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Qingjuan Zuo,1,2 Guorui Zhang,1,3 Lili He,2 Sai Ma,4 Huijuan Ma,5 Jianlong Zhai,6 Zhongli Wang,7 Tingting Zhang,2 Yan Wang,2 Yifang Guo1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Cardiology, the Third Hospital of Shijiazhuang City Affiliated to Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Internal Medicine, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 5Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 6Department of Cardiology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 7Department of Physical Examination Center, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yifang Guo, Department of Geriatric Cardiology, Hebei General Hospital, No. 348, Heping West Road, Xinhua District, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +86-15100189182, Email guoyifang@hotmail.comPurpose: To investigate the effect of canagliflozin (20 mg/kg) on hepatic steatosis and atherosclerosis, and further to explore its possible mechanism.Methods: Blood glucose, blood lipid, oxidative stress response and inflammatory cytokines were examined by intraperitoneal glucose tolerance test and ELISA assay. HE and Oil Red O staining were used to estimate the extent of hepatic steatosis and atherosclerosis. RNA-seq and qRT-PCR were used to further investigate the potential mechanism. The effects of canagliflozin on autophagy were detected using transmission electron microscopy and Western blotting. The endothelial function-related markers were determined by qRT-PCR.Results: Canagliflozin notably alleviated the elevation in blood glucose and insulin resistance in western diet-fed ApoE-/- mice. In ApoE-/-+Cana group, ApoE-/- mice had lower levels of TG, TC, LDL-C, TNF-α, IL-6, IL-1β, and MCP-1. HE and Oil Red O staining presented that canagliflozin restrained the atherosclerotic plaque development and lipid accumulation. RNA-seq showed that 87 DEGs were relevant to improvement of hepatic steatosis and atherosclerosis by canagliflozin. Among them, CPS1, ASS1, ASL, ARG1, MATLA, GLS2, GOT1, SREBP1, Plin5, Retreg1, and C/EBPβ were verified. KEGG enrichment analysis indicated that DEGs were mainly involved in amino acid metabolism. Besides, we observed that canagliflozin reduced the contents of aspartic acid and citrulline in liver. Western blotting showed that ASS1 and p-AMPK/AMPK was remarkably elevated after administration of canagliflozin. Correspondingly, canagliflozin down-regulated SREBP1, FAS, ACC1, HMGCR, p-mTOR/m-TOR, p-ULK1/ULK1 and p62, but up-regulated CPT1, Beclin 1 and LC3 II/LC3I. TEM showed that canagliflozin reduced the number of lipid droplets and increased the autophagosomes. Moreover, we found that canagliflozin elevated the aortic endothelial function-associated markers including ASS1, ASL and eNOS.Conclusion: Canagliflozin may attenuate hepatic steatosis by improving lipid metabolism, enhancing autophagy, and reducing inflammatory response through ASS1/AMPK pathway. Besides, canagliflozin further effectively improves the aortic endothelial function, thereby suppressing atherosclerosis development.Keywords: canagliflozin, hepatic steatosis, atherosclerosis, RNA-seq, dyslipidemia, inflammatory response, autophagy

Head and neck squamous cell carcinoma (HNSCC) is a lethal malignancy. Given the essential roles of E3 ligases in cancer immunotherapies, this paper explored the effect of E3 ubiquitin ligase ring finger protein 125 (RNF125) on immune escape in HNSCC. After delivering overexpressed (oe)-RNF125, interferon-gamma, or oe-programmed death-ligand 1 (PD-L1) into HNSCC cells and cell culture with carboxyfluorescein succinimidyl ester-labeled CD8

BACKGROUND: Deep learning has been employed using brain functional connectome data for evaluating the risk of cognitive deficits in very preterm infants. Although promising, training these deep learning models typically requires a large amount of labeled data, and labeled medical data are often very difficult and expensive to obtain. OBJECTIVE: This study aimed to develop a self-training deep neural network (DNN) model for early prediction of cognitive deficits at 2 years of corrected age in very preterm infants (gestational age ≤32 weeks) using both labeled and unlabeled brain functional connectome data. MATERIALS AND METHODS: We collected brain functional connectome data from 343 very preterm infants at a mean (standard deviation) postmenstrual age of 42.7 (2.5) weeks, among whom 103 children had a cognitive assessment at 2 years (i.e. labeled data), and the remaining 240 children had not received 2-year assessments at the time this study was conducted (i.e. unlabeled data). To develop a self-training DNN model, we built an initial student model using labeled brain functional connectome data. Then, we applied the trained model as a teacher model to generate pseudo-labels for unlabeled brain functional connectome data. Next, we combined labeled and pseudo-labeled data to train a new student model. We iterated this procedure to obtain the best student model for the early prediction task in very preterm infants. RESULTS: In our cross-validation experiments, the proposed self-training DNN model achieved an accuracy of 71.0%, a specificity of 71.5%, a sensitivity of 70.4% and an area under the curve of 0.75, significantly outperforming transfer learning models through pre-training approaches. CONCLUSION: We report the first self-training prognostic study in very preterm infants, efficiently utilizing a small amount of labeled data with a larger share of unlabeled data to aid the model training. The proposed technique is expected to facilitate deep learning with insufficient training data.

Microplastic pollution has become a worldwide concern in aquatic and terrestrial environments. Microplastics could also enter the food chain, causing potential harm to human health. To facilitate the risk assessment of microplastics to humans, it is critically important to have a reliable analytical technique to detect, quantify, and identify microplastics of various materials, sizes, and shapes from environmental, agricultural, and food matrices. Spectroscopic techniques, mainly vibrational spectroscopy (Raman and infrared), are commonly used techniques for microplastic analysis. This review focuses on recent advances of these spectroscopic techniques for the analysis of microplastics in food. The fundamental, recent technical advances of the spectroscopic techniques and their advantages and limitations were summarized. The food sample pretreatment methods and recent applications for detecting and quantifying microplastics in different types of food were reviewed. In addition, the current technical challenges and future research directions were discussed. It is anticipated that the advances in instrument development and methodology innovation will enable spectroscopic techniques to solve critical analytical challenges in microplastic analysis in food, which will facilitate the reliable risk assessment.

Facile fabrication of low cost photocatalyst with enhanced activity and high atomic utilization has been in increasing demand for solar energy usage and/or conversion. In this work, a series of mesoporous carbon nitride nanosheets with enlarged specific surface area were synthesized via an inorganic acid-assisted exfoliation method without any soft or hard templates. Ultralow loading of downsized noble metal Pt was anchored on these porous nanosheets and warranted enhanced photocatalytic activity. The formation of mesoporous nanosheets in carbon nitride was expected to boost mass transfer and shorten charge carrier transfer route during photocatalytic reaction. Characterizations revealed that the enlarged conductivity and photocurrent of carbon nitride nanosheets also contributed to the enhanced H2 evolution. The maximum H2 production rates of 172.92 μmol/h and 321 μmol/h could be achieved over these nanosheets derived from melamine and urea under visible light irradiation, which are 10.92 and 2.22 folds as high as that of corresponding bulk carbon nitride, respectively. This exfoliation method was demonstrated to be an efficient and universal method for the preparation of carbon nitride nanosheets with mesoporous structure and high atomic utilization of co-catalyst for H2 evolution from water.

Hepatic fibrosis (HF) is a precursor of liver cirrhosis, and activated hepatic stellate cells are an important driver of fibrosis. F-box and WD repeat domain containing 7 (FBXW7) expression level is down-regulated in HF, but the underlying mechanism is yet to be elucidated. The interaction between FBXW7 and delta-like ligand 1 (DLL1) was predicted. LX-2 cells were subjected to transfection of FBXW7/DLL1 silencing or overexpression plasmid. The expressions of FBXW7 and DLL1 in HF in vitro were measured by quantitative reverse transcription polymerase chain reaction and western blot. The LX-2 cell cycle, viability, proliferation, and ubiquitination were determined by flow cytometry, cell counting kit-8, colony formation, and ubiquitination assays, respectively. FBXW7 overexpression suppressed the cell viability and proliferation, facilitated cell cycle arrest, and down-regulated α-smooth muscle actin (α-SMA), Collagen I, and DLL1 protein levels, but FBXW7 silencing did the opposite. DLL1 was bound to and ubiquitin-dependently degraded by FBXW7 overexpression. DLL1 overexpression promoted the cell viability and proliferation, accelerated cell cycle, and up-regulated the levels of α-SMA, Collagen I, NOTCH2, NOTCH3, and HES1, but these trends were reversed by FBXW7 overexpression. To sum up, FBXW7 overexpression suppresses the progression of HF in vitro by ubiquitin-dependently degrading DLL1.

Mesangial cell (MC)-mediated glomerulonephritis is a frequent cause of end-stage renal disease, with immune inflammatory damage and fibrosis as its basic pathological processes. However, the treatment of glomerulonephritis remains challenging owing to limited drug accumulation and serious side effects. Hence, the specific codelivery of "anti-inflammatory/antifibrosis" drugs to the glomerular MC region is expected to yield better therapeutic effects. In this study, liposome-nanoparticle hybrids (Au-LNHy) were formed by coating the surface of gold nanoparticles with a phospholipid bilayer; the Au-LNHys formed were comodified with PEG and α8 integrin antibodies to obtain gold nanoparticle immunoliposomes (Au-ILs). Next, the Au-ILs were loaded with dexamethasone and TGFβ1 siRNA to obtain DXMS/siRNA@Au-ILs. Our results showed that the functionalized nanoparticles had a core-shell structure, a uniform and suitable particle size, low cytotoxicity, and good MC entry, and lysosomal escape abilities. The nanoparticles were found to exhibit enhanced retention in glomerular MCs due to anti-α8 integrin antibody mediation.

Hypertension is one of the major contributors to cardiovascular and chronic kidney disease (CKD). Sodium-glucose cotransporter 2 (SGLT2) inhibitors and angiotensin receptor blockers (ARBs) have become the preferred treatment for patients with CKD. However, the renoprotective effects of the combined therapy of the two drugs on hypertensive renal fibrosis are still largely understood. The aim of this study was to compare the antifibrotic effects of canagliflozin, with or without irbesartan, in the kidneys of Dahl salt-sensitive (Dahl SS) rats on a high salt (HS) diet. After the preconditioning stage, Dahl SS rats (n = 47) were divided into 5 experimental groups as follows: low salt control (n=7), HS control (n=10), high salt with canagliflozin (n=10), high salt with irbesartan (n=10), and high salt with canagliflozin plus irbesartan (n=10). Mean food and water intake, body weight (BW), and systolic blood pressure (SBP) were measured during the whole experimental period. After 12 weeks, the rats were euthanized, and the kidneys were excised for histomorphometric evaluation and immunohistochemical evaluation. An HS diet increased SBP, renal fibrosis, expression of fibrotic protein factors, and TGF-β/Smad2/3 pathway compared to the LS group. We found that irbesartan reduced SBP and slowed the loss of renal function. Canagliflozin significantly reduced BW and renal fibrosis and downregulated the TGF-β/Smad2/3 pathway. The combined therapy showed better renoprotection in all outcome parameters. In conclusion, these results indicate that canagliflozin and irbesartan exert different benefits on nephroprotection in salt-sensitive hypertensive rats.

Today, neural network models are widely used to predict whether a person will develop diabetes in the future. However, for fuzzy inference engine and Adaptive Network-based Fuzzy Inference System (ANFIS), it costs a lot when the number of features is large, and the model will be more explainable if we use feature selection methods. In this paper, we modify the ANFIS model, combine ANFIS and neural network, and propose the ANFIS-NN model. We use SMOTE to address the imbalance between different classes, and use RFE and Casual Inference to do feature selection work. Then, we train an ANFIS model, and use a 5-layer neural network to replace the last layers to improve prediction accuracy. Data comparison experiments shows that our models get 0.9812 on accuracy, 0.9790 on G-mean, 0.9776 on F1 score on PIMA dataset using Casual Inference feature selection method, much better than traditional ANFIS; and our model works better on other diabetes datasets. The ANFIS-NN proposed in this paper can also be applied to other datasets to predict diabetes.

Prenatal tobacco smoke exposure (TSE) and preterm birth are associated with abnormal brain and neurodevelopmental outcomes in infants. Studies that can disentangle indirect mediating effects from direct effects of prenatal TSE on sensitive early brain MRI biomarkers in very preterm infants are needed.We sought to determine whether prenatal TSE in preterm infants posed any direct effects on MRI-determined global brain abnormality score and secondary measures of brain abnormalities after removing any indirect mediating effects of preterm birth on neurostructural outcomes.We examined brain MRI findings collected at 39-44 weeks postmenstrual age from a prospective cohort of 395 infants born very preterm (≤32 weeks of gestational age). The primary outcome was global brain abnormality score and secondary outcomes were: global efficiency of structural connectome, diffuse white matter abnormality volume, total brain tissue volume, total gray and white matter volume, and cerebellar volume. Maternal reports of smoking during pregnancy were obtained. We performed multivariable linear regression analyses to examine the association between prenatal TSE and our MRI outcomes, controlling for prospectively collected confounders. We performed a mediation analysis to estimate the direct effects of prenatal TSE on brain abnormalities and any indirect effects through preterm birth.In total, 12.6% of infants had prenatal TSE. Compared to nonexposed infants, infants with prenatal TSE had a higher median(range) global brain abnormality score of 7(0, 41) vs. 5(0, 34) (p=.001); findings remained significant (p.001) after controlling for antenatal confounders. Global efficiency (p.001), diffuse white matter volume (p=.037), and total brain tissue volume (p=.047), were significantly different between TSE groups in multivariable analyses. On mediation analysis, preterm birth mediated between 0 and 29% of the indirect effect of prenatal TSE on several measures of brain abnormality outcomes. Thus, prenatal TSE had a direct adverse effect between 71% and 100% on brain injury or abnormal development.We identified multiple adverse effects of prenatal TSE on sensitive and objective measures of neonatal brain injury/abnormal development; most appear to be a direct effect of prenatal TSE on fetal brain development. Results underscore the significant adverse neurostructural effects of prenatal TSE to tobacco smoke pollutants.

Background: Preeclampsia (PE) is a severe manifestation of maternal hypertensive disease with high morbidity and mortality which microparticles (MPs) might be generated. But there is limited evidence on response MPs with PE. Objectives: To explore the relationship between MPs and PE. Search strategy: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in Pubmed, Embase, Web of Science and China National Knowledge Infrastructure (inception to September 20, 2022). Selection criteria: Studies on patients diagnosed as PE were included. Studies on patients with chronic hypertension, pre-gestational diabetes mellitus, and history of recurrent pregnancy loss, renal or hepatic diseases, and antiphospholipid syndrome were excluded. Data collection and analysis: Two authors independently screened the studies, extracted the data and assessed the quality of the studies. Results were combined descriptively and analyzed using a standardized Excel form. Main results: We included 25 studies with a total of 1885 patients (862 with PE and 1023 with healthy pregnancy). Any MPs level was found no significant difference between PE and healthy pregnant patients in the second trimester. However, CD31-marked EMPs, RMPs and MPs from placenta are significantly elevated in the third trimester of preeclampsia, while CD41-marked PMPs is significantly decreased. After postpartum, tMPs and EMPs were found no significant difference between PE and healthy pregnant patients. Conclusion: MPs level is significantly associated with PE in the third trimester, but the association is dependent on its cell source and labeled marker.

To gain superior signal-enhanced performance, metal nanocrystals serving as building blocks can be collectively assembled into a hierarchically ordered structure for creating multiple hotspots. However, the collaborative assembly of anisotropic crystals to form a hotspot-rich structure remains a challenging task. In this study, controllable shear was introduced to a soft liquid-liquid interface to provide a unique environment for the snowball assembly of silver pompon architectures (Ag-PAs). Micrometer-scale 3D plasmonic Ag pompon architectures composed of densely packed nanoparticles (NPs) are fabricated using shear-mediating crystal growth dynamics. The crystal morphology and size are easily controlled by tuning the interfacial shear and diffusion pathways. The hotspot-rich Ag-PAs with high sensitivity (LOD = 1.1 × 10

Background Sodium-glucose cotransporter 2 inhibitors reduce cardiovascular mortality in patients. We studied the effect of canagliflozin on cardiac remodeling and myocardial metabolism in a rat model of heart failure with preserved ejection fraction (HFpEF). Methods In this study, a rat model of HFpEF was treated with canagliflozin, and blood glucose, renal function, oxidative stress indexes, lipid parameters, biochemical indexes and echocardiographic left ventricular function were assessed in the normal control group (group A), heart failure group (group B) and treatment group (group C). Metabolomics was used to analyze the possible pathways involved in the activity of canagliflozin. Results After canagliflozin treatment, E/A significantly increased, the myocardial volume decreased, the fibrotic area decreased, and cardiac remodeling improved in the rats with HFpEF. Rats with HFpEF displayed higher levels of L-lysine, D-glucose, uridine, O-phosphoethanolamine, L-norleucine, ribothymidine, and UDP-N-acetyl-alpha-D-galactosamine, reflecting hypermetabolism, and these increases were reversed by canagliflozin treatment. Myocardial metabolomics analysis of HFpEF rats compared with normal controls showed enrichment of metabolites involved in β-alanine metabolism, pyrimidine metabolism, arginine metabolism, proline metabolism, the citrate cycle (TCA cycle), glycolysis or gluconeogenesis and pyruvate metabolism. Canagliflozin decreased starch and galactose metabolism; cysteine and methionine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and phenylalanine metabolism pathway activity and improved energy metabolism. Conclusions Canagliflozin had a cardioprotective effect in rats with HFpEF.

Particle Swarm Optimization with Migration (MPSO) is proposed to solve the issue that PSO will come across unbearable time cost problem when dealing with High-dimension, Expensive and Black-box objective function tasks. Migration operator is inspired by the migration of Salmon. Salmon will start a dangerous journey from the ocean to the home rivers for reproduction. The process of the entire behavior is similar with the reduction and recovery of dimension. Therefore, we design the Migration operator where a pre-trained Wasserstein Auto-encoders (WAE) is applied to simulates the migration behavior to accelerate the process of evolution in PSO, and we use Least-Squares Regression in lower space to product better generation. In comparison with famous baselines methods in some benchmark functions, MPSO converges more faster and more accurate which show the great potential of migration operation.