Exosomes: the next-generation therapeutic platform for ischemic stroke.

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood-brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

Dissociable Effects of Endogenous and Exogenous Attention on Crowding: Evidence from Event-Related Potentials.

BACKGROUND/OBJECTIVES: Crowding is a common visual phenomenon that can significantly impair the recognition of objects in peripheral vision. Two recent behavioral studies have revealed that both exogenous and endogenous attention can alleviate crowding, but exogenous attention seems to be more effective. METHODS: The present study employed the event-related potential (ERP) technique to explore the electrophysiological characteristics of the influence of these two types of attention on crowding. In the experiment, participants were required to judge whether the letter "T" was upright or inverted, which may be preceded by an exogenous cue or an endogenous cue indicating the location of the target letter. RESULTS: The behavioral results showed that while exogenous cues reduced crowding in all stimulus onset asynchronies (SOAs), endogenous attention took effects only in long SOA. The ERP results indicated that both endogenous and exogenous cues significantly alleviated the inhibition of visual crowding on the N1 component. However, the endogenous cue was effective only under long SOA, while the exogenous cue was effective only under short SOA conditions. In addition, invalid exogenous cues induced a larger P3 wave amplitude than valid ones in the short SOA condition, but endogenous attention did not show such a difference. CONCLUSIONS: These results indicate that both endogenous and exogenous attention can alleviate the effects of visual crowding, but they differ in effect size and temporal dynamics.

A comparison of the effects of lung protective ventilation and conventional ventilation on the occurrence of atelectasis during laparoscopic surgery in young infants: a randomized controlled trial.

Objective: This study utilized lung ultrasound to investigate whether lung protective ventilation reduces pulmonary atelectasis and improves intraoperative oxygenation in infants undergoing laparoscopic surgery. Methods: Eighty young infants (aged 1-6 months) who received general anesthesia for more than 2 h during laparoscopic surgery were randomized into the lung protective ventilation group (LPV group) and the conventional ventilation group (control group). The LPV group received mechanical ventilation starting at 6 mL/kg tidal volume, 5 cmH2O PEEP, 60% inspired oxygen fraction, and half-hourly alveolar recruitment maneuvers. Control group ventilation began with 8-10 mL/kg tidal volume, 0 cmH2O PEEP, and 60% inspired oxygen fraction. Lung ultrasound was conducted five times-T1 (5 min post-intubation), T2 (5 min post-pneumoperitoneum), T3 (at the end of surgery), T4 (post-extubation), and T5 (prior to discharge from the PACU)-for each infant. Simultaneous arterial blood gas analysis was performed at T1, T2, T3, and T4. Results: Statistically significant differences were observed in pulmonary atelectasis incidence, lung ultrasound scores, and the PaO2, PaCO2, PaO2/FiO2 ratios at T2, T3, and T4. However, at T5, no statistically significant differences were noted in terms of lung ultrasound scores (4.30 ± 1.87 vs. 5.00 ± 2.43, 95% CI: -1.67 to 0.27, p = 0.153) or the incidence of pulmonary atelectasis (32.5% vs. 47.5%, p = 0.171). Conclusion: In infants aged 1-6 months, lung protective ventilation during laparoscopy under general anesthesia significantly reduced the incidence of pulmonary atelectasis and enhanced intraoperative oxygenation and dynamic lung compliance compared to conventional ventilation. However, these benefits did not persist; no differences were observed in lung ultrasound scores or the incidence of pulmonary atelectasis at PACU discharge. Clinical trial registration: http://www.chictr.org.cn/, identifier: ChiCTR2200058653.

Prognostic Value of Fibrosis-4 in Acute Ischemic Stroke Patients Undergoing Intravenous Thrombolysis.

Purpose: Although recombinant tissue plasminogen activator (rt-PA) treatment is efficient in patients with acute ischemic stroke (AIS), a significant percentage of patients who received rt-PA intravenous thrombolysis (IVT) do not achieve a good prognosis. Therefore, the factors that affect the poor prognosis of patients with IVT are needed. The Fibrosis-4 (FIB-4) index has been used as a liver fibrosis biomarker. We aimed to investigate the relationship between the FIB-4 index and functional outcomes in patients with AIS receiving IVT. Patients and Methods: This study prospectively included consecutive patients with AIS receiving IVT between April 2015 and May 2022. We collected clinical and laboratory data and calculated the FIB-4 index. Clinical outcome was poor functional outcome (mRS ≥3) at 3 months after IVT. Multivariate logistic regression analysis was used to analyze the association between FIB-4 and outcome. We explored the interactive effect of FIB-4 and dyslipidemia on poor outcomes, and subgroup analysis was performed. Furthermore, an individualized prediction model based on the FIB-4 for functional outcome was established in the dyslipidemia group. Results: A total of 1135 patients were included, and 41.50% had poor 3-month outcomes. After adjusted by other variants that P value <0.05 in univariable analysis, FIB-4 was independently associated with poor outcomes (OR=1.420; 95% CI: 1.113-1.812; P=0.004). There was a significant interaction between FIB-4 and dyslipidemia on poor outcome (P=0.036), and the independent association between FIB-4 and poor outcome was maintained in the dyslipidemia subgroup (OR=1.646; 95% CI: 1.228-2.206; P=0.001). Furthermore, in the dyslipidemia group, the FIB-4-based prediction model had good predictive value (the AUC of the training and validation sets were 0.767 and 0.708, respectively), good calibration (P-values for the Hosmer-Lemeshow test >0.05), and clinical usefulness. Conclusion: FIB-4 is an independent risk factor for poor outcomes in IVT patients with dyslipidemia, which can be used as a simple predictor of their prognosis.

Forsythoside B, the active component of Frosythiae fructuse water extract, alleviates Streptococcus pneumoniae virulence by targeting pneumolysin.

AIMS: To explore the therapeutic potential of Forsythoside B in treating Streptococcus pneumoniae (S. pneumoniae) infections, focusing on its ability to inhibit pneumolysin activity and protect cells from damage. METHODS AND RESULTS: Hemolysis tests were used to evaluate Forsythoside B's inhibitory effect on pneumolysin activity, while growth curve analysis assessed its impact on S. pneumoniae growth. Western blotting and oligomerization analysis were conducted to examine its influence on pneumolysin oligomerization. Cytotoxicity assays, including LDH release and live/dead cell staining, evaluated the protective effects of Forsythoside B against pneumolysin-induced damage in A549 cells. Additionally, a mouse model was employed to test the effects on survival rates, lung bacterial load, and inflammation. The results showed that Forsythoside B significantly inhibited pneumolysin activity, reduced its oligomerization, and protected A549 cells from damage without affecting bacterial growth. In the mouse model, it improved survival rates and reduced lung inflammation, indicating its potential as a therapeutic agent against S. pneumoniae infections. CONCLUSIONS: Forsythoside B shows potential as a therapeutic agent for treating pneumonia, particularly in infections caused by S. pneumoniae.

Revision and validation of the "Motivational Climate in Physical Education Scale" (MCPES) in Chinese educational context.

This study evaluated the reliability and validity of the Chinese version of the "Motivational Climate in Physical Education Scale" (MCPES) among middle school students. Data were collected from 1,008 students, with 473 completing the MCPES, the Physical Needs Support in Physical Education Scale (PNS-PE), and the Youth Sports Friendship Quality Scale (YSFQS). Additionally, 437 students completed only the MCPES, and 200 valid retest questionnaires were gathered three weeks later. Exploratory factor analysis identified four factors: perceived mastery climate, perceived performance climate, perceived autonomy support, and perceived relatedness support with a total of 16 items. Confirmatory factor analysis supported the four-factor structure (χ2/df = 3.38, GFI = 0.92, NFI = 0.90, RMSEA = 0.07, CFI = 0.93, IFI = 0.93, SRMR = 0.05). The scale exhibited strict measurement invariance across genders and strong invariance across grade levels. It was positively correlated with teacher autonomy support (r = 0.34-0.53) and with each dimension and total score of sports friendship (r = 0.21-0.61). Cronbach's α coefficients for the MCPES and its dimensions were 0.75, 0.82, 0.79, 0.80, and 0.88, respectively. Intraclass correlation coefficients (ICCs) for the three-week retest were 0.64, 0.63, 0.72, and 0.76. In conclusion, the Chinese version of the MCPES demonstrates robust reliability and validity for use with middle school students.

Point-of-care testing of rpoB in Mycobacterium tuberculosis using multiply-primed-RCA coupled with CRISPR/Cas12a.

Purpose: Due to the serious threat of tuberculosis to global health and limitations of existing diagnostic methods, this study combined the CRISPR/Cas12a system with Multiply-primed-RCA (MRCA) technology for Mycobacterium tuberculosis Point-of-care Testing (POCT). Method: We utilized T4 and Taq DNA ligases, compared the effects of specific primers and random 6NS primers on the method, and integrated MRCA and the CRISPR-Cas12a system in one tube. By optimizing conditions such as the concentration of DNA ligase, the concentration of padlock probes, and the number of cycles, we finally established T4-MRCA-Cas12a and Taq-MRCA-Cas12a methods for both stepwise and one-step. Results: The limits of detection of the one-step T4/Taq-MRCA-Cas12a were 104aM and 103aM. With no cross-reactivity with DNA from other bacterial strains. The accuracy and specificity were 88 % and 100 % for T4-MRCA-Cas12a, and 96 % and 100 % for Taq-MRCA-Cas12a, respectively. Conclusion: We developed a POCT method that can directly identify MTB through the naked eye.

Mechanism of synergistic action of colistin with resveratrol and baicalin against mcr-1-positive Escherichia coli.

The rising incidence of colistin (COL) resistance poses a significant challenge, undermining the therapeutic efficacy of COL against life-threatening bacterial infections. Therefore, the urgent identification and development of new therapeutics are imperative. It has been proven that combinations of antibiotics and promising non-antibiotic agents could be a potential strategy to combat infections caused by MDR pathogens. Due to various antimicrobial properties, medicinal plants have attracted significant attention, which could be promising adjuvant. In this study, we investigated the synergistic effects of combining COL with resveratrol (RST) and baicalin (BAI) against mcr-1-positive Escherichia coli through antibiotic susceptibility testing, checkerboard method and time-killing assays. The mechanisms of combination treatment were analyzed using SEM, fluorometric assays and transcriptome analysis. The molecular docking assay was conducted to elucidate potential interactions between RST, BAI and the MCR-1 protein. Finally, we assessed the in vivo efficacy of combination against mcr-1-positive Escherichia coli. The results demonstrated that the combination of RST, BAI and COL showed significant synergistic activity both in vitro and in vivo. Further mechanistic study revealed that the combination could increase the membrane-damaging ability of COL, disrupt the homeostasis of proton motive force (PMF), inhibit the activity of efflux pumps and impair ATP supply. The molecular docking revealed that RST and BAI could bind to MCR-1 stably, indicating the combination of RST and BAI may be an effective MCR-1 inhibitor. Our findings demonstrated that the combination of RST and BAI might be potential COL adjuvant, providing an alternative approach to address mcr-1-positive Escherichia coli infections.

metaExpertPro: A Computational Workflow for Metaproteomics Spectral Library Construction and Data-Independent Acquisition Mass Spectrometry Data Analysis.

Analysis of large-scale data-independent acquisition mass spectrometry metaproteomics data remains a computational challenge. Here, we present a computational pipeline called metaExpertPro for metaproteomics data analysis. This pipeline encompasses spectral library generation using data-dependent acquisition MS, protein identification and quantification using data-independent acquisition mass spectrometry, functional and taxonomic annotation, as well as quantitative matrix generation for both microbiota and hosts. By integrating FragPipe and DIA-NN, metaExpertPro offers compatibility with both Orbitrap and timsTOF MS instruments. To evaluate the depth and accuracy of identification and quantification, we conducted extensive assessments using human fecal samples and benchmark tests. Performance tests conducted on human fecal samples indicated that metaExpertPro quantified an average of 45,000 peptides in a 60-min diaPASEF injection. Notably, metaExpertPro outperformed three existing software tools by characterizing a higher number of peptides and proteins. Importantly, metaExpertPro maintained a low factual false discovery rate of approximately 5% for protein groups across four benchmark tests. Applying a filter of five peptides per genus, metaExpertPro achieved relatively high accuracy (F-score = 0.67-0.90) in genus diversity and showed a high correlation (rSpearman = 0.73-0.82) between the measured and true genus relative abundance in benchmark tests. Additionally, the quantitative results at the protein, taxonomy, and function levels exhibited high reproducibility and consistency across the commonly adopted public human gut microbial protein databases IGC and UHGP. In a metaproteomic analysis of dyslipidemia patients, metaExpertPro revealed characteristic alterations in microbial functions and potential interactions between the microbiota and the host.

Antheraxanthin: Insights delving from biosynthesis to processing effects.

Antheraxanthin (C40H56O3) is one of fat-soluble carotenoids belonging to natural pigments. Its chemical structure is based on the unsaturated polyene chain skeleton, with a hydroxy-ß-ionone ring and an epoxy-ß-ionone ring on each side of the skeleton. It is found in a wide range of plants and photosynthetic bacteria, and external stimuli (high temperature, drought, ozone treatment, etc.) can significantly affect its synthesis. It also, like other carotenoids, exhibits a diverse potential pharmacological profile as well as nutraceutical values. However, it is worth noting that various food processing methods (extrusion, puffing, baking, etc.) and storage conditions for fruits and vegetables have distinct impacts on the bioaccessibility and retention of antheraxanthin. This compilation of antheraxanthin includes sources, biosynthesis, chemical analysis, and processing effects.

Catalyst-free regeneration of plasma-activated water via ultrasonic cavitation: Removing aggregation concealment of antibiotic-resistant bacteria with enhanced wastewater sustainability.

Aggregation is a crucial factor in bacterial biofilm formation, and comprehending its properties is vital for managing waterborne antibiotic-resistant bacteria. In this study, we examined Methicillin-resistant Staphylococcus aureus (MRSA) cell aggregation under varying conditions and assessed the inactivation efficiency of a novel disinfection method, micro-nano bubbles plasma-activated water via ultrasonic stirring cavitation (MPAW-US), on aggregated MRSA cells. Aggregation efficiency increased over time and at low salt concentrations but diminished at higher concentrations. Elevated MRSA cell aggregation in actual water samples represented significant real-life biohazard risks. Unlike conventional disinfection, MPAW-US treatment exhibited minimal change in the inactivation rate constant despite protective outer layers. Enhanced inactivation efficiency results from the synergistic effects of increased intracellular oxidative stress damage and extracellular substance disruption, triggered by ultrasound-activated micro-nano bubbles that improve PAW reactivity and applicability. This approach neither induced MRSA cross-resistance to unfavorable conditions nor increased toxicity or regrowth potential of aggregative MRSA, utilizing ATP levels as potential regrowth capability indicators. Ultimately, this energy-efficient disinfection technology functions effectively across diverse temperature ranges, showcasing exceptional sterilization and nutritional bean sprout production after cyclic filtering, thereby promoting wastewater sustainability amidst carbon emission concerns.

Identification of immune-related biomarkers for intracerebral hemorrhage diagnosis based on RNA sequencing and machine learning.

Background: Intracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers. Methods: We collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes. Results: In both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH. Conclusions: This study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis.

Panax notoginseng saponins loaded W/O microemulsion for alopecia therapy with panthenol as cosurfactant to reduce skin irritation.

The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of ß-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/ß-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion.

A multi-AS-PCR-coupled CRISPR/Cas12a assay for the detection of ten single-base mutations.

Single-nucleotide polymorphism (SNP) detection is critical for diagnosing diseases, and the development of rapid and accurate diagnostic tools is essential for treatment and prevention. Allele-specific polymerase chain reaction (AS-PCR) is widely used for detecting SNPs with multiplexing capabilities, while CRISPR-based technologies provide high sensitivity and specificity in targeting mutation sites through specific guide RNAs (gRNAs). In this study, we have integrated the high sensitivity and specificity of CRISPR technology with the multiplexing capabilities of AS-PCR, achieving the simultaneous detection of ten single-base mutations. As for Multi-AS-PCR, our research identified that competitive inhibition of primers targeting the same loci, coupled with divergent amplification efficiencies of these primers, could result in diminished amplification efficiency. Consequently, we adjusted and optimized primer combinations and ratios to enhance the amplification efficacy of Multi-AS-PCR. Finally, we successfully developed a novel nested Multi-AS-PCR-Cas12a method for multiplex SNPs detection. To evaluate the clinical utility of this method in a real-world setting, we applied it to diagnose rifampicin-resistant tuberculosis (TB). The limit of detection (LoD) for the nested Multi-AS-PCR-Cas12a was 102 aM, achieving sensitivity, specificity, positive predictive value, and negative predictive value of 100 %, 93.33 %, 90.00 %, and 100 %, respectively, compared to sequencing. In summary, by employing an innovative design that incorporates a universal reverse primer alongside ten distinct forward allele-specific primers, the nested Multi-AS-PCR-Cas12a technique facilitates the parallel detection of ten rpoB gene SNPs. This method also holds broad potential for the detection of drug-resistant gene mutations in infectious diseases and tumors, as well as for the screening of specific genetic disorders.

Changes in stresses sensitivity of ohmic heating-induced sublethally injured Staphylococcus aureus during repair: Potential mechanisms at the cellular and molecular levels.

Ohmic heating (OH), an emerging food processing technology employed in the food processing industry, raises potential food safety concerns due to the recovery of sublethally injured pathogens such as Staphylococcus aureus (S. aureus). In the present study, sensitivity to various stress conditions and the changes in cellular-related factors of OH-injured S. aureus during repair were investigated. The results indicated that liquid media differences (nutrient broth (NB), phosphate-buffered saline (PBS), milk, and cucumber juice) affected the recovery process of injured cells. Nutrient enrichment determines the bacterial repair rate, and the rates of repair for these media were milk > NB > cucumber juice > PBS. The sensitivity of injured cells to various stressors, including different acids, temperature, nisin, simulated gastric fluid, and bile salt, increased during the injury phase and subsequently diminished upon repair. Additionally, the intracellular ATP content, enzyme activities (Na+/K+-ATPase, Ca2+/Mg2+-ATPase, and T-ATPase) and ion concentrations (Mg2+, K+, and Ca2+) gradually increased during repair. After 5 h of repair, the intracellular substances content of cell's was significantly higher than that of the injured bacteria without repair, while some indicators (e.g., Na+/K+-ATPase, K+, and Ca2+) were not restored to the untreated level. The results of this study indicated that OH-injured S. aureus exhibited strengthened resistance post-recovery, potentially due to the restoration of cellular structures. These findings have implications for optimizing food storage conditions and advancing OH processes in the food industry.

Microplastics supply contaminants in food chain: non-negligible threat to health safety.

The occurrence of microplastics (MPs) and organic pollutants (OPs) residues is commonly observed in diverse environmental settings, where their interactions can potentially alter the behavior, availability, and toxicity of OPs, thereby posing risks to ecosystems. Herein, we particularly emphasize the potential for bioaccumulation and the biomagnification effect of MPs in the presence of OPs within the food chain. Despite the ongoing influx of novel information, there exists a dearth of data concerning the destiny and consequences of MPs in the context of food pollution. Further endeavors are imperative to unravel the destiny and repercussions of MPs/OPs within food ecosystems and processing procedures, aiming to gain a deeper understanding of the joint effect on human health and food quality. Nevertheless, the adsorption and desorption behavior of coexisting pollutants can be significantly influenced by MPs forming biofilms within real-world environments, including temperature, pH, and food constituents. A considerable portion of MPs tend to accumulate in the epidermis of vegetables and fruits, thus necessitating further research to comprehend the potential ramifications of MPs on the infiltration behavior of OPs on agricultural product surfaces.

Dual tobramycin and docosahexaenoic acid loaded nanoemulsions combating Pseudomonas aeruginosa-induced pulmonary infection.

Pseudomonas aeruginosa (P. aeruginosa) typically forms biofilms in vivo, which exhibit high resistance and complicate eradication efforts. Additionally, persistent inflammation and excessive oxidative stress can lead to severe lung dysfunction, facilitating bacterial colonization and infection. Herein, we prepared oil-in-water (O/W) nanoemulsions (TD-αT NEs) by using PEG5k-block-PCL5k and α-tocopherol to encapsulate tobramycin (TOB). To enhance TOB's drug load, a hydrophobic ion pair (TDIP) composed of TOB and docosahexaenoic acid (DHA) was pre-prepared. TD-αT NEs was not only easily prepared and aerosolized, but stable in both physics and chemistry. The negatively charged TD-αT NEs facilitated penetration through mucus, reaching infection sites. Subsequently, TD-αT NEs permeated biofilms due to their small size and released drugs via lipase-triggered carrier dissociation, aiding in eradicating internal bacteria within biofilms (with a 16-fold reduction in CFU vs. free TOB group). TD-αT NEs simultaneously exerted superior anti-inflammatory effects, reducing levels of pro-inflammatory cytokines (NO, IL-6, IL-8, and TNF-α) while increasing the level of anti-inflammatory cytokine (IL-10). It was achieved through the upregulation of PPAR-γ and downregulation of NF-κB signaling, thus mitigating the lung damage. In addition, TD-αT NEs demonstrated strong antioxidant activity, alleviating the oxidative stress induced by P. aeruginosa. Notably, when administered via inhalation, TD-αT NEs significantly reduced the lung bacterial burden, lung inflammation, and oxidative stress in vivo compared to TOB solution. TD-αT NEs could prove beneficial in treating chronic pulmonary infections induced by P. aeruginosa through a comprehensive strategy, specifically enhancing biofilm eradication, reducing inflammation, and alleviating oxidative stress.

Enhanced performance of thermally activated delayed fluorescent light emitting diodes by optimized host polarity.

The interaction between the intrinsic polarity of the host material and the TADF guest material affects charge injection and transport, exciton formation, charge recombination, and emission mechanisms. Therefore, understanding and controlling the interaction between the intrinsic polarity of the host material and the TADF guest material is very important to realize efficient TADF-OLED devices. This study investigated the molecular interaction between different polar host materials and a thermally activated delayed fluorescence material (DMAc-PPM). It has been found that interaction between the host and guest (π-π stacking interaction, multiple CH/π contacts) greatly influence the molecular transition dipole moment orientation of the guest. And the OLED devices based on the strong polar host (DPEPO) exhibited the highest EQEmax and lowest luminescence intensity, while devices using the weaker polar hosts mCP and CBP achieved higher luminance and lower EQEmax. Then, the strong polar host DPEPO was mixed with the weaker polar hosts CBP and mCP, respectively. The devices prepared based on the mixed-host DPEPO: mCP showed a 2.2 times improvement in EQEmax from 6.3% to 20.1% compared to the single-host mCP. The devices prepared based on the mixed-host DPEPO: CBP showed a 3.1 times improvement in luminance intensity from 1023 cd/m2 to 4236 cd/m2 compared to the single host of DPEPO. This suggests that optimizing the polarity of host materials has the potential to enhance the performance of solution prepared OLED devices.

A novel NIR-II albumin-escaping probe for cerebral arteries and perfusion imaging in stroke mice model.

In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment strategies.

Liangxue Tongyu prescription attenuates neuroinflammation by increasing cholecystokinin octapeptide in acute intracerebral hemorrhage rats.

Inflammatory reactions after acute intracerebral hemorrhage (AICH) contribute significantly to a poor prognosis. Liangxue Tongyu Prescription (LTP) has been proven to be clinically effective in treating AICH. Numerous studies have shown that LTP suppresses brain inflammatory damage in AICH, while the internal mechanisms underlying its action remain unclear. The aim of this study was to verify the anti-inflammatory effects of LTP on an AICH rat model and investigate the potential mechanisms. The AICH rat models were created by injecting autologous blood into the right caudate nucleus. LTP markedly decreased cerebral hematoma and brain water content and recovered from neurological deficits. Meanwhile, LTP prevented microglial activation and reduced the inflammatory reaction caused by pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Notably, the expression of cholecystokinin octapeptide (CCK-8) in the brain and intestine was increased by LTP or CCK-8 treatment. LTP further suppressed nuclear factor kappa B (NF-κB) in the brains of rats with AICH. Moreover, LTP increased the protein and mRNA expression of Occludin and Claudin-1 in the intestine and decreased the levels of lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum. Furthermore, the results showed that LTP increased the protein and mRNA expression of Claudin-5 and zonula occludens-1 (ZO-1) in the brain. CCK-8 receptor antagonists increased the expression of NF-κB and the concentration of pro-inflammatory cytokines. These findings suggested that LTP attenuated neuroinflammation by increasing CCK-8 in the brain and intestine, and its mechanism might be related to alterations in the gut-brain axis (GBA).