ABSTRACT
Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play a crucial role in accurate memory retrieval. However, the coordination mechanism of neuronal subpopulations within the dDG network during fear generalization is not well understood. Here, with the Tet-off system combined with immunostaining and two-photon calcium imaging, we report that dDG fear engram cells labeled in the conditioned context constitutes a significantly higher proportion of dDG neurons activated in a similar context where mice show generalized fear. The activation of these dDG fear engram cells encoding the conditioned context is both sufficient and necessary for inducing fear generalization in the similar context. Activities of mossy cells in the ventral dentate gyrus (vMCs) are significantly suppressed in mice showing fear generalization in a similar context, and activating the vMCs-dDG pathway suppresses generalized but not conditioned fear. Finally, modifying fear memory engrams in the dDG with "safety" signals effectively rescues fear generalization. These findings reveal that the competitive advantage of dDG engram cells underlies fear generalization, which can be rescued by activating the vMCs-dDG pathway or modifying fear memory engrams, and provide novel insights into the dDG network as the neuronal basis of fear generalization.
Subject(s)
Dentate Gyrus , Fear , Neurons , Animals , Fear/physiology , Dentate Gyrus/physiology , Mice , Male , Neurons/physiology , Neurons/metabolism , Mice, Inbred C57BL , Conditioning, Classical/physiology , Memory/physiology , Generalization, Psychological/physiologyABSTRACT
The eye presents a unique opportunity for complement component 3 (C3) therapeutics. Drugs can be delivered directly to specific parts of the eye, and growing evidence has established a pivotal role for C3 in age-related macular degeneration (AMD). Emerging data show that C3 may be important to the pathophysiology of other eye diseases as well. This article will discuss the location of C3 expression in the eye as well as the preclinical and clinical data regarding C3's functions in AMD. We will provide a comprehensive review of developing C3 inhibitors for the eye, including the Phase 2 and 3 data for the C3 inhibitor pegcetacoplan as a treatment for the geographic atrophy of AMD. Developing evidence also points toward C3 as a therapeutic target for stages of AMD preceding geographic atrophy. We will also discuss data illuminating C3's relationship to other eye diseases, such as Stargardt disease, diabetic retinopathy, and glaucoma. In addition to being a converging point and centerpiece of the complement cascade, C3 has broad effects as a multifaceted controller of opsonophagocytosis, microglia/macrophage recruitment, and downstream terminal pathway activity. C3 is a crucial player in the pathophysiology of AMD but also seems to have importance in other diseases that are major causes of blindness. Directions for further investigation will be highlighted, as culminating evidence suggests that we may be approaching an era of C3 therapeutics for the eye.
Subject(s)
Geographic Atrophy , Macular Degeneration , Humans , Geographic Atrophy/drug therapy , Geographic Atrophy/etiology , Macular Degeneration/drug therapy , Macular Degeneration/complications , Complement ActivationABSTRACT
Microorganisms can produce a vast array of bioactive secondary metabolites, including DNA-intercalating agents like actinomycin D, doxorubicin, which hold great potential for cancer chemotherapy. However, discovering novel DNA-intercalating compounds remains challenging due to the limited sensitivity and specificity of conventional activity assays, which require large-scale fermentation and purification. Here, we introduced the single-molecule stretching assay (SMSA) directly to microbial cultures or extracts for discovering DNA-intercalating agents, even in trace amounts of microbial cultures (5 µl). We showed that the unique changes of dsDNA in contour length and overstretching transition enable the specific detection of intercalators from complex samples without the need for extensive purification. Applying force to dsDNA also enhanced the sensitivity by increasing both the binding affinity Ka and the quantity of ligands intercalation, thus allowing the detection of weak intercalators, which are often overlooked using traditional methods. We demonstrated the effectiveness of SMSA, identified two DNA intercalator-producing strains: Streptomyces tanashiensis and Talaromyces funiculosus, and isolated three DNA intercalators: medermycin, kalafungin and ligustrone B. Interestingly, both medermycin and kalafungin, classified as weak DNA intercalators (Ka â¼103 M-1), exhibited potent anti-cancer activity against HCT-116 cancer cells, with IC50 values of 52 ± 6 and 70 ± 7 nM, respectively.
ABSTRACT
MOTIVATION: Molecular property prediction is a significant requirement in AI-driven drug design and discovery, aiming to predict the molecular property information (e.g. toxicity) based on the mined biomolecular knowledge. Although graph neural networks have been proven powerful in predicting molecular property, unbalanced labeled data and poor generalization capability for new-synthesized molecules are always key issues that hinder further improvement of molecular encoding performance. RESULTS: We propose a novel self-supervised representation learning scheme based on a Cascaded Attention Network and Graph Contrastive Learning (CasANGCL). We design a new graph network variant, designated as cascaded attention network, to encode local-global molecular representations. We construct a two-stage contrast predictor framework to tackle the label imbalance problem of training molecular samples, which is an integrated end-to-end learning scheme. Moreover, we utilize the information-flow scheme for training our network, which explicitly captures the edge information in the node/graph representations and obtains more fine-grained knowledge. Our model achieves an 81.9% ROC-AUC average performance on 661 tasks from seven challenging benchmarks, showing better portability and generalizations. Further visualization studies indicate our model's better representation capacity and provide interpretability.
Subject(s)
Benchmarking , Learning , Drug Design , Neural Networks, ComputerABSTRACT
BACKGROUND AND AIMS: Patients with acute myeloid leukaemia (AML) suffer from severe myocardial injury during daunorubicin (DNR)-based chemotherapy and are at high risk of cardiac mortality. The crosstalk between tumour cells and cardiomyocytes might play an important role in chemotherapy-related cardiotoxicity, but this has yet to be demonstrated. This study aimed to identify its underlying mechanism and explore potential therapeutic targets. METHODS: Cardiac tissues were harvested from an AML patient after DNR-based chemotherapy and were subjected to single-nucleus RNA sequencing. Cardiac metabolism and function were evaluated in AML mice after DNR treatment by using positron emission tomography, magnetic resonance imaging, and stable-isotope tracing metabolomics. Plasma cytokines were screened in AML mice after DNR treatment. Genetically modified mice and cell lines were used to validate the central role of the identified cytokine and explore its downstream effectors. RESULTS: In the AML patient, disruption of cardiac metabolic homeostasis was associated with heart dysfunction after DNR-based chemotherapy. In AML mice, cardiac fatty acid utilization was attenuated, resulting in cardiac dysfunction after DNR treatment, but these phenotypes were not observed in similarly treated tumour-free mice. Furthermore, tumour cell-derived interleukin (IL)-1α was identified as a primary factor leading to DNR-induced cardiac dysfunction and administration of an anti-IL-1α neutralizing antibody could improve cardiac functions in AML mice after DNR treatment. CONCLUSIONS: This study revealed that crosstalk between tumour cells and cardiomyocytes during chemotherapy could disturb cardiac energy metabolism and impair heart function. IL-1α neutralizing antibody treatment is a promising strategy for alleviating chemotherapy-induced cardiotoxicity in AML patients.
Subject(s)
Daunorubicin , Interleukin-1alpha , Leukemia, Myeloid, Acute , Animals , Leukemia, Myeloid, Acute/drug therapy , Humans , Interleukin-1alpha/metabolism , Mice , Cardiotoxicity/etiology , Antibiotics, Antineoplastic/adverse effects , Male , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolismABSTRACT
Increasing biological evidence indicated that microRNAs (miRNAs) play a vital role in exploring the pathogenesis of various human diseases (especially in tumors). Mining disease-related miRNAs is of great significance for the clinical diagnosis and treatment of diseases. Compared with the traditional experimental methods with the significant limitations of high cost, long cycle and small scale, the methods based on computing have the advantages of being cost-effective. However, although the current methods based on computational biology can accurately predict the correlation between miRNAs and disease, they can not predict the detailed association information at a fine level. We propose a knowledge-driven approach to the fine-grained prediction of disease-related miRNAs (KDFGMDA). Different from the previous methods, this method can finely predict the clear associations between miRNA and disease, such as upregulation, downregulation or dysregulation. Specifically, KDFGMDA extracts triple information from massive experimental data and existing datasets to construct a knowledge graph and then trains a depth graph representation learning model based on knowledge graph to complete fine-grained prediction tasks. Experimental results show that KDFGMDA can predict the relationship between miRNA and disease accurately, which is of far-reaching significance for medical clinical research and early diagnosis, prevention and treatment of diseases. Additionally, the results of case studies on three types of cancers, Kaplan-Meier survival analysis and expression difference analysis further provide the effectiveness and feasibility of KDFGMDA to detect potential candidate miRNAs. Availability: Our work can be downloaded from https://github.com/ShengPengYu/KDFGMDA.
Subject(s)
MicroRNAs , Neoplasms , Algorithms , Computational Biology/methods , Down-Regulation , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms/diagnosis , Neoplasms/geneticsABSTRACT
Ferroptosis is a newly discovered form of cell death that is featured in a wide range of diseases. Exosome therapy is a promising therapeutic option that has attracted much attention due to its low immunogenicity, low toxicity, and ability to penetrate biological barriers. In addition, emerging evidence indicates that exosomes possess the ability to modulate the progression of diverse diseases by regulating ferroptosis in damaged cells. Hence, the mechanism by which cell-derived and noncellular-derived exosomes target ferroptosis in different diseases through the system Xc-/GSH/GPX4 axis, NAD(P)H/FSP1/CoQ10 axis, iron metabolism pathway and lipid metabolism pathway associated with ferroptosis, as well as its applications in liver disease, neurological diseases, lung injury, heart injury, cancer and other diseases, are summarized here. Additionally, the role of exosome-regulated ferroptosis as an emerging repair mechanism for damaged tissues and cells is also discussed, and this is expected to be a promising treatment direction for various diseases in the future. Video Abstract.
Subject(s)
Exosomes , Ferroptosis , Lung Injury , Humans , Cell Death , NADABSTRACT
The expression level of PD-L1 in tumor tissue is considered one of the effective biomarkers to guide PD-1/PD-L1 therapy. Quantifying whole-body PD-L1 expression by SPECT imaging may help in selecting patients that potentially respond to PD-1/PD-L1 therapy. Nanobody is the smallest antibody fragment with antigen-binding ability that is well suited for radionuclide imaging. Nevertheless, high retention of radioactivity in the kidney may limit its clinical translation. The present study aimed to screen, design, and prepare a nanobody-based SPECT probe with rapid renal clearance to evaluate the PD-L1 expression level in vivo noninvasively. A phage library was constructed by immunizing alpaca with recombinant human PD-L1 protein, and 17 anti-PD-L1 nanobodies were screened by the phage display technique. After sequence alignment and flow cytometry analysis, APN09 was selected as the candidate nanobody, and a GGGC chelator was attached to its C-terminus for 99mTc labeling to prepare a SPECT imaging probe. The affinity and specificity of 99mTc-APN09 were evaluated by protein and cell-binding experiments, and SPECT imaging and biodistribution were performed in a mouse model with bilateral transplantation of A549 and A549PD-L1 tumors. The ability of 99mTc-APN09 to quantify the PD-L1 expression level in vivo was validated in tumor models with different PD-L1 expression levels. 99mTc-APN09 had a radiochemical purity higher than 99% and a binding equilibrium dissociation constant of 21.44 ± 1.65 nM with hPD-L1, showing high affinity. SPECT imaging results showed that 99mTc-APN09 could efficiently detect PD-L1-positive tumors within 0.5 h, and the quantitative results of SPECT were well correlated with the expression level of PD-L1 in cell lines. SPECT imaging and biodistribution results also showed that 99mTc-APN09 was rapidly cleared from the kidney in 2 h postinjection. 99mTc-APN09 was a simple and stable tool for visualizing PD-L1 expression in the whole body. In addition, due to its significant reduction in renal retention, it has better prospects for clinical translation.
Subject(s)
B7-H1 Antigen , Neoplasms , Animals , Humans , Mice , B7-H1 Antigen/metabolism , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/metabolism , Tissue Distribution , Tomography, Emission-Computed, Single-Photon/methods , Camelids, New WorldABSTRACT
Saccharomyces boulardii (Sb) is a probiotic yeast for the treatment of gastrointestinal disorders, including inflammatory bowel disease (IBD). Little is known about the modulatory capacity of the Sb in IBD. Here, we found that oral gavage of Sb supernatant (SbS) alleviated gut inflammation, protected the intestinal barrier, and reversed DSS-induced down-regulated activation of epidermal growth factor receptor (EGFR) in colitis. Mass spectrum analysis showed that thioredoxin (Trx) is one of the critical secreted soluble proteins participating in EGFR activation detected in SbS. Trx exerted an array of significant effects on anti-inflammatory activity, including alleviating inflammation, protecting gut barrier, suppressing apoptosis, as well as reducing oxidative stress. Mechanistically, Trx promoted EGFR ligand gene expression and transactivated EGFR in a concentration-dependent manner. EGFR kinase inhibitor could block Trx-mediated preventive effects of intestinal epithelial injury. Our data suggested that Sb-derived soluble protein Trx could serve as a potential prophylactic, as a novel postbiotic against colitis, which provides a new strategy for the precision prevention and treatment of IBD.
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BACKGROUND: Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear. METHODS: Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG. RESULTS: The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG. CONCLUSIONS: The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG.
Subject(s)
Macrophage Colony-Stimulating Factor , Neuralgia , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor , Trigeminal Neuralgia , Animals , Mice , Aminopyridines , Hyperalgesia , Interleukin-6/metabolism , Macrophage Colony-Stimulating Factor/metabolism , Neuralgia/metabolism , Pyrroles , Receptor Protein-Tyrosine Kinases/metabolism , Trigeminal Ganglion/metabolism , Trigeminal Ganglion/pathology , Trigeminal Neuralgia/metabolism , Trigeminal Neuralgia/pathology , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolismABSTRACT
BACKGROUND: Postoperative sore throat (POST) is a common postoperative complication. COMPLICATION: Chewing gum can inhibit the growth of oral bacteria, cleanse, and lubricate the oral cavity, which can help reduce postoperative sore throat. We hypothesize that chewing gum before surgery could relieve POST. METHODS: Patients planned to undergo total thyroidectomy under general anesthesia with tracheal intubation were randomized to swallow saliva twice or chew 1.4 g/2.8 g of gum for 2 minutes before surgery. A standard anesthesia protocol was performed. The numerical rating scale scores of POST at 1, 24, and 48 h after surgery were collected. The primary outcome was the incidence of moderate/severe POST (numerical rating scale score >3) within 48 h. RESULTS: Data from 148 patients (control group, n = 50; 1.4 g group, n = 48; and 2.8 g group, n = 50) were included in the analysis. Within 48 h, there was a significant difference among the three groups in the incidence of moderate/severe POST (control group: 74% vs. 1.4 g group: 65% vs. 2.8 g group: 50%. P = 0.04). The 2.8 g group had less incidence of moderate/severe POST than the control group (Odds Ratio = 0.351 95% Confidence Interval: (0.152 and 0.814) P = 0.02). CONCLUSION: Chewing 2.8 g gum before total thyroidectomy can reduce the incidence of moderate/severe POST within 48 h after surgery.
Subject(s)
Chewing Gum , Pharyngitis , Humans , Thyroidectomy/adverse effects , Pharyngitis/etiology , Pharyngitis/prevention & control , Pharyngitis/epidemiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Anesthesia, General , Intubation, Intratracheal/adverse effectsABSTRACT
PURPOSE: To determine factors associated with visual and anatomic outcomes of suprachoroidal hemorrhage in studies published between 1990 and 2022. METHODS: Individual participant data systematic review. The protocol was prospectively registered on Open Science Framework ( https://osf.io/69v3q/ ). PubMed, EMBASE, Web of Science, and Google Scholar were searched for peer-reviewed studies of suprachoroidal hemorrhage with ≥3 patients published between January 1, 1990, and September 1, 2022. The primary outcome was the change in logarithm of the minimum angle of resolution visual acuity from the time of suprachoroidal hemorrhage diagnosis to last follow-up. RESULTS: Four hundred thirteen eyes from 49 studies were included, with mean (SD) age 60.8 (22.4) years and mean (SD) follow-up of 13.8 (12.6) months. Among 145 eyes with at least 6 months of follow-up, the mean (SD) gain in visual acuity was -0.98 (0.89) logarithm of the minimum angle of resolution. In multivariable regression, treatment with systemic steroids was associated with greater improvement in logarithm of the minimum angle of resolution visual acuity (adjusted mean [SE] -1.29 [0.09] vs. -0.16 [0.30] for no systemic steroids; P < 0.001) and greater odds of achieving anatomic success (adjusted OR 10.59, 95% confidence interval 2.59-43.3; P = 0.001). CONCLUSION: The use of systemic steroids was associated with better visual and anatomic outcomes for suprachoroidal hemorrhage.
Subject(s)
Choroid Hemorrhage , Visual Acuity , Humans , Visual Acuity/physiology , Choroid Hemorrhage/diagnosis , Choroid Hemorrhage/etiology , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , FemaleABSTRACT
Although immunotherapy is a valuable treatment for gastric cancer (GC), identifying the patients who would benefit most from this approach presents a challenge. In this study, GC patients were divided into two subtypes by consensus clustering according to T cell-mediated tumor killing related genes (TTKRGs), and there were significant differences in tumor-infiltrating immune cells, signaling pathways, and gene expression of immunomodulators and inhibitory immune checkpoints between the two subtypes. Then, we developed an individualized signature based on TTKRGs, and its clinical and predictive value in GC patients for chemotherapeutic and immunotherapeutic responses was assessed. We confirmed the expression levels of signature genes in GC tumor tissue using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, to improve the accuracy of GC prognosis predictions, we established a nomogram. We further identified some compounds as sensitive drugs targeting GC risk groups. The signature showed significant predictive ability across RNA-seq, microarray, and qRT-PCR cohorts, which could assist in predicting survival, immunotherapeutic and chemotherapeutic outcomes in GC patients.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Prognosis , T-Lymphocytes , Cluster Analysis , RNA-SeqABSTRACT
Multiple evidence has supported that air pollution exposure has detrimental effects on the cardiovascular and respiratory systems. However, most investigations focus on the general population, with limited research conducted on medically insured populations. To address this gap, the current research was designed to examine the acute effects of inhalable particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), ground-level ozone (O3), and sulfur dioxide (SO2) on the incidence of upper respiratory tract infections (URTI), utilizing medical insurance data in Wuhan, China. Data on URTI were collected from the China Medical Insurance Basic Database for Wuhan covering the period from 2014 to 2018, while air pollutant data was gathered from ten national monitoring stations situated in Wuhan city. Statistical analysis was performed using generalized additive models for quasi-Poisson distribution with a log link function. The analysis indicated that except for ozone, higher exposure to four other pollutants (NO2, SO2, PM2.5, and PM10) were significantly linked to an elevated risk of URTI, particularly during the previous 0-3 days and previous 0-4 days. Additionally, NO2 and SO2 were found to be positively linked with laryngitis. Furthermore, the effects of air pollutants on the risk of URTI were more pronounced during cold seasons than hot seasons. Notably, females and the employed population were more susceptible to infection than males and non-employed individuals. Our findings gave solid proof of the link between ambient air pollution exposure and the risk of URTI in medically insured populations.
Subject(s)
Air Pollutants , Air Pollution , Particulate Matter , Respiratory Tract Infections , Sulfur Dioxide , Humans , China/epidemiology , Female , Male , Air Pollutants/analysis , Air Pollution/analysis , Air Pollution/adverse effects , Middle Aged , Particulate Matter/analysis , Adult , Respiratory Tract Infections/epidemiology , Sulfur Dioxide/analysis , Aged , Adolescent , Young Adult , Ozone/analysis , Ozone/adverse effects , Child , Child, Preschool , Insurance, Health/statistics & numerical data , Nitrogen Dioxide/analysis , Infant , Seasons , Infant, Newborn , Incidence , Environmental Exposure/analysis , Environmental Exposure/adverse effectsABSTRACT
An accurate calculation of the indicator diagram of a pumping unit is the key factor in analyzing the performance of an oilfield production and operation and in preparing and optimizing an oilfield development plan. Aiming at the problems of the poor stability of the conventional load-displacement sensor method and the wave equation method, owing to the influence of an alternating load on the force sensor and the difficulty in measuring the crank angle using the electrical parameter method, a new soft sensing method employing the input electrical parameters of the motor and the beam inclination has been proposed to obtain the indicator diagram. At first, this method is established based on the beam angle of the pumping unit, which is easily measured using the suspension point displacement mathematics calculation model and the torque factor. Subsequently, the electric motor input parameters, the parameters of the four-bar linkage, and the relationship between the polished rod load have been established. Finally, the motor and the beam angle of the measured electrical parameters have been substituted into the calculation of the suspension point displacement and load value and pull in accordance with the guidelines to eliminate the singularity mutation values. After processing the measured data through a Butterworth filter, the indicator diagram is obtained. The results of the engineering experiment and application show that the average relative error of the method is less than 3.95%, and the maximum relative error remains within 2% for 6 months, which verifies the stability of the soft sensing method.
ABSTRACT
Colorectal cancer (CRC) is related to gut microbiota dysbiosis, especially butyrate-producing bacteria reduction. Our previous study suggested that administration of Clostridium butyricum, a butyrate-producing bacterium, exerts a crucial effect against CRC, however the potential mechanism is not clear. We first found that methyltransferase-like 3 (METTL3) showed a positive correlation with proliferation, epithelial-mesenchymal transition (EMT), DNA repair, metastasis, and invasion in a database analysis. The expression of METTL3 gradually increased from human normal colon tissue, to adenoma, and carcinoma, and was positively correlated with E-cadherin and CD34 levels. Overexpression of METTL3 promoted the proliferation, migration, and invasion of CRC cells and induced vasculogenic mimicry (VM) formation. Clostridium butyricum could downregulate METTL3 expression in CRC cells and decrease the expression of vimentin and vascular endothelial growth factor receptor 2 to reduce EMT and VM formation. Clostridium butyricum alleviated the pro-oncogenic effect of METTL3 overexpressing plasmid in CRC cells. The anti-EMT effect on METTL3 reduction of C. butyricum could be blunted by knocking down G-protein coupled receptor 43. Moreover, C. butyricum prevented EMT and VM and inhibited tumor metastasis in nude mice. Accordingly, C. butyricum could inhibit EMT and VM formation of intestinal carcinogenesis through downregulating METTL3. These findings broaden our understanding of probiotics supplement in CRC prevention and treatment.
Subject(s)
Clostridium butyricum , Colorectal Neoplasms , Animals , Mice , Humans , Epithelial-Mesenchymal Transition/genetics , Vascular Endothelial Growth Factor A , Mice, Nude , Butyrates , Carcinogenesis/genetics , Cell Line, Tumor , Colorectal Neoplasms/pathology , Cell Movement , Methyltransferases/geneticsABSTRACT
The patient-acupuncturist interaction was a critical influencing factor for acupuncture effects but its mechanism remains unclear. This study aimed to examine the inter-brain mechanism of patient-acupuncturist dyad during acupuncture stimulation in a naturalistic clinical setting. Seventy healthy subjects (simulated "patients") were randomly assigned to two groups and received verum acupuncture group or sham acupuncture by one acupuncturist. Functional near-infrared spectroscopy hyperscanning was used to simultaneously record the neural responses of "patient"-acupuncturist dyad during acupuncture stimulation in each group. The results showed that inter-brain neural synchronization (INS) in the prefrontal cortex (PFC) of "patient"-acupuncturist dyad was significantly increased during verum but not sham acupuncture stimuli, and positively correlated with the needling sensations of "patients." Granger causality analysis demonstrated that there were no significant differences in INS direction between the "patient" and the acupuncturist. This study identified the increase of INS between "patient" and acupuncturist, and suggested that PFC was important to the interaction of "patient"-acupuncturist dyad.
Subject(s)
Acupuncture Therapy , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology , Sensation , Thalamus , Brain Mapping/methodsABSTRACT
Self-assembled colloidal crystals display structural colors due to light diffracted from their microscale, ordered structure. This color arises due to Bragg reflection (BR) or grating diffraction (GD); the latter mechanism is much less explored than the former. Here the design space for generating GD structural color is identified and its relative advantages are demonstrated. Electrophoretic deposition is used to self-assemble crystals with fine crystal grains from colloids of diameter 1.0 µm. The structural color in transmission is tunable across the full visible spectrum. The optimum optical response-represented by both color intensity and saturation-is observed at low layer number (≤5 layers). The spectral response is well predicted by Mie scattering of the crystals. Taken together, the experimental and theoretical results demonstrate that vivid grating colors with high color saturation can be produced from thin layers of micron-sized colloids. These colloidal crystals extend the potential of artificial structural color materials.
ABSTRACT
MOTIVATION: With the advancement of technology, we can generate and access large-scale, high dimensional and diverse genomics data, especially through single-cell RNA sequencing (scRNA-seq). However, integrative downstream analysis from multiple scRNA-seq datasets remains challenging due to batch effects. RESULTS: In this article, we propose a light-structured deep learning framework called ResPAN for scRNA-seq data integration. ResPAN is based on Wasserstein Generative Adversarial Network (WGAN) combined with random walk mutual nearest neighbor pairing and fully skip-connected autoencoders to reduce the differences among batches. We also discuss the limitations of existing methods and demonstrate the advantages of our model over seven other methods through extensive benchmarking studies on both simulated data under various scenarios and real datasets across different scales. Our model achieves leading performance on both batch correction and biological information conservation and maintains scalable to datasets with over half a million cells. AVAILABILITY AND IMPLEMENTATION: An open-source implementation of ResPAN and scripts to reproduce the results can be downloaded from: https://github.com/AprilYuge/ResPAN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Gene Expression Profiling , Single-Cell Analysis , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Gene Expression Profiling/methods , Cluster Analysis , Exome SequencingABSTRACT
X-ray detection, which plays an important role in medical and industrial fields, usually relies on inorganic scintillators to convert X-rays to visible photons; although several high-quantum-yield fluorescent molecules have been tested as scintillators, they are generally less efficient. High-energy radiation can ionize molecules and create secondary electrons and ions. As a result, a high fraction of triplet states is generated, which act as scintillation loss channels. Here we found that X-ray-induced triplet excitons can be exploited for emission through very rapid, thermally activated up-conversion. We report scintillators based on three thermally activated delayed fluorescence molecules with different emission bands, which showed significantly higher efficiency than conventional anthracene-based scintillators. X-ray imaging with 16.6 line pairs mm-1 resolution was also demonstrated. These results highlight the importance of efficient and prompt harvesting of triplet excitons for efficient X-ray scintillation and radiation detection.