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Background In recent years, a growing body of observational studies suggest that urticaria is associated with a higher risk of rheumatoid arthritis (RA). However, the causal association between urticaria and RA remains unknown. Objective To investigate the causal relationship of urticaria and RA in European populations by Mendelian randomisation (MR) approach. Methods We conducted two-sample MR analyses. Eleven single-nucleotide polymorphisms associated with urticaria were used as instrumental variables. The summary data on urticaria were derived from FinnGen Data Freeze 2. The summary data on RA were obtained from a published meta-analysis using European samples. Four MR methods were applied to the MR estimates. Three heterogeneity tests, including Cochran’s Q test, single variant analysis, and leave-one-out variant analysis, were used. The pleiotropy and horizontal pleiotropy among instrumental variables were assessed with MR-Egger regression intercept, MR pleiotropy residual sum and outlier global test, and PhenoScanner. Results The MR analysis suggested that urticaria was causally associated with RA (odds ratio = 1.114, 95% confidence interval = 1.024–1.211, p = .011). No genetic pleiotropy or horizontal pleiotropy was revealed by MR-Egger regression intercept and MR pleiotropy residual sum and outlier global test. The sensitivity analysis results were relatively robust. Conclusions The MR analysis suggested there was sufficient evidence to indicate urticaria is the cause of RA.

Myocarditis is a disease characterized by localized or diffuse inflammation of the myocardium without efficient treatment. This study explored the regulatory mechanism of microRNA-133 (miR-133) secreted from bone marrow mesenchymal stem cell-derived exosome (BMSC-Exo) on myocardial fibrosis and epithelial–mesenchymal transition (EMT) in viral myocarditis (VMC) rats through regulating mastermind-like 1 (MAML1). BMSCs in rats were isolated and cultured to identify their immune phenotype and osteogenic and adipogenic ability, and BMSC-Exo were extracted and identified. Exosomes were obtained through ultracentrifugation, which were identified by transmission electron microscope and western blot analysis. The rats were injected with Coxsackie B3 virus for preparation of VMC model, and cardiomyocytes were isolated, cultured and grouped in the same way as animal experiments (NCExo, Ad-miR-133aExo, Adas-miR-133aExo). In vivo and in vitro experiments were conducted to figure out the roles of exosomal miR-133a and MAML1 in inflammation, apoptosis, EMT, fibrosis, and cell viability. The targeting relationship between miR-133a and MAML1 was verified by dual luciferase reporter gene assay. BMSC-Exo raised miR-133a expression in VMC rats and effectively improved the VMC rat cardiac function and myocardial fibrosis, increased cardiomyocyte viability and inhibited the EMT process. Elevated miR-133a in exosomes strengthened the improvements. Silenced miR-133a effectively reversed the effects of BMSC-Exo on VMC rats. miR-133a targeted MAML1. Inhibition of MAML1 improved cardiac function and myocardial fibrosis in VMC rats and could reverse the effect of miR-133a-silenced exosomes on VMC rats. Our study suggests that elevated exosomal miR-133a suppresses myocardial fibrosis and EMT in rats with VMC via down-regulating MAML1, thereby inhibiting the progression of myocarditis. Supplementary Information The online version contains supplementary material available at 10.1186/s11671-021-03559-2.

Androgen-deprivation therapy (ADT) via targeting androgens/androgen receptor (AR) signals may suppress cell proliferation in both prostate cancer (PCa) and bladder cancer (BCa), yet its impact on the cell invasion of these two urological cancers remains unclear. Here we found targeting androgens/AR with either the recently developed antiandrogen Enzalutamide (Enz) or AR-shRNAs led to increase PCa cell invasion, yet decrease BCa cell invasion. Mechanistic dissection revealed that suppressing androgens/AR signals could result in differential alterations of the selective circular RNAs (circRNAs) as a result of differential endogenous AR transcription. A negative autoregulation in PCa, yet a positive autoregulation in BCa, as a result of differential binding of AR to different androgen-response elements (AREs) and a discriminating histone H3K4 methylation, likely contributes to this outcome between these two urological tumors. Further mechanistic studies indicated that AR-encoded circRNA-ARC1 might sponge/alter the availability of the miRNAs miR-125b-2-3p and/or miR-4736, to impact the metastasis-related PPARγ/MMP-9 signals to alter the PCa vs. BCa cell invasion. The preclinical study using the in vivo mouse model confirms in vitro cell lines data, showing that Enz treatment could increase PCa metastasis, which can be suppressed after suppressing circRNA-ARC1 with sh-circRNA-ARC1. Together, these in vitro/in vivo results demonstrate that antiandrogen therapy with Enz via targeting AR may lead to either increase PCa cell invasion or decrease BCa cell invasion. Targeting these newly identified AR/circRNA-ARC1/miR-125b-2-3p and/or miR-4736/PPARγ/MMP-9 signals may help in the development of new therapies to better suppress the Enz-altered PCa vs. BCa metastasis.

Background: Coronavirus disease 2019 (COVID-19) has caused over 3.8 million deaths globally. Up to date, the number of death in 2021 is more than that in 2020 globally. Here, we aimed to compare clinical characteristics of deceased patients and recovered patients, and analyze the risk factors of death to help reduce mortality of COVID-19. Methods: In this retrospective study, a total of 2719 COVID-19 patients were enrolled, including 109 deceased patients and 2610 recovered patients. Medical records of all patients were collected between February 4, 2020, and April 7, 2020. Clinical characteristics, laboratory indices, treatments, and deep-learning system- assessed lung lesion volumes were analyzed. The effect of different medications on survival time of fatal cases was also investigated. Results: The deceased patients were older (73 years versus 60 years) and had a male predominance. Nausea (10.1% versus 4.1%) and dyspnea (54.1% versus 39.2%) were more common in deceased patients. The proportion of patients with comorbidities in deceased patients was significantly higher than those in recovered patients. The median times from hospital admission to outcome in deceased patients and recovered patients were 9 days and 13 days, respectively. Patients with severe or critical COVID-19 were more frequent in deceased group. Leukocytosis (11.35×109/L versus 5.60×109/L) and lymphocytopenia (0.52×109/L versus 1.58×109/L) were shown in patients who died. The level of prothrombin time, activated partial prothrombin time, D-dimer, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, creatine kinase, glucose, brain natriuretic peptide, and inflammatory indicators were significantly higher in deceased patients than in recovered patients. The volumes of ground-glass, consolidation, total lesions and total lung in all patients were quantified. Complications were more common in deceased patients than in recovered patients; respiratory failure (57.8%), septic shock (36.7%), and acute respiratory distress syndrome (26.6%) were the most common complications in patients who died. Many treatments were more frequent in deceased patients, such as antibiotic therapy (88.1% versus 53.7%), glucocorticoid treatment (70.6% versus 11.0%), intravenous immunoglobin treatment (36.6% versus 4.9%), invasive mechanical ventilation (62.3% versus 3.8%). Antivirals, antibiotics, traditional Chinese medicines and glucocorticoid treatment may significantly increase the survival time of fatal cases. Quantitative computed tomography imaging results were correlated with biochemical markers. Conclusions: Most patients with fatal outcomes were more likely to have common comorbidities. The leading causes of death were respiratory failure and multiple organ dysfunction syndrome. Acute respiratory distress syndrome, respiratory failure and septic shock were the most common serious complications. Antivirals, antibiotics, traditional Chinese medicines, and glucocorticoid treatment may prolong the survival time of deceased patients with COVID-19.

Objective The purpose of the present study is to investigate whether angiopoietin-like 4 (ANGPTL4) can promote angiogenesis and neurogenesis following stroke, as well as to explore the potential underlying mechanisms. Methods ANGPTL4 (40 μg/kg) or a vehicle was administered via tail vein beginning 5 min prior to electrocoagulation-induced stroke in male C57/B6 J mice. Infarct volume was measured via Nissl staining at day 3 post-stroke. Angiogenesis, neurogenesis and activation of microglia were evaluated by immunofluorescence co-labelling bromodeoxyuridine (BrdU) with von Willebrand factor (vWF), doublecortin (DCX), neuronal nuclei (NeuN) and Iba1 at day 7 post-stroke. The levels of p-AKT, T-AKT, VEGF, MPO, Fas and FasL in the ipsilesional brain were detected by Western blot analysis at day 1 post-stroke. Results Compared with the Vehicle group, ANGPTL4 reduced infarct volume significantly at day 3 post-stroke. ANGPTL4 significantly increased the number of BrdU+, BrdU+/vWF+and BrdU+/DCX+ cells in the peri-infarct zone, subventricular zone and subgranular zone and inhibited BrdU+/Iba1+ cells in the peri-infarct zone at day 7 post-stroke. The level of p-AKT and the ratio of phospho-AKT to total-AKT in the ipsilesional brain were significantly elevated, the levels of MPO, Fas and FasL were significantly declined; however, there was no significant difference at day 1 post-stroke between the VEGF and total-AKT levels in both groups. Conclusions ANGPTL4 enhances angiogenesis and neurogenesis post-stroke by upregulating the phosphorylation of AKT, reduces neuronal death and inhibits inflammatory response, which resultes from the inhibition of FasL/Fas expression and its downstream pathway.

Introduction: Follicular thyroid carcinoma (FTC) is more aggressive than the most common papillary thyroid carcinoma (PTC). However, the current research on FTC is less than PTC. Here, we investigated the effects of long noncoding RNA (lncRNA) GAS5 and miR-221-3p in FTC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect GAS5 and miR-221-3p expression in the FTC tissues and cells. Cell proliferation was assessed by CCK8 and EdU assays. Flow cytometry was performed to determine the cell cycle. The dual-luciferase reporter assay was employed to validate the binding relationship of GAS5/miR-221-3p and miR-221-3p/cyclin-dependent kinase inhibitor 2B (CDKN2B). Western blot was conducted to measure the protein level of CDKN2B. Results: Our results displayed that GAS5 was downregulated, while miR-221-3p was upregulated in FTC tissues and cells. What’s more, overexpression of GAS5 or miR-221-3p inhibition induced G0/G1 phase arrest and inhibited cell proliferation of FTC cells. GAS5 acted as a sponge of miR-221-3p, and CDKN2B was a target gene of miR-221-3p. Additionally, GAS5 inhibited cell cycle and proliferation of FTC cells via reducing miR-221-3p expression to enhance CDKN2B expression. Conclusion: GAS5 induced G0/G1 phase arrest and inhibited cell proliferation via targeting miR-221-3p/CDKN2B axis in FTC. Thus, GAS5 may be a potential therapeutic target for the treatment of FTC.

Background: ADPRH is a modulator of CD8+ T cell functions, and dysregulation of ADPRH has been identified to involve in carcinogenesis of cancers. However, the association of ADPRH with low grade glioma (LGG) remains unclear. Methods: The expression of ADPRH in LGG was first analyzed in GLIOVIS and GEPIA databases and then validated by real-time PCR (rt-PCR), immunochemistry and human protein atlas (HPA). Univariate and multivariate Cox analysis and Kaplan-Meier plots were designed to assess the prognostic value of ADPRH in LGG. The correlation of ADPRH and immune infiltration was evaluated by data in TIMER and ESTIMATE databases. Gene set enrichment analysis was conducted to detect biological processes associated with ADPRH. Results: ADPRH was significantly upregulated in LGG in comparison to non-tumor brain samples in transcriptomic and proteomic levels. The high ADPRH expression indicated unfavorable overall survival (OS) and progression-free survival (PFS) in patients with LGG using Kaplan-Meier plots. And multivariate Cox analysis demonstrated the expression level of ADPRH was an independent prognosis-predicting index for OS and PFS of LGG patients in all cohorts separately. Gene Set Enrichment Analysis (GSEA) indicated that high expression of ADPRH was involved in the upregulation of P53 signaling pathway, KRAS signaling pathway, IL6/JAK-STAT3 signaling and TNF-beta signaling pathways. By TIMER and ESTIMATE databases, we identified ADPRH expression had strong correlation with tumor immune infiltrating cells (TIICs). Conclusions: In summary, our findings demonstrated that ADPRH might be a potential prognostic biomarker and correlated with TIICs in LGG.

Objective The optimal timing for glioma patients to stop taking antiepileptic drugs (AEDs) and the risk factors of seizure relapse have not been determined. Here, we explored the short-term outcomes and risk factors of seizure relapse in glioma patients after withdrawal of AEDs. Methods 91 patients with gliomas who had no seizures at least 2 years after surgery were enrolled in the study. The patients were followed up for 1 year or until the relapse of seizure after AEDs withdrawal. The risk factors of seizure relapse were analyzed by univariate and multivariate analysis. The optimal discrimination point was determined by plotting a receiver operating characteristic (ROC) curve to explore the relationship between the number of risk factors and seizure relapse. Results 28 patients (30.8%) relapsed during the follow-up period while 63 patients (69.2%) remained seizure-free. Of the 28 relapsed patients, 20 (71.4%) relapsed within the first 6 months after the AEDs withdrawal. Multivariate analyses revealed that subtotal resection (p = 0.026), IDH1 mutation (p = 0.019), and combined use of AEDs (p = 0.037) were independent risk factors for seizure relapse in glioma patients. ROC curve based on the seizure relapse showed that the sensitivity was 0.821 and 1–specificity was 0.238, corresponding to 1.5 independent risk factors for each patient. Conclusion To obtain a favorable outcome for glioma patients with preoperative seizures, only patients with less than two independent risk factors for seizure relapse should consider discontinuing AEDs.

Glioma is the most common malignant tumor in the central nervous system. Evidence shows that clinical efficacy of immunotherapy is closely related to the tumor microenvironment. This study aims to establish a microenvironment-related genes (MRGs) model to predict the prognosis of patients with Grade II/III gliomas. Gene expression profile and clinical data of 459 patients with Grade II/III gliomas were extracted from The Cancer Genome Atlas. Then according to the immune/stromal scores generated by the ESTIMATE algorithm, the patients were scored one by one. Weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network to identify potential biomarkers for predicting the prognosis of patients. When adjusting clinical features including age, histology, grading, IDH status, we found that these features were independently associated with survival. The predicted value of the prognostic model was then verified in 440 samples in CGGA part B dataset and 182 samples in CGGA part C dataset by univariate and multivariate cox analysis. The clinical samples of 10 patients further confirmed our signature. Our findings suggested the eight-MRGs signature identified in this study are valuable prognostic predictors for patients with Grade II/III glioma.

Light is an important variable affecting the plant growth. In present study, the effects of different color light-emitting diodes (mixed colors, red, blue, and orange light) on plant growth, gas exchange, and oxidative stress were investigated in Boehmeria nivea L., by means of measuring growth, photosynthesis, chlorophyll (Chl) content, reactive oxygen species (ROS), and activity of antioxidant enzymes under controlled conditions. Comparing to the mixed colors light, red light significantly increased shoot and leaf biomass, plant height, number of leaves per plant, and stem diameter by increasing the Chl content and therefore promoting the highest photosynthetic capacity. This might partially be explained by the decrease of malondialdehyde and proline contents as well as the activities of superoxide dismutase and peroxidase under red light, to keep a better internal environment of the cell. However, blue and orange light decreased plant growth, and increased the activities of antioxidant enzymes which suggest an environmental stress on plants. These results suggest that red light can enhance B. nivea growth by activating photosynthesis and reducing ROS accumulation.

Background Collateral status assessed with single- or multiphase CT angiography can be used to predict outcome in patients with acute ischemic stroke (AIS); however, little is known about whether these measures could be comparable with CT perfusion parameters. Purpose To compare the predictive ability of collateral score systems assessed with single- or multiphase CT angiography and CT perfusion parameters in determining clinical outcomes in patients with AIS. Materials and Methods In this retrospective study, data obtained from October 2017 to August 2018 in consecutive patients with AIS caused by isolated anterior circulation large artery occlusion and that were obtained within 24 hours after onset were reviewed. The collateral score was assessed by using established scoring systems described by Menon et al. The correlations between single- and multiphase collateral scores, hypoperfusion, and ischemic core volume and final infarct volume (FIV) determined by follow-up diffusion-weighted imaging or unenhanced CT were studied. Receiver operating characteristic curves and multivariable logistic regression analysis were performed to assess the predictive ability of scoring systems and CT perfusion parameters for a favorable clinical outcome. Results A total of 119 patients (median age, 75 years; interquartile range, 66-82 years; 74 men) were included. Both single- and multiphase Menon scores had a moderate negative correlation with FIV (r = -0.43, P < .001; r = -0.44, P < .001). Receiver operating characteristic curve analysis revealed the multiphase Menon score performed better than the single-phase Menon score (area under the curve [AUC], 0.72 vs 0.64; P = .045) in the prediction of a favorable 90-day modified Rankin scale score. There was no difference between multiphase Menon score and hypoperfusion volume (AUC, 0.72 vs 0.72; P = .97) or ischemic core volume (AUC, 0.72 vs 0.71; P = .94). Multivariable analysis showed multiphase Menon score was an independent predictor of good clinical outcomes (odds ratio = 3.04, P = .001). Conclusion Multiphase Menon score performed better than single-phase Menon score and was comparable with CT perfusion parameters in determining clinical outcomes in patients with acute ischemic stroke. © RSNA, 2020.

The detection data of IgM and IgG antibodies in 169 patients with coronavirus disease (COVID‐19) were analyzed to evaluate differences in clinical performance between the colloidal gold method and chemiluminescence method. In this study, chemiluminescence detection of IgM antibody showed a positive conversion earlier (about 1~2 days earlier), positive conversion rates higher in different stages of disease, and a trend of declining positive rate later than colloidal gold method. For IgG antibody, the chemiluminescence method showed a positive conversion earlier and the positive rate climbing more quickly than the colloidal gold method. No obvious negative‐converting tendency of IgG detection was observed within 35 days after the onset of disease. Although colloidal gold method is generally less sensitive than chemiluminescence method, it shows advantages of shorter turn‐around time, more simple procedure and no special equipment required. The two methodologies can be chosen according to different laboratory conditions. A reasonable understanding of the performance of reagents with different methodologies can help in clinical disease diagnosis effectively and assist in the diagnosis of the progression of COVID‐19, for which the dynamic changes of antibody will provide reliable evidence. This article is protected by copyright. All rights reserved.

The difference in prognosis between genders after abdominoperineal resection (APR) for low rectal cancer (LRC) is unclear. This study aimed to compare survival outcomes between genders in patients with LRC who underwent curative APR. This retrospective cohort study used a database of consecutive colorectal resections. Patients who received curative APR with LRC were grouped according to their gender. Female patients were frequency-matched 1:1 on American Joint Committee on Cancer (AJCC) stage to male patients. Overall survival (OS), disease-free survival (DFS), and their independent risk factors were examined. A total of 140 patients with APR for LRC were included after matching: 70 (50.0%) males and 70 (50.0%) females. No significant differences were found between the groups in terms of age, operation methods, AJCC stage, and adjuvant therapy (all P > 0.05). Median follow-up was 39 (range: 3–128) months. Male gender was independently associated with worse OS (adjusted hazard ratio [HR] = 2.755, 95% CI: 1.507–5.038, P = 0.001) and worse DFS (adjusted HR = 2.440, 95% CI: 1.254–4.746, P = 0.009). Subgroup analysis revealed that female patients with stage III disease had better OS (P = 0.001) and DFS (P

Purpose/aim: Lymphomatosis cerebri (LC) and cauda equina lymphoma are both rare forms of primary central nervous system lymphoma (PCNSL). LC is characterized by diffuse bilateral non-enhancing (or partially enhancing) inltrative lesions without mass effect, which can be easily confused with other forms of leukoencephalopathy and, thus, lead to delays in diagnosis.Case report: For the first time, a case of LC concomitant with cauda equina involvement confirmed by brain stereotactic biopsy is presented.Conclusions: This case highlights the necessity of using a multimodal strategy in diagnosing PCNSL, including multimodal magnetic resonance, cerebral spinal fluid cytology, flow cytometry and fluorodeoxyglucose positron emission tomography/computed tomography.

Breast cancer is the most common type of cancer in women. About 12% of all women in the United States will be diagnosed with breast cancer over their lifetimes. At the same time, incidences of brain metastases (BMs) are increasing and represent an emerging health threat. However, there is no effective chemotherapy for breast cancer brain metastases (BCBMs), which is largely due to lack of efficient delivery of antitumor drugs or drug combinations to the brain. In this study, oleanolic acid (OA), a natural pentacyclic triterpenoid compound with excellent antitumor activity, was found to form nanoparticles (NPs) and efficiently penetrate the brain for BCBMs treatment. On the basis of these findings, we developed a synergistic combinatorial chemotherapeutic regimen by formulating paclitaxel (PTX) into OA NPs and demonstrated that the resulting PTX-OA NPs effectively inhibited primary breast cancer and BCBMs in mouse xenografts. Collectively, this study introduces a new direction to treat primary breast cancer and BCBMs through noninvasive combination chemotherapy.

To explore the predictive factors and short-term outcomes of post-surgical seizures in patients with supratentorial low-grade gliomas (LGGs). A consecutive series of 70 supratentorial LGG patients with seizures were reviewed to determine the predictors and short-term outcomes of seizures. Univariate analyses and multivariate logistic regression analyses were performed to determine the predictive factors associated with postoperative seizure outcomes. We identified the preoperative seizure frequency threshold by plotting a receiver operating characteristic curve. A Kaplan-Meier curve was constructed to illustrate the seizure-free survival rate of our cohort over time. 54 patients who remained seizure -free post-surgery were classified into the Engel class I, and the other 16 patients whose seizures relapsed were classified into Engel classes II–IV. Univariate and multivariate logistic regression analyses showed that the preoperative seizure frequency (X2 = 16.069, P = 0.001), extent of resection (x2 = 5.031, P = 0.025), IDH1 mutation (x2 = 4.435, P = 0.035) and adjuvant chemotherapy of temozolomide (X2 = 4.081, P = 0.043) were related to the postoperative short-term seizure outcome. The ROC curve indicated that the area under the curve for the preoperative seizure frequency test was 0.805 (95% confidence interval 0.690–0.920, p

Despite being promising, the clinical application of magnetic hyperthermia for brain cancer treatment is limited by the requirement of highly invasive intracranial injections. To overcome this limitation, here we report the development of gallic acid-coated magnetic nanoclovers (GA-MNCs), which allow not only for noninvasive delivery of magnetic hyperthermia but also for targeted delivery of systemic chemotherapy to brain tumors. GA-MNCs are composed of clover-shaped MNCs in the core, which can induce magnetic heat in high efficiency, and polymerized GA on the shell, which enables tumor vessel-targeting. We demonstrate that intravenous administration of GA-MNCs following alternating magnetic field exposure effectively inhibited brain cancer development and preferentially disrupted tumor vasculature, making it possible to efficiently deliver systemic chemotherapy for further improved efficacy. Due to the noninvasive nature and high efficiency in killing tumor cells and enhancing systemic drug delivery, GA-MNCs have the potential to be translated for improved treatment of brain cancer.

Background: Aberrant expression and alternative splicing of oncogenes are the driving events in tumor initiation and development. But how these events are regulated in cancer cells is largely unknown. Functions of ATP5A1, an important mitochondrial ATP synthase gene, in transcriptional and posttranscriptional regulation were explored in this study. Methods: ATP5A1 was overexpressed using plasmid-transformed HeLa cells, and its influence on cell apoptosis and proliferation is evaluated. Transcriptome sequencing was then performed using RNA-seq to study the changes in gene expression and regulation of alternative splicing events. Validation of the implicated genes was achieved using RT-qPCR analysis. Results: It was found that ATP5A1 could significantly promote cellular apoptosis, but it had no influence on cell proliferation. ATP5A1 overexpression significantly increased the expression levels of genes associated with the innate immune response, angiogenesis, and collagen catabolic processes. This included enrichment of MMP2 and MMP19. It was also found that ATP5A1 could interfere with the alternative splicing of hundreds of genes associated with glucose homeostasis, HIF-1 signaling activation, and several pathways associated with cancers. Eight ATP5A1-regulated differentially expressed genes and 3 genes altered by splicing were selected and validated using RT-qPCR analysis. Conclusions: In summary, we illustrate the regulatory functions of ATP5A1 on the transcriptome of HeLa cells by exploring its influence on gene expression and alternative splicing. The results suggest that ATP5A1 may play an important regulatory role in cervical cancer cells by regulating expression and alternative splicing of cancer-associated genes. This study provides novel insights into the current understanding of the mechanisms of ATP5A1 on carcinogenesis and cancer progression.

As a class of novel biomaterials manufactured by synthetic biology technologies, recombinant collagens are candidates for a variety of medical applications. In this article, a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition, translation, classification and technical review. Recombinant collagens are categorized as recombinant human collagen, recombinant humanized collagen and recombinant collagen-like protein, as differentiated by specific compositions and structures. Based on their intended uses and associated risks, recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China. The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations. Taken together, opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound, which highlights the essential role of regulatory science to provide new tools, standards, guidelines and methods to evaluate the safety and efficacy of medical products.

Context Fruit of Avicennia marina (Forsk.) Vierh. (Acanthaceae) is used as a Chinese herb. Studies have found that it contains marinoid J, a novel phenylethanoid glycoside (PG) compound, but its neuroprotective functions are largely unknown. Objective This study evaluated the effects of marinoid J on vascular dementia (VD) and determined its potential mechanisms of action. Materials and methods The VD model was established by the ligation of the bilateral common carotid artery in Sprague–Dawley rats, who received daily intragastrically administration of saline, marinoid J (125 or 500 mg/kg body weight/d), or oxiracetam (250 mg/kg body weight/d) for 14 days (20 rats in each group). The Morris water maze (MWM) was used to evaluate cognitive performance. The hippocampus was subjected to histological and proteomic analyses. Results Marinoid J shortened the escape latency of VD rats (31.07 ± 3.74 s, p

Background PLEKHA5 has previously been identified as a novel molecule implicated in melanoma brain metastasis, a disease that continues to portend a poor prognosis. The aim of this study was to further investigate the functional role of PLEKHA5 in disseminated melanoma. Methods The impact of PLEKHA5 on proliferation and tumor growth was examined in vitro and in melanoma xenograft models, including brain-tropic melanomas (melanomas tending to disseminate to the brain). In vitro loss- and gain-of-function studies were used to explore the underlying mechanisms of PLEKHA5-mediated tumor growth and the crosstalk between PLEKHA5 and PI3K/AKT/mTOR or MAPK/ERK signaling. The clinical relevance of PLEKHA5 dysregulation was further investigated in a cohort of matched cranial and extracranial melanoma metastases. Results PLEKHA5 stable knockdown negatively regulated cell proliferation by inhibiting the G1 -to-S cell cycle transition, which coincided with upregulation of the cell cycle regulator PDCD4. Conversely, ectopic PLEKHA5 expression exhibited the inverse effect. PLEKHA5 knockdown significantly inhibited tumor growth, whereas its overexpression upregulated the growth of tumors, which was induced by cranial and subcutaneous inoculation of cells in nude mice. PLEKHA5 modulation affected PDCD4 protein stability and was coupled with changes in PI3K/AKT/mTOR pathway signaling. High PDCD4 expression in cerebral specimens was associated with better overall survival. Conclusions This study further supports the role of PLEKHA5 as a regulator of melanoma growth at distant sites, including the brain. Furthermore, the results highlight the significance of PDCD4 dysregulation in disseminated melanoma and implicate PDCD4 as a possible causal link between PLEKHA5 and cell proliferation and growth.

Objective: To assess the reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of atherosclerotic plaques in the middle cerebral artery. Methods: Sixty-nine consecutive patients with ischemic stroke or asymptomatic stenosis (>30%) of the middle cerebral artery underwent 3.0T high-resolution magnetic resonance imaging examinations. Two independent investigators reviewed all images with 1 investigator re-evaluating all images 4 weeks later. Wall characteristics of the middle cerebral artery, including plaque surface morphology, plaque location, plaque components, and burden were identified and measured. Results: Intraobserver and interobserver agreement were all substantial in identifying plaque surface irregularity (k = 0.741, 0.555-0.897; k = 0.685, 0.490-0.843; respectively) and intraplaque hemorrhage (k = 0.654, 0.446-0.838; k = 0.605, 0.369-0.792; respectively). Intraobserver agreement was substantial (k = 0.654) and interobserver agreement was moderate (k = 0.553) for the identification of plaque fibrous caps. The total intraobserver and interobserver reproducibility was almost excellent for the identification of plaque position. With regards to vessel area measurement at the site of maximal lumen narrowing, intraobserver and interobserver reproducibility was excellent (intraclass correlation coefficient was 0.886 and 0.885, respectively) and moderate for lumen area at the site of maximal lumen narrowing (intraclass correlation coefficient was 0.695 and 0.558, respectively). In addition, intraobserver and interobserver reproducibility was excellent for vessel area and lumen area measurements at the reference sites. Conclusions: The reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of artery wall characteristics was overall acceptable. However, the reliability for lumen area measurement at the maximum narrowing site and identification of the fibrous cap needs to be improved.

Background Icariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM. Methods 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting. Results Here, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis. Conclusion These results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.

Background and purpose: Traumatic brain injury (TBI) is a major disease without effective treatment. Recently, Tat-NR2B9c peptide emerged as a promising neuroprotective agent, but limited in clinical translation by it low brain penetrability. We synthesized Tat-NR2B9c loaded self-assembled activatable protein nanoparticles, termed TN-APNPs, and demonstrated that TN-APNPs enhanced the delivery of Tat-NR2B9c to the brain lesion in stroke. Herein we developed a novel approach to further engineering TN-APNPs for targeted delivery of Tat-NR2B9c to the injured brain with enhanced efficiency through conjugation of CAQK or CCAQK, a short peptide. Methods: Short peptide-conjugated TN-APNPs were synthesized by conjugated with CAQK or CCAQK via a click condensation reaction with CBT, then analyzed by dynamic light scattering, transmission electron microscopy and thrombin responsive assay. Characterization of short peptide-conjugated TN-APNPs were investigated by using cell excitotoxicity assay and transwell blood-brain-barrier model in vitro, and pharmacokinetics, IVIS imaging system and confocal analysis in TBI-bearing mice. Evaluation of therapeutic effects were analyzed by H&E staining, Elevated Plus Maze analysis and Rotarod test. Results: CAQK-conjugated TN-APNPs (C-TN-APNPs) and CCAQK-conjugated TN-APNPs (CC-TN-APNPs) were spherical in morphology and 30 nm in diameter. In vitro studies revealed that TN-APNPs, C-TN-APNPs and CC-TN-APNPs were responsive to thrombin cleavage, reduced the cytotoxicity of Tat-NR2B9c, and increased BBB permeability of Tat-NR2B9c. CC-TN-APNPs demonstrated the better circulation time, better targeting ability and penetrating efficiency to the injured brain, and better therapeutic benefits in vivo studies. Conclusion: This study demonstrated CC-TN-APNPs as a promising therapeutic for clinical management of TBI.

Purpose To construct the albumin-bilirubin (ALBI) grade and the Child-Turcotte-Pugh (CTP) score based on nomograms, as well as to develop an artificial neural network (ANN) to compare the prognostic performance of the 2 scores for hepatocellular carcinoma (HCC) that has undergone transarterial chemoembolization. Materials and Methods This multicentric retrospective study included patients with HCC who underwent transarterial chemoembolization monotherapy as an initial treatment at 4 institutions between January 2008 and December 2016. In the training cohort, significant risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The prognostic nomograms and ANN were established and then validated in 2 validation cohorts. Results A total of 838 patients (548, 115, and 175 in the training cohort and validation cohorts 1 and 2, respectively) were included. The median OS was 10.4, 15.7, and 9.2 months in the training cohort and validation cohorts 1 and 2, respectively. In the training cohort, both ALBI grade and CTP score were identified as significant risk factors. The ALBI grade and CTP score based on nomograms were established separately and showed similar prognostic performance when assessed externally in validation cohorts (C-index in validation cohort 1: 0.823 vs 0.802, P = .417; in validation cohort 2: 0.716 vs 0.729, P = .793). ANN showed that ALBI grade had higher importance on survival prediction than CTP score. Conclusions ALBI grade performs at least no worse than CTP score regarding survival prediction for HCC receiving transarterial chemoembolization. Considering the easy application, ALBI grade has the potential to be regarded as an alternative to CTP score.

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus.

Background The prognosis of lung cancer with synchronous brain metastasis (LCBM) is very poor, and patients often die within a short time. However, little is known about the early mortality and related factors in patients with LCBM. Methods Patients diagnosed with LCBM between 2010 and 2016 were enrolled from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate logistic regression analysis were used to identify significant independent prognostic factors, which were used to construct nomograms of overall and cancer-specific early death. Then, the prediction ability of the model was verified by receiver operating characteristic (ROC) curve. At last, the clinical application value of the model was tested through decision curve analysis (DCA). Results A total of 29,902 patients with LCBM were enrolled in this study. Among them, 13,275 (44.4%) patients had early death, and 11,425 (38.2%) cases died of lung cancer. The significant independent risk factors for overall and cancer-specific early death included age, race, gender, Gleason grade, histological type, T stage, N stage, bone metastasis, liver metastasis and marital status, which were used to construct the nomogram. The ROC curve demonstrated good predictive ability and clinical application value. The areas under the curve (AUC) of the training group was 0.793 (95% CI: 0.788–0.799) and 0.794 (95% CI: 0.788–0.799), in the model of overall and cancer-specific early death respectively. And the AUC of the validation group were 0.803 (95% CI: 0.788–0.818) and 0.806 (95% CI: 0.791–0.821), respectively. The calibration plots of the model showed that the predicted early death is consistent with the actual value. The DCA analysis indicated a good clinical application value of this model. Conclusions We established a comprehensive nomogram to predict early death in lung cancer patients with synchronous brain metastases. Nomograms may help oncologists develop better treatment strategies, such as clinical trials and hospice care.

Xiaonan Zhang,1,&ast; Huimin Fang,1,&ast; Zhigang Zeng,1 Kaijun Zhang,1 Zhanyi Lin,1,2 Gang Deng,1 Weiping Deng,1 Lichang Guan,1 Xuebiao Wei,1 Xinyi Li,2 Lei Jiang,1– 3 Lishu Xu1– 3 1Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, 510641, People’s Republic of China; 3The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Jiang; Lishu Xu Tel +86-20-83827812; +86-20-13660032429Email jianglei@smu.edu.cn; xulishu70@163.comPurpose: Gastric cancer is a common tumor type associated with nutritional and immune status. The aim of the current study was to investigate the prognostic value of a preoperative prognostic nutritional index (PNI), composed of nutritional factors and immune factors in elderly patients undergoing gastric cancer surgery.Patients and Methods: A total of 454 patients undergoing gastric cancer surgery were divided into two groups based on preoperative PNI scores: ≤ 45.1 (n = 307) and > 45.1 (n = 147). Survival analysis was performed using the Kaplan–Meier method and Log rank tests. Univariate and multivariate analyses were conducted to identify independent prognostic factors using a Cox proportional hazards model.Results: According to the X-tile program, the optimal cutoff value for predicting overall survival (OS) with the PNI was 45.1. The receiver operating characteristic analysis revealed that PNI exhibited 70.6% sensitivity and 56.5% speci&filig;city for predicting death during long-term follow-up. The cumulative incidence of postoperative 4-year mortality indicated that the risk of death increased significantly for PNI ≤ 45.1. In multivariate analysis, preoperative PNI was a significant independent predictor of mortality. In the age-stratified subgroup analysis, preoperative PNI was more sensitive for the old elderly subgroup than for the young elderly subgroup.Conclusion: Preoperative PNI is a sensitive and specific prognostic predictor among elderly patients undergoing gastric cancer surgery.Keywords: elderly patients, gastric cancer, prognostic nutritional index, radical gastrectomy

BackgroundDespite successful recanalization after endovascular treatment, many patients with acute ischemic stroke due to large vessel occlusion still show functional dependence, namely futile recanalization.MethodsPubMed and Embase were searched up to April 30, 2021. Studies that reported risk factors for futile recanalization following endovascular treatment of acute ischemic stroke were included. The mean difference (MD) or odds ratio (OR) and 95% confidence interval (95% CI) of each study were pooled for a meta-analysis.ResultsTwelve studies enrolling 2138 patients were included. The pooled analysis showed that age (MD 5.81, 95% CI 4.16 to 7.46), female sex (OR 1.40, 95% CI 1.16 to 1.68), National Institutes of Health Stroke Scale (NIHSS) score (MD 4.22, 95% CI 3.38 to 5.07), Alberta Stroke Program Early CT Score (ASPECTS) (MD −0.71, 95% CI −1.23 to –0.19), hypertension (OR 1.73, 95% CI 1.43 to 2.09), diabetes (OR 1.78, 95% CI 1.41 to 2.24), atrial fibrillation (OR 1.24, 95% CI 1.01 to 1.51), admission systolic blood pressure (MD 4.98, 95% CI 1.87 to 8.09), serum glucose (MD 0.59, 95% CI 0.37 to 0.81), internal carotid artery occlusion (OR 1.85, 95% CI 1.17 to 2.95), pre-treatment intravenous thrombolysis (OR 0.67, 95% CI 0.55 to 0.83), onset-to-puncture time (MD 16.92, 95% CI 6.52 to 27.31), puncture-to-recanalization time (MD 12.37, 95% CI 7.96 to 16.79), and post-treatment symptomatic intracerebral hemorrhage (OR 6.09, 95% CI 3.18 to 11.68) were significantly associated with futile recanalization.ConclusionThis study identified female sex, comorbidities, admission systolic blood pressure, serum glucose, occlusion site, non-bridging therapy, and post-procedural complication as predictors of futile recanalization, and also confirmed previously reported factors. Further large-scale prospective studies are needed.

The center of the stability island of super-heavy nuclei (SHN) is the subject of intense experimental and theoretical investigations and has potential technological applications. $$^{298}_{114}$$ Fl lies in the $$Z=$$ 114 isotopic chain as a persuasive candidate of the spherical double-magic nucleus in SHN, and in this study, the calculations of nuclear binding energies, one-nucleon and two-nucleon separation energies, $$\alpha $$ -decay energies, and the corresponding half-lives provide strong evidence for this point. These calculations within an improved Weizsacker-Skyrme nuclear mass model (WS*) were performed and compared with the calculations of the finite-range droplet model (FRDM2012) and experimental data for $$Z=114$$ isotopes and $$N=184$$ isotones. Concurrently, the corresponding single-particle levels in a Woods-Saxon potential well with a spin-orbit term are calculated, which can be used as a powerful indicator to identify the shell effects existing in $$^{298}_{114}$$ Fl. Both the study of the properties of the isotopic chain and microphysical quantities provide a vital signal that $$^{298}_{114}$$ Fl is a spherical double-magic nucleus and also the center of the SHN.

Pancreatic ductal adenocarcinoma (PDCA) is a leading cause of cancer death in the US. Patients diagnosed with PDCA generally present with advanced disease with poor prognosis and limited treatment options. African American patients have higher incidence and mortality of PDCA than Caucasian American or any other ethnic group. Different factors have been attributed to contribute to this health disparity, among them higher incidence of Diabetes Mellitus type 2. To address the need for new therapeutic approaches, we note epidemiologic reports that patients with diabetes mellitus-type 2 treated with the biguanide drug metformin, but not other antidiabetic drugs, have a reduced risk of PDCA and an increased survival rate among those with PDCA. The main physiologic effect of metformin is to lower blood glucose and reduce hyperinsulinemia associated with insulin resistance. In the cell, metformin stimulates AMP-activated protein kinase (AMPK) that in turn inhibits mTORC1 which integrates signals from an array of intracellular pathways to regulate cell growth. Recent clinical trials describe modest antiproliferative effects from use of neoadjuvant metformin, but no significant clinical benefit occurred when metformin was dosed at glycemic control levels in patients with advanced cancers. These findings suggest that development of more potent anticancer analogues of metformin may help to boost clinical benefit and patient survival. Hence, we have designed new biguanide analogues of metformin, and screening of these compounds in preclinical PDCA models show that selected analogues are more efficacious in blocking tumor progression than parental metformin at lower doses. Using proliferation assays in vitro, PDCA cells (Panc 1, MIA Paca-2) were treated 72-hrs with metformin or analogues, and greater dose-dependent inhibition of PDCA cell proliferation was found with analogues as compared to metformin (P

PurposeGiven that the novel coronavirus disease (COVID-19) pandemic has disrupted operations globally, an institution’s ability to repeat transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has also been affected. The aim of this study was to evaluate the impact of the COVID-19 on the intervals and outcomes of TACE in HCC patients.Materials and MethodsThis retrospective study included 154 HCC patients who underwent follow-up after TACE treatment from January 2020 to March 2020 (n = 71, study group) and January 2019 to March 2019 (n = 83, control group) at two institutions in China. The endpoints included the follow-up interval and overall response rate (ORR). Multivariate logistic regression analyses were performed to identify independent risk factors for a worse ORR. The cut-off point was determined to divide follow-up durations into long- and short-intervals.ResultsThe median follow-up interval was 82.0 days (IQR, 61–109) in the study group, which was significantly longer than 66.0 days (IQR, 51–94) in the control group (P = 0.004). The ORR was 23.9 and 39.8% in the study and control group, respectively (P = 0.037). The cut-off value was 95 days. The grouping (OR, 2.402; 95% CI, 1.040–5.546; P = 0.040), long interval (OR, 2.573; 95% CI, 1.022–6.478; P = 0.045), and China liver cancer staging system (OR, 2.500; 95% CI, 1.797–3.480; P <0.001) were independent predictors for the efficacy of TACE treatment.ConclusionsThe COVID-19 pandemic causes a longer follow-up interval in general, which may further lead to a lower ORR in HCC patients. Those with a follow-up interval of >95 days tend to have a worse prognosis.

Background: The prognosis of middle-aged patients with CRC treated by laparoscopic resection (LR) is unclear. This study aimed to evaluate the survival outcomes of LR compared with open resection (OR) for patients with CRC and 45-65 years of age.Methods: This retrospective cohort study used the data from a database of all consecutive colorectal resections performed between January 2009 and December 2017. Propensity score matching (PSM) was done to handle the selection bias based on age, gender, body mass index (BMI), tumor location, AJCC stage, and admission year. Univariate and multivariate COX regression model was used to identify risk factors of overall survival (OS) and progression-free survival (PFS).Results: After PSM, 217 patients were included in each group. There were no differences in OS and PFS between the two groups (all P>0.05). There was less blood loss for LR (PConclusions: In middle-aged patients with CRC, OR and LR have similar survival outcomes and complications.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) leads to severe disability and functional dependence. However, no reliable method exists to predict the clinical prognosis after aSAH. Thus, this study aimed to develop a web-based dynamic nomogram to precisely evaluate the risk of poor outcomes in patients with aSAH.Methods: Clinical patient data were retrospectively analyzed at two medical centers. One center with 126 patients was used to develop the model. Least absolute shrinkage and selection operator (LASSO) analysis was used to select the optimal variables. Multivariable logistic regression was applied to identify independent prognostic factors and construct a nomogram based on the selected variables. The C-index and Hosmer–Lemeshow p-value and Brier score was used to reflect the discrimination and calibration capacities of the model. Receiver operating characteristic curve and calibration curve (1,000 bootstrap resamples) were generated for internal validation, while another center with 84 patients was used to validate the model externally. Decision curve analysis (DCA) and clinical impact curves (CICs) were used to evaluate the clinical usefulness of the nomogram.Results: Unfavorable prognosis was observed in 46 (37%) patients in the training cohort and 24 (29%) patients in the external validation cohort. The independent prognostic factors of the nomogram, including neutrophil-to-lymphocyte ratio (NLR) (p = 0.005), World Federation of Neurosurgical Societies (WFNS) grade (p = 0.002), and delayed cerebral ischemia (DCI) (p = 0.0003), were identified using LASSO and multivariable logistic regression. A dynamic nomogram (https://hu-ping.shinyapps.io/DynNomapp/) was developed. The nomogram model demonstrated excellent discrimination, with a bias-corrected C-index of 0.85, and calibration capacities (Hosmer–Lemeshow p-value, 0.412; Brier score, 0.12) in the training cohort. Application of the model to the external validation cohort yielded a C-index of 0.84 and a Brier score of 0.13. Both DCA and CIC showed a superior overall net benefit over the entire range of threshold probabilities.Conclusion: This study identified that NLR on admission, WFNS grade, and DCI independently predicted unfavorable prognosis in patients with aSAH. These factors were used to develop a web-based dynamic nomogram application to calculate the precise probability of a poor patient outcome. This tool will benefit personalized treatment and patient management and help neurosurgeons make better clinical decisions.

Introduction: Recently, NA1, a peptide designed to protect neurons against NMDA receptor-mediated excitotoxicity, demonstrated promise for acute stroke treatment. Enhanced efficiency of peptide delivery may result in improved efficacy. Hypothesis: The bioactive fragment of NA1 is nine amino acids of the carboxyl tail of GluN2B. Delivery of NR2B9c to cells in the brain is achieved through fusion with TAT, a peptide that binds to biological membranes without selectivity. We hypothesize that enhancing targeted delivery of NA1 to the ischemic brain improve the efficacy of NA1. Methods: We previously identified betulinic acid (BA) forming nanoparticles (NPs) as a novel formulation of stroke treatment delivery. After intravenous administration, BA NP penetrate the ischemic brain, reduce ischemia-induced infarction as an antioxidant agent, and allow for encapsulation and delivery of drugs. In this study, we engineered BA NPs for improved drug delivery preferentially to the ischemic brain through surface conjugation of AMD3100, and for acid-triggered drug release to selectively in the ischemic region, which is known to be acidic, through chemical modification. The resulting acid responsive, stroke- targeting antioxidant NPs, or ARSTA NPs, were evaluated for stroke treatment in the mouse transient middle cerebral artery occlusion (MCAO) model either alone or in combination with NA1, based on changes of infarct volumes, edema, mortality, and outcomes. Results: We found that ARSTA NPs enabled targeted delivery of NA1 preferentially to the ischemic brain and allowed for prompt drug release. We showed that intravenous delivery of 50 ug NA1 (or 1nM/g) encapsulated in 1 mg ARSTAs effectively reduced infarct volumes by 69.8%, edema by 60.3%, mortality (median survival >14 days). In contrast, delivery of ARSTA NPs alone (52.2%, 30.2%, 10) or NA1 (0.7%, 3.3%, 6 days) alone at a comparable dose exhibited significantly less efficacy. Consistently, treatment with NA1-loaded ARSTAs improved neurological outcomes in a degree significantly greater than that by either ARSTA NPs or NA1 alone. Conclusion: BA-NP encapsulating NA-1 may represent a novel platform for improved delivery to the ischemic brain. Improved delivery may result in improved efficacy.