations. Future directions should focus on novel saponin compounds utilizing colon-specific delivery and osmotic pump systems to enhance oral bioavailability. Optimizing drug combinations, such as ginsenosides with aspirin, shows therapeutic potential. Rigorous clinical validation is essential for practical applications. This review emphasizes a transformative era in saponin research, highlighting the need for clinical validation. TCM saponin pharmacokinetics, guided by traditional principles, are in development, utilizing multidisciplinary approaches for a comprehensive understanding. This research provides a theoretical basis for new clinical drugs and supports rational clinical medication.

17.
Dev Comp Immunol ; 157: 105194, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38754572

RESUMO

In crustaceans, the steroid hormone 20-hydroxyecdysone (20E) initiates molting, and the molting process is also regulated by energy metabolism. AMPK is an energy sensor and plays a critical role in systemic energy balance. Here, the regulatory mechanism in the interaction between 20E and AMPK was investigated in Chinese mitten crab, Eriocheir sinensis. The results showed that the 20E concentration and the mRNA expression levels of 20E receptors in hepatopancreas were down-regulated post AMPK activator (AICAR) treatment, and were up-regulated after AMPK inhibitor (Compound C) injection in crabs. Besides, the molt-inhibiting hormone (MIH) gene expression in eyestalk showed the opposite patterns in response to the AICAR and Compound C treatment, respectively. Further investigation found that there was a significant reduction in 20E concentration post PI3K inhibitor (LY294002) treatment, and the phosphorylation level of PI3K was increased in hepatopancreas after AMPK inhibitor injection. On the other hand, the positive regulation of PI3K-mediated activation of AMPK was also observed, the phosphorylation levels of AMPKα, AMPKß and PI3K in hepatopancreas were significantly increased post 20E injection. In addition, the phosphorylation levels of AMPKα and AMPKß induced by 20E were decreased after the injection of PI3K inhibitor. Taken together, these results suggest that the regulatory cross-talk between 20E and AMPK is likely to act through PI3K pathway in E. sinensis, which appeared to be helpful for a better understanding in molting regulation.


Assuntos
Proteínas Quinases Ativadas por AMP , Braquiúros , Ecdisterona , Hepatopâncreas , Muda , Fosfatidilinositol 3-Quinases , Animais , Braquiúros/imunologia , Ecdisterona/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Hepatopâncreas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Hormônios de Invertebrado/metabolismo , Cromonas/farmacologia , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Ribonucleotídeos/farmacologia , Morfolinas/farmacologia , Proteínas de Artrópodes/metabolismo , Proteínas de Artrópodes/genética , Fosforilação , Metabolismo Energético
18.
Phys Rev E ; 109(4-1): 044101, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38755872

RESUMO

Temperature is a fundamental concept in thermodynamics. In macroscopic thermodynamics, systems possess their own intrinsic temperature which equals the reservoir temperature when they equilibrate. In stochastic thermodynamics for simple systems at the microscopic level, thermodynamic quantities other than temperature (a deterministic parameter of the reservoir) are stochastic. To bridge the disparity in the perspectives about temperature between the micro- and macroregimes, we assign a generic mesoscopic N-body system an intrinsic fluctuating temperature T in this work. We simplify the complicated dynamics of numerous particles to one stochastic differential equation with respect to T, where the noise term accounts for finite-size effects arising from random energy transfer between the system and the reservoir. Our analysis reveals that these fluctuations make the extensive quantities (in the thermodynamic limit) deviate from being extensive. Moreover, we derive finite-size corrections, characterized by heat capacity of the system, to the Jarzynski equality. A possible violation of the principle of maximum work that scales with N^{-1} is also discussed. Additionally, we examine the impact of temperature fluctuations in a finite-size Carnot engine. We show that irreversible entropy production resulting from the temperature fluctuations of the working substance diminishes the average efficiency of the cycle as η_{C}-〈η〉∼N^{-1}, highlighting the unattainability of the Carnot efficiency η_{C} for mesoscopic heat engines even under the quasistatic limit. Our general framework paves the way for further exploration of nonequilibrium thermodynamics and the corresponding finite-size effects in a mesoscopic regime.

19.
IEEE Trans Vis Comput Graph ; 30(5): 2507-2516, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38437114

RESUMO

While speech interaction finds widespread utility within the Extended Reality (XR) domain, conventional vocal speech keyword spotting systems continue to grapple with formidable challenges, including suboptimal performance in noisy environments, impracticality in situations requiring silence, and susceptibility to inadvertent activations when others speak nearby. These challenges, however, can potentially be surmounted through the cost-effective fusion of voice and lip movement information. Consequently, we propose a novel vocal-echoic dual-modal keyword spotting system designed for XR headsets. We devise two different modal fusion approches and conduct experiments to test the system's performance across diverse scenarios. The results show that our dual-modal system not only consistently outperforms its single-modal counterparts, demonstrating higher precision in both typical and noisy environments, but also excels in accurately identifying silent utterances. Furthermore, we have successfully applied the system in real-time demonstrations, achieving promising results. The code is available at https://github.com/caizhuojiang/VE-KWS.


Assuntos
Gráficos por Computador , Fala , Movimento
20.
ACS Appl Mater Interfaces ; 16(13): 16351-16362, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38515323

RESUMO

Poly(ethylene oxide) (PEO)-based electrolytes have been extensively studied for all-solid-state lithium-metal batteries due to their excellent film-forming capabilities and low cost. However, the limited ionic conductivity and poor mechanical strength of the PEO-based electrolytes cannot prevent the growth of undesirable lithium dendrites, leading to the failure of batteries. Metal-organic frameworks (MOFs) are functional materials with a periodic porous structure that can improve the electrochemical performance of PEO-based electrolytes. However, the enhancement effect of MOFs with different metal centers and the interaction mechanism with PEO remain unclear. Herein, MOF-74s with Cu or Ni centers are prepared and used as fillers of PEO-based electrolytes. Adding 15 wt % of Cu-MOF-74 to the PEO-based electrolyte (15%Cu-MOF/P-Li) effectively improves the ionic conductivity, lithium transference number, and mechanical strength of the PEO-based electrolyte simultaneously. Furthermore, the ordered pore channels of Cu-MOF-74 provide uniform Li-ion transport pathways, facilitating homogeneous Li+ deposition. As a result, the lithium symmetric cell with 15%Cu-MOF/P-Li shows stable cycles for 1080 h at 0.1 mA cm-2 and 0.1 mAh cm-2, and the Li | 15% Cu-MOF/P-Li | LFP full cell exhibits a long cycle life up to 200 cycles at 60 °C and 0.5 C, with a capacity retention rate of 89.7%.

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