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1.
Pestic Biochem Physiol ; 200: 105845, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582577

RESUMO

7-dehydrocholesterol (7-DHC) is a key intermediate product used for biosynthesis of molting hormone. This is achieved through a series of hydroxylation reactions catalyzed by the Halloween family of cytochrome P450s. Neverland is an enzyme catalyzes the first reaction of the ecdysteroidogenic pathway, which converts dietary cholesterol into 7-DHC. However, research on the physiological function of neverland in orthopteran insects is lacking. In this study, neverland from Locusta migratoria (LmNvd) was cloned and analyzed. LmNvd was mainly expressed in the prothoracic gland and highly expressed on days 6 and 7 of fifth instar nymphs. RNAi-mediated silencing of LmNvd resulted in serious molting delays and abnormal phenotypes, which could be rescued by 7-DHC and 20-hydroxyecdysone supplementation. Hematoxylin and eosin staining results showed that RNAi-mediated silencing of LmNvd disturbed the molting process by both promoting the synthesis of new cuticle and suppressing the degradation of the old cuticle. Quantitative real-time PCR results suggested that the mRNA expression of E75 early gene and chitinase 5 gene decreased and that of chitin synthase 1 gene was markedly upregulated after knockdown of LmNvd. Our results suggest that LmNvd participates in the biosynthesis process of molting hormone, which is involved in regulating chitin synthesis and degradation in molting cycles.


Assuntos
Locusta migratoria , Muda , Animais , Muda/genética , Ecdisona/metabolismo , Locusta migratoria/genética , Locusta migratoria/metabolismo , Interferência de RNA , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-38430150

RESUMO

Objective: Gaucher disease (GD) is a clinically rare single-gene recessive lysosomal storage disease mainly divided into three subtypes I to III. This report aims to present a case of type IIIb GD in a Chinese child with a focus on the manifestation of hearing loss and the importance of early diagnosis and monitoring. Methods: The patient underwent a routine physical examination upon admission, followed by CT scans of the chest and abdomen, MRI of the brain, and bone marrow smear examination. The patient's GBA enzyme activity, Lyso-GL-1 levels, and GBA gene expression were analyzed using tandem mass spectrometry (MS/MS) and next-generation sequencing technology. Finally, auditory brainstem response (ABR) testing was conducted. Results: This report presented a case of a Chinese boy with hematological manifestations as the first symptom, followed by hepatosplenomegaly, and the bilateral femurs showed obvious Erlenmeyer flask-like changes. Combined with GBA enzyme activity, Lyso-GL-1 and GBA genotype analysis results, the boy was initially diagnosed as type I GD. During the follow-up, the boy developed nystagmus, bilateral ABR V wave threshold increased, V/I amplitude ratio <0.5, accompanied by delayed growth and development, and finally diagnosed as type IIIb. Conclusions: This case suggests the necessity of neuropathy monitoring in patients with type I GD during the early stages of the disease. This includes EEG, neuro-ophthalmological examination, and auditory function assessment, which can help reflect the progression of neuropathy and facilitate the early diagnosis of type III GD.

3.
Commun Biol ; 7(1): 336, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493211

RESUMO

Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function. Using the HMM-based approach we screened 50 high-scoring candidate sequences in Escherichia coli, leading to the discovery of 13 new TDases. The X-ray crystal structures of two new enzymes from Legionella species were determined, and the ability of anhydrotetracycline to inhibit their tetracycline-inactivating activity was confirmed. Using the MSA-based approach we identified 31 amino acid positions 100% conserved across all known TDase sequences. The roles of these positions were analyzed by alanine-scanning mutagenesis in two TDases, to study the impact on cell and in vitro activity, structure, and stability. These results expand the diversity of TDase sequences and provide valuable insights into the roles of important residues in TDases, and flavin monooxygenases more broadly.


Assuntos
Antibacterianos , Tetraciclina , Tetraciclina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Tetraciclinas/farmacologia , Oxigenases de Função Mista , Escherichia coli/química , Resistência Microbiana a Medicamentos , Flavinas
4.
Heliyon ; 10(5): e26200, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495146

RESUMO

Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.

5.
ACS Appl Mater Interfaces ; 16(13): 16011-16028, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38529951

RESUMO

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.


Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Animais , Hidrogéis/farmacologia , Escherichia coli , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Fototerapia , Infecções Bacterianas/tratamento farmacológico , Antibacterianos/farmacologia , Carbono , Modelos Animais de Doenças , Nitrogênio
6.
Biomater Sci ; 12(6): 1558-1572, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38305728

RESUMO

In this work, positively charged N-carbazoleacetic acid decorated CuxO nanoparticles (CuxO-CAA NPs) as novel biocompatible nanozymes have been successfully prepared through a one-step hydrothermal method. CuxO-CAA can serve as a self-cascading platform through effective GSH-OXD-like and POD-like activities, and the former can induce continuous generation of H2O2 through the catalytic oxidation of overexpressed GSH in the bacterial infection microenvironment, which in turn acts as a substrate for the latter to yield ˙OH via Fenton-like reaction, without introducing exogenous H2O2. Upon NIR irradiation, CuxO-CAA NPs possess a high photothermal conversion effect, which can further improve the enzymatic activity for increasing the production rate of H2O2 and ˙OH. Besides, the photodynamic performance of CuxO-CAA NPs can produce 1O2. The generated ROS and hyperthermia have synergetic effects on bacterial mortality. More importantly, CuxO-CAA NPs are more stable and biosafe than Cu2O, and can generate electrostatic adsorption with negatively charged bacterial cell membranes and accelerate bacterial death. Antibacterial results demonstrate that CuxO-CAA NPs are lethal against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) through destroying the bacterial membrane and disrupting the bacterial biofilm formation. MRSA-infected animal wound models show that CuxO-CAA NPs can efficiently promote wound healing without causing toxicity to the organism.


Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Animais , Peróxido de Hidrogênio , Fototerapia , Nanopartículas/química , Infecções Bacterianas/tratamento farmacológico , Escherichia coli , Antibacterianos/química
7.
J Robot Surg ; 18(1): 39, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231274

RESUMO

The objective of this study is to compare the satisfaction of patients undergoing robot-assisted retroperitoneal laparoscopy adrenalectomy under the ambulatory mode and conventional mode. Basic information and clinical data of patients who underwent robotic-assisted posterior laparoscopic adrenalectomy between June 2020 and June 2023 were queried from our case system. The Outpatient and Ambulatory Surgery Consumer Assessment of Healthcare Providers and Systems Survey (OAS CAHPS®) was used to investigate patient satisfaction with preoperative preparation, discharge counseling, postoperative instructions, postoperative pain, and satisfaction with nursing work. The stats R package was used to select the appropriate statistic for the statistics based on the characteristics of the data. A total of 311 patients who underwent robot-assisted posterior laparoscopic adrenalectomy were enrolled in our case system. There were no statistical differences between the two groups in gender, age, body mass index, ASA classification, laterality, maximum tumor diameter, type of resection, hormonal activity, disease type, pathological classification, duration of surgery, estimated intraoperative bleeding, postoperative complications and follow-up period that were compared between the two groups of patients. There were no significant differences in preoperative preparation score, discharge counseling score, postoperative guidance score and nursing care satisfaction score (P > 0.05). Postoperative hospitalization, peristalsis time, defecation time, time to first postoperative mobilization, duration of indwelling drain and hospitalization costs in patients in the ambulatory model group were significantly less than patients in the conventional model group (P < 0.001). Patients in the ambulatory model group had significantly higher postoperative pain relief scores than patients in the conventional model group. In conclusion, our data suggest that patient satisfaction is equal between the conventional and ambulatory mode of performing robotic-assisted adrenalectomy. Patient satisfaction was probably associated with shorter hospitalization days, adequate preoperative preparation and standardized, high-quality post-discharge information and guidance.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Satisfação do Paciente , Adrenalectomia , Assistência ao Convalescente , Alta do Paciente , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Dor Pós-Operatória
8.
Biomater Sci ; 12(2): 425-439, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38050470

RESUMO

In this work, we successfully constructed Mn-coordinated nitrogen-carbon nanoparticles (Mn-N-C NPs) exhibiting multienzyme-like activities. In a bacterial infectious microenvironment, the POD-like and OXD-like activities of Mn-N-C NPs could synergistically trigger the generation of ROS (˙OH and O2˙-), causing oxidative damage to the bacterial cell membrane for killing bacteria. Alternatively, in neutral or weak alkaline normal tissues, the excessive O2˙- could be converted into O2 and H2O2via the SOD-like ability of Mn-N-C NPs, and subsequently their CAT-like activity catalyzed excess H2O2 into H2O and O2 for protecting normal cells through the antioxidant defense. Mn-N-C NPs also possessed a good NIR-photothermal performance, which could enhance their POD-like and OXD-like activities. Furthermore, Mn-N-C NPs could facilitate the GSH oxidation process and disrupt the intrinsic balance in the bacterial protection microenvironment with the assistance of H2O2, which is beneficial for rapid bacterial death. Undoubtedly, the Mn-N-C NPs + H2O2 system showed the highest antibacterial activity when irradiated with an 808 nm laser, destroying the bacterial membrane and causing the efflux of proteins. Moreover, the Mn-N-C NPs + H2O2 system was immune to the development of bacterial resistance and could efficiently disrupt the formation of a bacterial biofilm with negligible cytotoxicity and low hemolysis ratio. Finally, Mn-N-C NPs exhibited an excellent antibacterial performance in vivo and could accelerate wound healing without cellular inflammation production. Therefore, due to their significant therapeutic effects, Mn-N-C NPs show great potential in fighting antibiotic-resistant bacteria.


Assuntos
Infecções Bacterianas , Nanopartículas , Humanos , Peróxido de Hidrogênio , Antioxidantes , Infecções Bacterianas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
9.
Leukemia ; 38(2): 250-257, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38001171

RESUMO

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1+ rather than KMT2A-rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Criança , Humanos , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Neoplasia Residual/diagnóstico , China , Tetraspanina 29
11.
Pestic Biochem Physiol ; 196: 105627, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945261

RESUMO

BACKGROUND: The cap 'n' collar (Cnc) belongs to the Basic Leucine Zipper (bZIP) transcription factor super family. Cap 'n' collar isoform C (CncC) is highly conserved in the animal kingdom. CncC contributes to the regulation of growth, development, and aging and takes part in the maintenance of homeostasis and the defense against endogenous and environmental stress. Insect CncC participates in the regulation of various kinds of stress-responsive genes and is involved in the development of insecticide resistance. RESULTS: In this study, one full-length CncC sequence of Locusta migratoria was identified and characterized. Upon RNAi silencing of LmCncC, insecticide bioassays showed that LmCncC played an essential role in deltamethrin and imidacloprid susceptibility. To fully investigate the downstream genes regulated by LmCncC and further identify the LmCncC-regulated genes involved in deltamethrin and imidacloprid susceptibility, a comparative transcriptome was constructed. Thirty-five up-regulated genes and 73 down-regulated genes were screened from dsLmCncC-knockdown individuals. We selected 22 LmCncC-regulated genes and verified their gene expression levels using RT-qPCR. Finally, six LmCYP450 genes belonging to the CYP6 family were selected as candidate detoxification genes, and LmCYP6FD1 and LmCYP6FE1 were further validated as detoxification genes of insecticides via RNAi, insecticide bioassays, and metabolite identification. CONCLUSIONS: Our data suggest that the locust CncC gene is associated with deltamethrin and imidacloprid susceptibility via the regulation of LmCYP6FD1 and LmCYP6FE1, respectively.


Assuntos
Inseticidas , Locusta migratoria , Humanos , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Locusta migratoria/genética , Locusta migratoria/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
12.
Small ; : e2306713, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919863

RESUMO

Luminescent metal clusters have attracted great interest in current research; however, the design synthesis of Al clusters with color-tunable luminescence remains challenging. Herein, an [Al8 (OH)8 (NA)16 ] (Al8 , HNA = nicotinic acid) molecular cluster with dual luminescence properties of fluorescence and room-temperature phosphorescence (RTP) is synthesized by choosing HNA ligand as phosphor. Its prompt photoluminescence (PL) spectrum exhibits approximately white light emission at room temperature. Considering that halogen atoms can be used to regulate the RTP property by balancing the singlet and triplet excitons, different CdX2 (X- = Cl- , Br- , I- ) are introduced into the reactive system of the Al8 cluster, and three new Al8 cluster-based metal-organic frameworks, {[Al8 Cd3 Cl5 (OH)8 (NA)17 H2 O]·2HNA}n (CdCl2 -Al8 ), {[Al8 Cd4 Br7 (OH)8 (NA)16 CH3 CN]·NA·HNA}n (CdBr2 -Al8 ) and {[Al8 Cd8 I16 (OH)8 (NA)16 ]}n (CdI2 -Al8 ) are successfully obtained. They realize the color tunability from blue to yellow at room temperature. The origination of fluorescence and phosphorescence has also been illustrated by structure-property analysis and theoretical calculation. This work provides new insights into the design of multicolor luminescent metal cluster-based materials and develops advanced photo-functional materials for multicolor display, anti-counterfeiting, and encryption applications.

13.
J Cancer Res Clin Oncol ; 149(17): 15609-15622, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37656243

RESUMO

OBJECTIVE: To identify key gene in childhood acute lymphoblastic leukemia (ALL) through weighted gene co-expression network analysis (WGCNA), and their enriched biological functions and signaling pathways. METHODS: Array data of the GSE73578 dataset, involving 46 childhood ALL samples, were acquired from the Gene Expression Omnibus (GEO) database. Hub modules associated with childhood ALL were screened out by WGCNA. Enriched biological functions and signaling pathways were then identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by overlapping those between down-regulated genes in GSE73578, GSE4698 and the hub module. Guilt by association (GBA) was adopted to verify the function of the identified KIF11 gene and to predict its target genes. Regulatory effects of KIF11 on the proliferation and cell cycle progression of ALL in vitro were determined by cytological experiments. RESULTS: WGCNA showed that the yellow module was the most relevant to childhood ALL treatment, containing 698 genes that were enriched in cell division, mitotic nuclear division, DNA replication and DNA repair, cell cycle, DNA replication and the P53 signaling pathway. The KIF11 gene was screened out and predicted as a cell cycle mediator in childhood ALL. Knockdown of KIF11 in ALL cells inhibited cell proliferation and arrested cell cycle progression in G2/M phase. CONCLUSIONS: The KIF11 gene is critical in the treatment process of childhood ALL, which is a promising therapeutic target for childhood ALL.


Assuntos
Regulação Neoplásica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Ciclo Celular/genética , Perfilação da Expressão Gênica , Divisão Celular , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Redes Reguladoras de Genes , Cinesinas/genética
14.
iScience ; 26(10): 107857, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37752954

RESUMO

Optogenetic manipulation with single-cell resolution can be achieved by two-photon excitation. However, this frequently requires relatively high laser powers. Here, we developed a novel strategy that can improve the efficiency of current two-photon stimulation technologies by positioning fluorescent proteins or small fluorescent molecules with high two-photon cross-sections in the vicinity of opsins. This generates a highly localized source of endogenous single-photon illumination that can be tailored to match the optimal opsin absorbance. Through neuronal and vascular stimulation in the live mouse brain, we demonstrate the utility of this technique to achieve efficient opsin stimulation, without loss of cellular resolution. We also provide a theoretical framework for understanding the potential advantages and constrains of this methodology, with directions for future improvements. Altogether, this fluorescence transfer illumination method opens new possibilities for experiments difficult to implement in the live brain such as all-optical neural interrogation and control of regional cerebral blood flow.

15.
Cell Transplant ; 32: 9636897231193067, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37650431

RESUMO

Cord blood (CB) transplantation is a promising treatment for hematologic malignancies due to its strong graft-versus-leukemia effect and a low incidence of graft-versus-host disease. However, the risk of infection caused by delayed engraftment has limited its clinical application. In this study, we compared the single-cell RNA-seq of CB, bone marrow (BM), and granulocyte colony-stimulating factor primed BM to understand the differences between these grafts from a comprehensive view, and verified some differences in our clinical data of patients receiving transplantation. We focused on the biological features of key cell types involving the hematopoietic reconstitution and immune reconstitution. Based on the comparison of homing signal and differentiation potential of hematopoietic stem/progenitor cells (HSPCs), CB exhibited a lower content of HSPCs with weaker homing ability but higher stemness than BM. In addition, CB had a higher proportion of naïve T cells, while BM had a higher abundance of effector and memory T cells. Notably, the CD4+ naïve T cells in CB were prone to differentiate into Tregs. In response to neoantigens, the immune activation interactions between T cells and antigen-presenting cells were strong in CB, including CD40_CD40LG, IL16_CD4, and so on. In our clinical data, the subpopulation variations of T cells and the status of monocytes after transplantation were consistent with the results of the single-cell RNA-seq study above. CB, as a new birth system, is immature and active; several mechanisms contribute to its good anti-tumor effect, which can be introduced to other grafts. These findings provide insights into the development of new strategies for hematologic malignancies treatment.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Medula Óssea , Sangue Fetal , Análise da Expressão Gênica de Célula Única , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Medula Óssea/métodos
16.
Pediatr Blood Cancer ; 70(10): e30545, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37438860

RESUMO

BACKGROUND: Dysregulation of microRNAs (miRNAs) targeting genes in the PI3K/Akt pathway has been implicated in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). However, the impact of genetic variants in these miRNAs on ALL susceptibility has not been extensively explored in the Chinese population. METHODS: To address this gap, we conducted a case-control study to evaluate the association between genetic variants in five PI3K/AKT pathway-related miRNAs (miR-149, miR-126, miR-492, miR-612, and miR-423) and childhood ALL susceptibility in the Chinese population. Additionally, we investigated the effects of the rs2292832 mutation on ALL cell proliferation and apoptosis. RESULTS: Our analyses revealed that the miR-149 rs2292832 mutant heterozygous CT genotype was more frequent in the control group than in the ALL cases, indicating a protective effect against ALL (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63-0.97, p = .024). Stratification analyses further revealed that the miR-149 rs2292832 CC genotype was associated with an increased risk of childhood ALL in subgroups of older children, females, those with parents who never smoked or drank alcohol, those living in painted houses, those with B-ALL, and those with high-risk ALL. Finally, we observed that the rs2292832 mutation inhibited ALL cell proliferation and induced apoptosis (p = .001), providing a potential mechanism by which this genetic variant may influence ALL susceptibility. CONCLUSION: Our study highlights the significant association between the miR-149 rs2292832 genetic variant and childhood ALL susceptibility in the Chinese population. These findings expand our understanding of the complex genetic landscape underlying ALL and have implications for the development of personalized therapeutic strategies.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Feminino , Humanos , Adolescente , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Genótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Predisposição Genética para Doença
17.
PeerJ Comput Sci ; 9: e1227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346676

RESUMO

3D (three-dimensional) models are widely applied in our daily life, such as mechanical manufacture, games, biochemistry, art, virtual reality, and etc. With the exponential growth of 3D models on web and in model library, there is an increasing need to retrieve the desired model accurately according to freehand sketch. Researchers are focusing on applying machine learning technology to 3D model retrieval. In this article, we combine semantic feature, shape distribution features and gist feature to retrieve 3D model based on interactive attention convolutional neural networks (CNN). The purpose is to improve the accuracy of 3D model retrieval. Firstly, 2D (two-dimensional) views are extracted from 3D model at six different angles and converted into line drawings. Secondly, interactive attention module is embedded into CNN to extract semantic features, which adds data interaction between two CNN layers. Interactive attention CNN extracts effective features from 2D views. Gist algorithm and 2D shape distribution (SD) algorithm are used to extract global features. Thirdly, Euclidean distance is adopted to calculate the similarity of semantic feature, the similarity of gist feature and the similarity of shape distribution feature between sketch and 2D view. Then, the weighted sum of three similarities is used to compute the similarity between sketch and 2D view for retrieving 3D model. It solves the problem that low accuracy of 3D model retrieval is caused by the poor extraction of semantic features. Nearest neighbor (NN), first tier (FT), second tier (ST), F-measure (E(F)), and discounted cumulated gain (DCG) are used to evaluate the performance of 3D model retrieval. Experiments are conducted on ModelNet40 and results show that the proposed method is better than others. The proposed method is feasible in 3D model retrieval.

18.
Math Biosci Eng ; 20(5): 9062-9079, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37161234

RESUMO

With the development of multimedia technology, the number of 3D models on the web or in databases is becoming increasingly larger and larger. It becomes more and more important to classify and retrieve 3D models. 3D model classification plays important roles in the mechanical design field, education field, medicine field and so on. Due to the 3D model's complexity and irregularity, it is difficult to classify 3D model correctly. Many methods of 3D model classification pay attention to local features from 2D views and neglect the 3D model's contour information, which cannot express it better. So, accuracy the of 3D model classification is poor. In order to improve the accuracy of 3D model classification, this paper proposes a method based on EfficientNet and Convolutional Neural Network (CNN) to classify 3D models, in which view feature and shape feature are used. The 3D model is projected into 2D views from different angles. EfficientNet is used to extract view feature from 2D views. Shape descriptors D1, D2, D3, Zernike moment and Fourier descriptors of 2D views are adopted to describe the 3D model and CNN is applied to extract shape feature. The view feature and shape feature are combined as discriminative features. Then, the softmax function is used to determine the 3D model's category. Experiments are conducted on ModelNet 10 dataset. Experimental results show that the proposed method achieves better than other methods.

19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(3): 579-584, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37248587

RESUMO

Objective: To explore the potential interactions among obesity-related proteins in the pathogenic process of breast cancer (BC) in women. Methods: We conducted a case-control study, enrolling 279 primary breast cancer cases and 260 age-frequency-matched healthy women between April 2014 and May 2015. Based on the evidence of previous published literature on obesity-related proteins and BC risks, we selected proteins that received more attention and measured the plasma levels of these proteins by enzyme-linked immunosorbent assay (ELISA). After stratification of the subjects according to their menopausal status, an analytic strategy combining multivariate logistic regression and generalized multifactor dimensionality reduction (GMDR) was used to explore the effect of the possible interactions of these proteins on BC risk. Results: There were marginal high-order interactions among insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), C-reactive protein (CRP), resistin (RETN), soluble leptin receptor (sOB-R), and adiponectin (ADP) in premenopausal women (with the balanced accuracy for the testing set being 59.01%, cross-validation consistency being 10/10, and permutation test P=0.05). There were high-order interactions among leptin (LEP), sOB-R, ADP, CRP, IGFBP3 and visfatin (VF) in postmenopausal women (with the balanced accuracy for the testing set being 67.31%, cross-validation consistency being 10/10, and permutation test P=0.01). Along with an increase in the number of obesity-related proteins to which the subjects were exposed, the risk of developing breast cancer gradually increased in both pre- and postmenopausal women ( OR pre =2.18, 95% CI: 1.69-2.82; OR post =2.41, 95% CI: 1.75-3.32). Conclusions: This preliminary study suggested high-order interactions among obesity-related proteins on BC risk in both pre- and postmenopausal women. In future studies, close attention should be given to these potential interactions when these proteins are used jointly as predictors, as well as in developing a comprehensive risk scoring system for BC.


Assuntos
Neoplasias da Mama , Leptina , Feminino , Humanos , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Pós-Menopausa , Fatores de Risco , Fator de Crescimento Insulin-Like I/análise , Proteína C-Reativa/análise , Obesidade/complicações
20.
Int J Hyperthermia ; 40(1): 2211753, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37211351

RESUMO

OBJECTIVE: To investigate the influencing factors of ultrasound-guided HIFU (USgHIFU) ablation for adenomyosis with a non-perfused volume ratio (NPVR)≥50%. METHODS: A total of 299 patients with adenomyosis who underwent USgHIFU ablation were enrolled. Quantitative signal intensity (SI) analysis was performed on T2WI and dynamic enhancement type. The energy efficiency factor (EEF) was defined as the ultrasound energy delivered for ablating 1 mm3 of tissue. NPVR ≥ 50% was used as the criterion for technical success. Adverse effects and complications were recorded. Logistic regression analyses of variables were conducted to identify the factors affecting NPVR ≥ 50%. RESULTS: The median NPVR was 53.5% (34.7%). There were 159 cases in the NPVR ≥ 50% group and 140 cases in the NPVR < 50% group. The EEF in NPVR < 50.0% group was significantly higher than that in NPVR ≥ 50% group (p < 0.05). The incidence of intraoperative adverse effects and postoperative adverse events in the NPVR < 50% group were higher than those in the NPVR ≥ 50% group (p < 0.05 for both). Logistic regression analysis showed that abdominal wall thickness, SI difference on T2WI between adenomyosis and rectus abdominis, and enhancement type on T1WI were protective factors for NPVR ≥ 50% (p < 0.05), while the history of childbirth was an independent risk factor (p < 0.001). CONCLUSIONS: Compared with NPVR < 50%, NPVR ≥ 50% did not increase the intraprocedural and postprocedural adverse reactions. The possibility of NPVR ≥ 50% was higher in patients with thinner abdominal walls, showed slight enhancement of adenomyosis on T1WI, with a history of childbirth, or in whom the SI difference on T2WI between adenomyosis and rectus abdominis was more minor.


Assuntos
Adenomiose , Ablação por Ultrassom Focalizado de Alta Intensidade , Feminino , Gravidez , Humanos , Adenomiose/diagnóstico por imagem , Adenomiose/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Ultrassonografia , Fatores de Risco , Parto Obstétrico , Resultado do Tratamento , Imageamento por Ressonância Magnética , Estudos Retrospectivos
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