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1.
Biomaterials ; 313: 122769, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39208698

ABSTRACT

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.


Subject(s)
Coated Materials, Biocompatible , Extracellular Matrix , Wound Healing , Animals , Extracellular Matrix/metabolism , Dogs , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Wound Healing/drug effects , Collagen Type I/metabolism , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Human Umbilical Vein Endothelial Cells , Re-Epithelialization/drug effects , Cell Adhesion/drug effects
2.
J Diabetes ; 16(10): e70001, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39364793

ABSTRACT

AIMS: We intended to characterize the superiority of triglyceride glucose-body mass index (TyG-BMI) in predicting type 2 diabetes mellitus (T2DM) compared with triglyceride glucose (TyG) and homeostatic model assessment for insulin resistance (HOMA-IR). METHODS: A total of 699 nondiabetic participants in the Da Qing IGT and Diabetes Study were involved in the present analysis and classified according to the median of baseline TyG-BMI, namely the G1 (low TyG-BMI) and G2 (high TyG-BMI) groups. Information on developing diabetes was assessed from 1986 to 2020. RESULTS: During the 34-year follow-up, after adjustment for confounders, the G2 group had a higher risk of developing type 2 diabetes than the G1 group (hazard ratio [HR]: 1.92, 95% confidence interval [CI]: 1.51-2.45, p < 0.0001). Restricted cubic spline analyses showed that increased TyG-BMI was linearly related to higher risks of type 2 diabetes (p for non-linearity>0.05). Time-dependent receiver operator characteristics curves suggested that TyG-BMI exhibited higher predictive ability than TyG (6-year: area under the curve [AUC]TyG-BMI vs. AUCTyG, 0.78 vs. 0.70, p = 0.03; 34-year: AUCTyG-BMI vs. AUCTyG, 0.79 vs. 0.73, p = 0.04) and HOMA-IR (6-year: AUCTyG-BMI vs. AUCHOMA-IR, 0.78 vs. 0.70, p = 0.07; 34-year: AUCTyG-BMI vs. AUCHOMA-IR, 0.79 vs. 0.71, p = 0.04) in both short and long terms, and the thresholds of TyG-BMI to predict type 2 diabetes were relatively stable (195.24-208.41) over the 34-year follow-up. CONCLUSIONS: In this post hoc study, higher TyG-BMI was associated with an increased risk of type 2 diabetes and demonstrated better predictability than TyG and HOMA-IR, favoring the application of TyG-BMI as a potential tool for evaluating the risk of type 2 diabetes in clinical practice.


Subject(s)
Blood Glucose , Body Mass Index , Diabetes Mellitus, Type 2 , Triglycerides , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Female , Male , Middle Aged , Triglycerides/blood , Follow-Up Studies , Blood Glucose/analysis , Blood Glucose/metabolism , China/epidemiology , Risk Factors , Adult , Insulin Resistance , Risk Assessment/methods , Glucose Intolerance/blood , Glucose Intolerance/epidemiology , Prognosis , Aged , Asian People/statistics & numerical data , East Asian People
3.
Article in English | MEDLINE | ID: mdl-39358659

ABSTRACT

This study presents the synthesis and evaluation of a magnetic chitosan-modified biochar (M-BC-CS) composite, developed from waste maize straw, for the efficient removal of copper ions (Cu2+) and methylene blue (MB) dye from aqueous solutions. The composite was characterized using advanced techniques such as SEM, BET, FTIR, XPS, and XRD, confirming its enhanced surface area, porosity, and magnetic properties. The study is aimed at investigating the optimal conditions for adsorption of Cu2+ and MB by M-BC-CS through analysis of the influence of diverse adsorbent dosages, pH levels, reaction times, and initial solution concentrations. The findings demonstrated that the equilibrium duration for the adsorption of Cu2+ and MB by M-BC-CS was 60 min, resulting in corresponding equilibrium adsorption quantities of 54.42 mg/g and 67.23 mg/g, respectively. To elucidate the adsorption mechanism, the present investigation applied the pseudo-second-order kinetic model and the Langmuir isotherm. The outcomes suggested that the adsorption process is attributable to single molecular layer chemisorption. XPS and FTIR analysis determined that ion exchange and electrostatic interactions are the predominant mechanisms responsible for the simultaneous adsorption of Cu2+ and MB, and a competitive relationship exists between these mechanisms. In addition, M-BC-CS exhibited exceptional magnetic separation performance, enabling effortless and effective separation when exposed to an external magnetic field. Furthermore, the results demonstrated that M-BC-CS has good reusability and high adsorption capacity also in real wastewater, thus emphasizing its potential as a promising adsorbent for the elimination of Cu2+ and MB from aqueous solutions.

4.
New Phytol ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363422

ABSTRACT

The sweetness of apple fruit is a key factor in the improvement of apple varieties, with fructose being the sweetest of the soluble sugars, playing a crucial role in determining the overall sweetness of the apple. Therefore, uncovering the key genes controlling fructose accumulation and deciphering the regulatory mechanisms of fructose are vitally important for the improvement of apple varieties. In this study, through BSA-seq and transcriptome analysis of the 'Changfu 2' × 'Golden Delicious' F1 hybrid population, MdNAC5 was identified as a key regulatory gene for fructose content. MdNAC5 was shown to significantly influence fructose accumulation in both apples and tomatoes. Furthermore, we conducted a detailed identification of sugar transporters and metabolic enzymes in apples, discovering that MdNAC5 can enhance fructose accumulation in vacuoles and the conversion of sucrose to fructose by binding to and activating the promoters of the vacuolar sugar transporter MdTST2 and the neutral invertase MdNINV6. Additionally, MdNAC5 regulated the MdEIN3.4-MdSWEET15a module, strengthening the unloading of sucrose in the phloem of the fruit. Our results reveal a new mechanism by which MdNAC5 regulates fructose accumulation in apples and provide theoretical foundations for improving apple sweetness through genetic modification.

6.
Sci Total Environ ; 954: 176557, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39357758

ABSTRACT

Thermokarst landslide (TL) activity in the Qinghai-Tibet Plateau (QTP) is intensifying due to climate warming-induced permafrost degradation. However, the mechanisms driving landslide formation and evolution remain poorly understood. This study investigates the spatial distribution, annual frequency, and monthly dynamics of TLs along the Qinghai-Tibet engineering corridor (QTEC), in conjunction with in-situ temperature and rainfall observations, to elucidate the interplay between warming, permafrost degradation, and landslide activity. Through the analysis of high-resolution satellite imagery and field surveys, we identified 1298 landslides along the QTEC between 2016 and 2022, with an additional 386 landslides recorded in a typical landslide-prone sub-area. In 2016, 621 new active-layer detachments (ALDs) were identified, 1.3 times the total historical record. This surge aligned with unprecedented mean annual and August temperatures. The ALDs emerged primarily between late August and early September, coinciding with maximum thaw depth. From 2016 to 2022, 97.8 % of these ALDs evolved into retrogressive thaw slumps (RTSs), identified as active landslides. Landslides typically occur in alpine meadows at moderate altitudes and on gentle northward slopes. The thick ice layer near the permafrost table serves as the material basis for ALD occurrence. Abnormally high temperature significantly increased the active layer thickness (ALT), resulting in melting of the ice layer and formation of a thawed interlayer, which was the direct causing factor for ALD. By altering the local material, micro-topography, and thermal conditions, ALD activity significantly increases RTS susceptibility. Understanding the mechanisms of ALD formation and evolution into RTS provides a theoretical foundation for infrastructure development and disaster mitigation in extreme environments.

7.
Anal Methods ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39351625

ABSTRACT

Dual-mode-based sensors have drawn a lot of interest due to their high accuracy and sensitivity compared to single-response systems. A simple electrochemical and colorimetric dual-mode sensor based on enzyme-linked immunosorbent assay (ELISA), without complex electrode surface modification, was developed for accurate and sensitive detection of carcinoembryonic antigen (CEA). The target CEA is recognized by an antibody coupled to horseradish peroxidase (HRP), which then oxidizes the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to generate both a colorimetric and an electrochemical signal. A paper-based analysis device (µPAD) with dual-mode homogeneous sensing microfluidic was created; three paper-based detection areas for colorimetric testing, and a two-electrode embedded detection area for electrochemical testing. When applying colorimetric analysis technology, the linear range of CEA detection is 0.6-40 ng mL-1, and the limit of detection (LOD) is 0.2 ng mL-1. The linear range is 0.1-40 ng mL-1 and the LOD is 0.03 ng mL-1 by applying electrochemical analysis. The visibility and intuitiveness of colorimetry provide a reference for higher sensitivity and quick response of the electrochemical method. A smartphone application (APP) was also developed to realize the dual extraction of colorimetric signals. The colorimetric detection system based on ELISA can provide a new path for the development of electrochemical sensing and makes it have inherent self-verification and self-correction functions and is expected to provide more reliable and accurate detection results.

8.
Neurol Ther ; 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39369113

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) poses a significant challenge due to its diverse impact on individuals, emphasizing the need for personalized treatment plans. The financial burden of ASD-related healthcare is substantial, necessitating a comprehensive understanding of its prevalence and evolving trends. METHODS: This study aims to analyze the prevalence and trends of ASD, treatment patterns, gender differences, and racial-ethnic disparities in the United States from 2017 to 2020, utilizing nationally representative data from the National Survey of Children's Health (NSCH). The NSCH, a leading annual national survey, provided rich data on child health. A total of 108,142 participants aged 3-17 years were included, with ASD prevalence assessed based on self-reported diagnoses. RESULTS: Between 2017 and 2020, ASD prevalence in children aged 3-17 was 2.94% (95% confidence interval: 2.68-3.18). Significant disparities were observed: older age and male gender correlated with higher prevalence, while family income-to-poverty ratio and insurance coverage influenced prevalence. Racial/ethnic disparities existed, with Hispanics showing the highest prevalence. Treatment trends showed stability overall, but age influenced behavioral and medication interventions. The prevalence remained stable from 2017 to 2020, with variations in age groups and a significant increase among non-Hispanic Whites. CONCLUSIONS: This study highlights a higher but stable overall ASD prevalence, with nuanced disparities among different demographic groups. Gender differences persist, emphasizing the need for tailored interventions. Racial-ethnic disparities call for targeted healthcare strategies. The stability in treatment trends underscores the persistent challenge of addressing core ASD symptoms.

9.
Front Oncol ; 14: 1428910, 2024.
Article in English | MEDLINE | ID: mdl-39376980

ABSTRACT

The concurrent presence of gastrointestinal stromal tumor and schwannoma is extremely rare, and its pathological characteristics remain unclear. This case report reported the diagnostic and treatment process of a patient with a pancreatic GIST coexisting with esophageal schwannoma, who was admitted to West China Hospital (Sichuan, China) in April 2015. The patient did not undergo surgical resection of the tumor but instead received an 8-year regimen of imatinib therapy, during which no tumor progression was observed. However, the patient developed pleural effusion as a result of the localized enlargement of the esophageal schwannoma, which exerted pressure on the right inferior pulmonary vein. This case report provides valuable clinical insights into this distinctive disease presentation.

10.
Cell Mol Biol (Noisy-le-grand) ; 70(9): 91-98, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39380273

ABSTRACT

Triple-negative breast cancer TNBC with higher immunogenicity and tumor-infiltrating lymphocyte (TIL) enrichment can benefit from immunotherapy relative to other breast cancer subtypes. Our work was designed to identify the TIL-related hub genes in TNBC and construct a prognostic signature for TNBC. TNBC gene expression files were obtained from the TCGA database. CIBERSORT algorithm and random forest risk model were used for immune infiltration group division. The TIL-related differentially expressed genes (DEGs) were then selected and subject to GO, KEGG analyses and GSEA. Next, Lasso cox regression analyses were adopted for constructing a prognostic risk model, followed by evaluation using time-dependent ROC curves. The copy number variation between the two risk groups was also analyzed, and major genomic mutation types were identified. Additionally, the nomogram was constructed with calibration curve for clinical prognosis analysis. Our results showed that totally 113 TNBC samples were allocated into the high or low-immune risk groups. We identified 243 DEGs between groups, namely TIL-related DEGs, with 128 upregulated and 115 downregulated genes. Among the TIL-related DEGs, 6 hub genes (SLITRK3, PCDHGB3, NELL2, SRRM4, ASIC2 and B4GALNT2) were screened out and constructed a prognostic risk signature, which had good performance for long-term prognosis prediction. Analysis of genomic mutation showed that the TP53, PIK3CA, TTH, etc. showed high mutation frequency in the two prognostic risk groups. Moreover, the higher risk score of the prognostic risk model predicted poor overall survival in TNBC patients, and nomogram and calibration curve confirmed the potent prediction ability of this model. To sum up, six TIL-related biomarkers (SLITRK3, PCDHGB3, NELL2, SRRM4, ASIC2 and B4GALNT2) were identified and used for the construction of the prognostic risk model, which might provide novel insight for the clinical decisions.


Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Lymphocytes, Tumor-Infiltrating , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/pathology , Prognosis , Female , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Biomarkers, Tumor/genetics , Gene Expression Profiling/methods , Nomograms , Mutation/genetics , DNA Copy Number Variations/genetics , Transcriptome/genetics , ROC Curve , Middle Aged , Databases, Genetic
11.
PLoS One ; 19(10): e0310752, 2024.
Article in English | MEDLINE | ID: mdl-39383157

ABSTRACT

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory condition primarily affecting the digestive system. When dealing with complex cases like intestinal blockages or perforations, surgery becomes the primary treatment option. However, surgery doesn't offer a complete cure, and the possibility of recurrence remains. To manage CD recurrence after surgery, various treatment choices are available, including steroids, monoclonal antibodies, immunomodulators, and further surgery. Regrettably, the current body of evidence doesn't definitively establish which of these treatments is the most effective and safe. Thus, our research aims to provide insights into the Validity and security of different treatment approaches for managing CD recurrence after surgery. METHODS: Search of EMBASE, PubMed, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials will be conducted to include researches that examine the validity of treatments for recurrent CD after surgery. Our analysis will distinguish between two types of studies: randomized controlled trials (RCTs) and non-randomized studies with at least two different treatments, each evaluated separately. We will employ Bayesian network meta-analyses to systematically compare the effectiveness and safety of these treatments. Additionally, subgroup analyses will be performed according to recurrence status and postoperative prophylactic medication. To clarify the variation of studies, sensitivity analyses will be performed. And we may use meta-regression as an additional approach if relevant data are available. We will also rigorously access the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. DISCUSSION: This analysis will provide a comprehensive assessment of the latest evidence on available treatments for patients with postoperative recurrence of CD, which will provide recommendations for clinical practice. TRIAL REGISTRATION: Systematic review registration INPLASY2023110021. (DOI: 10.37766/inplasy2023.11.0021).


Subject(s)
Crohn Disease , Recurrence , Systematic Reviews as Topic , Crohn Disease/surgery , Crohn Disease/drug therapy , Humans , Network Meta-Analysis , Bayes Theorem , Postoperative Period , Meta-Analysis as Topic
12.
Int J Biol Macromol ; : 136396, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39383921

ABSTRACT

Promising novel α-glucanotransferases with starch-converting activity have recently emerged from the CAZy GH70 GtfB subfamily. In this study, we thoroughly investigated and elucidated the impact of the newly characterized 4,6-α-glucanotransferase II Limosilactobacillus reuteri N1 GtfB (LrN1 GtfB), which was capable of synthesizing linear (α1 → 6) and branched (α1 → 4,6) linkages, on the fine structure, rheology, and retrogradation properties of pea starch (PS). The results revealed that as the reaction time increased, the total (α1 → 6) linkages in linear chains and branching points of PS increased from 5.6 % to 18.7 %, the molecular weight decreased from 7.3 × 106 g/mol to 7.4 × 104 g/mol, and the percentage of short chains (DP ≤ 12) increased from 47.4 % to 92.7 %, thereby producing low-molecular-weight, short-clustered novel reuterans with new (α1 → 6) linkages in both linear chains and branches. Additionally, LrN1 GtfB-modified PS exhibited lower storage/loss modulus and weaker creep property, indicating a significant attenuation of the strength and rigidity of the modified gel structure. Moreover, products derived from pea starch and LrN1 GtfB exhibited notably low retrogradation properties. These findings provide insights into the potential application of GtfB-type α-glucanotransferases in starch-based products, thereby producing unique-structured α-glucans with versatile properties from starch.

13.
Future Oncol ; : 1-12, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39360943

ABSTRACT

Aim: We investigated association between skin adverse events (AEs) and efficacy with dacomitinib in patients with EGFR-positive non-small-cell lung cancer (NSCLC).Methods: Post hoc analyses from ARCHER 1050 evaluated efficacy in patients who did and did not experience grade ≥2 skin AEs with dacomitinib. Landmark analyses were performed at 3 and 6 months.Results: In patients who had skin AEs (72.2%) vs. those who did not (27.7%), median progression-free survival was 16.0 vs. 9.2 months, median overall survival (OS) was 37.7 vs. 21.6 months, and objective response rate was 80.2 vs. 61.5%; OS was improved at 3 and 6 months landmark analyses.Conclusion: Presence of grade ≥2 skin AEs was associated with numerically improved efficacy and represents a valuable biomarker of treatment outcome with dacomitinib in patients with advanced NSCLC.Clinical Trial Registration: NCT01774721 (ClinicalTrials.gov).


The ARCHER 1050 study assessed how the drugs called dacomitinib and gefitinib affected people with non-small-cell lung cancer (NSCLC) who had mutations in the EGFR gene. In this study, people who were treated with dacomitinib lived longer without their cancer getting worse than people who were treated with gefitinib. Skin adverse reactions were higher in people who were treated with dacomitinib than gefitinib. In this follow-up analysis, researchers wanted to see if the treatment effect of dacomitinib was different between people who had skin adverse reactions and people who did not have skin adverse reactions after treatment with dacomitinib. The results from this analysis showed that after treatment with dacomitinib, half of the people who had skin adverse reactions lived for 16.0 months, and half of the people who did not have skin adverse reactions lived for 9.2 months without their cancer getting worse. This study also showed that half of the people who had skin adverse reactions lived for 37.7 months, and half of the people who did not have skin adverse reactions lived for 21.6 months. In summary, the results from this study showed that the treatment effect of dacomitinib was better in people who had skin adverse reactions after treatment with dacomitinib. Therefore, skin adverse reactions can be a marker of better treatment effect in people with NSCLC who had mutations in the EGFR gene when treated with dacomitinib.

14.
IEEE Trans Med Imaging ; PP2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39361457

ABSTRACT

Semantic segmentation of ultrasound (US) images with deep learning has played a crucial role in computer-aided disease screening, diagnosis and prognosis. However, due to the scarcity of US images and small field of view, resulting segmentation models are tailored for a specific single organ and may lack robustness, overlooking correlations among anatomical structures of multiple organs. To address these challenges, we propose the Multi-Organ FOundation (MOFO) model for universal US image segmentation. The MOFO is optimized jointly from multiple organs across various anatomical regions to overcome the data scarcity and explore correlations between multiple organs. The MOFO extracts organ-invariant representations from US images. Simultaneously, the task prompt is employed to refine organ-specific representations for segmentation predictions. Moreover, the anatomical prior is incorporated to enhance the consistency of the anatomical structures. A multi-organ US database, comprising 7039 images from 10 organs across various regions of the human body, has been established to evaluate our model. Results demonstrate that the MOFO outperforms single-organ methods in terms of the Dice coefficient, 95% Hausdorff distance and average symmetric surface distance with statistically sufficient margins. Our experiments in multi-organ universal segmentation for US images serve as a pioneering exploration of improving segmentation performance by leveraging semantic and anatomical relationships within US images of multiple organs.

15.
Front Psychiatry ; 15: 1471969, 2024.
Article in English | MEDLINE | ID: mdl-39391085

ABSTRACT

Background: The National Health Interview Survey (NHIS) is a comprehensive health survey conducted by the National Center for Health Statistics (NCHS) in the U.S., providing valuable insights into the health status of the population. This study focuses on the NHIS child survey between 2019 and 2021, exploring developmental disabilities in U.S. children, including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder or attention-deficit disorder (ADHD/ADD), intellectual disability (ID), other developmental delay (other DD), and learning disability (LD). Objective: Leveraging NHIS data, our primary objective is to investigate the latest trends and disparities in the prevalence of developmental disabilities among various racial-ethnic groups. Methods: Employing a repeated cross-sectional design, we analyzed NHIS data from 2019 to 2021, focusing on children aged 3-17. The survey employed a meticulous stratified multi-stage sampling design. We utilized SAS version 9.4 for data analysis, calculating race-ethnicity-specific prevalence rates and employing weighted linear regression and the Rao-Scott chi-square test for trend analysis. Results: Among 19,490 children, prevalence rates varied: ASD (3.11%), ADHD/ADD (9.50%), ID (1.85%), other DD (5.66%), and LD (7.49%). Non-Hispanic black children exhibited higher rates of ID and LD, while non-Hispanic white children had the highest ADHD/ADD prevalence. Disparities persisted across sociodemographic subgroups, with variations in prevalence rates. Conclusion: Our study reveals an increase in ASD prevalence and persistent disparities among racial-ethnic groups. Non-Hispanic black children face elevated risks of ID and LD, while non-Hispanic white children exhibit higher rates of ADHD/ADD.

17.
Nat Commun ; 15(1): 8768, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39384754

ABSTRACT

RNAs and their encoded proteins intricately regulate diverse cell types and states within the human body. Dysregulated RNA expressions or mutations can lead to various diseased cell states, including tumorigenesis. Detecting and manipulating these endogenous RNAs offers significant promise for restoring healthy cell states and targeting tumors both in research and clinical contexts. This study presents an RNA-IN and RNA-OUT genetic circuit capable dynamically sensing and manipulating any RNA target in a programmable manner. The RNA-IN module employes a programmable CRISPR-associated protease (CASP) complex for RNA detection, while the RNA-OUT module utilizes an engineered protease-responsive dCas9-VPR activator. Additionally, the CASP module can detect point mutations by harnessing an uncovered dual-nucleotide synergistic switching effect within the CASP complex, resulting in the amplification of point-mutation signals from initially undetectable levels (1.5-fold) to a remarkable 94-fold. We successfully showcase the circuit's ability to rewire endogenous RNA-IN signals to activate endogenous progesterone biosynthesis pathway, dynamically monitor adipogenic differentiation of mesenchymal stem cells (MSCs) and the epithelial-to-mesenchmal trans-differentiation, as well as selective killing of tumor cells. The programmable RNA-IN and RNA-OUT circuit exhibits tremendous potential for applications in gene therapy, biosensing and design of synthetic regulatory networks.


Subject(s)
CRISPR-Cas Systems , Gene Regulatory Networks , Mesenchymal Stem Cells , RNA , Humans , RNA/metabolism , RNA/genetics , Mesenchymal Stem Cells/metabolism , Animals , Cell Differentiation/genetics , HEK293 Cells , Point Mutation
18.
Hortic Res ; 11(10): uhae212, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39385999

ABSTRACT

Anthocyanins are important compounds for fruit quality and nutrition. The R2R3 MYB transcription factor PpMYB10.1 is known to be critical for regulating anthocyanin accumulation in peach. However, regulatory factors upstream of PpMYB10.1 which control temperature-dependent, cultivar-contrasted and tissue-specific anthocyanin accumulation remain to be determined. In this study, differential anthocyanin accumulation in the outer flesh near the peel (OF) of peach [Prunus persica (L.) Batsch] was observed between cultivars 'Zhonghuashoutao' and 'Dongxuemi', as well as among different storage temperatures and different fruit tissues of 'Zhonghuashoutao'. By cross-comparisons of RNA-Seq data of samples with differential anthocyanin accumulation, transcription factor genes PpBBX32 and PpZAT5 were identified. These were functionally characterized as two positive regulators for anthocyanin accumulation via transient expression and genetic transformation. Various interaction assays revealed that both PpBBX32 and PpZAT5 can directly activate the PpMYB10.1 promoter and meanwhile interact at protein level as a PpZAT5-PpBBX32-PpMYB10.1 complex. Furthermore, the results of in silico analysis and exogenous application of methyl jasmonate (MeJA) indicated that MeJA favored anthocyanin accumulation, while it was also found that anthocyanin accumulation as well as PpBBX32 and PpZAT5 expression correlated significantly with endogenous JA and JA-Ile in different fruit tissues. In summary, PpBBX32 and PpZAT5 are upstream activators of PpMYB10.1, allowing JAs to take part in temperature-dependent and tissue-specific anthocyanin accumulation by modulating their expression. This work enriches the knowledge of the transcriptional regulatory mechanisms for differential anthocyanin accumulation under internal and external factors.

19.
Sci Rep ; 14(1): 23655, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39390095

ABSTRACT

Aiming at the problem of limited transmission energy of liquid crystal tunable filter (LCTF), a dual-wavelength transmission system with high signal-to-noise ratio (SNR) is proposed in this paper. The proposed transmission factor Qp is the main influence on the number and location of transmission wavelengths as well as the bandwidth of each transmission wavelength for dual-wavelength systems. Dual-wavelength LCTF can improve the effective transmission energy of the system by increasing the number of filtering channels, and the transmission energy can be increased by about 1.8 times and 70% at short and long wavelengths, respectively, which improves the signal-to-noise ratio (SNR) of the system. Moreover, the dual-wavelength LCTF system is even possible to increase the transmission energy by about 7% at a 33% increase in spectral resolution. Therefore, the dual-wavelength LCTF transmission method not only can improve the SNR of target detection with dual-wavelength response features, but also can effectively solve the problem of contradiction between spectral resolution and spectral transmission energy.

20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(9): 1110-1116, 2024 Sep 10.
Article in Chinese | MEDLINE | ID: mdl-39217492

ABSTRACT

OBJECTIVE: To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes. METHODS: Two patients treated at the Children's Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). RESULTS: Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.21q22.1)[40]/46,XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46,XY,r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11-21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them. CONCLUSION: Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.


Subject(s)
Chromosomes, Human, Pair 18 , Karyotyping , Ring Chromosomes , Humans , Male , Chromosomes, Human, Pair 18/genetics , DNA Copy Number Variations , Child, Preschool , Genetic Testing/methods , Infant , Child , Female , Exome Sequencing , Chromosome Deletion , Developmental Disabilities/genetics , Developmental Disabilities/diagnosis , Phenotype
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