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1.
Heart Views ; 25(1): 46-49, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774555

RESUMO

Patients who suffer from severe tricuspid regurgitation (TR) and who are at high surgical risk have no standard care therapy. Therefore, minimally invasive and safer methods are sought. K-clip™, the first ultrasound-positioned interventional tricuspid annuloplasty instrument intended for percutaneous transcatheter repair. We report a patient with severe functional TR and high surgical risk who underwent K-clip™ tricuspid annuloplasty under echocardiography and fluoroscopy guidance.

2.
Nat Med ; 30(5): 1395-1405, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693247

RESUMO

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.


Assuntos
Paralisia Cerebral , Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Heterogeneidade Genética , Humanos , Paralisia Cerebral/genética , Feminino , Masculino , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Exoma/genética , Lactente , Testes Genéticos , Estudos de Coortes , Predisposição Genética para Doença , Recém-Nascido
3.
Artigo em Inglês | MEDLINE | ID: mdl-38730084

RESUMO

PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

4.
Technol Cancer Res Treat ; 23: 15330338241248576, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38693824

RESUMO

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.


Assuntos
Biomarcadores Tumorais , Leucemia Mieloide Aguda , MicroRNAs , Tretinoína , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Biomarcadores Tumorais/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , Prognóstico , Tretinoína/farmacologia , Tretinoína/uso terapêutico
5.
BMJ Open ; 14(5): e081940, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719309

RESUMO

OBJECTIVES: This study aimed to determine the potential profiles of self-psychological adjustment in patients with lung cancer undergoing chemotherapy, including sense of coherence (SOC) and positive cognitive emotion regulation (PCER). The relationship between these profiles with post-traumatic growth (PTG) and the relevant factors of self-psychological adjustment in different profiles was analysed. DESIGN: Cross-sectional study. SETTING: Patients with lung cancer undergoing chemotherapy in China. PARTICIPANTS: A total of 330 patients with lung cancer undergoing chemotherapy were recruited out of which 321 completed the questionnaires effectively. METHODS: Latent profile analysis was used to identify self-psychological adjustment classes based on the two subscales of the Sense of Coherence Scale and Cognitive Emotion Regulation Questionnaire. One-way analysis of variance and multinomial logistic regression were performed to examine the subgroup association with characteristics and PTG. RESULTS: Three latent profiles of self-psychological adjustment were identified: low level (54.5%), high SOC-low PCER (15.6%) and high PCER (29.9%). The results of univariate analysis showed a significant difference in PTG scores among different self-psychological adjustment subgroups (F=11.55, p<0.001). Patients in the high-PCER group were more likely living in urban areas (OR=2.41, 95% CI 1.17 to 4.97, p=0.02), and time since cancer diagnosis was ≥6 months and <1 year (OR=3.54, 95% CI 1.3 to 9.64, p<0.001). CONCLUSION: This study revealed that most patients with lung cancer undergoing chemotherapy belonged to the low-level group. Three profiles are associated with PTG. There were differences in characteristics between patients treated with chemotherapy for lung cancer in the high-PCER and low-PCER groups. Thus, these profiles provide useful information for developing targeted individualised interventions based on demographic characteristics that would assist PTG in patients with lung cancer undergoing chemotherapy.


Assuntos
Neoplasias Pulmonares , Crescimento Psicológico Pós-Traumático , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/psicologia , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Idoso , Adaptação Psicológica , Senso de Coerência , Inquéritos e Questionários , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Adulto , Ajustamento Emocional
6.
Nanomaterials (Basel) ; 14(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38727372

RESUMO

Perovskite solar cells (PSCs) have attracted much attention due to their low cost, high efficiency, and solution processability. With the development of various materials in perovskite solar cells, self-assembled monolayers (SAMs) have rapidly become an important factor in improving power conversion efficiency (PCE) due to their unique physical and chemical properties and better energy level matching. In this topical review, we introduced important categories of self-assembled molecules, energy level modulation strategies, and various characteristics of self-assembled molecules. In addition, we focused on reviewing the application of self-assembled molecules in solar cells, and explained the changes that self-assembled molecules bring to PSCs by introducing the mechanism and effect of self-assembled molecules. Finally, we also elaborated on the challenges currently faced by self-assembled molecules and provided prospects for their applications in other optoelectronic devices.

7.
BMC Plant Biol ; 24(1): 426, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769488

RESUMO

To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L- 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L- 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L- 1 IAA.


Assuntos
Ácidos Indolacéticos , Reguladores de Crescimento de Plantas , Selênio , Vitis , Ácidos Indolacéticos/metabolismo , Selênio/metabolismo , Vitis/efeitos dos fármacos , Vitis/crescimento & desenvolvimento , Vitis/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Estresse Fisiológico , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/efeitos dos fármacos , Biomassa
8.
Nat Genet ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714866

RESUMO

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.

9.
Brain Behav Immun ; 119: 919-944, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38718909

RESUMO

Neuroinflammation and accumulation of Amyloid Beta (Aß) accompanied by deterioration of special memory are hallmarks of Alzheimer's disease (AD). Effective preventative and treatment options for AD are still needed. Microglia in AD brains are characterized by elevated levels of microRNA-17 (miR-17), which is accompanied by defective autophagy, Aß accumulation, and increased inflammatory cytokine production. However, the effect of targeting miR-17 on AD pathology and memory loss is not clear. To specifically inhibit miR-17 in microglia, we generated mannose-coated lipid nanoparticles (MLNPs) enclosing miR-17 antagomir (Anti-17 MLNPs), which are targeted to mannose receptors readily expressed on microglia. We used a 5XFAD mouse model (AD) that recapitulates many AD-related phenotypes observed in humans. Our results show that Anti-17 MLNPs, delivered to 5XFAD mice by intra-cisterna magna injection, specifically deliver Anti-17 to microglia. Anti-17 MLNPs downregulated miR-17 expression in microglia but not in neurons, astrocytes, and oligodendrocytes. Anti-17 MLNPs attenuated inflammation, improved autophagy, and reduced Aß burdens in the brains. Additionally, Anti-17 MLNPs reduced the deterioration in spatial memory and decreased anxiety-like behavior in 5XFAD mice. Therefore, targeting miR-17 using MLNPs is a viable strategy to prevent several AD pathologies. This selective targeting strategy delivers specific agents to microglia without the adverse off-target effects on other cell types. Additionally, this approach can be used to deliver other molecules to microglia and other immune cells in other organs.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38700663

RESUMO

PURPOSE: Enterobacteriaceae carrying mcr-9, in particularly those also co-containing metallo-ß-lactamase (MBL) and TEM type ß-lactamase, present potential transmission risks and lack adequate clinical response methods, thereby posing a major threat to global public health. The aim of this study was to assess the antimicrobial efficacy of a combined ceftazidime/avibactam (CZA) and aztreonam (ATM) regimen against carbapenem-resistant Enterobacter cloacae complex (CRECC) co-producing mcr-9, MBL and TEM. METHODS: The in vitro antibacterial activity of CZA plus ATM was evaluated using a time-kill curve assay. Furthermore, the in vivo interaction between CZA plus ATM was confirmed using a Galleria mellonella (G. mellonella) infection model. RESULTS: All eight clinical strains of CRECC, co-carrying mcr-9, MBL and TEM, exhibited high resistance to CZA and ATM. In vitro time-kill curve analysis demonstrated that the combination therapy of CZA + ATM exerted significant bactericidal activity against mcr-9, MBL and TEM-co-producing Enterobacter cloacae complex (ECC) isolates with a 100% synergy rate observed in our study. Furthermore, in vivo survival assay using Galleria mellonella larvae infected with CRECC strains co-harboring mcr-9, MBL and TEM revealed that the CZA + ATM combination significantly improved the survival rate compared to the drug-treatment alone and untreated control groups. CONCLUSION: To our knowledge, this study represents the first report on the in vitro and in vivo antibacterial activity of CZA plus ATM against CRECC isolates co-harboring mcr-9, MBL and TEM. Our findings suggest that the combination regimen of CZA + ATM provides a valuable reference for clinicians to address the increasingly complex antibiotic resistance situation observed in clinical microorganisms.

11.
Clin Oral Investig ; 28(6): 317, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38750335

RESUMO

OBJECTIVES: To evaluate the effects of costochondral grafting (CCG) used for temporomandibular joint ankylosis (TMJA) in growing patients. MATERIALS AND METHODS: Pediatric patients with TMJA treated by CCG from 2010.5 to 2021.7 were included in the study. CT scans were performed before and after operations with at least 1 year follow-up. The height of the mandibular ramus, menton deviation or retraction, osteotomy gap, etc. were measured by ProPlan CMF1.4 software. CCG growth, resorption, and relapse were evaluated and analyzed with influencing factors such as age, ostectomy gap, etc. by generalized estimating equation. RESULTS: There were 24 patients (29 joints) with an average age of 6.30 ± 3.13 years in the study. After operation, the mandibular ramus was elongated by 5.97 ± 3.53 mm. Mandibular deviation or retrusion was corrected by 4.82 ± 2.84 mm and 3.76 ± 2.97 mm respectively. After a mean follow-up of 38.91 ± 29.20 months, 58.62% CCG grew (4.18 ± 7.70 mm), 20.69% absorbed (2.23 ± 1.16 mm), and 20.69% re-ankylosed. The re-ankylosis was negatively correlated with the osteotomy gap (OR:0.348,0.172-0.702 95%CI, critical value = 6.10 mm). CCG resorption was positively correlated with the distance of CCG ramus elongation (OR:3.353,1.173-9.586 95%CI, critical value = 7.40 mm). CONCLUSIONS: An adequate osteotomy gap and CCG ramus elongation distance are the key factors for successful treatment of TMJA with jaw deformities in growing patients. CLINICAL RELEVANCE: TMJA affects mouth opening and jaw development in pediatric patients. The most common autogenous bone graft for pediatric patients is CCG due to its growth potential, convenient access and easy contouring. Also, it can simultaneously reconstruct the TMJ and improve jaw deformity by lengthening the mandibular ramus. But the growth of CCG is unpredictable. In this study, we explored several factors that may affect the absorption and re-ankylosis of CCG, expecting to provide several suggestions to improve future CCG treatment.


Assuntos
Anquilose , Transtornos da Articulação Temporomandibular , Tomografia Computadorizada por Raios X , Humanos , Criança , Transtornos da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Feminino , Anquilose/cirurgia , Masculino , Resultado do Tratamento , Costelas/transplante , Transplante Ósseo/métodos , Pré-Escolar , Estudos Retrospectivos , Cartilagem/transplante
12.
Artigo em Inglês | MEDLINE | ID: mdl-38750896

RESUMO

OBJECTIVES: Polymyxins are currently the last-resort treatment against multi-drug resistant Gram-negative bacterial infections, but plasmid-mediated mobile polymyxin resistance genes (mcr) threaten its efficacy, especially in carbapenem-resistant Enterobacter cloacae complex (CRECC). The objective of this study was to provide insights into the mechanism of polymyxin-induced bacterial resistance and the effect of overexpression of mcr-9. METHODS: The clinical strain CRECC414 carrying the mcr-9 gene was treated with a gradient concentration of polymyxin. Subsequently, the broth microdilution was used to determine the minimum inhibitory concentration (MIC) and RT-qPCR was utilized to assess mcr-9 expression. Transcriptome sequencing and Whole genome sequencing (WGS) was utilized to identify alterations in strains resulting from increased polymyxin resistance, and significant transcriptomic differences were analyzed alongside a comprehensive examination of metabolic networks at the genomic level. RESULTS: Polymyxin treatment induced the upregulation of mcr-9 expression and significantly elevated the MIC of the strain. Furthermore, the WGS and transcriptomic results revealed a remarkable up-regulation of arnBCADTEF gene cassette, indicating that the Arn/PhoPQ system-mediated L-Ara4N modification is the preferred mechanism for achieving high levels of resistance. Additionally, significant alterations in bacterial gene expression were observed with regards to multidrug efflux pumps, oxidative stress and repair mechanisms, cell membrane biosynthesis, as well as carbohydrate metabolic pathways. CONCLUSION: Polymyxin greatly disrupts the transcription of vital cellular pathways. A complete PhoPQ two-component system is a prerequisite for polymyxin resistance of Enterobacter cloacae, even though mcr-9 is highly expressed. These findings provide novel and important information for further investigation of polymyxin resistance of CRECC.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38574253

RESUMO

Background: Clonorchiasis remains a serious public health problem. However, the molecular mechanism underlying clonorchiasis remains largely unknown. Amino acid (AA) metabolism plays key roles in protein synthesis and energy sources, and improves immunity in pathological conditions. Therefore, this study aimed to explore the AA profiles of spleen in clonorchiasis and speculate the interaction between the host and parasite. Methods: Here targeted ultrahigh performance liquid chromatography multiple reaction monitoring mass spectrometry was applied to discover the AA profiles in spleen of rats infected with Clonorchis sinensis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) was performed to characterize the dysregulated metabolic pathways. Results: Pathway analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis and ß-alanine metabolism were significantly altered in clonorchiasis. There were no significant correlations between 14 significant differential AAs and interleukin (IL)-1ß. Although arginine, asparagine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were positively correlated with IL-6, IL-10, tumor necrosis factor (TNF)-α as well as aspartate aminotransferase and alanine aminotransferase; ß-alanine and 4-hydroxyproline were negatively correlated with IL-6, IL-10, and TNF-α. Conclusion: This study reveals the dysregulation of AA metabolism in clonorchiasis and provides a useful insight of metabolic mechanisms at the molecular level.

14.
Nanomaterials (Basel) ; 14(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38607175

RESUMO

The AlxCoCrFeNi2.1 (x = 0, 0.3, 0.7, 1.0, 1.3) multi-component high-entropy alloy (HEA) was synthesized by mechanical alloying (MA) and Spark Plasma Sintering (SPS), The impact of the percentage of Al on crystal structure transition, microstructure evolution and mechanical properties were studied. Crystal structure was investigated by X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The results show that with the increasing of Al content, the crystal structure of the alloys gradually transformed from a nanocrystalline phase of FCC to a mix of FCC and BCC nanocrystalline. The hardness was found to increase steadily from 433 HV to 565 HV due to the increase in fraction of BCC nanocrystalline phase. Thus, the compressive fracture strength increased from 1702 MPa to 2333 MPa; in contrast, the fracture strain decreased from 39.8% to 15.6%.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38614958

RESUMO

BACKGROUND AND HYPOTHESIS: Activation of NF-κB-signalling is key in the pathogenesis of chronic kidney diseases (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair. METHODS: To investigate the relationship between activated and inactivated NF-κB signaling on the pathogenesis of CKD using mouse models of NF-κB partial inactivation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into alanine) and activation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into serine). RESULTS: The density of CD3, CD8, CD68 positive cells, as well as the expression of IL-6, TRAF-1, and NAF-1 in the kidney tissues of NF-κBC59A mice were reduced, whereas an opposing pattern was observed in the NF-κBC59S mice. Blood pressure, kidney fibrosis (analyzed by PAS-, Masson trichrome-, and Sirius-Red-staining as well as α-SMA immunofluorescence), serum creatinine and urinary albumin-to-creatinine-ratio are markedly increased in NF-κB activated and inactivated mice compared to controls. Transmission electron microscopy indicated that the glomerular basement membrane was thicker in both NF-κBC59A and NF-κBC59S mice compared to wild-type mice. CONCLUSIONS: Using mice models with partially activated and inactivated NF-κB pathways suggests that there is an apparently U-shaped relationship between blood pressure, kidney function as well as morphology and the activation of the NF-κB pathway. A certain optimal activity of the NF-κB pathway seems to be important to maintain optimal kidney function and morphology.

16.
Front Plant Sci ; 15: 1370949, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590746

RESUMO

Impatiens uliginosa is a plant of the Impatiens, with peculiar flowers. In this study, we combined morphogenesis and molecular biology to explore its development of flowers. An analysis of basic observational data and paraffin sectioning showed that it took approximately 13 d for the floral organs to differentiate. An analysis of the development of inflorescences and floral organs by scanning electron microscopy showed that the inflorescence of I. uliginosa is a spiral raceme. The floral organs differentiated in the following order: lateral sepals (Ls), posterior sepal (Ps), anterior sepals (As), anterior petal (Ap), lateral petals (Lp), stamens (St) and gynoecium (Gy). I. uliginosa was found to have four sepals, and the connate stamens are caused by the fusion and growth of filament appendages. The results of fluorescence quantification and virus-induced gene silencing showed that I. uliginosa had its own unique model for flower development, and there was functional diversity of IuAP1 and IuDEF. Among them, IuAP1 controls the formation of bract s (Br), regulates the morphogenesis of posterior sepal, controls the anthocyanin precipitation of the anterior petals and the formation of lateral petals. IuDEF regulates the morphogenesis of lateral sepals, the length of development of the spur, and controls the size of yellow flower color plaques of the lateral petals. In this study, the process of flower development and the function of flower development genes of I. uliginosa were preliminarily verified. This study provides basic guidance and new concepts that can be used to study the development of Impatiens flowers.

17.
Blood Adv ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38607381

RESUMO

Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized treatment for relapsed/refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL). Robust biomarkers and a complete understanding of CAR-T cell function in the post-infusion phase remain limited. Here we used a 37-color spectral flow cytometry panel to perform high dimensional single cell analysis of post-infusion samples in 26 patients treated with CD28 co-stimulatory domain containing commercial CAR-T (CD28-CAR-T) for NHL and focused on computationally gated CD8+ CAR-T cells. We found that the presence of post-infusion PD-1+ CD8+ CAR-T cells at the Day 14 timepoint highly correlated with the ability to achieve complete response (CR) by 6 months. Further analysis identified multiple subtypes of CD8+ PD-1+ CAR-T cells including PD-1+ TCF1+ stem-like CAR-T cells and PD-1+ TIM3+ effector-like CAR-T cells that correlated with improved clinical outcomes such as response and progression free survival. Additionally, we identified a subset of PD-1+ CD8+ CAR+ T cells with effector-like function that was increased in patients who achieved a CR and was associated with Grade 3 or higher immune effector cell-associated neurotoxicity syndrome. Here we identified robust biomarkers of response to CD28-CAR-T and highlight the importance of PD-1 positivity in CD8+ CAR-T cells post-infusion in achieving CR.

18.
Curr Med Imaging ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38616748

RESUMO

BACKGROUND: In the end stage of kidney disease, abnormal levels of blood calcium, phosphorus, and parathyroid hormone lead to bone metabolism disorders, manifesting as osteoporosis or fibrocystic osteoarthritis. X-ray, CT, and MR are useful for detecting bone lesions in dialysis patients, but currently, computer vision has not yet been used for this purpose. METHODS: ResNet is a powerful deep CNN model, which has not yet been used to distinguish between the bones of dialysis patients and healthy people. Therefore, this study aimed to investigate the ability of the Resnet50 model to identify the bone of dialysis patients from normal bone. RESULTS: CT images of 200 cases (100 dialysis patients and 100 healthy people aged 31-72 years with male:female ratio of 51:49) were randomly divided into the training and testing groups at the ratio of 8:2. The module of 'torch' was used to train the model of Resnet50 for the current task of image classification. In the test cohort, the accuracy, sensitivity, and specificity with hyper-parameter=0 were 60%, 65%, and 55%, respectively. When the hyper-parameter was 0.6 or 0.7 versus 0, the accuracy was significantly higher (P<0.05). When the hyper-parameter was another number, the accuracy was not significantly different from that with no hyper-parameter (P>0.05). CONCLUSION: This study has indicated computer vision to be suitable for identifying bone changes caused by dialysis; a hyper-parameter has been found necessary for improving model accuracy. The ResNet50 model with hyper-parameter = 0.7 has exhibited 90% sensitivity in identifying the bone of dialysis patients.

19.
Nutr Rev ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38626282

RESUMO

The gut barrier is the first line of defense against harmful substances and pathogens in the intestinal tract. The balance of proliferation and apoptosis of intestinal epithelial cells (IECs) is crucial for maintaining the integrity of the intestinal mucosa and its function. However, oxidative stress and inflammation can cause DNA damage and abnormal apoptosis of the IECs, leading to the disruption of the intestinal epithelial barrier. This, in turn, can directly or indirectly cause various acute and chronic intestinal diseases. In recent years, there has been a growing understanding of the vital role of dietary ingredients in gut health. Studies have shown that certain amino acids, fibers, vitamins, and polyphenols in the diet can protect IECs from excessive apoptosis caused by oxidative stress, and limit intestinal inflammation. This review aims to describe the molecular mechanism of apoptosis and its relationship with intestinal function, and to discuss the modulation of IECs' physiological function, the intestinal epithelial barrier, and gut health by various nutrients. The findings of this review may provide a theoretical basis for the use of nutritional interventions in clinical intestinal disease research and animal production, ultimately leading to improved human and animal intestinal health.

20.
ACS Appl Mater Interfaces ; 16(15): 18400-18410, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38576193

RESUMO

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.


Assuntos
Infecções Bacterianas , Curcumina , Staphylococcus aureus Resistente à Meticilina , Infecção dos Ferimentos , Animais , Camundongos , Hidrogéis , Antibacterianos , Peptídeos , Cicatrização , Concentração de Íons de Hidrogênio
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