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1.
Artigo em Inglês | MEDLINE | ID: mdl-39288783

RESUMO

This study discussed comparing result accuracy and time cost under different tally methods using MCNP6 for a novel transmission X-ray tube which was designed for the Auger electron yield with specific material (eg. iodine). The assessment included photon spectrum, percent depth dose, mass-energy absorption coefficient corresponding to air and water, and figure of merit comparison. The mean energy of in-air phantom was from 41.8 keV (0 mm) to 40.9 keV (100 mm), and the mean energy of in-water phantom was from 41.41 keV (0 mm) to 45.2 keV (100 mm). The specific dose conversion factors based mass-energy absorption coefficient corresponding to different materials was established and the difference was less than 2% for the dose conversion of FMESH comparing to measurement data. FMESH had better figure of merit (FOM) than the F6 tally for the dose parameter assessment, which mean the dose calculation that focused on the superficial region could be assessed with more calculation efficiency by FMESH tally for this novel transmission X-ray tube. The results of this study could help develop treatment planning system (TPS) to quickly obtain the calculated data for phase space data establishment and heterogeneous correction under different physical condition settings. .

3.
Plant J ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312631

RESUMO

In plants, RNA silencing constitutes a strong defense against viral infection, which viruses counteract with RNA-silencing suppressors (RSSs). Understanding the interactions between viral RSSs and host factors is crucial for elucidating the molecular arms race between viruses and host plants. We report that the helicase motif (Hel) of the replicase encoded by apple stem grooving virus (ASGV)-the main virus affecting pear trees in China-is an RSS that can inhibit both local and systemic RNA silencing, possibly by binding double-stranded (ds) siRNA. The transcription factor related to ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 from pear (PbRAV1) enters the cytoplasm and binds Hel through its C terminus, thereby attenuating its RSS activity by reducing its binding affinity to 21- and 24-nt ds siRNA, and suppressing ASGV infection. PbRAV1 can also target p24, an RSS encoded by grapevine leafroll-associated virus 2 (GLRaV-2), with similar negative effects on p24's suppressive function and inhibition of GLRaV-2 infection. Moreover, like the positive role of the PbRAV1 homolog from grapevine (VvRAV1) in p24's previously reported RSS activity, ASGV Hel can also hijack VvRAV1 and employ the protein to sequester 21-nt ds siRNA, thereby enhancing its own RSS activity and promoting ASGV infection. Furthermore, PbRAV1 neither interacts with CP, an RSS encoded by grapevine inner necrosis virus, nor has any obvious effect on CP's RSS activity. Our results identify an RSS encoded by ASGV and demonstrate that PbRAV1, representing a novel type of RAV transcription factor, plays a defensive role against viral infection by targeting viral RSSs.

4.
Foods ; 13(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39272592

RESUMO

Applications of millet bran dietary fiber (MBDF) in the food industry are limited by its poor hydration properties. Herein, MBDF was modified by heating, xylanase and cellulase treatment separately combined with carboxymethylation, acetylation, and phosphate crosslinking, and the effects of the modified MBDFs on heat-induced egg white protein gel (H-EWG) were studied. The results showed that three composite modifications, especially heating and dual enzymolysis combined with carboxymethylation, increased the surface area, soluble fiber content, and hydration properties of MBDF (p < 0.05). MBDF and the modified MBDFs all made the microstructure of H-EWG denser and decreased its α-helix content. Three composite modifications, especially heating and dual enzymolysis combined with carboxymethylation, enhanced the improving effect of MBDF on the WRA (from 24.89 to 35.53 g/g), pH, hardness (from 139.93 to 323.20 g), chewiness, and gumminess of H-EWPG, and enhanced the gastric stability at 3-5 g/100 g. MBDFs modified with heating and dual enzymolysis combined with acetylation or crosslinking were more effective in increasing the antioxidant activity of the gastrointestinal hydrolysates of H-EWG than MBDF (p < 0.05). Overall, heating, xylanase and cellulase treatment separately combined with carboxymethylation, acetylation and crosslinking can enhance the hydration properties and the improving effect of millet bran fibers on H-EWG properties.

5.
Int J Mol Sci ; 25(17)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39273180

RESUMO

Rubisco small subunit (RbcS), a core component with crucial effects on the structure and kinetic properties of the Rubisco enzyme, plays an important role in response to plant growth, development, and various stresses. Although Rbcs genes have been characterized in many plants, their muti-functions in soybeans remain elusive. In this study, a total of 11 GmRbcS genes were identified and subsequently divided into three subgroups based on a phylogenetic relationship. The evolutionary analysis revealed that whole-genome duplication has a profound effect on GmRbcSs. The cis-acting elements responsive to plant hormones, development, and stress-related were widely found in the promoter region. Expression patterns based on the RT-qPCR assay exhibited that GmRbcS genes are expressed in multiple tissues, and notably Glyma.19G046600 (GmRbcS8) exhibited the highest expression level compared to other members, especially in leaves. Moreover, differential expressions of GmRbcS genes were found to be significantly regulated by exogenous plant hormones, demonstrating their potential functions in diverse biology processes. Finally, the function of GmRbcS8 in enhancing soybean resistance to soybean mosaic virus (SMV) was further determined through the virus-induced gene silencing (VIGS) assay. All these findings establish a strong basis for further elucidating the biological functions of RbcS genes in soybeans.


Assuntos
Regulação da Expressão Gênica de Plantas , Glycine max , Filogenia , Reguladores de Crescimento de Plantas , Potyvirus , Glycine max/genética , Glycine max/virologia , Glycine max/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Potyvirus/patogenicidade , Ribulose-Bifosfato Carboxilase/genética , Ribulose-Bifosfato Carboxilase/metabolismo , Perfilação da Expressão Gênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Doenças das Plantas/virologia , Doenças das Plantas/genética , Genoma de Planta , Estudo de Associação Genômica Ampla , Resistência à Doença/genética , Família Multigênica
6.
Ital J Pediatr ; 50(1): 185, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294681

RESUMO

BACKGROUND: Echocardiography-based ultrasomics analysis aids Kawasaki disease (KD) diagnosis but its role in predicting coronary artery lesions (CALs) progression remains unknown. We aimed to develop and validate a predictive model combining echocardiogram-based ultrasomics with clinical parameters for CALs progression in KD. METHODS: Total 371 KD patients with CALs at baseline were enrolled from a retrospective cohort (cohort 1, n = 316) and a prospective cohort (cohort 2, n = 55). CALs progression was defined by increased Z scores in any coronary artery branch at the 1-month follow-up. Patients in cohort 1 were split randomly into training and validation set 1 at the ratio of 6:4, while cohort 2 comprised validation set 2. Clinical parameters and ultrasomics features at baseline were analyzed and selected for models construction. Model performance was evaluated by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) and decision curve analysis (DCA) in the training and two validation sets. RESULTS: At the 1-month follow-ups, 65 patients presented with CALs progression. Three clinical parameters and six ultrasomics features were selected to construct the model. The clinical-ultrasomics model exhibited a good predictive capability in the training, validation set 1 and set 2, achieving AUROCs of 0.83 (95% CI, 0.75-0.90), 0.84 (95% CI, 0.74-0.94), and 0.73 (95% CI, 0.40-0.86), respectively. Moreover, the AUPRC values and DCA of three model demonstrated that the clinical-ultrasomics model consistently outperformed both the clinical model and the ultrasomics model across all three sets, including the training set and the two validation sets. CONCLUSIONS: Our study demonstrated the effective predictive capacity of a prediction model combining echocardiogram-based ultrasomics features and clinical parameters in predicting CALs progression in KD.


Assuntos
Doença da Artéria Coronariana , Progressão da Doença , Ecocardiografia , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Lactente , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Prospectivos , Valor Preditivo dos Testes
7.
Cognition ; 254: 105951, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39276726

RESUMO

Different organizational structures have been argued to underlie semantic knowledge about concepts; taxonomic organization, based on shared features, and thematic organization based on co-occurrence in common scenes and scenarios. The goal of the current study is to examine which of the two organizational systems are more engaged in the semantic context of a picture naming task. To address this question, we examined the representational structure underlying the semantic space in different picture naming tasks by applying representational similarity analysis (RSA) to electroencephalography (EEG) datasets. In a series of experiments, EEG signals were collected while participants named pictures under different semantic contexts. Study 1 reanalyzes existing data from semantic contexts directing attention to taxonomic organization and semantic contexts that are not biased towards either taxonomic or thematic organization. In Study 2 we keep the stimuli the same and vary semantic contexts to draw attention to either taxonomic or thematic organization. The RSA approach allows us to examine the pairwise similarity in scalp-recorded amplitude patterns at each time point following the onset of the picture and relate it to theoretical taxonomic and thematic measures derived from computational models of semantics. Across all tasks, the similarity structure of scalp-recorded neural activity correlated better with taxonomic than thematic measures, in time windows associated with semantic processing. Most strikingly, we found that the scalp-recorded patterns of neural activity between taxonomically related items were more similar to each other than the scalp-recorded patterns of neural activity for thematically related or unrelated items, even in tasks that makes thematic information more salient. These results suggest that the principle semantic organization of these concepts during picture naming is taxonomic, at least in the context of picture naming.

8.
Biochim Biophys Acta Mol Basis Dis ; 1870(8): 167454, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39122224

RESUMO

Increasing evidence indicated that neuroinflammation was involved in progression of Parkinson's disease (PD). Long noncoding RNAs (lncRNAs) played important roles in regulating inflammatory processes in multiple kinds of human diseases such as cancer diabetes, cardiomyopathy, and neurodegenerative disorders. The mechanisms by which lncRNAs regulated PD related inflammation and dopaminergic neuronal loss have not yet been fully elucidated. In current study, we intended to explore the function and potential mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in regulating inflammasome activation in PD. Functional assays confirmed that knockdown of KCNQ1OT1 suppress microglial NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and attenuated dopaminergic neuronal loss in PD model mice. As KCNQ1OT1 located in both cytoplasm and nucleus of microglia, we demonstrated that KCNQ1OT1 promoted microglial NLRP3 inflammasome activation by competitive binding with miR-186 in cytoplasm and inhibited pri-miR-186 mediated NLRP3 silencing through recruitment of DiGeorge syndrome critical region gene 8 (DGCR8) in nucleus, respectively. Our study found a novel lncRNA-pri-miRNA/mature miRNA-mRNA regulatory network in microglia mediated NLRP3 inflammasome activation and dopaminergic neuronal loss, provided further insights for the treatment of Parkinson's disease.


Assuntos
Inflamassomos , MicroRNAs , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doença de Parkinson , RNA Longo não Codificante , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Inflamassomos/metabolismo , Inflamassomos/genética , Camundongos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Humanos , Microglia/metabolismo , Microglia/patologia , Camundongos Endogâmicos C57BL , Masculino , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia
9.
Antioxidants (Basel) ; 13(8)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39199249

RESUMO

Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS's anti-CC effects, and SS's inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.

10.
Life Sci ; 354: 122945, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39127319

RESUMO

Renal fibrosis is the common final pathway of progressive renal diseases, in which the macrophages play an important role. ELISA was used to detect CD5 antigen-like (CD5L) in serum samples from end-stage renal disease (ESRD), as well as in mice serum with unilateral ureteral occlusion (UUO). Recombinant CD5L was injected into UUO mice to assess renal injury, fibrosis, and macrophage infiltration. The expression of CD5L was significantly upregulated in the serum of patients with ESRD and UUO mice. Histological analysis showed that rCD5L-treated UUO mice had more severe renal injury and fibrosis. Furthermore, rCD5L promoted the phenotypic transfer of monocytes from Ly6Chigh to LyC6low. RCD5L promoted TGF-ß signaling pathway activation by promoting Smad2/3 phosphorylation. We used Co-IP to identify HSPA5 interact with CD5L on cell membrane could inhibit the formation of the Cripto/HSPA5 complex, and promote the activation of the TGF-ß signaling pathway. The CD5L antibody could reduce the degree of renal fibrosis in UUO mice.


Assuntos
Chaperona BiP do Retículo Endoplasmático , Fibrose , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fator de Crescimento Transformador beta , Regulação para Cima , Animais , Camundongos , Fator de Crescimento Transformador beta/metabolismo , Humanos , Masculino , Chaperona BiP do Retículo Endoplasmático/metabolismo , Proteínas Ligadas por GPI/metabolismo , Rim/patologia , Rim/metabolismo , Obstrução Ureteral/patologia , Obstrução Ureteral/metabolismo , Feminino , Pessoa de Meia-Idade , Proteínas Reguladoras de Apoptose , Receptores Depuradores
11.
Assist Technol ; : 1-15, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137956

RESUMO

UNav is a computer-vision-based localization and navigation aid that provides step-by-step route instructions to reach selected destinations without any infrastructure in both indoor and outdoor environments. Despite the initial literature highlighting UNav's potential, clinical efficacy has not yet been rigorously evaluated. Herein, we assess UNav against standard in-person travel directions (SIPTD) for persons with blindness or low vision (PBLV) in an ecologically valid environment using a non-inferiority design. Twenty BLV subjects (age = 38 ± 8.4; nine females) were recruited and asked to navigate to a variety of destinations, over short-range distances (<200 m), in unfamiliar spaces, using either UNav or SIPTD. Navigation performance was assessed with nine dependent variables to assess travel confidence, as well as spatial and temporal performances, including path efficiency, total time, and wrong turns. The results suggest that UNav is not only non-inferior to the standard-of-care in wayfinding (SIPTD) but also superior on 8 out of 9 metrics, as compared to SIPTD. This study highlights the range of benefits computer vision-based aids provide to PBLV in short-range navigation and provides key insights into how users benefit from this systematic form of computer-aided guidance, demonstrating transformative promise for educational attainment, gainful employment, and recreational participation.

12.
Ecotoxicol Environ Saf ; 284: 116903, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39205354

RESUMO

Ice, water, and sediment represent three interconnected habitats in lake ecosystems, and bacteria are crucial for maintaining ecosystem equilibrium and elemental cycling across these habitats. However, the differential characteristics and driving mechanisms of bacterial community structures in the ice, water, and sediments of seasonally frozen lakes remain unclear. In this study, high-throughput sequencing technology was used to analyze and compare the structure, function, network characteristics, and assembly mechanisms of bacterial communities in the ice, water, and sediment of Wuliangsuhai, a typical cold region in Inner Mongolia. The results showed that the bacterial communities in the ice and water phases had similar diversity and composition, with Proteobacteria, Bacteroidota, Actinobacteria, Campilobacterota, and Cyanobacteria as dominant phyla. The bacterial communities in sediments displayed significant differences from ice and water, with Chloroflexi, Proteobacteria, Firmicutes, Desulfobacterota, and Acidobacteriota being the dominant phyla. Notably, the bacterial communities in water exhibited higher spatial variability in their distribution than those in ice and sediment. This study also revealed that during the frozen period, the bacterial community species in the ice, water, and sediment media were dominated by cooperative relationships. Community assembly was primarily influenced by stochastic processes, with dispersal limitation and drift identified as the two most significant factors within this process. However, heterogeneous selection also played a significant role in the community composition. Furthermore, functions related to nitrogen, phosphorus, sulfur, carbon, and hydrogen cycling vary among bacterial communities in ice, water, and sediment. These findings elucidate the intrinsic mechanisms driving variability in bacterial community structure and changes in water quality across different media phases (ice, water, and sediment) in cold-zone lakes during the freezing period, offering new insights for water environmental protection and ecological restoration efforts in such environments.

13.
Front Cell Dev Biol ; 12: 1412909, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206091

RESUMO

Introduction: The potential neuroprotective and regenerative properties of electrical stimulation (ES) were studied in rhodopsin knockout mice (Rho -/- ), a murine model of inherited retinal degeneration. The study focused on assessing the impact of varying ES frequencies on visual functions and photoreceptor cell survival in Rho -/- mice. Methods: To elucidate the impact of electrical stimulation on cone survival, Rho -/- mice received either sham or transpalpebral ES using biphasic ramp or rectangular waveforms at 100 µA amplitude, starting at six weeks of age. The treatment duration spanned from one to three weeks. The optimal treatment frequency of ES sessions was determined by applying ES every one, two, or three days in three separate groups of Rho -/- mice. The sham group received daily treatments without the application of ES. Results: Our study revealed significant improvement of visual function in Rho -/- mice following daily or every-other-day noninvasive transpalpebral ES, as evidenced by electroretinogram and optomotor response-based visual behavior assays. Concurrently, assessment of outer nuclear thickness and immunohistochemistry for the cone photoreceptor cell marker PNA demonstrated pronounced increases in the survival of rods and cones and improvement in the morphology of the inner and outer segments. Discussion: This study underscores the protective effect of non-invasive ES in rhodopsin knockout-induced retinal degenerative disorders, providing a foundation for developing targeted therapeutic interventions for retinitis pigmentosa.

14.
Front Plant Sci ; 15: 1414844, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988631

RESUMO

Background: Border row effects impact the ecosystem functions of intercropping systems, with high direct interactions between neighboring row crops in light, water, and nutrients. However, previous studies have mostly focused on aboveground, whereas the effects of intercropping on the spatial distribution of the root system are poorly understood. Field experiments and planting box experiments were combined to explore the yield, dry matter accumulation, and spatial distribution of root morphological indexes, such as root length density (RLD), root surface area density (RSAD), specific root length (SRL), and root diameter (RD), of maize and peanut and interspecific interactions at different soil depths in an intercropping system. Results: In the field experiments, the yield of intercropped maize significantly increased by 33.45%; however, the yield of intercropped peanut significantly decreased by 13.40%. The land equivalent ratio (LER) of the maize-peanut intercropping system was greater than 1, and the advantage of intercropping was significant. Maize was highly competitive (A = 0.94, CR=1.54), and the yield advantage is mainly attributed to maize. Intercropped maize had higher RLD, RSAD, and SRL than sole maize, and intercropped peanut had lower RLD, RSAD, and SRL than sole peanut. In the interspecific interaction zone, the increase in RLD, RSAD, SRL, and RD of intercropped maize was greater than that of intercropped peanut, and maize showed greater root morphological plasticity than peanut. A random forest model determined that RSAD significantly impacted yield at 15-60 cm, while SRL had a significant impact at 30-60 cm. Structural equation modeling revealed that root morphology indicators had a greater effect on yield at 30-45 cm, with interactions between indicators being more pronounced at this depth. Conclusion: These results show that border-row effects mediate the plasticity of root morphology, which could enhance resource use and increase productivity. Therefore, selecting optimal intercropping species and developing sustainable intercropping production systems is of great significance.

15.
Curr Gene Ther ; 24(5): 347-355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005061

RESUMO

Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patterns and functions of HGF in ovarian and testicular physiology from the prenatal to the adult stage. HGF regulates folliculogenesis and steroidogenesis by modulating the functions of theca cells and granulosa cells in the ovary. It also mediates somatic cell proliferation and steroidogenesis, thereby affecting spermatogenesis in males. In addition to its physiological effects on the reproductive system, HGF has shown advantages in preclinical studies over recent years for the treatment of male and female infertility, particularly in women with premature ovarian insufficiency. This review aims to summarize the pleiotropic functions of HGF in the reproductive system and to provide prospects for its clinical application.


Assuntos
Fator de Crescimento de Hepatócito , Humanos , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Feminino , Masculino , Reprodução/genética , Animais , Ovário/metabolismo , Espermatogênese , Testículo/metabolismo , Células da Granulosa/metabolismo
16.
Sci Bull (Beijing) ; 69(16): 2596-2603, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39025777

RESUMO

This was a single-arm, multicenter, open-label phase I trial. Lentiviral vectors (LV) carrying the ABCD1 gene (LV-ABCD1) was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy (CCALD), and multi-site injection was performed. The injection dose increased from 200 to 1600 µL (vector titer: 1×109 transduction units per mL (TU/mL)), and the average dose per kilogram body weight ranges from 8 to 63.6 µL/kg. The primary endpoint was safety, dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein. A total of 7 patients participated in this phase I study and were followed for 1 year. No injection-related serious adverse event or death occurred. Common adverse events associated with the injection were irritability (71%, 5/7) and fever (37.2-38.5 â„ƒ, 57%, 4/7). Adverse events were mild and self-limited, or resolved within 3 d of symptomatic treatment. The maximal tolerable dose is 1600 µL. In 5 cases (83.3%, 5/6), no lentivirus associated antibodies were detected. The overall survival at 1-year was 100%. The ABCD1 protein expression was detected in neutrophils, monocytes and lymphocytes. This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo; even the maximal dose did not increase the risk of adverse events. Furthermore, the direct LV-ABCD1 injection displayed low immunogenicity. In addition, the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed. This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, registration number: ChiCTR1900026649).


Assuntos
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP , Adrenoleucodistrofia , Terapia Genética , Vetores Genéticos , Lentivirus , Humanos , Adrenoleucodistrofia/terapia , Adrenoleucodistrofia/genética , Lentivirus/genética , Masculino , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP/genética , Criança , Vetores Genéticos/administração & dosagem , Feminino , Terapia Genética/métodos , Adolescente , Pré-Escolar , Encéfalo/metabolismo , Encéfalo/patologia , Resultado do Tratamento
17.
Free Radic Biol Med ; 223: 493-505, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39048340

RESUMO

Increasing evidence underscores the pivotal role of ferroptosis in Parkinson's Disease (PD) pathogenesis. Acteoside (ACT) has been reported to possess neuroprotective properties. However, the effects of ACT on ferroptosis and its molecular mechanisms remain unknown. This study aimed to explore whether ACT can regulate ferroptosis in dopaminergic (DA) neurons within both in vitro and in vivo PD models and to elucidate the underlying regulatory mechanisms. PD models were established and treated with various concentrations of ACT. Cell viability assays, Western blot, lipid peroxidation assessments, immunohistochemistry, and transmission electron microscopy were employed to confirm ACT's inhibition of ferroptosis and its protective effect on DA neurons across PD models. Immunofluorescence staining, MitoSOX staining, and confocal laser scanning microscopy further validated ACT's regulation regulatory effects on ferroptosis via the Nrf2-mitophagy pathway. Four animal behavioral tests were used to assess behavioral improvements in PD animals. ACT inhibited ferroptosis in PD models in vitro, as evidenced by increased cell viability, the upregulation of GPX4 and SLC7A11, reduced lipid peroxides, and attenuation of mitochondrial morphological alterations typical of ferroptosis. By activating the Nrf2-mitophagy axis, ACT enhanced mitochondrial integrity and reduced lipid peroxidation, mitigating ferroptosis. These in vitro results were consistent with in vivo findings, where ACT treatment significantly preserved DA neurons, curbed ferroptosis in these cells, and alleviated cognitive and behavioral deficits. This study is the first demonstration of ACT's capability to inhibit neuronal ferroptosis and protect DA neurons, thus alleviating behavioral and cognitive impairments in both in vitro and in vivo PD models. Furthermore, The suppression of ferroptosis by ACT is achieved through the activation of the Nrf2-mitophagy signaling pathway. Our results show that ACT is beneficial for both treating and preventing PD. They also offer novel therapeutic options for treating PD and molecular targets for regulating ferroptosis.


Assuntos
Neurônios Dopaminérgicos , Ferroptose , Glucosídeos , Peroxidação de Lipídeos , Mitofagia , Fator 2 Relacionado a NF-E2 , Fármacos Neuroprotetores , Doença de Parkinson , Fenóis , Ferroptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Glucosídeos/farmacologia , Camundongos , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Fármacos Neuroprotetores/farmacologia , Mitofagia/efeitos dos fármacos , Fenóis/farmacologia , Masculino , Modelos Animais de Doenças , Humanos , Sobrevivência Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Polifenóis
18.
Plants (Basel) ; 13(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891251

RESUMO

Owing to the rising demand for vegetable soybean products, there is an increasing need for high-yield soybean varieties. However, the complex correlation patterns among quantitative traits with genetic architecture pose a challenge for improving vegetable soybean through breeding. Herein, a genome-wide association study (GWAS) was applied to 6 yield-related traits in 188 vegetable soybean accessions. Using a BLINK model, a total of 116 single nucleotide polymorphisms (SNPs) were identified for plant height, pod length, pod number, pod thickness, pod width, and fresh pod weight. Furthermore, a total of 220 genes were found in the 200 kb upstream and downstream regions of significant SNPs, including 11 genes encoding functional proteins. Among them, four candidate genes, Glyma.13G109100, Glyma.03G183200, Glyma.09G102200, and Glyma.09G102300 were analyzed for significant haplotype variations and to be in LD block, which encode MYB-related transcription factor, auxin-responsive protein, F-box protein, and CYP450, respectively. The relative expression of candidate genes in V030 and V071 vegetable soybean (for the plant height, pod number, and fresh pod weight of V030 were lower than those of the V071 strains) was significantly different, and these genes could be involved in plant growth and development via various pathways. Altogether, we identified four candidate genes for pod yield and plant height from vegetable soybean germplasm. This study provides insights into the genomic basis for improving soybean and crucial genomic resources that can facilitate genome-assisted high-yielding vegetable soybean breeding.

19.
BMC Genomics ; 25(1): 578, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858635

RESUMO

BACKGROUND: Rose myrtle (Rhodomyrtus tomentosa (Ait.) Hassk), is an evergreen shrub species belonging to the family Myrtaceae, which is enriched with bioactive volatiles (α-pinene and ß-caryophyllene) with medicinal and industrial applications. However, the mechanism underlying the volatile accumulation in the rose myrtle is still unclear. RESULTS: Here, we present a chromosome-level genomic assembly of rose myrtle (genome size = 466 Mb, scaffold N50 = 43.7 Mb) with 35,554 protein-coding genes predicted. Through comparative genomic analysis, we found that gene expansion and duplication had a potential contribution to the accumulation of volatile substances. We proposed that the action of positive selection was significantly involved in volatile accumulation. We identified 43 TPS genes in R. tomentosa. Further transcriptomic and TPS gene family analyses demonstrated that the distinct gene subgroups of TPS may contribute greatly to the biosynthesis and accumulation of different volatiles in the Myrtle family of shrubs and trees. The results suggested that the diversity of TPS-a subgroups led to the accumulation of special sesquiterpenes in different plants of the Myrtaceae family. CONCLUSIONS: The high quality chromosome-level rose myrtle genome and the comparative analysis of TPS gene family open new avenues for obtaining a higher commercial value of essential oils in medical plants.


Assuntos
Cromossomos de Plantas , Evolução Molecular , Genoma de Planta , Genômica , Myrtaceae , Terpenos , Terpenos/metabolismo , Genômica/métodos , Myrtaceae/genética , Myrtaceae/metabolismo , Cromossomos de Plantas/genética , Filogenia , Família Multigênica
20.
Sci Rep ; 14(1): 14290, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906992

RESUMO

To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48-86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery.


Assuntos
Stents , Artéria Subclávia , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Artéria Subclávia/cirurgia , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento , Síndrome do Roubo Subclávio/terapia , Síndrome do Roubo Subclávio/cirurgia , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversos , Angioplastia/métodos , Angioplastia/efeitos adversos , Constrição Patológica/terapia , Angioplastia com Balão/métodos , Angioplastia com Balão/efeitos adversos , Arteriopatias Oclusivas/terapia , Arteriopatias Oclusivas/cirurgia
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