Small non-coding RNA signatures in atrial appendages of patients with atrial fibrillation.

The development of high-throughput technologies has enhanced our understanding of small non-coding RNAs (sncRNAs) and their crucial roles in various diseases, including atrial fibrillation (AF). This study aimed to systematically delineate sncRNA profiles in AF patients. PANDORA-sequencing was used to examine the sncRNA profiles of atrial appendage tissues from AF and non-AF patients. Differentially expressed sncRNAs were identified using the R package DEGseq 2 with a fold change >2 and p < 0.05. The target genes of the differentially expressed sncRNAs were predicted using MiRanda and RNAhybrid. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. In AF patients, the most abundant sncRNAs were ribosomal RNA-derived small RNAs (rsRNAs), followed by transfer RNA-derived small RNAs (tsRNAs), and microRNAs (miRNAs). Compared with non-AF patients, 656 rsRNAs, 45 miRNAs, 191 tsRNAs and 51 small nucleolar RNAs (snoRNAs) were differentially expressed in AF patients, whereas no significantly differentially expressed piwi-interacting RNAs were identified. Two out of three tsRNAs were confirmed to be upregulated in AF patients by quantitative reverse transcriptase polymerase chain reaction, and higher plasma levels of tsRNA 5006c-LysCTT were associated with a 2.55-fold increased risk of all-cause death in AF patients (hazard ratio: 2.55; 95% confidence interval, 1.56-4.17; p < 0.001). Combined with our previous transcriptome sequencing results, 32 miRNA, 31 snoRNA, 110 nucleus-encoded tsRNA, and 33 mitochondria-encoded tsRNA target genes were dysregulated in AF patients. GO and KEGG analyses revealed enrichment of differentially expressed sncRNA target genes in AF-related pathways, including the 'calcium signaling pathway' and 'adrenergic signaling in cardiomyocytes.' The dysregulated sncRNA profiles in AF patients suggest their potential regulatory roles in AF pathogenesis. Further research is needed to investigate the specific mechanisms of sncRNAs in the development of AF and to explore potential biomarkers for AF treatment and prognosis.

DDR1 Drives Malignant Progression of Gastric Cancer by Suppressing HIF-1α Ubiquitination and Degradation.

The extracellular matrix (ECM) has been demonstrated to be dysregulated and crucial for malignant progression in gastric cancer (GC), but the mechanism is not well understood. Here, that discoidin domain receptor 1 (DDR1), a principal ECM receptor, is recognized as a key driver of GC progression is reported. Mechanistically, DDR1 directly interacts with the PAS domain of hypoxia-inducible factor-1α (HIF-1α), suppresses its ubiquitination and subsequently strengthens its transcriptional regulation of angiogenesis. Additionally, DDR1 upregulation in GC cells promotes actin cytoskeleton reorganization by activating HIF-1α/ Ras Homolog Family Member A (RhoA)/Rho-associated protein kinase 1 (ROCK1) signaling, which in turn enhances the metastatic capacity. Pharmacological inhibition of DDR1 suppresses GC progression and angiogenesis in patient-derived xenograft (PDX) and organoid models. Taken together, this work first indicates the effects of the DDR1-HIF-1α axis on GC progression and reveals the related mechanisms, providing experimental evidence for DDR1 as a therapeutic target for GC.

Association of serum pertussis antibodies with acute asthma attacks in children.

Objective: The aim of this study was to examine the serum antibody levels against pertussis toxin (PT) in children experiencing an acute asthma attack and to explore the potential association between these levels and asthma. Methods: A prospective investigation was conducted, which involved 107 children with acute asthma attacks and 77 children diagnosed with bronchitis. The serum immunoglobulin G (IgG) antibody levels specific to PT were measured by using an in-house enzyme-linked immunosorbent assay. Based on the serum PT-IgG antibody levels, the children with asthma were categorized into three groups: non-pertussis infected, suspected pertussis infected, and recent pertussis infected. The clinical manifestations and pulmonary function of pediatric patients diagnosed with asthma were assessed and compared across various groups. Results: Of the total asthma group, 25 patients tested positive for PT-IgG, whereas only six patients in the bronchitis group were PT-IgG positive. The prevalence of recent pertussis infection was observed to be higher in the asthma group compared with the bronchitis group. Within the asthma group, those with recent pertussis infection exhibited a higher likelihood of experiencing wheezing and impaired lung function in comparison with the non-pertussis infection group. Conclusion: Pertussis infection is relatively common in children with asthma and correlates with the severity of asthma.

Clinicopathologic and prognostic significance of tumor-associated macrophages in cervical cancer: a systematic review and meta-analysis.

OBJECTIVES: The role of tumor-associated macrophages (TAMs) in cervical cancer (CC) remains controversial. Here, we report a meta-analysis of the association between TAMs infiltration and clinical outcomes. METHODS: PubMed, Embase, Web of Science, and CNKI were searched systematically from inception until December 20, 2023. Studies involving TAMs and prognosis, clinical, or pathological features were included. Quality assessments of the selected studies were assessed. The fixed-effect or random-effects model, standard mean difference (SMD), odds ratios (OR), or hazard ratios (HR) with 95% confidence intervals (CIs) were used as the effect size estimate. RESULTS: 26 eligible studies with 2,295 patients were identified. Our meta-analysis revealed that TAMs were overexpressed in CC (OR = 12.93, 95% CI = 7.73-21.61 and SMD = 1.58, 95% CI = 0.95-2.21) and that elevated TAM levels were strongly associated with lymph node metastasis (LNM) (SMD = 0.51, 95% CI = 0.90-2.01) and FIGO stages (SMD = 0.46, 95% CI = 0.08-0.85). Subgroup analysis indicated a significant positive correlation between LNM and TAMs density in tumor stroma, but not in cancer nests (SMD = 0.58, 95% CI = 0.31-0.58). Furthermore, in early stage, a stronger correlation exists between LNM and TAM density (SMD = 1.21, 95% CI = 0.75-1.66). In addition, it revealed that patients with high TAMs expression had poorer overall survival (OS) (HR = 2.55 95% CI = 1.59-4.07) and recurrence-free survival (RFS) (HR = 2.17, 95% CI = 1.40-3.35). CONCLUSIONS: Our analyses suggest that a high density of TAMs predicts adverse outcomes in CC.

[Value of calprotectin S100 A8/A9 in predicting the severity of Mycoplasma pneumoniae pneumonia in children]. / 钙卫蛋白S100 A8/A9å¯¹è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žæ‚£å„¿ç— æƒ ä¸¥é‡ç¨‹åº¦çš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia (MPP) and 30 healthy controls. According to the severity of the condition, the children with MPP were divided into mild subgroup (40 children) and SMPP subgroup (96 children). The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group, as well as between the two subgroups of MPP. The role of S100 A8/A9 in assessing the severity of MPP was explored. RESULTS: The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group, with a significantly greater increase in the SMPP subgroup (P<0.05). The multivariate logistic regression analysis showed that the increases in serum C reactive protein (CRP) and S100A8/A9 were closely associated with SMPP (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP, which was significantly higher than the AUC of S100 A8/A9 or CRP alone (P<0.05), with a specificity of 0.718 and a sensitivity of 0.952. CONCLUSIONS: S100 A8/A9 is closely associated with the severity of MPP, and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

Exploring machine learning applications in Meningioma Research (2004-2023).

Objective: This study aims to examine the trends in machine learning application to meningiomas between 2004 and 2023. Methods: Publication data were extracted from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WOSCC). Using CiteSpace 6.2.R6, a comprehensive analysis of publications, authors, cited authors, countries, institutions, cited journals, references, and keywords was conducted on December 1, 2023. Results: The analysis included a total of 342 articles. Prior to 2007, no publications existed in this field, and the number remained modest until 2017. A significant increase occurred in publications from 2018 onwards. The majority of the top 10 authors hailed from Germany and China, with the USA also exerting substantial international influence, particularly in academic institutions. Journals from the IEEE series contributed significantly to the publications. "Deep learning," "brain tumor," and "classification" emerged as the primary keywords of focus among researchers. The developmental pattern in this field primarily involved a combination of interdisciplinary integration and the refinement of major disciplinary branches. Conclusion: Machine learning has demonstrated significant value in predicting early meningiomas and tailoring treatment plans. Key research focuses involve optimizing detection indicators and selecting superior machine learning algorithms. Future efforts should aim to develop high-performance algorithms to drive further innovation in this field.

DDB2 promotes melanoma cell growth by transcriptionally regulating the expression of KMT2A and predicts a poor prognosis.

Identification of potential key targets of melanoma, a fatal skin malignancy, is critical to the development of new cancer therapies. Lysine methyltransferase 2A (KMT2A) promotes melanoma growth by activating the human telomerase reverse transcriptase (hTERT) signaling pathway; however, the exact mechanism remains elusive. This study aimed to reveal new molecular targets that regulate KMT2A expression and melanoma growth. Using biotin-streptavidin-agarose pull-down and proteomics, we identified Damage-specific DNA-binding protein 2 (DDB2) as a KMT2A promoter-binding protein in melanoma cells and validated its role as a regulator of KMT2A/hTERT signaling. DDB2 knockdown inhibited the expression of KMT2A and hTERT and inhibited the growth of melanoma cells in vitro. Conversely, overexpression of DDB2 activated the expression of KMT2A and promoted the growth of melanoma cells. Additionally, we demonstrated that DDB2 expression was higher in tumor tissues of patients with melanoma than in corresponding normal tissues and was positively correlated with KMT2A expression. Kaplan-Meier analysis showed a poor prognosis in patients with high levels of DDB2 and KMT2A. Overall, our data suggest that DDB2 promotes melanoma cell growth through the transcriptional regulation of KMT2A expression and predicts poor prognosis. Therefore, targeting DDB2 may regulate the effects of KMT2A on melanoma growth and progression, providing a new potential therapeutic strategy for melanoma.

Bioinformatic analysis combined with immune infiltration to explore osteoarthritis biomarkers and drug prediction.

Along with global aging, osteoarthritis (OA) appears to have a high incidence and disability rate, which seriously affects the quality of life of patients, making age a major risk factor. However, the pathology of OA is under-researched, and there is no obvious and effective treatment. Research has demonstrated the importance of aging, inflammation, and immunology in the onset and course of OA. This study aims to anticipate therapeutic drugs based on critical genes associated with OA and to elucidate the roles of genes and possible biomarkers associated with inflammation, immunology, and cellular senescence in OA. The OA gene expression matrix was first obtained from the Gene Expression Omnibus database. Screening for OA significant differentially expressed genes by bioinformatics identification. Specific biological processes and related signaling pathways of the differential genes were enriched. Then elucidate the status of immune cell involvement in OA based on immune infiltration analysis. Finally predict therapeutic agents based on pivotal genes. A total of 198 differentially expressed genes were identified in OA, and TP53, EGFR, TGFB1, LEP, CD4, MAPK8, SCARB1, ADIPOQ, JAK2, and SERPINE1 were further identified as important hub genes. The enrichment results showed that the development of arthritis was mainly related to immune cell differentiation, amino acid metabolism and cellular senescence process. The validation of immune infiltration results indicated that NK_cells, CD4_Tcells, Macrophages, Monocytic_lineage, Dendritic_cells, Basophils, CD8+_naive_T-cells may play an important role in the immune process of OA. Key Drug Prediction of Hub Genes found that Halicin, Ruxolitinib, Tofacitinib, Clenoliximab, Baricitinib may be a key drug or component in the treatment of OA.

Flexible Aqueous Cr-Ion Hybrid Supercapacitors with Remarkable Electrochemical Properties in all Climates.

The integration of hostless battery-like metal anodes for hybrid supercapacitors is a realistic design method for energy storage devices with promising future applications. With significant Cr element deposits on Earth, exceptionally high theoretical capacity (1546 mAh g-1), and accessible redox potential (-0.74 V vs. reversible hydrogen electrode) of Cr metals, the design of Cr anodes has rightly come into our focus. This work presents a breakthrough design of a flexible Cr-ion hybrid supercapacitor (CHSC) based on a porous graphitized carbon fabric (PGCF) substrate prepared by K2FeO4 activation. In the CHSC device, PGCF acts as both a current collector and cathode material due to its high specific surface area and superior conductivity. The use of a highly concentrated LiCl-CrCl3 electrolyte with high Cr plating/stripping efficiency and excellent antifreeze properties enables the entire PGCF-based CHSC to achieve well-balanced performance in terms of energy density (up to 1.47 mWh cm-2), power characteristics (reaching 9.95 mW cm-2) and durability (95.4 % capacity retention after 30,000 cycles), while realizing it to work well under harsh conditions of -40 °C. This work introduces a new concept for low-temperature energy storage technology and confirms the potential application of Cr anodes in hybrid supercapacitors.

Development of Peptide Paratope Mimics Derived from the Anti-ROR1 Antibody and Long-Acting Peptide-Drug Conjugates for Targeted Cancer Therapy.

Antibody-based targeted therapy in cancer faces a challenge due to uneven antibody distribution in solid tumors, hindering effective drug delivery. We addressed this by developing peptide mimetics with nanomolar-range affinity for Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using computational methods. These peptides showed both specific targeting and deep penetration in vitro and in vivo. Additionally, we created peptide-drug conjugates (PDCs) by linking targeting peptides to toxin drugs via various linkers and enhancing their in vivo half-life with fatty side chains for albumin binding. The antitumor candidate II-3 displayed exceptional affinity (KD = 1.72 × 10-9 M), internalization efficiency, anticancer potency (IC50 = 0.015 ± 0.002 µM), and pharmacokinetics (t1/2 = 2.6 h), showcasing a rational approach for designing PDCs with favorable tissue distribution and strong tumor penetration.

Molecular Transmission Network and Drug Resistance in Treatment-Naive HIV-1-Infected Patients in the Liangshan District, China.

This study aimed to investigate the molecular transmission network and drug resistance in treatment-naive HIV-1-infected patients in the Liangshan District, China. The research subjects for this study were HIV-1-infected patients who did not receive any antiretroviral therapy (ART) in the Liangshan District between January 2022 and July 2023. Peripheral venous whole-blood samples were collected from the research subjects. Two milliliters of blood was used for CD4+ T lymphocyte counting detection. Ten milliliters of blood was centrifuged to separate the plasma and blood cells for quantitative detection of HIV-1 RNA and DNA and drug resistance testing of HIV-1. A total of 156 participants were included in this study (88 males and 68 females). The median age of the participants was 37 years. The findings revealed a positive correlation between the HIV-1 DNA and the HIV-1 RNA levels (r = 0.478, p < 0.001). However, a negative correlation was observed between the HIV-1 DNA levels and CD4+ T lymphocyte counts (r = -0.186, p = 0.020). Of the 156 participants, 145 were successfully tested for drug resistance of HIV-1 RNA and HIV-1 DNA simultaneously. Four cases failed the HIV-1 RNA drug resistance testing, and another two failed the HIV-1 DNA drug resistance testing. The most common HIV-1 subtype was the CRF07_BC recombinant. In this study, the overall incidence of transmitted drug resistance (TDR) was 8.33%. The resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) were 7.69% and 0.64%, respectively. In addition, 32 participants were found to have drug-resistant mutations. The primary drug-resistant mutations were K103N, V179D, E157Q, and A128T, mainly against efavirenz (EFV) and nevirapine (NVP) resistance. The drug resistance of HIV-1-infected ART-naive patients in the Liangshan District cannot be ignored. HIV-1 drug resistance testing is recommended before initiating ART.

The low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells.

The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells.

[Activated phosphoinositide 3-kinase delta syndrome: report of seven cases]. / PI3Kδ过度活化综合征7例报道.

OBJECTIVES: To summarize the clinical data of 7 children with activated phosphoinositide 3-kinase delta syndrome (APDS) and enhance understanding of the disease. METHODS: A retrospective analysis was conducted on clinical data of 7 APDS children admitted to Hunan Provincial People's Hospital from January 2019 to August 2023. RESULTS: Among the 7 children (4 males, 3 females), the median age of onset was 30 months, and the median age at diagnosis was 101 months. Recurrent respiratory tract infections, hepatosplenomegaly, and multiple lymphadenopathy were observed in all 7 cases. Sepsis was observed in 5 cases, otitis media and multiple caries were observed in 3 cases, and diarrhea and joint pain were observed in 2 cases. Lymphoma and systemic lupus erythematosus were observed in 1 case each. Fiberoptic bronchoscopy was performed in 4 cases, revealing scattered nodular protrusions in the bronchial lumen. The most common respiratory pathogen was Streptococcus pneumoniae (4 cases). Six patients had a p.E1021K missense mutation, and one had a p.434-475del splice site mutation. CONCLUSIONS: p.E1021K is the most common mutation site in APDS children. Children who present with one or more of the following symptoms: recurrent respiratory tract infections, hepatosplenomegaly, multiple lymphadenopathy, otitis media, and caries, and exhibit scattered nodular protrusions on fiberoptic bronchoscopy, should be vigilant for APDS. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(5): 499-505.

Deficiency of CBL and CBLB ubiquitin ligases leads to hyper T follicular helper cell responses and lupus by reducing BCL6 degradation.

Recent evidence reveals hyper T follicular helper (Tfh) cell responses in systemic lupus erythematosus (SLE); however, molecular mechanisms responsible for hyper Tfh cell responses and whether they cause SLE are unclear. We found that SLE patients downregulated both ubiquitin ligases, casitas B-lineage lymphoma (CBL) and CBLB (CBLs), in CD4+ T cells. T cell-specific CBLs-deficient mice developed hyper Tfh cell responses and SLE, whereas blockade of Tfh cell development in the mutant mice was sufficient to prevent SLE. ICOS was upregulated in SLE Tfh cells, whose signaling increased BCL6 by attenuating BCL6 degradation via chaperone-mediated autophagy (CMA). Conversely, CBLs restrained BCL6 expression by ubiquitinating ICOS. Blockade of BCL6 degradation was sufficient to enhance Tfh cell responses. Thus, the compromised expression of CBLs is a prevalent risk trait shared by SLE patients and causative to hyper Tfh cell responses and SLE. The ICOS-CBLs axis may be a target to treat SLE.

Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

A Frog Skin-Derived Peptide Targeting SCD1 Exerts Radioprotective Effects Against Skin Injury by Inhibiting STING-Mediated Inflammation.

The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation-induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs (Pelophylax nigromaculatus) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats. Specifically, radiation-induced frog skin peptide-2 (RIFSP-2), from histone proteolysis exerted membrane permeability property, maintained cellular homeostasis, and reduced pyroptosis of irradiated cells with decreased TBK1 phosphorylation. Subsequently, stearyl-CoA desaturase 1 (SCD1) is identified, a critical enzyme in biogenesis of monounsaturated fatty acids (MUFAs) as a direct target of RIFSP-2 based on streptavidin-biotin system. The lipidomic analysis further assured the restrain of MUFAs biogenesis by RIFSP-2 following radiation. Moreover, the decreased MUFA limited radiation-induced and STING-mediated inflammation response. In addition, genetic depletion or pharmacological inhibition of STING counteracted the decreased pyroptosis by RIFSP-2 and retarded tissue repair process. Altogether, RIFSP-2 restrains radiation-induced activation of SCD1-MUFA-STING axis. Thus, the stress-induced amphibian peptides can be a bountiful source of novel radiation mitigators.

Dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood. Objectives: This study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology shedding light on its potential as a dietary intervention for AD prevention and treatment. Methods: The APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1ß, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aß in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice. Results: No significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aß levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1ß, IL-6) compared to the VAN and VAS groups. Conclusion: Dietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aß protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.

Development and validation of health-oriented personal evaluation for the community-dwelling older person based on the International Classification of Functioning, Disability and Health.

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) offers a standardized international terminology to operationalize function management across multiple domains, but the summary score of the ICF qualifier scale provides limited information on the comparison of personal abilities and functioning difficulties. OBJECTIVES: To enhance the interpretative power of the ICF-based Health-oriented Personal Evaluation for the community-dwelling older person (iHOPE-OP) scale through the implementation of the item response theory (IRT) modelling. METHODS: This cross-sectional, multi-centre study administrated 161 ICF categories (58 on body functions, 15 on body structures, 60 on activities or participation and 28 on environmental factors) to evaluate the functional level of 338 older citizens (female = 158, male = 180) residing in community or supportive living facilities. The validation process encompassed assessing the IRT model fitness and evaluating the psychometric properties of the IRT-derived iHOPE-OP scale. RESULTS: The age of participants ranged from 60 to 94.57, with the mean age of 70. The analysis of non-parametric and parametric models revealed that the three-parameter logistic IRT model, with a dichotomous scoring principle, exhibited the best fit. The 53-item iHOPE-OP scale demonstrated high reliability (Cronbach's α = 0.9729, Guttman's lambda-2 = 0.9749, Molenaar-Sijtsma Statistic = 0.9803, latent class reliability coefficient = 0.9882). There was a good validity between person abilities and the Barthel Index (p < .001, r = .83), as well as instrumental activities of daily living (p < .001, r = .84). CONCLUSIONS: IRT methods generate the reliable and valid iHOPE-OP scale with the most discriminable and minimal items to represent the older person's functional performance at a comprehensive level. The use of the Wright map can aid in presby-functioning management by visualizing item difficulties and person abilities. IMPLICATIONS FOR PRACTICE: Considering the intricate and heterogeneous health status of older persons, a single functional assessment tool might not fulfil the need to fully understand the multifaceted health status. For use in conjunction with the IRT and ICF framework, the reliable and valid iHOPE-OP scale was developed and can be applied to capture presby-functioning. The Wright map depicts the distribution of item difficulties and person abilities on the same scale that facilitates person-centred goal setting and tailors intervention.

Inclusion of reeling wastewater-derived sericin peptides in high-protein nutrition bars for antihardening and storage stability.

The utilization of agroindustrial wastes to enrich food protein resources and the exploration of their broader applications are crucial for addressing the food crisis and achieving sustainable development goals. In this study, reeling wastewater-derived sericin was hydrolyzed using papain and trypsin to prepare sericin peptide (SRP) and was used as an antihardening ingredient of high-protein nutrition bars (HPNBs). The mechanism of the antihardening effect of SRP was elucidated by investigating the content of advanced glycation end products and protein oxidation products (carbonyl and free sulfhydryl), and the molecular weight change of HPNBs during storage before and after the addition of SRP. Our results confirmed the fortification of HPNBs with SRP, which is beneficial for the promotion and expansion of sericin applications in the food industry, with positive implications for the rational utilization of protein resources and the enrichment of food protein sources.

Effects of Clip Anchoring on Preventing Migration of Fully Covered Self-Expandable Metal Stent in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Fully covered self-expandable metal stents (FCSEMSs) are commonly placed in patients with biliary stricture during endoscopic retrograde cholangiopancreatography (ERCP). However, up to 40% of migration has been reported, resulting in treatment failure or the requirement for further intervention. Here, we aimed to investigate the effects of metal clip anchoring on preventing the migration of FCSEMS. METHODS: Consecutive patients requiring placement of FCSEMS were included in this multicenter randomized trial. The enrolled patients were randomly assigned in a 1:1 ratio to receive clip anchoring (clip group) or not (control group). The primary outcome was the migration rate at 6 months after stent insertion. The secondary outcomes were the rates of proximal and distal migration and stent-related adverse events. The analysis followed the intention-to-treat principle. RESULTS: From February 2020 to November 2022, 180 patients with biliary stricture were enrolled, with 90 in each group. The baseline characteristics were comparable between the 2 groups. The overall rate of stent migration at 6 months was significantly lower in the clip group compared with the control group (16.7% vs 30.0%, P = 0.030). The proximal and distal migration rates were similar in the 2 groups (2.2% vs 5.6%, P = 0.205; 14.4% vs 22.2%, P = 0.070). Notably, none of the patients (0/8) who received 2 or more clips experienced stent migration. There were no significant differences in stent-related adverse events between the 2 groups. DISCUSSION: Our data suggest that clip-assisted anchoring is an effective and safe method for preventing migration of FCSEMS without increasing the adverse events.