Specifying the choice of EGFR-TKI based on brain metastatic status for advanced NSCLC with EGFR p.L861Q mutation.

BACKGROUND: In-depth insight into the genomic features of the uncommon EGFR p.L861Q mutant NSCLC is scarcely performed, and no consensus on the preferred treatment strategy has been established. Moreover, the therapeutic implications of EGFR-TKI stratified by clinical and molecular features remained largely unknown. METHODS: A multi-center NGS database comprising 44,993 NSCLC samples was utilized for the genomic landscape profiling of EGFR p.L861Q mutation. Furthermore, a real-world cohort of 207 patients harboring EGFR p.L861Q mutation with complete treatment history was curated for comprehensive clinical analysis. RESULTS: L861Q is prevalent in approximately 2.1% of EGFR-mutated NSCLC and is typically co-mutated with EGFR p.G719X on the same allele (20%) and exhibits co-occurrent EGFR copy number amplification in approximately 17% of cases. In the first-line setting, afatinib and third-generation EGFR-TKI have been shown to yield notably superior treatment outcomes compared to first-generation EGFR-TKI (1st vs.2nd vs.3rd generations, ORR: 15.8% vs.56.5% vs.46.7%, P=0.01; median PFS: 6.4 vs.13.5 vs.15.1 months, P=0.002). This finding consistently held for patients without CNS metastases (1st vs.2nd vs.3rd generations, median PFS:6.0 vs.18.2 vs.14.1 months, P=0.003). In contrast, third-generation EGFR-TKI demonstrated superior efficacy compared to afatinib or first-generation TKI among the subgroup of brain metastasis (Pooled 1st/2nd-generation vs.3rd-generation TKI, brain ORR:0.00% vs.33.33%; median PFS:7.9 vs.19.3 months, P=0.021). Additional concurrent EGFR mutations or EGFR amplification did not yield a discernible impact on the efficacy of EGFR-TKI. CONCLUSIONS: The present study comprehensively elucidates the molecular features of EGFR p.L861Q mutation and underscores the optimal therapeutic choice of first-line EGFR-TKI based on brain metastatic status.

Structure and physicochemical properties of starches from six accessions of the genus Pueraria in China.

Kudzu (Pueraria lobata) root contains abundant starch, but the physicochemical properties of kudzu starch are not well understood. In this study, we compared the compositions and physicochemical properties of starches isolated from six Pueraria accessions in China. Caige starch exhibited the highest purity (96.99 %) and amylose content (24.76 %), while Yege starch contained higher levels of puerarin (493.37 µg/g) and daidzein (38.68 µg/g). All kudzu starches were rich in resistant starch, with RS2 content ranging from 38.61 % to 46.22 % and RS3 content from 3.59 % to 6.04 %. The granules of kudzu starches varied in morphology, with Yege starch featuring larger polygonal granules. The kudzu starches presented either A-type or A-type-like C-type diffraction patterns. Caige starch had a higher IR2 value (1.28), higher gelatinization temperatures, wider temperature ranges, and greater enthalpy changes. Yege (JX) starch exhibited the highest peak viscosity but the lowest setback viscosity and pasting temperature. Fenge starch showed the highest final viscosity, with Fenge (ZJ) starch demonstrating the highest crystallinity (25.7 %) and IR1 value (0.80). These results indicated that kudzu starches derived from various Pueraria species possess unique structural and physicochemical properties, which provide significant potential for applications in food and other industrial fields.

Current status of research on polysaccharide-based functional gradient gel materials: A review.

Functional gradient materials with material property anisotropy are one of the hotspots of current new material research. The gradient change of material properties comes from the change of the content of one or more components in the material, which is closely related to the preparation process of the material. Meanwhile, polysaccharide materials, as an environmentally friendly and green material, have attracted extensive attention from researchers. This paper focuses on the preparation process of functional gradient gel materials based on polysaccharides, analyzes the laws affecting the distribution of substances during the molding process from the basic principles of material molding, and clarifies the advantages and disadvantages of various methods, so as to promote the innovation of the theory of the preparation method of functional gradient gel materials. At the same time, the specific applications that can be realized by the gradient materials are introduced and compared with the traditional homogeneous materials to elucidate the enhancement of the usage properties brought by their unique gradient structure or properties, which will play a certain role as a reference for the direction of the application of the subsequent materials.

A review of groundwater iodine mobilization, and application of isotopes in high iodine groundwater.

Excessive intake of iodine will do harm to human health. In recent years, high iodine groundwater has become a global concern after high arsenic and high fluorine groundwater. A deep understanding of the environmental factors affecting iodine accumulation in groundwater and the mechanism of migration and transformation is the scientific prerequisite for effective prevention and control of iodine pollution in groundwater. The paper comprehensively investigated the relevant literature on iodine pollution of groundwater and summarized the present spatial distribution and hydrochemical characteristics of iodine-enriched groundwater. Environmental factors and hydrogeological conditions affecting iodine enrichment in aquifers are systematically summarized. An in-depth analysis of the hydrologic geochemistry, physical chemistry, biogeochemistry and human impacts of iodine transport and transformation in the surface environment was conducted, the results and conclusions in the field of high iodine groundwater research are summarized comprehensively and systematically. Stable isotope can be used as a powerful tool to track the sources of hydrochemical components, biogeochemistry processes, recharge sources and flow paths of groundwater in hydrogeological systems, to provide effective research methods and means for the study of high iodine groundwater system, and deepen the understanding of the formation mechanism of high iodine groundwater, the application of isotopic technique in high iodine groundwater is also systematically summarized, which enriches the method and theory of high iodine groundwater research. This paper provides more scientific basis for the prevention and control of groundwater iodine pollution and the management of groundwater resources in water-scarce areas.

Trends in nonsugar sweetener use among United States adults by chronic diseases presence: 1999 to March 2020.

BACKGROUND: Although long-term health effects of nonsugar sweeteners (NSSs) are uncertain, they are widely used as a common alternative to added sugar, especially among people with chronic diseases. It is essential to evaluate trends in NSS use to inform policy makers. OBJECTIVES: This study aimed to investigate trends in NSS use overall and by chronic diseases presence in United States adults. METHODS: The analysis used data of United States adults (≥20 y) collected in National Health and Nutrition Examination Survey [NHANES (1999 to March 2020)]. Age-adjusted percentage of individuals consuming NSS beverages, NSS foods, tabletop NSS, or any of them during the first 24-h dietary recall period was calculated in each NHANES survey cycle. Weighted multivariable logistic or linear regression models were used to examine trends in NSS use over time. RESULTS: A total of 51,703 United States adults were included in the analysis. In total population, age-adjusted percentage of individuals consuming NSS in the past day increased from 29.3% in 1999-2000 to 37.5% in 2005-2006 and decreased to 24.1% in 2017 to March 2020 (P < 0.001 for nonlinear trend). Similar trends were observed for different subcategories of NSS-containing product consumption (NSS beverages, foods, and tabletop sweeteners). Similar trends were found among individuals with or without chronic disease. Among individuals with ≥1 chronic disease (cancer, cardiovascular disease, diabetes, hypertension, obesity, hyperlipemia), age-adjusted percentage of individuals consuming NSS in the past day increased from 34.5% in 1999-2000 to 41.1% in 2005-2008 and decreased to 28.1% in 2017 to March 2020, while NSS consumption increased from 20.0% in 1999-2000 to 27.4% in 2005-2008 and decreased to 14.3% in 2017 to March 2020 among individuals without chronic diseases (all P < 0.001 for nonlinear trend). CONCLUSIONS: NSS use increased from 1999 to 2006 and decreased until March 2020 among entire United States adults and individuals with or without chronic diseases. Moreover, NSS use is generally higher among individuals with chronic diseases during study periods.

A preliminary investigation into the impact of soft tissue augmentation-based periodontal phenotype modification therapy for patients exhibiting class III decompensation.

BACKGROUND: Patients with skeletal angle Class III malocclusion usually have inadequate hard and soft tissue volume at the mandibular anterior teeth. The labial proclination at the teeth may lead to gingival recession. The purpose of this study was to explore whether periodontal phenotype modification therapy with soft tissue augmentation (PhMT-s) can prevent gingival recession in these patients. METHODS: Four patients with skeletal Class III malocclusion and a thin periodontal phenotype underwent surgical-orthodontic treatment. Prior to tooth movement, they underwent a minimally invasive vestibular incision with subperiosteal tunnel access combined with autogenous connective tissue grafts for periodontal phenotype modification with soft tissue augmentation (PhMT-s). The labial gingival thickness of the anterior mandibular teeth was measured at three distinct levels: at the cementoenamel junction (GT0), 3 mm apical to the CEJ (GT3), and 6 mm apical to the CEJ (GT6). These measurements were taken at baseline, three months following PhMT-s, and after tooth decompensation. Additionally, a biopsy sample was obtained from the PhMT-s site of one patient. All sections were subsequently stained using hematoxylin and eosin, Masson trichrome, Sirius Red, and immunohistochemistry. RESULTS: The thickness of the labial gingiva was increased about 0.42 to 2.00 mm after PhMT-s. At the end of pre-orthognathic surgical orthodontic treatment, the thickness of the labial gingiva was increased about - 0.14 to 1.32 mm compared to the baseline and no gingival recession occurred after the pre-orthognathic surgical orthodontic treatment. The histologic results demonstrated that the grafts obtained from the PhMT-s site exhibited increased deposition of collagen fibers. Moreover, the proportion of type III collagen increased and the grafts displayed significantly reduced positive expression of CD31 and OCN. CONCLUSIONS: PhMT-s increased the thickness of the soft tissue, stabilizing the gingival margin for teeth exhibiting a thin periodontal phenotype and undergoing labial movement. This is attributed to the increased deposition of collagen fibers.

A sophisticated mechanism governs Pol ζ activity in response to replication stress.

DNA polymerase ζ (Pol ζ) plays an essential role in replicating damaged DNA templates but contributes to mutagenesis due to its low fidelity. Therefore, ensuring tight control of Pol ζ's activity is critical for continuous and accurate DNA replication, yet the specific mechanisms remain unclear. This study reveals a regulation mechanism of Pol ζ activity in human cells. Under normal conditions, an autoinhibition mechanism keeps the catalytic subunit, REV3L, inactive. Upon encountering replication stress, however, ATR-mediated phosphorylation of REV3L's S279 cluster activates REV3L and triggers its degradation via a caspase-mediated pathway. This regulation confines the activity of Pol ζ, balancing its essential role against its mutations causing potential during replication stress. Overall, our findings elucidate a control scheme that fine tunes the low-fidelity polymerase activity of Pol ζ under challenging replication scenarios.

Cai's herbal tea enhances mitochondrial autophagy of type 1 diabetic mellitus ß cells through the AMPK/mTOR pathway and alleviates inflammatory response.

BACKGROUND: This study investigates the therapeutic mechanisms of Cai's Herbal Tea in Type 1 Diabetes Mellitus (T1DM) mice, focusing on its effects on mitochondrial change and autophagy via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway. METHODS: The composition of Cai's Herbal Tea was analyzed by Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-Q/TOF-MS). C57BL/6 mice and Min6 pancreatic beta cells were divided into control, diabetic mellitus (DM)/high glucose (HG), and treatment groups (low, medium, and high doses of Cai's Tea, and Metformin). Key physiological parameters, pancreatic islet health, Min6 cell morphology, viability, and insulin (INS) secretion were assessed. Small Interfering RNA-AMPK (si-AMPK) was utilized to confirm the pathway involvement. RESULTS: Cai's Herbal Tea improved body weight, pancreatic islet pathological injury, and INS secretion whereas reduced total triglycerides, fasting blood sugar, and Interferon gamma (INF-γ) in T1DM mice, particularly at higher doses. In Min6 cells, Cai's Tea mitigated HG-induced damage and proinflammatory response, enhancing cell viability and INS secretion. Notably, it reduced swelling and improved cristae structure in treated groups of mitochondria and promoted autophagy via the AMPK-mTOR pathway, evidenced by increased LC3II/LC3I and P-AMPK/AMPK ratios, and decreased P-mTOR/mTOR and P62 expressions in pancreatic islet ß-cells. Furthermore, these effects were converted by si-AMPK interference. CONCLUSION: Cai's Herbal Tea exhibits significant therapeutic efficacy in T1DM mice by improving mitochondrial health and inducing autophagy through the AMPK-mTOR pathway in pancreatic islet ß-cells. These findings highlight its potential as a therapeutic approach for T1DM management.

Lysosomal dysfunction-derived autophagy impairment of gingival epithelial cells in diabetes-associated periodontitis with altered protein acetylation.

Diabetes-associated periodontitis (DP) presents severe inflammation and resistance to periodontal conventional treatment, presenting a significant challenge in clinical management. In this study, we investigated the underlying mechanism driving the hyperinflammatory response in gingival epithelial cells (GECs) of DP patients. Our findings indicate that lysosomal dysfunction under high glucose conditions leads to the blockage of autophagy flux, exacerbating inflammatory response in GECs. Single-cell RNA sequencing and immunohistochemistry analyses of clinical gingival epithelia revealed dysregulation in the lysosome pathway characterized by reduced levels of lysosome-associated membrane glycoprotein 2 (LAMP2) and V-type proton ATPase 16 kDa proteolipid subunit c (ATP6V0C) in subjects with DP. In vitro stimulation of human gingival epithelial cells (HGECs) with a hyperglycemic microenvironment showed elevated release of proinflammatory cytokines, compromised lysosomal acidity and blocked autophagy. Moreover, HGECs with deficiency in ATP6V0C demonstrated impaired autophagy and heightened inflammatory response, mirroring the effects of high glucose stimulation. Proteomic analysis of acetylation modifications identified altered acetylation levels in 28 autophagy-lysosome pathway-related proteins and 37 sites in HGECs subjected to high glucose stimulation or siATP6V0C. Overall, our finding highlights the pivotal role of lysosome impairment in autophagy obstruction in DP and suggests a potential impact of altered acetylation of relevant proteins on the interplay between lysosome dysfunction and autophagy blockage. These insights may pave the way for the development of effective therapeutic strategies against DP.

Synergistic enhancement of plant growth and cadmium stress defense by Azospirillum brasilense and plant heme: Modulating the growth-defense relationship.

Plant growth-promoting rhizobacteria (PGPR) play important roles in plant growth and defense under heavy metal (HM) stress. The direct integration of microbial and plant signals is key to the regulation of plant growth and HM stress defense, but the underlying mechanisms are still limited. Herein, we reveal a novel mechanism by which PGPR regulates plant growth-regulating substances in plant tissues and coordinates plant growth and defense in pak choi under cadmium (Cd) stress. This might be an efficient strategy and an extension of the mechanism by which plant-microbe interactions improve plant stress resistance. Azospirillum brasilense and heme synergistically reduced the shoot Cd content and promoted the growth of pak choi. The interaction between abscisic acid of microbial origin and heme improved Cd stress tolerance through enhancing Cd accumulation in the root cell wall. The interaction between A. brasilense and heme induced the growth-defense shift in plants under Cd stress. Plants sacrifice growth to enhance Cd stress defense, which then transforms into a dual promotion of both growth and defense. This study deepens our understanding of plant-microbe interactions and provides a novel strategy to improve plant growth and defense under HM stress, ensuring future food production and security.

Characteristics of duplicated gene expression and DNA methylation regulation in different tissues of allopolyploid Brassica napus.

Plant polyploidization increases the complexity of epigenomes and transcriptional regulation, resulting in genome evolution and enhanced adaptability. However, few studies have been conducted on the relationship between gene expression and epigenetic modification in different plant tissues after allopolyploidization. In this study, we studied gene expression and DNA methylation modification patterns in four tissues (stems, leaves, flowers and siliques) of Brassica napusand its diploid progenitors. On this basis, the alternative splicing patterns and cis-trans regulation patterns of four tissues in B. napus and its diploid progenitors were also analyzed. It can be seen that the number of alternative splicing occurs in the B. napus is higher than that in the diploid progenitors, and the IR type increases the most during allopolyploidy. In addition, we studied the fate changes of duplicated genes after allopolyploidization in B. napus. We found that the fate of most duplicated genes is conserved, but the number of neofunctionalization and specialization is also large. The genetic fate of B. napus was classified according to five replication types (WGD, PD, DSD, TD, TRD). This study also analyzed generational transmission analysis of expression and DNA methylation patterns. Our study provides a reference for the fate differentiation of duplicated genes during allopolyploidization.

A comprehensive review on preparation and functional application of the wood aerogel with natural cellulose framework.

As the traditional aerogel has defects such as poor mechanical properties, complicated preparation process, high energy consumption and non-renewable, wood aerogel as a new generation of aerogel shows unique advantages. With a natural cellulose framework, wood aerogel is a novel nano-porous material exhibiting exceptional properties such as light weight, high porosity, large specific surface area, and low thermal conductivity. Furthermore, its adaptability to further functionalization enables versatile applications across diverse fields. Driven by the imperative for sustainable development, wood aerogel as a renewable and eco-friendly material, has garnered significant attention from researchers. This review introduces preparation methods of wood aerogel based on the top-down strategy and analyzes the factors influencing their key properties intending to obtain wood aerogels with desirable properties. Avenues for realizing its functionality are also explored, and research progress across various domains are surveyed, including oil-water separation, conductivity and energy storage, as well as photothermal conversion. Finally, potential challenges associated with wood aerogel exploitation and utilization are addressed, alongside discussions on future prospects and research directions. The results emphasize the broad research value and future prospects of wood aerogels, which are poised to drive high-value utilization of wood and foster the development of green multifunctional aerogels.

Genome-wide identification of the ICS family genes and its role in resistance to Plasmodiophora brassicae in Brassica napus L.

The isochorismate synthase (ICS) proteins are essential regulators of salicylic acid (SA) synthesis, which has been reported to regulate resistance to biotic and abiotic stresses in plants. Clubroot caused by Plasmodiophora brassicae is a common disease that threatens the yield and quality of Oilseed rape (Brassica napus L.). Exogenous application of salicylic acid reduced the incidence of clubroot in oilseed rape. However, the potential importance of the ICS genes family in B. napus and its diploid progenitors has been unclear. Here, we identified 16, 9, and 10 ICS genes in the allotetraploid B. napus, diploid ancestor Brassica rapa and Brassica oleracea, respectively. These ICS genes were classified into three subfamilies (I-III), and member of the same subfamilies showed relatively conserved gene structures, motifs, and protein domains. Furthermore, many hormone-response and stress-related promoter cis-acting elements were observed in the BnaICS genes. Exogenous application of SA delayed the growth of clubroot galls, and the expression of BnaICS genes was significantly different compared to the control groups. Protein-protein interaction analysis identified 58 proteins involved in the regulation of ICS in response to P. brassicae in B. napus. These results provide new clues for understanding the resistance mechanism to P. brassicae.

Enhancing barley yield potential and germination rate: gene editing of HvGA20ox2 and discovery of novel allele sdw1.ZU9.

Several dwarf and semi-dwarf genes have been identified in barley. However, only a limited number have been effectively utilized in breeding programs to cultivate lodging resistant varieties. This is due to the common association of dwarf and semi-dwarf traits with negative effects on malt quality. In this study, we employed gene editing to generate three new haplotypes of sdw1/denso candidate gene gibberellin (GA) 20-oxidase2 (GA20ox2). These haplotypes induced a dwarfing phenotype and enhancing yield potential, and promoting seed dormancy, thereby reducing pre-harvest sprouting. Moreover, ß-amylase activity in the grains of the mutant lines was significantly increased, which is beneficial for malt quality. The haplotype analysis revealed significant genetic divergence of this gene during barley domestication and selection. A novel allele (sdw1.ZU9), containing a 96-bp fragment in the promoter region of HvGA20ox2, was discovered and primarily observed in East Asian and Russian barley varieties. The 96-bp fragment was associated with lower gene expression, leading to lower plant height but higher germination rate. In conclusion, HvGA20ox2 can be potentially used to develop semi-dwarf barley cultivars with high yield and improved malt quality.

Application progress of nanocellulose in food packaging: A review.

With the increasing environmental and ecological problems caused by petroleum-based packaging materials, the focus has gradually shifted to natural resources for the preparation of functional food packaging materials. In addition to biodegradable properties, nanocellulose (NC) mechanical properties, and rich surface chemistry are also fascinating and desired to be one of the most probable green packaging materials. In this review, we firstly introduce the recent progress of novel applications of NC in food packaging, including intelligent packaging, nano(bio)sensors, and nano-paper; secondly, we focus on the modification techniques of NC to summarize the properties (antimicrobial, mechanical, hydrophobic, antioxidant, and so on) that are required for food packaging, to expand the new synthetic methods and application areas. After presenting all the latest advances related to material design and sustainable applications, an overview summarizing the safety of NC is presented to promote a continuous and healthy movement of NC toward the field of truly sustainable packaging.

Peripheral Blood Lymphocyte Subsets and Heterogeneity of B Cell Subsets in Patients of Idiopathic Inflammatory Myositis with Different Myositis-specific Autoantibodies.

Idiopathic inflammatory myopathies (IIM) are a group of myopathies that present with muscle weakness and multiple extra-muscular manifestations, in which lymphocytes play central roles in myositis pathogenesis. This study aimed to explore the clinical characteristics of lymphocyte subsets, especially B cell subsets, in patients with IIM. Our study included 176 patients with active IIM and 210 gender/age-matched healthy controls (HCs). Compared to HCs, patients have reduced counts of T cells, B cells, and natural killer cells. In addition, B cell subsets from 153 patients with IIM and 92 HCs were characterized. Patients had a lower percentage of memory B cells and translational memory B cells, while those patients were with an elevated percentage of CD19+ B cells, plasmablast and naïve B cells compared with HCs. Moreover, to further explore the heterogeneity of B cells in IIM, patients were categorized into three clusters based on clustering analysis. Cluster 1 was dominated by CD19+ B cells, Bregs and naïve B cells, cluster 3 was dominated by memory B cells and plasmablast, and cluster 2 had the highest proportion of translational memory B cells. Notably, patients in cluster 1 presented with higher CK levels, indicating muscle damage, whereas patients in cluster 3 showed a higher incidence of chest tightness. Our study indicated that lymphopenia is a common manifestation in patients with IIM. B cell subsets are abnormally expressed and showed high heterogeneity in patients with IIM. The patients with IIM were divided into three different clusters with different percentages of chest tightness and distinct CK levels.

Risk chain identification of single-vehicle accidents considering multi-risk factors coupling effect.

The real-time monitoring on the risk status of the vehicle and its driver can provide the assistance for the early detection and blocking control of single-vehicle accidents. However, complex risk coupling relationship is one of the main features of single-vehicle accidents with high mortality rate. On the basis of investigating the coupling effect among multi-risk factors and establishing a safety management database throughout the life cycle of vehicles, single-vehicle driving risk network (SVDRN) with a three-level threshold was developed, and its topology features were analyzed to assessment the importance of nodes. To avoid the one-sidedness of single indicator, the multi-attribute comprehensive evaluation model was applied to measure the comprehensive effect of characteristic indicators for nodes importance. A algorithm for real-time monitoring of vehicle driving risk status was proposed to identify key risk chains. The result revealed that improper operation, speeding, loss of vehicle control and inefficient driver management were the sequence of top four risk factors in the comprehensive evaluation result of nodes importance (mean value = 0.185, SD = 0.119). There were minor differences of 0.017 in the node importance among environmental factors, among which non-standard road alignment had the larger value. The improper operation and non-standard road alignment were the highest combination correlation of factors affecting road safety, with the support of 51.81% and the confidence of 69.35%. This identification algorithm of key risk chains that combines node importance and its risk state threshold can effectively determine the high-frequency risk transmission paths and risk factors through multi-vehicle test, providing a basis for centralization management of transport enterprises.

Ethylenedioxythiophene-Based Small Molecular Donor with Multiple Conformation Locks for Organic Solar Cells with Efficiency of 19.3 .

Ternary organic solar cells (T-OSCs) represent an efficient strategy for enhancing the performance of OSCs. Presently, the majority of high-performance T-OSCs incorporates well-established Y-acceptors or donor polymers as the third component. In this study, a novel class of conjugated small molecules has been introduced as the third component, demonstrating exceptional photovoltaic performance in T-OSCs. This innovative molecule comprises ethylenedioxythiophene (EDOT) bridge and 3-ethylrhodanine as the end group, with the EDOT unit facilitating the creation of multiple conformation locks. Consequently, the EDOT-based molecule exhibits two-dimensional charge transport, distinguishing it from the thiophene-bridged small molecule, which displays fewer conformation locks and provides one-dimensional charge transport. Furthermore, the robust electron-donating nature of EDOT imparts the small molecule with cascade energy levels relative to the electron donor and acceptor. As a result, OSCs incorporating the EDOT-based small molecule as the third component demonstrate enhanced mobilities, yielding a remarkable efficiency of 19.3 %, surpassing the efficiency of 18.7 % observed for OSCs incorporating thiophene-based small molecule as the third component. The investigations in this study underscore the excellence of EDOT as a building block for constructing conjugated materials with multiple conformation locks and high charge carrier mobilities, thereby contributing to elevated photovoltaic performance in OSCs.

U-shaped association between sleep duration and biological aging: Evidence from the UK Biobank study.

Previous research on sleep and aging largely has failed to illustrate the optimal dose-response curve of this relationship. We aimed to analyze the associations between sleep duration and measures of predicted age. In total, 241,713 participants from the UK Biobank were included. Habitual sleep duration was collected from the baseline questionnaire. Four indicators, homeostatic dysregulation (HD), phenoAge (PA), Klemera-Doubal method (KDM), and allostatic load (AL), were chosen to assess predicted age. Multivariate linear regression models were utilized. The association of sleep duration and predicted age followed a U-shape (All p for nonlinear <0.05). Compared with individuals who sleep for 7 h/day, the multivariable-adjusted beta of ≤5 and ≥9 h/day were 0.05 (95% CI 0.03, 0.07) and 0.03 (95% CI 0.02, 0.05) for HD, 0.08 (95% CI 0.01, 0.14) and 0.36 (95% CI 0.31, 0.41) for PA, and 0.21 (95% CI 0.12, 0.30) and 0.30 (95% CI 0.23, 0.37) for KDM. Significant independent and joint effects of sleep and cystatin C (CysC) and gamma glutamyltransferase (GGT) on predicted age metrics were future found. Similar results were observed when conducting stratification analyses. Short and long sleep duration were associated with accelerated predicted age metrics mediated by CysC and GGT.

Diabetic Macrophage Exosomal miR-381-3p Inhibits Epithelial Cell Autophagy Via NR5A2.

PURPOSE: To explore the mechanism underlying autophagy disruption in gingival epithelial cells (GECs) in diabetic individuals. METHODS AND MATERIALS: Bone marrow-derived macrophages (BMDMs) and GECs were extracted from C57/bl and db/db mice, the exosomes (Exo) were isolated from BMDMs. qRT‒PCR and Western blotting were performed to analyse gene expression. The AnimalTFDB database was used to identify relevant transcription factors, and miRNA sequencing was utilised to identify relevant miRNAs with the aid of the TargetScan/miRDB/miRWalk databases. A dual-luciferase assay was conducted to verify intermolecular targeting relationships. RESULTS: Similar to BMDMs, BMDM-derived Exos disrupted autophagy and exerted proinflammatory effects in GEC cocultures, and ATG7 may play a vital role. AnimalTFDB database analysis and dual-luciferase assays indicated that NR5A2 is the most relevant transcription factor that regulates Atg7 expression. SiRNA-NR5A2 transfection blocked autophagy in GECs and exacerbated inflammation, whereas NR5A2 upregulation restored ATG7 expression and ameliorated ExoDM-mediated inflammation. MiRNA sequencing, with TargetScan/miRDB/miRWalk analyses and dual-luciferase assays, confirmed that miR-381-3p is the most relevant miRNA that targets NR5A2. MiR-381-3p mimic transfection blocked autophagy in GECs and exacerbated inflammation, while miR-381-3p inhibitor transfection restored ATG7 expression and attenuated ExoDM-mediated inflammation. CONCLUSION: BMDM-derived Exos, which carry miR-381-3p, inhibit NR5A2 and disrupt autophagy in GECs, increasing periodontal inflammation in diabetes.