Charge-assisted hydrogen bonding in a bicyclic amide cage: an effective approach to anion recognition and catalysis in water.

Hydrogen bonding is prevalent in biological systems, dictating a myriad of life-sustaining functions in aqueous environments. Leveraging hydrogen bonding for molecular recognition in water encounters significant challenges in synthetic receptors on account of the hydration of their functional groups. Herein, we introduce a water-soluble hydrogen bonding cage, synthesized via a dynamic approach, exhibiting remarkable affinities and selectivities for strongly hydrated anions, including sulfate and oxalate, in water. We illustrate the use of charge-assisted hydrogen bonding in amide-type synthetic receptors, offering a general molecular design principle that applies to a wide range of amide receptors for molecular recognition in water. This strategy not only revalidates the functions of hydrogen bonding but also facilitates the effective recognition of hydrophilic anions in water. We further demonstrate an unconventional catalytic mechanism through the encapsulation of the anionic oxalate substrate by the cationic cage, which effectively inverts the charges associated with the substrate and overcomes electrostatic repulsions to facilitate its oxidation by the anionic MnO4 -. Technical applications using this receptor are envisioned across various technical applications, including anion sensing, separation, catalysis, medical interventions, and molecular nanotechnology.

Associations between gut microbiota and osteoporosis or osteopenia in a cohort of Chinese Han youth.

Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass and microstructural deterioration of bone. Changes in the composition and structure of gut microbiota (GM) are related to changes of bone mass and bone microstructure. However, the relationship between GM and bone mineral density (BMD) is complex, and data are especially scarce for Chinese Han youth. Therefore, 62 Chinese Han youth participants were recruited. Furthermore, according to the T-score evaluation criteria of the World Health Organization (WHO), we divided the BMD levels of participants into three groups: osteoporosis\BDL, osteopenia\BDM, normal bone density\BDH, and the associations between GM community and BMD groups were conducted. According to alpha and beta diversity analysis, significant differences were found in the microbial richness and composition between groups. The dominant phyla of GM in a cohort of Chinese Han youth were Bacteroidota (50.6%) and Firmicutes (41.6%). Anaerobic microorganisms, such as g_Faecalibacterium and g_Megamonas, account for the largest proportion in the gut, which were mainly Firmicutes phylum. The dominant genera and species in the three BMD groups were g_Prevotella, g_Bacteroides, g_Faecalibacterium, g_Megamonas, s_Prevotella copri, s_unclassified_g_Faecalibacterium, s_unclassified_g_Prevotella, s_unclassified_g_Bacteroides and s_Bacteroides plebeius. g_Faecalibacterium, g_Bacteroides and g_Ruminococcus differed between the BDH and BDL groups as well as between the BDH and BDM groups. LEfSe showed three genus communities and eight species communities were enriched in the three BMD groups, respectively. The associations between microbial relative abundance and T-score was not statistically significant by Spearman and regression analysis. In conclusion, the alpha diversity indexes in the BDH group were higher than in the BDL group, and several taxa were identified that may be the targets for diagnosis and therapy of OP.

Factors associated with cognitive impairment in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of cognitive impairment. Therefore, exploring factors which may be associated with cognitive impairment is important. Correspondingly, this study aimed to systematically evaluate factors associated with cognitive impairment in AF patients by synthesizing relevant evidence. METHODS: A database search of the PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, Wanfang, and VIP databases was conducted from inception until December 21, 2023. The effect size was expressed as a combined odds ratio (OR) and 95 % confidence interval (95 % CI). The heterogeneity was qualitatively analyzed by Cochran's Q test and quantified by the I2 statistic. RESULTS: A total of 7,128 studies were identified from the 8 databases, and 39 studies of 3,491,423 participants were included. A meta-analysis was performed on 19 influencing factors. Advanced age (OR=1.38, 95 % CI: 1.11-1.71), female sex (OR=2.19, 95 % CI: 1.18-4.06), smoking (OR=2.44, 95 % CI: 1.24-4.80), hypertension (OR=1.61, 95 % CI: 1.27-2.03), diabetes (OR=1.42, 95 % CI: 1.20-1.67), and hearing impairment (OR=1.37, 95 % CI: 1.05-1.81) were risk factors for cognitive impairment. A higher education level (OR=0.57, 95 % CI: 0.46-0.72), oral anticoagulants (OR=0.61, 95 % CI: 0.48-0.78), novel oral anticoagulants (OR=0.63, 95 % CI: 0.54-0.73), warfarin (OR=0.55, 95 % CI: 0.39-0.79), novel oral anticoagulants relative to warfarin (OR=0.88, 95 % CI: 0.81-0.97), catheter ablation (OR=0.74, 95 % CI: 0.58-0.94) and exercise (OR=0.66, 95 % CI: 0.61-0.72) were protective factors for cognitive impairment. CONCLUSIONS: Age, sex, education level, smoking, exercise, hypertension, diabetes, hearing impairment, anticoagulation therapy, and catheter ablation were associated with cognitive impairment in AF patients.

Association of coffee consumption with cardiometabolic multimorbidity: A prospective cohort study in the UK biobank.

BACKGROUND AND AIMS: Previous observational studies have investigated the association between coffee consumption and single cardiometabolic disease. Yet, the extent to which coffee might confer health advantages to individuals with a singular cardiometabolic disease remains unclear. This study aimed to further investigate the association of coffee consumption and the onset and progression from single cardiometabolic disease to cardiometabolic multimorbidity (CMM). METHODS AND RESULTS: This prospective cohort study included 185,112 participants from the UK Biobank who were enrolled between 2006 and 2010 and followed up until 2020. Coffee consumption was collected using a 24-h dietary questionnaire. CMM was defined as the coexistence of at least two cardiometabolic diseases, including type 2 diabetes (T2D), coronary heart disease (CHD) and stroke. Cox proportional hazards and multi-state models estimated the associations between coffee consumption and CMM. During a median follow-up of 11.4 years, 1585 participants developed CMM. Compared with nonconsumers, coffee consumers had lower risks for the transitions from baseline to single cardiometabolic disease, with the respective lowest hazard ratios and 95% confidence intervals (CIs) for the transitions from baseline to T2D, CHD and stroke after multivariable adjustment being 0.79 (CI, 0.72-0.87), 0.91 (CI, 0.86-0.97) and 0.87 (CI, 0.78-0.96). Coffee consumption resulted in a significant reduction in the risk of the transitions from CHD and stroke to CMM, with the lowest estimates were 0.56 (CI, 0.43-0.73) and 0.60 (CI, 0.43-0.83). Similar associations were observed in unsweetened coffee. Sugar-sweetened coffee was associated with some transitions at low levels of consumption. The associations between artificially sweetened coffee and CMM were less consistent. CONCLUSIONS: Coffee consumption was associated with lower risk for almost all transition phases of CMM development and consistent findings were observed with unsweetened coffee.

Synthesis and antiproliferative evaluation of new hybrids of piperine and acylhydrazone.

Piperine, a natural amide isolated from the genus of Piper, serves as a pharmacophore in medicinal chemistry. In this study, we synthesised and evaluated 18 novel piperine-acylhydrazone hybrids (4a-4r) for their antiproliferative activities in vitro. The structures of these hybrids were validated using 1H,13C NMR, and HR-ESI-MS data. Furthermore, we screened all synthesised compounds for their antiproliferative activities against three human cancer cell lines: FaDu (laryngeal carcinoma cells), HepG2 (hepatoblastoma carcinoma cells), and MGC803 (gastric carcinoma cells). Among them, compound 4o exhibited significantly inhibitory activities against FaDu, HepG2, and MGC803 with IC50 values of 13.85 ± 0.19, 11.02 ± 1.45, and 13.47 ± 3.43 µM, respectively, which was approximately two-fold lower than the positive control cisplatin. These findings suggest that compound 4o has the potential to be promising leads for the design of anti-cancer drugs.

The predictors of lymphopenia and its effects on survival in locally advanced esophageal squamous cell carcinoma.

To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (r= -0.389, p < .001) and GTV (r= -0.211, p < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group (p = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm3 group (p = .242) and GTV ≤ 68.8 cm3 group(p = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.

IL-17A/F double producing T cells, unstable Tregs and quiescent TRMs in clinically healed lesions are potential cellular candidates for recurrence of psoriasis.

Biological antibodies targeting key cytokines such as IL-17 and IL-23 have revolutionized psoriasis outcome. However, the recurrence remains an urgent challenge to be addressed. Currently, most of the descriptions of skin T-cell characteristics in psoriasis are derived from lesional and non-lesional skin, and their characteristics in resolved lesions (clinically healed lesions) remain vague. In order to further elucidate the cellular mechanism of recurrence, we performed single-cell sequencing and multiplexed immunohistochemical staining of T-cell subsets in autologous resolved lesion (RL), on-site recurrent psoriatic lesion (PL), and adjacent normal-appearing skin (NS) of psoriasis. By comparing with PL and NS tissues, we identified three potential cellular candidates for recurrence in clinically healed lesions: IL-17A/F double producing T cells, unstable Tregs and quiescent TRMs. Our results provide research clues for elucidating the immunological recurrence mechanism of psoriasis, and further work is needed to deepen our findings.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Phenolic Constituents with Glucose Uptake and GLUT4 Translocation Bioactivities from the Fruits of Cordia dichotoma.

From the fruits of Cordia dichotoma, 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H (8) and dichotomin I (9) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3, 5, 7, 17, 18, 23-25, and 27-30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 µg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 µg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).

Theoretical study on lithium storage performance of V-doped Ti2CO2 MXene.

With the increasing application of lithium-ion batteries, the demand for high energy density, high-rate performance and high stability lithium-ion batteries is becoming more and more urgent. Ti2CO2 MXene, as a two-dimensional material with multilayer atomic structure and multiple active sites, has great advantages in lithium-ion battery electrode materials. However, the original Ti2CO2 MXene has been unable to meet the requirements of lithium-ion batteries due to its semiconductor properties. Doping is an effective means to regulate the conductivity and electrochemical properties of Ti2CO2 and improve the capacity of lithium-ion batteries and other energy storage devices. Hence, we use first-principles calculations to study the effect of V atom doping on the adsorption and diffusion of Li on the MXene surface. The density of states (DOS) and partial density of states (PDOS) of TiVCO2 and Ti2CO2 MXene indicated the transition of their conductive types from semiconductors to conductors. In addition, we observed that TiVCO2 has higher electrical conductivity and ion transport speed than the original Ti2CO2 MXene, and at the same time, Li atoms can be adsorbed well on the surface of MXene and show a lower diffusion energy barrier. Therefore, TiVCO2 is expected to become the anode material for the next generation of lithium-ion batteries and has good lithium storage performance.

A Whole-Course-Repair System Based on Stimulus-Responsive Multifunctional Hydrogels for Myocardial Tissue Regeneration.

Myocardial infarction (MI) has emerged as the predominant cause of cardiovascular morbidity globally. The pathogenesis of MI unfolds as a progressive process encompassing three pivotal phases: inflammation, proliferation, and remodeling. Smart stimulus-responsive hydrogels have garnered considerable attention for their capacity to deliver therapeutic drugs precisely and controllably at the MI site. Here, a smart stimulus-responsive hydrogel with a dual-crosslinked network structure is designed, which enables the precise and controlled release of therapeutic drugs in different pathological stages for the treatment of MI. The hydrogel can rapidly release curcumin (Cur) in the inflammatory phase of MI to exert anti-apoptotic/anti-inflammatory effects. Recombinant humanized collagen type III (rhCol III) is loaded in the hydrogel and released as the hydrogel swelled/degraded during the proliferative phase to promote neovascularization. RepSox (a selective TGF-ß inhibitor) releases from Pluronic F-127 grafted with aldehyde nanoparticles (PF127-CHO@RepSox NPs) in the remodeling phase to against fibrosis. The results in vitro and in vivo suggest that the hydrogel improves cardiac function and alleviates cardiac remodeling by suppressing inflammation and apoptosis, promoting neovascularization, and inhibiting myocardial fibrosis. A whole-course-repair system, leveraging stimulus-responsive multifunctional hydrogels, demonstrates notable effectiveness in enhancing post-MI cardiac function and facilitating the restoration of damaged myocardial tissue.

Glycoengineering-based anti-PD-1-iRGD peptide conjugate boosts antitumor efficacy through T cell engagement.

Despite the important breakthroughs of immune checkpoint inhibitors in recent years, the objective response rates remain limited. Here, we synthesize programmed cell death protein-1 (PD-1) antibody-iRGD cyclic peptide conjugate (αPD-1-(iRGD)2) through glycoengineering methods. In addition to enhancing tissue penetration, αPD-1-(iRGD)2 simultaneously engages tumor cells and PD-1+ T cells via dual targeting, thus mediating tumor-specific T cell activation and proliferation with mild effects on non-specific T cells. In multiple syngeneic mouse models, αPD-1-(iRGD)2 effectively reduces tumor growth with satisfactory biosafety. Moreover, results of flow cytometry and single-cell RNA-seq reveal that αPD-1-(iRGD)2 remodels the tumor microenvironment and expands a population of "better effector" CD8+ tumor infiltrating T cells expressing stem- and memory-associated genes, including Tcf7, Il7r, Lef1, and Bach2. Conclusively, αPD-1-(iRGD)2 is a promising antibody conjugate therapeutic beyond antibody-drug conjugate for cancer immunotherapy.

Measurement of medical students' knowledge, attitude and practice towards antibiotic use and resistance: A scoping review.

OBJECTIVE: Medical students are demanders and future suppliers of antibiotic use. Understanding their knowledge, attitude and practice is important for appropriately using antibiotics and controlling antibiotic resistance. The objective of this study was to assess the measurement properties of existed instruments and summarize measurement items and results. METHODS: Five English and Chinese databases were searched to comprehensively identify related studies between January 2000 and May 2023. Included instruments were assessed using consensus-based standards for the selection of health measurement instruments checklist. Descriptive tables and narrative texts were applied to summary the data. RESULTS: Of 3524 studies identified, 25 were finally included, from which 22 measurement instruments were included. Of these, 14 instruments were found with adequate content validity, only one study reported structural validation process and two studies reported reliability test results. Similar items were divided into different dimensions in different studies. Gaps and misconceptions in knowledge and attitude were indicated in antibiotic use principles, including antibiotic use indications and selection. CONCLUSIONS: Limitations existed in the current measurement instrument including lacking validation, inconsistent classification of item and lacking item regarding the perspective of suppliers. Scientific tools for objective and accurate measure are needed.

Hydrogen peroxide serves as pivotal fountainhead for aerosol aqueous sulfate formation from a global perspective.

Traditional atmospheric chemistry posits that sulfur dioxide (SO2) can be oxidized to sulfate (SO42-) through aqueous-phase reactions in clouds and gas-phase oxidation. Despite adequate knowledge of traditional mechanisms, several studies have highlighted the potential for SO2 oxidation within aerosol water. Given the widespread presence of tropospheric aerosols, SO42- production through aqueous-phase oxidation in aerosol water could have a pervasive global impact. Here, we quantify the potential contributions of aerosol aqueous pathways to global sulfate formation based on the GEOS-Chem simulations and subsequent theoretical calculations. Hydrogen peroxide (H2O2) oxidation significantly influences continental regions both horizontally and vertically. Over the past two decades, shifts in the formation pathways within typical cities reveal an intriguing trend: despite reductions in SO2 emissions, the increased atmospheric oxidation capacities, like rising H2O2 levels, prevent a steady decline in SO42- concentrations. Abating oxidants would facilitate the benefit of SO2 reduction and the positive feedback in sulfate mitigation.

Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study.

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234.

Advances in nano-immunotherapy for hematological malignancies.

Hematological malignancies (HMs) encompass a diverse group of blood neoplasms with significant morbidity and mortality. Immunotherapy has emerged as a validated and crucial treatment modality for patients with HMs. Despite notable advancements having been made in understanding and implementing immunotherapy for HMs over the past decade, several challenges persist. These challenges include immune-related adverse effects, the precise biodistribution and elimination of therapeutic antigens in vivo, immune tolerance of tumors, and immune evasion by tumor cells within the tumor microenvironment (TME). Nanotechnology, with its capacity to manipulate material properties at the nanometer scale, has the potential to tackle these obstacles and revolutionize treatment outcomes by improving various aspects such as drug targeting and stability. The convergence of nanotechnology and immunotherapy has given rise to nano-immunotherapy, a specialized branch of anti-tumor therapy. Nanotechnology has found applications in chimeric antigen receptor T cell (CAR-T) therapy, cancer vaccines, immune checkpoint inhibitors, and other immunotherapeutic strategies for HMs. In this review, we delineate recent developments and discuss current challenges in the field of nano-immunotherapy for HMs, offering novel insights into the potential of nanotechnology-based therapeutic approaches for these diseases.

Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.

AURKA is a threonine or serine kinase that needs to be activated by TPX2, Bora and other factors. AURKA is located on chromosome 20 and is amplified or overexpressed in many human cancers, such as breast cancer. AURKA regulates some basic cellular processes, and this regulation is realized via the phosphorylation of downstream substrates. AURKA can function in either the cytoplasm or the nucleus. It can promote the transcription and expression of oncogenes together with other transcription factors in the nucleus, including FoxM1, C-Myc, and NF-κB. In addition, it also sustains carcinogenic signaling, such as N-Myc and Wnt signaling. This article will focus on the role of AURKA in the nucleus and its carcinogenic characteristics that are independent of its kinase activity to provide a theoretical explanation for mechanisms of resistance to kinase inhibitors and a reference for future research on targeted inhibitors.

AURKA plays an important role in the control of the proliferation, invasion, cell cycle regulation and self-renewal of cancer stem cells.Small molecule kinase inhibitors targeting AURKA have been developed, but the overall response rate of patients in clinical trials is not ideal, prompting us to pay attention to the non-kinase activity of AURKA.This review focuses on the nuclear function of AURKA and its oncogenic properties independent of kinase activity, demonstrating that the nuclear substrate of AURKA and the remote allosteric site of the kinase may be targets of anticancer therapy.

Remodeling brain pathological microenvironment to lessen cerebral ischemia injury by multifunctional injectable hydrogels.

Ischemia stroke is one of the leading causes of death and disability worldwide. Owing to the limited delivery efficiency to the brain caused by the blood-brain barrier (BBB) and off-target effects of systemic treatment, it is crucial to develop an in situ drug delivery system to improve the therapeutic effect in ischemic stroke. Briefly, we report a multifunctional in situ hydrogel delivery system for the co-delivery of reactive oxygen species (ROS)-responsive nanoparticles loaded with atorvastatin calcium (DSPE-se-se-PEG@AC NPs) and ß-nerve growth factor (NGF), which is expected to remodel pathological microenvironment for improving cerebral ischemia injury. The in vitro results exhibited the multifunctional hydrogel scavenged oxygen-glucose deprivation (OGD)-induced free radical, rescued the mitochondrial function, and maintained the survival and function of neurons, hence reducing neuronal apoptosis and neuroinflammation, consequently relieving ischemia injury in hippocampal neurons cell line (HT22). In the rat ischemia stroke model, the hydrogel significantly minified cerebral infarction by regulating inflammatory response, saving apoptotic neurons, and promoting angiogenesis and neurogenesis. Besides, the hydrogel distinctly improved the rats' neurological deficits after cerebral ischemia injury over the long-term observation. In conclusion, the in-situ hydrogel platform has demonstrated promising therapeutic effects in both in vitro and in vivo studies, indicating its potential as a new and effective therapy.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.