ABSTRACT
Paired mapping of single-cell gene expression and electrophysiology is essential to understand gene-to-function relationships in electrogenic tissues. Here, we developed in situ electro-sequencing (electro-seq) that combines flexible bioelectronics with in situ RNA sequencing to stably map millisecond-timescale electrical activity and profile single-cell gene expression from the same cells across intact biological networks, including cardiac and neural patches. When applied to human-induced pluripotent stem-cell-derived cardiomyocyte patches, in situ electro-seq enabled multimodal in situ analysis of cardiomyocyte electrophysiology and gene expression at the cellular level, jointly defining cell states and developmental trajectories. Using machine-learning-based cross-modal analysis, in situ electro-seq identified gene-to-electrophysiology relationships throughout cardiomyocyte development and accurately reconstructed the evolution of gene expression profiles based on long-term stable electrical measurements. In situ electro-seq could be applicable to create spatiotemporal multimodal maps in electrogenic tissues, potentiating the discovery of cell types and gene programs responsible for electrophysiological function and dysfunction.
Subject(s)
Electronics , Sequence Analysis, RNA , Humans , Cell Differentiation , Induced Pluripotent Stem Cells/physiology , Myocytes, Cardiac/metabolism , Single-Cell Analysis , Transcriptome , Electronics/methodsABSTRACT
Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions. Single-cell RNA sequencing has profiled molecular cell types in the mouse brain1,2, but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS3,4, to profile 1,022 genes in 3D at a voxel size of 194 × 194 × 345 nm3, mapping 1.09 million high-quality cells across the adult mouse brain and spinal cord. We developed computational pipelines to segment, cluster and annotate 230 molecular cell types by single-cell gene expression and 106 molecular tissue regions by spatial niche gene expression. Joint analysis of molecular cell types and molecular tissue regions enabled a systematic molecular spatial cell-type nomenclature and identification of tissue architectures that were undefined in established brain anatomy. To create a transcriptome-wide spatial atlas, we integrated STARmap PLUS measurements with a published single-cell RNA-sequencing atlas1, imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB5,6. Together, this annotated dataset provides a single-cell resource that integrates the molecular spatial atlas, brain anatomy and the accessibility to genetic manipulation of the mammalian central nervous system.
Subject(s)
Central Nervous System , Imaging, Three-Dimensional , Single-Cell Analysis , Transcriptome , Animals , Mice , Brain/anatomy & histology , Brain/cytology , Brain/metabolism , Central Nervous System/anatomy & histology , Central Nervous System/cytology , Central Nervous System/metabolism , Single-Cell Analysis/methods , Spinal Cord/anatomy & histology , Spinal Cord/cytology , Spinal Cord/metabolism , Transcriptome/genetics , Single-Cell Gene Expression Analysis , Viral Tropism , Datasets as Topic , Transgenes/genetics , Imaging, Three-Dimensional/methodsABSTRACT
Spatiotemporal regulation of the cellular transcriptome is crucial for proper protein expression and cellular function. However, the intricate subcellular dynamics of RNA remain obscured due to the limitations of existing transcriptomics methods. Here, we report TEMPOmap-a method that uncovers subcellular RNA profiles across time and space at the single-cell level. TEMPOmap integrates pulse-chase metabolic labeling with highly multiplexed three-dimensional in situ sequencing to simultaneously profile the age and location of individual RNA molecules. Using TEMPOmap, we constructed the subcellular RNA kinetic landscape in various human cells from transcription and translocation to degradation. Clustering analysis of RNA kinetic parameters across single cells revealed 'kinetic gene clusters' whose expression patterns were shaped by multistep kinetic sculpting. Importantly, these kinetic gene clusters are functionally segregated, suggesting that subcellular RNA kinetics are differentially regulated in a cell-state- and cell-type-dependent manner. Spatiotemporally resolved transcriptomics provides a gateway to uncovering new spatiotemporal gene regulation principles.
Subject(s)
RNA , Transcriptome , Humans , RNA/genetics , Kinetics , Gene Expression Profiling/methods , Gene Expression Regulation , Single-Cell Analysis/methodsABSTRACT
Cell-in-cell (CIC) structures have been suggested to mediate intracellular substance transport between cells and have been found widely in inflammatory lung tissue of asthma. The aim of this study was to investigate the significance of CIC structures in inflammatory progress of asthma. CIC structures and related inflammatory pathways were analyzed in asthmatic lung tissue and normal lung tissue of mouse model. In vitro, the activation of inflammatory pathways by CIC-mediated intercellular communication was analyzed by RNA-Seq and verified by Western blotting and immunofluorescence. Results showed that CIC structures of lymphocytes and alveolar epithelial cells in asthmatic lung tissue mediated intercellular substance (such as mitochondria) transfer and promoted pro-inflammation in two phases. At early phase, internal lymphocytes triggered inflammasome-dependent pro-inflammation and cell death of itself. Then, degraded lymphocytes released cellular contents such as mitochondria inside alveolar epithelial cells, further activated multi-pattern-recognition receptors and NF-kappa B signaling pathways of alveolar epithelial cells, and thereby amplified pro-inflammatory response in asthma. Our work supplements the mechanism of asthma pro-inflammation progression from the perspective of CIC structure of lymphocytes and alveolar epithelial cells, and provides a new idea for anti-inflammatory therapy of asthma.
Subject(s)
Asthma , Cell Communication , Inflammation , Asthma/metabolism , Asthma/pathology , Animals , Mice , Inflammation/metabolism , Inflammation/pathology , Mice, Inbred BALB C , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Lymphocytes/metabolism , Lymphocytes/pathology , Disease Models, Animal , Humans , Signal Transduction , Disease ProgressionABSTRACT
Uncontrolled and excessive photothermal heating in photothermal therapy (PTT) inevitably causes thermal damage to surrounding normal tissues, severely limiting the universality and safety of PTT. To address this issue, an intelligent cooling thermal-responsive (ICTR) gel containing poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-AM))microgel is applied onto the skin to realize intelligent PTT, which can avoid excessive heating and accidental injury. The high near-infrared (NIR) light transmittance (> 95%) of the ICTR gel ensures effective light delivery at low temperatures, while the refractive index of the P(NIPAM-AM) microgel increases remarkably when the temperature exceeds a predetermined threshold, resulting in progressively enhanced light scattering and weakened photothermal conversion. In animal studies, the negative feedback regulation of ICTR gel on light transmittance and photothermal heating allows the photothermal temperature in the lesion site to be stabilized within the effective therapeutic range (45 °C) while ensuring that the skin surface temperature does not exceed 35 °C. Compared with the severe skin thermal damage found in the histological staining of mice skin receiving conventional PTT, the mice skin receiving the ICTR gel-enabled intelligent PTT remains in good condition. This study establishes an intelligent and universal paradigm for PTT thermal regulation, which is of great significance for achieving safe and effective PTT.
Subject(s)
Gels , Photothermal Therapy , Animals , Photothermal Therapy/methods , Gels/chemistry , Mice , Temperature , Skin/pathology , Acrylic Resins/chemistry , Phototherapy/methodsABSTRACT
PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.
Subject(s)
Diffusion Tensor Imaging , Facial Nerve , Neuroma, Acoustic , Humans , Neuroma, Acoustic/diagnostic imaging , Neuroma, Acoustic/surgery , Diffusion Tensor Imaging/methods , Facial Nerve/diagnostic imaging , Female , Male , Middle Aged , Adult , Aged , Algorithms , Image Processing, Computer-Assisted/methods , Preoperative Care/methods , Young AdultABSTRACT
INTRODUCTION: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated. MATERIALS AND METHODS: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed. RESULTS: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage. CONCLUSIONS: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.
ABSTRACT
BACKGROUND: In-vivo diffusion tensor cardiovascular magnetic resonance (DT-CMR) is an emerging technique for microstructural tissue characterization in the myocardium. Most studies are performed at 3T, where higher signal-to-noise ratio (SNR) should benefit this signal-starved method. However, a few studies have suggested that DT-CMR is possible at 1.5T, where echo planar imaging artifacts may be less severe and 1.5T hardware is more widely available. METHODS: We recruited 20 healthy volunteers and performed mid-ventricular short-axis DT-CMR at 1.5T and 3T. Acquisitions were performed at peak systole and end-diastole using both stimulated echo acquisition mode (STEAM) and motion-compensated spin-echo (MCSE) sequences at matched spatial resolutions. DT-CMR parameters were averaged over the left ventricle and compared between 1.5T and 3T sequences using both datasets with and without the blow reference data included. RESULTS: Eleven (1.5T) and 12 (3T) diastolic MCSE acquisitions were rejected as the helix angle (HA) demonstrated <50% normal appearance circumferentially or the acquisition was abandoned due to poor image quality; a maximum of one acquisition was rejected for other datasets. Subjective HA map quality was significantly better at 3T than 1.5T for STEAM (p < 0.05), but not for MCSE and other DT-CMR quality measures were consistent with improvements in STEAM at 3T over 1.5T. When blow data were excluded, no significant differences in mean diffusivity were observed between field strengths, but fractional anisotropy was significantly higher at 1.5T than 3T for STEAM systole (p < 0.05). Absolute second eigenvector orientation (E2A, sheetlet angle) was significantly higher at 1.5T than 3T for MCSE systole and STEAM diastole, but significantly lower for STEAM systole (all p < 0.05). Transmural HA distribution was less steep at 1.5T than 3T for STEAM diastole data (p < 0.05). SNR was higher at 3T than 1.5T for all acquisitions (p < 0.05). CONCLUSION: While 3T provides benefits in terms of SNR, both STEAM and MCSE can be performed at 1.5T. However, MCSE is unreliable in diastole at both field strengths and STEAM benefits from the improved SNR at 3T over 1.5T. Future clinical research studies may be able to leverage the wider availability of 1.5T CMR hardware where MCSE acquisitions are desirable.
ABSTRACT
Heterotypic cell-in-cell structure (CICs) is the definition of the entry of one type of living cells into another type of cell. CICs between immune cells and tumor cells have been found to correlate with malignancy in many cancers. Since tumor immune microenvironment promotes non-small cell lung cancer (NSCLC) progression and drug resistance, we wondered the potential significance of heterotypic CICs in NSCLC. Heterotypic CICs was analyzed by histochemistry in an expanded spectrum of clinical lung cancer tissue specimens. In vitro study was performed using the mouse lung cancer cell line LLC and splenocytes. Our results revealed that CICs formed by lung cancer cells and infiltrated lymphocytes were correlated with malignancy of NSCLC. In addition, we found CICs mediated the transfer of lymphocyte mitochondria to tumor cells, and promoted cancer cell proliferation and anti-cytotoxicity by activating MAPK pathway and up-regulating PD-L1 expression. Furthermore, CICs induces glucose metabolism reprogramming of lung cancer cells by upregulating glucose intake and glycolytic enzyme. Our findings suggest that CICs formed by lung cancer cell and lymphocyte contribute to NSCLC progression and reprogramming of glucose metabolism, and might represent a previously undescribed pathway for drug resistance of NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Mice , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Mitochondria/metabolism , Glucose/metabolism , B7-H1 Antigen , Tumor MicroenvironmentABSTRACT
BACKGROUND: Bedtime procrastination refers to an individual's inability to go to bed at a predetermined time without external obstacles. Previous researchers have found that the bedtime procrastination is harmful to human physical and mental health, but these research on bedtime procrastination have mostly focused on exploring individual factors, while ignoring the external environmental factors. Therefore, this is the first study to investigate bedtime procrastination from the perspective of family environments. METHODS: The study was conducted using a convenient sampling method and online questionnaires. Family Cohesion Scale, Coping Styles Questionnaire, Mobile Phone Addiction Tendency Scale and Bedtime Procrastination Scale were used to measure sleep and psychological condition of 1,048 college students. RESULTS: Family cohesion negatively predicted bedtime procrastination. Additionally, positive coping style and mobile phone addiction had significant independent mediating effects. Furthermore, positive coping style and mobile phone addiction had chain mediating effects between family cohesion and bedtime procrastination. CONCLUSION: This study revealed the effect of coping styles and mobile phone addiction on the relationship between family cohesion and bedtime procrastination among Chinese college students. These findings explained the mechanisms of bedtime procrastination from the perspective of environment, so as to effectively intervene the bedtime procrastination of college students from the perspective of external environment.
Subject(s)
Family Relations , Procrastination , Humans , Coping Skills , Students , Technology Addiction , East Asian PeopleABSTRACT
Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 (KMT2B) are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) oocytes using ultra-low input ChIP-seq, with comparisons to DNA methylation and gene expression analyses. H3K4me3 was redistributed in Setd1b cKO oocytes showing losses at active gene promoters associated with downregulated gene expression. Remarkably, many regions also gained H3K4me3, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich, which are hallmarks of MLL2 targets. Consequently, loss of SETD1B disrupts the balance between MLL2 and de novo DNA methyltransferases in determining the epigenetic landscape during oogenesis. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression and MLL2 to CpG content.
Subject(s)
Histones , Lysine , Animals , CpG Islands/genetics , DNA Methylation , Histone Methyltransferases/genetics , Histones/genetics , Histones/metabolism , Lysine/metabolism , Mammals/genetics , Oogenesis/geneticsABSTRACT
The leakage of gases and chemical vapors is a common accident in laboratory processes that requires a rapid response to avoid harmful effects if humans and instruments are exposed to this leakage. In this paper, the performance of a portable sensor node designed for integration with mobile and stationary robots used to transport chemical samples in automated laboratories was tested and evaluated. The sensor node has four main layers for executing several functions, such as power management, control and data preprocessing, sensing gases and environmental parameters, and communication and data transmission. The responses of three metal oxide semiconductor sensors, BME680, ENS160, and SGP41, integrated into the sensing layer have been recorded for various volumes of selected chemicals and volatile organic compounds, including ammonia, pentane, tetrahydrofuran, butanol, phenol, xylene, benzene, ethanol, methanol, acetone, toluene, and isopropanol. For mobile applications, the sensor node was attached to a sample holder on a mobile robot (ASTI ProBOT L). In addition, the sensor nodes were positioned close to automation systems, including stationary robots. The experimental results revealed that the tested sensors have a different response to the tested volumes and can be used efficiently for hazardous gas leakage detection and monitoring.
ABSTRACT
BACKGROUND: Atopic march has long been recognized as the progression from atopic dermatitis (AD) to food allergy and asthma during infancy and childhood. However, effective blocking is hampered by the lack of specific biomarkers. OBJECTIVES: We aimed to investigate the pathologic progression of atopic march trajectories from skin to gut. METHODS: We built an atopic march mouse model by mechanical skin injury and percutaneous sensitization to peanut allergen. Anaphylaxis from the skin to the small intestine was then investigated by ELISA, RNA sequencing, quantitative real-time PCR, histopathologic analysis, and flow cytometry. The findings from the mice results were also verified by the serum samples of allergic pediatric patients. RESULTS: After modeling, inflammation in the skin and small intestine manifested as a mixed type of TH2 and TH17. Further analysis identified elevated succinate in the circulation and expanded tuft cells with upregulated IL-25 in the small intestine, resulting in increased intestinal type 2 innate lymphoid cells and an enhanced type 2 inflammatory response. In addition, free mitochondrial DNA (mtDNA) released after tissue damage was also involved in inflammation march from injured skin to small intestine through the STING pathway. Analysis of clinical samples verified that serum concentrations of succinate and mtDNA were higher in AD allergic children than non-AD allergic children. CONCLUSIONS: Succinate and mtDNA play key roles in skin-to-gut cross talk during the atopic march from AD to food allergy, and can be considered as biomarkers for risk assessment or targets for atopic march prevention strategies.
Subject(s)
Dermatitis, Atopic , Food Hypersensitivity , Mice , Animals , Dermatitis, Atopic/genetics , Dermatitis, Atopic/pathology , Immunity, Innate , Succinic Acid , DNA, Mitochondrial/genetics , Lymphocytes/pathology , Succinates , InflammationABSTRACT
Studies have shown that maladaptive parenting styles, particularly parental psychological control may be an important risk factor for emotional problems in adolescence. However, the potential mechanisms behind this association are still not fully understood. To fill the research gap, this study investigated the relationship between parental psychological control and depression and anxiety among adolescents. It also explored the mediating effect of bedtime procrastination and the moderating effect of neuroticism through a moderated mediation analysis. A sample of 665 adolescents (331 girls) were recruited from two secondary schools in southern China. All participants completed standardized self-report questionnaires measuring the severity of parental psychological control, bedtime procrastination, depression, anxiety, and neuroticism. Data were analyzed using SPSS 25.0 and PROCESS macros. The results indicated that parental psychological control had a positive predictive effect on depression and anxiety among adolescents. Bedtime procrastination partially mediated the relationship between parental psychological control and depression, as well as parental psychological control and anxiety. Neuroticism was found to play a moderating role in the path from bedtime procrastination to depression and from bedtime procrastination to anxiety, with these effects being stronger for adolescents with higher levels of neuroticism. This study advances a deeper understanding of how and when or for whom parental psychological control is related to adolescents' severe depression and anxiety. Our findings suggest that intervention programs or strategies aimed at reducing parental psychological control and assisting adolescents in establishing healthy sleep hygiene practices should be developed to decrease the risk of depression and anxiety in adolescents.
Subject(s)
Anxiety , Depression , Neuroticism , Parenting , Procrastination , Humans , Female , Adolescent , Male , Depression/psychology , Surveys and Questionnaires , Parenting/psychology , Anxiety/psychology , China , Parent-Child Relations , Parents/psychology , Self ReportABSTRACT
Although epigallocatechin-3-gallate (EGCG) can potentiate chemotherapeutic drugs at high concentrations, its clinical translation is hampered by exceeding possible concentration thresholds. This study proposes a dichotomous use of low-concentration EGCG in chemotherapy. During the first cycle of combined treatment with oxaliplatin (OXA), low-concentration EGCG antagonized the cytotoxic effect of OXA on colorectal cancer (CRC) cells. However, when OXA was subsequently administered, the sensitivity of CRC cells markedly increased. Although low-concentration EGCG counteracted OXA, it reduced the OXA-induced secretion of vascular endothelial growth factor by tumor cells, thereby contributing to the increase in the sensitivity of tumor cells to the second round of OXA treatment. Therefore, low-concentration EGCG showed potential as a viable adjunct to modulate chemosensitivity in CRC.
Subject(s)
Antineoplastic Agents , Catechin/analogs & derivatives , Colorectal Neoplasms , Humans , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Vascular Endothelial Growth Factor A , Colorectal Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, TumorABSTRACT
OBJECTIVES: To explore the performance of a deep learning-based algorithm for automatic patellofemoral joint (PFJ) parameter measurements from the Laurin view. METHODS: A total of 1431 consecutive Laurin views of the PFJ were retrospectively collected and divided into two parts: (1) the model development dataset (dataset 1, n = 1230) and (2) the hold-out test set (dataset 2, n = 201). Dataset 1 was used to develop the U-shaped fully convolutional network (U-Net) model to segment the landmarks of the PFJ. Based on the predicted landmarks, the PFJ parameters were calculated, including the sulcus angle (SA), congruence angle (CA), patellofemoral ratio (PFR), and lateral patellar tilt (LPT). Dataset 2 was used to assess the model performance. The mean of three radiologists who independently measured the PFJ parameters was defined as the reference standard. Model performance was assessed by the intraclass correlation coefficient (ICC), mean absolute difference (MAD), and root mean square (RMS) compared to the reference standard. Ninety-five percent limits of agreement (95% LoA) were calculated pairwise for each radiologist, reference standard, and model. RESULTS: Compared with the reference standard, U-Net showed good performance for predicting SA, CA, PFR, and LPT, with ICC = 0.85-0.97, MAD = 0.06-5.09, and RMS = 0.09-6.90 in the hold-out test set. Except for the PFR, the remaining parameters measured between the reference standard and the model were within the 95% LoA in the hold-out test dataset. CONCLUSIONS: The U-Net-based deep learning approach had a relatively high model performance in automatically measuring SA, CA, PFR, and LPT. KEY POINTS: ⢠The U-Net model could be used to segment the landmarks of the PFJ and calculate the SA, CA, PFR, and LPT, which could be used to evaluate the patellar instability. ⢠In the hold-out test, the automatic measurement model yielded comparable performance with reference standard. ⢠The automatic measurement model could still accurately predict SA, CA, PFR, and LPT in patients with PI and/or PFOA.
Subject(s)
Deep Learning , Joint Instability , Patellofemoral Joint , Humans , Patellofemoral Joint/diagnostic imaging , Retrospective Studies , PatellaABSTRACT
To realize advanced electrical applications for ferroelectric liquid crystalline polymers, high spontaneous polarization (Ps ) is highly desired. However, current ferroelectric liquid crystalline polymers usually exhibit a low Ps . In this work, mesogen-free, chiral polyethers containing sulfonylated methyl-branched alkyl side chains with a (CH2 )3 O spacer between the sulfonyl and the branched alkyl groups are designed and synthesized. In contrast to the linear n-alkyl side chains, the methyl-branched alkyl side chains induce chain tilting in the smectic layers. When double chirality exists in both the main chain and the side chains, a crystalline structure is observed after mechanical stretching. Intriguingly, when single chirality exists in either the backbone or the side chains, a liquid crystalline smectic C phase is obtained. The electric displacement-electric field study, however, does not show typical ferroelectric switching, although the dielectric constants are relatively high for these liquid crystalline polymers. This is likely because the dipole-dipole interactions among neighboring sulfonyl groups along the main chain are so strong that the ferroelectric switching is hindered in the samples. For the future work, it is desired to weaken the dipole-dipole interaction to achieve ferroelectricity in these mesogen-free liquid crystalline polymers.
Subject(s)
Polymers , Polymers/chemistryABSTRACT
BACKGROUND: Simple and rapid tools for screening high-risk patients for perioperative neurocognitive disorders (PNDs) are urgently needed to improve patient outcomes. We developed an online tool with machine-learning algorithms using routine variables based on multicenter data. METHODS: The entire dataset was composed of 49,768 surgical patients from 3 representative academic hospitals in China. Surgical patients older than 45 years, those undergoing general anesthesia, and those without a history of PND were enrolled. When the patient's discharge diagnosis was PND, the patient was in the PND group. Patients in the non-PND group were randomly extracted from the big data platform according to the surgical type, age, and source of data in the PND group with a ratio of 3:1. After data preprocessing and feature selection, general linear model (GLM), artificial neural network (ANN), and naive Bayes (NB) were used for model development and evaluation. Model performance was evaluated by the area under the receiver operating characteristic curve (ROCAUC), the area under the precision-recall curve (PRAUC), the Brier score, the index of prediction accuracy (IPA), sensitivity, specificity, etc. The model was also externally validated on the multiparameter intelligent monitoring in intensive care (MIMIC) â £ database. Afterward, we developed an online visualization tool to preoperatively predict patients' risk of developing PND based on the models with the best performance. RESULTS: A total of 1051 patients (242 PND and 809 non-PND) and 2884 patients (6.2% patients with PND) were analyzed on multicenter data (model development, test [internal validation], external validation-1) and MIMIC â £ dataset (external validation-2). The model performance based on GLM was much better than that based on ANN and NB. The best-performing GLM model on validation-1 dataset achieved ROCAUC (0.874; 95% confidence interval [CI], 0.833-0.915), PRAUC (0.685; 95% CI, 0.584-0.786), sensitivity (72.6%; 95% CI, 61.4%-81.5%), specificity (84.4%; 95% CI, 79.3%-88.4%), Brier score (0.131), and IPA (44.7%), and of which the ROCAUC (0.761, 95% CI, 0.712-0.809), the PRAUC (0.475, 95% CI, 0.370-0.581), Brier score (0.053), and IPA (76.8%) on validation-2 dataset. Afterward, we developed an online tool (https://pnd-predictive-model-dynnom.shinyapps.io/ DynNomapp/) with 10 routine variables for preoperatively screening high-risk patients. CONCLUSIONS: We developed a simple and rapid online tool to preoperatively screen patients' risk of PND using GLM based on multicenter data, which may help medical staff's decision-making regarding perioperative management strategies to improve patient outcomes.
Subject(s)
Clinical Decision-Making , Nomograms , Humans , Adult , Bayes Theorem , Algorithms , Risk Factors , Retrospective StudiesABSTRACT
BACKGROUND: Previous studies on bedtime procrastination mainly focused on the influencing factors of stress and draw less attention on the role of family environment. AIM: This study aimed to explore the effect of psychological stress reaction on bedtime procrastination in young adults, with considering the mediating effect of smartphone addiction, and the moderating effect of family cohesion during the COVID-19 pandemic. METHODS: A sample of 1217 young adults completed psychological stress reaction scale, Smartphone addiction tendency scale for young adults, bedtime procrastination scale and family cohesion scale. A moderated mediation model was conducted to clarify the effect of psychological stress reaction on bad bedtime procrastination in young adults. RESULTS: The findings showed that: (1) The individual level of psychological stress reaction was positively associated with bedtime procrastination; (2) Smartphone addiction mediated the effect of psychological stress reaction on bedtime procrastination; (3) Family cohesion moderated the relationship among psychological stress reaction, smartphone addiction and bedtime procrastination. CONCLUSIONS: This study revealed the effect of smartphone addiction on the relationship between psychological stress reaction and bedtime procrastination during the COVID-19 pandemic, and these findings could provide novel evidence that family cohesion may serve as a protective factor against the negative consequences of smartphone addiction on bad bedtime procrastination.