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1.
iScience ; 27(5): 109617, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38660401

RESUMO

Long-term manned spaceflight and extraterrestrial planet settlement become the focus of space powers. However, the potential influence of closed and socially isolating spaceflight on the brain function remains unclear. A 180-day controlled ecological life support system integrated experiment was conducted, establishing a spaceflight analog environment to explore the effect of long-term socially isolating living. Three crewmembers were enrolled and underwent resting-state fMRI scanning before and after the experiment. We performed both seed-based and network-based analyses to investigate the functional connectivity (FC) changes of the default mode network (DMN), considering its key role in multiple higher-order cognitive functions. Compared with normal controls, the leader of crewmembers exhibited significantly reduced within-DMN and between-DMN FC after the experiment, while two others exhibited opposite trends. Moreover, individual differences of FC changes were further supported by evidence from behavioral analyses. The findings may shed new light on the development of psychological protection for space exploration.

2.
Wei Sheng Yan Jiu ; 53(2): 243-256, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38604960

RESUMO

OBJECTIVE: To understand the prevalence, genetic characteristics and drug resistance features of Salmonella Kentucky ST314 in Shenzhen. METHODS: Whole genome sequencing of 14 strains of Salmonella Kentucky ST314 collected from 2010-2021 by the Foodborne Disease Surveillance Network of Shenzhen Center for Disease Control and Prevention for phylogenetic evolutionary analysis, drug resistance gene and plasmid detection; drug susceptibility experiments were performed by micro-broth dilution method. RESULTS: A total of 57 strains of Salmonella Kentucky were collected from the foodborne disease surveillance network, 14 of which were ST314. The Shenzhen isolates were clustered with isolates from Southeast Asian countries such as Vietnam and Thailand on clade 314.2, and the single nucleotide polymorphism distance between local strains in Shenzhen was large, indicating dissemination. In this study, a total of 17 drug resistance genes/mutations in 9 categories were detected in the genome of Salmonella Kentucky ST314, carrying 3 extended spectrum beta-lactamases(ESBLs), including bla_(CTX-M-24)(14.3%, 2/14), bla_(CTX-M-55)(7.1%, 1/14), and bla_(CTX-M-130)(14.3%, 2/14), all located on plasmids. Regarding quinolone resistance factors, two plasmid-mediated quinolone resistance(PMQR) genes were identified in the genome: qnrB6(71.4%, 10/14) and aac(6')Ib-cr(78.6%, 11/14), a quinolone resistance quinolone resistance-determining regions(QRDR) mutation T57 S(100%, 14/14). The multi-drug resistance rate of Salmonella Kentucky ST314 in Shenzhen was 92.86%(13/14)with the highest rate of resistance to tetracycline and cotrimoxazole(100%, 14/14), followed by chloramphenicol(92.86%, 13/14), cefotaxime and ampicillin(78.57%, 11/14), ciprofloxacin and nalidixic acid(71.43%, 10/14), and ampicillin-sulbactam had the lowest resistance rate(21.43%, 3/14). CONCLUSION: ST314 is the second most prevalent ST type among Salmonella Kentucky in Shenzhen, mainly isolated from food, especially poultry; phylogenetic analysis suggests that ST314 is a disseminated infection and the genome shows a highly genetically conserved phenotype. Drug resistance of Salmonella Kentucky ST314 is very serious, especially QRDR mutation, PMQR gene co-mediated quinolone resistance and plasmid-mediated cephalosporin resistance are prominent and deserve extensive attention.


Assuntos
Doenças Transmitidas por Alimentos , Quinolonas , Humanos , Kentucky , Filogenia , Salmonella , Antibacterianos/farmacologia , Plasmídeos/genética , Resistência a Medicamentos , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/genética , beta-Lactamases/genética
3.
Protein Cell ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635907

RESUMO

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

4.
Signal Transduct Target Ther ; 9(1): 86, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584163

RESUMO

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.


Assuntos
Células-Tronco Pluripotentes , Ausência de Peso , Humanos , 60645 , Miócitos Cardíacos/metabolismo , Cálcio/metabolismo , Diferenciação Celular , Células-Tronco Pluripotentes/metabolismo
5.
Sci Rep ; 14(1): 1388, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438385

RESUMO

Aircraft icing deteriorates aerodynamic performance and reduces stall angle of attack, the fast convergence rate of tracking error is required to stabilize the aircraft when aircraft icing occurs. The state-of-the-art control methods for icing aircraft mostly assume that the icing of aircraft is instantaneous. Aiming at these issues, a fixed-time angle of attack-constrained control strategy is designed considering dynamic icing process. In order to explore the variation of aerodynamic coefficients in the process of dynamic icing, an ice wind tunnel experiment is implemented, and the relationship between lift coefficient, drag coefficient and pitching moment coefficient with angle of attack and icing intensity is obtained by fitting method. In order to prevent the stalling problem caused by the decrease of the stalling angle of attack in the process of dynamic icing, a method to determine the stalling angle of attack based on deep neural network is proposed. Considering the asymmetric and time-varying angle of attack constraint, a fixed-time convergent angle of attack-constrained robust control method is designed. The ice wind tunnel experiment shows the process of dynamic icing of the airfoil, and the simulation results verify the effectiveness of the proposed control method.

6.
Nat Commun ; 15(1): 2513, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514625

RESUMO

In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression.


Assuntos
Mieloma Múltiplo , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Transcriptoma , Epigenoma , Transdução de Sinais/genética , Subunidade p52 de NF-kappa B/metabolismo
7.
Nanomicro Lett ; 16(1): 160, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512500

RESUMO

MgH2 is a promising high-capacity solid-state hydrogen storage material, while its application is greatly hindered by the high desorption temperature and sluggish kinetics. Herein, intertwined 2D oxygen vacancy-rich V2O5 nanosheets (H-V2O5) are specifically designed and used as catalysts to improve the hydrogen storage properties of MgH2. The as-prepared MgH2-H-V2O5 composites exhibit low desorption temperatures (Tonset = 185 °C) with a hydrogen capacity of 6.54 wt%, fast kinetics (Ea = 84.55 ± 1.37 kJ mol-1 H2 for desorption), and long cycling stability. Impressively, hydrogen absorption can be achieved at a temperature as low as 30 °C with a capacity of 2.38 wt% within 60 min. Moreover, the composites maintain a capacity retention rate of ~ 99% after 100 cycles at 275 °C. Experimental studies and theoretical calculations demonstrate that the in-situ formed VH2/V catalysts, unique 2D structure of H-V2O5 nanosheets, and abundant oxygen vacancies positively contribute to the improved hydrogen sorption properties. Notably, the existence of oxygen vacancies plays a double role, which could not only directly accelerate the hydrogen ab/de-sorption rate of MgH2, but also indirectly affect the activity of the catalytic phase VH2/V, thereby further boosting the hydrogen storage performance of MgH2. This work highlights an oxygen vacancy excited "hydrogen pump" effect of VH2/V on the hydrogen sorption of Mg/MgH2. The strategy developed here may pave a new way toward the development of oxygen vacancy-rich transition metal oxides catalyzed hydride systems.

8.
NPJ Vaccines ; 9(1): 28, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341504

RESUMO

Hantaan virus (HTNV) is a pathogenic orthohantavirus prevalent in East Asia that is known to cause hemorrhagic fever with severe renal syndrome (HFRS), which has a high fatality rate. However, a Food and Drug Administration (FDA)-approved vaccine is not currently available against this virus. Although inactivated vaccines have been certified and used in endemic regions for decades, the neutralizing antibody (NAb) titer induced by inactivated vaccines is low and the immunization schedule is complicated, requiring at least three injections spanning approximately 6 months to 1 year. Replication-competent vesicular stomatitis virus (VSV)-based vaccines provide prolonged protection after a single injection. In this study, we successfully engineered the HTNV glycoprotein (GP) in the VSV genome by replacing the VSV-G open reading frame. The resulting recombinant (r) rVSV-HTNV-GP was rescued, and the immunogenicity of GP was similar to that of HTNV. BALB/c mice immunized with rVSV-HTNV-GP showed a high titer of NAb against HTNV after a single injection. Notably, the cross-reactive NAb response induced by rVSV-HTNV-GP against Seoul virus (an orthohantavirus) was higher than that induced by three sequential injections of inactivated vaccines. Upon challenge with HTNV, rVSV-HTNV-GP-immunized mice showed a profoundly reduced viral burden in multiple tissues, and inflammation in the lungs and liver was nearly undetectable. Moreover, a single injection of rVSV-HTNV-GP established a prolonged immunological memory status as the NAbs were sustained for over 1 year and provided long-term protection against HTNV infection. The findings of our study can support further development of an rVSV-HTNV-GP-based HTNV vaccine with a simplified immunization schedule.

10.
Plant Dis ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381966

RESUMO

Stripe rust, caused by Puccinia striiformis f. sp tritici (Pst), is a destructive wheat disease pathogen. Thinopyrum elongatum is a valuable germplasm including diploid, tetraploid, and decaploid with plenty of biotic and abiotic resistance. In a previous study, we generated a stripe rust resistance wheat-tetraploid Th. elongatum 1E/1D substitution line K17-841-1. To further apply the wild germplasm for wheat breeding, we selected and obtained a new homozygous wheat-tetraploid Th. elongatum translocation line T1BS·1EL using genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), oligo-FISH-Painting, and the wheat 55K single nucleotide polymorphisms (SNPs) genotyping array. The T1BS·1EL is highly resistant to stripe rust at the seedling and adult stage. Pedigree and molecular marker analyses revealed that the resistance gene was located on chromosome arm 1EL of tetraploid Th. elongatum, tentatively named Yr1EL. Besides, we developed and validated 32 Simple Sequence Repeats (SSR) markers and two kompititive allele specific PCR (KASP) assays which were specific to tetraploid Th. elongatum chromosome arm 1EL to facilitate marker-assisted selection for alien 1EL stripe rust resistance breeding. This will help us explore and locate the stripe rust resistance gene mapping on the 1E chromosome and deploy it in the wheat breeding program.

11.
ACS Biomater Sci Eng ; 10(2): 932-945, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38275448

RESUMO

Periodontitis is a bacterially induced chronic destructive inflammatory disease that leads to irreversible destruction of the tooth supporting structure, including connective tissue destruction, bone resorption, and even tooth loss. Until now, there has been no effective treatment to repair inflammatory bone loss in periodontitis. Recently, small extracellular vesicles (sEVs) emerged as the essential paracrine factors of mesenchymal stem cells (MSCs) that mediated tissue regeneration. However, limitations of antimicrobial activity associated with the use of sEVs have led to the urgency of new alternative strategies. Currently, we investigated the potential of a biocompatible oxygen-releasing thermosensitive hydrogel laded with sEVs secreted by bone marrow MSCs (BMMSCs) for the alveolar bone defect in periodontitis. The hydrogel composed of different polymers such as chitosan (CS), poloxamer 407 (P407), and cross-linked hyaluronic acid (c-HA) conglomerating is a kind of nanoporous structure material. Then, the gel matrix further encapsulated sEVs and calcium peroxide nanoparticles to realize the control of sEVs and oxygen release. Furthermore, ascorbic acid was added to achieve the REDOX equilibrium and acid-base equilibrium. The experiments in vivo and in vitro proved its good biocompatibility and effectively inhibited the growth of the periodontal main anaerobe, relieved periodontal pocket anaerobic infections, and promoted the periodontal defect regeneration. Therefore, this finding demonstrated that it was a promising approach for combating anaerobic pathogens with enhanced and selective properties in periodontal diseases, even in other bacteria-induced infections, for future clinical application.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Periodontite , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Periodontite/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
12.
J Neurophysiol ; 131(2): 311-320, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38264801

RESUMO

Body mass index (BMI) has been found to have an impact on neurodegenerative diseases such as Parkinson's disease (PD). Several studies suggested that patients with PD have a lower BMI compared with controls. However, some studies indicated the differences between patients and controls as statistically insignificant. We performed this meta-analysis to clarify the relationship between BMI and PD based on the studies published from 1975 to April 2023 in the PubMed, Embase, and Cochrane Library databases. In total, 18 case-control studies met the inclusion criteria for meta-analysis. We found a statistically significant difference in mean BMI between patients with PD and healthy controls {standardized mean difference (SMD) [95% confidence interval (CI)] = -0.36 (-0.43, -0.29), P < 0.05}. Regarding sex, seven studies were included in the meta-analysis for female/male patients with PD. The mean BMI was significantly different between males with PD and healthy males [SMD (95% CI) = -0.34 (-0.47, -0.22), P < 0.05]. Moreover, the mean BMI of females with PD was significantly different from that of corresponding healthy females [SMD (95% CI) = -0.44 (-0.57, -0.30), P < 0.05]. The meta-analysis demonstrates a significantly lower BMI in patients with PD, but no gender differences, when compared with their respective healthy individuals.NEW & NOTEWORTHY The meta-analysis demonstrates a significantly lower body mass index in patients with PD, but no gender differences, when compared with their respective healthy individuals.


Assuntos
Doença de Parkinson , Humanos , Masculino , Feminino , Índice de Massa Corporal , Fatores Sexuais , Estudos de Casos e Controles
13.
BMC Oral Health ; 24(1): 7, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172784

RESUMO

PURPOSE: To investigate the balance between post-treatment effect and continued nature growth after maxillary protraction treatment in patients with skeletal class III malocclusion. METHODS: 31 patients aged 8.79 ± 1.65 years with skeletal Class III malocclusion had been treated with maxillary protraction and the treatment lasted an average of 1.16 years. The average observation duration after treatment in the maxillary protraction group was 2.05 ± 0.39 years. In the control groups, a sample of 22 patients (9.64 ± 2.53 years) with untreated skeletal class III malocclusion and 24 patients (9.28 ± 0.96 years) with skeletal class I malocclusion were matched to the treatment group according to age, sex and observation period. The mean observation interval of the control groups was 2.39 ± 1.29 years in the class III group and 1.97 ± 0.49 years in the class I group. RESULTS: The active orthopedic treatment effect showed a opposite trend to the natural craniomaxillofacial growth effect after treatment in many aspects. In the observation duration of treatment group, decrease in ANB, Wits appraisal and BAr-AAr were statistically significant compared to class I control group (p < 0.001), and there was a significant increase in NA-FH (P < 0.001) which was contrary to class III control group. Treatment group presented a significant increase in Gn-Co (P < 0.01) and Co-Go (P < 0.001), except for changes in the extent of the mandibular base (Pog-Go, P = 0.149) compared to class I control group. The vertical maxillomandibular skeletal variables (Gonial; MP-SN; MP-FH; Y-axis) in treatment group decreased significantly compared to those in class III control group (P < 0.01). U1-SN and L1-MP showed a significant increase, which was similar to the class I group (P > 0.05), and overjet decreased significantly relative to both of the two control groups (P < 0.05). CONCLUSION: Maxillary protraction therapy led to stable outcomes in approximately 77.42% of children with Class III malocclusion approximately 2 years after treatment. Unfavorable skeletal changes were mainly due to the greater protrusion of the mandible but maxillary protraction did have a certain degree of postimpact on the mandibular base. Protraction therapy does not fundamentally change the mode of maxillary growth in Class III subjects except for the advancement of the maxilla. Craniomaxillofacial region tend to restabilize after treatment and lead to skeletal growth rotation and more dentoalveolar compensation.


Assuntos
Má Oclusão Classe III de Angle , Má Oclusão , Criança , Humanos , Maxila , Estudos Retrospectivos , Grupos Controle , Cefalometria , Má Oclusão Classe III de Angle/terapia , Mandíbula
14.
NPJ Microgravity ; 10(1): 9, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233425

RESUMO

The elevation in the optic nerve sheath (ONS) pressure (ONSP) due to microgravity-induced headward fluid shift is the primary hypothesized contributor to SANS. This longitudinal study aims to quantify the axial plane of the optic nerve subarachnoid space area (ONSSA), which is filled with cerebrospinal fluid (CSF) and expands with elevated ONSP during and after head-down tilt (HDT) bed rest (BR). 36 healthy male volunteers (72 eyes) underwent a 90-day strict 6° HDT BR. Without obtaining the pre-HDT data, measurements were performed on days 30, 60, and 90 during HDT and at 6 recovery time points extended to 180-days (R + 180) in a supine position. Portable B-scan ultrasound was performed using the 12 MHz linear array probe binocularly. The measurements of the ONS and the calculation of the ONSSA were performed with ImageJ 1.51 analysis software by two experienced observers in a masked manner. Compared to R + 180, the ONSSA on HDT30, HDT60, and HDT90 exhibited a consistently significant distention of 0.44 mm2 (95% CI: 0.13 to 0.76 mm2, P = 0.001), 0.45 mm2 (95% CI: 0.15 to 0.75 mm2, P = 0.001), and 0.46 mm2 (95% CI: 0.15 to 0.76 mm2, P < 0.001), respectively, and recovered immediately after HDT on R + 2. Such small changes in the ONSSA were below the lateral resolution limit of ultrasound (0.4 mm) and may not be clinically relevant, possibly due to ONS hysteresis causing persistent ONS distension. Future research can explore advanced quantitative portable ultrasound-based techniques and establish comparisons containing the pre-HDT measurements to deepen our understanding of SANS.

15.
CNS Neurosci Ther ; 30(3): e14431, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37697956

RESUMO

INTRODUCTION: Cerebral malaria (CM) is a lethal neuroinflammatory disease caused by Plasmodium infection. Immune cells and brain parenchyma cells contribute to the pathogenesis of CM. However, a systematic examination of the changes that occur in the brain parenchyma region during CM at the single-cell resolution is still poorly studied. AIMS: To explore cell composition and CD8+ T cell infiltration, single-cell RNA sequencing (scRNA-seq) was performed on the brainstems of healthy and experimental cerebral malaria (ECM) mice. Then CD8+ T cell infiltration was confirmed by flow cytometry and immunofluorescence assays. Subsequently, the characteristics of the brain-infiltrated CD8+ T cells were analyzed. Finally, the interactions between parenchyma cells and brain-infiltrated CD8+ T cells were studied with an astrocytes-CD8+ T cell cocultured model. RESULTS: The brainstem is the most severely damaged site during ECM. ScRNA-seq revealed a large number of CD8+ T cells infiltrating into the brainstem in ECM mice. Brain-infiltrated CD8+ T cells were highly activated according to scRNA-seq, immunofluorescence, and flow cytometry assays. Further analysis found a subset of ki-67+ CD8+ T cells that have a higher transcriptional level of genes related to T cell function, activation, and proliferation, suggesting that they were exposed to specific antigens presented by brain parenchyma cells. Brain-infiltrated CD8+ T cells were the only prominent source of IFN-γ in this single-cell analysis. Astrocytes, which have a high interferon response, act as cross-presenting cells to recruit and re-activate brain-infiltrated CD8+ T cells. We also found that brain-infiltrated CD8+ T cells were highly expressed immune checkpoint molecule PD-1, while parenchyma cells showed up-regulation of PD-L1 after infection. CONCLUSIONS: These findings reveal a novel interaction between brain-infiltrated CD8+ T cells and parenchyma cells in the ECM brainstem, suggesting that the PD-1/PD-L1 signal pathway is a promising adjunctive therapeutic strategy for ECM targeting over-activated CD8+ T cells.

17.
Neurochem Res ; 49(2): 466-476, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37917337

RESUMO

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of iron in the substantia nigra. While iron accumulation and inflammation are implicated in PD pathogenesis, their impact on oligodendrocytes, the brain's myelin-forming cells, remains elusive. This study investigated the influence of interleukin-1ß (IL-1ß), an elevated proinflammatory cytokine in PD, on iron-related proteins in MO3.13 oligodendrocytes. We found that IL-1ß treatment in undifferentiated MO3.13 oligodendrocytes increased iron regulatory protein 1 and transferrin receptor 1 (TfR1) expression while decreasing ferroportin 1 (FPN1) expression. Consequently, iron uptake was enhanced, and iron release was reduced, leading to intracellular iron accumulation. Conversely, IL-1ß treatment in differentiated MO3.13 oligodendrocytes exhibited the opposite effect, with decreased TfR1 expression, increased FPN1 expression, and reduced iron uptake. These findings suggest that IL-1ß-induced dysregulation of iron metabolism in oligodendrocytes may contribute to the pathological processes observed in PD. IL-1ß can increase the iron content in undifferentiated oligodendrocytes, thus facilitating the differentiation of undifferentiated MO3.13 oligodendrocytes. In differentiated oligodendrocytes, IL-1ß may facilitate iron release, providing a potential source of iron for neighboring dopaminergic neurons, thereby initiating a cascade of deleterious events. This study provides valuable insights into the intricate interplay between inflammation, abnormal iron accumulation, and oligodendrocyte dysfunction in PD. Targeting the IL-1ß-mediated alterations in iron metabolism may hold therapeutic potential for mitigating neurodegeneration and preserving dopaminergic function in PD.


Assuntos
Proteína 1 Reguladora do Ferro , Doença de Parkinson , Humanos , Interleucina-1beta/metabolismo , Proteína 1 Reguladora do Ferro/metabolismo , Doença de Parkinson/metabolismo , Ferro/metabolismo , Inflamação/metabolismo , Oligodendroglia/metabolismo
18.
Plant Commun ; 5(1): 100646, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37415333

RESUMO

Gene cloning in repeat-rich polyploid genomes remains challenging. Here, we describe a strategy for overcoming major bottlenecks in cloning of the powdery mildew resistance gene (R-gene) Pm69 derived from tetraploid wild emmer wheat. A conventional positional cloning approach was not effective owing to suppressed recombination. Chromosome sorting was compromised by insufficient purity. A Pm69 physical map, constructed by assembling Oxford Nanopore Technology (ONT) long-read genome sequences, revealed a rapidly evolving nucleotide-binding leucine-rich repeat (NLR) R-gene cluster with structural variations. A single candidate NLR was identified by anchoring RNA sequencing reads from susceptible mutants to ONT contigs and was validated by virus-induced gene silencing. Pm69 is likely a newly evolved NLR and was discovered in only one location across the wild emmer wheat distribution range in Israel. Pm69 was successfully introgressed into cultivated wheat, and a diagnostic molecular marker was used to accelerate its deployment and pyramiding with other R-genes.


Assuntos
Genes de Plantas , Triticum , Triticum/genética , Genes de Plantas/genética , Mapeamento Cromossômico , Clonagem Molecular , Família Multigênica
19.
Inorg Chem ; 63(2): 928-933, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38157444

RESUMO

Alkylamine ligand-induced evolutions of ZnSe magic sized clusters (MSCs) toward divergent products have been discovered for the first time. With correspondingly assigned molecular structures, the same ZnSe MSC was found to undergo either single-atom growth or dissolution through the elaborate tailoring of alkylamine ligands.

20.
Plant Biotechnol J ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070185

RESUMO

Soybean is a short-day plant that typically flowers earlier when exposed to short-day conditions. However, the identification of genes associated with earlier flowering time but without a yield penalty is rare. In this study, we conducted genome-wide association studies (GWAS) using two re-sequencing datasets that included 113 wild soybeans (G. soja) and 1192 cultivated soybeans (G. max), respectively, and simultaneously identified a candidate flowering gene, qFT13-3, which encodes a protein homologous to the pseudo-response regulator (PRR) transcription factor. We identified four major haplotypes of qFT13-3 in the natural population, with haplotype H4 (qFT13-3H4 ) being lost during domestication, while qFT13-3H1 underwent natural and artificial selection, increasing in proportion from 4.5% in G. soja to 43.8% in landrace and to 81.9% in improve cultivars. Notably, most cultivars harbouring qFT13-3H1 were located in high-latitude regions. Knockout of qFT13-3 accelerated flowering and maturity time under long-day conditions, indicating that qFT13-3 functions as a flowering inhibitor. Our results also showed that qFT13-3 directly downregulates the expression of GmELF3b-2 which is a component of the circadian clock evening complex. Field trials revealed that the qft13-3 mutants shorten the maturity period by 11 days without a concomitant penalty on yield. Collectively, qFT13-3 can be utilized for the breeding of high-yield cultivars with a short maturity time suitable for high latitudes.

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