Mesenchymal Stem Cell-Derived Exosomes as Drug Delivery Vehicles in Disease Therapy.

Exosomes are small vesicles containing proteins, nucleic acids, and biological lipids, which are responsible for intercellular communication. Studies have shown that exosomes can be utilized as effective drug delivery vehicles to accurately deliver therapeutic substances to target tissues, enhancing therapeutic effects and reducing side effects. Mesenchymal stem cells (MSCs) are a class of stem cells widely used for tissue engineering, regenerative medicine, and immunotherapy. Exosomes derived from MSCs have special immunomodulatory functions, low immunogenicity, the ability to penetrate tumor tissues, and high yield, which are expected to be engineered into efficient drug delivery systems. Despite the promising promise of MSC-derived exosomes, exploring their optimal preparation methods, drug-loading modalities, and therapeutic potential remains challenging. Therefore, this article reviews the related characteristics, preparation methods, application, and potential risks of MSC-derived exosomes as drug delivery systems in order to find potential therapeutic breakthroughs.

The NAC transcription factor MdNAC4 positively regulates nitrogen deficiency-induced leaf senescence by enhancing ABA biosynthesis in apple.

Although it is well established that nitrogen (N) deficiency induces leaf senescence, the molecular mechanism of N deficiency-induced leaf senescence remains largely unknown. Here, we show that an abscisic acid (ABA)-responsive NAC transcription factor (TF) is involved in N deficiency-induced leaf senescence. The overexpression of MdNAC4 led to increased ABA levels in apple calli by directly activating the transcription of the ABA biosynthesis gene MdNCED2. In addition, MdNAC4 overexpression promoted N deficiency-induced leaf senescence. Further investigation showed that MdNAC4 directly bound the promoter of the senescence-associated gene (SAG) MdSAG39 and upregulated its expression. Interestingly, the function of MdNAC4 in promoting N deficiency-induced leaf senescence was enhanced in the presence of ABA. Furthermore, we identified an interaction between the ABA receptor protein MdPYL4 and the MdNAC4 protein. Moreover, MdPYL4 showed a function similar to that of MdNAC4 in ABA-mediated N deficiency-induced leaf senescence. These findings suggest that ABA plays a central role in N deficiency-induced leaf senescence and that MdPYL4 interacts with MdNAC4 to enhance the response of the latter to N deficiency, thus promoting N deficiency-induced leaf senescence. In conclusion, our results provide new insight into how MdNAC4 regulates N deficiency-induced leaf senescence.

Direct Immunofluorescence of IgG on Formalin-Fixed Paraffin-Embedded Tissue by Heat-Induced Antigen Retrieval as a Sensitive Method for the Diagnosis of Pemphigus.

Purpose: Direct immunofluorescence (DIF) on frozen sections (DIF-F) plays a key role in the identification and differential diagnosis of bullous dermatoses, which are a group of critical autoimmune diseases that include pemphigus, bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). However, this technique requires specialized laboratory equipment conditions, sample acquisition and sample preservation. In this study, the application value of DIF on paraffin-embedded tissue sections (DIF-P) detecting IgG using heat-induced antigen retrieval (HIAR) in the diagnosis of bullous dermatosis was explored. Patients and Methods: Samples from 12 patients with pemphigus vulgaris (PV), 10 patients with pemphigus foliaceus (PF), 17 patients with BP, and 4 patients with EBA were retrospectively studied for DIF-P IgG detection. Formalin-fixed, paraffin-embedded tissue (FFPE) was used, and the antigen retrieval method used in the experiment was HIAR. All patients were diagnosed with the autoimmune bullous disease (AIBD) based on clinical presentation, histopathology, DIF-F, and enzyme-linked immunosorbent assay (ELISA). Results: Intercellular staining for IgG in the epidermis was successful in paraffin-embedded tissue sections in 11 of 12 PV samples and in all 10 PF samples. IgG at the basement membrane zone (BMZ) was not detected by immunofluorescent staining in 17 BP samples and 4 EBA samples. Conclusion: The detection of IgG by DIF-P using HIAR can be used for the diagnosis of pemphigus as an alternative method to DIF-F.

Improving image quality and resolution of coronary arteries in coronary computed tomography angiography by using high-definition scans and deep learning image reconstruction.

Background: Coronary computed tomography angiography (CTA) has been increasingly used to identify the degree of coronary artery stenosis and plaque lesions in vessels. This study evaluated the feasibility of using high-definition (HD) scanning with high-level deep learning image reconstruction (DLIR-H) to improve the image quality and spatial resolution when imaging calcified plaques and stents in coronary CTA as compared to the standard definition (SD) reconstruction mode with adaptive statistical iterative reconstruction-V (ASIR-V). Methods: A total of 34 patients (age 63.3±10.9 years; 55.88% female) with calcified plaques and/or stents who underwent coronary CTA in HD-mode were included in this study. Images were reconstructed with SD-ASIR-V, HD-ASIR-V, and HD-DLIR-H. Subjective image quality with image noise and clarity of vessels, calcifications, and stented lumens was evaluated by 2 radiologists using a 5-point scale. The kappa (κ) test was used to analyze the interobserver agreement. Objective image quality with image noise, signal-to-noise-ratio (SNR), and contrast-to-noise-ratio (CNR) was measured and compared. Image spatial resolution and beam-hardening artifacts (BHAs) were also evaluated using the calcification diameter and CT numbers in 3 points along the stented lumen (inside, at the proximal and distal ends just outside stent). Results: There were 45 calcified plaques and 4 coronary stents. HD-DLIR-H images had the highest overall image quality score (4.50±0.63) with the lowest image noise (22.59±3.59 HU) and the highest SNR (18.30±4.88) and CNR (26.56±6.33), followed by SD-ASIR-V50% image quality score (4.06±2.49), image noise (35.02±8.09 HU), SNR (12.77±1.59), CNR(15.67±1.92) and HD-ASIR-V50% image quality score (3.90±0.64), image noise (57.7±12.03 HU), SNR (8.16±1.86), CNR (10.01±2.39). HD-DLIR-H images also had the smallest calcification diameter measurement (2.36±1.58 mm), followed by HD-ASIR-V50% (3.46±2.07 mm) and SD-ASIR-V50% (4.06±2.49 mm). HD-DLIR-H images had the closest CT value measurements for the 3 points along the stented lumen, indicating much less BHA. Interobserver agreement on the image quality assessment was good to excellent (HD-DLIR-H: κ value =0.783; HD-ASIR-V50%: κ value =0.789; SD-ASIR-V50%: κ value =0.671). Conclusions: Coronary CTA with HD scan mode and DLIR-H significantly improves the spatial resolution for displaying calcifications and in-stent lumens while simultaneously reducing image noise.

Improving image quality with deep learning image reconstruction in double-low-dose head CT angiography compared with standard dose and adaptive statistical iterative reconstruction.

OBJECTIVE: To demonstrate similar image quality with deep learning image reconstruction (DLIR) in reduced contrast medium (CM) and radiation dose (double-low-dose) head CT angiography (CTA), in comparison with standard-dose and adaptive statistical iterative reconstruction-Veo (ASIR-V). METHODS: A prospective study was performed in 63 patients who under head CTA using 256-slice CT. Patients were randomized into either the standard-dose group (n = 38) with 40 ml of Iopromide (370 mgI ml-1 at 4.5 ml s-1); or a double-low-dose group (n = 25) with CM of 25 ml at 3.0 ml s-1. For image reconstruction, the double-low-dose group used DLIR-M and DLIR-H strength, and the standard-dose group used ASIR-V with 50% strength. The CT value and standard deviation, signal-to-noise ratio and contrast-to-noise ratio of posterior fossa, neck muscles, carotid, vertebral and middle cerebral arteries were measured. The image noise, vessel edge and structure blurring and overall image quality were assessed by using a 5-grade method. The double-low-dose group reduced CM dose by 37.5% and CT dose index by 41% compared with the standard-dose group. DLIR further reduced the standard deviation value of the middle cerebral artery and posterior fossa and provided better overall subjective image quality (p < 0.05). CONCLUSION: DLIR significantly reduces image noise and provides higher overall image quality in the double-low-dose CTA. ADVANCES IN KNOWLEDGE: It is feasible to reduce CM dose by 37.5% and volume CT dose index by 41% with the combination of 80 kVp and DLIR in head CTA. Compared with ASIR-V, DLIR further reduces image noise and achieves better image quality with reduced contrast and radiation dose.

Facile Surface Depolymerization Promotes the Welding of Hard Epoxy Vitrimer.

Welding via bond exchange reactions has provided advances in obtaining high-quality joining performance. However, the reported welding method requires a relatively high press force, and challenges are still encountered in welding hard vitrimer. In this work, a facile surface depolymerization strategy was introduced to weld high-performance epoxy vitrimer. The vitrimers were firstly dissolved into ethylene glycol for depolymerization based on the solvent-assisted bond exchange reactions. Then, the depolymerized vitrimers were welded under heat and press force. The effect of the depolymerizing time, welding pressure, welding temperature and welding time on the welding strength were further investigated. It was found that there were optimal values for the depolymerizing time, welding pressure, and welding temperature, respectively, for the welding strength, while the welding strength increased with increasing welding time. Through facile surface degradation, the welding pressure was highly reduced, while the welding strength was increased. With surface depolymerization, the welding strength was 1.55-times higher, but the magnitude of press force was 1/1000-times than that with no surface depolymerization. It is elucidative that surface depolymerization can be used to weld hard vitrimer composites alongside reducing the press force effectively.

MdNAC4 Interacts With MdAPRR2 to Regulate Nitrogen Deficiency-Induced Leaf Senescence in Apple (Malus domestica).

Nitrogen (N) is one of the important macronutrients in plants, and N deficiency induces leaf senescence. However, the molecular mechanism underlying how N deficiency affects leaf senescence is unclear. Here, we report an apple NAC TF, MdNAC4, that participates in N deficiency-induced leaf senescence. The senescence phenotype of apple leaves overexpressing MdNAC4 was enhanced after N deficiency. Consistently, the chlorophyll content of transgenic leaves was significantly lower than that in the WT control leaves, the expression of chlorophyll catabolism-related genes (MdNYC1, MdPAO, and MdSGR1) was significantly higher than that in the WT controls, and the expression of chlorophyll synthesis-related genes (MdHEMA, MdCHLI, and MdCHLM) was significantly lower than that in the WT control leaves. Furthermore, MdNAC4 was found to directly activate the transcription of the chlorophyll catabolism-related genes MdNYC1 and MdPAO. Additionally, MdNAC4 was proven to interact with MdAPRR2 proteins both in vitro and in vivo, and overexpression of MdAPRR2 seemed to delay N deficiency-induced leaf senescence. Correspondingly, the chlorophyll loss of MdAPRR2-overexpressing (MdAPRR2-OE) lines was significantly lower than in WT control plants. Although downregulated, the expression of the chlorophyll synthesis-related genes MdHEMA, MdCHLI, and MdCHLM in the transgenic plants was more than twice that in the WT control plants. Taken together, our results enrich the regulatory network of leaf senescence induced by N deficiency through the interaction between MdNAC4 and MdAPRR2.

PET/MR fusion texture analysis for the clinical outcome prediction in soft-tissue sarcoma.

BACKGROUND: Various fusion strategies (feature-level fusion, matrix-level fusion, and image-level fusion) were used to fuse PET and MR images, which might lead to different feature values and classification performance. The purpose of this study was to measure the classification capability of features extracted using various PET/MR fusion methods in a dataset of soft-tissue sarcoma (STS). METHODS: The retrospective dataset included 51 patients with histologically proven STS. All patients had pre-treatment PET and MR images. The image-level fusion was conducted using discrete wavelet transformation (DWT). During the DWT process, the MR weight was set as 0.1, 0.2, 0.3, 0.4, …, 0.9. And the corresponding PET weight was set as 1- (MR weight). The fused PET/MR images was generated using the inverse DWT. The matrix-level fusion was conducted by fusing the feature calculation matrix during the feature extracting process. The feature-level fusion was conducted by concatenating and averaging the features. We measured the predictive performance of features using univariate analysis and multivariable analysis. The univariate analysis included the Mann-Whitney U test and receiver operating characteristic (ROC) analysis. The multivariable analysis was used to develop the signatures by jointing the maximum relevance minimum redundancy method and multivariable logistic regression. The area under the ROC curve (AUC) value was calculated to evaluate the classification performance. RESULTS: By using the univariate analysis, the features extracted using image-level fusion method showed the optimal classification performance. For the multivariable analysis, the signatures developed using the image-level fusion-based features showed the best performance. For the T1/PET image-level fusion, the signature developed using the MR weight of 0.1 showed the optimal performance (0.9524(95% confidence interval (CI), 0.8413-0.9999)). For the T2/PET image-level fusion, the signature developed using the MR weight of 0.3 showed the optimal performance (0.9048(95%CI, 0.7356-0.9999)). CONCLUSIONS: For the fusion of PET/MR images in patients with STS, the signatures developed using the image-level fusion-based features showed the optimal classification performance than the signatures developed using the feature-level fusion and matrix-level fusion-based features, as well as the single modality features. The image-level fusion method was more recommended to fuse PET/MR images in future radiomics studies.

Comparison of Guidelines for Management of Pemphigus: a Review of Systemic Corticosteroids, Rituximab, and Other Immunosuppressive Therapies.

Pemphigus is a severe autoimmune bullous dermatosis that affects the skin and/or mucosa, and it may be life-threatening without proper treatment. The guidelines and/or consensus statements for treatment vary widely between groups. We selected 6 guidelines and consensus statements established by different associations about the management of pemphigus vulgaris (PV) and/or pemphigus foliaceus (PF) to review, compare, and contrast the similarities and differences of these recommendations and provide optimal management suggestions to physicians. Corticosteroids remain a first-line therapy for pemphigus, but there are many differences in initial dose, tapering schedule, and management of relapse between different guidelines. Rituximab is a monoclonal antibody targeting CD20-positive B lymphocytes that is approved as a first-line therapy in moderate-to-severe pemphigus. Immunosuppressive agents, such as azathioprine (AZA) and mycophenolate mofetil (MMF), are also widely used as corticosteroid-sparing drugs, but the adjuvant applications and dosage regimens of different recommendations are not standardized. We attribute these differences to the clinical scoring adopted, the standards for disease severity evaluation, the publication year of each guideline, and local and regional healthcare differences.

Recyclable High-Performance Epoxy-Anhydride Resins with DMP-30 as the Catalyst of Transesterification Reactions.

Epoxy-anhydride resins are widely used in engineering fields due to their excellent performance. However, the insolubility and infusibility make the recycling of epoxy resins challenging. The development of degradable epoxy resins with stable covalent networks provides an efficient solution to the recycling of thermosets. In this paper, 2,4,6-tris(dimethylaminomethyl)phenol (DMP-30) is incorporated into the epoxy-glutaric anhydride (GA) system to prepare high-performance epoxy resins that can be recycled below 200 °C at ordinary pressure via ethylene glycol (EG) participated transesterification. The tertiary amine groups in DMP-30 can catalyze the curing reaction of epoxy and anhydride, as well as the transesterification between ester bonds and alcoholic hydroxyl groups. Compared with early recyclable anhydride-cured epoxy resins, the preparation and recycling of diglycidyl ether of bisphenol A (DGEBA)/GA/DMP-30 systems do not need any special catalysts such as TBD, Zn(Ac)2, etc., which are usually expensive, toxic, and have poor compatibility with other compounds. The resulting resins have glass transition temperatures and strengths similar to those of conventional epoxy resins. The influences of GA content, DMP-30 content, and temperature on the dissolution rate were studied. The decomposed epoxy oligomer (DEO) is further used as a reaction ingredient to prepare new resins. It is found that the DEO can improve the toughness of epoxy resins significantly. This work provides a simple method to prepare readily recyclable epoxy resins, which is of low-cost and easy to implement.

[Comparison of the methods for detecting R wave in electrocardiogram].

In an ECG auto-analysis system, correct QRS detection is most important. For this detection there are several methods, such as derivative-based algorithms, filter-bank methods and wavelet based methods and neural network approaches, but there is no single method that is extensively used. These methods are compared and analyzed in this paper.