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1.
ArXiv ; 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38947917

RÉSUMÉ

Fiber orientation distributions (FODs) is a popular model to represent the diffusion MRI (dMRI) data. However, imaging artifacts such as susceptibility-induced distortion in dMRI can cause signal loss and lead to the corrupted reconstruction of FODs, which prohibits successful fiber tracking and connectivity analysis in affected brain regions such as the brain stem. Generative models, such as the diffusion models, have been successfully applied in various image restoration tasks. However, their application on FOD images poses unique challenges since FODs are 4-dimensional data represented by spherical harmonics (SPHARM) with the 4-th dimension exhibiting order-related dependency. In this paper, we propose a novel diffusion model for FOD restoration that can recover the signal loss caused by distortion artifacts. We use volume-order encoding to enhance the ability of the diffusion model to generate individual FOD volumes at all SPHARM orders. Moreover, we add cross-attention features extracted across all SPHARM orders in generating every individual FOD volume to capture the order-related dependency across FOD volumes. We also condition the diffusion model with low-distortion FODs surrounding high-distortion areas to maintain the geometric coherence of the generated FODs. We trained and tested our model using data from the UK Biobank (n = 1315). On a test set with ground truth (n = 43), we demonstrate the high accuracy of the generated FODs in terms of root mean square errors of FOD volumes and angular errors of FOD peaks. We also apply our method to a test set with large distortion in the brain stem area (n = 1172) and demonstrate the efficacy of our method in restoring the FOD integrity and, hence, greatly improving tractography performance in affected brain regions.

2.
Toxics ; 12(6)2024 Jun 13.
Article de Anglais | MEDLINE | ID: mdl-38922107

RÉSUMÉ

Esketamine is a widely used intravenous general anesthetic. However, its safety, particularly its effects on the heart, is not fully understood. In this study, we investigated the effects of esketamine exposure on zebrafish embryonic heart development. Zebrafish embryos were exposed to esketamine at concentrations of 1, 10, and 100 mg/L from 48 h post-fertilization (hpf) to 72 hpf. We found that after exposure, zebrafish embryos had an increased hatching rate, decreased heart rate, stroke volume, and cardiac output. When we exposed transgenic zebrafish of the Tg(cmlc2:EGFP) strain to esketamine, we observed ventricular dilation and thickening of atrial walls in developing embryos. Additionally, we further discovered the abnormal expression of genes associated with cardiac development, including nkx2.5, gata4, tbx5, and myh6, calcium signaling pathways, namely ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a3, slc8a4a, and cacna1aa, as well as an increase in acetylcholine concentration. In conclusion, our findings suggest that esketamine may impair zebrafish larvae's cardiac development and function by affecting acetylcholine concentration, resulting in weakened cardiac neural regulation and subsequent effects on cardiac function. The insights garnered from this research advocate for a comprehensive safety assessment of esketamine in clinical applications.

3.
Int J Mol Sci ; 25(11)2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38892156

RÉSUMÉ

Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of malignant tumor with a poor prognosis and low quality of life in the otolaryngology department. It has been found that microRNA (miRNA) plays an important role in the occurrence and development of various tumors. This study found that the expression level of miRNA-107 (miR-107) in HSCC was significantly reduced. Subsequently, we screened out the downstream direct target gene Neuronal Vesicle Trafficking Associated 1 (NSG1) related to miR-107 through bioinformatics analysis and found that the expression of NSG1 was increased in HSCC tissues. Following the overexpression of miR-107 in HSCC cells, it was observed that miR-107 directly suppressed NSG1 expression, leading to increased apoptosis, decreased proliferation, and reduced invasion capabilities of HSCC cells. Subsequent experiments involving the overexpression and knockdown of NSG1 in HSCC cells demonstrated that elevated NSG1 levels enhanced cell proliferation, migration, and invasion, while the opposite effect was observed upon NSG1 knockdown. Further investigations revealed that changes in NSG1 levels in the HSCC cells were accompanied by alterations in ERK signaling pathway proteins, suggesting a potential regulatory role of NSG1 in HSCC cell proliferation, migration, and invasion through the ERK pathway. These findings highlight the significance of miR-107 and NSG1 in hypopharyngeal cancer metastasis, offering promising targets for therapeutic interventions and prognostic evaluations for HSCC.


Sujet(s)
Mouvement cellulaire , Prolifération cellulaire , Régulation de l'expression des gènes tumoraux , Tumeurs de l'hypopharynx , Système de signalisation des MAP kinases , microARN , Humains , Mâle , Apoptose/génétique , Carcinome épidermoïde/génétique , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/métabolisme , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Prolifération cellulaire/génétique , Évolution de la maladie , Tumeurs de l'hypopharynx/génétique , Tumeurs de l'hypopharynx/anatomopathologie , Tumeurs de l'hypopharynx/métabolisme , Système de signalisation des MAP kinases/génétique , microARN/génétique , microARN/métabolisme , Invasion tumorale , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Carcinome épidermoïde de la tête et du cou/métabolisme , Protéines du transport vésiculaire/génétique , Protéines du transport vésiculaire/métabolisme
4.
Small Methods ; : e2400664, 2024 Jun 12.
Article de Anglais | MEDLINE | ID: mdl-38864527

RÉSUMÉ

DL-Lactic acid and D-glucose are important human health indicators. Their aberrant levels in body fluids may indicate a variety of human pathological conditions, suggesting an urgent need of daily monitoring. However, simultaneous and rapid analysis of DL-lactic acid and D-glucose using a sole but simple sensing system has never been reported. Here, an engineered Mycobacterium smegmatis porin A (MspA) nanopore is used to simultaneously identify DL-lactic acid and D-glucose. Highly distinguishable nanopore event features are reported. Assisted with a custom machine learning algorithm, direct identification of DL-lactic acid and D-glucose is performed with human serum, demonstrating its sensing reliability against complex and heterogeneous samples. This sensing strategy is further applied in the analysis of different animal serum samples, according to which gluconic acid is further identified. The serum samples from different animals report distinguishable levels of DL-lactic acid, D-glucose and gluconic acid, suggesting its potential applications in agricultural science and breeding industry. This sensing strategy is generally direct, rapid, economic and requires only ≈µL of input serum, suitable for point of care testing (POCT) applications.

5.
Theor Appl Genet ; 137(7): 152, 2024 Jun 08.
Article de Anglais | MEDLINE | ID: mdl-38850423

RÉSUMÉ

KEY MESSAGE: The durable stripe rust resistance gene Yr30 was fine-mapped to a 610-kb region in which five candidate genes were identified by expression analysis and sequence polymorphisms. The emergence of genetically diverse and more aggressive races of Puccinia striiformis f. sp. tritici (Pst) in the past twenty years has resulted in global stripe rust outbreaks and the rapid breakdown of resistance genes. Yr30 is an adult plant resistance (APR) gene with broad-spectrum effectiveness and its durability. Here, we fine-mapped the YR30 locus to a 0.52-cM interval using 1629 individuals derived from residual heterozygous F5:6 plants in a Yaco"S"/Mingxian169 recombinant inbred line population. This interval corresponded to a 610-kb region in the International Wheat Genome Sequencing Consortium (IWGSC) RefSeq version 2.1 on chromosome arm 3BS harboring 30 high-confidence genes. Five genes were identified as candidate genes based on functional annotation, expression analysis by RNA-seq and sequence polymorphisms between cultivars with and without Yr30 based on resequencing. Haplotype analysis of the target region identified six haplotypes (YR30_h1-YR30_h6) in a panel of 1215 wheat accessions based on the 660K feature genotyping array. Lines with YR30_h6 displayed more resistance to stripe rust than the other five haplotypes. Near-isogenic lines (NILs) with Yr30 showed a 32.94% higher grain yield than susceptible counterparts when grown in a stripe rust nursery, whereas there was no difference in grain yield under rust-free conditions. These results lay a foundation for map-based cloning Yr30.


Sujet(s)
Cartographie chromosomique , Résistance à la maladie , Gènes de plante , Haplotypes , Maladies des plantes , Puccinia (genre) , Triticum , Triticum/génétique , Triticum/microbiologie , Résistance à la maladie/génétique , Maladies des plantes/génétique , Maladies des plantes/microbiologie , Cartographie chromosomique/méthodes , Puccinia (genre)/pathogénicité , Basidiomycota/pathogénicité , Polymorphisme de nucléotide simple , Chromosomes de plante/génétique
6.
Materials (Basel) ; 17(9)2024 Apr 25.
Article de Anglais | MEDLINE | ID: mdl-38730815

RÉSUMÉ

The synergistic effects of boron (B) and rare earth (RE) elements on the microstructure and stress rupture properties were investigated in a Ni-based superalloy. The stress rupture lifetime at 650 °C/873 MPa significantly increased with the addition of B as a single element. Furthermore, the stress rupture lifetime reached its peak (303 h), with a certain amount of B and RE added together in test alloys. Although the grain size and morphology of the γ' phase varied a little with the change in B and RE addition, they were not considered to be the main reasons for stress rupture performance. The enhancement in stress rupture lifetime was mostly attributed to the segregation of the B and RE elements, which increased the binding force of the grain boundary and improved its strength and plasticity. In addition, the enrichment of B and RE inhabited the precipitation of carbides along grain boundaries. Furthermore, nano-scale RE precipitates containing sulfur (S) and phosphorus (P) were observed to be distributed along the grain boundaries. The purification of grain boundaries by B and RE elements was favorable to further improve the stress rupture properties.

7.
Reprod Sci ; 2024 May 20.
Article de Anglais | MEDLINE | ID: mdl-38769248

RÉSUMÉ

Endometrial elasticity is a potential new marker for assessing endometrial receptivity and pregnancy outcomes based on endometrial thickness and type. Currently, little research has been conducted on the elasticity of the endometrium using shear wave elasticity imaging (SWEI). This study aimed to explore whether endometrial elasticity is an ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer. A total of 245 infertile women underwent ultrasonography before embryo transfer at the Peking University Third Hospital. We compared the endometrial elasticity and sub-endometrial blood flow rate using SWEI in the groups with different pregnancy outcomes. Trends in clinical pregnancy outcomes across the quartiles of endometrial elasticity in the fundus of the uterus (E1) were assessed. Logistic regression analysis was performed to obtain odds ratios for clinical pregnancy outcomes based on the quartiles of E1, with or without adjusting for potential confounding variables. Women in the clinical pregnancy group had higher E1 values and sub-endometrial blood flow rates in the uterine fundus than those in the non-pregnancy group. Women in the highest quartile of E1 had the most favorable clinical pregnancy rates. Endometrial elasticity measured using SWEI is a promising ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer.

8.
Front Immunol ; 15: 1381919, 2024.
Article de Anglais | MEDLINE | ID: mdl-38799424

RÉSUMÉ

Introduction: CD8+T cell tolerance plays an important role in tumor escape. Recent studies have shown that CD45+ erythroid progenitor cells (CD45+EPCs) generated through splenic extramedullary erythropoiesis suppress tumor immunity. However, the mechanism underlying how CD45+EPCs mediate CD8+T cell tolerance remains incompletely understood and requires further research. Methods: In this study, the antigen-processing abilities of CD45+EPCs was verified through both in vitro and in vivo experiments. We have used the method of co-culture in vitro and adoptive transfer experiments in vivo to explore the effects of CD45+EPCs on CD8+T cell tolerance. RNA-sequencing analysis and blocking experiments were used to evaluate the role of ROS in the CD45+EPC mediated tolerance of CD8+T cells. Finally, we incorporated uric acid into the adoptive transfer experiments to rescue the CD45+EPC mediated tumor-promoting effect. Results and discussion: We found that CD45+EPCs take up soluble proteins, present antigenic epitopes on their surface, and induce antigen-specific CD8+T cell anergy. In addition, we found that CD45+EPC directly nitrates tyrosine within the TCR/CD8 complex via the production of reactive oxygen species and peroxynitrite, preventing CD8+ T cells from responding to their specific peptide antigens. Furthermore, uric acid treatment effectively abolished the immunosuppressive effects of CD45+EPCs during CD8+T cell adoptive transfer, thereby enhancing the anti-tumor efficacy. These results demonstrated that CD8+T cell tolerance in tumor-bearing mice is induced by CD45+EPCs. The results of this study have direct implications for tumor immunotherapy.


Sujet(s)
Lymphocytes T CD8+ , Précurseurs érythroïdes , Tolérance immunitaire , Animaux , Lymphocytes T CD8+/immunologie , Souris , Précurseurs érythroïdes/immunologie , Précurseurs érythroïdes/métabolisme , Antigènes CD45/métabolisme , Souris de lignée C57BL , Transfert adoptif , Espèces réactives de l'oxygène/métabolisme , Échappement de la tumeur à la surveillance immunitaire/immunologie , Lignée cellulaire tumorale , Acide urique
9.
bioRxiv ; 2024 Mar 14.
Article de Anglais | MEDLINE | ID: mdl-38559090

RÉSUMÉ

Bacteria perform diverse redox chemistries in the periplasm, cell wall, and extracellular space. Electron transfer for these extracytosolic activities is frequently mediated by proteins with covalently bound flavins, which are attached through post-translational flavinylation by the enzyme ApbE. Despite the significance of protein flavinylation to bacterial physiology, the basis and function of this modification remains unresolved. Here we apply genomic context analyses, computational structural biology, and biochemical studies to address the role of ApbE flavinylation throughout bacterial life. We find that ApbE flavinylation sites exhibit substantial structural heterogeneity. We identify two novel classes of flavinylation substrates that are related to characterized proteins with non-covalently bound flavins, providing evidence that protein flavinylation can evolve from a non-covalent flavoprotein precursor. We further find a group of structurally related flavinylation-associated cytochromes, including those with the domain of unknown function DUF4405, that presumably mediate electron transfer in the cytoplasmic membrane. DUF4405 homologs are widespread in bacteria and related to ferrosome iron storage organelle proteins that may facilitate iron redox cycling within ferrosomes. These studies reveal a complex basis for flavinylated electron transfer and highlight the discovery power of coupling comparative genomic analyses with high-quality structural models.

10.
J Cell Mol Med ; 28(8): e18348, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38652105

RÉSUMÉ

Tumour immune microenvironment (TIME) plays an indispensable role in tumour progression, and tumour-associated macrophages (TAMs) are the most abundant immune cells in TIME. Non-apoptotic regulated cell death (RCD) can avoid the influence of tumour apoptosis resistance on anti-tumour immune response. Specifically, autophagy, ferroptosis, pyroptosis and necroptosis mediate the crosstalk between TAMs and tumour cells in TIME, thus reprogram TIME and affect the progress of tumour. In addition, although some achievements have been made in immune checkpoint inhibitors (ICIs), there is still defect that ICIs are only effective for some people because non-apoptotic RCD can bypass the apoptosis resistance of tumour. As a result, ICIs combined with targeting non-apoptotic RCD may be a promising solution. In this paper, the basic molecular mechanism of non-apoptotic RCD, the way in which non-apoptotic RCD mediates crosstalk between TAMs and tumour cells to reprogram TIME, and the latest research progress in targeting non-apoptotic RCD and ICIs are reviewed.


Sujet(s)
Tumeurs , Mort cellulaire régulée , Microenvironnement tumoral , Macrophages associés aux tumeurs , Animaux , Humains , Apoptose , Autophagie , Ferroptose/immunologie , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Tumeurs/immunologie , Tumeurs/anatomopathologie , Tumeurs/thérapie , Mort cellulaire régulée/effets des médicaments et des substances chimiques , Macrophages associés aux tumeurs/immunologie , Macrophages associés aux tumeurs/métabolisme , Macrophages associés aux tumeurs/anatomopathologie
11.
Small ; : e2310912, 2024 Mar 04.
Article de Anglais | MEDLINE | ID: mdl-38438937

RÉSUMÉ

All-solid-state lithium batteries (ASSLBs) are highly promising as next-generation energy storage devices owing to their potential for great safety and high energy density. This work demonstrates that composite solid polymer electrolyte with vertically-aligned card-house structure can simultaneously improve the high rate and long-term cycling performance of ASSLBs. The vertical alignment of laponite nanosheets creates fast and uniform Li+ ion transport channels at the nanosheets/polymer interphase, resulting in high ionic conductivity of 8.9 × 10-4 S cm-1 and Li+ transference number of 0.32 at 60 °C, as well as uniformly distributed solid electrolyte interphase. Such electrolyte is characterized by high mechanical strength, low flammability, excellent structural stability and stable ion transport channels. In addition, the ASSLB cell with the electrolyte and LiFePO4 cathode delivers a high discharge specific capacity of 124.8 mAh g-1 , which accounts for 85.6% of its initial capacity after 500 cycles at 1C. The reasonable design through structural control strategy by interconnecting the vertically-aligned nanosheets open a way to fabricate high performance composite solid polymer electrolytes.

12.
Dermatol Ther (Heidelb) ; 14(3): 713-728, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38451424

RÉSUMÉ

INTRODUCTION: Observational studies and clinical trials have supported the association between gut microbiota and psoriatic arthritis. However, the causal link between gut microbiota and psoriatic arthritis is still unclear. METHODS: A two-sample bi-directional Mendelian randomization analysis was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium. The summary statistics of psoriatic arthritis were extracted directly from the FinnGen consortium, which consists of 3186 psoriatic arthritis patients and 24,086 controls. Sensitivity analyses were conducted to assess the validity of our findings. Enrichment analyses were used to investigate the biofunction and pathways. RESULTS: Inverse variance weighted (IVW) estimates suggested that family Rikenellaceae (P = 0.032) and genus Ruminococcaceae UCG011 (P = 0.014) had a detrimental effect on psoriatic arthritis. We also noticed the negative association between the class Methanobacteria (P = 0.032), order Methanobacteriales (P = 0.032), family Methanobacteriaceae (P = 0.032), genus Eubacterium fissicatena group (P = 0.010), genus Methanobrevibacter (P = 0.031), and genus Butyricicoccus (P = 0.041) with psoriatic arthritis. Sensitivity analyses showed that genus Butyricicoccus had pleiotropy and heterogeneity. According to the results of reverse MR analysis, the causal effect of psoriatic arthritis was found on six taxa, respectivelyc family Clostridiaceae1, family Defluviitaleaceae, genus Butyrivibrio, genus Defluviitaleaceae UCG011, genus Clostridium sensu stricto1, and genus Ruminococcaceae UCG011. CONCLUSION: This two-sample bidirectional Mendelian randomization analysis suggested that the gut microbiota had a causal effect on psoriatic arthritis and implied the potential role of probiotics in the management and prevention of psoriatic arthritis.

13.
Int Immunopharmacol ; 131: 111876, 2024 Apr 20.
Article de Anglais | MEDLINE | ID: mdl-38493688

RÉSUMÉ

Colorectal cancer (CRC) is the third most common cancer and has the second highest mortality rate among cancers. The development of CRC involves both genetic and epigenetic abnormalities, and recent research has focused on exploring the ex-transcriptome, particularly post-transcriptional modifications. RNA-binding proteins (RBPs) are emerging epigenetic regulators that play crucial roles in post-transcriptional events. Dysregulation of RBPs can result in aberrant expression of downstream target genes, thereby affecting the progression of colorectal tumors and the prognosis of patients. Recent studies have shown that RBPs can influence CRC pathogenesis and progression by regulating various components of the tumor microenvironment (TME). Although previous research on RBPs has primarily focused on their direct regulation of colorectal tumor development, their involvement in the remodeling of the TME has not been systematically reported. This review aims to highlight the significant role of RBPs in the intricate interactions within the CRC tumor microenvironment, including tumor immune microenvironment, inflammatory microenvironment, extracellular matrix, tumor vasculature, and CRC cancer stem cells. We also highlight several compounds under investigation for RBP-TME-based treatment of CRC, including small molecule inhibitors such as antisense oligonucleotides (ASOs), siRNAs, agonists, gene manipulation, and tumor vaccines. The insights gained from this review may lead to the development of RBP-based targeted novel therapeutic strategies aimed at modulating the TME, potentially inhibiting the progression and metastasis of CRC.


Sujet(s)
Vaccins anticancéreux , Tumeurs colorectales , Humains , Microenvironnement tumoral , Protéines de liaison à l'ARN/génétique , Tumeurs colorectales/traitement médicamenteux , Tumeurs colorectales/génétique , Matrice extracellulaire
14.
ACS Sens ; 9(3): 1359-1371, 2024 03 22.
Article de Anglais | MEDLINE | ID: mdl-38449100

RÉSUMÉ

N-Acetyl modification, a chemical modification commonly found on biomacromolecules, plays a crucial role in the regulation of cell activities and is related to a variety of diseases. However, due to the instability of N-acetyl modification, accurate and rapid identification of N-acetyl modification with a low measurement cost is still technically challenging. Here, based on hydroxylamine deacetylation and nanopore single molecule chemistry, a universal sensing strategy for N-acetyl modification has been developed. Acetohydroxamic acid (AHA), which is produced by the hydroxylamine deacetylation reaction and serves as a reporter for N-acetylation identification, is specifically sensed by a phenylboronic acid (PBA)-modified Mycobacterium smegmatis porin A (MspA). With this strategy, N-acetyl modifications on RNA, DNA, proteins, and glycans were identified, demonstrating its generality. Specifically, histones can be treated with hydroxylamine deacetylation, from which the generated AHA can represent the amount of N-acetyl modification detected by a nanopore sensor. The unique event features of AHA also demonstrate the robustness of sensing against other interfering analytes in the environment.


Sujet(s)
Nanopores , Hydroxylamine/métabolisme , Acétylation , Mycobacterium smegmatis/génétique , Mycobacterium smegmatis/métabolisme , Hydroxylamines
15.
Ultrason Sonochem ; 105: 106854, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38537562

RÉSUMÉ

Ultrasound-stimulated contrast agents have gained significant attention in the field of tumor treatment as drug delivery systems. However, their limited drug-loading efficiency and the issue of bulky, imprecise release have resulted in inadequate drug concentrations at targeted tissues. Herein, we developed a highly efficient approach for doxorubicin (DOX) precise release at tumor site and real-time feedback via an integrated strategy of "programmable ultrasonic imaging guided accurate nanodroplet destruction for drug release" (PND). We synthesized DOX-loaded nanodroplets (DOX-NDs) with improved loading efficiency (15 %) and smaller size (mean particle size: 358 nm). These DOX-NDs exhibited lower ultrasound activation thresholds (2.46 MPa). By utilizing a single diagnostic transducer for both ultrasound stimulation and imaging guidance, we successfully vaporized the DOX-NDs and released the drug at the tumor site in 4 T1 tumor-bearing mice. Remarkably, the PND group achieved similar tumor remission effects with less than half the dose of DOX required in conventional treatment. Furthermore, the ultrasound-mediated vaporization of DOX-NDs induced tumor cell apoptosis with minimal damage to surrounding normal tissues. In summary, our PND strategy offers a precise and programmable approach for drug delivery and therapy, combining ultrasound imaging guidance. This approach shows great potential in enhancing tumor treatment efficacy while minimizing harm to healthy tissues.


Sujet(s)
Tumeurs du sein , Doxorubicine , Nanoparticules , Nanomédecine théranostique , Doxorubicine/composition chimique , Doxorubicine/pharmacologie , Animaux , Nanomédecine théranostique/méthodes , Tumeurs du sein/imagerie diagnostique , Tumeurs du sein/anatomopathologie , Tumeurs du sein/traitement médicamenteux , Souris , Nanoparticules/composition chimique , Échographie/méthodes , Femelle , Libération de médicament , Médecine de précision/méthodes , Lignée cellulaire tumorale , Humains , Apoptose/effets des médicaments et des substances chimiques
16.
J Mol Med (Berl) ; 102(5): 693-707, 2024 05.
Article de Anglais | MEDLINE | ID: mdl-38492027

RÉSUMÉ

Physical therapy is extensively employed in clinical settings. Nevertheless, the absence of suitable animal models has resulted in an incomplete understanding of the in vivo mechanisms and cellular distribution that respond to physical stimuli. The objective of this research was to create a mouse model capable of indicating the cells affected by physical stimuli. In this study, we successfully established a mouse line based on the heat shock protein 70 (Hsp70) promoter, wherein the expression of CreERT2 can be induced by physical stimuli. Following stimulation of the mouse tail, ear, or cultured calvarias with heat shock (generated by heating, ultrasound, or laser), a distinct Cre-mediated excision was observed in cells stimulated by these physical factors with minimal occurrence of leaky reporter expression. The application of heat shock to Hsp70-CreERT2; FGFR2-P253R double transgenic mice or Hsp70-CreERT2 mice infected with AAV-BMP4 at calvarias induced the activation of Cre-dependent mutant FGFR2-P253R or BMP4 respectively, thereby facilitating the premature closure of cranial sutures or the repair of calvarial defects. This novel mouse line holds significant potential for investigating the underlying mechanisms of physical therapy, tissue repair and regeneration, lineage tracing, and targeted modulation of gene expression of cells in local tissue stimulated by physical factor at the interested time points. KEY MESSAGES: In the study, an Hsp70-CreERT2 transgenic mouse was generated for heat shock-induced gene modulation. Heat shock, ultrasound, and laser stimulation effectively activated Cre expression in Hsp70-CreERT2; reporter mice, which leads to deletion of floxed DNA sequence in the tail, ear, and cultured calvaria tissues of mice. Local laser stimuli on cultured calvarias effectively induce Fgfr2-P253R expression in Hsp70-mTmG-Fgfr2-P253R mice and result in accelerated premature closure of cranial suture. Heat shock activated AAV9-FLEX-BMP4 expression and subsequently promoted the repair of calvarial defect of Hsp70-CreERT2; Rosa26-mTmG mice.


Sujet(s)
Protéine morphogénétique osseuse de type 4 , Protéines du choc thermique HSP70 , Souris transgéniques , Régions promotrices (génétique) , Animaux , Protéines du choc thermique HSP70/génétique , Protéines du choc thermique HSP70/métabolisme , Souris , Protéine morphogénétique osseuse de type 4/métabolisme , Protéine morphogénétique osseuse de type 4/génétique , Réaction de choc thermique/génétique , Crâne/métabolisme , Régulation de l'expression des gènes , Integrases/métabolisme , Integrases/génétique
17.
Nat Commun ; 15(1): 1970, 2024 Mar 05.
Article de Anglais | MEDLINE | ID: mdl-38443335

RÉSUMÉ

Natural herbs, which contain pharmacologically active compounds, have been used historically as medicines. Conventionally, the analysis of chemical components in herbal medicines requires time-consuming sample separation and state-of-the-art analytical instruments. Nanopore, a versatile single molecule sensor, might be suitable to identify bioactive compounds in natural herbs. Here, a phenylboronic acid appended Mycobacterium smegmatis porin A (MspA) nanopore is used as a sensor for herbal medicines. A variety of bioactive compounds based on salvianolic acids, including caffeic acid, protocatechuic acid, protocatechualdehyde, salvianic acid A, rosmarinic acid, lithospermic acid, salvianolic acid A and salvianolic acid B are identified. Using a custom machine learning algorithm, analyte identification is performed with an accuracy of 99.0%. This sensing principle is further used with natural herbs such as Salvia miltiorrhiza, Rosemary and Prunella vulgaris. No complex sample separation or purification is required and the sensing device is highly portable.


Sujet(s)
Alcènes , Nanopores , Plantes médicinales , Polyphénols , Algorithmes , Extraits de plantes
18.
Nat Commun ; 15(1): 1969, 2024 Mar 05.
Article de Anglais | MEDLINE | ID: mdl-38443434

RÉSUMÉ

Natural fruits contain a large variety of cis-diols. However, due to the lack of a high-resolution sensor that can simultaneously identify all cis-diols without a need of complex sample pretreatment, direct and rapid analysis of fruits in a hand-held device has never been previously reported. Nanopore, a versatile single molecule sensor, can be specially engineered to perform this task. A hetero-octameric Mycobacterium smegmatis porin A (MspA) nanopore modified with a sole phenylboronic acid (PBA) adapter is prepared. This engineered MspA accurately recognizes 1,2-diphenols, alditols, α-hydroxy acids and saccharides in prune, grape, lemon, different varieties of kiwifruits and commercial juice products. Assisted with a custom machine learning program, an accuracy of 99.3% is reported and the sample pretreatment is significantly simplified. Enantiomers such as DL-malic acids can also be directly identified, enabling sensing of synthetic food additives. Though demonstrated with fruits, these results suggest wide applications of nanopore in food and drug administration uses.


Sujet(s)
Citrus , Nanopores , États-Unis , Fruit , Polyols , Acides carboxyliques , Mycobacterium smegmatis , Porines
19.
BMC Cardiovasc Disord ; 24(1): 178, 2024 Mar 23.
Article de Anglais | MEDLINE | ID: mdl-38521897

RÉSUMÉ

AIMS: The current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA. METHODS AND RESULTS: A total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the '2021 Universal Definition of HF' criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76-0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07-0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05). CONCLUSIONS: The improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.


Sujet(s)
Fibrillation auriculaire , Ablation par cathéter , Défaillance cardiaque , Dysfonction ventriculaire gauche , Humains , Fibrillation auriculaire/diagnostic , Fibrillation auriculaire/chirurgie , Fibrillation auriculaire/complications , Fonction ventriculaire gauche , Débit systolique , Défaillance cardiaque/imagerie diagnostique , Défaillance cardiaque/complications , Dysfonction ventriculaire gauche/étiologie , Dysfonction ventriculaire gauche/complications , Ablation par cathéter/effets indésirables , Ablation par cathéter/méthodes , Résultat thérapeutique
20.
Micromachines (Basel) ; 15(3)2024 Feb 28.
Article de Anglais | MEDLINE | ID: mdl-38542583

RÉSUMÉ

Laser-based additive manufacturing has garnered significant attention in recent years as a promising 3D-printing method for fabricating metallic components. However, the surface roughness of additive manufactured components has been considered a challenge to achieving high performance. At present, the average surface roughness (Sa) of AM parts can reach high levels, greater than 50 µm, and a maximum distance between the high peaks and the low valleys of more than 300 µm, which requires post machining. Therefore, laser polishing is increasingly being utilized as a method of surface treatment for metal alloys, wherein the rapid remelting and resolidification during the process significantly alter both the surface quality and subsurface material properties. In this paper, the surface roughness, microstructures, microhardness, and wear resistance of the as-received, continuous wave laser polishing (CWLP), and pulsed laser polishing (PLP) processed samples were investigated systematically. The results revealed that the surface roughness (Sa) of the as-received sample was 6.29 µm, which was reduced to 0.94 µm and 0.84 µm by CWLP and PLP processing, respectively. It was also found that a hardened layer, about 200 µm, was produced on the Ti6Al4V alloy surface after laser polishing, which can improve the mechanical properties of the component. The microhardness of the laser-polished samples was increased to about 482 HV with an improvement of about 25.2% compared with the as-received Ti6Al4V alloy. Moreover, the coefficient of friction (COF) was slightly reduced by both CWLP and LPL processing, and the wear rate of the surface layer was improved to 0.790 mm3/(N∙m) and 0.714 mm3/(N∙m), respectively, under dry fraction conditions.

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