Exploring Present and Future Directions in Nano-Enhanced Optoelectronic Neuromodulation.

Electrical neuromodulation has achieved significant translational advancements, including the development of deep brain stimulators for managing neural disorders and vagus nerve stimulators for seizure treatment. Optoelectronics, in contrast to wired electrical systems, offers the leadless feature that guides multisite and high spatiotemporal neural system targeting, ensuring high specificity and precision in translational therapies known as "photoelectroceuticals". This Account provides a concise overview of developments in novel optoelectronic nanomaterials that are engineered through innovative molecular, chemical, and nanostructure designs to facilitate neural interfacing with high efficiency and minimally invasive implantation.This Account outlines the progress made both within our laboratory and across the broader scientific community, with particular attention to implications in materials innovation strategies, studying bioelectrical activation with spatiotemporal methods, and applications in regenerative medicine. In materials innovation, we highlight a nongenetic, biocompatible, and minimally invasive approach for neuromodulation that spans various length scales, from single neurons to nerve tissues using nanosized particles and monolithic membranes. Furthermore, our discussion exposes the critical unresolved questions in the field, including mechanisms of interaction at the nanobio interface, the precision of cellular or tissue targeting, and integration into existing neural networks with high spatiotemporal modulation. In addition, we present the challenges and pressing needs for long-term stability and biocompatibility, scalability for clinical applications, and the development of noninvasive monitoring and control systems.In addressing the existing challenges in the field of nanobio interfaces, particularly for neural applications, we envisage promising strategic directions that could significantly advance this burgeoning domain. This involves a deeper theoretical understanding of nanobiointerfaces, where simulations and experimental validations on how nanomaterials interact spatiotemporally with biological systems are crucial. The development of more durable materials is vital for prolonged applications in dynamic neural interfaces, and the ability to manipulate neural activity with high specificity and spatial resolution, paves the way for targeting individual neurons or specific neural circuits. Additionally, integrating these interfaces with advanced control systems, possibly leveraging artificial intelligence and machine learning algorithms and programming dynamically responsive materials designs, could significantly ease the implementation of stimulation and recording. These innovations hold the potential to introduce novel treatment modalities for a wide range of neurological and systemic disorders.

Devastating the Supply Wagons: Multifaceted Liposomes Capable of Exhausting Tumor to Death via Triple Energy Depletion.

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.

Ionic Peltier effect in Li-ion electrolytes.

The coupled transport of charge and heat provide fundamental insights into the microscopic thermodynamics and kinetics of materials. We describe a sensitive ac differential resistance bridge that enables measurements of the temperature difference on two sides of a coin cell with a resolution of better than 10 µK. We use this temperature difference metrology to determine the ionic Peltier coefficients of symmetric Li-ion electrochemical cells as a function of Li salt concentration, solvent composition, electrode material, and temperature. The Peltier coefficients Π are negative, i.e., heat flows in the direction opposite to the drift of Li ions in the applied electric field, large, -Π > 30 kJ mol-1, and increase with increasing temperature at T > 300 K. The Peltier coefficient is approximately constant on time scales that span the characteristic time for mass diffusion across the thickness of the electrolyte, suggesting that heat of transport plays a minor role in comparison to the changes in partial molar entropy of Li at the interface between the electrode and electrolyte. Our work demonstrates a new platform for studying the non-equilibrium thermodynamics of electrochemical cells and provides a window into the transport properties of electrochemical materials through measurements of temperature differences and heat currents that complement traditional measurements of voltages and charge currents.

Phosphorylation: new star of pathogenesis and treatment in steatotic liver disease.

Steatotic liver disease poses a serious threat to human health and has emerged as one of the most significant burdens of chronic liver disease worldwide. Currently, the research mechanism is not clear, and there is no specific targeted drug for direct treatment. Phosphorylation is widely regarded as the most common type of protein modification, closely linked to steatotic liver disease in previous studies. However, there is no systematic review to clarify the relationship and investigate from the perspective of phosphorylation. Phosphorylation has been found to mainly regulate molecule stability, affect localization, transform molecular function, and cooperate with other protein modifications. Among them, adenosine 5'-monophosphate-activated protein kinase (AMPK), serine/threonine kinase (AKT), and nuclear factor kappa-B (NF-kB) are considered the core mechanisms in steatotic liver disease. As to treatment, lifestyle changes, prescription drugs, and herbal ingredients can alleviate symptoms by influencing phosphorylation. It demonstrates the significant role of phosphorylation as a mechanism occurrence and a therapeutic target in steatotic liver disease, which could be a new star for future exploration.

Cutting-Edge HEK293T Protein-Integrated Lipid Nanostructures: Boosting Biocompatibility and Efficacy.

Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards.

A Bioengineered Nanovesicle Vaccine Boosts T-B cell Interaction for Immunotherapy of Echinococcus multilocularis.

Alveolar echinococcosis (AE) is a zoonotic parasitic disease, resulting from being infected with the metacestode larvae of the tapeworm Echinococcus multilocularis (E. multilocularis). Novel prophylactic and therapeutic interventions are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. Bioengineered nano cellular membrane vesicles are widely used for displaying the native conformational epitope peptides because of their unique structure and biocompatibility. In this study, four T-cells and four B-cells dominant epitope peptides of E. multilocularis with high immunogenicity were engineered into the Vero cell surface to construct a membrane vesicle nanovaccine for the treatment of AE. The results showed that the nanovesicle vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit E. multilocularis infection. This study presents for the first time a nanovaccine strategy that can completely eliminate the burden of E. multilocularis.

Prediction of compressive comfort of graded compression sleeves based on calf feature classification.

This study explored the relationship between the design of calf compression sleeves and the comfort of young women in long sitting and standing work environments. By studying the relationship between material elongation and comfort pressure, a prediction model was obtained. The characteristics of the calf models of 94 women were classified, and the influence of different calf characteristics on the pressure distribution and tensile value design was objectively analyzed through simulation tests. The samples were then produced based on the simulation results, and subjective and objective try-on tests and evaluations were carried out. The results show that the difference in the shape of the calf has a certain impact on the pressure distribution and comfort. The predicted value of the theoretical model is in good agreement with the actual test value. The sample can bring a suitable gradient pressure and meet the comfort requirements and safety standards.

Effects of Grinding Methods of Tartary Buckwheat Leaf Powder on the Characteristics and Micromorphology of Wheat Dough.

The functional components in tartary buckwheat leaf powder can give flour products higher nutritional value. To comprehensively realize the high-value utilization of tartary buckwheat and its by-products, electric stone mill powder (EMP), ultra-fine mill powder (UMP), steel mill powder (SMP), and grain mill powder (GMP) from tartary buckwheat leaves were used in the preparation of wheat dough, and this was used to explore their effects on dough properties and protein microstructure. With an increase in tartary buckwheat leaf powder, the hydration characteristics, protein weakening rate, and starch gelatinization characteristics of the dough changed, and the water holding capacity and swelling capacity decreased. The retrogradation value increased, which could prolong the shelf life of related products. The water solubility of the dough showed an upward trend and was the lowest at 10% UMP. The addition of UMP produced a more uniform dough stability time and the lowest degree of protein weakening, which made the dough more resistant to kneading. An increasing amount of tartary buckwheat leaf powder augmented the free sulfhydryl content of the dough and decreased the disulfide bond content. The disulfide bond content of the dough containing UMP was higher than that of the other doughs, and the stability of the dough was better. The peaks of the infrared spectrum of the dough changed after adding 10% UMP and 20% EMP. The content of α-helical structures was the highest at 10% UMP, and the content of ordered structures was enhanced. The polymerization of low molecular weight proteins to form macromolecular polymers led to a reduction in surface hydrophobic regions and the aggregation of hydrophobic groups. The SEM results also demonstrated that at 10% tartary buckwheat leaf powder, the addition of UMP was significantly different from that of the other three leaf powders, and at 20%, the addition of EMP substantially altered the structure of the dough proteins. Considering the effects of different milling methods and different added amounts of tartary buckwheat leaf powder on various characteristics of dough, 10% UMP is the most suitable amount to add to the dough.

Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.

Aerobic glycolysis is a pivotal hallmark of cancers, including colorectal cancer. Evidence shows glycolytic enzymes are regulated by post-translational modifications (PTMs), thereby affecting the Warburg effect and reprograming cancer metabolism. Lysine lactylation is a PTM reported in 2019 in histones. In this study, we identified protein lactylation in FHC cells and SW480 colon cancer cells through mass spectrometry. Totally, 637 lysine lactylation sites in 444 proteins were identified in FHC and SW480 cells. Lactylated proteins were enriched in the glycolysis pathway, and we identified lactylation sites in phosphofructokinase, platelet (PFKP) lysine 688 and aldolase A (ALDOA) lysine 147. We also showed that PFKP lactylation directly attenuated enzyme activity. Collectively, our study presented a resource to investigate proteome-wide lactylation in SW480 cells and found PFKP lactylation led to activity inhibition, indicating that lactic acid and lactylated PFKP may form a negative feedback pathway in glycolysis and lactic acid production.

HTR2B as a novel biomarker of chronic obstructive pulmonary disease with lung squamous cell carcinoma.

Chronic obstructive pulmonary disease (COPD) is often associated with lung squamous cell carcinoma (LUSC), which has the same etiology (smoking, inflammation, oxidative stress, microenvironmental changes, and genetics). Smoking, inflammation, and airway remodeling are the most important and classical mechanisms of COPD comorbidity in LUSC patients. Cancer can occur during repeated airway damage and repair (airway remodeling). Changes in the inflammatory and immune microenvironments, which can cause malignant transformation of some cells, are currently being revealed in both LUSC and COPD patients. We obtained the GSE76925 dataset from the Gene Expression Omnibus database. Screening for possible COPD biomarkers was performed using the LASSO regression model and a random forest classifier. The compositional patterns of the immune cell fraction in COPD patients were determined using CIBERSORT. HTR2B expression was analyzed using validation datasets (GSE47460, GSE106986, and GSE1650). HTR2B expression in COPD cell models was determined via real-time quantitative PCR. Epithelial-mesenchymal transition (EMT) marker expression levels were determined after knocking down or overexpressing HTR2B. HTR2B function and mechanism in LUSC were analyzed with the Kaplan‒Meier plotter database. HTR2B expression was inhibited to detect changes in LUSC cell proliferation. A total of 1082 differentially expressed genes (DEGs) were identified in the GSE76925 dataset (371 genes were significantly upregulated, and 711 genes were significantly downregulated). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were mainly enriched in the p53 signaling and ß-alanine metabolism pathways. Gene Ontology enrichment analysis indicated that the DEGs were largely related to transcription initiation from the RNA polymerase I promoter and to the regulation of mononuclear cell proliferation. The LASSO regression model and random forest classifier results revealed that HTR2B, DPYS, FRY, and CD19 were key COPD genes. Immune cell infiltration analysis indicated that these genes were closely associated with immune cells. Analysis of the validation sets suggested that HTR2B was upregulated in COPD patients. HTR2B was significantly upregulated in COPD cell models, and its upregulation was associated with increased EMT marker expression. Compared with that in bronchial epithelial cells, HTR2B expression was upregulated in LUSC cells, and inhibiting HTR2B expression led to the inhibition of LUSC cell proliferation. In conclusions, HTR2B might be a new biomarker and therapeutic target in COPD patients with LUSC.

Single-cell transcriptomic profiling of heart reveals ANGPTL4 linking fibroblasts and angiogenesis in heart failure with preserved ejection fraction.

INTRODUCTION: Despite the high morbidity and mortality, the effective therapies for heart failure with preserved fraction (HFpEF) are limited as the poor understand of its pathophysiological basis. OBJECTIVE: This study was aimed to characterize the cellular heterogeneity and potential mechanisms of HFpEF at single-cell resolution. METHODS: An HFpEF mouse model was induced by a high-fat diet with N-nitro-L-arginine methyl ester. Cells from the hearts were subjected to single-cell sequencing. The key protein expression was measured with Immunohistochemistry and immunofluorescence staining. RESULTS: In HFpEF hearts, myocardial fibroblasts exhibited higher levels of fibrosis. Furthermore, an increased number of fibroblasts differentiated into high-metabolism and high-fibrosis phenotypes. The expression levels of genes encoding certain pro-angiogenic secreted proteins were decreased in the HFpEF group, as confirmed by bulk RNA sequencing. Additionally, the proportion of the endothelial cell (EC) lineages in the HFpEF group was significantly downregulated, with low angiogenesis and high apoptosis phenotypes observed in these EC lineages. Interestingly, the fibroblasts in the HFpEF heart might cross-link with the EC lineages via over-secretion of ANGPTL4, thus displaying an anti-angiogenic function. Immunohistochemistry and immunofluorescence staining then revealed the downregulation of vascular density and upregulation of ANGPTL4 expression in HFpEF hearts. Finally, we predicted ANGPTL4as a potential druggable target using DrugnomeAI. CONCLUSION: In conclusion, this study comprehensively characterized the angiogenesis impairment in HFpEF hearts at single-cell resolution and proposed that ANGPTL4 secretion by fibroblasts may be a potential mechanism underlying this angiogenic abnormality.

Pulmonary Nodule Classification Using a Multiview Residual Selective Kernel Network.

Lung cancer is one of the leading causes of death worldwide and early detection is crucial to reduce the mortality. A reliable computer-aided diagnosis (CAD) system can help facilitate early detection of malignant nodules. Although existing methods provide adequate classification accuracy, there is still room for further improvement. This study is dedicated to investigating a new CAD scheme for predicting the malignant likelihood of lung nodules in computed tomography (CT) images in light of a deep learning strategy. Conceived from the residual learning and selective kernel, we investigated an efficient residual selective kernel (RSK) block to handle the diversity of lung nodules with various shapes and obscure structures. Founded on this RSK block, we established a multiview RSK network (MRSKNet), to which three anatomical planes in the axial, coronal, and sagittal directions were fed. To reinforce the classification efficiency, seven handcrafted texture features with a filter-like computation strategy were explored, among which the homogeneity (HOM) feature maps are combined with the corresponding intensity CT images for concatenation input, leading to an improved network architecture. Evaluated on the public benchmark Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) challenge database with ten-fold cross validation of binary classification, our experimental results indicated high area under receiver operating characteristic (AUC) and accuracy scores. A better compromise between recall and specificity was struck using the suggested concatenation strategy comparing to many state-of-the-art approaches. The proposed pulmonary nodule classification framework exhibited great efficacy and achieved a higher AUC of 0.9711. The association of handcrafted texture features with deep learning models is promising in advancing the classification performance. The developed pulmonary nodule CAD network architecture is of potential in facilitating the diagnosis of lung cancer for further image processing applications.

Traditional herbal pair Portulacae Herba and Granati Pericarpium alleviates DSS-induced colitis in mice through IL-6/STAT3/SOCS3 pathway.

BACKGROUND: Portulacae Herba and Granati Pericarpium pair (PGP) is a traditional Chinese herbal medicine treatment for colitis, clinically demonstrating a relatively favorable effect on relieving diarrhea and abnormal stools. However, the underlying mechanism remain uncertain. PURPOSE: The present study intends to evaluate the efficacy of PGP in treating colitis in mice and investigate its underlying mechanism. METHODS: The protective effect of PGP against colitis was determined by monitoring body weight, colon length, colon weight, and survival rate in mice. Colonic inflammation was assessed by serum cytokine levels, colonic H&E staining, and local neutrophil infiltration. The reversal of intestinal epithelial barrier damage by PGP was subsequently analyzed with Western blot and histological staining. Furthermore, RNA-seq analysis and molecular docking were performed to identify potential pathways recruited by PGP. Following the hints of the transcriptomic results, the role of PGP through the IL-6/STAT3/SOCS3 pathway in DSS-induced colitis mice was verified by Western blot. RESULTS: DSS-induced colitis in mice was significantly curbed by PGP treatment. PGP treatment significantly mitigated DSS-induced colitis in mice, as evidenced by improvements in body weight, DAI severity, survival rate, and inflammatory cytokines levels in serum and colon. Moreover, PGP treatment up-regulated the level of Slc26a3, thereby increasing the expressions of the tight junction/adherens junction proteins ZO-1, occludin and E-cadherin in the colon. RNA-seq analysis revealed that PGP inhibits the IL-6/STAT3/SOCS3 pathway at the transcriptional level. Molecular docking indicated that the major components of PGP could bind tightly to the proteins of IL-6 and SOCS3. Meanwhile, the result of Western blot revealed that the IL-6/STAT3/SOCS3 pathway was inhibited at the protein level after PGP administration. CONCLUSION: PGP could alleviate colonic inflammation and reverse damage to the intestinal epithelial barrier in DSS-induced colitis mice. The underlying mechanism involves the inhibition of the IL-6/STAT3/SOCS3 pathway.

Development of a novel predictive model for interstitial lung disease in ANCA-associated vasculitis prognostications within the Chinese population.

Antineutrophil cytoplasmic antibody vasculitis-associated interstitial lung disease (AAV-ILD) is a potentially life-threatening disease. However, very little research has been done on the condition's mortality risk. Hence, our objective is to find out the factors influencing the prognosis of AAV-ILD and employ these findings to create a nomogram model. Patients with AAV-ILD who received treatment at the First Affiliated Hospital of Zhengzhou University during the period from March 1, 2011, to April 1, 2022 were selected for this research. The development of nomogram entailed a synergistic integration of univariate, Lasso, and multivariate Cox regression analyses. Internal validation ensued through bootstrap techniques involving 1000 re-sampling iterations. Discrimination and calibration were assessed utilizing Harrell's C-index, receiver operating characteristic (ROC) curve, and calibration curve. Model performance was evaluated through integrated discrimination improvement (IDI), net reclassification improvement (NRI), and likelihood ratio test. The net benefit of the model was evaluated using decision curve analysis (DCA). A cohort comprising 192 patients was enrolled for analysis. Throughout observation period, 32.29% of the population died. Key factors such as cardiac involvement, albumin, smoking history, and age displayed substantial prognostic relevance in AAV-ILD. These factors were incorporated to craft a predictive nomogram. Impressively, the model exhibited robust performance, boasting a Harrell's C index of 0.826 and an AUC of 0.940 (95% CI 0.904-0.976). The calibration curves depicted a high degree of harmony between predicted outcomes and actual observations. Significantly enhancing discriminative ability compared to the ILD-GAP model, the nomogram was validated through the IDI, NRI, and likelihood ratio test. DCA underscored the superior predictive value of the predictive model over the ILD-GAP model. The internal validation further affirmed this efficacy, with a mean Harrell's C-index of 0.815 for the predictive model. The nomogram model can be employed to predict the prognosis of patients with AAV-ILD. Moreover, the model performance is satisfactory. In the future, external datasets could be utilized for external validation.

Intergenic sequences harboring potential enhancer elements contribute to Axenfeld-Rieger syndrome by regulating PITX2.

Recent studies have uncovered that noncoding sequence variants may relate to Axenfeld-Rieger syndrome (ARS), a rare developmental anomaly with genetic heterogeneity. However, how these genomic regions are functionally and structurally associated with ARS is still unclear. In this study, we performed genome-wide linkage analysis and whole-genome sequencing in a Chinese family with ARS and identified a heterozygous deletion of about 570 kb (termed LOH-1) in the intergenic sequence between paired-like homeodomain transcription factor 2 (PITX2) and family with sequence similarity 241 member A. Knockout of LOH-1 homologous sequences caused ARS phenotypes in mice. RNA-Seq and real-time quantitative PCR revealed a significant reduction in Pitx2 gene expression in LOH-1-/- mice, while forkhead box C1 expression remained unchanged. ChIP-Seq and bioinformatics analysis identified a potential enhancer region (LOH-E1) within LOH-1. Deletion of LOH-E1 led to a substantial downregulation of the PITX2 gene. Mechanistically, we found a sequence (hg38 chr4:111,399,594-111,399,691) that is on LOH-E1 could regulate PITX2 by binding to RAD21, a critical component of the cohesin complex. Knockdown of RAD21 resulted in reduced PITX2 expression. Collectively, our findings indicate that a potential enhancer sequence that is within LOH-1 may regulate PITX2 expression remotely through cohesin-mediated loop domains, leading to ARS when absent.

Hsa_circ_0021205 enhances lipolysis via regulating miR-195-5p/HSL axis and drives malignant progression of glioblastoma.

Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.

ROS are required for the germinative cell proliferation and metacestode larval growth of Echinococcus multilocularis.

The potentially lethal zoonotic disease alveolar echinococcosis (AE) is caused by the metacestode larval stages of the tapeworm Echinococcus multilocularis. Metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular parasite-host interactions. The host has developed various ways to resist a parasitic infection, and the production of reactive oxygen species (ROS) is one of the most important strategies. Here, we found that scavenging of ROS reduced metacestode larval growth and germinative cell proliferation in in vivo models. Furthermore, using in vitro-cultured metacestode vesicles, we found that increased ROS levels enhanced metacestode growth and germinative cell proliferation, which was achieved by positively activating the ROS-EmERK-EmHIF1α axis. These results indicate that, beside its capacity to damage the parasite, ROS also play critical roles in metacestode growth and germinative cell proliferation. This study suggests that the effects of ROS on parasite may be bidirectional during AE infection, reflecting the parasite's adaptation to the oxidative stress microenvironment.

Prospective randomized controlled trial on the safety and neuroprotective efficacy of remote administration of hypothermia over spleen during acute ischemic stroke with mechanical thrombectomy: rationale, design, and protocol.

Background: Brain inflammation plays a key role in ischemia/reperfusion (I/R) injury and is the main cause of "ineffective or futile recanalization" after successful mechanical thrombectomy (MT) in acute ischemic stroke (AIS). One of the primary sources of inflammatory cells after AIS are derived from the spleen. As an innovative and potential neuroprotective strategy after stroke, Remote Administration of Hypothermia (RAH) temporarily suppresses immune activities in the spleen, reduces the release of inflammatory cells and cytokines into blood, and thus reversibly diminishes inflammatory injury in the brain. Methods: This single-center, prospective, randomized controlled study (RCT) is proposed for AIS patients with anterior circulation large vessel occlusion (LVO). Subjects will be randomly assigned to either the control or intervention groups in a 1:1 ratio (n = 40). Participants allocated to the intervention group will receive RAH on the abdomen above the spleen prior to recanalization until 6 h after thrombectomy. All enrolled patients will receive standard stroke Guideline care. The main adverse events associated with RAH are focal cold intolerance and abdominal pain. The primary outcome will assess safety as it pertains to RAH application. The secondary outcomes include the efficacy of RAH on spleen, determined by spleen volumes, blood inflammatory factor (cells and cytokines), and on brain injury, determined by infarction volumes and poststroke functional outcomes. Discussion: This study aims to examine the safety and preliminary effectiveness of RAH over the spleen during endovascular therapy in AIS patients. The results of this study are expected to facilitate larger randomized clinical trials and hopefully prove RAH administration confers adjuvant neuroprotective properties in AIS treated with MT. Clinical trial registration: https://www.chictr.org.cn/. Identifier ChiCTR 2300077052.

Low serum alanine aminotransferase (ALT) levels are associated with poor outcomes in acute ischemic stroke patients regardless of age.

Studies have indicated that reduced serum ALT levels are commonly linked to aging and are known to predict poor outcomes in many clinical conditions as potential frailty indicators. There are close connections between the brain and peripheral organs, particularly the liver. In patients with acute ischemic stroke (AIS), the interactive effects may change ALT levels, which in turn influence stroke outcomes. Whether ALT has potential neuroprotective effects or is an indicator of frailty in AIS patients remains unknown. This retrospective analysis examined 572 AIS patients in Beijing Luhe Hospital between August 2020 and June 2021. Patient demographics and laboratory results were assembled. The National Institutes of Health Stroke Scale (NIHSS) was used to analyze stroke severity. Modified Rankin Score (mRS) determined stroke outcome 3 months after AIS, with mRS≤2 indicating a favorable outcome. Based on serum ALT measurements, patients were classified into three tertiles (T1-T3). Binary logistic regression analysis evaluated the correlation between ALT tertiles and AIS outcomes. Of the patients, 66 exhibited unfavorable outcomes. The median ALT level in this group was 13 (IQR: 11-18.25), which was lower than in the favorable outcomes cohort (16; IQR: 11-22). A decline in ALT corresponded with a higher incidence of poor outcomes at 3 months (T1, 15.5 %; T2, 11.4 %; T3, 7.0 %; p = 0.03). The lowest ALT tertile (T1) was independently linked to an adverse 3-month outcome (OR 2.50 95 %CI 1.24-5.07, p = 0.038) compared to the highest tertile. ALT levels demonstrated no correlation with age (T1, 62.59 ± 12.64; T2, 64.01 ± 11.47; T3, 65.12 ± 11.27; p > 0.05). Regardless of age, lower serum ALT levels are independently associated with poorer outcomes in AIS patients. This finding suggests the potential pivotal part of the liver in AIS outcomes, highlighting the need to consider both neurological and liver functions post-stroke.

Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID): A potential neuroprotection strategy for acute ischemic stroke (AIS) patients.

Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. We evaluated the safety and feasibility of intravenous GTN in AIS patients. Subsequently, we conducted a secondary analysis to assess for possible efficacy of GTN as a neuroprotectant. We conducted a prospective, double-blind, randomized controlled trial in the Stroke Intervention & Translational Center (SITC) in Beijing Luhe Hospital, Capital Medical University (ChiCTR2100046271). AIS patients within 24 h of stroke onset were evenly divided into GTN or control groups (n = 20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP<110 mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin score (mRS) and the national institutes of health stroke score (NIHSS). Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and pre-mRS scores showed no significant difference between the groups. Safety measures of SBP<110 mmHg and headache occurrence were comparable. Overall, 90-day mRS (1 vs. 1) and NIHSS (1 vs. 1) did not significantly differ between groups. However, the GTN-treated group had a benefit in enhancing NIHSS recovery (△NIHSS 4.5 vs. 3, p = 0.028), indicating that GTN may augment recovery. Subgroup analyses revealed a benefit in the GTN group at the 90-day NIHSS score and △NIHSS follow up for non-thrombolysis patients (1 vs. 2, p = 0.016; 5 vs. 2, p = 0.001). Moreover, the GTN group may benefit mild stroke patients in NIHSS score at 90 day and △NIHSS observed at 90 days (1 vs. 1, p = 0.025; 3 vs. 2 p = 0.002). Overall, while preliminary data suggest GTN might aid recovery in NIHSS improvement, the evidence is tempered due to sample size limitations. The RIGID study confirms the safety and feasibility of intravenous GTN administration for AIS patients. Preliminary data also suggest that the GTN group may provide improvement in NIHSS recovery compared to the control group. Furthermore, a potential benefit for non-thrombolysis patients and those with mild stroke symptoms was identified, suggesting a possible potential role as a tailored intervention in specific AIS subgroups. Due to the limited sample size, further larger RCT will be necessary to replicate these results. TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR2100046271.