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A single-atomic sulfur anode, constructed by ∼32 wt% single-atomic sulfur uniformly incorporated into the carbon lattice of hollow carbon nanospheres, demonstrates an outstanding combination of capacity, cyclability, and rate for potassium storage.

Extracellular vesicles (EVs) derived from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) have better cardioprotective effects against myocardial infarction (MI) in the early stage than EVs isolated from normoxic (NC)-MSCs. However, the cardioprotective mechanisms of HP-EVs are not fully understood.To explore the cardioprotective mechanism of EVs derived from HP MSCs.We evaluated the cardioprotective effects of HP-EVs or NC-EVs from mouse adipose-derived MSCs (ADSCs) following hypoxiaHP-EVs derived from MSCs reduced both infarct size (necrosis area) and apoptotic degree to a greater extent than NC-EVs from CMs subjected to hypoxiaThe anti-apoptotic effects of HP-EVs in alleviating MI and the hypoxic conditions of CMs until reperfusion therapy may partly result from EV miR-224-5p targeting TXNIP.

This review summarizes the recent progress and reasonable designs of Fe-MOF derivatives as electrodes and electrocatalysts in various batteries.

Vision transformers are a type of deep learning model that has shown promising results in various computer vision tasks, including image classification, object detection, and segmentation. In the context of retinal imaging, vision transformers have been applied to various problems such as lesion detection, vessel segmentation, and optic disc and fovea localization. One major advantage of vision transformers is their ability to process input sequences of variable length, making them well-suited for tasks such as retinal image analysis where the size of the input images can vary significantly. In contrast to convolutional neural networks (CNNs), which typically require fixed-size input, vision transformers can process images of different sizes by using self-attention mechanisms to learn contextual relationships between different parts of the input sequence. Another advantage of vision transformers is their ability to handle long-range dependencies, which can be important in retinal imaging where the relationships between different structures within the retina can be complex and non-local. For example, vision transformers have been used to analyze retinal images to identify abnormalities such as diabetic retinopathy, which can be difficult to detect using traditional CNN-based approaches. In summary, vision transformers have shown great potential for applications in retinal imaging, with the ability to handle variable-sized inputs and long-range dependencies making them well-suited for tasks such as lesion detection and vessel segmentation. However, further research is needed to fully understand their capabilities and limitations in this context.

Contains the supplementary material file for the manuscript entitled "Vision Transformers for Retinal Image Analysis: A Systematic Review"

Background Coronary heart disease is one of the most common cardiovascular diseases worldwide and is often associated with vascular endothelial injury. Endothelial-mesenchymal transition (EndMT) is an important process in vascular endothelial injury. Objectives This study investigated the function of miR-221 in the EndMT process of endothelial progenitor cells (EPCs). Material and methods Transforming growth factor beta (TGF-β1) was used to induce EndMT in EPCs, and SM22α expression was detected using immunocytochemistry. Western blot was used to detect alpha smooth muscle actin (αSMA) expression, and miR-221 function was evaluated using inhibitors or mimics of the miR-221 sequences that were transfected into EPCs. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of miR-221 and western blot was used to detect the expression of αSMA, myocardin, phosphatase and tensin homolog (PTEN), p-FoxO3a, and FoxO3a in EPCs. Finally, the expression of the miR-221 target genes was determined using RT-PCR. Results The expression of SM22α and αSMA increased in EPCs treated with TGF-β1, while the expression of miR-221 was decreased in EPCs on the 5th day, when compared with the control. The expression of SM22α increased after inhibiting miR-221 in EPCs treated with TGF-β1 and this was reversed by the overexpression of miR-221. The expression of αSMA and myocardin was significantly increased after inhibiting miR-221 in EPCs treated with TGF-β1 and decreased in EPCs overexpressing miR-221. Conversely, PTEN was increased in TGF-β1-treated EPCs and decreased following the overexpression of miR-221. The decrease in phosphorylated-FoxO3a expression in EPCs was accompanied by an increase in αSMA expression, which was reversed in the presence of miR-221 mimics. This effect was nearly abolished following the addition of PTEN cDNA. Conclusions The overexpression of miR-221 inhibits EndMT in EPCs, possibly by interacting with PTEN to regulate FoxO3a signaling, to facilitate the repair of the endothelium by EPCs.

Objective V-set and transmembrane domain-containing protein 1 (VSTM1) is negatively correlated with inflammation. However, its effect on atherosclerosis (AS) remains largely unexplored. In this study, we aimed to assess the effect of VSTM1 on the biological function of human peripheral blood mononuclear cells /macrophages stimulated by oxidized low-density lipoprotein (ox-LDL). Methods U937 cells were divided into three groups as follows: control group, pLenti-VSTM1 shRNA group (VSTM1 depletion), and pLenti-VSTM1 group (VSTM1 overexpression). Cellular migration, chemotaxis, apoptosis, and secretion of inflammatory factors of monocytes/macrophages stimulated by ox-LDL were studied. Results Overexpression of VSTM1 decreased the proliferation of U937 cells and induced cellular apoptosis. Depletion of VSTM1 enhanced the invasiveness and chemotaxis, increased the inflammatory response, and reduced the incidence of cell necrosis and apoptosis. Nuclear factor κ of B cells (NF-κB) was activated in VSTM1-depleted U937 cells. Conclusion VSTM1 might play an important role in the activation of monocytes/macrophages and participate in the pathogenesis of AS via regulating NF-κB activity.

The aim of this study was to investigate the correlation between v-set and transmembrane domain-containing 1 (VSTM1) expression and incidence of major adverse cardiac events (MACE) in patients with coronary heart disease (CHD). A total of 310 patients were divided into a non-acute coronary syndrome (non-ACS) group (containing the stable angina group, and the asymptomatic coronary artery diseaseand other patients group) and an ACS group (containing unstable angina and acute myocardial infarction patients). Monocytic VSTM1 expression levels (assessed via average fluorescence intensity derived from antibody binding to VSTM1) in each group were detected and analyzed. The cut-off value of monocytic VSTM1 expression to predict the onset of ACS and MACE was confirmed. VSTM1 expression in monocytes from the ACS group was lower than that of the non-ACS group. The incidence of MACEs in the high VSTM1-expression group was much less than that of those in the low VSTM1 expression group at the 1 year follow-up stage. VSTM1 expression had an independent-inversed association with increased incidence of MACE and ACS. VSTM1 expression in monocytes may help to predict the occurrence of ACS in patients with CHD, and moreover it may provide the means to evaluate MACE prognosis during CHD patient follow-up.

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.

Clinical translation of poly (lactic-co-glycolic acid) (PLGA)-based nanomedicine is limited, partly because of the poor delivery efficiency resulting from non-specific phagocytosis by phagocytes. Understanding the nanoparticle interplay between cancer cells and immune cells remains largely elusive. In this study, a quantitative investigation on cellular internalization of fluorescent PLGA particles (100 nm, 500 nm, and 1 µm) against laryngeal carcinoma cells with or without monocytes/macrophages in monoculture or co-culture systems was first performed. PLGA particles at concentrations of 5–20 µg/mL show superior biocompatibility except for 500 nm and 1 µm PLGA particles at 20 µg/mL slightly reduce cell viability. Microscopic observation has discovered all three sizes of particles are effectively ingested by both cancer cells and macrophages; however, quantitative fluorescence examination has disclosed that the uptake index of cancer cells (mean intracellular particle fluorescence per cancer cell normalized to that of per macrophage) is substantially declined for all PLGA particles in co-cultures compared to that in monocultures (1.35–1.05, 1.50–0.59, and 1.4–0.47 for 100 nm, 500 nm, and 1 µm particles, respectively). Quantitative analysis using flow cytometry further confirmed the reduced uptake index of cancer cells in co-cultures, but higher particle counts per macrophage. It has also been found that the formation of multinucleated giant cells via the fusion of macrophages increased after PLGA treatment, which could be further exploited as a potential approach for tumor drug delivery. Overall, these findings provide new insights into the interaction of nanoparticle-immune-cancer cells, which may facilitate the application of PLGA-based nanocarriers for the treatment of laryngeal carcinoma.

Dongjiu Li,1,* Chengyu Mao,1,* En Zhou,1,* Jiayin You,2,* Erhe Gao,3 Zhihua Han,1 Yuqi Fan,1 Qing He,1 Changqian Wang1 1Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 2Department of Emergency, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 3Center for Translational Medicine, Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA*These authors contributed equally to this workCorrespondence: Changqian Wang Email wangcqdr17@163.comObjective: Post myocardial infarction (MI) fibrosis has been identified as an important factor in the progression of heart failure. Previous studies have revealed that microRNA-21 (miR-21) plays an important role in the pathogenesis of fibrosis. The purpose of this study was to explore the role of miR-21 in post-MI cardiac fibrosis.Material and Methods: MI was established in wild-type (WT) and miR-21 knockout (KO) mice. Primary mice cardiac fibroblasts (CFs) were isolated from WT and miR-21 KO mice and were treated with angiotensin II (Ang II) or Sprouty1 (Spry1) siRNA. Histological analysis and echocardiography were used to determine the extent of fibrosis and cardiac function.Results: Compared with WT mice, miR-21 KO mice displayed smaller fibrotic areas and decreased expression of fibrotic markers and inflammatory cytokines. In parallel, Ang II-induced myofibroblasts transformation was partially inhibited upon miR-21 KO in primary CFs. Mechanistically, we found that the expression of Spry1, a previously reported target of miR-21, was markedly increased in miR-21 KO mice post MI, further inhibiting ERK1/2 activation. In vitro studies showed that Ang II activated ERK1/2/TGF-β/Smad2/3 pathway. Phosphorylated Smad2/3 further enhanced the expression of α-SMA and FAP and may promote the maturation of miR-21, thereby downregulating Spry1. Additionally, these effects of miR-21 KO on fibrosis were reversed by siRNA-mediated knockdown of Spry1.Conclusion: Our findings suggest that miR-21 promotes post-MI fibrosis by targeting Spry1. Furthermore, it mediates a positive feedback on Ang II, thereby inducing the ERK/TGF-β/Smad pathway. Therefore, targeting the miR-21–Spry1 axis may be a promising therapeutic option for ameliorating post-MI cardiac fibrosis.Keywords: cardiac fibrosis, myocardial infarction, microRNA-21, Sprouty1, ERK/TGF-β/Smad signaling pathway

Objective Post myocardial infarction (MI) fibrosis has been identified as an important factor in the progression of heart failure. Previous studies have revealed that microRNA-21 (miR-21) plays an important role in the pathogenesis of fibrosis. The purpose of this study was to explore the role of miR-21 in post-MI cardiac fibrosis. Material and methods MI was established in wild-type (WT) and miR-21 knockout (KO) mice. Primary mice cardiac fibroblasts (CFs) were isolated from WT and miR-21 KO mice and were treated with angiotensin II (Ang II) or Sprouty1 (Spry1) siRNA. Histological analysis and echocardiography were used to determine the extent of fibrosis and cardiac function. Results Compared with WT mice, miR-21 KO mice displayed smaller fibrotic areas and decreased expression of fibrotic markers and inflammatory cytokines. In parallel, Ang II-induced myofibroblasts transformation was partially inhibited upon miR-21 KO in primary CFs. Mechanistically, we found that the expression of Spry1, a previously reported target of miR-21, was markedly increased in miR-21 KO mice post MI, further inhibiting ERK1/2 activation. In vitro studies showed that Ang II activated ERK1/2/TGF-β/Smad2/3 pathway. Phosphorylated Smad2/3 further enhanced the expression of α-SMA and FAP and may promote the maturation of miR-21, thereby downregulating Spry1. Additionally, these effects of miR-21 KO on fibrosis were reversed by siRNA-mediated knockdown of Spry1. Conclusion Our findings suggest that miR-21 promotes post-MI fibrosis by targeting Spry1. Furthermore, it mediates a positive feedback on Ang II, thereby inducing the ERK/TGF-β/Smad pathway. Therefore, targeting the miR-21-Spry1 axis may be a promising therapeutic option for ameliorating post-MI cardiac fibrosis.

Atrial fibrillation (AF) is one of the most prevalent arrhythmias. Myocardial sleeves of the pulmonary vein are critical in the occurrence of AF. Our study aims to investigate the effect of synthetic vascular smooth muscle cells (SMCs) on gap junction proteins in cardiomyocytes. (1) Extraction of vascular SMCs from the pulmonary veins of Norway rats. TGF-β1 was used to induce the vascular SMCs switching to the synthetic phenotype and 18-α-GA was used to inhibit gap junctions of SMCs. The contractile and synthetic phenotype vascular SMCs were cocultured with HL-1 cells; (2) Western blotting was used to detect the expression of Cx43, Cx40 and Cx45 in HL-1 cells, and RT-PCR to test microRNA 27b in vascular SMCs or in HL-1 cells; (3) Lucifer yellow dye transfer experiment was used to detect the function of gap junctions. (1) TGF- β1 induced the vascular SMCs switching to synthetic phenotype; (2) Cx43 was significantly increased, and Cx40 and Cx45 were decreased in HL-1 cocultured with synthetic SMCs; (3) The fluorescence intensity of Lucifer yellow was higher in HL-1 cocultured with synthetic SMCs than that in the cells cocultured with contractile SMCs, which was inhibited by18-α-GA; (4) the expression of microRNA 27b was increased in HL-1 cocultured with synthetic SMCs, which was attenuated markedly by 18-α-GA. (5) the expression of ZFHX3 was decreased in HL-1 cocultured with synthetic SMCs, which was reversed by 18-α-GA. The gap junction proteins of HL-1 were regulated by pulmonary venous SMCs undergoing phenotypic transition in this study, accompanied with the up-regulation of microRNA 27b and the down-regulation of ZFHX3 in HL-1 cells, which was associated with heterocellular gap junctions between HL-1 and pulmonary venous SMCs.

Objectives This study aimed to determine the function of Cx43 in the endothelial-to-mesenchymal transition (EndMT) process of endothelial cells (ECs) and to explore the potential signaling pathways underlying these functions. Methods Endothelial cells (ECs) were extracted from rat aorta. ECs was transfected with Cx43 cDNA, Cx43 siRNA and then exposed to 5 or 12 dyne/cm2. Immunofluorescence staining was used to detect the expression of SM22α in ECs, Cx43 and acetylated-α tubulin in ECs. Western Blotting was used to detected the protein expression of α-SMA, CD31, Cx43, H1-caponin, Ift88 and p-smad3 in ECs. Results The expression of αSMA, SM22α and Cx43 was significantly increased and CD31 was markedly decreased in ECs treated with laminar shear stress at 5 dyn/cm2. The Cx43 cDNA transfection could induce the expression of SM22α or H1-caponin, and attenuate CD31 expression in the ECs. Also, Cx43 overexpression harms cilia formation in ECs exposed to 5dyn/cm2, accompanied with the regulated Ift88 and smad signaling. Conclusions This study found that laminar shear stress at 5 dyn/cm2 would increase the expression of Cx43, and interfere with primary cilia formation by inhibiting the expression of Ift88 in ECs.

Background Prostate cancer is the second most common cancer in men, and some new target genes are needed to predict the risk of prostate cancer progression and the treatment. Methods In this study, the effects of UAP1L1 (UAP1-like-1) on prostate cancer were investigated by detecting the proliferation, migration, invasion and apoptosis of prostate cancer cells in vitro using MTT, wound healing, Transwell and flow cytometry assay, and the tumor growth in vivo. The downstream genes and pathways of UAP1L1 were explored using Ingenuity Pathway Analysis (IPA), and screened by qRT-PCR and western blot. The effects of CDCA8 on prostate cancer cells were also verified in vitro, which was through detecting the change of proliferation, migration, invasion and apoptosis of prostate cancer cells after CDCA8 knockdown. Results The results indicated that UAP1L1 promoted the proliferation, migration and invasion of prostate cancer cells, which was inhibited by downregulating CDCA8. Furthermore, the promotion of CDCA8 knockdown on cell apoptosis was reduced when UAP1L1 was simultaneously overexpressed. Conclusions In conclusion, the results in this study revealed that UAP1L1 promoted the progression of prostate cancer through the downstream gene CDCA8.

Aim. To determine the role and underlying mechanism of lncRNA HCP5 in nasopharyngeal carcinoma (NPC). Method. The expression of HCP5 and miR-128-3p was assessed by qRT-PCR. CCK-8, EdU staining, and transwell were performed to determine cell progression. A nude mouse xenograft tumor model was carried out to detect the role of HCP5 in vivo. The luciferase assay was performed to confirm the function between lncRNA HCP5 and miR-128-3p. Results. The increased level of HCP5 was observed in NPC tissues. Silencing of HCP5 prevented tumor progression in vitro and in vivo. The luciferase assay verified that HCP5 could bind with miR-128-3p. Furthermore, forced expression of miR-128-3p could prevent the function of HCP5 on NPC cells. Conclusion. lncRNA HCP5 could regulate NPC cell progression via sponging miR-128-3p, which might serve as a potential therapy target of NPC.

Background Previous studies have revealed that current secondhand smoke exposure showed highly suggestive evidence for increased risk of simultaneous sleep problems in children. Data on the associations between early-life exposure to SHS with subsequent sleep problems in children were scarce. We aimed to evaluate the associations of early-life SHS exposure with sleep problems in children. Methods In this cross-sectional study, children were recruited from elementary and middle schools in Liaoning Province, China between April 2012 and January 2013. We assessed early-life SHS exposure (pregnancy and the first 2 years of life) via questionnaires. Sleep problems and different types of sleep-related symptoms were measured based on the validated tool of the Sleep Disturbance Scale for Children (SDSC). Generalized linear mixed models were applied to estimate the associations of early-life SHS exposure with sleep problems. Results We included a total of 45,562 children (22,657 [49.7%] males; mean [SD] age, 11.0 [2.6] years) and 6167 of them (13.5%) were exposed to early-life SHS during both pregnancy and the first 2 years of life. Compared with unexposed counterparts, children exposed to early-life SHS had higher total T-scores of SDSC (β = 4.32; 95%CI: 4.06, 4.58) and higher odds of increased sleep problems (OR = 2.14; 95%CI: 1.89, 2.42). When considering different sleep-related symptoms, the associations between early-life SHS exposure and symptom of sleep-wake transition disorders (i.e., bruxism) were the strongest in all analyses. Conclusions Early-life SHS exposure was associated with higher odds of global sleep problems and different sleep-related symptoms in children aged 6–18 years. Our findings highlight the importance to strengthen efforts to support the critical importance of maintaining a smoke-free environment especially in early life.

IntroductionAnalysis of multimodal medical images often requires the selection of one or many anatomical regions of interest (ROIs) for extraction of useful statistics. This task can prove laborious when a manual approach is used. We have previously developed a user-friendly software tool for image-to-image translation using deep learning. Therefore, we present herein an update to the DeepImageTranslator software with the addition of a tool for multimodal medical image segmentation analysis (hereby referred to as the MMMISA).MethodsThe MMMISA was implemented using the Tkinter library; backend computations were implemented using the Pydicom, Numpy, and OpenCV libraries. We tested our software using 4188 slices from whole-body axial 2-deoxy-2-[18F]-fluoroglucose-position emission tomography/computed tomography scans ([18F]-FDG-PET/CT) of 10 patients from the American College of Radiology Imaging Network-Head and Neck Squamous Cell Carcinoma (ACRIN-HNSCC) database. Using the deep learning software DeepImageTranslator, a model was trained with 36 randomly selected CT slices and manually labelled semantic segmentation maps. Utilizing the trained model, all the CT scans of the 10 HNSCC patients were segmented with high accuracy. Segmentation maps generated using the deep convolutional network were then used to measure organ specific [18F]-FDG uptake. We also compared measurements performed using the MMMISA and those made with manually selected ROIs.ResultsThe MMMISA is a tool that allows user to select ROIs based on deep learning-generated segmentation maps and to compute accurate statistics for these ROIs based on coregistered multimodal images. We found that organ-specific [18F]-FDG uptake measured using multiple manually selected ROIs is concordant with whole-tissue measurements made with segmentation maps using the MMMISA tool.

Numerous studies have demonstrated that exposure to ambient ozone (O3) could have adverse effects on children’s respiratory health. However, previous studies mainly focused on asthma and wheezing. Evidence for allergic rhinitis and bronchitic symptoms (e.g., persistent cough and phlegm) associated with O3 is limited, and results from existing studies are inconsistent. This study included a total of 59,754 children from the seven northeastern cities study (SNEC), who were aged 2 to 17 years and from 94 kindergarten, elementary and middle schools. Information on doctor-diagnosed allergic rhinitis (AR), persistent cough, and persistent phlegm was collected during 2012–2013 using a standardized questionnaire developed by the American Thoracic Society (ATS). Information for potential confounders was also collected via questionnaire. Individuals’ exposure to ambient ozone (O3) during the four years before the investigation was estimated using a satellite-based random forest model. A higher level of O3 was significantly associated with increased risk of AR and bronchitic symptoms. After controlling for potential confounders, the OR (95% CI) were 1.13 (1.07–1.18), 1.10 (1.06–1.16), and 1.12 (1.05–1.20) for AR, persistent cough, and persistent phlegm, respectively, associated with each interquartile range (IQR) rise in O3 concentration. Interaction analyses showed stronger adverse effects of O3 on AR in children aged 7–17 years than those aged 2–6 years, while the adverse association of O3 with cough was more prominent in females and children aged 7–12 years than in males and children aged 2–6 and 13–17 years. This study showed that long-term exposure to ambient O3 was significantly associated with higher risk of AR and bronchitic symptoms in children, and the association varies across age and gender. Our findings contribute additional evidence for the importance of controlling O3 pollution and protecting children from O3 exposure.