Phenotypic, genomic, and transcriptomic heterogeneity in a pancreatic cancer cell line.

OBJECTIVES: To evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells' phenotypic, genomic, and transcriptomic heterogeneity. METHODS: MIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively. RESULTS: Four MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, migration potential, and drug sensitivity. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations and single nucleotide variations, suggesting the genomic heterogeneity of the population, and the intrinsic genomic instability of MIA PaCa-2 cells. Lastly, transcriptomic analysis of the clones also revealed gene expression profile differences between the clones, including the uniquely regulated ITGAV, which dictates the morphology of MIA PaCa-2 clones. CONCLUSIONS: MIA PaCa-2 is comprised of cells with distinctive phenotypes, heterogeneous genomes, and differential transcriptomic profiles, suggesting its suitability as a model to study the underlying mechanisms behind pancreatic cancer heterogeneity.

Genetic regulation of human brain proteome reveals proteins implicated in psychiatric disorders.

Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified hundreds of genomic susceptibility loci with susceptibility to psychiatric disorders; however, the contribution of these loci to the underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled with two-dimensional liquid chromatography-tandem mass spectrometry. Our analysis revealed 788 cis-acting protein quantitative trait loci associated with the expression of 883 proteins at a genome-wide false discovery rate <5%. In contrast to expression at the transcript level and complex diseases that are found to be mainly influenced by noncoding variants, we found protein expression level tends to be regulated by non-synonymous variants. We also provided evidence of 76 shared regulatory signals between gene expression and protein abundance. Mediation analysis revealed that for most (88%) of the colocalized genes, the expression levels of their corresponding proteins are regulated by cis-pQTLs via gene transcription. Using summary data-based Mendelian randomization analysis, we identified 4 proteins and 19 genes that are causally associated with schizophrenia. We further integrated multiple omics data with network analysis to prioritize candidate genes for schizophrenia risk loci. Collectively, our findings underscore the potential of proteome-wide linkage analysis in gaining mechanistic insights into the pathogenesis of psychiatric disorders.

Self-Assembled DNA Machine and Selective Complexation Recognition Enable Rapid Homogeneous Portable Quantification of Lung Cancer CTCs.

In this study, we systematically investigated the interactions between Cu2+ and various biomolecules, including double-stranded DNA, Y-shaped DNA nanospheres, the double strand of the hybridization chain reaction (HCR), the network structure of cross-linked HCR (cHCR), and small molecules (PPi and His), using Cu2+ as an illustrative example. Our research demonstrated that the coordination between Cu2+ and these biomolecules not only is suitable for modulating luminescent material signals through complexation reactions with Cu2+ but also enhances signal intensities in materials based on chemical reactions by increasing spatial site resistance and local concentration. Building upon these findings, we harnessed the potential for signal amplification in self-assembled DNA nanospheres and the selective complexation modulation of calcein in conjunction with the aptamer targeting mucin 1 as a recognition probe. We applied this approach to the analysis of circulating tumor cells, with the lung cancer cell line A549 serving as a representative model. Our assay, utilizing both a fluorometer and a handheld detector, achieved impressive detection limits of ag/ml and single-cell levels for mucin 1 and A549 cells, and this approach was successfully validated using 46 clinical samples, yielding 100% specificity and 86.5% sensitivity. Consequently, our strategy has paved the way for more portable and precise disease diagnosis.

Drosophila Larvae-Inspired Soft Crawling Robot with Multimodal Locomotion and Versatile Applications.

Soft crawling robots have been widely studied and applied because of their excellent environmental adaptability and flexible movement. However, most existing soft crawling robots typically exhibit a single-motion mode and lack diverse capabilities. Inspired by Drosophila larvae, this paper proposes a compact soft crawling robot (weight, 13 g; length, 165 mm; diameter, 35 mm) with multimodal locomotion (forward, turning, rolling, and twisting). Each robot module uses 4 sets of high-power-density shape memory alloy actuators, endowing it with 4 degrees of motion freedom. We analyze the mechanical characteristics of the robot modules through experiments and simulation analysis. The plug-and-play modules can be quickly assembled to meet different motion and task requirements. The soft crawling robot can be remotely operated with an external controller, showcasing multimodal motion on various material surfaces. In a narrow maze, the robot demonstrates agile movement and effective maneuvering around obstacles. In addition, leveraging the inherent bistable characteristics of the robot modules, we used the robot modules as anchoring units and installed a microcamera on the robot's head for pipeline detection. The robot completed the inspection in horizontal, vertical, curved, and branched pipelines, adjusted the camera view, and twisted a valve in the pipeline for the first time. Our research highlights the robot's superior locomotion and application capabilities, providing an innovative strategy for the development of lightweight, compact, and multifunctional soft crawling robots.

mTOR promotes an inflammatory response through the HIF1 signaling pathway in ulcerative colitis.

The imbalance between T helper cell 17 （Th17）and regulatory T cells (Treg) cells leading to inflammation has an important role in the pathogenesis of ulcerative colitis (UC). Mammalian target of rapamycin (mTOR) can regulate the differentiation of T cells, but the specific pathway leading mTOR to regulate Th17/Treg cells in UC remains unclear. Our aim with this study was to investigate the effects of mTOR overexpression and silencing on the hypoxia inducible factor-1α (HIF-1α) - Th17/Treg signaling pathway. To mimic a human study, we established a colon cancer epithelial cell line (HT-29) co-culture system with human CD4+ T cells, and we treated the cells with TNF-α. We observed the effects of mTOR on the HIF-Th17/Treg signaling pathway to determine whether mTOR is involved in the regulatory mechanism. Under the stimulation of TNF-α, the levels of HIF-1α in CD4+T cells were increased in the HT-29 co-culture with CD4+ T cells, promoting glycolysis, increasing the Th17 proportion, decreasing the Treg proportion, increasing the pro-inflammatory factors levels, and decreasing the anti-inflammatory factors levels. Moreover, after mTOR silencing, the HIF-1α level and cell glycolysis levels decreased, Th17 cell differentiation decreased, the pro-inflammatory factor levels decreased, and the anti-inflammatory factor levels increased. In contrast, mTOR overexpression lead to the opposite results.mTOR promotes inflammation by regulating the HIF signaling pathway during UC, and silencing mTOR may alleviate inflammation. An mTOR inhibitor is a potential therapeutic target for UC treatment.

Urea cycle promotion via ammonia-upregulated CPS1 is involved in arsenite-induced pulmonary fibrosis through enhancing collagen synthesis.

Arsenic exposure is connected with lung toxicity and is related to lung fibrotic changes. Idiopathic pulmonary fibrosis (IPF) is characterized by extracellular matrix (ECM) deposition. Various genetic mechanisms and environmental factors induce or exacerbate pulmonary fibrosis. Collagen synthesis induced by sodium arsenite (NaAsO2) is closely associated with IPF. Fibroblasts tend to fine-tune their metabolic networks to support their synthetic requirements in response to environmental stimuli. Alterations in metabolism have an influential role in the pathogenesis of IPF. However, it is unclear how arsenic affects the metabolism in IPF. The urea cycle (UC) is needed for collagen formation, which provides adequate levels of proline (Pro) for biosynthesis of collagen. Carbamoyl phosphate synthetase 1 (CPS1) converts the ammonia to carbamoyl phosphate, which controls the first reaction of the UC. We show that, in arsenite-exposed mice, high amounts of ammonia in the lung microenvironment promotes the expression levels of CPS1 and the Pro metabolism. Reduction of ammonia and CPS1 ablation inhibit collagen synthesis and ameliorate IPF phenotypes induced by arsenite. This work takes advantage of multi-omics data to enhance understanding of the underlying pathogenic mechanisms, the key molecules and the complicated cellular responses to this pollutant, which provide a target for the prevention of pulmonary fibrosis caused by arsenic.

Distributed electrified heating for efficient hydrogen production.

This study introduces a distributed electrified heating approach that is able to innovate chemical engineering involving endothermic reactions. It enables rapid and uniform heating of gaseous reactants, facilitating efficient conversion and high product selectivity at specific equilibrium. Demonstrated in catalyst-free CH4 pyrolysis, this approach achieves stable production of H2 (530 g h-1 L reactor -1) and carbon nanotube/fibers through 100% conversion of high-throughput CH4 at 1150 °C, surpassing the results obtained from many complex metal catalysts and high-temperature technologies. Additionally, in catalytic CH4 dry reforming, the distributed electrified heating using metallic monolith with unmodified Ni/MgO catalyst washcoat showcased excellent CH4 and CO2 conversion rates, and syngas production capacity. This innovative heating approach eliminates the need for elongated reactor tubes and external furnaces, promising an energy-concentrated and ultra-compact reactor design significantly smaller than traditional industrial systems, marking a significant advance towards more sustainable and efficient chemical engineering society.

The combination therapy of oncolytic virotherapy.

Introduction: Compared to other cancer immunotherapies, oncolytic viruses possess several advantages, including high killing efficiency, excellent targeting capabilities, minimal adverse reactions, and multiple pathways for tumor destruction. However, the efficacy of oncolytic viruses as a monotherapy often falls short of expectations. Consequently, combining oncolytic viruses with traditional treatments to achieve synergistic effects has emerged as a promising direction for the development of oncolytic virus therapies. Methods: This article provides a comprehensive review of the current progress in preclinical and clinical trials exploring the combination therapies involving oncolytic viruses. Results: Specifically, we discuss the combination of oncolytic viruses with immune checkpoint inhibitors, chemotherapy, targeted therapy, and cellular therapy. Discussion: The aim of this review is to offer valuable insights and references for the further advancement of these combination strategies in clinical applications. Further research is necessary to refine the design of combination therapies and explore novel strategies to maximize the therapeutic benefits offered by oncolytic viruses.

Erythrocyte-Membrane-Camouflaged Magnetic Nanocapsules With Photothermal/Magnetothermal Effects for Thrombolysis.

Venous/arterial thrombosis poses significant threats to human health. However, drug-enabled thrombolysis treatment often encounters challenges such as short half-life and low bioavailability. To address these issues, the design of erythrocyte-membrane (EM) camouflaged nanocapsules (USIO/UK@EM) incorporating ultra-small iron oxide (USIO) and urokinase (UK) drug, which exhibits remarkable photothermal/magnetothermal effects and drug delivery ability for venous/arterial thrombolysis, is reported. USIO, UK, and EM are coextruded to fabricate USIO/UK@EM with average sizes of 103.7 nm. As USIO/UK@EM possesses wide photoabsorption and good magnetic properties, its solution demonstrates a temperature increase to 41.8-42.9 °C within 5 min when exposed to an 808 nm laser (0.33 mW cm-2) or alternating magnetic field (AMF). Such photothermal/magnetothermal effect along with UK confers impressive thrombolytic rates of 82.4% and 74.2%, higher than that (≈15%) achieved by UK alone. Further, the EM coating extends the circulating half-life (t1/2 = 3.28 h). When USIO/UK@EM is administered to mice and rabbits, tail vein thrombus in mice and femoral artery thrombus in rabbits can be dissolved by the synergetic effect of thermothrombolysis and UK. Therefore, this study not only offers insights into the rational design of multifunctional biomimetic nanocapsules but also showcases a promising thrombolysis strategy utilizing nanomedicine.

Crucial role of SWL1 in chloroplast biogenesis and development in Arabidopsis thaliana.

KEY MESSAGE: The disruption of the SWL1 gene leads to a significant down regulation of chloroplast and secondary metabolites gene expression in Arabidopsis thaliana. And finally results in a dysfunction of chloroplast and plant growth. Although the development of the chloroplast has been a consistent focus of research, the corresponding regulatory mechanisms remain unidentified. In this study, the CRISPR/Cas9 system was used to mutate the SWL1 gene, resulting in albino cotyledons and variegated true leaf phenotype. Confocal microscopy and western blot of chloroplast protein fractions revealed that SWL1 localized in the chloroplast stroma. Electron microscopy indicated chloroplasts in the cotyledons of swl1 lack well-defined grana and internal membrane structures, and similar structures have been detected in the albino region of variegated true leaves. Transcriptome analysis revealed that down regulation of chloroplast and nuclear gene expression related to chloroplast, including light harvesting complexes, porphyrin, chlorophyll metabolism and carbon metabolism in the swl1 compared to wild-type plant. In addition, proteomic analysis combined with western blot analysis, showed that a significant decrease in chloroplast proteins of swl1. Furthermore, the expression of genes associated with secondary metabolites and growth hormones was also reduced, which may be attributed to SWL1 associated with absorption and fixation of inorganic carbon during chloroplast development. Together, the above findings provide valuable information to elucidate the exact function of SWL1 in chloroplast biogenesis and development.

Study on plasma metabolomics profiling of depression in Chinese community-dwelling older adults based on untargeted LC/GC‒MS.

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways.

Visual scanning patterns of a talking face when evaluating phonetic information in a native and non-native language.

When comprehending speech, listeners can use information encoded in visual cues from a face to enhance auditory speech comprehension. For example, prior work has shown that the mouth movements reflect articulatory features of speech segments and durational information, while pitch and speech amplitude are primarily cued by eyebrow and head movements. Little is known about how the visual perception of segmental and prosodic speech information is influenced by linguistic experience. Using eye-tracking, we studied how perceivers' visual scanning of different regions on a talking face predicts accuracy in a task targeting both segmental versus prosodic information, and also asked how this was influenced by language familiarity. Twenty-four native English perceivers heard two audio sentences in either English or Mandarin (an unfamiliar, non-native language), which sometimes differed in segmental or prosodic information (or both). Perceivers then saw a silent video of a talking face, and judged whether that video matched either the first or second audio sentence (or whether both sentences were the same). First, increased looking to the mouth predicted correct responses only for non-native language trials. Second, the start of a successful search for speech information in the mouth area was significantly delayed in non-native versus native trials, but just when there were only prosodic differences in the auditory sentences, and not when there were segmental differences. Third, (in correct trials) the saccade amplitude in native language trials was significantly greater than in non-native trials, indicating more intensely focused fixations in the latter. Taken together, these results suggest that mouth-looking was generally more evident when processing a non-native versus native language in all analyses, but fascinatingly, when measuring perceivers' latency to fixate the mouth, this language effect was largest in trials where only prosodic information was useful for the task.

Construction of a Physiologically Based Pharmacokinetic Model of Paclobutrazol and Exposure Estimation in the Human Body.

Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil-water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration-time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.

Response of photosynthetic characteristics and antioxidant system in the leaves of safflower to NaCl and NaHCO3.

KEY MESSAGE: Compared with NaCl, NaHCO3 caused more serious oxidative damage and photosynthesis inhibition in safflower by down-regulating the expression of related genes. Salt-alkali stress is one of the important factors that limit plant growth. NaCl and sodium bicarbonate (NaHCO3) are neutral and alkaline salts, respectively. This study investigated the physiological characteristics and molecular responses of safflower (Carthamus tinctorius L.) leaves treated with 200 mmol L-1 of NaCl or NaHCO3. The plants treated with NaCl treatment were less effective at inhibiting the growth of safflower, but increased the content of malondialdehyde (MDA) in leaves. Meanwhile, safflower alleviated stress damage by increasing proline (Pro), soluble protein (SP), and soluble sugar (SS). Both fresh weight and dry weight of safflower was severely decreased when it was subjected to NaHCO3 stress, and there was a significant increase in the permeability of cell membranes and the contents of osmotic regulatory substances. An enrichment analysis of the differentially expressed genes (DEGs) using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes identified significant enrichment of photosynthesis and pathways related to oxidative stress. Furthermore, a weighted gene co-expression network analysis (WGCNA) showed that the darkgreen module had the highest correlation with photosynthesis and oxidative stress traits. Large numbers of transcription factors, primarily from the MYB, GRAS, WRKY, and C2H2 families, were predicted from the genes within the darkgreen module. An analysis of physiological indicators and DEGs, it was found that under saline-alkali stress, genes related to chlorophyll synthesis enzymes were downregulated, while those related to degradation were upregulated, resulting in inhibited chlorophyll biosynthesis and decreased chlorophyll content. Additionally, NaCl and NaHCO3 stress downregulated the expression of genes related to the Calvin cycle, photosynthetic antenna proteins, and the activity of photosynthetic reaction centers to varying degrees, hindering the photosynthetic electron transfer process, suppressing photosynthesis, with NaHCO3 stress causing more pronounced adverse effects. In terms of oxidative stress, the level of reactive oxygen species (ROS) did not change significantly under the NaCl treatment, but the contents of hydrogen peroxide and the rate of production of superoxide anions increased significantly under NaHCO3 stress. In addition, treatment with NaCl upregulated the levels of expression of the key genes for superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the ascorbate-glutathione cycle, and the thioredoxin-peroxiredoxin pathway, and increased the activity of these enzymes, thus, reducing oxidative damage. Similarly, NaHCO3 stress increased the activities of SOD, CAT, and POD and the content of ascorbic acid and initiated the glutathione-S-transferase pathway to remove excess ROS but suppressed the regeneration of glutathione and the activity of peroxiredoxin. Overall, both neutral and alkaline salts inhibited the photosynthetic process of safflower, although alkaline salt caused a higher level of stress than neutral salt. Safflower alleviated the oxidative damage induced by stress by regulating its antioxidant system.

Anode-Free Aqueous Aluminum Ion Batteries.

Aqueous aluminum ion batteries (AAIBs) possess the advantages of high safety, cost-effectiveness, eco-friendliness and high theoretical capacity. However, the Al2O3 film on the Al anode surface, a natural physical barrier to the plating of hydrated aluminum ions, is a key factor in the decomposition of the aqueous electrolyte and the severe hydrogen precipitation reaction. To circumvent the obnoxious Al anode, a proof-of-concept of an anode-free AAIB is first proposed, in which Al2TiO5, as a cathode pre-aluminum additive (Al source), can replenish Al loss by over cycling. The Al-Cu alloy layer, formed by plating Al on the Cu foil surface during the charge process, possesses a reversible electrochemical property and is paired with a polyaniline (cathode) to stimulate the battery to exhibit high initial discharge capacity (175 mAh g-1), high power density (≈410 Wh L-1) and ultra-long cycle life (4000 cycles) with the capacity retention of ≈60% after 1000 cycles. This work will act as a primer to ignite the enormous prospective researches on the anode-free aqueous Al ion batteries.

From metabolism to malignancy: the multifaceted role of PGC1α in cancer.

PGC1α, a central player in mitochondrial biology, holds a complex role in the metabolic shifts seen in cancer cells. While its dysregulation is common across major cancers, its impact varies. In some cases, downregulation promotes aerobic glycolysis and progression, whereas in others, overexpression escalates respiration and aggression. PGC1α's interactions with distinct signaling pathways and transcription factors further diversify its roles, often in a tissue-specific manner. Understanding these multifaceted functions could unlock innovative therapeutic strategies. However, challenges exist in managing the metabolic adaptability of cancer cells and refining PGC1α-targeted approaches. This review aims to collate and present the current knowledge on the expression patterns, regulators, binding partners, and roles of PGC1α in diverse cancers. We examined PGC1α's tissue-specific functions and elucidated its dual nature as both a potential tumor suppressor and an oncogenic collaborator. In cancers where PGC1α is tumor-suppressive, reinstating its levels could halt cell proliferation and invasion, and make the cells more receptive to chemotherapy. In cancers where the opposite is true, halting PGC1α's upregulation can be beneficial as it promotes oxidative phosphorylation, allows cancer cells to adapt to stress, and promotes a more aggressive cancer phenotype. Thus, to target PGC1α effectively, understanding its nuanced role in each cancer subtype is indispensable. This can pave the way for significant strides in the field of oncology.

Construction and Validation of Novel Ferroptosis-related Risk Score Signature and Prognostic Prediction Nomogram for Patients with Colorectal Cancer.

Background: Colorectal cancer (CRC) has a high morbidity and mortality. Ferroptosis is a phenomenon in which metabolism and cell death are closely related. The role of ferroptosis-related genes in the progression of CRC is still not clear. Therefore, we screened and validated the ferroptosis-related genes which could determine the prevalence, risk and prognosis of patients with CRC. Methods: We firstly screened differentially expressed ferroptosis-related genes by The Cancer Genome Atlas (TCGA) database. Then, these genes were used to construct a risk-score model using the least absolute shrinkage and selection operator (LASSO) regression algorithm. The function and prognosis of the ferroptosis-related genes were confirmed using multi-omics analysis. The gene expression results were validated using publicly available databases and qPCR. We also used publicly available data and ferroptosis-related genes to construct a prognostic prediction nomogram. Results: A total of 24 differential expressed genes associated with ferroptosis were screened in this study. A three-gene risk score model was then established based on these 24 genes and GPX3, CDKN2A and SLC7A11 were selected. The significant prognostic value of this novel three-gene signature was also assessed. Furthermore, we conducted RT-qPCR analysis on cell lines and tissues, and validated the high expression of CDKN2A, GPX3 and low expression of SLC7A11 in CRC cells. The observed mRNA expression of GPX3, CDKN2A and SLC7A11 was consistent with the predicted outcomes. Besides, eight variables including selected ferroptosis related genes were included to establish the prognostic prediction nomogram for patients with CRC. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations. Also, the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomogram. Conclusions: The present study constructed and validated a novel ferroptosis-related three-gene risk score signature and a prognostic prediction nomogram for patients with CRC. Also, we screened and validated the ferroptosis-related genes GPX3, CDKN2A, and SLC7A11 which could serve as novel biomarkers for patients with CRC.

Structurally Tunable Donor-Bridge-Fluorophore Architecture Enables Highly Efficient and Concentration-Independent Narrowband Electroluminescence.

Luminescent materials with narrowband emission have extraordinary significance for developing ultrahigh-definition display. B-N-containing multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are strong contenders. However, their device performances pervasively encounter detrimental aggregation-caused quenching effect that is highly vulnerable to doping concentration, complicating device fabrication. Therefore, constructing highly efficient and concentration-independent MR-TADF emitters is of pragmatic importance for improving device controllability and reproducibility, simplifying manufacturing procedures, and conserving production costs. Here, by systematic arrangement of donor triphenylamine and fluorophore BNCz on distinct bridges, we have developed a spatial confinement strategy with a donor-bridge-fluorophore (D-B-F) architecture. Structurally fine modulation and progressive evolution to construct molecular entities with congested steric hindrance effect that can suppress intermolecular interactions without substantially affecting the luminescence tone of fluorophore BNCz, resulting in highly efficient and concentration-independent narrowband emitters; through isomer engineering, two isomers BN-PCz-TPA and TPA-PCz-BN with different crystal stacking patterns are synthesized by altering the connection mode between triphenylamine and BNCz. As a result, BN-PCz-TPA-based device showcases maximum external quantum efficiency (EQE) of 36.3% with narrow full-width at half-maximum (FWHM) of 27 nm at 10 wt% doping concentration. Even at 20 wt% doping concentration, the maximum EQE remains at 32.5% and the emission spectrum is almost unchanged. This article is protected by copyright. All rights reserved.

Influence on the temporomandibular joint induced by mandibular malpositioning caused by vertical dimension elevation and occlusal loss in adult rats: An imaging, histological and immunohistochemical study.

BACKGROUND: Mandibular malpositioning may result in an abnormal concentration of stresses within the temporomandibular joint (TMJ) in adult rats, which may further lead to a series of pathological changes, such as articular cartilage wear, subchondral bone sclerosis and osteophyte formation. However, the pathological and adaptive changes in condylar cartilage caused by different stress distributions are still controversial. OBJECTIVE: The aim of this study was to observe the effect of sagittal changes in mandibular position on condylar cartilage by changing the occlusal vertical dimension (OVD) in adult rats. METHODS: Fifteen-week-old female rats were divided into three groups: control (CON), increased OVD (iOVD) and loss of occlusion (LO) groups. An occlusal plate and tooth extraction were used to establish the animal model. TMJ samples of the experimental and CON groups were observed and investigated by bone morphological, histomorphological and immunohistochemical staining analyses at 3 days, 1 week, 2 weeks, 4 weeks and 8 weeks. Weight curves were plotted. RESULTS: Micro-computed tomography showed that, compared with the CON group, cartilage destruction followed by repair occurred in both experimental groups, which was similar to the trend observed in haematoxylin-eosin staining. All experimental results for the iOVD group showed an approximately similar time trend. Compared with the iOVD group, the toluidine blue and immunohistochemical staining results in the LO group showed no obvious change trend over time. CONCLUSION: Compared with occlusal loss, an increase in OVD caused faster and more severe damage to condylar cartilage, and subchondral bone repair occurred later.