3D-MRI super-resolution reconstruction using multi-modality based on multi-resolution CNN.

BACKGROUND AND OBJECTIVE: High-resolution (HR) MR images provide rich structural detail to assist physicians in clinical diagnosis and treatment plan. However, it is arduous to acquire HR MRI due to equipment limitations, scanning time or patient comfort. Instead, HR MRI could be obtained through a number of computer assisted post-processing methods that have proven to be effective and reliable. This paper aims to develop a convolutional neural network (CNN) based super-resolution reconstruction framework for low-resolution (LR) T2w images. METHOD: In this paper, we propose a novel multi-modal HR MRI generation framework based on deep learning techniques. Specifically, we construct a CNN based on multi-resolution analysis to learn an end-to-end mapping between LR T2w and HR T2w, where HR T1w is fed into the network to offer detailed a priori information to help generate HR T2w. Furthermore, a low-frequency filtering module is introduced to filter out the interference from HR-T1w during high-frequency information extraction. Based on the idea of multi-resolution analysis, detailed features extracted from HR T1w and LR T2w are fused at two scales in the network and then HR T2w is reconstructed by upsampling and dense connectivity module. RESULTS: Extensive quantitative and qualitative evaluations demonstrate that the proposed method enhances the recovered HR T2w details and outperforms other state-of-the-art methods. In addition, the experimental results also suggest that our network has a lightweight structure and favorable generalization performance. CONCLUSION: The results show that the proposed method is capable of reconstructing HR T2w with higher accuracy. Meanwhile, the super-resolution reconstruction results on other dataset illustrate the excellent generalization ability of the method.

Induced domestication of humic reduction-denitrification coupled bacteria improved treatment of sediment: Performance, remediation effect, and metabolic mechanisms.

The high organic matter in river sediment primarily induces black and odorous rebound. Traditional humic-reducing bacteria demonstrate relatively single metabolic functions and restrain the remediation within complex sediment environments. In addition, Ca(NO3)2 is commonly utilized in synergistic with bioremediation to improve the reducing environment of sediments. In this study, a multifunctional bacterial community with humic reduction-denitrification coupled bacteria was domesticated by the step-feeding strategy in an anaerobic baffle reactor (ABR). The performance, remediation effect, and metabolic mechanisms were analyzed. The results indicated that humic-reducing bacteria (HRB) and denitrifying-humic-reducing bacteria (DF/HRB) have quinone-reduction and denitrification capabilities. The synergistic effect of DF/HRBs and Ca(NO3)2 was superior to HRBs and Ca(NO3)2 on the removal of total organic matter(TOM). Microbial community structure analysis revealed an enhanced relative abundance of denitrification and humic-reducing bacteria (e.g., Thauera, Pseudomonas, Sulfurospirillum, Desulfovibrio, Geobacter) in the DF/HRB, resulting in a superior synergistic effect of DF/HRBs with Ca(NO3)2. This work helps to present an innovative approach to domesticate humic-reducing bacteria suited for the remediation environment effectively. It also expands the application of humic-reducing bacteria for in-situ anaerobic remediation of river sediments.

Deciphering the role of SMARCA4 in cardiac disorders: Insights from single-cell studies on dilated cardiomyopathy and coronary heart disease.

BACKGROUND: Dilated cardiomyopathy (DCM) and coronary heart disease (CHD) stand as two of the foremost causes of mortality. However, the comprehensive comprehension of the regulatory mechanisms governing DCM and CHD remains limited, particularly from the vantage point of single-cell transcriptional analysis. METHOD: We used the GSE121893 dataset from the GEO database, analyzing single-cell expressions with tools like DropletUtils, Seurat, and Monocle. We also utilized the GSVA package for comparing gene roles in DCM and CHD, Finally, we conducted qRT-PCR and Western blot analyses to measure the expression levels of SMARCA4, Col1A1, Col3A1 and α-SMA, and the role of SMARCA4 on fibroblasts were explored by EdU and Transwell assay. RESULTS: Our analysis identified six cell types in heart tissue, with fibroblasts showing the most interaction with other cells. DEGs in fibroblasts were linked to muscle development and morphogenesis. Pseudotime analysis revealed the dynamics of fibroblast changes in both the normal and disease groups and many transcription factors (TFs) potentially involved in this process. Among these TFs, SMARCA4 which was translated into protein BRG1, showed the most significantly difference. In vivo experiments have demonstrated that SMARCA4 indeed promoted fibroblasts proliferation and migration. CONCLUSION: This study provides a clearer understanding of cell-type dynamics in heart diseases, emphasizing the role of fibroblasts and the significance of SMARCA4 in their function. Our results offer insights into the cellular mechanisms underlying DCM and CHD, potentially guiding future therapeutic strategies.

Targeting ERBB2 and PIK3R1 as a therapeutic strategy for dilated cardiomyopathy: A single-cell sequencing and mendelian randomization analysis.

Background: Dilated cardiomyopathy (DCM) is widely recognized as a significant contributor to heart failure. Nevertheless, the absence of pharmaceutical interventions capable of reversing disease progression and improving prognosis underscores the imperative for additional research in this area. Methods: First, we identified and evaluated three gene sets, namely "SC-DCM", "EP-DCM" and "Drug", using big data and multiple bioinformatics analysis methods. Accordingly, drug-treatable ("Hub") genes in DCM were identified. Following this, four microarray expression profile datasets were employed to authenticate the expression levels and discriminatory efficacy of "Hub" genes. Additionally, mendelian randomization analysis was conducted to ascertain the causal association between the "Hub genes" and heart failure. Finally, the "DGIdb" was applied to identify "Hub" genes-targeted drugs. The "ssGSEA" algorithm assessed the level of immune cell infiltration in DCM. Results: Enrichment analysis showed that the "SC-DCM" and "EP-DCM" gene sets were closely associated with DCM. PIK3R1 and ERBB2 were identified as drug-treatable genes in DCM. Additional analysis using MR supported a causal relationship between ERBB2 and heart failure, but not PIK3R1. Moreover, PIK3R1 was positively correlated with immune activation, while ERBB2 was negatively correlated. We found that everolimus was a pharmacological inhibitor for both PIK3R1 and ERBB2. However, no pharmacological agonist was found for ERBB2. Conclusion: PIK3R1 and ERBB2 are drug-treatable genes in DCM. ERBB2 has a causal effect on heart failure, and its normal expression may play a role in preventing the progression of DCM to heart failure. In addition, there is a cross-expression of PIK3R1 and ERBB2 genes in both DCM and tumors. The adaptive immune system and PIK3R1 may be involved in DCM disease progression, while ERBB2 exerts a protective effect against DCM.

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Time Convolutional Network-Based Maneuvering Target Tracking with Azimuth-Doppler Measurement.

In the field of maneuvering target tracking, the combined observations of azimuth and Doppler may cause weak observation or non-observation in the application of traditional target-tracking algorithms. Additionally, traditional target tracking algorithms require pre-defined multiple mathematical models to accurately capture the complex motion states of targets, while model mismatch and unavoidable measurement noise lead to significant errors in target state prediction. To address those above challenges, in recent years, the target tracking algorithms based on neural networks, such as recurrent neural networks (RNNs), long short-term memory (LSTM) networks, and transformer architectures, have been widely used for their unique advantages to achieve accurate predictions. To better model the nonlinear relationship between the observation time series and the target state time series, as well as the contextual relationship among time series points, we present a deep learning algorithm called recursive downsample-convolve-interact neural network (RDCINN) based on convolutional neural network (CNN) that downsamples time series into subsequences and extracts multi-resolution features to enable the modeling of complex relationships between time series, which overcomes the shortcomings of traditional target tracking algorithms in using observation information inefficiently due to weak observation or non-observation. The experimental results show that our algorithm outperforms other existing algorithms in the scenario of strong maneuvering target tracking with the combined observations of azimuth and Doppler.

[Decreased DNase1L3 secretion and associated antibodies induce impaired degradation of NETs in patients with sporadic SLE].

Objective To evaluate the correlation between alterations in DNase1 and DNase1L3 enzyme activities and impairment of NET degradation in patients with sporadic SLE, and to investigate the underlying mechanism. Methods 46 sporadic SLE patients and 30 age- and sex-matched healthy individuals were recruited. Serum levels of DNase1, DNase1L3 and corresponding autoantibodies were detected by ELISA. DNase1 and DNase1L3 were isolated by immunoprecipitation; NETs and enzyme degradation activities were detected using a modified immunofluorescence. DNase1L3 secretion by PBMCs was analyzed by ELISPOT, Western blotting and reverse transcription PCR. Results Levels of H3-dsDNA and Ela-dsDNA complexes were significantly elevated in SLE patients. LDGs in SLE population was significantly higher than in the control group, and LDGs was positively correlated with H3-dsDNA and Ela-dsDNA NETs complexes. The ability of SLE patients to degrade NET in vitro was significantly lower than that of the control group. Degradation experiments of DNase1 and DNase1L3 in different proportions showed that the decrease in DNase1L3 activity was the primary contributor to the elevated NET residue level. The concentration of DNase1L3 autoantibodies in SLE patients was significantly elevated compared to the control group. In addition, the capacity of PBMCs to secrete DNase1L3 was significantly lower in the SLE patients compared to the control group. Conclusion Decreased secretion of DNase1L3 and the presence of relevant autoantibodies notably impede NET degradation in patients with SLE, offering new directions for the monitoring and treatment of SLE patients.

Effect of cinnamon spice on continuously monitored glycemic response in adults with prediabetes: a 4-week randomized controlled crossover trial.

BACKGROUND: Previous clinical studies showing that cinnamon spice lowers blood glucose concentrations had inconsistent results. OBJECTIVES: To determine the effect of daily cinnamon spice supplementation in an amount commonly used for seasoning on glucose concentrations in adults with obesity and prediabetes. METHODS: Following a 2-wk run-in period of maintaining a low polyphenol/fiber diet, 18 participants with obesity and prediabetes underwent a 10-wk randomized, controlled, double-blind, crossover trial (mean age 51.1 y; mean fasting plasma glucose 102.9 mg/dL). The participants were randomly assigned to take cinnamon (4 g/d) or placebo for 4-wk, followed by a 2-wk washout period, and then crossed over to the other intervention for an additional 4-wk. Glucose changes were measured with continuous glucose monitoring. Oral glucose tolerance testing immediately following ingestion of cinnamon or placebo was performed at 4-time points to assess their acute effects both at the baseline and end of each intervention phase. Digestive symptom logs were obtained daily. RESULTS: There were 694 follow-up days with 66,624 glucose observations. When compared with placebo, 24-h glucose concentrations were significantly lower when cinnamon was administered [mixed-models; effect size (ES) = 0.96; 95 % confidence interval (CI): -2.9, -1.5; P < 0.001]. Similarly, the mean net-area-under-the-curve (netAUC) for glucose was significantly lower than for placebo when cinnamon was given (over 24 h; ES = -0.66; 95 % CI: 2501.7, 5412.1, P = 0.01). Cinnamon supplementation resulted in lower glucose peaks compared with placebo (Δpeak 9.56 ± 9.1 mg/dL compared with 11.73 ± 8.0 mg/dL; ES = -0.57; 95 % CI: 0.8, 3.7, P = 0.027). Glucose-dependent-insulinotropic-polypeptide concentrations increased during oral glucose tolerance testing + cinnamon testing (mixed-models; ES = 0.51; 95 % CI: 1.56, 100.1, P = 0.04), whereas triglyceride concentrations decreased (mixed-models; ES = 0.55; 95 % CI: -16.0, -1.6, P = 0.02). Treatment adherence was excellent in both groups (cinnamon: 97.6 ± 3.4 % compared with placebo: 97.9 ± 3.7 %; ES = -0.15; 95 % CI: -1.8, 0.2, P = 0.5). No differences were found in digestive symptoms (abdominal pain, borborygmi, bloating, excess flatus, and stools/day) between cinnamon and placebo groups. CONCLUSIONS: Cinnamon, a widely available and low-cost supplement, may contribute to better glucose control when added to the diet in people who have obesity-related prediabetes. This trial was registered at clinicaltrials.gov as NCT04342624.

Triglyceride-Glucose Index and Its Correlates: Associations with Serum Creatinine and Estimated Glomerular Filtration Rate in a Cross-Sectional Study from CHARLS 2011-2015.

Background: Chronic kidney disease (CKD) has emerged as a significant global public health challenge, and the estimated glomerular filtration rate (eGFR) is widely used due to its convenience, low cost, and broad clinical applicability. Concurrently, insulin resistance (IR) serves as a crucial marker of metabolic disturbance, and alternative indicators have garnered increasing attention in CKD research in recent years. Objective: This study aims to investigate the relationship between IR-related indices (TyG index, TyG-BMI index, and TyG-WC index) and serum creatinine levels, as well as the eGFR, with the intention of uncovering their potential roles in the assessment of renal function. Methods: We analyzed nationally representative cross-sectional data from a cohort of individuals aged 45 and above in China, comprising 11,608 participants. Participants were categorized into different groups based on quartiles of the TyG index, and multiple factors, including gender, age, lifestyle, and co-morbidities, were adjusted for using linear regression models. Results: By linear regression, TyG, TyG-BMI, and TyG-WC indices were significantly positively correlated with serum creatinine and significantly negatively correlated with eGFR. Results showed similar trends when TyG, TyG-BMI, and TyG-WC indices were used as categorical variables. In the fully adjusted model, the highest quartile of serum creatinine was higher than the first quartile for TyG, TyG-BMI, and TyG-WC indices, with ß values of 2.673, 3.67, and 1.937 mg/dL, respectively; the highest quartile of eGFR was lower than the first quartile, with ß values of -2.4, -2.955, and -1.823 mL/min/1.73 m2. P values were statistically significant. Conclusions: This study indicates a consistent correlation between the TyG index and its related indices with serum creatinine levels and eGFR among the middle aged and elderly population in China. These findings suggest the potential utility of these indices in early screening and management of the risk of chronic kidney disease.

Serum Secreted Protein Acidic and Rich in Cysteine-Like 1 as a Biochemical Predictor for Prognosticating Clinical Outcomes After Acute Supratentorial Intracerebral Hemorrhage: A Prospective Cohort Study.

Background: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability and is up-regulated during axonal regeneration. Here, serum SPARCL1 was determined for estimating severity and prognosticating early neurological deterioration (END) and functional outcomes of acute intracerebral hemorrhage (ICH). Methods: In this prospective observational cohort study of 156 patients with supratentorial ICH, blood samples of 53 were acquired not only at admission but also ad days 1, 3, 5, 7 and 10. Another group of 53 healthy controls were recruited. The modified Rankin Scale (mRS) scores of 3-6 at poststroke six months were regarded as poor prognosis. Results: As opposed to controls, serum SPARCL1 levels were markedly elevated during the early ten days after ICH, with the highest levels at days 1 and 3. Admission serum SPARCL1 levels were independently correlated with National Institutes of Health Stroke Scale scores and hematoma volume, were significantly increased in the order of six-month mRS scores from 0 to 6 and were independently correlated with six-month mRS scores. Serum SPARCL1 levels were linearly related to risks of poor six-month prognosis and END under restricted cubic spline, had significant efficiency under receiver operating characteristic (ROC) curve and were independently associated with END and poor prognosis. Subgroup analysis confirmed that no interactions existed for associations of serum SPARCL1 levels with other variables, such as age, gender and some specific vascular risk factors. END and poor prognosis prediction models integrating serum SPARCL1 were displayed using the two nomograms. The poor prognosis prediction model, but END prediction model not, performed well under calibration curve, decision curve and ROC curve. Conclusion: A substantial elevation of serum SPARCL1 levels during the early period after ICH is independently related to illness severity and poor neurological outcomes, thus signifying that serum SPARCL1 may appear as a prognostic biomarker of ICH.

Concentrated Grape Powder Consumption Modulates Cholesterol Metabolism and Homeostasis in Healthy Subjects.

SCOPE: Four weeks' of concentrated grape powder (GP) consumption reduces circulating cholesterol in healthy free-living subjects consuming a low-fiber/low-polyphenol diet. Here, the study aims to investigate the underlying mechanisms for cholesterol reduction by evaluating biomarkers of cholesterol de novo biosynthesis, intestinal absorption, miRNA involved in transcriptional regulation of cholesterol metabolism, as well as cholesterol oxidation. METHODS AND RESULTS: Fasting plasma samples collected from 19 healthy free-living subjects at baseline and week 4 of GP consumption are used in this study. Gas chromatography-mass (GC-MS) analysis of plasma samples shows that lathosterol, a precursor of cholesterol synthesis, is significantly decreased after GP consumption indicating reduced cholesterol de novo biosynthesis. Markers of intestinal absorption, campesterol, and ß-sitosterol are not changed. Realtime PCR shows that plasma exosomal miRNA-1 is increased after GP consumption. GC-MS also shows that GP consumption reduces the plasma cholesterol oxidation product 27-hydroxycholesterol (27-HC). CONCLUSIONS: This study enhances the understanding of the mechanisms of the cholesterol lowering effects of GP, and provides new insights into the potential health benefits of grape consumption.

Passive smoking and risk of gestational diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: Pregestational smoking increases the risk of gestational diabetes mellitus (GDM) and is a common health problem during pregnancy, with its incidence on the rise worldwide, especially in China. This study is a meta-analysis of passive smoking as a risk factor associated with GDM. METHODS: Two independent reviewers searched passive smoking and the risk of GDM in PubMed, Medline, Web of Knowledge, Science Direct, China National Knowledge Internet (CNKI) and Wanfang databases (up to May 2023). The authors extracted the study data independently and used the Newcastle-Ottawa scale (NOS) to evaluate the quality of the included articles. A meta-analysis was conducted using a random effects model depending on the size of the heterogeneity. Begg's and Egger's tests were performed to assess publication bias. RESULTS: The overall relative risk for GDM caused by passive smoking was 1.47 (95% CI: 1.31-1.64), with moderate heterogeneity between studies (I2=41.7%, p=0.079). Subgroup and sensitivity analyses were stable, and no evidence of publication bias was found. CONCLUSIONS: Passive smoking is a risk factor for GDM, even in those who are not active smokers. To eliminate the effects of other confounding factors, larger prospective cohort studies are required to clarify the relationship between passive smoking and the occurrence of GDM.

Hydroxyfasudil regulates immune balance and suppresses inflammatory responses in the treatment of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a central nervous system (CNS) disease with complicated etiology. Multifocal demyelination and invasion of inflammatory cells are its primary pathological features. Fasudil has been confirmed to improve experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, Fasudil is accompanied by several shortcomings in the clinical practice. Hydroxyfasudil is a metabolite of Fasudil in the body with better pharmaceutical properties. Therefore, we attempted to study the influence of Hydroxyfasudil upon EAE mice. The results demonstrated that Hydroxyfasudil relieved the symptoms of EAE and the associated pathological damage, reduced the adhesion molecules and chemokines, decreased the invasion of peripheral immune cells. Simultaneously, Hydroxyfasudil modified the rebalance of peripheral T cells. Moreover, Hydroxyfasudil shifted the M1 phenotype to M2 polarization, inhibited inflammatory signaling cascades as well as inflammatory factors, and promoted anti-inflammatory factors in the CNS. In the end, mice in the Hydroxyfasudil group expressed more tight junction proteins, indirectly indicating that the blood-brain barrier (BBB) was protected. Our results indicate that Hydroxyfasudil may be a prospective treatment for MS.

Design and synthesis of a BOAHY-derived tracker for fluorescent labeling of mitochondria.

Fluorescence microscopy has proven to be a crucial powerful tool to specifically visualize cellular organelles. In-depth visualization of the structure of mitochondria in living cells is of great value to better understand their function. Herein, based on our experience in construction of fluorescent difluoroboronate anchored acylhydrazones (BOAHY) chromophores, we rationally designed a novel monoboron complex with a connected triphenylphosphonium moiety, and evaluated its spectroscopic properties, cytotoxicity and intracellular localization. Owing to the positive charge on our fluorescent dye, the molecule had an excellent mitochondria-targeting ability (Pearson's correlation is 0.86).To the best of our knowledge, this is the first example of a BOAHY dye which has been applied as an efficient tracker to target mitochondria in living cells.

Endothelial progenitor cell-derived exosomes promote anti-inflammatory macrophages via SOCS3/JAK2/STAT3 axis and improve the outcome of spinal cord injury.

BACKGROUND: Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism. METHODS: We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement. RESULTS: We found that EPC-EXOs decreased the macrophages' pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P's effects on macrophage polarization and mouse motor behavior. CONCLUSION: Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs' role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.

Systemic evaluation of lymphocyte-bound C4d and immunoglobulins for diagnosis and activity monitoring of systemic lupus erythematosus.

OBJECTIVE: To investigate the role of lymphocyte-bound C4d (LB-C4d: T-C4d, B-C4d) and immunoglobulins (LB-Igs: T-IgG, T-IgM, B-κ and B-λ) in the diagnosis and monitoring of SLE. DESIGN & METHODS: The levels of C4d and Igs on peripheral lymphocytes were measured in 172 patients with SLE, 174 patients with other non-SLE inflammatory diseases and 100 healthy individuals. Immunobinding and blocking experiments were performed to characterize Igs from SLE patients to generate LB-C4d/Igs in vitro. Sixty-five patients with SLE were followed up longitudinally. Disease activity was assessed for each SLE patient. RESULTS: Patients with SLE had the highest median LB-C4d/Igs levels. LB-C4d had a significant but weak positive association with LB-Igs, with correlation coefficients ranging from 0.008 to 0.316. Anti-cardiolipin IgG and anti-ß2GP1 IgG, but not C3 and C4, were found to be closely associated with LB-C4d/Igs formation, with correlations as high as 0.337. Compared to anti-dsDNA, LB-C4d performed better in SLE diagnosis, while B-κ and B-λ performed better in disease activity monitoring. CONCLUSIONS: Both autoantibodies and receptors on lymphocytes contribute to LB-C4d/Igs formation. LB-C4d/Igs could be used as reliable indicators for SLE diagnosis and activity monitoring.

A distribution information sharing federated learning approach for medical image data.

In recent years, federated learning has been believed to play a considerable role in cross-silo scenarios (e.g., medical institutions) due to its privacy-preserving properties. However, the non-IID problem in federated learning between medical institutions is common, which degrades the performance of traditional federated learning algorithms. To overcome the performance degradation problem, a novelty distribution information sharing federated learning approach (FedDIS) to medical image classification is proposed that reduce non-IIDness across clients by generating data locally at each client with shared medical image data distribution from others while protecting patient privacy. First, a variational autoencoder (VAE) is federally trained, of which the encoder is uesd to map the local original medical images into a hidden space, and the distribution information of the mapped data in the hidden space is estimated and then shared among the clients. Second, the clients augment a new set of image data based on the received distribution information with the decoder of VAE. Finally, the clients use the local dataset along with the augmented dataset to train the final classification model in a federated learning manner. Experiments on the diagnosis task of Alzheimer's disease MRI dataset and the MNIST data classification task show that the proposed method can significantly improve the performance of federated learning under non-IID cases.

Curcumin alleviated oxidation stress injury by mediating osteopontin in nephrolithiasis rats.

PURPOSE: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). METHODS: Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups. RESULTS: The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment. CONCLUSIONS: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.