Discovery of electromagnetic polarization in Asian rice wine deterioration process and its applications.

Rice wine, known as yellow wine in China and Japan, possesses considerable nutritional value and holds significant global influence. This study addresses the challenge of preserving rice wine, which is prone to rancidity due to its low alcohol content. Conventional storage techniques employing pottery jars often result in substantial spoilage losses. Through rigorous investigation, this research identifies a polarization phenomenon exhibited by degraded rice wine when subjected to high-frequency microwaves(>60GHz), presenting a pioneering method for detecting spoilage, even within sealed containers. Employing a multi-channel microwave radar apparatus, the study delves into the susceptibility of rice wine to electromagnetic waves across various frequencies, uncovering pronounced polarization traits in deteriorated samples within the E-band microwave spectrum. Furthermore, lab-controlled simulations elucidate a direct correlation between physicochemical alterations and high-frequency Radar Cross Section (RCS) signals during the wine's deterioration process. A novel six-membered Hydrated Cluster hypothesis is proposed, offering insights into the molecular mechanisms underlying this phenomenon. Additionally, dielectric property assessments conducted using vector network analyzers (VNA) reveal noteworthy enhancements in the dielectric constant of deteriorated rice wine, particularly within the high-frequency domain, thereby augmenting detectability. These findings carry implications for refining rice wine preservation techniques and contribute to the advancement of non-destructive testing technologies, enabling the detection of rice wine deterioration or indications thereof, even within sealed vessels.

Diagnostic value of cervical vascular ultrasound in large arterial lesions of the neck in patients with transient ischemic attack.

OBJECTIVE: To assess the diagnostic value of cervical vascular ultrasound in identifying large arterial lesions in patients with transient ischemic attack (TIA). METHODS: The current study matched 84 TIA patients (disease group) with 66 healthy controls (control group). The baseline patient profiles and biochemical indices of the patients were analyzed. All patients received color Doppler ultrasonography, and outcome measures of its diagnostic efficiency included plaque status, plaque properties, and the degree of carotid stenosis. The patients in the disease group were assigned to group A (TIA of the internal carotid artery system, n = 40) and group B (TIA of the vertebrobasilar artery system, n = 44), and the plaque distribution of the patients was analyzed. RESULTS: TIA patients had higher rates of diabetes, hypertension, hyperlipidemia, obesity, and smoking compared to controls (p < 0.05). Their serum TC, LDL-C, and FBG levels were significantly elevated, while HDL-C levels were decreased (p < 0.05). TIA patients had more plaques, especially soft plaques, than controls (p < 0.05). They also showed higher rates of moderate to severe carotid stenosis (p < 0.05). TIA involving the internal carotid artery system was associated with a higher risk of plaques at the entrance of the subclavian artery compared to TIA involving the vertebrobasilar artery system (p < 0.05). CONCLUSION: The diagnostic value of cervical vascular ultrasound in patients with TIA is remarkable, and it provides a reliable monitoring approach as well as an essential screening modality for TIA. The rational use of this technique will markedly benefit the diagnosis, treatment, and prevention of TIA.

The relationship between epicardial adipose tissue volume on coronary computed tomography angiography and idiopathic ventricular tachycardia: a propensity score matching case-control study in Chinese population.

Background: Large epicardial adipose tissue (EAT) volume is associated with the incidence of premature ventricular beats. The relationship between EAT volume and idiopathic ventricular tachycardia (IVT) is not yet clear. We aimed to investigate the effect of EAT volume on the risk of IVT. Methods: This is a retrospective consecutive case-control study from January 2020 to September 2022. IVT patients (n=81) and control patients (n=162) undergoing coronary computed tomography angiography (CCTA) were retrospectively recruited. The patients in the control group were all hospitalized patients for different reasons, such as chest tightness, shortness of breath, chest pain, and so on. Demographic parameters and clinical characteristics of each individual were collected from the patient's medical records. We selected evaluation criteria for the conduct of a 1:1 propensity score (PS)-adjusted analysis. Multivariable logistic analysis was used to investigate risk factors for IVT. Furthermore, the impact of EAT volume on cardiac repolarization indices was assessed in IVT patients. Results: Patients with IVT had a larger EAT volume than control group patients in the unadjusted cohort. Variables with P<0.10 in the univariable analysis and important factors were included in the multivariable analysis model, including body mass index (BMI), left ventricular ejection fraction (LVEF), early peak/artial peak (E/A) ratios <1, EAT attenuation, and EAT volume (per increase 10 mL). The multivariable logistic analysis found that EAT volume [per increase 10 mL, odds ratio (OR): 1.29, 95% confidence interval (CI): 1.17-1.41, P<0.001] was an independent risk factor for IVT. EAT volume (per increase 10 mL, OR: 1.43, 95% CI: 1.25-1.64, P<0.001) independent effect was demonstrated in the PS adjusted cohort (n=57 in both groups). The area under the curve of EAT volume to predict the risk of IVT patients in the PS adjusted cohort was 0.859. The sensitivity and specificity were 86.0%, and 75.4%, respectively. Furthermore, A large EAT volume of IVT patients had a longer time in Tp-e, and Tp-e/QTc, compared with low EAT volume. Conclusions: Patients with IVT had increased EAT volume compared to control subjects. Our study revealed that large EAT volume is associated with an extended repolarization process in IVT patients. These insights are essential for understanding the mechanisms linking EAT with IVT.

Data-driven classification of left atrial morphology and its predictive impact on atrial fibrillation catheter ablation.

INTRODUCTION: Various left atrial (LA) anatomical structures are correlated with postablative recurrence for atrial fibrillation (AF) patients. Comprehensively integrating anatomical structures, digitizing them, and implementing in-depth analysis, which may supply new insights, are needed. Thus, we aim to establish an interpretable model to identify AF patients' phenotypes according to LA anatomical morphology, using machine learning techniques. METHODS AND RESULTS: Five hundred and nine AF patients underwent first ablation treatment in three centers were included and were followed-up for postablative recurrent atrial arrhythmias. Data from 369 patients were regarded as training set, while data from another 140 patients, collected from different centers, were used as validation set. We manually measured 57 morphological parameters on enhanced computed tomography with three-dimensional reconstruction technique and implemented unsupervised learning accordingly. Three morphological groups were identified, with distinct prognosis according to Kaplan-Meier estimator (p < .001). Multivariable Cox model revealed that morphological grouping were independent predictors of 1-year recurrence (Group 1: HR = 3.00, 95% CI: 1.51-5.95, p = .002; Group 2: HR = 4.68, 95% CI: 2.40-9.11, p < .001; Group 3 as reference). Furthermore, external validation consistently demonstrated our findings. CONCLUSIONS: Our study illustrated the feasibility of employing unsupervised learning for the classification of LA morphology. By utilizing morphological grouping, we can effectively identify individuals at different risks of postablative recurrence and thereby assist in clinical decision-making.

Non-insulin-based insulin resistance indexes in predicting atrial fibrillation recurrence following ablation: a retrospective study.

BACKGROUND: Insulin resistance (IR) is involved in the pathophysiological processes of arrhythmias. Increasing evidence suggests triglyceride and glucose (TyG) index, metabolic score for insulin resistance (METS-IR), triglyceride glucose-body mass index (TyG-BMI), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio are simple and reliable surrogates for IR. Although they have been associated with atrial fibrillation (AF), evidence supporting this is limited. Here, this is the first study to investigate the association between TyG-BMI index and AF recurrence following radiofrequency catheter ablation (RFCA). The performance of the four non-insulin-based IR indexes in predicting AF recurrence after ablation was explored. METHODS: A total of 2242 AF patients who underwent a de novo RFCA between June 2018 to January 2022 at two hospitals in China were included in this retrospective study. The predictive values of IR indexes for AF recurrence after ablation were assessed. RESULTS: During 1-year follow-up, 31.7% of patients experienced AF recurrence. The multivariable analysis revealed that TyG index, METS-IR, and TyG-BMI index were independent risk factors for AF recurrence. Restricted cubic spline analysis revealed a connection between METS-IR, TyG-BMI index, and AF recurrence (P < 0.001). Furthermore, incorporating the METS-IR or TyG-BMI index to the basic risk model with fully adjusted factors considerably enhanced the forecast of AF recurrence, as demonstrated by the C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: TyG index, METS-IR, and TyG-BMI index were independently associated with AF recurrence following ablation. Among the four non-insulin-based IR indexes, TyG-BMI had the highest predictive value, followed by METS-IR.

Relationship Between Epicardial Adipose Tissue Volume and Recurrence After Ablation in Premature Ventricular Complexes.

BACKGROUND: Epicardial adipose tissue (EAT) is recognized as a clinical diagnostic marker for cardiometabolic disease. Thicker EAT may be associated with recurrence of ventricular tachycardia after ablation. The association between EAT volume and recurrence of premature ventricular complexes (PVC) following ablation has not been clarified. We investigated the association between EAT volume and PVC recurrence following radiofrequency catheter ablation.Methods and Results: This retrospective study included 401 patients with PVC undergoing catheter ablation with preprocedural non-contrast computed tomography between 2017 and 2022. The impact of EAT volume in predicting PVC recurrence after ablation was analyzed. The mean (±SD) age of patients was 50.2±13.3 years. Multivariable Cox analysis revealed that a large EAT volume was an independent predictor of PVC recurrence after ablation during a median follow-up of 16.3 months. Kaplan-Meier analysis showed a difference in postablation PVC recurrence between the 2 groups dichotomized around the EAT volume cut-off. The risk of recurrence increased with increasing EAT volume according to restricted cubic spline regression. Furthermore, PVC originating from epicardial locations had larger EAT volumes than those originating from the right ventricular outflow tract. CONCLUSIONS: A large EAT volume was independently associated with PVC recurrence following ablation. Patients with PVC originating from epicardial sites had large EAT volumes. EAT volume may help stratify patients according to their risk of PVC recurrence after ablation.

Late paleozoic climate revealed by coral fossil patterns.

The study of coral fossils with clear growth lines inShiqiantan Formation (310 Ma) in China showed the growth line increments of a single coral growing in this area is related to the sunlight illumination time. Moreover, the daily increment of the growth line caused by calcium carbonate depositions has an unusual bimodal curve. The study of this bimodal curve indicated Shiqiantan had evident four-season changes in the Late Carboniferous period, and the climate at that time was similar to that of modern North China. The present paper updates the oldest existing record of climate analysis materials and provides important information for the study of Late Paleozoic climate, as well as the ancient obliquity of ecliptic.

BTN2A2-Ig protein inhibits the differentiation of pathogenic Th17 cells and attenuates EAE in mice.

Pathogenic Th17 cells play a key role in the pathogenesis of many autoimmune diseases. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the commonly used animal model for human MS and is characterized by autoreactive CD4+T cells attacking autoantigens in the CNS and causing myelin sheath damage. Although the recombinant BTN2A2-IgG2aFc (BTN2A2-Ig) fusion protein has been shown to inhibit T cell functions in vitro, it's unclear whether BTN2A2-Ig affects pathogenic Th17 cells and EAE development. We show here that BTN2A2-Ig protein attenuates established EAE, as compared with control Ig protein treatment. This is associated with reduced activation and proliferation of T cells in BTN2A2-Ig-treated EAE mice. Furthermore, BTN2A2-Ig protein inhibits the differentiation of CD4 naïve T cells into pathogenic Th17 cells and reduces the expression levels of Th1/Th17 cytokines and the Th1/Th17 pathway related genes and proteins but increases the expression levels of Th2-related genes and proteins. Our studies not only provide new insights into the mechanisms by which BTN2A2-Ig affects T cells, but also have the potential to provide a new strategy to treat MS and other autoimmune diseases.

Impact of carotid atherosclerosis on arrhythmia recurrence following atrial fibrillation catheter ablation.

BACKGROUND: It remains unclear whether carotid atherosclerosis (CAS) increases the atrial fibrillation (AF) recurrence rate after ablation. The aim was to assess the association between CAS, defined as carotid intima-media thickness (CIMT) ≥1 mm and or presence of carotid plaques, and AF recurrence rate after ablation. METHODS: We retrospectively collected patients who underwent carotid ultrasonography and AF ablation at the First Affiliated Hospital of Zhengzhou University. The AF recurrence was defined as documented atrial arrhythmias over 30 s on ECG or 24-h Holter monitoring after the first three months blanking period. Cox regression models were used to analyze the risk of AF recurrence. RESULTS: Overall, 385 patients were analyzed (mean age, 60.58±10.98 years old; female, 41.30%; persistent AF, 47.27%). After a follow-up of 1 year, 138 (35.84%) patients experienced recurrence, Kaplan-Meier analysis showed that patients with the presence of carotid plaques, CIMT ≥1 mm, and CAS had a higher risk of recurrence compared with the absence (all log-rank p < .05). In multivariate Cox regression analysis, CAS (HR 2.159, ±95% CI 1.320-3.532, p = .002), carotid plaque (HR 1.815, ±95%CI 1.160-2.841, p = .009), and CIMT ≥1 mm (HR 1.696, ±95%CI 1.192-2.413, p = .003) were independently associated with a higher risk of recurrence. In subgroup analysis, the association of CAS, carotid plaque, and AF recurrence rate was weaker in men than women. CONCLUSION: Carotid atherosclerosis, CIMT ≥1 mm, and carotid plaque were significantly associated with a higher AF recurrence rate after radiofrequency catheter ablation. They were all risk factors for the recurrence of AF.

Semantic Segmentation of Hyperspectral Remote Sensing Images Based on PSE-UNet Model.

With the development of deep learning, the use of convolutional neural networks (CNN) to improve the land cover classification accuracy of hyperspectral remote sensing images (HSRSI) has become a research hotspot. In HSRSI semantics segmentation, the traditional dataset partition method may cause information leakage, which poses challenges for a fair comparison between models. The performance of the model based on "convolutional-pooling-fully connected" structure is limited by small sample sizes and high dimensions of HSRSI. Moreover, most current studies did not involve how to choose the number of principal components with the application of the principal component analysis (PCA) to reduce dimensionality. To overcome the above challenges, firstly, the non-overlapping sliding window strategy combined with the judgment mechanism is introduced, used to split the hyperspectral dataset. Then, a PSE-UNet model for HSRSI semantic segmentation is designed by combining PCA, the attention mechanism, and UNet, and the factors affecting the performance of PSE-UNet are analyzed. Finally, the cumulative variance contribution rate (CVCR) is introduced as a dimensionality reduction metric of PCA to study the Hughes phenomenon. The experimental results with the Salinas dataset show that the PSE-UNet is superior to other semantic segmentation algorithms and the results can provide a reference for HSRSI semantic segmentation.

Impact of advanced liver fibrosis on atrial fibrillation recurrence after ablation in non-alcoholic fatty liver disease patients.

Aim: Advanced liver fibrosis is independently associated with new onset of atrial fibrillation (AF). Non-invasive liver fibrosis scores are considered an effective strategy for assessing liver fibrosis. This study aimed to investigate the association between advanced liver fibrosis and AF recurrence after ablation in patients with non-alcoholic fatty liver disease (NAFLD). Materials and methods: A total of 345 AF patients with NAFLD who underwent de novo ablation between 2019 and 2020 at two large hospitals in China were included in this study. AF recurrence was defined as the occurrence of atrial arrhythmia for more than 30 s by electrocardiogram or 24 h Holter monitoring after the first 3 months of ablation. Predictive values of non-alcoholic fatty liver disease fibrosis score (NFS) and Fibrosis-4 (FIB-4) scores for AF burden and recurrence after ablation were assessed. Results: At the 1 year follow-up after ablation, 38.8% of patients showed recurrence. Patients with recurrence who had higher FIB-4 and NFS scores were more likely to have persistent AF and a duration of AF ≥ 3 years. In Kaplan-Meier analysis, patients with intermediate and high NFS and FIB-4 risk categories had a higher risk of AF recurrence. Compared to patients with the low risk, intermediate and high NFS, and FIB-4 risk were independently associated with AF recurrence in multivariate Cox regression analysis (high risk: NFS, hazard ratio (HR): 3.11, 95% confidence interval (CI): 1.68∼5.76, p < 0.001; FIB-4, HR: 3.91, 95% CI: 2.19∼6.98, p < 0.001; intermediate risk: NFS, HR: 1.85, 95% CI: 1.10∼3.10, p = 0.020; FIB-4, HR: 2.08, 95% CI: 1.27∼3.41, p = 0.003). Conclusion: NFS and FIB-4 scores for advanced liver fibrosis are associated with AF burden. Advanced liver fibrosis is independently associated with AF recurrence following ablation. Advanced liver fibrosis might be meaningful in risk classification for patients after AF ablation.

Effect of Dapagliflozin on the Outcome of Radiofrequency Catheter Ablation in Patients with Type 2 Diabetes Mellitus and Atrial Fibrillation.

INTRODUCTION: Dapagliflozin, one of the sodium-glucose cotransporter-2 inhibitors, has been widely used for the treatment of type 2 diabetes mellitus (T2DM) and heart failure. In this study, we sought to determine the impact of dapagliflozin on the outcome of radiofrequency catheter ablation (RFCA) for patients with T2DM and atrial fibrillation (AF). METHODS: This retrospective study included patients who underwent AF ablation between January 2019 to February 2021 at the First Affiliated Hospital of Zhengzhou University. All patients had a history of T2DM and were divided into the dapagliflozin group (n = 79) and the control group (n = 247) according to whether the patients were treated with dapagliflozin after ablation. The definition of AF recurrence was documented atrial arrhythmias over 30 s after a 1-month blanking period. Cox regression models were used to analyze the risk of AF recurrence. RESULTS: Overall, 326 patients were analyzed (mean age, 63.7±10.0 years old; male, 58.9%; paroxysmal AF, 52.8%; recurrence rate, 40.8%). We found that hemoglobin A1c before ablation was higher in the dapagliflozin group than in the control group (7.7±1.4 vs. 7.3±1.2, P = 0.007). After a mean follow-up of 15.5±8.9 months, the dapagliflozin group had a lower recurrence rate than the control group (27.8% vs. 44.9%, P = 0.007). Treatment with dapagliflozin (HR 0.614, ±95%CI 0.387-0.974, P = 0.038) was associated with a lower risk of recurrence of atrial arrhythmias (ATa) after ablation in multivariable Cox regression models that adjusted for duration of AF, BMI, AF type, left atrial diameter (LAD), and eGFR. The Cox regression model that incorporated hemoglobin A1c and other antidiabetic agents also demonstrated a similar reduction in the risk of recurrent atrial arrhythmias with dapagliflozin treatment (HR 0.611, ±95% CI 0.379-0.985, P = 0.043). CONCLUSIONS: In patients with T2DM, treatment with dapagliflozin appears to be independently associated with a significant reduction in the risk of recurrent atrial arrhythmias after RFCA.

Result and technique consideration of radiofrequency catheter ablation of tachycardia in patients with dextrocardia.

BACKGROUND: Patients with tachycardia, in the context of pre-existing dextrocardia, could benefit from catheter ablation. However, anatomical complexities hinder effective conduct of this procedure. We aimed to retrospectively summarize the clinical characteristics and the safety and efficiency, and recommended the technique considerations. METHODS: Twenty-one cases from 19 patients with tachycardia and dextrocardia, who underwent catheter ablation between 2009 and 2021, were enrolled. All patients underwent echocardiography and computed tomography (CT) to confirm the anatomical malformations. Transseptal puncture was guided by fluoroscopy or intracardiac echocardiography when left atrial access was necessary and the ablation process was guided by three-dimensional (3D) mapping. RESULTS: Six cases exhibited situs solitus while nine cases exhibited situs inversus. Fourteen cases had atrial fibrillation, seven had atrial flutter, and two had atrioventricular reentrant tachycardia (AVRT); two cases had combined atrial fibrillation and atrial flutter. Acute success was achieved in 18 cases (85.7%, 18/21). The 3D mapping system was not employed in the three cases which failed. During long-term follow-up (20.71 ± 21.86 months), eight cases (72.7%, 8/11) of atrial fibrillation with dextrocardia successfully attained sinus rhythm. None of AVRT cases had recurrence. Half of the atrial flutter cases with dextrocardia, especially those with a history of surgical correction for cardiac malformations, underwent recurrence. One case had cardiac tamponade. CONCLUSIONS: Catheter ablation for tachycardia patients with dextrocardia is safe, efficient, and feasible. It is imperative to integrate echocardiography, cardiac computer tomography, and 3D mapping, and apply 3D reconstruction to facilitate the success of catheter ablation.

Recombinant Human Bone Morphogenic Protein-2 Immobilized Fabrication of Magnesium Functionalized Injectable Hydrogels for Controlled-Delivery and Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Necrosis Repair.

Femoral head necrosis (FHN) is a clinically progressive disease that leads to overwhelming complications without an effective therapeutic approach. In recent decades, transplantation of mesenchymal stem cells (MSCs) has played a promising role in the treatment of FHN in the initial stage; however, the success rate is still low because of unsuitable cell carriers and abridged osteogenic differentiation of the transplanted MSCs. Biopolymeric-derived hydrogels have been extensively applied as effective cell carriers and drug vesicles; they provide the most promising contributions in the fields of tissue engineering and regenerative medicine. However, the clinical potential of hydrogels may be limited because of inappropriate gelation, swelling, mechanical characteristics, toxicity in the cross-linking process, and self-healing ability. Naturally, gelated commercial hydrogels are not suitable for cell injection and infiltration because of their static network structure. In this study, we designed a novel thermogelling injectable hydrogel using natural silk fibroin-blended chitosan (CS) incorporated with magnesium (Mg) substitutes to improve physical cross-linking, stability, and cell osteogenic compatibility. The presented observations demonstrate that the developed injectable hydrogels can facilitate the controlled delivery of immobilized recombinant human bone morphogenic protein-2 (rhBMP-2) and rat bone marrow-derived MSCs (rBMSCs) with greater cell encapsulation efficiency, compatibility, and osteogenic differentiation. In addition, outcomes of in vivo animal studies established promising osteoinductive, bone mineral density, and bone formation rate after implantation of the injectable hydrogel scaffolds. Therefore, the developed hydrogels have great potential for clinical applications of FHN therapy.

CircFAM120B knockdown inhibits osteosarcoma tumorigenesis via the miR-1205/PTBP1 axis.

BACKGROUND: Osteosarcoma (OS) is a highly prevalent bone malignancy with poor clinical outcomes. Expression of the circular RNA, hsa_circ_0078767 (circFAM120B) is elevated in OS, however, its mechanisms in OS are unclear. METHODS: CircFAM120B levels were detected in OS tissue and cell lines. Silenced circFAM120B experiments were performed to assess its effects on OS in vitro cancer phenotypes and in vivo tumor growth. Then, bioinformatics analyses were used to predict circFAM120B target microRNAs (miRNAs) and associated genes. RESULTS: CircFAM120B and the transcription factor, PTBP1 were elevated in OS tissue and cell lines, while miR-1205 was poorly expressed. Silenced circFAM120B significantly suppressed in vitro OS cell proliferation and invasion, and inhibited in vivo tumor growth. CircFAM120B also appeared to function as an miR-1205 sponge, as miR-1205 bound to PTBP1. Interestingly, overexpressed PTBP1 (or miR-1205 inhibition) reversed the inhibitory effects mediated by circFAM120B downregulation in OS cells. CONCLUSION: We hypothesize circFAM120B functions as a miR-1205 sponge to elevate PTBP1 levels, enhancing OS progression and associated malignant phenotypes. Thus, circFAM120B may function as a crucial mediator during OS progression.

BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mice.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)-induced arthritis (CIA) is the most used animal model for human RA. Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. In this study, we investigate the ability of a recombinant BTN2A2-IgG2a Fc (BTN2A2-Ig) fusion protein to treat CIA. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment. This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. BTN2A2-Ig also inhibits CII-specific T cell proliferation and Th1/Th17 cytokine production. Although the percentage of effector T cells is decreased in BTN2A2-Ig-treated CIA mice, the proportions of naive T cells and regulatory T cells is increased. Furthermore, BTN2A2-Ig reduces the percentage of proinflammatory M1 macrophages but increases the percentage of anti-inflammatory M2 macrophages in the CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models.

Gypenoside XVII protects against spinal cord injury in mice by regulating the microRNA­21­mediated PTEN/AKT/mTOR pathway.

Gypenoside XVII (GP­17), one of the dominant active components of Gynostemma pentaphyllum, has been studied extensively and found to have a variety of pharmacological effects, including neuroprotective properties. However, the neuroprotective effects of GP­17 against spinal cord injury (SCI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP­17 on motor recovery and histopathological changes following SCI and to elucidate the mechanisms underlying its neuroprotective effects in a mouse model of SCI. Motor recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was detected by the wet/dry weight method. H&E staining was performed to examine the effect of GP­17 on spinal cord damage. Inflammatory response production was assessed by ELISA. Candidate miRNAs were identified following the integrated analysis of the Gene Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the expression levels of associated proteins. The results revealed that GP­17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR­21 expression was downregulated following SCI, whereas it was upregulated following the administration of GP­17. The inhibition of miR­21 eliminated the protective effects of GP­17 on SCI­induced neuronal apoptosis and the inflammatory response. In addition, phosphatase and tensin homologue (PTEN), a key molecule in the activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, was identified as a target of miR­21, and PTEN expression was downregulated by GP­17 through miR­21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by SCI, whereas it was re­activated by GP­17 through the regulation of miR­21 in mice with SCI. On the whole, the findings of the present study suggest that GP­17 plays a protective role in SCI via regulating the miR­21/PTEN/AKT/mTOR pathway.

Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis.

BACKGROUND: Soft tissue sarcomas (STS) has a high rate of early metastasis. In this study, we aimed to uncover the potential metastasis mechanisms and related signaling pathways in STS with differentially expressed genes and tumor-infiltrating cells. METHODS: RNA-sequencing (RNA-seq) of 261 STS samples downloaded from the Cancer Genome Atlas (TCGA) database were used to identify metastasis-related differentially expressed immune genes and transcription factors (TFs), whose relationship was constructed by Pearson correlation analysis. Metastasis-related prediction model was established based on the most significant immune genes. CIBERSORT algorithm was performed to identify significant immune cells co-expressed with key immune genes. The GSVA and GSEA were performed to identify prognosis-related KEGG pathways. Ultimately, we used the Pearson correlation analysis to explore the relationship among immune genes, immune cells, and KEGG pathways. Additionally, key genes and regulatory mechanisms were validated by single-cell RNA sequencing and ChIP sequencing data. RESULTS: A total of 204 immune genes and 12 TFs, were identified. The prediction model achieved a satisfactory effectiveness in distant metastasis with the Area Under Curve (AUC) of 0.808. LTB was significantly correlated with PAX5 (P < 0.001, R = 0.829) and hematopoietic cell lineage pathway (P < 0.001, R = 0.375). The transcriptional regulatory pattern between PAX5 and LTB was validated by ChIP sequencing data. CONCLUSIONS: We hypothesized that down-regulated LTB (immune gene) modulated by PAX5 (TF) in STSs may have the capability of inducing cancer cell metastasis in patients with STS.

PTEN Controls the DNA Replication Process through MCM2 in Response to Replicative Stress.

PTEN is a tumor suppressor frequently mutated in human cancers. PTEN inhibits the phosphatidylinositol 3-kinase (PI3K)-AKT cascade, and nuclear PTEN guards the genome by multiple mechanisms. Here, we report that PTEN physically associates with the minichromosome maintenance complex component 2 (MCM2), which is essential for DNA replication. Specifically, PTEN dephosphorylates MCM2 at serine 41 (S41) and restricts replication fork progression under replicative stress. PTEN disruption results in unrestrained fork progression upon replication stalling, which is similar to the phenotype of cells expressing the phosphomimic MCM2 mutant S41D. Moreover, PTEN is necessary for prevention of chromosomal aberrations under replication stress. This study demonstrates that PTEN regulates DNA replication through MCM2 and loss of PTEN function leads to replication defects and genomic instability. We propose that PTEN plays a critical role in maintaining genetic stability through a replication-specific mechanism, and this is a crucial facet of PTEN tumor suppressor activity.