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1.
Int Urol Nephrol ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955940

RESUMEN

PURPOSE: This investigation sought to validate the clinical precision and practical applicability of AI-enhanced three-dimensional sonographic imaging for the identification of anterior urethral stricture. METHODS: The study enrolled 63 male patients with diagnosed anterior urethral strictures alongside 10 healthy volunteers to serve as controls. The imaging protocol utilized a high-frequency 3D ultrasound system combined with a linear stepper motor, which enabled precise and rapid image acquisition. For image analysis, an advanced AI-based segmentation process using a modified U-net algorithm was implemented to perform real-time, high-resolution segmentation and three-dimensional reconstruction of the urethra. A comparative analysis was performed against the surgically measured stricture lengths. Spearman's correlation analysis was executed to assess the findings. RESULTS: The AI model completed the entire processing sequence, encompassing recognition, segmentation, and reconstruction, within approximately 5 min. The mean intraoperative length of urethral stricture was determined to be 14.4 ± 8.4 mm. Notably, the mean lengths of the urethral strictures reconstructed by manual and AI models were 13.1 ± 7.5 mm and 13.4 ± 7.2 mm, respectively. Interestingly, no statistically significant disparity in urethral stricture length between manually reconstructed and AI-reconstructed images was observed. Spearman's correlation analysis underscored a more robust association of AI-reconstructed images with intraoperative urethral stricture length than manually reconstructed 3D images (0.870 vs. 0.820). Furthermore, AI-reconstructed images provided detailed views of the corpus spongiosum fibrosis from multiple perspectives. CONCLUSIONS: The research heralds the inception of an innovative, efficient AI-driven sonographic approach for three-dimensional visualization of urethral strictures, substantiating its viability and superiority in clinical application.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 324-328, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38953255

RESUMEN

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group (n=270) or the self-administered group (n=262) to complete the generalized anxiety disorder (GAD-7) and the patient health questionnaire (PHQ-9) scales.The total scores and prevalence rates of anxiety and depression were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups (all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group (P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression (P<0.001,P=0.002).The prevalence rates of moderate to severe anxiety (GAD-7≥10) and depression (PHQ-9≥10) showed no statistically significant difference between the two groups (P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.


Asunto(s)
Ansiedad , Depresión , Humanos , Encuestas y Cuestionarios , Depresión/epidemiología , Depresión/diagnóstico , Femenino , Ansiedad/epidemiología , Masculino , Adulto , Traumatismos en Atletas/psicología , Traumatismos en Atletas/epidemiología , China/epidemiología , Persona de Mediana Edad , Adulto Joven
3.
Front Plant Sci ; 15: 1410554, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974983

RESUMEN

Introduction: Several studies of MADS-box transcription factors in flowering plants have been conducted, and these studies have indicated that they have conserved functions in floral organ development; MIKC-type MADS-box genes has been proved to be expanded in ferns, however, few systematic studies of these transcription factors have been conducted in non-seed plants. Although ferns and seed plants are sister groups, they exhibit substantial morphological differences. Methods: Here, we clarified the evolution of MADS-box genes across 71 extant fern species using available transcriptome, genome, and gene expression data. Results: We obtained a total of 2,512 MADS-box sequences, ranging from 9 to 89 per species. The most recent common ancestor (MRCA) of ferns contained approximately three type I genes and at least 5-6 type II MADS-box genes. The domains, motifs, expression of type I and type II proteins, and the structure of the both type genes were conserved in ferns as to other land plants. Within type II genes, MIKC*-type proteins are involved in gametophyte development in ferns; MIKCC-type proteins have broader expression patterns in ferns than in seed plants, and these protein sequences are likely conserved in extant seed plants and ferns because of their diverse roles in diploid sporophyte development. More than 90% of MADS-box genes are type II genes, and MIKCC genes, especially CRM1 and CRM6-like genes, have undergone a large expansion in leptosporangiate ferns; the diverse expression patterns of these genes might be related to the fuctional diversification and increased complexity of the plant body plan. Tandem duplication of CRM1 and CRM6-like genes has contributed to the expansion of MIKCC genes. Conclusion or Discussion: This study provides new insights into the diversity, evolution, and functions of MADS-box genes in extant ferns.

4.
Ecotoxicology ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026048

RESUMEN

The use of some organophosphate insecticides is restricted or even banned in paddy fields due to their high toxicity to aquatic organisms. The aim of this study is to elucidate the main pathways and target organs of organophosphate insecticide toxicity to fish exposed via different routes by integrating histopathological and biochemical techniques. Using malathion as the model drug, when the dosage is 20-60 mg/L, the toxicity of whole body and head immersion drugs to zebrafish is much higher than that of trunk immersion drugs. A dose of 21.06-190.44 mg/kg of malathion feed was fed to adult zebrafish. Although the dosage was already high, no obvious toxicity was observed. Therefore, we believe that the drug mainly enters the fish body through the gills. When exposed to a drug solution of 20 mg/L and 60 mg/L, the fish showed significant neurological behavioral abnormalities, and the pathological damage to key organs and brain tissue was the most severe, showing obvious vacuolization and the highest residual amount (8.72-47.78 mg/L). The activity of acetylcholinesterase was the most inhibited (54.69-74.68%). Therefore, brain tissue is the key toxic target organ of malathion in fish. In addition, we compared the bioaccumulation effects of different water-soluble organophosphorus insecticides in fish and their toxic effects. We found that the higher the water solubility of organophosphorus insecticides, the lower their toxicity to fish.

5.
Life Sci ; 352: 122891, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38977060

RESUMEN

There is a growing body of evidence suggesting that the composition of intestinal flora plays a significant role in regulating lipid metabolism. 2', 3', 5'-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine (IMMH007) is a new candidate compound for regulating blood cholesterol and other lipids. In this study, we conducted metagenomic and metabolomic analyses on samples from high-fat diet-fed (HFD) hamsters treated with IMMH007. Our findings revealed that IMM-H007 reversed the imbalance of gut microbiota caused by a high-fat diet. Additionally, it activated adiponectin receptor and pantothenate and CoA biosynthesis pathway-related genes, which are known to regulate lipid and glucose metabolism. Furthermore, IMM-H007 promotes cholesterol metabolism by reducing the abundance of genes and species associated with 7α-dehydroxylation and bile salt hydrolase (BSH). Metabolomics and pharmacological studies have shown that IMM-H007 effectively improved glucose and lipid metabolism disorders caused by HFD, reduced the aggregation of secondary bile acids (SBAs), significantly increased the content of hyodeoxycholic acid (HDCA), and also activated the expression of VDR in the small intestine. As a result, there was a reduction in the leakage of diamine oxidase (DAO) into the bloodstream in hamsters, accompanied by an upregulation of ZO-1 expression in the small intestine. The results suggested that IMM-H007 regulated glucose and lipid metabolism, promoted cholesterol metabolism through activating the expression of VDR, inhibiting inflammatory and improving the permeability of the intestinal barrier. Thus, our study provides new understanding of how IMM-H007 interacts with intestinal function, microbiota, and relevant targets, shedding light on its mechanism of action.

6.
Zhongguo Fei Ai Za Zhi ; 27(6): 480-484, 2024 Jun 20.
Artículo en Chino | MEDLINE | ID: mdl-39026500

RESUMEN

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide. For lung adenocarcinoma, identifying specific gene mutations, fusions, and giving corresponding targeted drugs can greatly improve the survival time of the patients. Among them, anaplastic lymphoma kinase (ALK) fusion occurs in 3%-7% of non-small cell lung cancer (NSCLC). In clinical practice, a variety of detection methods can be used to determine the ALK fusion status, but false negative test results are possible. This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adenocarcinoma, judged the ALK fusion status by various detection methods. Among them, immunohistochemistry (IHC)(Ventana D5F3), RNA based next-generation sequencing (RNA-based NGS) confirmed positive echinoderm microtubule associated protein like 4 (EML4)-ALK fusion, while DNA-based NGS was negative. This paper analyzed the detection methods of ALK fusion, in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.
.


Asunto(s)
Adenocarcinoma del Pulmón , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Pulmonares , Proteínas de Fusión Oncogénica , Humanos , Proteínas de Fusión Oncogénica/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Femenino
7.
Antonie Van Leeuwenhoek ; 117(1): 93, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954062

RESUMEN

A Gram-negative, rod-shaped, non-motile, aerobic bacterium, designated as strain TK19101T, was isolated from the intermediate seawater of yellow vent in the shallow-sea hydrothermal system located near Kueishantao Island. The strain was found to grow at 10-40 °C (optimum, 35 °C), at pH 6.0-8.0 (optimum, 7.0), and in 0-5% (w/v) NaCl (optimum, 1%). Strain TK19101T was catalase-positive and oxidase-positive. The predominant fatty acids (> 10%) in strain TK19101T cells were C16:0, summed feature 8 (C18:1 ω6c and/or C18:1 ω7c), and C18:0. The predominant isoprenoid quinone of strain TK19101T was ubiquinone-10. The polar lipids of strain TK19101T comprised phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phospholipid, and unknown polar lipid. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain TK19101T belonged to the genus Mesobacterium. Strain TK19101T exhibited highest 16S rRNA gene sequence similarity value to Mesobacterium pallidum MCCC M24557T (97.48%). The estimated average nucleotide identity and digital DNA-DNA hybridization values between strain TK19101T and the closest related species Mesobacterium pallidum MCCC M24557T were 74.88% and 20.30%, respectively. The DNA G + C content was 63.49 mol%. On the basis of the analysis of 16S rRNA gene sequences, genotypic and phylogenetic data, strain TK19101T has a unique phylogenetic status and represents a novel species of genus Mesobacterium, for which the name Mesobacterium hydrothermale sp. nov. is proposed. The type strain is TK19101T (= MCCC 1K08936T = KCTC 8354T).


Asunto(s)
Composición de Base , ADN Bacteriano , Ácidos Grasos , Respiraderos Hidrotermales , Filogenia , ARN Ribosómico 16S , Agua de Mar , ARN Ribosómico 16S/genética , Respiraderos Hidrotermales/microbiología , ADN Bacteriano/genética , Ácidos Grasos/análisis , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Islas , Fosfolípidos/análisis , Análisis de Secuencia de ADN , China
8.
Adv Sci (Weinh) ; : e2309387, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38889281

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer with a dismal overall prognosis. NSD2 is an H3K36-specific di-methyltransferase that has been reported to play a crucial role in promoting tumorigenesis. Here, the study demonstrates that NSD2 acts as a putative tumor suppressor in Kras-driven pancreatic tumorigenesis. NSD2 restrains the mice from inflammation and Kras-induced ductal metaplasia, while NSD2 loss facilitates pancreatic tumorigenesis. Mechanistically, NSD2-mediated H3K36me2 promotes the expression of IκBα, which inhibits the phosphorylation of p65 and NF-κB nuclear translocation. More importantly, NSD2 interacts with the DNA binding domain of p65, attenuating NF-κB transcriptional activity. Furthermore, inhibition of NF-κB signaling relieves the symptoms of Nsd2-deficient mice and sensitizes Nsd2-null PDAC to gemcitabine. Clinically, NSD2 expression decreased in PDAC patients and negatively correlated to nuclear p65 expression. Together, the study reveals the important tumor suppressor role of NSD2 and multiple mechanisms by which NSD2 suppresses both p65 phosphorylation and downstream transcriptional activity during pancreatic tumorigenesis. This study opens therapeutic opportunities for PDAC patients with NSD2 low/loss by combined treatment with gemcitabine and NF-κBi.

9.
Reprod Biomed Online ; 49(3): 104099, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38889591

RESUMEN

RESEARCH QUESTION: Is intra-abdominal fat obesity associated with infertility? DESIGN: This study analysed data from the 2013-2018 National Health and Nutrition Examination Survey, with a total of 3013 women enrolled. The participants were divided into two groups: infertility and non-infertility. Differences between the two groups were analysed using a weighted Student's t-test or Mann-Whitney U-test for continuous variables, or a weighted chi-squared test for categorical data. Visceral adipose tissue area (VATA) was assessed by dual-energy X-ray absorptiometry. The independent association between infertility and log VATA was assessed by weighted multivariate logistic regression models. Subgroup analyses were performed to assess the strength of the results. Interaction tests were used to examine whether covariates interacted with log VATA to influence infertility. RESULTS: Log VATA was significantly higher in the infertility group compared with the non-infertility group (P < 0.001). After adjustment for potential confounders, the results of multivariate logistic regression analysis revealed that an increase in log VATA was associated with increased prevalence of female infertility (OR = 2.453, 95% CI 1.278-4.792). Subgroup analyses showed this association in individuals aged <35 years (P = 0.002), Mexican-Americans (P = 0.033), non-hypertensive individuals (P = 0.013) and non-diabetic individuals (P = 0.003). CONCLUSIONS: An enlarged VATA is associated with increased risk of infertility. The direct effect of VATA on female infertility needs to be clarified further to provide a basis for future prevention and treatment of female infertility.

10.
Nutrients ; 16(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38892715

RESUMEN

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.


Asunto(s)
Microbioma Gastrointestinal , Gynostemma , Enfermedad del Hígado Graso no Alcohólico , Extractos Vegetales , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Ratones , Gynostemma/química , Extractos Vegetales/farmacología , Masculino , Inflamación/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Antiinflamatorios/farmacología
11.
FASEB J ; 38(13): e23760, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38924449

RESUMEN

Hyponatremia is the most common disorder of electrolyte imbalances. It is necessary to develop new type of diuretics to treat hyponatremia without losing electrolytes. Urea transporters (UT) play an important role in the urine concentrating process and have been proved as a novel diuretic target. In this study, rat and mouse syndromes of inappropriate antidiuretic hormone secretion (SIADH) models were constructed and analyzed to determine if UTs are a promising drug target for treating hyponatremia. Experimental results showed that 100 mg/kg UT inhibitor 25a significantly increased serum osmolality (from 249.83 ± 5.95 to 294.33 ± 3.90 mOsm/kg) and serum sodium (from 114 ± 2.07 to 136.67 ± 3.82 mmol/L) respectively in hyponatremia rats by diuresis. Serum chemical examination showed that 25a neither caused another electrolyte imbalance nor influenced the lipid metabolism. Using UT-A1 and UT-B knockout mouse SIADH model, it was found that serum osmolality and serum sodium were lowered much less in UT-A1 knockout mice than in UT-B knockout mice, which suggest UT-A1 is a better therapeutic target than UT-B to treat hyponatremia. This study provides a proof of concept that UT-A1 is a diuretic target for SIADH-induced hyponatremia and UT-A1 inhibitors might be developed into new diuretics to treat hyponatremia.


Asunto(s)
Hiponatremia , Síndrome de Secreción Inadecuada de ADH , Proteínas de Transporte de Membrana , Ratones Noqueados , Transportadores de Urea , Animales , Masculino , Ratones , Ratas , Modelos Animales de Enfermedad , Diuréticos/farmacología , Hiponatremia/tratamiento farmacológico , Hiponatremia/metabolismo , Síndrome de Secreción Inadecuada de ADH/tratamiento farmacológico , Síndrome de Secreción Inadecuada de ADH/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Ratones Endogámicos C57BL , Concentración Osmolar , Ratas Sprague-Dawley , Sodio/metabolismo
12.
Ann Biol Clin (Paris) ; 82(2): 174-186, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38832689

RESUMEN

Dyslipidemia plays a key role in metabolic syndrome (MS), intricately linked to type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences in low-density lipoprotein cholesterol (LDL-C) subfraction levels between T2DM and T2DM with MS, and identify the risk factors associated with the disease. A total of 246 individuals diagnosed with T2DM, including 144 T2DM patients with MS, and 147 healthy subjects were recruited. All participants underwent a comprehensive clinical evaluation. Lipoprotein subfraction analysis was performed using the Lipoprint LDL system. Multivariate logistic regression analysis revealed that several lipid markers, including triglyceride (TG), LDL-C, large buoyant LDL-C (lbLDL-C), small dense LDL-C (sdLDL-C), LDLC2-5, and sdLDL-C/lbLDL-C ratio, were identified as independent risk factors for T2DM. Additionally, TG, sdLDL-C, LDLC-4, LDLC-5, and sdLDL-C/lbLDL-C ratio were found to be independent risk factors for T2DM with MS. Furthermore, the results of the receiver operating characteristic (ROC) curves demonstrated that sdLDL-C, LDLC-4, LDLC-3, and sdLDL-C/lbLDL-C ratio exhibited excellent predictive performance for the risk of T2DM (AUC > 0.9). The sdLDL-C/lbLDL-C ratio emerges as a shared independent risk factor for T2DM and MS complications. Furthermore, sdLDL-C/lbLDL-C ratio, along with LDL-4 and LDL-3, exhibits noteworthy predictive capabilities for T2DM.


Asunto(s)
Biomarcadores , LDL-Colesterol , Diabetes Mellitus Tipo 2 , Síndrome Metabólico , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Factores de Riesgo , LDL-Colesterol/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Anciano
13.
Mol Pharm ; 21(7): 3425-3433, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38836286

RESUMEN

Fibrinogen-like protein 1 (FGL1) is a potential novel immune checkpoint target for malignant tumor diagnosis and therapy. Accurate detection of FGL1 levels in tumors via noninvasive PET imaging might be beneficial for managing the disease. To achieve this, multiple FGL1-targeting peptides (FGLP) were designed, and a promising candidate, 68Ga-NOTA-FGLP2, was identified through a high-throughput screening approach using microPET imaging of 68Ga-labeled peptides. Subsequent in vitro cell experiments showed that uptake values of 68Ga-NOTA-FGLP2 in FGL1 positive Huh7 tumor cells were significantly higher than those in FGL1 negative U87 MG tumor cells. Further microPET imaging showed that the Huh7 xenografts were clearly visualized with a favorable contrast. ROI analysis showed that the uptake values of the tracer in Huh7 xenografts were 2.63 ± 0.07% ID/g at 30 min p.i.. After treatment with an excess of unlabeled FGLP2, the tumor uptake significantly decreased to 0.54 ± 0.05% ID/g at 30 min p.i.. Moreover, the uptake in U87 MG xenografts was 0.44 ± 0.06% ID/g at the same time point. The tracer was excreted mainly through the renal system. 18F-FDG PET imaging was also performed in mice bearing Huh7 and U87 MG xenografts, respectively. However, there was no significant difference in the uptake between the tumors with different FGL1 expressions. Preclinical data indicated that 68Ga-NOTA-FGLP2 might be a suitable radiotracer for in vivo noninvasive visualization of tumors with abundant expression of FGL1. Further investigation of 68Ga-NOTA-FGLP2 for tumor diagnosis and therapy is undergoing.


Asunto(s)
Radioisótopos de Galio , Tomografía de Emisión de Positrones , Radiofármacos , Animales , Humanos , Ratones , Tomografía de Emisión de Positrones/métodos , Línea Celular Tumoral , Radiofármacos/farmacocinética , Ratones Desnudos , Distribución Tisular , Péptidos/química , Ratones Endogámicos BALB C , Femenino , Compuestos Heterocíclicos con 1 Anillo/química
14.
Invest Ophthalmol Vis Sci ; 65(6): 34, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38913005

RESUMEN

Purpose: The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms. Methods: In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected. Results: We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice. Conclusions: Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.


Asunto(s)
Neovascularización Coroidal , Modelos Animales de Enfermedad , Macrófagos , Ratones Endogámicos C57BL , Ratones Noqueados , Semaforinas , Transducción de Señal , Quinasas Asociadas a rho , Proteína de Unión al GTP rhoA , Animales , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/genética , Neovascularización Coroidal/patología , Ratones , Macrófagos/metabolismo , Quinasas Asociadas a rho/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Transducción de Señal/fisiología , Proteína de Unión al GTP rhoA/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Western Blotting , Masculino , Angiografía con Fluoresceína
15.
Sci Total Environ ; 946: 174205, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38909796

RESUMEN

Plant uptake of organic contaminants generally occurs through either root, gas-phase foliar, or particle-phase foliar uptake. Understanding these pathways is essential for food-system practitioners to reduce human exposures, and to clean contaminated-sites with phytoremediation. Herein, we conducted a field-based experiment using an improved specific exposure chamber to elucidate the uptake pathways of organophosphate esters, phthalates, and polycyclic aromatic compounds, and quantitatively assessed their contributions to organic contaminant accumulations in field-grown rice. For most target compounds, all three uptake pathways (root, foliar gas, and foliar particle uptakes) contributed substantially to the overall contaminant burden in rice. Compounds with lower octanol-water partition coefficients (Kow) were more readily translocated from roots to leaves, and compounds with higher octanol-air partition coefficients (Koa) tended to enter rice leaves mostly through particle deposition. Most compounds were mostly stored in the inner leaves (55.3-98.2 %), whereas the relatively volatile compounds were more readily absorbed by the waxy layer and then transferred to the inner leaves. Air particle desorption was a key process regulating foliar uptake of low-volatility compounds. The results can help us to better understand and predict the environmental fate of those contaminants, and develop more effective management strategies for reducing their human exposure through food ingestion.


Asunto(s)
Oryza , Ácidos Ftálicos , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Oryza/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Hidrocarburos Policíclicos Aromáticos/análisis , Ácidos Ftálicos/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/análisis , Organofosfatos/metabolismo , Ésteres/metabolismo , Monitoreo del Ambiente
16.
Theor Appl Genet ; 137(7): 157, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861001

RESUMEN

KEY MESSAGE: Through the histological, physiological, and transcriptome-level identification of the abscission zone of Pennisetum alopecuroides 'Liqiu', we explored the structure and the genes related to seed shattering, ultimately revealing the regulatory network of seed shattering in P. alopecuroides. Pennisetum alopecuroides is one of the most representative ornamental grass species of Pennisetum genus. It has unique inflorescence, elegant appearance, and strong stress tolerance. However, the shattering of seeds not only reduces the ornamental effect, but also hinders the seed production. In order to understand the potential mechanisms of seed shattering in P. alopecuroides, we conducted morphological, histological, physiological, and transcriptomic analyses on P. alopecuroides cv. 'Liqiu'. According to histological findings, the seed shattering of 'Liqiu' was determined by the abscission zone at the base of the pedicel. Correlation analysis showed that seed shattering was significantly correlated with cellulase, lignin, auxin, gibberellin, cytokinin and jasmonic acid. Through a combination of histological and physiological analyses, we observed the accumulation of cellulase and lignin during 'Liqiu' seed abscission. We used PacBio full-length transcriptome sequencing (SMRT) combined with next-generation sequencing (NGS) transcriptome technology to improve the transcriptome data of 'Liqiu'. Transcriptomics further identified many differential genes involved in cellulase, lignin and plant hormone-related pathways. This study will provide new insights into the research on the shattering mechanism of P. alopecuroides.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Pennisetum , Reguladores del Crecimiento de las Plantas , Semillas , Transcriptoma , Pennisetum/genética , Pennisetum/fisiología , Pennisetum/crecimiento & desarrollo , Semillas/genética , Semillas/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas/metabolismo , Perfilación de la Expresión Génica , Lignina/metabolismo
17.
Microbiol Res ; 286: 127789, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38870619

RESUMEN

Plants have developed intricate immune mechanisms to impede Phytophthora colonization. In response, Phytophthora secretes RxLR effector proteins that disrupt plant defense and promote infection. The specific molecular interactions through which Phytophthora RxLR effectors undermine plant immunity, however, remain inadequately defined. In this study, we delineate the role of the nuclear-localized RxLR effector PcAvh87, which is pivotal for the full virulence of Phytophthora cinnamomi. Gene expression analysis indicates that PcAvh87 expression is significantly upregulated during the initial infection stages, interacting with the immune responses triggered by the elicitin protein INF1 and pro-apoptotic protein BAX. Utilizing PEG/CaCl2-mediated protoplast transformation and CRISPR/Cas9-mediated gene editing, we generated PcAvh87 knockout mutants, which demonstrated compromised hyphal growth, sporangium development, and zoospore release, along with a marked reduction in pathogenicity. This underscores PcAvh87's crucial role as a virulence determinant. Notably, PcAvh87, conserved across the Phytophthora genus, was found to modulate the activity of plant immune protein 113, thereby attenuating plant immune responses. This implies that the PcAvh87-mediated regulatory mechanism could be a common strategy in Phytophthora species to manipulate plant immunity. Our findings highlight the multifaceted roles of PcAvh87 in promoting P. cinnamomi infection, including its involvement in sporangia production, mycelial growth, and the targeting of plant immune proteins to enhance pathogen virulence.


Asunto(s)
Muerte Celular , Phytophthora , Enfermedades de las Plantas , Inmunidad de la Planta , Phytophthora/patogenicidad , Phytophthora/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Virulencia , Factores de Virulencia/genética , Núcleo Celular/metabolismo , Interacciones Huésped-Patógeno , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/inmunología , Nicotiana/microbiología , Nicotiana/inmunología , Hifa/genética , Hifa/crecimiento & desarrollo , Hifa/inmunología
18.
STAR Protoc ; 5(3): 103134, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38900632

RESUMEN

Fundus fluorescein angiography (FFA) examinations are widely used in the evaluation of fundus disease conditions to facilitate further treatment suggestions. Here, we present a protocol for performing deep learning-based FFA image analytics with classification and segmentation tasks. We describe steps for data preparation, model implementation, statistical analysis, and heatmap visualization. The protocol is applicable in Python using customized data and can achieve the whole process from diagnosis to treatment suggestion of ischemic retinal diseases. For complete details on the use and execution of this protocol, please refer to Zhao et al.1.

19.
Front Pediatr ; 12: 1383342, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827220

RESUMEN

Objective: This study aimed to analyse the research hotspots and frontiers in the field of paediatric fever between 2013 and 2023. Methods: The included articles were visually analysed using CiteSpace 6.1.R6 software. Results: A total of 2,662 Chinese-language articles and 1,456 English-language articles were included in the study. Based on the Chinese literature, research groups were identified represented by Xinmin Li, Jinling Hong and Hongshuang Luo. Based on the English literature, research groups were formed represented by Henriette Moll, Santiago Mintegi and Elizabeth Alpern. Tianjin University of Traditional Chinese Medicine was the institution with the largest number of publications in the Chinese literature, and the Centers For Disease Control And Prevention was the institution with the largest number of publications in the English literature. The research on paediatric fever mainly focused on mechanism exploration, green treatment and clinical management. Conclusion: Several relatively stable research groups have been formed. Future studies on the differential diagnosis, rational drug use, standardised management and clinical practice guidelines for paediatric fever are needed.

20.
Eur J Med Res ; 29(1): 336, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890700

RESUMEN

BACKGROUND: Femoral head varus triggers poor clinical prognosis in intertrochanteric fracture patients with proximal femoral nail antirotation (PFNA) fixation. Studies present that changes in nail position and screw insertion angles will affect fixation stability, but the biomechanical significance of these factors on the risk of femoral head varus has yet to be identified in PFNA fixed patients. METHODS: Clinical data in PFNA fixed intertrochanteric fracture patients have been reviewed, the relative position of intermedullary nail has been judged in the instant postoperative lateral radiography. Regression analyses have been performed to identify the effect of this factor on femoral head varus. Corresponding biomechanical mechanism has been identified by numerical mechanical simulations. RESULTS: A clinical review revealed that ventral side nail insertion can trigger higher risk of femoral head varus, corresponding numerical mechanical simulations also recorded poor fixation stability in models with ventral side nail insertion, and changes in the trajectory of anti-rotation blade will not obviously affect this tendency. CONCLUSIONS: Ventral side insertion of intramedullary nail can trigger higher risk of femoral head varus in PFNA fixed patients by deteriorating the instant postoperative biomechanical environment, and changes in blade trajectory cannot change this tendency biomechanically. Therefore, this nail position should be adjusted to optimize patients' prognosis.


Asunto(s)
Clavos Ortopédicos , Cabeza Femoral , Fijación Intramedular de Fracturas , Fracturas de Cadera , Humanos , Fenómenos Biomecánicos , Cabeza Femoral/cirugía , Cabeza Femoral/fisiopatología , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/instrumentación , Fracturas de Cadera/cirugía
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