Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis.

BACKGROUND: Atrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, a major pathological contributor. Central to the development of atrial fibrosis is myocardial inflammation. This study focuses on Atrial Natriuretic Peptide (ANP) and its role in mitigating atrial fibrosis, aiming to elucidate the specific mechanisms by which ANP exerts its effects, with an emphasis on fibroblast dynamics. METHODS AND RESULTS: The study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II. CONCLUSIONS: The study demonstrates ANP's potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP's effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.

The Correlation of Dynamic Magnetic Resonance Imaging Evaluation With Histological, Biochemical, and Biomechanical Properties in Healing Progress After Achilles Tendon Injury: A Review.

Achilles tendon injury is a common sports injury, and an in-depth understanding of its healing process is essential for improving rehabilitation strategies. As a non-invasive imaging technology with excellent anatomical and functional information extraction abilities, magnetic resonance imaging (MRI) has been widely used in the evaluation and monitoring of Achilles tendon injury. MRI scans at different stages of Achilles tendon healing can provide information about the structure of the Achilles tendon tissue, blood supply, composition, and metabolism. The change pattern on dynamic MRI evaluation is closely related to the specific stage of Achilles tendon healing and tissue characteristics. For example, the signal strength of dynamic enhanced MRI sequences can reflect blood supply to the Achilles tendon, whereas some quantitative MRI techniques can provide information on the recovery of water and collagen contents in the Achilles tendon. This article discusses the pathophysiological changes after Achilles tendon injury and summarizes the clinical and research status of the MRI techniques used for monitoring Achilles tendon healing. The feasibility of various MRI techniques for monitoring Achilles tendon healing and their correlation with histology, biochemistry, and biomechanics are reviewed, along with the challenges, limitations, and potential opportunities for their application. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF-1α pathway by improving the blood preservation solution.

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1ß, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.

Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway.

BACKGROUND: Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid. METHODS: Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α. RESULTS: The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice. CONCLUSIONS: Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice.

A Comparison of the Efficacy and Tolerability of the Treatments for Sciatica: A Network Meta-Analysis.

BACKGROUND: There remains a lack of a systematic summary of the efficacy and safety of various medicines for sciatica, and discrepancies among these exist. OBJECTIVE: The aim of this study is to comprehensively assess the efficacy of and tolerance to several medical options for the treatment of sciatica. METHODS: We performed a network meta-analysis and illustrated the results by the mean difference or odds ratio. The surface under the cumulative ranking curve (SUCRA) was used for indicating the preferable treatments. All data analyses and graphs were achieved via R 3.3.2 and Stata 13.0. RESULTS: The subcutaneous anti-tumor necrosis factor-α (anti-TNF-α) was superior to the epidural steroid + anesthetic in reducing lumbar pain in both acute + chronic sciatica patients and acute sciatica patients. The epidural steroid demonstrated a better ability regarding the Oswestry disability score (ODI) compared to the subcutaneous anti-TNF-α. In addition, for total pain relief, the use of nonsteroidal antiinflammatory drugs was inferior to the epidural steroid + anesthetic. The epidural anesthetic and epidural steroid + anesthetic both demonstrated superiority over the epidural steroid and intramuscular steroid. The intravenous anti-TNF-α ranked first in leg pain relief, while the subcutaneous anti-TNF-α ranked first in lumbar pain relief, and the epidural steroid ranked first in the ODI on the basis of SUCRA. In addition, their safety outcome (withdrawal) rankings were all medium to high. CONCLUSIONS: Intravenous and subcutaneous anti-TNF-α were identified as the optimal treatments for both acute + chronic sciatica patients and acute sciatica patients. In addition, the epidural steroid was also recommended as a good intervention due to its superiority in reducing ODI.

microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer.

BACKGROUND: miR-139-5p was identified to be significantly down-regulated in colon tumor tissues by miRNA array. We aimed to clarify its biological function, molecular mechanisms and direct target gene in colorectal cancer (CRC). METHODS: The biological function of miR-139-5p was examined by cell growth, cell cycle and apoptosis analysis in vitro and in vivo. miR-139-5p target gene and signaling pathway was identified by luciferase activity assay and western blot. RESULTS: miR-139-5p was significantly down-regulated in primary tumor tissues (P < 0.0001). Ectopic expression of miR-139-5p in colon cancer cell lines significantly suppressed cell growth as evidenced by cell viability assay (P < 0.001) and colony formation assay (P < 0.01) and in xenograft tumor growth in nude mice (P < 0.01). miR-139-5p induced apoptosis (P < 0.01), concomitantly with up-regulation of key apoptosis genes including cleaved caspase-8, caspase-3, caspase-7 and PARP. miR-139-5p also caused cell cycle arrest in G0/G1 phase (P < 0.01), with upregulation of key G0/G1 phase regulators p21Cip1/Waf1 and p27Kip1. Moreover, miR-139-5p inhibited cellular migration (P < 0.001) and invasiveness (P < 0.001) through the inhibition of matrix metalloproteinases (MMP)7 and MMP9. Oncogene NOTCH1 was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression (r = -0.3862, P = 0.0002). CONCLUSIONS: miR-139-5p plays a pivotal role in colon cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis and cell cycle arrest by targeting oncogenic NOTCH1.

Radiomics in Diagnosis, Grading, and Treatment Response Assessment of Soft Tissue Sarcomas: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: To evaluate radiomics in soft tissue sarcomas (STSs) for diagnostic accuracy, grading, and treatment response assessment, with a focus on clinical relevance. METHODS: In this diagnostic accuracy study, radiomics was applied using multiple MRI sequences and AI classifiers, with histopathological diagnosis as the reference standard. Statistical analysis involved meta-analysis, random-effects model, and Deeks' funnel plot asymmetry test. RESULTS: Among 579 unique titles and abstracts, 24 articles were included in the systematic review, with 21 used for meta-analysis. Radiomics demonstrated a pooled sensitivity of 84% (95% CI: 80-87) and specificity of 63% (95% CI: 56-70), AUC of 0.93 for diagnosis, sensitivity of 84% (95% CI: 82-87) and specificity of 73% (95% CI: 68-77), AUC of 0.91 for grading, and sensitivity of 83% (95% CI: 67-94) and specificity of 67% (95% CI: 59-74), AUC of 0.87 for treatment response assessment. CONCLUSION: Radiomics exhibits potential for accurate diagnosis, grading, and treatment response assessment in STSs, emphasizing the need for standardization and prospective trials. CLINICAL RELEVANCE STATEMENT: Radiomics offers precise tools for STS diagnosis, grading, and treatment response assessment, with implications for optimizing patient care and treatment strategies in this complex malignancy.

Transcriptomic analysis of epicardial adipose tissue reveals the potential crosstalk genes and immune relationship between type 2 diabetes mellitus and atrial fibrillation.

BACKGROUND: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. METHOD: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. RESULTS: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. CONCLUSION: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes.

HTR1B regulates mitochondrial homeostasis and mitophagy by activating the ERK/ MAPK signalling pathway during human embryonic arrest.

Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.

Metabolome and Transcriptome Analyses Reveal Flower Color Differentiation Mechanisms in Various Sophora japonica L. Petal Types.

Sophora japonica L. is an important landscaping and ornamental tree species throughout southern and northern parts of China. The most common color of S. japonica petals is yellow and white. In this study, S. japonica flower color mutants with yellow and white flag petals and light purple-red wing and keel petals were used for transcriptomics and metabolomics analyses. To investigate the underlying mechanisms of flower color variation in S. japonica 'AM' mutant, 36 anthocyanin metabolites were screened in the anthocyanin-targeting metabolome. The results demonstrated that cyanidins such as cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside in the 'AM' mutant were the key metabolites responsible for the red color of the wing and keel petals. Transcriptome sequencing and differentially expressed gene (DEG) analysis identified the key structural genes and transcription factors related to anthocyanin biosynthesis. Among these, F3'5'H, ANS, UFGT79B1, bHLH, and WRKY expression was significantly correlated with the cyanidin-type anthocyanins (key regulatory factors affecting anthocyanin biosynthesis) in the flag, wing, and keel petals in S. japonica at various flower development stages.

Influence of Oxytocin Usage and Dose Difference During Delivery on Pregnancy Outcome of VBAC Pregnant Women.

In order to explore the influence of oxytocin usage and dose difference during delivery on the pregnancy outcome of VBAC pregnant women, the clinical data of 166 VBAC pregnant women from January 2017 to March 2020 are retrospectively analyzed. All women are divided into different groups according to the usage of oxytocin during delivery and the oxytocin dose difference. Binary logistic regression is used to analyze the factors affecting the pregnancy outcome of pregnant women with VBAC. The gestational weeks and the thickness of the lower uterine segment in the oxytocin group are significantly more than those in the nonoxytocin group (P < 0.05). The time of the first stage of labor, second stage of labor, and total stage of labor in the oxytocin group are significantly longer than the nonoxytocin group (P < 0.05). The proportion of entering NICU in the oxytocin group is significantly lower than the nonoxytocin group (P < 0.05). There is no significant difference in labor duration and pregnancy outcome between low-dose and medium-dose oxytocin groups. Binary logistic regression analysis shows that prenatal BMI <30 kg/cm2, gestational age ≤40 weeks, history of vaginal delivery, uterine expansion, and admission to hospital are the influencing factors for pregnancy success of pregnant women with VBAC. The usage of oxytocin in VBAC pregnant women during delivery may increase the duration of labor. For those with poor uterine contraction, oxytocin can be increased to 4∼18 mU/min to speed up the labor process, without increasing the risk of adverse pregnancy outcomes.

Retraction Notice to: lncRNA MALAT1 Accelerates Wound Healing of Diabetic Mice Transfused with Modified Autologous Blood via the HIF-1α Signaling Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.05.020.].

BERTtoCNN: Similarity-preserving enhanced knowledge distillation for stance detection.

In recent years, text sentiment analysis has attracted wide attention, and promoted the rise and development of stance detection research. The purpose of stance detection is to determine the author's stance (favor or against) towards a specific target or proposition in the text. Pre-trained language models like BERT have been proven to perform well in this task. However, in many reality scenes, they are usually very expensive in computation, because such heavy models are difficult to implement with limited resources. To improve the efficiency while ensuring the performance, we propose a knowledge distillation model BERTtoCNN, which combines the classic distillation loss and similarity-preserving loss in a joint knowledge distillation framework. On the one hand, BERTtoCNN provides an efficient distillation process to train a novel 'student' CNN structure from a much larger 'teacher' language model BERT. On the other hand, based on the similarity-preserving loss function, BERTtoCNN guides the training of a student network, so that input pairs with similar (dissimilar) activation in the teacher network have similar (dissimilar) activation in the student network. We conduct experiments and test the proposed model on the open Chinese and English stance detection datasets. The experimental results show that our model outperforms the competitive baseline methods obviously.

Soft Rod-Climbing Robot Inspired by Winding Locomotion of Snake.

Soft climbing robots have attracted much attention of researchers for their potential applications on the wall or inside the tube. However, making a soft robot climb on the outer surface of a rod or tube by agile and efficient motion has long been a challenge. Inspired by the winding climbing locomotion of arboreal snakes, a tethered pneumatic-actuated winding-styled soft rod-climbing robot that consists of two winding actuators and a telescopic actuator is proposed in this work. Based on constant curvature assumption, we develop a theoretical model to analyze the linear and bending motion of the actuators. We demonstrate that our robot can perform climbing locomotion similar to snakes, including turning around a corner along a rod, climbing a vertical rod with a maximum speed of 30.85 mm/s (0.193 body length/s), and carrying a larger payload (weight, 500 g, more than 25 times its self-weight) than existing soft climbing robots do on a vertical surface. In addition, the experimental tests exhibit the potential applications of the robot in special environments such as high-voltage cables, nuclear power plants, and underwater sites.

lncRNA MALAT1 Accelerates Wound Healing of Diabetic Mice Transfused with Modified Autologous Blood via the HIF-1α Signaling Pathway.

Impaired wound healing is a debilitating complication of diabetes. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized to be differentially expressed in various diseases. However, its underlying mechanism in diabetes has not been fully understood. Notably, we aim to examine the expression of MALAT1 in diabetic mice and its role in wound healing involving the hypoxia-inducible factor-1α (HIF-1α) signaling pathway with a modified autologous blood preservative solution reported. A mouse model of diabetes was established. MALAT1 was identified to promote the activation of the HIF-1α signaling pathway and to be enriched in autologous blood through modified preservation, which might facilitate the improvement of physiological function of blood cells. Through gain- or loss-of-function approaches, viability of fibroblasts cultured in high glucose, wound healing of mice, and collagen expression in wound areas were enhanced by MALAT1 and HIF-1α. Taken together, the present study demonstrated that the physiological status of mouse blood was effectively improved by modified autologous blood preservation, which exhibited upregulated MALAT1, thereby accelerating the fibroblast activation and wound healing in diabetic mice via the activation of the HIF-1α signaling pathway. The upregulation of MALAT1 activating the HIF-1α signaling pathway provides a novel insight into drug targets against diabetes.

Augmentation of hypoxia-inducible factor-1-alpha in reinfused blood cells enhances diabetic ischemic wound closure in mice.

Diabetes-associated dysfunction in angiogenesis predominantly contributes to impairment of wound closure, but a role of hypoxia-inducible factor 1 alpha (HIF-1a) in the process remain poorly understood. Here, we examined whether expression of HIF-1a in re-infused blood cells may improve the diabetic wound closure in mice. We found that that expression of HIF-1a in re-infused isogeneic blood cells significantly improved diabetic wound healing in mice, seemingly through augmentation of wound-associated angiogenesis. Mechanistically, expression of HIF-1a in re-infused blood cells significantly increased macrophage infiltration at the wound site, and macrophages produced vascular endothelial growth factor A (VEGF-A) to promote wound-associated angiogenesis. Together, our data suggest that augmentation of HIF-1a in reinfused blood cells may enhance diabetic ischemic wound closure.