DNA Damage Atlas: an atlas of DNA damage and repair.

DNA damage and its improper repair are the major source of genomic alterations responsible for many human diseases, particularly cancer. To aid researchers in understanding the underlying mechanisms of genome instability, a number of genome-wide profiling approaches have been developed to monitor DNA damage and repair events. The rapid accumulation of published datasets underscores the critical necessity of a comprehensive database to curate sequencing data on DNA damage and repair intermediates. Here, we present DNA Damage Atlas (DDA, http://www.bioinformaticspa.com/DDA/), the first large-scale repository of DNA damage and repair information. Currently, DDA comprises 6,030 samples from 262 datasets by 59 technologies, covering 16 species, 10 types of damage and 135 treatments. Data collected in DDA was processed through a standardized workflow, including quality checks, hotspots identification and a series of feature characterization for the hotspots. Notably, DDA encompasses analyses of highly repetitive regions, ribosomal DNA and telomere. DDA offers a user-friendly interface that facilitates browsing, searching, genome browser visualization, hotspots comparison and data downloading, enabling convenient and thorough exploration for datasets of interest. In summary, DDA will stand as a valuable resource for research in genome instability and its association with diseases.

Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target.

Immunotherapy of PD-L1/PD-1 blockage elicited impressive clinical benefits for cancer treatment. However, the relative low response and therapy resistance highlight the need to better understand the molecular regulation of PD-L1 in tumors. Here, we report that PD-L1 is a target of UFMylation. UFMylation of PD-L1 destabilizes PD-L1 by synergizing its ubiquitination. Inhibition of PD-L1 UFMylation via silencing of UFL1 or Ubiquitin-fold modifier 1 (UFM1), or the defective UFMylation of PD-L1, stabilizes the PD-L1 in multiple human and murine cancer cells, and undermines antitumor immunity in vitro and mice, respectively. Clinically, UFL1 expression was decreased in multiple cancers and lower expression of UFL1 negatively correlated with the response of anti-PD1 therapy in melanoma patients. Moreover, we identified a covalent inhibitor of UFSP2 that promoted the UFMylation activity and contributed to the combination therapy with PD-1 blockade. Our findings identified a previously unrecognized regulator of PD-L1 and highlighted UFMylation as a potential therapeutic target.

Interlayer and Phase Engineering Modifications of K-MoS2@C Nanoflowers for High-Performance Degradable Zn-Ion Batteries.

2D transition metal dichalcogenides (TMDs) have garnered significant interest as cathode materials for aqueous zinc-ion batteries (AZIBs) due to their open transport channels and abundant Zn2+ intercalation sites. However, unmodified TMDs exhibit low electrochemical activity and poor kinetics owing to the high binding energy and large hydration radius of divalent Zn2+. To overcome these limitations, an interlayer engineering strategy is proposed where K+ is preintercalated into K-MoS2 nanosheets, which then undergo in situ growth on carbon nanospheres (denoted as K-MoS2@C nanoflowers). This strategy stimulates in-plane redox-active sites, expands the interlayer spacing (from 6.16 to 9.42 Å), and induces the formation of abundant MoS2 1T-phase. The K-MoS2@C cathode demonstrates excellent redox activity and fast kinetics, attributed to the potassium ions acting as a structural "stabilizer" and an electrostatic interaction "shield," accelerating charge transfer, promoting Zn2+ diffusion, and ensuring structural stability. Meanwhile, the carbon nanospheres serve as a 3D conductive network for Zn2+ and enhance the cathode's hydrophilicity. More significantly, the outstanding electrochemical performance of K-MoS2@C, along with its superior biocompatibility and degradability of its related components, can enable an implantable energy supply, providing novel opportunities for the application of transient electronics.

Classifying self-management clusters of patients with mild cognitive impairment associated with diabetes: A cross-sectional study.

AIMS AND OBJECTIVES: This study aims to propose a self-management clusters classification method to determine the self-management ability of elderly patients with mild cognitive impairment (MCI) associated with diabetes mellitus (DM). BACKGROUND: MCI associated with DM is a common chronic disease in old adults. Self-management affects the disease progression of patients to a large extent. However, the comorbidity and patients' self-management ability are heterogeneous. DESIGN: A cross-sectional study based on cluster analysis is designed in this paper. METHOD: The study included 235 participants. The diabetes self-management scale is used to evaluate the self-management ability of patients. SPSS 21.0 was used to analyse the data, including descriptive statistics, agglomerative hierarchical clustering with Ward's method before k-means clustering, k-means clustering analysis, analysis of variance and chi-square test. RESULTS: Three clusters of self-management styles were classified as follows: Disease neglect type, life oriented type and medical dependence type. Among all participants, the percentages of the three clusters above are 9.78%, 32.77% and 57.45%, respectively. The difference between the six dimensions of each cluster is statistically significant. CONCLUSION(S): This study classified three groups of self-management styles, and each group has its own self-management characteristics. The characteristics of the three clusters may help to provide personalized self-management strategies and delay the disease progression of MCI associated with DM patients. RELEVANCE TO CLINICAL PRACTICE: Typological methods can be used to discover the characteristics of patient clusters and provide personalized care to improve the efficiency of patient self-management to delay the progress of the disease. PATIENT OR PUBLIC CONTRIBUTION: In our study, we invited patients and members of the public to participate in the research survey and conducted data collection.

High-Performance Biodegradable Energy Storage Devices Enabled by Heterostructured MoO3 -MoS2 Composites.

Biodegradable implantable devices are of growing interest in biosensors and bioelectronics. One of the key unresolved challenges is the availability of power supply. To enable biodegradable energy-storage devices, herein, 2D heterostructured MoO3 -MoS2 nanosheet arrays are synthesized on water-soluble Mo foil, showing a high areal capacitance of 164.38 mF cm-2 (at 0.5 mA cm-2 ). Employing the MoO3 -MoS2 composite as electrodes of a symmetric supercapacitor, an asymmetric Zn-ion hybrid supercapacitor, and an Mg primary battery are demonstrated. Benefiting from the advantages of MoO3 -MoS2 heterostructure, the Zn-ion hybrid supercapacitors deliver a high areal capacitance (181.86 mF cm-2 at 0.5 mA cm-2 ) and energy density (30.56 µWh cm-2 ), and the Mg primary batteries provide a stable high output voltage (≈1.6 V) and a long working life in air/liquid environment. All of the used materials exhibit desirable biocompatibility, and these fabricated devices are also fully biodegradable. Demonstration experiments display their potential applications as biodegradable power sources for various electronic devices.

Stratified support pattern-based internet-assisted self-management therapy for diabetes mellitus -mild cognitive impairment: a randomized controlled trial protocol.

BACKGROUND: Mild cognitive impairment (MCI) associated with diabetes mellitus (DM) is common among older adults, and self-management is critical to controlling disease progression. However, both MCI and DM are heterogeneous diseases, and existing integrated self-management interventions do not consider patient differences. Grouping patients by disease characteristics could help to individualize disease management and improve the use of available resources. The current study sought to explore the feasibility and effectiveness of a stratified support model for DM-MCI patients. METHODS: Eighty-four DM-MCI patients will be randomly divided into an intervention group and a control group in a 1:1 ratio. The intervention group will receive a self-management intervention using the stratified support pattern-based internet-assisted therapy (SISMT), while the control group will receive the health manual intervention (HMI). The study recruiter will be blinded to the group allocation and unable to foresee which group the next participant will be assigned to. At the same time, the allocation will be also hidden from the research evaluators and participants. After 12 weeks and 24 weeks, cognitive function, blood glucose, self-management ability, psychological status, health literacy, and self-management behavior of patients in both groups will be measured and compared. DISCUSSION: This study developed a stratified support pattern-based internet-assisted to provide self-management intervention for patients with DM-MCI. The impact of different models and forms of self-management intervention on cognitive function, blood glucose management, and psychological status health literacy and self-management behavior of patients will be assessed. The results of this study will inform related intervention research on the stratified support pattern-based internet-assisted self-management therapy, and help to slow the decline of cognitive function in patients with DM-MCI. TRIAL REGISTRATION: ChiCTR2200061991. Registered 16 July 2022.

Effects of dance therapy on cognitive and mental health in adults aged 55 years and older with mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Individuals with mild cognitive impairment are at high risk of developing dementia. Dance therapy has promising applications in delaying cognitive decline. However, the effectiveness of dance therapy for older adults with mild cognitive impairment is unclear. The objective of this review was to evaluate the effectiveness of dance therapy on global cognitive function, specific cognitive subdomains, quality of life, and mental health in older adults with mild cognitive impairment to enrich health management strategies for dementia. METHODS: Electronic databases and grey literature were searched from inception up to September 23, 2023. The language was limited to English and Chinese. Relevant studies were screened and assessed for risk of bias. A meta-analysis and subgroup analyses stratified by measurement instrument, dance type, intervention duration, and frequency were conducted using the STATA 16.0 software. This review was conducted in accordance with the PRISMA guidelines. RESULTS: Ten studies involving 984 participants aged 55 years and over who met the eligibility criteria were included. Dance therapy significantly improved global cognitive function, memory, executive function, attention, language, and mental health (i.e., depression and neuropsychiatric symptoms). However, the effects of dance therapy on processing speed, visuospatial ability, and quality of life in older adults with mild cognitive impairment remain inconclusive. Moreover, dance interventions of longer duration (> 3 months) improved global cognition more than shorter interventions. CONCLUSION: This review reported that dance therapy was effective in improving global cognitive function, memory, executive function, attention, language, and mental health (i.e., depression and neuropsychiatric symptoms). Hence, it may be an effective non-pharmacological complementary treatment for older adults with mild cognitive impairment.

Effect of self-determination theory-based integrated creative art (SDTICA) program on older adults with mild cognitive impairment in nursing homes: Study protocol for a cluster randomised controlled trial.

BACKGROUND: The cognitive benefits of early non-pharmacological approaches have been demonstrated in older adults with mild cognitive impairment (MCI). However, older adults living in nursing homes have more severe cognitive impairment problems and lower initiative and compliance to participate in complex interventions. Hence, it important to investigate more attractive and sustainable methods to prevent or delay cognitive decline. The present study adopts the self-determination theory (SDT) as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes in China and aims to evaluate its effects on cognitive function, mental health, and other health-related outcomes. METHODS: The study is a nursing home-based, cluster randomised controlled trial (RCT) that targets older adults (aged ≥ 60 years) with MCI in Fuzhou City, China. All nursing homes in the area covered by Fuzhou City are invited to participate. Eligible nursing homes are randomised to one of two groups: intervention group (receive a 14-week, 27-session intervention) and waitlist control group (receive the usual care). The SDT-based integrated creative art (SDTICA) program reasonably adopts the SDT as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes. The primary (global cognitive function and psychological indicator) and secondary (daily activity function, social function, and specific domains of cognitive function) outcomes will be measured at baseline, after the intervention, and during follow-up. DISCUSSION: This study aims to evaluate the effects of SDTICA program on neuropsychological outcomes in older adults with MCI and provide scientific evidence for art-based non-pharmacologic interventions in nursing homes, which may reduce dementia risk in older adults with MCI. TRIAL REGISTRATION: The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022.

Performance evaluation of sperm concentration, motility, and morphological analysis for GSA-810 series of sperm quality analysis system.

BACKGROUND: The performance evaluation of each computer-assisted sperm analysis (CASA) system may provide a basis for the interpretation of clinical results and further improvement of the CASA system. METHODS: The accuracy of the GSA-810 CASA system was evaluated by detecting latex bead quality control products. The precision of sperm concentration, morphology, and percentages of progressively motile sperm (PR) were evaluated by coefficient of variation (CV). Three samples with sperm concentration of about 100 × 106 /mL were diluted to evaluate the linear range. RESULTS: The detection values of latex beads were within the range of target values. The CVs of sperm concentration and PR were significantly and negatively correlated with sperm concentration (r = -0.561, p = 0.001) and PR value (r = -0.621, p < 0.001), respectively. The R2 values of the linear range of sperm concentration were ≥0.99. There was no significant difference in sperm motility and PR within 1-10 min at 36.5°C ± 0.5°C. The coincidence rates of sperm morphology and sperm head morphology for 36 semen samples analyzed by the GSA-810 system and manual method were 99.40% and 99.67%, respectively. The CVs of the percentage of sperm with abnormal morphology and percentage of sperm with abnormal head morphology were less than 5%. CONCLUSION: The GSA-810 system can accurately analyze normal semen samples, but the repeatability of the results is poor for oligozoospermia and asthenozoospermia samples. The future CASA system for analyzing sperm morphology should focus on recognizing the middle and tail segments of a spermatozoon.

Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry.

Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10-03), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10-02), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10-03). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10-48). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10-125). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1, PCAT1 and PCAT10/CTBP1-AS, were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes.

Effects of an art-based intervention in older adults with mild cognitive impairment: a randomised controlled trial.

BACKGROUND: Art-based interventions may delay cognitive decline and improve health-related outcomes in older adults with mild cognitive impairment (MCI). OBJECTIVE: To examine the effects of the Creative Expressive Arts-based Storytelling (CrEAS) program compared to active and waitlist controls on neurocognitive and other health-related outcomes in older people with MCI. DESIGN: Three-arm parallel-group, randomised controlled design. PARTICIPANTS: One-hundred and thirty-five adults with MCI (mean age: 70.93 ± 6.91 years). METHODS: Participants were randomly assigned to intervention (CrEAS, n = 45), active control (n = 45) or waitlist control (n = 45) groups. Interventions were applied once per week for 24 weeks. The primary outcome was global cognitive function; secondary outcomes were specific cognition domains (memory, executive function, language and attention) and other health-related outcomes (anxiety, depression and quality of life [QoL]). All variables were measured at baseline (T0), 24-week follow-up (T1) and 48-week follow-up (T2). RESULTS: Participants in the CrEAS group showed significantly higher global cognitive function (adjusted mean difference [MD] = -0.905, 95% confidence interval [CI] -1.748 to -0.062; P = 0.038) and QoL (adjusted MD = -4.150, 95% CI -6.447 to -1.853; P = 0.001) and lower depression symptoms (adjusted MD = 2.902, 95% CI 0.699-5.104; P = 0.011) post-intervention at the 24-week follow-up compared with the active control group. At 48-week follow-up, only the Auditory Verbal Learning Test Immediate recall score was significantly improved compared with the active control group (adjusted MD = -2.941, 95% CI -5.262 to -0.620; P = 0.014). CONCLUSIONS: Older adults with MCI who participated in the CrEAS program improved their neuropsychological outcomes and QoL and reduced their rate of cognitive deterioration.

Effects of a staged integral art-based cognitive intervention (SIACI) program in older adults with cognitive impairments: protocol for a randomized controlled trial.

BACKGROUND: Given the aging population worldwide and the COVID-19 pandemic, which has been found to be associated with a deterioration in Alzheimer's disease (AD) symptoms, investigating methods to prevent or delay cognitive decline in preclinical AD and AD itself is important. The trial described in this protocol aims to evaluate the effects of a staged integral art-based cognitive intervention (SIACI) in older adults with CIs (preclinical AD [SCD or MCI] and mild AD), in order to gather evidence on the effects of SIACI on cognition and psychological/psychosocial health gains and determine the mechanisms. METHODS: The planned study is a single-center, parallel-arm, randomized controlled trial with allocation concealment and outcome assessor blinding. A total of 88 participants will be randomized to two groups: (i) an intervention group that receives the 16-week, 24-session SIACI program and (ii) a waitlist control group (which will receive the SIACI program after completing the follow-up assessment). Global cognitive function, specific domains of cognition (memory, language, executive function, and visuospatial skills), and other health-related outcomes (quality of life, anxiety, depression, sleep quality, and physical activity level) will be measured at baseline, immediately after the intervention, and at the 6-month follow-up. Blood biomarkers, event-related potential (ERP)-P300, and magnetic resonance imaging (MRI) data will be collected at baseline and immediately after the intervention to explore the mechanisms of SIACI. DISCUSSION: The trial will elucidate the immediate and long-term effects of SIACI based on neuropsychological testing and blood biomarkers, and neuroscience involving ERP-P300 and MRI parameters will make it possible to explore the mechanisms of SIACI in older adults with CIs. The results will provide evidence on the effectiveness of an AT-based cognitive intervention, which may delay or even halt cognitive decline in preclinical AD and AD itself. TRIAL REGISTRATION: ChiCTR, ChiCTR2100044959 . Registered 03 April 2021.

Chromium [Cr(VI)] Exposure Causes Cytotoxicity of Human Bronchial Epithelial Cells (16-HBE) and Proteomic Alterations.

Hexavalent chromium [Cr(VI)] is a common industrial pollutant, and exposure may cause toxic effects in multiple organ systems and carcinogenesis, including lung cancer. However, the toxic effect of Cr(VI) on the respiratory system is poorly understood. In the present study, it was demonstrated that Cr(VI) exposure significantly decreased the viability of human bronchial epithelial cells (16-HBE) in a dose-dependent manner. Flow cytometry demonstrated that Cr(VI) enhanced the transition of 16-HBE cells from G1 to S phase and arrested S-phase progression. Reverse transcription-quantitative polymerase chain reaction analysis revealed a significant alteration in the expression of apoptosis-associated genes in Cr(VI)-treated 16-HBE cells. In addition, using two-dimensional fluorescence differential gel electrophoresis with mass spectrometry, 15 differentially expressed proteins (1 upregulated and 14 downregulated) were identified in 16-HBE cells with Cr(VI) treatment compared with controls. Functional classification revealed that these differentially expressed proteins were involved in apoptosis, cytoskeletal structure, and energy metabolism. In conclusion, these data suggested that Cr(VI) caused toxic effects in bronchial epithelial cells and the mechanisms may involve the abnormal expression of apoptosis-associated proteins, cytoskeletal proteins, and energy metabolism-associated proteins.

Effects of motor imagery training on lower limb motor function of patients with chronic stroke: A pilot single-blind randomized controlled trial.

AIMS: This pilot study aimed to evaluate the effects of motor imagery training on lower limb motor function of stroke patients. BACKGROUND: Motor imagery training has played an important role in rehabilitation outcomes of stroke patients. METHODS: In this pilot randomized controlled trial 32 stroke patients were randomly divided into experimental and control groups from January to June 2017. Patients in both groups received conventional neuro-rehabilitation five times a week in 3-h segments for 6 weeks. Patients in the experimental group underwent an additional 20 min of motor imagery training. Measures were evaluated by motor function of the lower extremity, activities of daily living and balance ability. RESULTS: The outcomes significantly improved by motor imagery training were the Fugl-Meyer Assessment of the lower extremity, the Functional Independence Measure dealing with transfers and locomotion, and the Berg Balance Scale. CONCLUSION: Motor imagery training could be used as a complement to physical rehabilitation of stroke patients. Our findings may be helpful to develop nursing strategies aimed at improving functional ability of stroke patients and thus enhancing their quality of life.

Effects of mindfulness in patients with mild cognitive impairment with insomnia: A double-blind randomized controlled trial.

OBJECTIVE: Current research on the effects of mindfulness therapy on MCI and insomnia has been inconsistent. It is still a hot topic of research and discussion. This study aimed to improve the sleep quality, cognition, and mental state of patients with mild cognitive impairment (MCI) with insomnia. METHODS: A double-blind randomized controlled trial was conducted. Seventy-five patients who met the eligibility criteria were randomly assigned to the mindfulness (n = 38) or health education (n = 37) treatment group. The primary outcomes were sleep, measured by the Pittsburgh Sleep Quality Inventory, and cognition, measured by The Montreal Cognitive Assessment and Mini-Mental State Examination. Secondary outcomes included insomnia, measured by the Insomnia Severity Index, depression, anxiety, and perceived stress. EEG signals were collected at rest with eyes closed in the mindfulness state. The power spectrum was analyzed from these data. RESULTS: Cognitive function and sleep quality were significantly improved in the mindfulness group (95% confidence interval 0.04 - 0.05, 0.03 - 0.04, -5.58 - -1.55, respectively). Anxiety and perceived stress scores were significantly lower than those in the control group (95% confidence interval 0.002 - 0.004, 0.009 - 0.013, respectively). The power spectrum differences in δ, θ, ß, and γ bands were significant between the rest and mindfulness states (P < .05). Good safety was achieved in both groups with no deaths or serious adverse events. CONCLUSION: Mindfulness improved sleep quality, cognitive function, and mentality of patients. Mindfulness practice caused deep relaxation in the brain and changes in electrical frequency bands associated with attention and cognitive tasks. Mindfulness learning can be performed successfully for individuals with MCI. Additionally, it is suitable for adoption in nursing homes.

Outcome of Chinese patients with hepatitis B at 96 weeks after functional cure with IFN versus combination regimens.

BACKGROUND & AIMS: Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse. METHODS: Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse. RESULTS: 420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group. CONCLUSION: NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).

Cargo-laden erythrocyte ghosts target liver mediated by macrophages.

Liver-targeted cargo delivery possesses great potential for the treatment of liver disease. It is urgent to find an efficient and biocompatible liver targeted delivery system. This study focused on the liver targeting properties of erythrocyte ghosts and its possible mechanism. Herein, we optimized conditions to fabricate human and mouse erythrocyte ghosts with sufficient room capable of incorporating various model substances. Erythrocyte ghosts are biocompatible cargo carriers because it is derived from autologous red blood cells (RBCs), and the cell size, zeta potential, and biconcave-disk shape of the ghosts were consistent with those of RBCs. An in vivo imaging system and positron emission tomography/computed tomography imaging showed that the ghosts were captured mainly in the liver by intravenous injection of fluorescence or 18F-fluorodeoxyglucose (FDG)-labelled ghosts into mice. In contrast, the main concentration of naked octreotide was trapped in the lungs while naked 18F-FDG was trapped in the heart. However, the concentration of cargo-loaded ghosts decreased significantly in the liver in macrophage-depleted mice. Accordingly, in vitro experiments showed that higher phosphatidylserine exposure was observed in the ghosts (38.9 %) compared to normal erythrocytes (0.69 %), and the phagocytic activity of the macrophage RAW 264.7. on the ghosts was significantly higher than that of normal erythrocytes (p < 0.001). Together they indicate that erythrocyte ghosts show liver targeting properties, and possibly owing to macrophage phagocytosis. This promising and effective therapeutic delivery system may provide therapeutic benefits for liver disease.

Effects of expressive arts therapy in older adults with mild cognitive impairment: A pilot study.

Expressive arts therapy (EAT) can potentially improve cognition and mental health in patients with dementia. However, limited studies have been conducted for older adults with mild cognitive impairment (MCI). The aim of this study was to examine the effects of EAT in older adults with MCI. A total of 48 participants with MCI were assigned to the EAT intervention (n = 24) or waiting list control (n = 24) group. The former received 60-90 min of EAT twice a week for 6 weeks. The findings showed that the EAT program had a high retention and attendance rate and a high level of general satisfaction. Moreover, the intervention group showed significant improvements in general cognitive function, language function, anxiety, depression, and the psychological and social relationship domains of quality of life. The results provide preliminary evidence for the feasibility and efficacy of EAT intervention in older adults with MCI.

Hellinger distance-based stable sparse feature selection for high-dimensional class-imbalanced data.

BACKGROUND: Feature selection in class-imbalance learning has gained increasing attention in recent years due to the massive growth of high-dimensional class-imbalanced data across many scientific fields. In addition to reducing model complexity and discovering key biomarkers, feature selection is also an effective method of combating overlapping which may arise in such data and become a crucial aspect for determining classification performance. However, ordinary feature selection techniques for classification can not be simply used for addressing class-imbalanced data without any adjustment. Thus, more efficient feature selection technique must be developed for complicated class-imbalanced data, especially in the context of high-dimensionality. RESULTS: We proposed an algorithm called sssHD to achieve stable sparse feature selection applied it to complicated class-imbalanced data. sssHD is based on the Hellinger distance (HD) coupled with sparse regularization techniques. We stated that Hellinger distance is not only class-insensitive but also translation-invariant. Simulation result indicates that HD-based selection algorithm is effective in recognizing key features and control false discoveries for class-imbalance learning. Five gene expression datasets are also employed to test the performance of the sssHD algorithm, and a comparison with several existing selection procedures is performed. The result shows that sssHD is highly competitive in terms of five assessment metrics. In addition, sssHD presents limited differences between performing and not performing re-balance preprocessing. CONCLUSIONS: sssHD is a practical feature selection method for high-dimensional class-imbalanced data, which is simple and can be an alternative for performing feature selection in class-imbalanced data. sssHD can be easily extended by connecting it with different re-balance preprocessing, different sparse regularization structures as well as different classifiers. As such, the algorithm is extremely general and has a wide range of applicability.

MicroRNA-425-5p promotes tau phosphorylation and cell apoptosis in Alzheimer's disease by targeting heat shock protein B8.

Alzheimer's disease (AD) is the most prevalent and age-related dementia accompanied by neurodegenerative disorder, memory loss, and abnormal behaviors. Recent studies have shown an increasing interest in studying the role of microRNAs (miRNAs) and their potential values in the early diagnostics of AD. MiR-425-5p has extensively expression within various tissues and organs, acting as an important regulator in many pathological procedures. The functions of miR-425-5p involved in AD were investigated in the present study. The results showed that miR-425-5p was upregulated in patients with AD and HEK293/tau cells. Transfections with miR-425-5p overexpression vector significantly enhanced cell apoptosis, activated glycogen synthase kinase-3ß (GSK-3ß), and increased tau phosphorylation in HEK293/tau cells. Heat shock protein B8 (HSPB8) was directly targeted by miR-425-5p. Upregulation of miR-425-5p induced cell apoptosis and promoted tau phosphorylation partially via targeting HSPB8 in AD. Therefore, miR-425-5p might act as a new therapeutic target for AD treatment.