An Extended Application of the Fast Multi-Locus Ridge Regression Algorithm in Genome-Wide Association Studies of Categorical Phenotypes.

Categorical (either binary or ordinal) quantitative traits are widely observed to measure count and resistance in plants. Unlike continuous traits, categorical traits often provide less detailed insights into genetic variation and possess a more complex underlying genetic architecture, which presents additional challenges for their genome-wide association studies. Meanwhile, methods designed for binary or continuous phenotypes are commonly used to inappropriately analyze ordinal traits, which leads to the loss of original phenotype information and the detection power of quantitative trait nucleotides (QTN). To address these issues, fast multi-locus ridge regression (FastRR), which was originally designed for continuous traits, is used to directly analyze binary or ordinal traits in this study. FastRR includes three stages of continuous transformation, variable reduction, and parameter estimation, and it can computationally handle categorical phenotype data instead of link functions introduced or methods inappropriately used. A series of simulation studies demonstrate that, compared with four other continuous or binary or ordinal approaches, including logistic regression, FarmCPU, FaST-LMM, and POLMM, the FastRR method outperforms in the detection of small-effect QTN, accuracy of estimated effect, and computation speed. We applied FastRR to 14 binary or ordinal phenotypes in the Arabidopsis real dataset and identified 479 significant loci and 76 known genes, at least seven times as many as detected by other algorithms. These findings underscore the potential of FastRR as a very useful tool for genome-wide association studies and novel gene mining of binary and ordinal traits.

Comparison of Intercostal Nerve Block and Serratus Anterior Plane Block for Perioperative Pain Management and Impact on Chronic Pain in Thoracoscopic Surgery: A Randomized Controlled Trial.

OBJECTIVES: This study compares the analgesic efficacy of Intercostal Nerve Block (ICNB) under direct thoracoscopic visualization and Serratus Anterior Plane Block (SAPB) with ultrasound guidance during thoracoscopic surgery's perioperative period. Furthermore, it examines their impact on chronic pain and identifies potential risk factors associated with its development. METHODS: In this prospective randomized controlled study, 74 thoracoscopic surgery patients were randomly assigned to ICNB or SAPB groups. Attending surgeons administered ICNB, while anesthesiologists performed SAPB, both using 20 mL of 0.5% ropivacaine. Primary outcomes included Visual Analog Scale (VAS) scores for resting and coughing pain at 6, 12, 24, and 48 hours postoperatively, perioperative opioid and NSAID consumption, and chronic pain incidence at 3 months postoperatively. Secondary outcomes aimed to identify independent risk factors for chronic pain. RESULTS: The primary results reveal that SAPB group exhibited significantly lower VAS scores than ICNB group for postoperative coughing at 24 hours (P<0.001, 95% CI=[0.5, 1]) and for resting pain at 48 hours (P=0.001, 95% CI=[0.2, 1]). Conversely, ICNB group demonstrated reduced VAS score for resting pain at 6 hours compared to SAPB group (P=0.014, 95% CI=[-0.5, 0.5]). SAPB group required significantly less intraoperative sulfentanil (P<0.001, 95% CI=[2.5, 5]), remifentanil (P=0.005, 95% CI=[-0.4, -0.1]), and flurbiprofen ester (P=0.003, 95% CI=[0, 50]) than ICNB group. Chronic pain incidence was similar (P=0.572, 95% CI=[0.412, 1.279]), with mild pain in both ICNB and SAPB groups. Secondary findings indicate that resting VAS score at 12 hours (OR=7.59, P=0.048, 95% CI=[1.02, 56.46]), chest tube duration (OR=3.35, P=0.029, 95% CI=[1.13, 9.97]), and surgical duration (OR=1.02, P=0.049, 95% CI=[1.00, 1.03]) were significant predictors of chronic pain occurrence. DISCUSSION: ICNB and SAPB demonstrated comparable analgesic effects, with similar rates of chronic pain occurrence. Chronic pain independent risk factors included resting VAS score at 12 hours, chest tube duration, and surgical duration.

Construction of tissue engineered cornea with skin-derived corneal endothelial-like cell and mechanism research for the cell differentiation.

Introduction: Corneal endothelial transplantation accounts for most of corneal transplantation for treating corneal diseases, however severe shortage of corneal donors is the biggest obstacle. In our previous study, we differentiated human skin-derived precursors (SKPs) into corneal endothelial cell (CEC)-like cells with a co-culture system. In this study, we aimed to investigate cell differentiation molecular mechanism and evaluate the function of CEC-like cells by developing tissue-engineered corneas in order to improve cell production efficiency and provide basic research for clinical transformation. Methods: We performed transcriptome sequencing of SKPs and CEC-like cells. Further, we focused on the possible enriching pathways, including PI3K/Akt, MAPK/Erk, WNT/ß-catenin, and important transcription factors Pitx2 and Foxc1. The PI3K and ß-catenin inhibitors were also added to the culture system to observe the differentiation alteration. We developed a graft for a tissue-engineered cornea (TEC) using CEC-like cells and acellular porcine cornea matrix scaffold. The tissue-engineered corneas were transplanted into rabbits via penetrating keratoplasty. Results: The PI3K/Akt, MAPK/Erk, and WNT/ß-catenin pathways play important roles during the differentiation of SKPs into CEC-like cells. Crosstalk existed between the PI3K/Akt and MAPK/Erk pathways. The PI3K/Akt and WNT/ß-catenin pathways were connected. Pitx2 and Foxc1 were subject to temporal and spatial controls of the WNT/ß-catenin pathway. The inhibition of the PI3K/Akt and WNT/ß-catenin pathways both prevented cell differentiation. CEC-like cells grew well on the acellular porcine cornea matrix scaffold, and the tissue-engineered corneal graft performed well after transplantation into rabbits. Conclusion: We provide experimental basis for CEC-like cell industrial production and drive the cells to be clinically applied in cellular replacement therapy or alternative graft substitution for treating corneal diseases in the future.

Nomilin Reversed Cardiotoxicity Caused by Co-exposure to Zearalenone and Deoxynivalenol via the Keap1/Nrf2 Signaling Pathway in Zebrafish.

The contamination of food and feed by mycotoxins, particularly zearalenone (ZEA) and deoxynivalenol (DON), is a global issue. Prenatal exposure to ZEA and DON can result in congenital cardiac malformations in fetuses. Addressing the prevention and mitigation of embryonic cardiotoxicity caused by these toxins is crucial. Citrus limonoid nomilin (NOM) is an extract known for its pathological properties in various diseases. This study investigated the potential mechanism of NOM in mitigating cardiotoxicity caused by ZEA and DON co-exposure in a zebrafish model. The findings indicated that NOM pretreatment alleviated cardiac developmental toxicity induced by ZEA and DON and normalized the expression of key genes involved in heart development, including gata4, vmhc, nkx2.5, and sox9b. Co-exposure to NOM, ZEA, and DON enhanced SOD and catalase activity, increased glutathione levels, and reduced ROS and malondialdehyde production. Furthermore, NOM reduced cardiac oxidative damage by activating the Keap1/Nrf2 signaling pathway. In summary, this study offers new insights for preventive interventions against congenital heart disease caused by mycotoxin exposure.

Evaluating the toxicity effects of thiamethoxam and its main metabolite clothianidin to earthworms (Eisenia fetida) from the perspective of endogenous metabolites.

The widespread application of neonicotinoid insecticides (NNIs) has attracted widespread attention to their potential ecotoxicological effects. In this study, we systematically evaluated the toxic effects of thiamethoxam (TMX) and its metabolite clothianidin (CLO) on earthworms (Eisenia fetida). Specifically, the antioxidant system responses and endogenous metabolite metabolism responses in earthworms were analyzed in the temporal dimension after 7, 14, 21 and 28 days of exposure to TMX and CLO. The results found that TMX and CLO could inhibit the growth phenotype of earthworms and cause significant changes in antioxidant system related indicators. More importantly, we found that TMX and CLO could cause significant changes in the metabolic profiles of earthworms through NMR-based metabolomics. From the changes in endogenous metabolites, the toxicity effects of TMX on earthworms gradually increases with prolonged exposure time. Differently, the toxicity effects of CLO on earthworms is significantly higher than that of TMX in the early stages of exposure. Meanwhile, these impacts will not weaken with prolonged exposure time. Furthermore, the results of KEGG enrichment pathway analysis indicated that TMX and CLO could significantly interfere with energy homeostasis, redox homeostasis, osmotic regulation, amino acid metabolism and protein synthesis in earthworms. These findings further deepen our understanding of the ecotoxicological effects of NNIs on soil organism.

Self-assembly and dynamic exchange of cuboctahedral metal-organic cages.

Due to their unique physical and chemical properties, metal-organic cage structures have great potential for applications in various fields. However, current studies have mainly focused on highly symmetric structures assembled from single metal ions and organic ligands, limiting their diversity and complexity, and there are still relatively few studies on the dynamic formation process of metal-organic cages. Herein, we constructed a series of metal-organic cages with different sizes assembled from the highly-stable coordination of 2,2':6',2''-terpyridine-based tetratopic ligands and various metals ions such as Zn, Cu, Co and Fe. Furthermore, the intermolecular exchange process between the metal-organic cages was explored through the dynamic exchange of ligands, and the formation of a series of hybrid supramolecular nanocages together with their final tendency to form a predominant structure of M24L14L28 was observed. In addition, the binding of metal-organic cages with 5,10,15,20-tetrakis(3,4,5-trimethoxyphenyl) porphyrin-Zn was also investigated. This study not only expands the complexity and diversity of metal-organic cages, but also provides a new perspective for studying the dynamic behaviour of metal-organic cages.

[Research progress on the relationship between TRAF6 and neurodegenerative diseases].

Given the increasing trend of aging population in the world, neurodegenerative diseases (NDDs), a common type of diseases that mostly occur in the elderly, have attracted much more attention. It has been shown that tumor necrosis factor receptor-associated factor 6 (TRAF6) is involved in the regulation of neuroinflammation, an important pathological feature of NDDs, and affects the occurrence and development of NDDs. Most importantly, the regulatory effect of TRAF6 is related to its ubiquitination. Therefore, in the present paper, the molecular structure, biological function, and ubiquitination mechanism of TRAF6, and its relationship with some common NDDs, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, were analyzed and summarized. The possible molecular mechanisms by which TRAF6 regulates the occurrence of NDDs were also elucidated, providing a theoretical basis for exploring the etiology and treatment of NDDs.

MSR1-dependent efferocytosis improved ischemia-reperfusion injury following aged-donor liver transplantation in mice by regulating the pro-resolving polarisation of macrophages.

Compared with young liver donors, aged liver donors are more susceptible to ischemia-reperfusion injury (IRI) following transplantation, which may be related to excessive inflammatory response and macrophage dysfunction, but the specific mechanism is unclear. Macrophage scavenger receptor 1 (MSR1) is a member of the scavenger receptor family, and plays an important regulatory role in inflammation response and macrophage function regulation. But its role in IRI following aged-donor liver transplantation is still unclear. This study demonstrates that MSR1 expression is decreased in macrophages from aged donor livers, inhibiting their efferocytosis and pro-resolving polarisation. Decreased MSR1 is responsible for the more severe IRI suffered by aged donor livers. Overexpression of MSR1 using F4/80-labelled AAV9 improved intrahepatic macrophage efferocytosis and promoted pro-resolving polarisation, ultimately ameliorating IRI following aged-donor liver transplantation. In vitro co-culture experiments further showed that overexpression of MSR1 promoted an increase in calcium concentration, which further activated the PI3K-AKT-GSK3ß pathway, and induced the upregulation of ß-catenin. Overall, MSR1-dependent efferocytosis promoted the pro-resolving polarisation of macrophages through the PI3K-AKT-GSK3ß pathway-induced up-regulating of ß-catenin leading to improved IRI following aged-donor liver transplantation.

Highly efficient removal of aqueous phosphate via iron-manganese fabricated biochar: Performance and mechanism.

Biochar (BC) has emerged as a potential solution to phosphate removal from wastewater primarily resulting from global overuse of fertilizers. Further modification by embedment of iron (Fe)-manganese (Mn) oxides on BC can enhance phosphate removal; however, the modification method serves as a vital factor underlying distinctive removal performances and mechanisms, which have yet been systematically examined. Herein, two Fe-Mn modified BC, Fe/MnBC (comprised of Fe3O4 and MnO2) and Fe-MnBC (comprised of MnFe2O4), were comprehensively investigated for gaining insights into the unsolved perspectives. The results indicated that Fe-MnBC exhibited a markedly greater maximum phosphate adsorption capacity of 135.88 mg g-1 than that of Fe/MnBC with 17.93 mg g-1. The comparative results based on microstructure and spectroscopic analyses suggested that different Fe and Mn oxides were successfully loaded, which played a distinctive role in phosphate removal. Further characterizations unveiled that the key mechanisms for phosphate removal by Fe/MnBC are inner-sphere complexation and precipitation, while electrostatic interaction and outer-sphere complexation are the dominant mechanisms underlying the notable performance of Fe-MnBC. The delicately designed Fe-MnBC with special structure and property also enabled a superior regeneration capacity, which presented a promisingly high phosphate removal efficacy of over 81.34% after five cycles. These results enhance comprehension regarding the impact of biochar modification techniques on phosphate removal, offering positive indications for the remediation of excessive phosphate and other pollutant-containing water through feasible design and green chemicals.

The Incremental Value of Native T1 Mapping-Derived Radiomics for The Diagnosis of Amyloid Light-Chain Cardiac Amyloidosis.

RATIONALE AND OBJECTIVES: This study aimed to assess the incremental diagnostic value of non-contrast T1 mapping-derived radiomics in patients with amyloid light-chain cardiac amyloidosis (AL-CA). METHODS: We retrospectively collected 86 patients with suspected AL-CA and 28 control patients who underwent cardiac MRI at 3.0 T in our institution, and the MRI data were divided into a training set and a test set. Radiomic features were extracted based on native T1 maps using a freely available software package. We applied LASSO logistic regression method to select radiomic features with high diagnostic value of AL-CA and develop a predictive model. The diagnostic performance of the radiomics model was evaluated using receiver operating characteristic curve analysis and compared to T1 values. RESULTS: A total of 70 people were diagnosed with AL-CA, and cardiac involvement was observed in 202 myocardial slicers. The accuracy of T1 values for the diagnosis of myocardial involvement was 0.886, with a threshold value of 1375 ms. The radiomics score comprised a total of three features. The radiomics score demonstrated significantly higher sensitivity in detecting myocardial involvement compared to T1 values in both the training set (AUC 0.886 vs. 0.924, P = 0.025) and the test set (0.862 vs 0.915, P = 0.026). The combined model comprising T1 values and a radiomic feature named S(4,-4) Correlat showed higher diagnostic performance in comparison to T1 values alone both in the training and test sets, with AUC values of 0.929 and 0.909, respectively. CONCLUSION: The radiomic features derived from native T1 mapping demonstrated incremental value for the diagnosis of AL-CA, which may be an alternative to T1-derived ECV to avoid the use of contrast in patients with suspected myocardial involvement in systemic amyloidosis.

The Pathogenic Mechanisms of and Novel Therapies for Lamin A/C-Related Dilated Cardiomyopathy Based on Patient-Specific Pluripotent Stem Cell Platforms and Animal Models.

Variants (pathogenic) of the LMNA gene are a common cause of familial dilated cardiomyopathy (DCM), which is characterised by early-onset atrioventricular (AV) block, atrial fibrillation and ventricular tachyarrhythmias (VTs), and progressive heart failure. The unstable internal nuclear lamina observed in LMNA-related DCM is a consequence of the disassembly of lamins A and C. This suggests that LMNA variants produce truncated or alternative forms of protein that alter the nuclear structure and the signalling pathway related to cardiac muscle diseases. To date, the pathogenic mechanisms and phenotypes of LMNA-related DCM have been studied using different platforms, such as patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) and transgenic mice. In this review, point variants in the LMNA gene that cause autosomal dominantly inherited forms of LMNA-related DCM are summarised. In addition, potential therapeutic targets based on preclinical studies of LMNA variants using transgenic mice and human iPSC-CMs are discussed. They include mitochondria deficiency, variants in nuclear deformation, chromatin remodelling, altered platelet-derived growth factor and ERK1/2-related pathways, and abnormal calcium handling.

Aging-Related CYP3A Functional Changes in Chinese Older Patients: New Findings from Model-Based Assessment of Amlodipine.

Aging-related alterations in hepatic enzyme activity, particularly of the CYP3A, significantly impact drug efficacy and safety in older adults, making it essential to understand how aging affects CYP function for optimal drug therapy. The exogenous probe substrate method, a minimally invasive approach to assess liver metabolic enzyme activity in vivo, is effective in studying these changes. Amlodipine being extensively metabolized (> 90%) in the liver, primarily via cytochrome P450 enzyme CYP3A was selected as a probe to investigate and quantify the factors affecting the aging-related changes of CYP3A in the Chinese older population. Amlodipine concentration data were collected from an ongoing noninterventional clinical study conducted at Peking University Third Hospital. A physiologically-based pharmacokinetic modeling approach, grounded in population pharmacokinetic (PPK) analysis, was employed to physiologically quantify the aging-related changes in CYP3A function. A total of 132 amlodipine concentrations from 69 patients were obtained from the clinical study. PPK analysis shows that frailty phenotype but not age is a significant influence and frail patients have 37% greater plasma amlodipine exposure than nonfrail patients. This difference in CYP3A function may be attributed to a 63.2% lower CYP3A relative abundance in the frail patients, compared with that in the nonfrail patients. In the context of dose selection for older adults, focusing on frailty rather than chronological age should be recognized as a more relevant approach, because frailty might more accurately reflect the individual's biological age. Our study suggested a need to shift the research focus from chronological age to biological age.

Comprehensive Analysis of Immune Responses to Neoadjuvant Immunotherapy in Resectable Non-small Cell Lung Cancer.

BACKGROUND: Neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of early stage non-small cell lung cancer (NSCLC). However, little is known about which patients are likely to benefit most from neoadjuvant immunotherapy. In this study, we performed a multiplatform analysis on samples from resectable NSCLC treated with neoadjuvant immunotherapy to explore molecular characteristics related to immune responses. PATIENTS AND METHODS: A total of 17 patients with resectable stage IB-IIIA NSCLC treated with neoadjuvant immunotherapy were included. A multiplex cytokine assay, bulk TCR sequencing in peripheral blood, and multiplexed immunohistochemistry were performed. RESULTS: Low levels of stromal cell-derived factor (SDF)-1alpha at baseline were associated with unfavorable disease-free survival (DFS). Patients with major pathologic response (MPR) showed a decrease in HGF after one cycle of neoadjuvant immunotherapy. An increase in IDO and IP-10 was observed in patients who developed immune-related adverse events (irAEs) after neoadjuvant immunotherapy. There were no correlations between irAEs and MPR or DFS. The MPR group presented a significant decrease in white blood cells and neutrophil count after neoadjuvant immunotherapy. The high peripheral baseline TCR convergence was correlated with MPR and favorable DFS in lung squamous cell carcinoma (LUSC) receiving neoadjuvant immunotherapy. Neoadjuvant immunotherapy led to a significant increase in CD4+, CD8+, and CD8+CD39+ T-cell infiltration in tumor areas. CONCLUSIONS: This study suggests the potential roles of cytokines and TCR convergence for predicting ICIs response in resectable NSCLC and LUSC. CD8+CD39+T cells and CD4+ T cells could be involved in the action of neoadjuvant immunotherapy.

N-acetyltransferase 10 mediates cognitive dysfunction through the acetylation of GABABR1 mRNA in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a critical neurological complication of sepsis and represents a crucial factor contributing to high mortality and adverse prognosis in septic patients. This study explored the contribution of NAT10-mediated messenger RNA (mRNA) acetylation in cognitive dysfunction associated with SAE, utilizing a cecal ligation and puncture (CLP)-induced SAE mouse model. Our findings demonstrate that CLP significantly upregulates NAT10 expression and mRNA acetylation in the excitatory neurons of the hippocampal dentate gyrus (DG). Notably, neuronal-specific Nat10 knockdown improved cognitive function in septic mice, highlighting its critical role in SAE. Proteomic analysis, RNA immunoprecipitation, and real-time qPCR identified GABABR1 as a key downstream target of NAT10. Nat10 deletion reduced GABABR1 expression, and subsequently weakened inhibitory postsynaptic currents in hippocampal DG neurons. Further analysis revealed that microglia activation and the release of inflammatory mediators lead to the increased NAT10 expression in neurons. Microglia depletion with PLX3397 effectively reduced NAT10 and GABABR1 expression in neurons, and ameliorated cognitive dysfunction induced by SAE. In summary, our findings revealed that after CLP, NAT10 in hippocampal DG neurons promotes GABABR1 expression through mRNA acetylation, leading to cognitive dysfunction.

Unraveling the role of Major Vault Protein as a novel immune-related biomarker that promotes the proliferation and migration in pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma (PAAD) is a formidable challenge in oncology research, with a complex pathogenesis that requires to be explored. Major Vault Protein (MVP) is the principal structural component of the vault complex, and its expression level is remarkably upregulated in various cancers. Extensive investigations have been conducted to explore the role of MVP in specific cancer contexts, yet the potential molecular mechanisms and biological functions of MVP in PAAD still remain considerably elusive. This study aims to explore the role of MVP as a novel immune-related biomarker in the pathogenesis and clinical treatment of PAAD. Methods: Gene expression data and clinical information were collected from TCGA, GTEx and GEO databases. Survival, prognostic and functional enrichment analysis were employed with R software. Immunological correlation analysis was performed using TIMER2.0, TIDE scores, TISIDB and TISCH. Epigenetic analysis was implemented by MethSurv, CPTAC, UALCAN, and cBioPortal. Drug analysis was conducted using Enrichr and CellMiner. Moreover, cellular experiments, like RNA interference, qRT-PCR, Western blot, cell cycle analysis, cell apoptosis analysis, colony formation assay, transwell assay, and wound healing assay, were performed for verifying the functional properties of MVP in the PAAD progression. Results: We demonstrated an abnormally upregulated expression of MVP in PAAD tissues, which notably correlated with an adverse prognosis in PAAD patients. Functional analysis suggested the conceivable involvement of MVP in immune modulation, and immunotherapy. Additionally, we identified genetic alterations, reduced promoter methylation, and heightened phosphorylation in MVP. We also clarified Suloctidil and Tetradioxin as the most notable potential drugs targeting MVP in PAAD. Moreover, our experimental observations consistently highlighted the significant impact of MVP deficiency on impeding PAAD cell proliferation, inhibiting cell migration, and accelerating cell apoptosis. Interestingly, a potential link between MVP and ERK or AKT pathways was displayed, which opens new avenues for further exploration of the molecular mechanisms of MVP-targeted therapies in PAAD. Conclusions: This study systematically describes MVP as an immune-related biomarker with remarkable potential for predicting the prognosis, tumor progression and immunotherapeutic efficacy in PAAD.

Animation-guided family empowerment program on perioperative care after neurosurgery: A randomized controlled trial for preventing respiratory complications.

Background: This study aimed to evaluate the effectiveness of using animation as education material for family empowerment program on perioperative care for caregivers whose children were to undergo neurosurgery. Methods: A total of 204 caregivers were randomly assigned to either the face-to-face oral nursing educated group (Oral Group) or the animation-assisted nursing educated group (Animated Group). The nursing education primarily focused on instructing caregivers about the manual vibration method. The primary outcome of interest in this study was participants' knowledge level, collected by a 10-item questionnaire. Secondary outcomes included child patients' clinical data, including hospitalization days, treatments, and signs of pneumonia. Results: Participants in the Animated Group exhibited significantly higher accuracy in perioperative care knowledge assessment, and patients in this group had a lower chance of requiring atomization therapy compared to the Oral Group. Conclusions: The animation-assisted nursing education program effectively enhances pediatric caregivers' knowledge, reduces respiratory complications after surgery, and offers valuable insights for future studies on the use of such programs to instruct caregivers.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and obstructive sleep apnea: a cross-sectional study from NHANES.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a widespread sleep disturbance linked to metabolic and cardiovascular conditions. The Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratios (NHHR) has been proposed as being a potential biomarker to gauge cardiovascular risk. However, its relationship with OSA remains unclear. METHODS: This survey investigated the link NHHR to OSA in American citizens aged 20 and older using information collected via the National Health and Nutrition Examination Survey (NHANES) during the years 2017 to 2020. Logistic regression models with multivariable adjustments were employed to assess this relationship. Nonlinear associations were explored using smooth curve fitting, with a two-part linear regression model identifying a threshold effect. Subgroup analyses were conducted to evaluate population-specific differences. RESULTS: The survey encompassed 6763 participants, with an average age of 50.75 ± 17.32. The average NHHR stood at 2.74, accompanied by a standard deviation of 1.34, while the average frequency of OSA was 49.93%. Upon adjusting for covariates, each unit increase in NHHR may be associated with a 9% rise in OSA incidence. (95% confidence intervals 1.04-1.14; P < 0.0001). Notably, a U-shaped curve depicted the NHHR-OSA relationship, with an inflection point at 4.12. Subgroup analyses revealed consistent associations, with educational attainment and diabetes status modifying the NHHR-OSA relationship. CONCLUSION: The study highlights NHHR as a potential tool for OSA prediction, presenting avenues for advanced risk evaluation, tailored interventions, personalized treatment approaches, and preventive healthcare.

Elucidating Microglial Heterogeneity and Functions in Alzheimer's Disease Using Single-cell Analysis and Convolutional Neural Network Disease Model Construction.

In this study, we conducted an in-depth exploration of Alzheimer's Disease (AD) by integrating state-of-the-art methodologies, including single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and a convolutional neural network (CNN) model. Focusing on the pivotal role of microglia in AD pathology, our analysis revealed 11 distinct microglial subclusters, with 4 exhibiting obviously alterations in AD and HC groups. The investigation of cell-cell communication networks unveiled intricate interactions between AD-related microglia and various cell types within the central nervous system (CNS). Integration of WGCNA and scRNA-seq facilitated the identification of critical genes associated with AD-related microglia, providing insights into their involvement in processes such as peptide chain elongation, synapse-related functions, and cell adhesion. The identification of 9 hub genes, including USP3, through the least absolute shrinkage and selection operator (LASSO) and COX regression analyses, presents potential therapeutic targets. Furthermore, the development of a CNN-based model showcases the application of deep learning in enhancing diagnostic accuracy for AD. Overall, our findings significantly contribute to unraveling the molecular intricacies of microglial responses in AD, offering promising avenues for targeted therapeutic interventions and improved diagnostic precision.

Stimuli-responsive antioxidant Pickering emulsions stabilized by functionalized cellulose nanocrystals.

Stimuli-responsive antioxidant Pickering emulsions play crucial role in many industrial areas. This study demonstrated for the first time oil-in-water Pickering emulsions with outstanding antioxidation and responsive demulsification stabilized by functionalized cellulose nanocrystals (CNCs). Dialdehyde cellulose nanocrystals (DACs) were first prepared through the oxidation of CNCs with periodate, followed by the grafting of p-aminophenols (PAPs) onto their surfaces through Schiff base reaction, affording PAP grafted DACs (DAC-g-PAP) via dynamic covalent linkage. The degree of the oxidation (DO) of DACs had a significant effect on the yield of the targeting DAC-g-PAP nanoparticles. High DO (≥40 %) potentially led to the degradation of DACs during the grafting of PAP. The introduced PAP endowed DACs with excellent radical scavenging capability, thereby providing antioxidant properties while improving the hydrophobicity. DAC-g-PAP nanoparticles were then applied as Pickering emulsifiers to prepare oil-in-water Pickering emulsions. The resultant Pickering emulsions indicated exceptional antioxidant and pH-responsiveness together with good freezing-thaw stability. The structures of DAC-g-PAP nanoparticles were thoroughly characterized in this study.

Hsa_Circ_0008035 drives immune evasion of gastric cancer via promoting EXT1-mediated nuclear translocation of PKM2.

Circular RNAs (circRNAs) have been reported to be associated with the malignant phenotypes of cancer. However, the role and underlying mechanism of hsa_Circ_0008035 in colorectal cancer (CRC) remains unclear. In this study, we elucidated the pivotal role of hsa_circ_0008035 in gastric cancer progression and immune evasion. Elevated hsa_circ_0008035 levels in gastric cancer patient serum correlated positively with disease advancement, including tumor stages and lymph node metastasis. Functional analyses revealed a negative association between hsa_circ_0008035 and CD8+ T cell number and function. Mechanistically, hsa_circ_0008035 encoded the novel protein EXT1-219aa, suppressing EXT1 phosphorylation and expression. Additionally, hsa_circ_0008035 regulated pyruvate metabolism by influencing the nucleus localization of PKM2. The identified EXT1/PKM2 axis further underscored the intricate regulatory mechanisms orchestrated by hsa_circ_0008035 in gastric cancer, offering potential diagnostic and therapeutic implications in the ongoing pursuit of targeted therapies for gastric cancer patients.