ITGAM is a critical gene in ischemic stroke.

BACKGROUND: Globally, ischemic stroke (IS) is ranked as the second most prevailing cause of mortality and is considered lethal to human health. This study aimed to identify genes and pathways involved in the onset and progression of IS. METHODS: GSE16561 and GSE22255 were downloaded from the Gene Expression Omnibus (GEO) database, merged, and subjected to batch effect removal using the ComBat method. The limma package was employed to identify the differentially expressed genes (DEGs), followed by enrichment analysis and protein-protein interaction (PPI) network construction. Afterward, the cytoHubba plugin was utilized to screen the hub genes. Finally, a ROC curve was generated to investigate the diagnostic value of hub genes. Validation analysis through a series of experiments including qPCR, Western blotting, TUNEL, and flow cytometry was performed. RESULTS: The analysis incorporated 59 IS samples and 44 control samples, revealing 226 DEGs, of which 152 were up-regulated and 74 were down-regulated. These DEGs were revealed to be linked with the inflammatory and immune responses through enrichment analyses. Overall, the ROC analysis revealed the remarkable diagnostic potential of ITGAM and MMP9 for IS. Quantitative assessment of these genes showed significant overexpression in IS patients. ITGAM modulation influenced the secretion of critical inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, and had a distinct impact on neuronal apoptosis. CONCLUSIONS: The inflammation and immune response were identified as potential pathological mechanisms of IS by bioinformatics and experiments. In addition, ITGAM may be considered a potential therapeutic target for IS.

Profiling of immune infiltration landscape of ruptured intracranial aneurysm.

BACKGROUND: Previous research has indicated that the rupture of intracranial aneurysm (IA) is a significant contributor to mortality from stroke. The objective of this present study was to examine the infiltration patterns in ruptured intracranial aneurysm (RIA), with the aim of generating insights that could inform the development of effective immunotherapeutic approaches. METHODS: To achieve this, we obtained Gene Expression Omnibus datasets pertaining to ruptured aneurysms, encompassing a total of 19 unruptured intracranial aneurysms (UIA) and 27 RIA. Subsequently, we conducted differential gene analysis and immune cell analysis specifically for the RIA. RESULTS: According to the conducted studies, the analysis has identified 10 hub genes within key modules. Through the utilization of Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology terms analyses, it has been established that genes exhibiting differential expression are associated with immune cell infiltration in the aneurysm wall. Furthermore, the implementation of the CIBERSORT algorithm has revealed that there are 22 distinct immune cells between RIA and tissues of UIA. IA samples contained a higher proportion of macrophages M1, mast cells resting, and CD4 naive T cells, while macrophages M0 and neutrophils were relatively lower in RIA compared with those in UIA. CONCLUSION: The current study initially identified highly conservative hub genes and immune cell infiltration patterns in IA. Data presented in the current study improved understanding of immune genes that drive IA which can be exploited in development of effective immunotherapies.

Identification of qGL4.1 and qGL4.2, two closely linked QTL controlling grain length in rice.

Grain size is an important appearance quality trait in rice, which also affects grain yield. In this study, a recombinant inbred line (RIL) population derived from a cross between indica variety 9311 and japonica variety Cypress was constructed. And 181 out of 600 RILs were sequenced, and a high-density genetic map containing 2842 bin markers was constructed, with a total map length of 1500.6 cM. A total of 10 quantitative trait loci (QTL) related to grain length (GL), grain width (GW), grain length-to-width ratio (LWR), and 1000-grain weight (TGW) were detected under two environments. The genetic effect of qGL4, a minor QTL for GL and TGW, was validated using three heterogeneous inbred family (HIF) segregation populations. It was further dissected into two closed linked QTL, qGL4.1 and qGL4.2. By progeny testing, qGL4.1 and qGL4.2 were successfully delimited to intervals of 1304-kb and 423-kb, respectively. Our results lay the foundation for the map-based cloning of qGL4.1 and qGL4.2 and provide new gene resources for the improvement of grain yield and quality in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01447-y.

Biodegradable Cardiac Occluder with Surface Modification by Gelatin-Peptide Conjugate to Promote Endogenous Tissue Regeneration.

Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long-term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l-lactic acid)-gelatin-A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein-derived peptides (A5G81) to the surface of polydioxanone and poly (l-lactic acid) fibers. The polymer microfiber-biomacromolecule-peptide frame with biophysical and biochemical cues could orchestrate the biomaterial-host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti-inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell-biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell-material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.

A case of brain arteriovenous malformation treated by high-pressure cooker technique assisted with anhydrous alcohol embolization: A case report.

RATIONALE: Brain arteriovenous malformations (BAVMs) are a relatively rare but very dangerous developmental abnormality of the blood vessels. Intracranial hemorrhage is the most common clinical manifestation of BAVMs, and has a high rate of rebleeding, disability, and mortality, which has a serious impact on patients' quality of life and working ability. Endovascular intervention was a new technique that emerged in recent years. Anhydrous ethanol embolization has been used with satisfactory results in the treatment of peripheral arteriovenous malformations, but there is a lack of practice in the treatment of BAVMs. We tried to treat BAVMs by embolizing malformed vessels with anhydrous alcohol in order to provide a safe and effective treatment for more patients with BAVMs. PATIENT CONCERNS: The patient was admitted to our hospital in the emergency department with "sudden onset of headache for more than 4 hours." At the time of admission, the patient was clearly conscious, not mentally alert, spoke fluently, and had a normal level of orientations. The direct and indirect responses to light were blunted. The patient's muscle strength, muscle tone, and sensation of the extremities were normal. National Institute of Health stroke scale score was 1. Head computed tomography at the onset suggested a right occipital hemorrhage and hematoma formation. DIAGNOSES: Brain arteriovenous malformations (BAVMs) were suspected based on preoperative imaging findings. INTERVENTIONS: After obtaining the consent of the patient and their family members, we performed whole brain angiography to determine the location of the lesion, and then, with the help of high-pressure cooker technology, targeted embolization of interventional BAVM was performed. The high-pressure cooker technology was achieved through spring coils, and the embolic material was anhydrous ethanol. OUTCOMES: The surgery was successful, and the patient recovered well without recurrence. LESSON: The successful performance of this surgery illustrates the feasibility of anhydrous ethanol-targeted ablation for BAVMs.

PFT-α protects the blood-brain barrier through the Wnt/ß-catenin pathway after acute ischemic stroke.

The dysfunction of blood-brain barrier (BBB) plays a pivotal role in brain injury and subsequent neurological deficits of ischemic stroke. The current study aimed to examine the potential correlation between p53 inhibition and the neuroprotective effect of on the BBB. Rat middle cerebral artery occlusion and reperfusion model (MCAO/R) and oxygen-glucose deprivation/re-oxygenation model (OGD/R) were employed to simulate cerebral ischemia-reperfusion (CI/R) injury occurrence in vivo and in vitro. mNSS and TTC staining were applied to evaluate neurological deficits and brain infarct volumes. Evans blue (EB) staining was carried out to examine the permeability of BBB. RT-qPCR and Western blot to examine the mRNA and protein levels. Cell viabilities were detected by CCK-8. Flow cytometry and ELISA assay were employed to examine apoptosis and neuroinflammation levels. TEER value and sodium fluorescein were carried out to explore the permeability of HBMEC cells. PFT-α inhibited P53 and promoted the expression of ß-catenin and cyclin D1, which were reversed by DKK1. PFT-α inhibited neurological deficits, brain infarct volume, neuroinflammation, apoptosis, and BBB integrity than the MCAO/R rats; however, this inhibition was reversed by DKK1. PFT-α promoted OGD/R-induced cell viability in NSCs, and suppressed inflammation and apoptosis, but DKK1 weakened the effect of PFT-α. PFT-α increased OGD/R-induced TEER values in cerebrovascular endothelial cells, inhibited sodium fluorescein permeability, and increased the mRNA levels of tight junction protein, but they were all attenuated by DKK1. PFT-α protects the BBB after acute ischemic stroke via the Wnt/ß-catenin pathway, which in turn improves neurological function.

Middle Meningeal Artery Embolization Combined With Endoscopic Treatment for Chronic Subdural Hematoma.

OBJECTIVE: To explore the clinical feasibility of middle meningeal artery (MMA) embolization combined with endoscopic treatment for new or recurrent chronic subdural hematoma (CSDH). METHODS: Twenty patients with CSDH treated in the Binzhou Medical University Hospital from June 2020 to October 2022 were analyzed retrospectively. The clinical information, prognosis, imaging results, and surgical results of the patients were collected and analyzed. The authors first performed MMA embolization, and then endoscopic treatment of CSDH was performed after successful embolization of MMA. Results: All 20 patients with CSDH were successfully treated with MMA embolization combined with endoscope-assisted evacuation. The symptoms of all patients were relieved, no surgical complications occurred, and no rebleeding and recurrence were found in follow-up computed tomography. CONCLUSION: Middle meningeal artery embolization combined with endoscopic treatment of CSDH has a good clinical effect, and it may prevent postoperative recurrence.

The diagnostic value of circulating miR-532-5p in patients with asymptomatic carotid artery stenosis and its predictive significance for the occurrence of cerebral ischaemic events.

Introduction: Circulating microRNAs (miRNAs) are widely identified as promising and novel biomarkers for the diagnosis of human diseases. This study investigated the clinical value of miR-532-5p for asymptomatic carotid artery stenosis (CAS) patients and detected its predictive value for the occurrence of future cerebral ischaemic events (CIE). Material and methods: Serum expression of miR-532-5p was measured using qRT-PCR. A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of miR-532-5p in asymptomatic CAS patients, and the area under the curve (AUC) was calculated. The predictive value of miR-532-5p for the occurrence of CIE was evaluated by using Kaplan-Meier methods and Cox regression analysis. Results: Serum expression of miR-532-5p was identified to be significantly decreased in CAS patients compared with healthy controls. The ROC curve with an AUC of 0.903 indicated high diagnostic accuracy of serum miR-532-5p expression in asymptomatic CAS patients. As Kaplan-Meier analysis results suggested, more CIE events were observed in cases with low miR-532-5p expression. Low miR-532-5p and high degree of carotid stenosis were independent factors for the occurrence of CIE in asymptomatic CAS patients. Conclusions: The study suggests the potential clinical value of miR-532-5p for the early diagnosis of asymptomatic CAS patients. MiR-532-5p might have predictive value for the risk of future CIE in asymptomatic CAS patients.

Three-dimensional laser combined with C-arm computed tomography-assisted puncture of intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is the deadliest subtype of stroke, with a 30-day case fatality rate of approximately 40%. Timely and accurate treatment is essential to facilitate recovery. The introduction of stereotactic instruments and navigation systems has greatly improved the accuracy of surgical treatment. In this study, we explored the application and effects of a three-dimensional (3D) laser combined with C-arm computed tomography (CT) on ICH puncture. Materials and methods: According to the principle of randomness, 118 patients with ICH were divided into control and experimental groups. The control group was treated with CT-guided puncture, and the experimental group was treated with 3D laser combined with C-arm CT puncture. The hematoma clearance rates at 3, 5, and 7 days after surgery and the prognosis at 1, 3, and 6 months after surgery were compared between the two groups. Results: The hematoma clearance rates of the group using 3D laser combined with C-arm CT at 3, 5, and 7 days after surgery were significantly higher than those of the control group, and the difference was statistically significant (p < 0.05). One month postoperatively, the daily living ability (ADL) grading and recovery of the patients in the test group was significantly better than those of the control group (p < 0.05), but there was no statistically significant difference in ADL 3 and 6 months after surgery (p > 0.05). Conclusion: 3D laser combined with C-arm CT puncture has the advantages of real-time guidance, accurate positioning, and simple operation. It is an effective minimally invasive surgical method that is easy to master.

CRISPR/Cas9-mediated editing of Wx and BADH2 genes created glutinous and aromatic two-line hybrid rice.

Amylose content (AC) is one of the physicochemical indexes of rice quality, which is largely determined by the Waxy (Wx) gene. Fragrance in rice is favored because it adds good flavor and a faint scent. Loss of function of the BADH2 (FGR) gene promotes the biosynthesis of 2-acetyl-1-pyrroline (2AP), which is the main compound responsible for aroma in rice. Here, we used a CRISPR/Cas9 system to simultaneously knock out Wx and FGR genes in 1892S and M858, which are the parents of an indica two-line hybrid rice, Huiliangyou 858 (HLY858). Four T-DNA-free homozygous mutants (1892Swxfgr-1, 1892Swxfgr-2, M858wxfgr-1, and M858wxfgr-2) were obtained. The 1892Swxfgr and M858wxfgr were crossed to generate double mutant hybrid lines HLY858wxfgr-1 and HLY858wxfgr-2. Size-exclusion chromatography (SEC) data indicated that true AC of the wx mutant starches ranged from 0.22 to 1.63%, much lower than those of the wild types (12.93 to 13.76%). However, the gelatinization temperature (GT) of the wx mutants in backgrounds of 1892S, M858, and HLY858 were still high, and showed no significant differences with the wild type controls. The aroma compounds 2AP content in grains of HLY858wxfgr-1 and HLY858wxfgr-2 were 153.0 µg/kg and 151.0 µg/kg, respectively. In contrast, 2AP was not detected in grains of HLY858. There were no significant differences in major agronomic traits between the mutants and HLY858. This study provides guidelines for cultivation of ideal glutinous and aromatic hybrid rice by gene editing.

Extracellular Matrix/Glycopeptide Hybrid Hydrogel as an Immunomodulatory Niche for Endogenous Cardiac Repair after Myocardial Infarction.

The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage-endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.

Transfrontal External Ventricular Drainage Combined with OMMAYA Sac Implantation under Laser Navigation were Performed: A Technical Note.

BACKGROUND: Hydrocephalus caused by spontaneous intracerebral hemorrhage (ICH) is an independent risk factor with adverse effects on the progression of the disease. Until now, the choice of intraventricular catheter placement and intraventricular fibrinolysis (IVF) has been mainly based on the personal experience of the neurosurgeon. OBJECTIVE: We will introduce the clinical effect of the new external ventricular drainage (EVD), an independent innovation of our medical center, on ICH patients, hoping to inspire more neurosurgeons to apply our method. METHODS: In this open retrospective study, We analyzed the clinical data, radiological manifestations, and prognostic scores of 10 patients with the spontaneous intracerebral hemorrhage who received transfrontal lateral ventricle puncture and drainage under laser navigation in our hospital. RESULTS: A total of 10 patients with an average age of 58.10±9.97 years were enrolled for emergency surgery. All operations were completed according to the consensus specifications. It took 11.25±3.81 days for the intracranial pressure to return to normal. On admission, patients had a median GCS of 10. The median preoperative GCS was 8. The median GCS at discharge score was 15. At discharge, the median NIHSS score was 4. After 6 months of follow-up, patients had a median NIHSS score of 4. At discharge, the median ADL score of patients was 85. After 6 months of follow-up, the median ADL score of the patients was 95. CONCLUSION: In treating patients with ICH, the emergency treatment of transfrontal external ventricular drainage combined with OMMAYA sac implantation under laser navigation is a surgical method worthy of further study.

Laser navigation combined with XperCT technology-assisted puncture of basal ganglia intracerebral hemorrhage.

Basal ganglia hemorrhage, which is characterized by excessive incapacity charge and high mortality rates, is surgically treated by minimally invasive hematoma puncture and drainage. We aimed at determining the efficacy of laser-guided minimally invasive hematoma puncture and drainage for treatment of basal ganglia hemorrhage. A total of 61 patients with hypertensive basal ganglia hemorrhage were recruited at the Binzhou Medical University Hospital, between October 2019 and January 2021, and their clinical information retrospectively analyzed. Based on the surgical approach used, patients were assigned into either laser navigation or small bone window groups depending on the surgical approach. Then, we compared the operation times, intraoperative blood loss, clinic stay, Glasgow Outcome Score (GOS) rating at 30 days, Barthel index (BI) rating at 6 months, postoperative pneumonia incidences, and intracranial contamination complications between groups. Intraoperative blood loss, operation time, and sanatorium were significantly low in laser navigation group, relative to the small bone window group. At the same time, there were no significant differences between the groups with regard to postoperative hematoma volume, lung contamination, cerebrospinal fluid (CSF) leak, and intracranial contamination, as well as the 6-month BI and 30-day GOS rating. There were no deaths in either group. Compared with the traditional small bone window surgery, laser-guided puncture and drainage is a low-cost, accurate, and safe method for the treatment of basal ganglia hemorrhage, which is suitable for promotion in developing countries and economically underdeveloped areas.

Transcatheter closure of perimembranous ventricular septal defect using a novel fully bioabsorbable occluder: multicenter randomized controlled trial.

Although the use of bioabsorbable occluder is expected to reduce the risk of metal occluder-related complications, it has not been approved due to incomplete degradation and new complications. Novel fully bioabsorbable occluders were designed to overcome such limitations. The aim of this study was to investigate the efficacy and safety of a fully biodegradable occluder in patients with ventricular septal defects. 125 patients with perimembranous ventricular septal defect (VSD) larger than 3 mm were screened from April 2019 to January 2020 in seven centers. 108 patients were enrolled and randomized into the bioabsorbable occluder group (n = 54 patients) and nitinol occluder group (n = 54). A non-inferiority design was utilized and all patients underwent transcatheter device occlusion. Outcomes were analyzed with a 24-month follow-up. All patients were successfully implanted and completed the trial. No residual shunt >2 mm was observed during follow-up. Transthoracic echocardiography showed a hyperechoic area corresponding to the bioabsorbable occluder which decreased primarily during the first year after implantation and disappeared within 24 months. Postprocedural arrhythmia was the only occluder-related complication with an incidence of 5.56% and 14.81% for the bioabsorbable and nitinol groups, respectively (P = 0.112). The incidence of sustained conduction block was lower in the bioabsorbable occluder group (0/54 vs. 6/54, P = 0.036) at 24-month follow-up. In conclusion, the novel fully bioabsorbable occluder can be successfully and safely implanted under echocardiography guidance and reduce the incidence of sustained postprocedural arrythmia. The efficacy and safety of this fully biodegradable occluder are non-inferior to that of a traditional nitinol one.

Hypertensive intracerebral hemorrhage: Which one should we choose between laser navigation and 3D navigation mold?

Background: Hypertensive intracerebral hemorrhage (HICH) is a severe life-threatening disease, and its incidence has gradually increased in recent years. Due to the particularity and diversity of its bleeding sites, the early treatment of hematoma needs to be more meticulous and accurate, and minimally invasive surgery is often one of the measures that are commonly adopted now. The lower hematoma debridement and the navigation template created by 3D printing technology were compared in the external drainage of a hypertensive cerebral hemorrhage. Then the effect and feasibility of the two operations were explicitly evaluated. Material and methods: We performed a retrospective analysis of all eligible patients with HICH who underwent laser-guided hematoma evacuation or hematoma puncture under 3D-navigated molds at the Affiliated Hospital of Binzhou Medical University from January 2019 to January 2021. A total of 43 patients were treated. Twenty-three patients were treated with laser navigation-guided hematoma evacuation (group A); 20 patients were treated with 3D navigation minimally invasive surgery (group B). A comparative study was conducted between the two groups to evaluate the preoperative and postoperative conditions. Results: The preoperative preparation time of the laser navigation group was significantly shorter than that of the 3D printing group. The operation time of the 3D printing group was better than that of the laser navigation group (0.73 ± 0.26 h vs. 1.03 ± 0.27 h P = 0.00070). In the improvement in the short-term postoperatively, there was no statistically significant difference between the laser navigation group and the 3D printing group (Median hematoma evacuation rate P = 0.14); And in the three-month follow-up NIHESS score, there was no significant difference between the two (P = 0.82). Conclusion: Laser-guided hematoma removal is more suitable for emergency operations, with real-time navigation and shortened preoperative preparation time; hematoma puncture under a 3D navigation mold is more personalized and shortens the intraoperative time course. There was no significant difference in therapeutic effect between the two groups.

Identification of Chromatin Regulatory Factors Related to Immunity and Treatment of Alzheimer's Disease.

Alzheimer's disease is one of the common neurodegenerative diseases in the elderly, which mainly manifests as progressively severe cognitive impairment, which seriously affects the quality of life of patients. Chromatin regulators have been shown to be associated with a variety of biological processes, and we mainly explore the relationship between chromatin regulators and Alzheimer's disease. Eight hundred seventy chromatin regulators were collected from previous studies, and data related to Alzheimer's disease patients were downloaded from the GEO database. Finally, we screened chromatin regulators related to Alzheimer's disease immunity, established prediction models, and screened related drugs and miRNAs. We screened 160 differentially expressed CRs, constructed an interaction network, obtained 10 hub genes, successfully constructed a prediction model based on immune-related 5 CRs, and obtained 520 related drugs and 3 related miRNA, which provided an idea for the treatment of Alzheimer's disease. Our study identified 5 chromatin regulators related to Alzheimer's disease, which are expected to be new targets for Alzheimer's disease immunotherapy.

An enriched environment improves long-term functional outcomes in mice after intracerebral hemorrhage by mechanisms that involve the Nrf2/BDNF/glutaminase pathway.

Post-stroke depression exacerbates neurologic deficits and quality of life. Depression after ischemic stroke is known to some extent. However, depression after intracerebral hemorrhage (ICH) is relatively unknown. Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective effects in animal models, but its impact after ICH is unknown. In this study, we investigated the effect of EE on long-term functional outcomes in mice subjected to collagenase-induced striatal ICH. Mice were subjected to ICH with the standard environment (SE) or ICH with EE for 6 h/day (8:00 am-2:00 pm). Depressive, anxiety-like behaviors and cognitive tests were evaluated on day 28 with the sucrose preference test, tail suspension test, forced swim test, light-dark transition experiment, morris water maze, and novel object recognition test. Exposure to EE improved neurologic function, attenuated depressive and anxiety-like behaviors, and promoted spatial learning and memory. These changes were associated with increased expression of transcription factor Nrf2 and brain-derived neurotrophic factor (BDNF) and inhibited glutaminase activity in the perihematomal tissue. However, EE did not change the above behavioral outcomes in Nrf2-/- mice on day 28. Furthermore, exposure to EE did not increase BDNF expression compared to exposure to SE in Nrf2-/- mice on day 28 after ICH. These findings indicate that EE improves long-term outcomes in sensorimotor, emotional, and cognitive behavior after ICH and that the underlying mechanism involves the Nrf2/BDNF/glutaminase pathway.

A fully biodegradable polydioxanone occluder for ventricle septal defect closure.

Ventricular septal defect (VSD) is one of the commonest congenital heart diseases (CHDs). Current occluders for VSD treatment are mainly made of nitinol, which has the risk of nickel allergy, persistent myocardial abrasion and fatal arrythmia. Herein, a fully biodegradable polydioxanone (PDO) occluder equipped with a shape line and poly-l-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker. PDO occluder showed great mechanical strength, fatigue resistance, geometry fitness, biocompatibility and degradability. In a rat subcutaneous implantation model, PDO filaments significantly alleviated inflammation response, mitigated fibrosis and promoted endothelialization compared with nitinol. The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up, demonstrating the biodegradable PDO occluder could not only effectively repair VSD, induce cardiac remodeling but also address the complications associated with metal occluders. Furthermore, a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up. Collectively, the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.