Relationship between sodium-glucose cotransporter 2 inhibitors and atrial fibrillation recurrence after pulmonary vein isolation in patients with type 2 diabetes and persistent atrial fibrillation.

BACKGROUND: The impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the postoperative recurrence of atrial fibrillation (AF) in patients with persistent AF undergoing an initial radiofrequency ablation is not yet established. The objective of this study is to assess the impact of SGLT2 inhibitors on the recurrence of AF after radiofrequency ablation in patients with type 2 diabetes complicated persistent AF. METHODS: A total of 182 patients with type 2 diabetes and persistent AF, who underwent their first radiofrequency ablation for AF at our center, were enrolled and divided into two groups: the SGLT2 inhibitor group and the non-SGLT2 inhibitor group. The main outcome of the follow-up was the postoperative recurrence of AF. RESULTS: A total of 49 participants experienced AF recurrence. The use of SGLT2 inhibitors in patients with type 2 diabetes who underwent AF ablation was associated with a significantly lower risk of AF recurrence (adjusted hazard ratio: 0.65; 95% confidence interval: 0.28-0.83; p < .01). CONCLUSIONS: The use of SGLT2 inhibitors is associated with a decreased risk of arrhythmia recurrence after AF ablation in patients with type 2 diabetes complicated with persistent AF.

Ablation apprentices and their first experience of pulmonary vein isolation procedure on paroxysmal atrial fibrillation with different sheaths.

OBJECTIVES: This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. METHODS: 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. RESULTS: Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p < 0.001). X-ray exposure was lowest with visualized sheath (17.6 ± 5 vs. 18.6 ± 6 vs. 5.2 ± 6, p < 0.001). CF SD differed significantly, especially at the anterior aspect of LSPV (7.90 ± 2.90 vs. 5.04 ± 2.18 vs. 4.52 ± 2.40, p < 0.001) and posterior aspect of RSPV (6.84 ± 2.79 vs. 3.42 ± 2.04 vs. 3.50 ± 2.30, p < 0.001) in the fixed-curve group. Impedance drop was significantly smaller in the fixed-curve group at the anterior aspect of LSPV (8.74 ± 3.02 vs. 11.49 ± 5.48 vs. 12.57 ± 5.96, p = 0.005). CONCLUSION: Even for the very first ablation procedure of an ablation apprentice, the use of steerable sheaths will significantly reduce the procedure duration and improve the catheter stability, but only visualized steerable sheath can reduce fluoroscopic time.

Laser-Printed All-Carbon Responsive Material and Soft Robot.

Responsive materials and actuators are the basis for the development of various leading-edge technologies but have so far mostly been designed based on polymers, incurring key limitations related to sensitivity and environmental tolerance. This work reports a new responsive material, laser-printed carbon film (LPCF), produced via direct laser transformation of a liquid organic precursor and consists of graphitic and amorphous carbons. The high activity of amorphous carbon combined with the dual-gradient structure enables the LPCF to have a actuation speed of 9400° s-1 in response to the stimulus of organic vapor. LPCF exhibits a conductivity of 950 S m-1 and excellent resistance to various extreme environmental conditions, which are unachievable for polymer-based materials. Additionally, an LPCF-based all-carbon soft robot that can mimic the complex continuous backward somersaulting motions without manual intervention is constructed. The locomotion velocity of the robot reaches a value of 1.19 BL s-1, which is almost one to two orders of magnitude faster than that of reported soft robots. This work not only offers a new paradigm for highly responsive materials but also provides a great design and engineering example for the next generation of biomimetic robots with life-like performance.

The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

Hydrophobic Ion Barrier-Enabled Ultradurable Zn (002) Plane Orientation towards Long-Life Anode-Less Zn Batteries.

Gradual disability of Zn anode and high negative/positive electrode (N/P) ratio usually depreciate calendar life and energy density of aqueous Zn batteries (AZBs). Herein, within original Zn2+-free hydrated electrolytes, a steric hindrance/electric field shielding-driven "hydrophobic ion barrier" is engineered towards ultradurable (002) plane-exposed Zn stripping/plating to solve this issue. Guided by theoretical simulations, hydrophobic adiponitrile (ADN) is employed as a steric hindrance agent to ally with inert electric field shielding additive (Mn2+) for plane adsorption priority manipulation, thereby constructing the "hydrophobic ion barrier". This design robustly suppresses the (002) plane/dendrite growth, enabling ultradurable (002) plane-exposed dendrite-free Zn stripping/plating. Even being cycled in Zn‖Zn symmetric cell over 2150 h at 0.5 mA cm-2, the efficacy remains well-kept. Additionally, Zn‖Zn symmetric cells can be also stably cycled over 918 h at 1 mA cm-2, verifying uncompromised Zn stripping/plating kinetics. As-assembled anode-less Zn‖VOPO4·2H2O full cells with a low N/P ratio (2:1) show a high energy density of 75.2 Wh kg-1full electrode after 842 cycles at 1 A g-1, far surpassing counterparts with thick Zn anode and low cathode loading mass, featuring excellent practicality. This study opens a new avenue by robust "hydrophobic ion barrier" design to develop long-life anode-less Zn batteries.

Preparing Retinal Organoid Samples for Transmission Electron Microscopy.

Retinal organoids (ROs) are a three-dimensional culture system mimicking human retinal features that have differentiated from induced pluripotent stem cells (iPSCs) under specific conditions. Synapse development and maturation in ROs have been studied immunocytochemically and functionally. However, the direct evidence of the synaptic contact ultrastructure is limited, containing both special ribbon synapses and conventional chemical synapses. Transmission electron microscopy (TEM) is characterized by high resolution and a respectable history elucidating retinal development and synapse maturation in humans and various species. It is a powerful tool to explore synaptic structure in ROs and is widely used in the research field of ROs. Therefore, to better explore the structure of RO synaptic contacts at the nanoscale and obtain high-quality microscopic evidence, we developed a simple and repeatable method of RO TEM sample preparation. This paper describes the protocol, reagents used, and detailed steps, including RO fixation preparation, post fixation, embedding, and visualization.

A label-free fluorescence aptamer sensor for point-of-care serotonin detection.

Serotonin, a pivotal neurotransmitter regulating various physiological functions, plays a crucial role in disease diagnosis, necessitating precise monitoring of its levels in biological fluids for accurate assessment. Aptamers, known for their high specificity and affinity, have emerged as innovative molecular probes for serotonin analysis. However, existing serotonin aptamer sensing platforms exhibit limitations in terms of portability and rapid detection capabilities. In this study, we introduce a novel, portable, label-free serotonin aptamer sensor utilizing a dye replacement strategy, achieving a short sample-to-result turnaround time and convenient signal readout through a smartphone. The performance of this aptamer sensor was thoroughly assessed across diverse physiological media, demonstrating robust stability in buffer, urine, and serum. Importantly, the detection limit was in the nanomolar range, emphasizing its suitability for the rapid, sensitive, and user-friendly detection of serotonin. This research pioneers an approach for the development of a point-of-care testing (POCT) system for serotonin with practical implications, particularly in resource-limited settings.

Synthesis of Indole-Fused Pyrazino[1,2-a]quinazolinones by Copper(I)-Catalyzed Selective Hydroamination-Cyclization of Alkynyl-tethered Quinazolinones.

We described a copper(I)-catalyzed atom economic and selective hydroamination-cyclization of alkynyl-tethered quinazolinones to prepare a variety of indole-fused pyrazino[1,2-a]quinazolinones in good to excellent yields ranging from 39% to 99% under mild reaction conditions. Control experiments revealed that coordination-directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination-cyclization of alkynes at the N1-atom instead of N3-atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole-fused pyrazino[1,2-a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions.

Cytomegalovirus antigen-specific multi-cytokine immune responses in patients with rheumatic diseases under different cytomegalovirus infection status: A case-control study.

OBJECTIVE: To explore Cytomegalovirus (CMV) antigen-specific multi-cytokine immune responses in patients with rheumatic disease (RD) under different CMV infection status. METHODS: A total of 60 RD patients in our center from March 2023 to August 2023 were enrolled. The patients were divided into latent CMV infection and active CMV infection, the latter was classified as subclinical CMV infection or CMV disease based on presence or absence of symptoms related to CMV. Whole blood was collected and stimulated with QuantiFERON-CMV antigen. The levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17 and CXCL-2 in supernatant were measured by Luminex Assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different CMV infection status. RESULTS: The proportion of patients with severe lymphopenia was lowest in the latent CMV infection group, while there were no significant differences in medication usage in different CMV infection status. After stimulation with QF-CMV antigens, the levels of IFN-γ, TNF-α and IL-2 in the CMV disease group were significantly lower than those in the latent CMV infection group. CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia together provided the best discriminatory performance for distinguishing between latent and either active CMV infection patients (AUC = 0.854) or CMV disease patients (AUC = 0.935). CONCLUSION: Noninvasive peripheral blood biomarkers (the combination of CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia) may have the potential to diferentiate different status of CMV infection in RD population.

Updated Efficacy and Safety of Lorlatinib in a Phase 2 Study in Chinese Patients With Previously Treated Advanced ALK-Positive Non-small Cell Lung Cancer.

OBJECTIVES: Lorlatinib, a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated robust overall and intracranial antitumor activity in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) previously treated with an ALK inhibitor in a global phase 1/2 study (NCT01970865) and a multicenter phase 2 study conducted in China (NCT03909971). We report updated 3-year follow-up data from the phase 2 study. MATERIALS AND METHODS: Chinese patients with locally advanced or metastatic ALK-positive NSCLC that progressed after crizotinib as the only prior ALK inhibitor (cohort 1) or after 1 non-crizotinib ALK inhibitor (cohort 2), were enrolled in the study. All patients received lorlatinib 100 mg once daily. RESULTS: At data cutoff, of 109 enrolled patients, the median duration of follow-up for progression-free survival (PFS) was 35.8 months in cohort 1 (n = 67) and 33.1 months in cohort 2 (n = 42). Median PFS (95% CI) per independent central review was 26.3 months (16.6-35.9) and 5.6 months (2.9-12.4), respectively. The median duration of follow-up for overall survival (OS) was 36.4 months and 37.5 months, respectively. Median OS (95% CI) was not reached (NR; NR-NR) and 21.9 months (11.9-NR), respectively. Median intracranial time to progression (95% CI) was NR (NR-NR) and NR (9.7 months-NR), respectively. No new safety signals emerged with long-term treatment. CONCLUSION: The long-term data confirm robust overall and intracranial clinical activity of lorlatinib, with no new safety signals emerging. These results support using lorlatinib in Chinese patients with previously treated ALK-positive NSCLC with or without brain metastases. CLINICALTRIALS: gov NCT03909971.

Engineering of a double targeting nanoplatform to elevate ROS generation and DSF anticancer activity.

Intracellular oxidative protection mechanisms and adverse systemic toxicity are major obstacles for the success of chemodynamic therapy (CDT)/chemotherapy (CT) synergistic therapy. To tackle the fundamental challenges of current CDT and circumvent the side effects of conventional CT, we developed a copper peroxide (CP) and disulfiram (DSF)-loaded 3-aminotriazole (3-AT) doped ZIF-8 (MAF) with partial sequence-specificity using hyaluronic acid (HA) and triphenylphosphine (TPP) in this study. Upon intravenous administration, CP@MAF-DSF@PEG-TPP@HA (CPMDTH) nanoparticles (NPs) were enriched in tumor tissues through HA-mediated endocytosis, followed by enhanced accumulation in mitochondria by the TPP target. The acidic tumor environment (TME) triggered the decomposition of MAF to release CP, DSF and 3-AT. Cu2+ and H2O2 hydrated from CP NPs produced ˙OH via a Fenton-like reaction. CAT activity inhibition and GSH consumption induced by 3-AT dramatically amplified mitochondrial oxidative stress, thereby promoting the overproduction of ˙OH. In addition, the accumulation of DSF and Cu2+ led to the formation of a cytotoxic bis(N,N-diethyldithiocarbamate) copper(II) complex (Cu(DTC)2) in situ, achieving efficient CT. CPMDTH NPs demonstrated significantly improved antitumor efficiency and excellent biosafety both in vitro and in vivo. This study offers a promising therapeutic strategy for CDT/CT synergistic oncotherapy.

Correlation between small-cell lung cancer serum protein/peptides determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and chemotherapy efficacy.

BACKGROUND: Currently, no effective measures are available to predict the curative efficacy of small-cell lung cancer (SCLC) chemotherapy. We expect to develop a method for effectively predicting the SCLC chemotherapy efficacy and prognosis in clinical practice in order to offer more pertinent therapeutic protocols for individual patients. METHODS: We adopted matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinPro Tools system to detect serum samples from 154 SCLC patients with different curative efficacy of standard chemotherapy and analyze the different peptides/proteins of SCLC patients to discover predictive tumor markers related to chemotherapy efficacy. Ten peptide/protein peaks were significantly different in the two groups. RESULTS: A genetic algorithm model consisting of four peptides/proteins was developed from the training group to separate patients with different chemotherapy efficacies. Among them, three peptides/proteins (m/z 3323.35, 6649.03 and 6451.08) showed high expression in the disease progression group, whereas the peptide/protein at m/z 4283.18 was highly expressed in the disease response group. The classifier exhibited an accuracy of 91.4% (53/58) in the validation group. The survival analysis showed that the median progression-free survival (PFS) of 30 SCLC patients in disease response group was 9.0 months; in 28 cases in disease progression group, the median PFS was 3.0 months, a statistically significant difference (χ2 = 46.98, P < 0.001). The median overall survival (OS) of the two groups was 13.0 months and 7.0 months, a statistically significant difference (χ2 = 40.64, P < 0.001). CONCLUSIONS: These peptides/proteins may be used as potential biological markers for prediction of the curative efficacy and prognosis for SCLC patients treated with standard regimen chemotherapy.

A Methylation-Gated DNAzyme Circuit for Spatially Controlled Imaging of MicroRNA in Cells and Animals.

Epigenetic modification plays an indispensable role in regulating routine molecular signaling pathways, yet it is rarely used to modulate molecular self-assembly networks. Herein, we constructed a bioorthogonal demethylase-stimulated DNA circuitry (DSC) system for high-fidelity imaging of microRNA (miRNA) in live cells and mice by eliminating undesired off-site signal leakage. The simple and robust DSC system is composed of a primary cell-specific circuitry regulation (CR) module and an ultimate signal-transducing amplifier (SA) module. After the modularly designed DSC system was delivered into target live cells, the DNAzyme of the CR module was site-specifically activated by endogenous demethylase to produce fuel strands for the subsequent miRNA-targeting SA module. Through the on-site and multiply guaranteed molecular recognitions, the lucid yet efficient DSC system realized the reliably amplified in vivo miRNA sensing and enabled the in-depth exploration of the demethylase-involved signal pathway with miRNA in live cells. Our bioorthogonally on-site-activated DSC system represents a universal and versatile biomolecular sensing platform via various demethylase regulations and shows more prospects for more different personalized theragnostics.

Fate and mitigation of antibiotics and antibiotic resistance genes in microbial fuel cell and coupled systems.

Microbial fuel cells (MFCs), known for their low energy consumption, high efficiency, and environmental friendliness, have been widely utilized for removing antibiotics from wastewater. Compared to conventional wastewater treatment methods, MFCs produce less sludge while exhibiting superior antibiotic removal capacity, effectively reducing the spread of antibiotic resistance genes (ARGs). This study investigates 1) the mechanisms of ARGs generation and proliferation in MFCs; 2) the influencing factors on the fate and removal of antibiotics and ARGs; and 3) the fate and mitigation of ARGs in MFC and MFC-coupled systems. It is indicated that high removal efficiency of antibiotics and minimal amount of sludge production contribute the mitigation of ARGs in MFCs. Influencing factors, such as cathode potential, electrode materials, salinity, initial antibiotic concentration, and additional additives, can lead to the selection of tolerant microbial communities, thereby affecting the abundance of ARGs carried by various microbial hosts. Integrating MFCs with other wastewater treatment systems can synergistically enhance their performance, thereby improving the overall removal efficiency of ARGs. Moreover, challenges and future directions for mitigating the spread of ARGs using MFCs are suggested.

Circularly Polarized Room Temperature Phosphorescence through Twisting-Induced Helical Structures from Polyvinyl Alcohol-Based Fibers Containing Hydrogen-Bonded Dyes.

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.

Superhalide-Anion-Motivator Reforming-Enabled Bipolar Manipulation toward Longevous Energy-Type Zn||Chalcogen Batteries.

Neutrophilic superhalide-anion-triggered chalcogen conversion-based Zn batteries, despite latent high-energy merit, usually suffer from a short lifespan caused by dendrite growth and shuttle effect. Here, a superhalide-anion-motivator reforming strategy is initiated to simultaneously manipulate the anode interface and Se conversion intermediates, realizing a bipolar regulation toward longevous energy-type Zn batteries. With ZnF2 chaotropic additives, the original large-radii superhalide zincate anion species in ionic liquid (IL) electrolytes are split into small F-containing species, boosting the formation of robust solid electrolyte interphases (SEI) for Zn dendrite inhibition. Simultaneously, ion radius reduced multiple F-containing Se conversion intermediates form, enhancing the interion interaction of charged products to suppress the shuttle effect. Consequently, Zn||Se batteries deliver a ca. 20-fold prolonged lifespan (2000 cycles) at 1 A g-1 and high energy/power density of 416.7 Wh kgSe-1/1.89 kW kgSe-1, outperforming those in F-free counterparts. Pouch cells with distinct plateaus and durable cyclability further substantiate the practicality of this design.

An Artificial Intelligence-Driven Approach for Automatic Evaluation of Right-to-Left Shunt Grades in Saline-Contrasted Transthoracic Echocardiography.

BACKGROUND: Intracardiac or pulmonary right-to-left shunt (RLS) is a common cardiac anomaly associated with an increased risk of neurological disorders, specifically cryptogenic stroke. Saline-contrasted transthoracic echocardiography (scTTE) is often used for RLS diagnosis. However, the identification of saline microbubbles in the left heart can be challenging for novice residents, potentially leading to a delay in diagnosis and treatment. In this study, we proposed an artificial intelligence (AI)-based algorithm designed to automatically detect microbubbles in scTTE images and evaluate right-to-left shunt grades. This tool aims to support residency training and decrease the workload of cardiologists. METHODS: A dataset of 23,665 scTTE images obtained from 174 individuals was included in this study. This dataset was partitioned into a training set (n = 20,475) and an internal validation set (n = 3,190) on a patient-level basis. An additional cohort of 33 patients diagnosed with cryptogenic ischemic stroke was enrolled as an external validation set. The proposed algorithm for right-to-left shunt degree classification employed the EfficientNet-b4 model, and the model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and compared to the performance of residents. RESULTS: Our AI model demonstrated robust performance with an accuracy of 0.926, sensitivity of 0.827, and specificity of 0.951 on the internal testing dataset. In the external validation set, our AI model exhibited diagnostic accuracy, sensitivity, and specificity of 0.864, 0.818, and 0.909, respectively. In comparison, residents achieved values of 0.727, 0.636, and 0.818, respectively. CONCLUSION: Our AI model provides a swift, precise, and easily deployable methodology for grading the degree of right-to-left shunt in scTTE, carrying substantial implications for routine clinical practice. Residents can benefit from our artificial intelligence-based algorithm, enhancing both the accuracy and efficiency of RLS diagnosis.

Multifunctional Drug- and AuNRs-Loaded ROS-Responsive Selenium-Containing Polyurethane Nanofibers for Smart Wound Healing.

Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.

Cell-specific localization of ß-synuclein in the mouse retina.

ß-synuclein, a member of the synuclein family, is frequently co-expressed with α-synuclein in the neural system, where it serves to inhibit abnormal aggregation of α-synuclein in neurodegenerative diseases. Beyond its role in pathological conditions, ß-synuclein plays various functions independently of α-synuclein. In our investigation, we discovered a broader expression of ß-synuclein in the mouse retina compared to α-synuclein. This widespread pattern implies its potential significance in the retina. Through detailed examination via light- and electron-microscopic immunocytochemistry, we identified ß-synuclein expression from the inner segment (IS) and outer segment (OS) of photoreceptor cells to the ganglion cell layer (GCL). Our findings unveiled unique features, including ß-synuclein immunoreactive IS and OS of cones, higher expression in cone pedicles than in rod spherules, absence in horizontal cells, limited expression in cone bipolar dendrites and somas, higher expression in cone bipolar terminals, presence in most amacrine cells, and expression in almost majority of somas in GCL with an absence in intrinsically photosensitive retinal ganglion cell (ipRGCs) processes. Notably, all cholinergic amacrine cells express high ß- but not α-synuclein, while dopaminergic amacrine cells express α-synuclein exclusively. These distinctive expression patterns offer valuable insights for further exploration into the functions of ß-synuclein and its potential role in synuclein pathology within the retina.

Effectiveness of the acute stroke care map program in reducing in-hospital delay for acute ischemic stroke in a Chinese urban area: an interrupted time series analysis.

Background: Timely intravenous thrombolysis (IVT) is crucial for improving outcomes in acute ischemic stroke (AIS) patients. This study evaluates the effectiveness of the Acute Stroke Care Map (ASCaM) initiative in Shenyang, aimed at reducing door-to-needle times (DNT) and thus improving the timeliness of care for AIS patients. Methods: An retrospective cohort study was conducted from April 2019 to December 2021 in 30 hospitals participating in the ASCaM initiative in Shenyang. The ASCaM bundle included strategies such as EMS prenotification, rapid stroke triage, on-call stroke neurologists, immediate neuroimaging interpretation, and the innovative Pre-hospital Emergency Call and Location Identification feature. An interrupted time series analysis (ITSA) was used to assess the impact of ASCaM on DNT, comparing 9 months pre-intervention with 24 months post-intervention. Results: Data from 9,680 IVT-treated ischemic stroke patients were analyzed, including 2,401 in the pre-intervention phase and 7,279 post-intervention. The ITSA revealed a significant reduction in monthly DNT by -1.12 min and a level change of -5.727 min post-ASCaM implementation. Conclusion: The ASCaM initiative significantly reduced in-hospital delays for AIS patients, demonstrating its effectiveness as a comprehensive stroke care improvement strategy in urban settings. These findings highlight the potential of coordinated care interventions to enhance timely access to reperfusion therapies and overall stroke prognosis.