Reduction of Oxidative Stress and Excitotoxicity by Mesenchymal Stem Cell Biomimetic Co-Delivery System for Cerebral Ischemia-Reperfusion Injury Treatment.

A cerebral ischemia-reperfusion injury is ensued by an intricate interplay between various pathological processes including excitotoxicity, oxidative stress, inflammation, and apoptosis. For a long time, drug intervention policies targeting a single signaling pathway have failed to achieve the anticipated clinical efficacy in the intricate and dynamic inflammatory environment of the brain. Moreover, inadequate targeted drug delivery remains a significant challenge in cerebral ischemia-reperfusion injury therapy. In this study, a multifunctional nanoplatform (designated as PB-006@MSC) is developed using ZL006-loaded Prussian blue nanoparticles (PBNPs) camouflaged by a mesenchymal stem cell (MSC) membrane (MSCm). ZL006 is a neuroprotectant. It can be loaded efficiently into the free radical scavenger PBNP through mesoporous adsorption. This can simultaneously modulate multiple targets and pathways. MSCm biomimetics can reduce the nanoparticle immunogenicity, efficiently enhance their homing capability to the cerebral ischemic penumbra, and realize active-targeting therapy for ischemic stroke. In animal experiments, PB-006@MSC integrated reactive oxygen species (ROS) scavenging and neuroprotection. Thereby, it selectively targeted the cerebral ischemic penumbra (about fourfold higher accumulation at 24 h than in the non-targeted group), demonstrated a remarkable therapeutic efficacy in reducing the volume of cerebral infarction (from 37.1% to 2.3%), protected the neurogenic functions, and ameliorated the mortality.

Prediction of clinical risk assessment and survival in chronic obstructive pulmonary disease with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non-invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD-PH). METHODS: This study included 535 patients with COPD-PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD-PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan-Meier curves were used for a survival analysis. The nomograms were developed as online network software. RESULTS: Tricuspid regurgitation velocity, right ventricular diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), the red blood cell count, New York Heart Association functional class and sex were non-invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT-proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD-PH and were used to create a predictive nomogram of overall survival rates. CONCLUSIONS: The proposed nomograms based on a large sample size of patients with COPD-PH could be used as non-invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD-PH. Additionally, the online network has the potential to provide artificial intelligence-assisted diagnosis and treatment. HIGHLIGHTS: A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non-invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD-PH.

Efficacy of transcutaneous electrical nerve stimulation combined with mirabegron therapy compared with mirabegron monotherapy for overactive bladder: a prospective randomized controlled study.

PURPOSE: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). METHODS: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. RESULTS: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. CONCLUSIONS: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. TRIAL REGISTRATION NUMBER: ChiCTR2400080528 (31.01.2024, retrospectively registered).

Care model selection for older adult stroke survivors with disabilities: insights from the eighth wave of CLHLS data and influencing factors.

Background: Analyzing the differences in caregiving models for disabled older adult individuals after stroke and the influencing factors, to provide a basis for addressing relevant social demographic issues. Methods: The older adult diagnosed with stroke were screened from the Chinese Geriatric Health Survey (CLHLS), and were further divided into subgroups of disability, which was based on their ability of or whether they need help in performing activities such as dressing, bathing, eating, toileting or bowel and bladder control using the international common Katz scale. The care model was divided into formal care, informal care and home care. Multivariate logistic regression was used to screen the influencing factors of the choice of care model for the disabled older adult after stroke. Results: The results of univariate analysis showed that there were statistical differences in the choice of care mode among different ages, household registration types, number of children, years of education, degree of disability, community services, retirement pension, marital status and medical insurance. Multiple logistic regression showed that, The rural older adult with more children, shorter education years, living with spouse and no help from community tend to choose informal care. Older adult people with higher levels of education, urban household registration, and access to community services are more likely to choose formal care. Older adult women with multiple children are more likely to receive care from their children. Conclusion: In the future, vigorous support for the development of formal caregiving institutions and the improvement of the management system of formal caregiving will help enhance the subjective initiative of disabled older adult individuals in choosing caregiving models and alleviate the burden of family caregiving.

The moderating role of work environment in the relationship between proactive personality and personal growth initiative among nurses: a cross-sectional study.

BACKGROUNDS: Personal growth initiative (PGI) is regarded as a meaningful concept with potential value at both the individual and organizational levels, but little is known about the factors that contribute to nurses' PGI. This study aimed to explore how proactive personality and hospital work environment affect PGI of clinical nurses. METHODS: A cross-sectional study was conducted between September and October 2022 among 4414 nurses from 10 tertiary general hospitals in 10 cities in Sichuan, China, using a two-stage sampling method. Self-reported anonymous online questionnaires, such as sociodemographic information survey, personal growth initiative scale II, the 10-item proactive personality scale, and practice environment scale-nursing work index were used to collect data. Multiple hierarchical regression analyses were performed to examine research hypotheses. RESULTS: Among the control variables in this study, nurses' self-perceptions of general health status and professional title positively predicted PGI (ß = 0.462, 95%CI = 0.272-0.653; ß = 1.078, 95%CI = 0.508-1.648). After adding control variables, both proactive personality (ß = 1.143, 95%CI = 1.096-1.190) and work environment (ß = 3.391, 95%CI = 2.904-3.879) positively predicted PGI. The work environment positively moderated the association between proactive personality and PGI (ß = 0.108, 95%CI = 0.025-0.191). These predictors jointly explained 50.3% of the variance in PGI. CONCLUSIONS: Nurses with a greater tendency to have a typical proactive personality have higher levels of personal growth initiative, and this positive effect will be better highlighted in a healthier work environment. Nursing managers should prioritize the employment of people with proactive personality traits, focus on the development and stimulation of proactive personality traits in nurses, and establish a supportive work environment to maximize the personal growth initiative of nurses.

In situ densification and heparin immobilization of bacterial cellulose vascular patch for potential vascular applications.

Nowadays, developing vascular grafts (e.g., vascular patches and tubular grafts) is challenging. Bacterial cellulose (BC) with 3D fibrous network has been widely investigated for vascular applications. In this work, different from BC vascular patch cultured with the routine culture medium, dopamine (DA)-containing culture medium is employed to in situ synthesize dense BC fibrous structure with significantly increased fiber diameter and density. Simultaneously, BC fibers are modified by DA during in situ synthesis process. Then DA on BC fibers can self-polymerize into polydopamine (PDA) accompanied with the removal of bacteria in NaOH solution, obtaining PDA-modified dense BC (PDBC) vascular patch. Heparin (Hep) is subsequently covalently immobilized on PDBC fibers to form Hep-immobilized PDBC (Hep@PDBC) vascular patch. The obtained results indicate that Hep@PDBC vascular patch exhibits remarkable tensile and burst strength due to its dense fibrous structure. More importantly, compared with BC and PDBC vascular patches, Hep@PDBC vascular patch not only displays reduced platelet adhesion and improved anticoagulation activity, but also promotes the proliferation, adhesion, spreading, and protein expression of human umbilical vein endothelial cells, contributing to the endothelialization process. The combined strategy of in situ densification and Hep immobilization provides a feasible guidance for the construction of BC-based vascular patches.

Characteristics and antioxidant activities of seed oil from okra (Abelmoschus esculentus L.).

To investigate the potential functional properties and added value of okra seed oil and provide a scientific basis for further industrial development and production of okra seed oil, its fatty acid profile, total phenolic, fat-soluble vitamin composition, mineral element composition, and antioxidant activities were examined in this study. Also, correlations between bioactive components and the antioxidant activities of okra seed oil were explored. The study results show that okra seed oil contains 12 types of fatty acids, 65.22% of which are unsaturated acids, and among these unsaturated acids, linoleic acid (43%) and oleic acid (20.16%) are two dominant acid types. Compared with walnut oil and peanut oil, okra seed oil contains relatively high total phenols, fat-soluble vitamins, and a variety of essential mineral nutrients, with a total phenolic content (TPC) of 959.65 µg/mL, a total tocopherol content of 742.71 µg/mL, a vitamin A content of 0.0017 µg/100 mL, a vitamin D content of 1.44 µg/100 mL, and a vitamin K1 content of 52.54 ng/100 mg. Also, okra seed oil exhibits better scavenging activities on hydroxyl (IC50 = 0.50 mg/mL) and ammonium salt (ABTS) free radicals (IC50 = 6.46 mg/mL) and certain reducing power (IC50 = 17.22 mg/mL) at the same concentration. The scavenging activities of okra seed oil on hydroxyl radicals and ABTS radicals, as well as its reducing power, are significantly correlated with its contents of total phenol, total tocopherol, α-tocopherol, and γ-tocopherol (p < .01). These results show that okra seed oil is rich in bioactive substances, thus presenting great nutritional potential.

BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension.

BACKGROUND: An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-ß (transforming growth factor-ß) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-ß family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-ßR2/R1, and receptor-regulated Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination. By modulating the posttranslational modifications of the BMP/TGF-ß-PPARγ pathway, BRCC3 may play a role in pulmonary vascular remodeling, hence the pathogenesis of PAH. METHODS: Bioinformatic analyses were used to explore the mechanism by which BRCC3 deubiquitinates ALK2. Cultured pulmonary artery smooth muscle cells (PASMCs), mouse models, and specimens from patients with idiopathic PAH were used to investigate the rebalance between BMP and TGF-ß signaling in regulating ALK2 phosphorylation and ubiquitination in the context of pulmonary hypertension. RESULTS: BRCC3 was significantly downregulated in PASMCs from patients with PAH and animals with experimental pulmonary hypertension. BRCC3, by de-ubiquitinating ALK2 at Lys-472 and Lys-475, activated receptor-regulated Smad1/5/9, which resulted in transcriptional activation of BMP-regulated PPARγ, p53, and Id1. Overexpression of BRCC3 also attenuated TGF-ß signaling by downregulating TGF-ß expression and inhibiting phosphorylation of Smad3. Experiments in vitro indicated that overexpression of BRCC3 or the de-ubiquitin-mimetic ALK2-K472/475R attenuated PASMC proliferation and migration and enhanced PASMC apoptosis. In SM22α-BRCC3-Tg mice, pulmonary hypertension was ameliorated because of activation of the ALK2-Smad1/5-PPARγ axis in PASMCs. In contrast, Brcc3-/- mice showed increased susceptibility of experimental pulmonary hypertension because of inhibition of the ALK2-Smad1/5 signaling. CONCLUSIONS: These results suggest a pivotal role of BRCC3 in sustaining pulmonary vascular homeostasis by maintaining the integrity of the BMP signaling (ie, the ALK2-Smad1/5-PPARγ axis) while suppressing TGF-ß signaling in PASMCs. Such rebalance of BMP/TGF-ß pathways is translationally important for PAH alleviation.

Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients.

Background: The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer. Methods: We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). Results: The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p<0.001), liver metastasis (p<0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels. Conclusion: Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.

Lung microdialysis and in vivo PK/PD integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model.

This study aim to explore the application of microdialysis in pharmacokinetic (PK) and pharmacodynamic (PD) integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model. The model was established via intratracheal inoculation where average bacterial counts (CFU) in the lungs of infected pigs reached 6.57 log10 CFU/g after 3 h. The PK profiles of unbound cefquinome in lung dialysates were determined following intramuscular injection of single doses of 0.125, 0.25, 0.5, 1, 2, and 4 mg/kg. Lung dialysate samples were collected using microdialysis at a flow rate of 1.5 µL/min until 24 h. The PD studies were conducted over 24 h based on 10 intermittent dosing regimens and total daily doses ranged from 0.25 to 4 mg/kg and dosage intervals included 12 and 24 h. The lung tissue was collected after 24 h of treatment and homogenized for bacterial counts. The relationships between PK/PD parameters derived from lung dialysates and drug efficacy were analyzed using an inhibitory sigmoid Emax model. The percentage of time the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) was the PK/PD index best describing the antimicrobial activity (R2 = 0.96) in the porcine experimental infection model. The %fT > MIC values required to achieve net bacterial stasis, 1, 2 and 3 log10 CFU/g reductions in the lung were 22.45, 28.86, 37.62, and 56.46%, respectively. Cefquinome exhibited time-dependent characteristics against A. pleuropneumoniae in vivo. These results provide valuable insights into the application of microdialysis in PK/PD integration model studies and optima regimen of cefquinome for the treatment of porcine respiratory diseases caused by A. pleuropneumoniae.

Efficient and Robust Parameter Optimization of the Unitary Coupled-Cluster Ansatz.

The variational quantum eigensolver (VQE) framework has been instrumental in advancing near-term quantum algorithms. However, parameter optimization remains a significant bottleneck for VQE, requiring a large number of measurements for successful algorithm execution. In this paper, we propose sequential optimization with approximate parabola (SOAP) as an efficient and robust optimizer specifically designed for parameter optimization of the unitary coupled-cluster ansatz on quantum computers. SOAP leverages sequential optimization and approximates the energy landscape as quadratic functions, minimizing the number of energy evaluations required to optimize each parameter. To capture parameter correlations, SOAP incorporates the average direction from previous iterations into the optimization direction set. Numerical benchmark studies on molecular systems demonstrate that SOAP achieves significantly faster convergence and greater robustness to noise compared with traditional optimization methods. Furthermore, numerical simulations of up to 20 qubits reveal that SOAP scales well with the number of parameters in the ansatz. The exceptional performance of SOAP is further validated through experiments on a superconducting quantum computer using a 2-qubit model system.

A Nature-Derived, Hetero-Structured, Pro-Healing Bioadhesive Patch for High-Performance Sealing of Wet Tissues.

Tissue adhesives are promising alternatives to sutures and staples to achieve wound closure and hemostasis. However, they often do not work well on tissues that are soaked in blood or other biological fluids, and organs that are typically exposed to a variety of harsh environments such as different pH values, nonhomogeneous distortions, continuous expansions and contractions, or high pressures. In this study, a nature-derived multilayered hetero-bioadhesive patch (skin secretion of Andrias davidianus (SSAD)-Patch) based on hydrophilic/hydrophobic pro-healing bioadhesives derived from the SSAD is developed, which is designed to form pressure-triggered strong adhesion with wet tissues. The SSAD-Patch is successfully applied for the sealing and healing of tissue defects within 10 s in diverse extreme injury scenarios in vivo including rat stomach perforation, small intestine perforation, fetal membrane defect, porcine carotid artery incision, and lung lobe laceration. The findings reveal a promising new type of self-adhesive regenerative SSAD-Patch, which is potentially adaptable to broad applications (under different pH values and air or liquid pressures) in sutureless wound sealing and healing.

Single-Electron Reduction of "Push-Pull" C-C Single Bond and Decyanation Using Tertiary Amines as the Organic Electron Donor.

Using commercially available tertiary amines as an organic electron donor (OED), the reduction of "push-pull" C-C single bond and reductive decyanation of tetrahydroisoquinolines were realized. These reactions exhibited higher reaction efficiency and better functional group tolerance compared with those of metallic reductants, and the mechanistic study indicated that a radical intermediate was involved in the reduction of the C-C single bond, which provides a new way to the OED-enabled mild reduction.

Endothelium-specific SIRT7 targeting ameliorates pulmonary hypertension through Krüpple-like factor 4 deacetylation.

AIMS: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodelling during the onset of PH. This study aimed to illustrate the role of Sirtuin 7 (SIRT7) in endothelial dysfunction during PH and explore the potential therapeutic strategy for PH. METHODS AND RESULTS: SIRT7 levels were measured in human and murine experimental PH samples. Bioinformatic analysis, immunoprecipitation, and deacetylation assay were used to identify the association between SIRT7 and Krüpple-like factor 4 (KLF4), a key transcription factor essential for endothelial cell (EC) homeostasis. Sugen5416 + hypoxia (SuHx)-induced PH mouse models and cell cultures were used for the study of the therapeutic effect of SIRT7 for PH. SIRT7 level was significantly reduced in lung tissues and PAECs from PH patients and the SuHx-induced PH mouse model as compared with healthy controls. Pulmonary endothelium-specific depletion of Sirt7 increased right ventricular systolic pressure and exacerbated right ventricular hypertrophy in the SuHx-induced PH model. At the molecular level, we identified KLF4 as a downstream target of SIRT7, which deacetylated KLF4 at K228 and inhibited the ubiquitination-proteasome degradation. Thus, the SIRT7/KLF4 axis maintained PAEC homeostasis by regulating proliferation, migration, and tube formation. PAEC dysfunction was reversed by adeno-associated virus type 1 vector-mediated endothelial overexpression of Sirt7 or supplementation with nicotinamide adenine dinucleotide (NAD)+ intermediate nicotinamide riboside which activated Sirt7; both approaches successfully reversed PH phenotypes. CONCLUSION: The SIRT7/KLF4 axis ensures PAEC homeostasis, and pulmonary endothelium-specific SIRT7 targeting might constitute a PH therapeutic strategy.

CBr4 as a Mild Oxidant-Enabled Oxidation of a sp3 C-H Bond: A Facile Synthesis of the Persistent Iminium Salts of Tetrahydroisoquinolines.

Using CBr4 as a mild oxidant, the direct C-H bond oxidation of N-aryltetrahydroisoquinolines was achieved, giving a series of the corresponding iminium salts in high yields under metal- and photo-free reaction conditions. This reaction is superior in high yields and good functional group tolerance, and the late-stage derivatization showed that these iminium salts can readily be applied to the synthesis of the functionalized THIQs.

Genetic evaluation for twin pregnancies using karyotyping and single nucleotide polymorphism array analysis.

The study aimed to assess chromosomal abnormalities in twin pregnancies using karyotyping and SNP array analysis. The research involved 530 twin pregnancies from two prenatal diagnosis centers between October 2012 and October 2022. Two types of twin pregnancies were considered: monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA), with a total of 177 MCDA and 353 DCDA cases. Chromosomal abnormalities were examined based on chorionic and amniotic sac properties and clinical indications. Among 42 twin pregnancies, 50 fetuses showed chromosomal abnormalities by karyotyping, with 35 cases of aneuploidy in DCDA and 10 in MCDA. Trisomy 21 was the most common aberration, affecting 15 fetuses in DCDA and 4 in MCDA. The rate of discordant karyotypes in MCDA and DCDA groups was 1.1% and 8.8%, respectively. Ultrasound abnormalities and advanced maternal age were frequent indications (55.3% and 39.2%, respectively). Aneuploidy frequencies in DCDA and MCDA pregnancies with advanced maternal age were 10.6% and 4.5%. Cardiac defects and increased nuchal translucency were common anomalies, with higher incidences of chromosomal abnormalities in DCDA (12.5% and 6.9%) and MCDA groups (23.5% and 3.7%). SNP array identified 1.6% clinically significant copy number variants in DCDA fetuses with ultrasound abnormalities, while no significant CNVs were found in MCDA pregnancies. Chromosomal aneuploidies were the primary abnormalities in twin pregnancies, with detectable abnormalities and clinically significant CNVs more likely in DCDA pregnancies, especially those with ultrasound abnormalities.

Oxidants Controlled C-H Bond Functionalization of N-Aryltetrahydroisoquinolines: The Construction of the Quaternary Carbon Center and Cleavage of the C-N Bond.

Initiated by triarylamine radical cation salt (TBPA), the direct C-H bond functionalization of α-N-aryltetrahydroisoquinoline esters was smoothly realized, giving a series of α-hydroxylated derivatives with a quaternary carbon center in good yields. Differently, in the presence of tert-butyl nitrite (TBN), the C-N single bond was cleaved to keto esters. The mechanistic study revealed that these reactions were mediated by a similar mechanism, in which the N-nitrosation might provide a driving force to the C-N bond cleavage.

Enhanced the treatment of ischemic stroke through intranasal temperature-sensitive hydrogels of edaravone and borneol inclusion complex.

Since ischemic stroke occurs by a combination of multiple mechanisms, therapies that modulate multiple mechanisms are required for its treatment. The combination of edaravone (EDA) and borneol can significantly ameliorate the symptoms of neurological deficits in cerebral ischemia-reperfusion model in rats. In this study, the solubility of borneol and edaravone was improved by hydroxypropyl-ß-cyclodextrin and PEG400. Furthermore, a nasal temperature-sensitive hydrogel containing both edaravone and borneol inclusion complex (EDA-BP TSGS) was developed to overcome the obstacles of ischemic stroke treatment including the obstruction of the blood-brain barrier (BBB) and the unavailability and untimely of intravenous injection. The effectiveness of the thermosensitive hydrogel was investigated in transient middle cerebral artery occlusion/reperfusion model rats (MCAO/R). The results showed that EDA-BP TSGS could significantly alleviate the symptoms of neurological deficits and decrease the cerebral infarct area and the degree of brain damage. In summary, nasal EDA-BP TSGS is a secure and effective brain-targeting formulation that may provide a viable option for the clinical prophylaxis and treatment of ischemic stroke.

Size Segregation of Gold Nanoparticles into Bilayer-like Vesicular Assembly.

Size segregation of nanoparticles with different sizes into highly ordered, unique nanostructures is important for their practical applications. Herein, we demonstrate spontaneous self-assembly of the binary mixtures of small and large gold nanoparticles (GNPs; 5/15, 5/20, or 10/20 in diameter) in the presence of a tetra(ethylene glycol)-terminated octafluoro-4,4'-biphenol ligand, namely, TeOFBL, resulting in a size-segregated assembly. The outer single layer of large GNPs forming a gold nanoparticle vesicle (GNV) encapsulated the inner vesicle-like assembly composed of small GNPs, which is referred to as bilayer-like GNV and similar to the molecular bilayer structure of a liposome. The size segregation was driven by the solvophobic feature of the TeOFBLs on the surface of GNPs. A time-course study indicated that size segregation occurred instantaneously during the mixing stage of the self-organization process. The size-segregated precursors quickly fused with each other through the inner-inner and outer-outer layer fashion to form the bilayer-like GNV. This study provides a new approach to creating biomimetic bilayer capsules with different physical properties for potential applications such as surface-enhanced Raman scattering and drug delivery.