Effects of a nurse-led motor function rehabilitation training program for patients with ischemic stroke and family caregivers: study protocol for a randomized controlled trial.

BACKGROUND: Both individuals and society bear a considerable burden from ischemic stroke (IS), not only do patients continue suffering from motor dysfunction after discharge from hospital, but their caregivers also undertake the principal responsibility of assisting them in reintegrating into the family and society. To better improve the IS patients' limb function and daily life activities, their caregivers should also be involved in the training of the motor function rehabilitation during the period transitioning from hospital back home. This study mainly aims to investigate the effects of a nurse-led training for IS patients and their family caregivers on the improvement of the patients' physical function and the burden of caregivers. METHODS/DESIGN: A randomized controlled trial with blind assessment will be conducted in hospitals and during the follow-ups at home. Fifty-eight pairs of adults diagnosed with ischemic stroke and their primary caregivers will be included. Participants will be randomly given with (1) a nurse-led, home-based motor rehabilitation training participated by caregivers (intervention group) or (2) routine self-care (control group). Both groups will receive assessment and health guidance on the day of discharge, and the intervention group will receive an additional home-based training program and supervision. These two groups will be followed up every week after discharge. The primary results are drawn from the evaluation of physical function and caregiver-related burden, and the secondary results derived from statistics of the modified Barthel index, stroke-specific quality of life, and National Institutes of Health Stroke Scale. Differences between the two groups will be measured by two-way repeated measures ANOVA, considering the data at baseline and at 1-week and 4-week follow-up after training. DISCUSSION: Results may provide novel and valuable information on the effects of this culturally appropriate, caregiver-involved, and home-based rehabilitation training on the physical function of IS patients and caregiver-related burden. TRIAL REGISTRATION: Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2300078798. Registered on December 19, 2023.

Engineered Mitochondrial Transplantation as An Anti-Aging Therapy.

Aging is an inevitable and complex biological process involving multi-factorial mechanisms. Mitochondrial dysfunction is a critical factor in the aging process, characterized by a decline in mitochondrial quality and activity, leading to aging and aging-related diseases. Therefore, mitochondria have become an attractive target in anti-aging therapies. Several senolytic drugs targeting mitochondria and antioxidant agents have been used in anti-aging research in the past few years. However, these strategies may cause adverse effects with long-term medication. In this extensive review, we propose "mitochondrial transplantation," which transfers healthy mitochondria from donor cells to recipient cells to replace damaged or dysfunctional mitochondria, as a new alternative strategy for treating mitochondrial dysfunction and aging-associated diseases. In this review, we introduce the contemporary landscape of mitochondrial transplantation, then discuss intensely the successful applications of mitochondrial transplantation therapy in aging diseases such as neurodegenerative diseases, cardiovascular aging, and reproductive aging, highlighting its translational potential. Finally, we summarize and prospect the challenges and opportunities mitochondrial transplantation faces in anti-aging therapy.

Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study.

Background: Circulating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC's progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression. Material and methods: We conducted a two-sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Results: In the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10-4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10-4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation. Conclusion: Our research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.

Single Nucleus Total RNA Sequencing of Formalin-Fixed Paraffin-Embedded Gliomas.

Gliomas, the predominant form of brain cancer, comprise diverse malignant subtypes with limited curative therapies available. The insufficient understanding of their molecular diversity and evolutionary processes hinders the advancement of new treatments. Technical complexities associated with formalin-fixed paraffin-embedded (FFPE) clinical samples hinder molecular-level analyses of gliomas. Current single-cell RNA sequencing (scRNA-seq) platforms are inadequate for large-scale clinical applications. In this study, automated snRandom-seq is developed, a high-throughput single-nucleus total RNA sequencing platform optimized for archival FFPE samples. This platform integrates automated single-nucleus isolation and droplet barcoding systems with the random primer-based scRNA-seq chemistry, accommodating a broad spectrum of sample types. The automated snRandom-seq is applied to analyze 116 492 single nuclei from 17 FFPE samples of various glioma subtypes, including rare clinical samples and matched primary-recurrent glioblastomas (GBMs). The study provides comprehensive insights into the molecular characteristics of gliomas at the single-cell level. Abundant non-coding RNAs (ncRNAs) with distinct expression profiles across different glioma clusters and uncovered promising recurrence-related targets and pathways in primary-recurrent GBMs are identified. These findings establish automated snRandom-seq as a robust tool for scRNA-seq of FFPE samples, enabling exploration of molecular diversities and tumor evolution. This platform holds significant implications for large-scale integrative and retrospective clinical research.

Overexpression of miR-20a-5p in mesenchymal stem cell derived-exosomes from systemic lupus erythematosus patients restored therapeutic effect and Treg immune regulation.

We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.

Molecular Orientation-Dependent Photonic Polarization Engineering in Organic Single-Crystal-Filled Microcavities.

Designing the polarization degree of freedom of light is crucial in many fields and has widespread application in, for example, all-optical circuits. In this work, we find that in an organic microcavity filled with anisotropic single crystals the cavity modes can be modulated to be elliptically polarized, i.e., partially circularly polarized and partially linearly polarized. The circular polarization component originates from the Rashba-Dresselhaus spin splitting, while the linear polarization component is due to the dislocation of linearly polarized modes. The dislocation of the linear polarizations is ascribed to the orientation of individual molecules and the molecular packing arrangement; hence, the linear polarizations can be controlled by properly structuring the molecular distributions. Our results pave the way for enriching and engineering the polarization properties of individual optical cavity modes in organic microstructures, which may favor the development of polarized lasers with various polarizations.

RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.

TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20-CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.

Interleukin-1 beta (IL-1ß) as adjuvant enhances the immune effects of Aeromonas veronii inactivated vaccine in largemouth bass (Micropterus salmoides).

Largemouth bass (Micropterus salmoides) has emerged as a significant economic fish species, with a rise in Aeromonas veronii infections in farming. However, research on adjuvants for vaccines against A. veronii in largemouth bass remains scarce. In present study, recombinant largemouth bass IL-1ß (LbIL-1ß) was expressed to explore its adjuvant effect on the A. veronii inactivated vaccine. Following vaccination with recombinant LbIL-1ß (rLbIL-1ß) and the inactivated A. veronii, higher serum SOD levels and lysozyme activities were observed in largemouth bass from inactivated A. veronii + rLbIL-1ß vaccinated group. Furthermore, it was discovered that rLbIL-1ß was able to boost the serum-specific antibody levels induced by the inactivated A. veronii. The qRT-PCR analysis revealed that rLbIL-1ß also enhanced the expression of IgM, CD4, and MHC II in largemouth bass triggered by the inactivated A. veronii. After challenged with live A. veronii, the outcomes demonstrated that the relative percentage survival (RPS) for largemouth bass resulting from the inactivated A. veronii in combination with rLbIL-1ß was 76.67 %, surpassing the RPS of 60 % in the inactivated A. veronii group. Collectively, these findings indicate that rLbIL-1ß enhances the protective effect of the A. veronii inactivated vaccine on largemouth bass, showcasing potential as an adjuvant for further development.

Comparative dosimetric study of h-IMRT and VMAT plans for breast cancer after breast-conserving surgery.

AIM: To compare the dosimetric advantages and disadvantages between hybrid intensity-modulated radiation therapy (h-IMRT) and the volumetric modulated arc therapy (VMAT) technique in hypofractionated whole-breast irradiation (HF-WBI) for early-stage breast cancer (BC). METHODS: The dose distribution of h-IMRT and VMAT plans was compared in 20 breast cancer patients. This comparison included evaluation of dosimetric parameters using dose volume histograms (DVHs) for the planning target volume (PTV) and organs-at-risk (OARs). Additionally, the study examined the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) and the tumor control probability (TCP) based on different models. RESULTS: Significant differences were detected between the two plans, in terms of Machine units (MUs), the control points, 95 % volume (V95 %), dose homogeneity index (DHI) and conformity index (CI). The endpoint of grade II radiation pneumonitis and cardiac death due to ischemic heart disease were assessed. In h-IMRT plan, the NTCP values were marginally lower for radiation pneumonitis and slightly higher for cardiac death compared to VMAT plan, as determined by the Lyman-Kutcher-Burman model. The Schneider model was employed to predict the SCCP for both the bilateral lungs and contralateral breast, the results demonstrate that the h-IMRT plan outperforms the VMAT plan, with statistical significance. Additionally, the LQ-Poisson model was employed to forecast the TCP of the PTV, showing that the h-IMRT plan outperformed the VMAT plan (P > 0.05). CONCLUSION: The h-IMRT technique, offering superior dose coverage and better therapeutic efficacy with fewer side effects as calculated by models, is more suitable for HF-WBI compared to the VMAT technique.

Comprehensive characterization of stemness-related lncRNAs in triple-negative breast cancer identified a novel prognostic signature related to treatment outcomes, immune landscape analysis and therapeutic guidance: a silico analysis with in vivo experiments.

BACKGROUND: Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are known to play a crucial role in the growth, migration, recurrence, and drug resistance of tumor cells, particularly in triple-negative breast cancer (TNBC). This study aims to investigate stemness-related lncRNAs (SRlncRNAs) as potential prognostic indicators for TNBC patients. METHODS: Utilizing RNA sequencing data and corresponding clinical information from the TCGA database, and employing Weighted Gene Co-expression Network Analysis (WGCNA) on TNBC mRNAsi sourced from an online database, stemness-related genes (SRGs) and SRlncRNAs were identified. A prognostic model was developed using univariate Cox and LASSO-Cox analysis based on SRlncRNAs. The performance of the model was evaluated using Kaplan-Meier analysis, ROC curves, and ROC-AUC. Additionally, the study delved into the underlying signaling pathways and immune status associated with the divergent prognoses of TNBC patients. RESULTS: The research identified a signature of six SRlncRNAs (AC245100.6, LINC02511, AC092431.1, FRGCA, EMSLR, and MIR193BHG) for TNBC. Risk scores derived from this signature were found to correlate with the abundance of plasma cells. Furthermore, the nominated chemotherapy drugs for TNBC exhibited considerable variability between different risk score groups. RT-qPCR validation confirmed abnormal expression patterns of these SRlncRNAs in TNBC stem cells, affirming the potential of the SRlncRNAs signature as a prognostic biomarker. CONCLUSION: The identified signature not only demonstrates predictive power in terms of patient outcomes but also provides insights into the underlying biology, signaling pathways, and immune status associated with TNBC prognosis. The findings suggest the possibility of guiding personalized treatments, including immune checkpoint gene therapy and chemotherapy strategies, based on the risk scores derived from the SRlncRNA signature. Overall, this research contributes valuable knowledge towards advancing precision medicine in the context of TNBC.

Gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia.

Aims: This study aims to explore the gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia (FES). Methods: 82 patients with FES, including 50 male patients and 32 female patients, were enrolled in the present study. Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were respectively conducted to evaluate the clinical symptoms and cognitive function of patients with FES at baseline and after treatment. Repeated measure ANOVA was performed to compare gender differences in cognitive domains scores between baseline and 2-month follow-up. Stepwise liner regression model was performed to explore the effect factors of cognitive improvements in patients. Results: There was no significant difference in age of onset, education years, PANSS scores, duration of untreated psychosis and Olanzapine equivalent doses between male and female patients (all p > 0.05). In the comparisons of cognition function, male patients exhibited better performance in social cognition compared with female patients at baseline (t = 3.20, p < 0.05). After treatment, improvements of attention/vigilance and working memory were both found in male patients and female patients (attention/vigilance, F = 11.867, p < 0.05; working memory, F = 18.265, p < 0.05). In addition, improvement of speed of information processing was only found in female patients (F = 11.65, p < 0.01). Significant interaction between time and gender was found in speed information of processing (F = 4.140, p = 0.045). Stepwise liner regression model revealed that improvements of negative symptoms promote improvements of cognitive function in female patients (all p < 0.05). Conclusions: Our findings revealed gender differences of cognitive improvements in patients with FES after 2-month treatment. It provides new evidence for gender differences in cognitive symptoms of schizophrenia, and also provides preliminary clues for further individualized cognitive intervention strategies.

Construction of a novel disulfidptosis-related lncRNAs signature for prognosis prediction and anti-tumor immunity in laryngeal squamous cell carcinoma.

Disulfidptosis, an innovative type of controlled cellular death linked to metabolic dysfunction, has garnered attention. However, there is limited knowledge regarding the involvement of disulfidptosisrelated lnRNAs (DRlncRNAs) in laryngeal squamous cell carcinoma (LSCC). The objective of our team in this study seeks to establish a DRlncRNAs signature, investigate their prognostic value in LSCC, and explore their associations with immune cell subpopulations, biological signaling pathways, and exploring implications for drug sensitivity. We accessed LSCC patients' RNA-seq data and pertinent clinical data for subsequent further analysis from The Cancer Genome Atlas (TCGA) portal. A literature search was conducted focusing on disulfidptosis-related genes. Pearson correlation coefficients were calculated to identify DRlncRNAs. Differential expression analysis of lncRNAs was performed. Utilizing univariate Cox regression analysis, we identified disulfidptosis-associated prognostic lncRNAs. The LASSO-Cox regression analysis was employed to refine this set of lncRNAs and construct a disulfidptosis-related lncRNAs signature. Various statistical techniques were employed to appraise model predictive performance. Subsequently, risk groups were stratified based on the risk score derived from the DRlncRNAs signature. The superiority of the risk score in prognostication over traditional clinicopathological features in LSCC patients was demonstrated. Evident distinctions emerged between risk groups, particularly in immune cell subpopulations like activated mast cells, eosinophils, and activated NK cells. Finally, the low-risk group demonstrated reduced IC50 values for specific chemotherapeutics like cisplatin and gemcitabine. The in vitro experiments indicated differential behavior of our DRlncRNAs. The DRlncRNAs signature can serve as a robust biomarker with the ability to predict both prognosis and therapeutic responses among patients with LSCC.

Association between incorrect postures and curve magnitude of adolescent idiopathic scoliosis in china.

BACKGROUND: Despite advancements in school scoliosis screening (SSS), there are still no effective indicators to estimate the severity of spinal curvature. We aim to investigate the association between incorrect postures and curve magnitude of adolescent idiopathic scoliosis (AIS) among Chinese adolescents. METHODS: In this SSS program, we examined the incorrect posture, Adam's forward bending test (FBT) results, and angle of trunk rotation (ATR) in adolescents. Those with suspected scoliosis were referred for a standing anteroposterior whole-spine radiography as outpatients. The radiographic data of 426 students with lateral Cobb angles were collected from 2016 to 2022 and the associations were studied using logistic regression (LR) models and receiver operating characteristic (ROC) curves. RESULTS: Univariate LR revealed that female gender [odds ratio (OR) = 2.92, 95% confidence interval (CI) 1.67-5.09, P < 0.001], age 16-19y (OR = 2.83, 95%CI 1.10-7.28, P = 0.031), right shoulder height (OR = 2.15, 95%CI 1.23-3.75, P = 0.007), right scapula tilt (OR = 2.03, 95%CI 1.18-3.50, P = 0.010), right rib hump (OR = 1.88, 95%CI 1.23-2.85, P = 0.003), right thoracic rotation ≥ 5° (OR = 2.14, 95%CI 1.43-3.20, P < 0.001), and left thoracolumbar kyphosis (OR = 3.79, 95%CI 1.06-13.56, P = 0.041) were all significantly associated with the severity of the curve magnitude. Multivariate LR showed that female gender [adjusted OR (AOR) = 3.23, 95%CI 1.81-5.73, P < 0.001], those aged 16-19y (AOR = 5.08, 95%CI 1.86-13.91, P = 0.002), and with a right rib hump (AOR = 1.72, 95%CI 1.11-2.64, P = 0.015) presented with a higher risk of severe curve magnitude than men, those aged 7-12y, and without a rib hump, respectively. ROC curves further proved that sex, age, shoulder-height difference, scapula tilt, flat back, rib hump, angle of thoracic rotation were the risk predictors for curve magnitude. CONCLUSION: Incorrect posture and ATR, especially the right rib hump, were significantly associated with the curve magnitude of AIS. Early screening for incorrect postures and ATR could be an effective and economical strategy to predict the severity of AIS through SSS in Chinese adolescents.

Childhood Trauma and Depressive Level Among Chinese College Students in Guangzhou: The Roles of Rumination and Perceived Stress.

OBJECTIVE: Although previous studies have validated the effect of childhood trauma on depressive level, few studies have utilized the diathesis-stress theory to investigate the specific roles of perceived stress and rumination in the pathway between childhood trauma and depression in Chinese college students. This study aims to demonstrate the mediation effect of perceived stress and the moderation effect of rumination in the pathway between childhood trauma and depressive level in Chinese college students. METHODS: A total of 995 Chinese college students in Guangzhou were included in this study by recruitment advertisement from October to December 2021. And they were asked to finish four self-report questionnaires, including Childhood Trauma Questionnaire-Short Form, Perceived Stress Scale, the 22-item Ruminative Response Scale, and Beck Depression Scale-II. Then the data were analyzed with Mplus 8.3. RESULTS: Results revealed significant correlations among childhood trauma, perceived stress, rumination and depressive level. Further analyses revealed that perceived stress played a mediation role between childhood trauma and depressive level (estimate=0.09, standard error [SE]=0.02, t=5.93, 95% confidence interval [CI]=0.06-0.12), and rumination played a moderation role between childhood trauma and perceived stress (estimate=-0.17, SE=0.06, t=-2.86, 95% CI=-0.28- -0.05]) as well as between childhood trauma and depressive level (estimate=0.10, SE=0.04, t=2.74, 95% CI=0.03-0.16). CONCLUSION: These results revealed the mediation effect of perceived stress and the moderation effect of rumination in the pathway between childhood trauma and depressive level in Chinese college students, which helped us to understand how the childhood trauma influenced the depressive level and gave us multi-dimensional indications for reducing the effect of childhood trauma on depressive level.

Tissue-resident C1q + macrophages exert anti-aging potential through the Sirt1 pathway.

OBJECTIVE: Resident immune cells are at the forefront of sensory organ-specific signals, and changes in these cells are closely related to the aging process. The Sirt pathway can regulate NAD + metabolism during aging, thereby affecting the accumulation of ROS. However, the role of the Sirt pathway in resident immune cells in aged tissues is currently unclear. METHODS: We investigated Sirt1 signalling in resident immune cells during chronic inflammation in an aged mouse model. Integrated single-cell RNA sequencing data from young and aged mice were used to refine the characterization of immune cells in aged tissues RESULTS: We found that C1q + macrophages could affect chronic inflammation during aging. C1q + macrophages acted in an opposing manner to Il1b + macrophages and were responsible for anti-inflammatory effects during aging. Sirt1 agonists inhibited the decrease in C1qb in macrophages during aging, and anti-aging drugs could affect the expression of C1qb in macrophages via the Sirt1 pathway. CONCLUSIONS: In this study, we first identified the relevance of C1q + macrophages in chronic inflammation during aging. The potential anti-aging effect of C1q + macrophages was mediated by the Sirt1 pathway, suggesting new strategies for aging immunotherapy.

NIR-II light in clinical oncology: opportunities and challenges.

Novel strategies utilizing light in the second near-infrared region (NIR-II; 900-1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities.

Preparation of Eudragit S100-pullulan/hydroxypropyl-ß-cyclodextrin complex-Eudragit S100 multilayer nanofiber film for resveratrol colon delivery.

Cyclodextrin-based electrospun nanofibers are promising for encapsulating and preserving unstable compounds, but quick dissolution of certain nanofibers hinders their delivery application. In this study, hydroxypropyl-ß-cyclodextrin (HPßCD) was used as an effective carrier of resveratrol (RSV) to obtain the RSV/HPßCD inclusion complex (HPIC), which was then incorporated into pullulan nanofibers. For enhancement of RSV release toward colon target, multilayer structure with a pullulan/HPIC film sandwiched between two layers of hydrophobic Eudragit S100 (ES100) nanofibers was employed. The relationship between the superiority of the ES100-pullulan/HPIC-ES100 film and its multilayer structure was verified. The intimate interactions of hydrogen bonds between two adjacent layers enhanced thermal stability, and the hydrophobic outer layers improved water contact resistance. According to release results, multilayer films also showed excellent colon-targeted delivery property and approximately 78.58 % of RSV was observed to release in colon stage. In terms of release mechanism, complex mechanism best described RSV colonic release. Additionally, ES100-pullulan/HPIC-ES100 multilayer films performed higher encapsulation efficiency when compared to the structures without HPIC, which further increased the antioxidant activity and total release amount of RSV. These results suggest a promising strategy for designing safe colonic delivery systems based on multilayer and HPIC structures with superior preservation for RSV.

Association between air pollution and skin cutaneous melanoma: A Mendelian randomization study.

There has been a consistent and notable increase in the global prevalence of skin cutaneous melanoma (SKCM). Although genetic factors are closely associated with the occurrence and development of melanoma, the potential influence of environmental factors cannot be overlooked. The existing literature lacks a definitive consensus on the correlation between air pollution and the incidence rate of SKCM. This study seeks to investigate the causal relationship between air pollution, specifically focusing on particulate matter (PM) 2.5, PM2.5-10, PM10, and nitrogen oxides, and the risk of SKCM. A 2-sample Mendelian randomization (MR) method was applied, utilizing extensive publicly accessible genome-wide association studies summary datasets within European populations. The primary analytical method employed was the inverse variance weighted method. Supplementary methods, including the weighted median model, MR-Egger, simple model, and weighted model, were chosen to ensure robust analysis. Heterogeneity assessment was conducted using Cochran's Q test. To identify potential pleiotropy, both MR-Egger regression and the MR-PRESSO global test were employed. Additionally, a sensitivity analysis was performed using the leave-one-out method. The analysis revealed no statistically significant association between air pollution and SKCM risk, with specific findings as follows: PM2.5 (P = .485), PM2.5-10 (P = .535), PM10 (P = .136), and nitrogen oxides (P = .745). While some results exhibited heterogeneity, all findings demonstrated an absence of pleiotropy. This study did not find substantive evidence supporting a causal relationship between air pollution and the risk of SKCM within European populations. The comprehensive MR analysis, encompassing various pollutants, suggests that environmental factors such as air pollution may not be significant contributors to the development of SKCM.

Nanobody activator improves sensitivity of the von Willebrand factor activity assay to multimer size.

BACKGROUND: The activity of von Willebrand factor (VWF) in facilitating platelet adhesion and aggregation correlates with its multimer size. Traditional ristocetin-dependent functional assays lack sensitivity to multimer sizes. Recently, nanobodies targeting the autoinhibitory module and activating VWF were identified. OBJECTIVES: To develop an assay that can differentiate the platelet-binding activity of VWF multimers. METHODS: A novel enzyme-linked immunosorbent assay (nanobody-triggered glycoprotein Ib binding assay [VWF:GPIbNab]) utilizing a VWF-activating nanobody was developed. Recombinant VWF, plasma-derived VWF (pdVWF), and selected gel-filtrated fractions of pdVWF were evaluated for VWF antigen and activity levels. A linear regression model was developed to estimate the specific activity of VWF multimers. RESULTS: Of the 3 activating nanobodies tested, 6C11 with the lowest activation effect exhibited the highest sensitivity for high-molecular-weight multimers (HMWMs) of VWF. VWF:GPIbNab utilizing 6C11 (VWF:GPIbNab6C11) produced significantly higher activity/antigen ratios for recombinant VWF (>2.0) and HMWM-enriched pdVWF fractions (>2.0) than for pdVWF (∼1.0) or fractions enriched with shorter multimers (<1.0). The differences were much larger than those produced by VWF:GPIbNab utilizing other nanobodies, VWF:GPIbM, VWF:GPIbR, or VWF:CB assays. Linear regression analysis of 5 pdVWF fractions of various multimer sizes produced an estimated specific activity of 2.7 for HMWMs. The analysis attributed >90% of the VWF activity measured by VWF:GPIbNab6C11 to that of HMWMs, which is significantly higher than all other activity assays tested. CONCLUSION: The VWF:GPIbNab6C11 assay exhibits higher sensitivity to HMWMs than ristocetin-based and collagen-binding assays. Future studies examining the application of this assay in clinical settings and any associated therapeutic benefit of doing so are warranted.

Trends and hotspots in tea and Alzheimer's disease research from 2014 to 2023: A bibliometric and visual analysis.

Objectives: The positive effects of tea on Alzheimer's disease (AD) have increasingly captured researchers' attention. Nevertheless, the quantitative comprehensive analysis in the relevant literatur is lack. This paper aims to thoroughly examine the current research status and hotspots from 2014 to 2023, providing a valuable reference for subsequent research. Methods: Documents spanning from 2014 to 2023 were searched from the Web of Science, and the R software, VOSviewer, and Citespace software were used for analysis and visualization. Results: A total of 374 documents were contained in the study. The rate of article publications exhibited a consistent increase each year from 2014 to 2023. Notably, China emerged as the leading country in terms of published articles, followed by the United States and India. Simultaneously, China is also in a leading position in cooperation with other countries. Molecules emerged as the most frequently published journal, while the Journal of Alzheimer's Disease secured the top spot in terms of citations. The identified main keywords included oxidative stress, amyloid, epigallocatechin gallate, and green tea polyphenol, among others. These focal areas delved into the antioxidative and anti-amyloid aggregation actions of tea's polyphenolic components. Furthermore, the particularly way in which epigallocatechin gallate delivers neuroprotective outcomes by influencing molecules related to AD represents a focal point of research. Conclusion: The increasing attention from researchers on the role of tea in ameliorating AD positions it as a hot spot in the development of anti-AD drugs in the development of future. Through our generalized analysis of the current landscape and hotspots regarding tea's application in AD, this study provides an estimable reference for future research endeavors.