ABSTRACT
Chromosomal instability (CIN) drives cancer cell evolution, metastasis and therapy resistance, and is associated with poor prognosis1. CIN leads to micronuclei that release DNA into the cytoplasm after rupture, which triggers activation of inflammatory signalling mediated by cGAS and STING2,3. These two proteins are considered to be tumour suppressors as they promote apoptosis and immunosurveillance. However, cGAS and STING are rarely inactivated in cancer4, and, although they have been implicated in metastasis5, it is not known why loss-of-function mutations do not arise in primary tumours4. Here we show that inactivation of cGAS-STING signalling selectively impairs the survival of triple-negative breast cancer cells that display CIN. CIN triggers IL-6-STAT3-mediated signalling, which depends on the cGAS-STING pathway and the non-canonical NF-κB pathway. Blockade of IL-6 signalling by tocilizumab, a clinically used drug that targets the IL-6 receptor (IL-6R), selectively impairs the growth of cultured triple-negative breast cancer cells that exhibit CIN. Moreover, outgrowth of chromosomally instable tumours is significantly delayed compared with tumours that do not display CIN. Notably, this targetable vulnerability is conserved across cancer types that express high levels of IL-6 and/or IL-6R in vitro and in vivo. Together, our work demonstrates pro-tumorigenic traits of cGAS-STING signalling and explains why the cGAS-STING pathway is rarely inactivated in primary tumours. Repurposing tocilizumab could be a strategy to treat cancers with CIN that overexpress IL-6R.
Subject(s)
Chromosomal Instability , Interleukin-6 , Membrane Proteins , Nucleotidyltransferases , Triple Negative Breast Neoplasms , Antibodies, Monoclonal, Humanized/pharmacology , Cell Survival/drug effects , Chromosomal Instability/genetics , Drug Repositioning , Humans , Interleukin-6/antagonists & inhibitors , Interleukin-6/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , NF-kappa B/metabolism , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism , Receptors, Interleukin-6/antagonists & inhibitors , Receptors, Interleukin-6/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathologyABSTRACT
Genomic DNA of the cyanophage S-2L virus is composed of 2-aminoadenine (Z), thymine (T), guanine (G), and cytosine (C), forming the genetic alphabet ZTGC, which violates Watson-Crick base pairing rules. The Z-base has an extra amino group on the two position that allows the formation of a third hydrogen bond with thymine in DNA strands. Here, we explored and expanded applications of this non-Watson-Crick base pairing in protein expression and gene editing. Both ZTGC-DNA (Z-DNA) and ZUGC-RNA (Z-RNA) produced in vitro show detectable compatibility and can be decoded in mammalian cells, including Homo sapiens cells. Z-crRNA can guide CRISPR-effectors SpCas9 and LbCas12a to cleave specific DNA through non-Watson-Crick base pairing and boost cleavage activities compared to A-crRNA. Z-crRNA can also allow for efficient gene and base editing in human cells. Together, our results help pave the way for potential strategies for optimizing DNA or RNA payloads for gene editing therapeutics and give insights to understanding the natural Z-DNA genome.
Subject(s)
Base Pairing , CRISPR-Cas Systems , DNA, Z-Form , Gene Editing , Humans , DNA/genetics , DNA/chemistry , DNA, Z-Form/genetics , Gene Editing/methods , RNA/genetics , RNA, Guide, CRISPR-Cas Systems , Thymine/chemistryABSTRACT
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a crucial role in antitumor immunity. However, the role of MIF in influencing the tumor microenvironment (TME) and prognosis of triple-negative breast cancer (TNBC) remains to be elucidated. Using R, we analyzed single-cell RNA sequencing (scRNA-seq) data of 41 567 cells from 10 TNBC tumor samples and spatial transcriptomic data from two patients. Relationships between MIF expression and immune cell infiltration, clinicopathological stage, and survival prognosis were determined using samples from The Cancer Genome Atlas (TCGA) and validated in a clinical cohort using immunohistochemistry. Analysis of scRNA-seq data revealed that MIF secreted by epithelial cells in TNBC patients could regulate the polarization of macrophages into the M2 phenotype, which plays a key role in modulating the TME. Spatial transcriptomic data also showed that epithelial cells (tumor cells) and MIF were proximally located. Analysis of TCGA samples confirmed that tumor tissues of patients with high MIF expression were enriched with M2 macrophages and showed a higher T stage. High MIF expression was significantly associated with poor patient prognosis. Immunohistochemical staining showed high MIF expression was associated with younger patients and worse clinicopathological staging. MIF secreted by epithelial cells may represent a potential biomarker for the diagnosis and prognosis of TNBC and may promote TNBC invasion by remodeling the tumor immune microenvironment.
Subject(s)
Biomarkers, Tumor , Intramolecular Oxidoreductases , Macrophage Migration-Inhibitory Factors , Macrophages , Triple Negative Breast Neoplasms , Tumor Microenvironment , Humans , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/genetics , Macrophage Migration-Inhibitory Factors/metabolism , Macrophage Migration-Inhibitory Factors/genetics , Female , Intramolecular Oxidoreductases/metabolism , Intramolecular Oxidoreductases/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Macrophages/metabolism , Macrophages/immunology , Prognosis , Middle Aged , Gene Expression Regulation, NeoplasticABSTRACT
Replication stress (RS) is a key trait of cancer cells, and a potential actionable target in cancer treatment. Accurate methods to measure RS in tumour samples are currently lacking. DNA fibre analysis has been used as a common technique to measure RS in cell lines. Here, we investigated DNA fibre analysis on fresh breast cancer specimens and correlated DNA replication kinetics to known RS markers and genomic alterations. Fresh, treatment-naïve primary breast cancer samples (n = 74) were subjected to ex vivo DNA fibre analysis to measure DNA replication kinetics. Tumour cell proliferation was confirmed by EdU incorporation and cytokeratin AE1/AE3 (CK) staining. The RS markers phospho-S33-RPA and γH2AX and the RS-inducing proto-oncogenes Cyclin E1 and c-Myc were analysed by immunohistochemistry. Copy number variations (CNVs) were assessed from genome-wide single nucleotide polymorphism (SNP) arrays. We found that the majority of proliferating (EdU-positive) cells in each sample were CK-positive and therefore considered to be tumour cells. DNA fibre lengths varied largely in most tumour samples. The median DNA fibre length showed a significant inverse correlation with pRPA expression (r = -0.29, p = 0.033) but was not correlated with Cyclin E1 or c-Myc expression and global CNVs in this study. Nuclear Cyclin E1 expression showed a positive correlation with pRPA levels (r = 0.481, p < 0.0001), while cytoplasmic Cyclin E1 expression exhibited an inverse association with pRPA expression (r = -0.353, p = 0.002) and a positive association with global CNVs (r = 0.318, p = 0.016). In conclusion, DNA fibre analysis performed with fresh primary breast cancer samples is feasible. Fibre lengths were associated with pRPA expression. Cyclin E1 expression was associated with pRPA and the percentage of CNVs. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Subject(s)
Breast Neoplasms , Cyclin E , DNA Replication , Humans , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Cyclin E/genetics , Cyclin E/metabolism , DNA Replication/genetics , Polymorphism, Single Nucleotide , Cell Proliferation , DNA Copy Number Variations , Middle Aged , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Oncogene Proteins/genetics , Oncogene Proteins/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Aged , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , AdultABSTRACT
Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.
Subject(s)
Biomarkers , Cellular Senescence , Computational Biology , Fibroblasts , Skin Aging , Humans , Skin Aging/genetics , Fibroblasts/metabolism , Biomarkers/metabolism , Machine Learning , Transcriptome , Collagen/metabolism , Down-Regulation , Skin/metabolism , Ultraviolet Rays , Hydrogen Peroxide/metabolismABSTRACT
BACKGROUND: EV71 is one of the important pathogens of Hand-foot-and-mouth disease (HFMD), which causes serious neurological symptoms. Several studies have speculated that there will be interaction between 5'UTR and 3D protein. However, whether 5'UTR interacts with the 3D protein in regulating virus replication has not been clarified. METHODS: Four 5'UTR mutation sites (nt88C/T, nt90-102-3C, nt157G/A and nt574T/A) and two 3D protein mutation sites (S37N and R142K) were mutated or co-mutated using virulent strains as templates. The replication of these mutant viruses and their effect on autophagy were determined. RESULTS: 5'UTR single-point mutant strains, except for EGFP-EV71(nt90-102-3C), triggered replication attenuation. The replication ability of them was weaker than that of the parent strain the virulent strain SDLY107 which is the fatal strain that can cause severe neurological complications. While the replication level of the co-mutant strains showed different characteristics. 5 co-mutant strains with interaction were screened: EGFP-EV71(S37N-nt88C/T), EGFP-EV71(S37N-nt574T/A), EGFP-EV71(R142K-nt574T/A), EGFP-EV71(R142K-nt88C/T), and EGFP-EV71(R142K-nt157G/A). The results showed that the high replicative strains significantly promoted the accumulation of autophagosomes in host cells and hindered the degradation of autolysosomes. The low replicative strains had a low ability to regulate the autophagy of host cells. In addition, the high replicative strains also significantly inhibited the phosphorylation of AKT and mTOR. CONCLUSIONS: EV71 5'UTR interacted with the 3D protein during virus replication. The co-mutation of S37N and nt88C/T, S37N and nt574T/ A, R142K and nt574T/A induced incomplete autophagy of host cells and promoted virus replication by inhibiting the autophagy pathway AKT-mTOR. The co-mutation of R142K and nt88C/T, and R142K and nt157G/A significantly reduced the inhibitory effect of EV71 on the AKT-mTOR pathway and reduced the replication ability of the virus.
Subject(s)
5' Untranslated Regions , Enterovirus A, Human , Proto-Oncogene Proteins c-akt , TOR Serine-Threonine Kinases , Virus Replication , Enterovirus A, Human/genetics , Enterovirus A, Human/physiology , Enterovirus A, Human/pathogenicity , 5' Untranslated Regions/genetics , Humans , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Autophagy , Animals , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Signal Transduction , Chlorocebus aethiops , Mutation , Cell Line , Vero CellsABSTRACT
Background: Inducible co-stimulator (ICOS) shows great potential in the regulation of innate and adaptive immunity. However, previous studies of ICOS have often been limited to one or two levels. Methods: Using the data from the online database, the immunohistochemistry, and enzyme-linked immunosorbent assays, we investigated the role of ICOS / PD-L1 on patients with NSCLC at the mRNA, protein, and serum levels. Results: Our data revealed that unlike most solid tumors, the mRNA expression of ICOS was down-regulated in NSCLC. In addition, our data also showed that mRNA expression levels in ICOS are negatively associated with poor clinicopathologic grading but positively associated with better prognostic outcomes and higher Tregs infiltration level. Immunohistochemistry showed that ICOS correlated negatively with the T stage; while PD-L1 levels correlated positively with the N stage and FOXP3 levels. Serological biomarker analysis showed that patients with NSCLC had lower sICOS levels, which increased significantly post-surgery, and combined sICOS and sPD-L1 diagnosis improved efficacy and accuracy of disease diagnosis. Conclusion: Our findings support that ICOS suggests lower pathological staging and better prognosis. ICOS is a potential diagnostic and prognostic biomarker for NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , B7-H1 Antigen/genetics , Prognosis , Multiomics , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , RNA, Messenger/genetics , Biomarkers , Inducible T-Cell Co-Stimulator Protein/geneticsABSTRACT
Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.
Subject(s)
MicroRNAs , Pulmonary Fibrosis , Humans , Mice , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , Alveolar Epithelial Cells , Epithelial-Mesenchymal Transition/genetics , Cyclin-Dependent Kinase 8/metabolism , Cell Adhesion Molecules/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolismABSTRACT
OBJECTIVE: To assess the correlation between lesion location and swallowing function characteristics in post-stroke dysphagia (PSD) patients. MATERIALS AND METHODS: We enrolled 133 PSD. The patients were divided into supratentorial and infratentorial stroke groups. We compared the measurements in the videofluoroscopic swallowing study (VFSS) with 3ml and 5 ml of diluted and thickened barium liquid data between supratentorial and brainstem stroke groups. We further compared the difference of VFSS measurements between patients with left hemispheric or right hemispheric lesions (further divided into unilateral hemispheric cortical and subcortical subgroups) and brianstem leison stroke group.To explore the lesion location's effect on different bolus volume, the VFSS measurements of 3ml and 5ml in each subgroups were compared respectively. The measurements of VFSS included the oral transit time, soft palate elevation duration, hyoid bone movement duration (HMD), UES opening duration, pharyngeal transit duration (PTD), stage of ansition duration, and laryngeal closure duration (LCD), the upper esophageal sphincter opening (UESO), hyoid bone superior horizontal displacement, and hyoid bone anterior horizontal displacement. General swallowing function was assessed using the Penetration Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). We performed the paired t-test, Spearman's correlation, and Kruskal-Wallis test analysis to characterize the parameters among the groups. RESULTS: Fifty-eight patients were assessed in the final analysis. The HMD (p = 0.019), PTD (p = 0.048) and LCD (p = 0.013) were significantly different between the supratentorial and brainstem lesion groups in 5ml volume. The HMD was significantly different (p = 0.045) between the left cortical and brainstem lesion groups. Significant differences in the HMD (p = 0.037) and LCD (p = 0.032) between the left subcortical and brainstem lesion groups were found in 5ml volume bolus. There was no group different when taking the 3ml volume bolus. Regarding the relationship between food bolus volume and swallowing functions, only the UESO demonstrated a significant difference in the subcortical lesion of the right hemisphere (p = 0.0032) compared the 3 ml and 5 ml volume bolus. The PTD demonstrated a moderate correlation with the PAS scores (r = 0.38, p = 0.0044). The HMD (r = 0.32, p = 0.018) and LCD (r = 0.29, p = 0.039) demonstrated weak correlations with the PAS scores. We did not identify any correlation between the VFSS parameters and FOIS scores in each subgroup level. CONCLUSION: The PSD with brainstem lesion shows more sever dysfunction in the pharyngeal phases. The left hemisphere was engaged in both the oral and pharyngeal phases. Lesions in the bilateral cortical, subcortical, and brainstem regions may impair sensory input.
Subject(s)
Deglutition Disorders , Deglutition , Stroke , Video Recording , Humans , Deglutition Disorders/physiopathology , Deglutition Disorders/etiology , Deglutition Disorders/diagnosis , Deglutition Disorders/diagnostic imaging , Male , Female , Aged , Middle Aged , Stroke/physiopathology , Stroke/complications , Stroke/diagnosis , Fluoroscopy , Predictive Value of Tests , Aged, 80 and over , Time Factors , Risk Factors , Retrospective StudiesABSTRACT
Red guava, distinguished by its elevated lycopene content, emerges as a promising natural source of carotenoids. This study systematically evaluates the impact of diverse processing techniques on the efficient release of carotenoids. The primary objective is to facilitate the transfer of carotenoids into the juice fraction, yielding carotenoid-enriched juice seamlessly integrable into aqueous-based food matrices. The untreated guava puree exhibited a modest release of carotenoids, with only 66.26% of ß-carotene and 57.08% of lycopene reaching the juice. Contrastly, both high-pressure homogenization (HPH) at 25 MPa and enzyme (EM) treatment significantly enhanced carotenoid release efficiency (p < 0.05), while high hydrostatic pressure (HHP) at 400 MPa and pulsed electric field (PEF) of 4 kV/cm did not (p > 0.05). Notably, HPH demonstrated the most substantial release effect, with ß-carotene and lycopene reaching 90.78% and 73.85%, respectively. However, the stability of EM-treated samples was relatively poor, evident in a zeta-potential value of -6.51 mV observed in the juice. Correlation analysis highlighted the interactions between pectin and carotenoids likely a key factor influencing the stable dissolution or dispersion of carotenoids in the aqueous phase. The findings underscore HPH as a potent tool for obtaining carotenoid-enriched guava juice, positioning it as a desirable ingredient for clean-label foods.
Subject(s)
Psidium , beta Carotene , Lycopene , Carotenoids , ElectricityABSTRACT
Point-of-care testing (POCT), with its portability and high sensitivity, is an analytical device for rapid on-site sensing and detection. In this study, a POCT device was designed for the portable detection of illegal additives by integrating a coil device that can visually sense color distance and a two-electrode electrochemical system. Real-time monitoring of pressure changes was achieved by driving CeO2@Pt/Au nanoparticle (NP)-labeled antibodies into a competitive immunoreaction, in which CeO2 and Pt/Au synergistically catalyzed the production of large amounts of O2 from H2O2, leading to a significant increase in gas within the closed chamber. Attractively, the coil device converted the pressure stimulus into visually readable change in distance for semi-quantitative detection of the target substance, while the electrical signal output caused by the changes of the solution around the electrodes achieved accurate and reliable quantification of the target. In addition, the proposed dual-mode pressure immunoassay device has acceptable selectivity, stability, and reproducibility. Herein, this portable device, which enables target concentration readings by converting pressure into multiple signals, provides an effective way to visualize POCT assays in resource-limited areas.
Subject(s)
Biosensing Techniques , Metal Nanoparticles , Point-of-Care Systems , Gold/chemistry , Hydrogen Peroxide/chemistry , Reproducibility of Results , Metal Nanoparticles/chemistry , Limit of Detection , ImmunoassayABSTRACT
Inspired by the molecular crowding effect in biological systems, a novel heterogeneous quadratic amplification molecular circuit (HEQAC) was developed for sensitive bimodal miRNA profiling (HEQAC-BMP) by combining an MNAzyme-based DNA nanomachine with an entropy-driven catalytic hairpin assembly (E-CHA) autocatalytic circuit. Utilizing ferromagnetic nanomaterials as the substrate for DNA nanomachines, a biomimetic heterogeneous interface was established; thus, a localized molecular crowding system was created that can elevate the local reaction concentration and accelerate the molecular recognition process for a significant threshold signal. Simultaneously, the threshold signal undergoes further amplification by E-CHA and is transformed into a chemical signal, enabling a colorimetric-fluorescence bimodal signal readout. The HEQAC-BMP enables miRNA detection from 10 aM to 10 nM with detection limits of 3.7 aM (colorimetry) and 4.8 aM (fluorometry), respectively. Moreover, the design principle and strategy of HEQAC-BMP can be customized to address other critical viruses or diseases with life-threatening and socioeconomic impacts, enhancing healthcare outcomes for individuals.
ABSTRACT
The medicinal fungus Wolfiporia cocos colonizes and then grows on the wood of Pinus species, and utilizes a variety of Carbohydrate Active Enzymes (CAZymes) to degrades wood for the development of large sclerotia that is mostly built up of beta-glucans. Some differentially expressed CAZymes were revealed by comparisons between the mycelia cultured on potato dextrose agar (PDA) and sclerotia formed on pine logs in previous studies. Here, different profile of expressed CAZymes were revealed by comparisons between the mycelia colonization on pine logs (Myc.) and sclerotia (Scl.b). To further explore the regulation and function of carbon metabolism in the conversion of carbohydrates from Pine species by W. cocos, the transcript profile of core carbon metabolism was firstly analyzed, and it was characterized by the up-regulated expression of genes in the glycolysis pathway (EMP) and pentose phosphate pathway (PPP) in Scl.b, as well as high expression of genes in the tricarboxylic acid cycle (TCA) in both Myc. and Scl.b stages. The conversion between glucose and glycogen and between glucose and ß-glucan was firstly identified as the main carbon flow in the differentiation process of W. cocos sclerotia, with a gradual increase in the content of ß-glucan, trehalose and polysaccharide during this process. Additionally, gene functional analysis revealed that the two key genes (PGM and UGP1) may mediate the formation and development of W. cocos sclerotia possibly by regulating ß-glucan synthesis and hyphal branching. This study has shed light on the regulation and function of carbon metabolism during large W. cocos sclerotium formation and may facilitate its commercial production.
Subject(s)
Wolfiporia , Wolfiporia/genetics , Wolfiporia/metabolism , Carbon/metabolism , Mycelium , Glucose/metabolismABSTRACT
Herbivore-induced plant defence responses share common components with plant responses to abiotic stresses. However, whether abiotic stress-responsive factors influence the resistance of plants to herbivores by regulating these components remains largely unknown. Here, we cloned a dehydration-responsive element-binding gene in rice, OsDREB1A, and investigated its role in the resistance of rice to the phloem-feeding herbivore, brown planthopper (BPH, Nilaparvata lugens), under normal and low temperatures. We found that OsDREB1A localized to the nucleus, and its transcripts in rice were up-regulated in response to BPH infestation, low temperatures and treatment with methyl jasmonate or salicylic acid. Silencing OsDREB1A changed transcript levels of two defence-related WRKY and two PLD genes, enhanced levels of jasmonic acid (JA), JA-isoleucine and abscisic acid, and decreased the ethylene level in rice; these changes subsequently enhanced the resistance of plants to BPH, especially at 17°C, by decreasing the hatching rate and delaying the development of BPH eggs. Moreover, silencing OsDREB1A increased the growth of rice plants. These findings suggest that OsDREB1A, which positively regulates the resistance of rice to abiotic stresses, negatively regulates the resistance of rice to BPH.
Subject(s)
Hemiptera , Oryza , Animals , Cyclopentanes/pharmacology , Dehydration , Gene Expression Regulation, Plant , Hemiptera/physiology , Herbivory , Oryza/physiology , Oxylipins/pharmacology , Phloem/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/metabolismABSTRACT
The application of pressure can achieve novel structures and exotic phenomena in condensed matters. However, such pressure-induced transformations are generally reversible and useless for engineering materials for ambient-environment applications. Here, we report comprehensive high-pressure investigations on a series of Dion-Jacobson (D-J) perovskites A'A n-1Pb n I3n+1 [A' = 3-(aminomethyl) piperidinium (3AMP), A = methylammonium (MA), n = 1, 2, 4]. Our study demonstrates their irreversible behavior, which suggests pressure/strain engineering could viably improve light-absorber material not only in situ but also ex situ, thus potentially fostering the development of optoelectronic and electroluminescent materials. We discovered that the photoluminescence (PL) intensities are remarkably enhanced by one order of magnitude at mild pressures. Also, higher pressure significantly changes the lattices, boundary conditions of electronic wave functions, and possibly leads to semiconductor-metal transitions. For (3AMP)(MA)3Pb4I13, permanent recrystallization from 2D to three-dimensional (3D) structure occurs upon decompression, with dramatic changes in optical properties.
ABSTRACT
Nanozymes and cyclic GMP-AMP synthase (cGAS) the stimulator of interferon genes (STING) signaling pathway, as powerful organons, can remodel the tumor microenvironment (TME) to increase efficacy and overcome drug resistance in cancer immunotherapy. Nanozymes have the potential to manipulate the TME by producing reactive oxygen species (ROS), which lead to positive oxidative stress in tumor cells. Cyclic dinucleotide (2',3'-cGAMP), as a second messenger, exists in the TME and can regulate it to achieve antitumor activity. In this work, Co,N-doped carbon dots (CoNCDs) were used as a model nanozyme to evaluate the properties of the anti-tumor mechanism, and effective inhibition of S180 tumor was achieved. Based on CoNCDs' good biocompatibility and therapeutic effect on the tumor, we then introduced the cGAS-STING agonist, and the combination of the CoNCDs and STING agonist significantly inhibited tumor growth, and no significant systemic toxicity was observed. The combined system achieved the enhanced tumor synergistic immunotherapy through TME reprogramming via the peroxidase-like activity of the CoNCDs and cGAS-STING signaling pathway agonist synergistically. Our work provides not only a new effective way to reprogram TME in vivo, but also a promising synergic antitumor therapy strategy.
Subject(s)
Neoplasms , Tumor Microenvironment , Signal Transduction , Second Messenger Systems , Immunotherapy , Carbon , Nucleotidyltransferases , Neoplasms/therapyABSTRACT
Allylic alcohols typically produced through selective hydrogenation of α,ß-unsaturated aldehydes are important intermediates in fine chemical industry, but it is still a challenge to achieve its high selectivity transformation. Herein, we report a series of TiO2-supported CoRe bimetallic catalysts for the selective hydrogenation of cinnamaldehyde (CAL) to cinnamyl alcohol (COL) using formic acid (FA) as a hydrogen donor. The resultant catalyst with the optimized Co/Re ratio of 1:1 can achieve an exceptional COL selectivity of 89% with a CAL conversion of 99% under mild conditions of 140 °C for 4 h, and the catalyst can be reused four times without loss of activity. Meanwhile, the Co1Re1/TiO2/FA system was efficient for the selective hydrogenation of various α,ß-unsaturated aldehydes to the corresponding α,ß-unsaturated alcohols. The presence of ReOx on the Co1Re1/TiO2 catalyst surface was advantageous to the adsorption of C=O, and the ultrafine Co nanoparticles provided abundant hydrogenation active sites for the selective hydrogenation. Moreover, FA as a hydrogen donor improved the selectivity to α,ß-unsaturated alcohols.
ABSTRACT
Mycotoxin contamination in foods and other goods has become a broad issue owing to serious toxicity, tremendous threat to public safety, and terrible loss of resources. Herein, it is necessary to develop simple, sensitive, inexpensive, and rapid platforms for the detection of mycotoxins. Currently, the limitation of instrumental and chemical methods cannot be massively applied in practice. Immunoassays are considered one of the best candidates for toxin detection due to their simplicity, rapidness, and cost-effectiveness. Especially, the field of dual-mode immunosensors and corresponding assays is rapidly developing as an advanced and intersected technology. So, this review summarized the types and detection principles of single-mode immunosensors including optical and electrical immunosensors in recent years, then focused on developing dual-mode immunosensors including integrated immunosensors and combined immunosensors to detect mycotoxins, as well as the combination of dual-mode immunosensors with a portable device for point-of-care test. The remaining challenges were discussed with the aim of stimulating future development of dual-mode immunosensors to accelerate the transformation of scientific laboratory technologies into easy-to-operate and rapid detection platforms.
Subject(s)
Biosensing Techniques , Mycotoxins , Mycotoxins/analysis , Biosensing Techniques/methods , Immunoassay/methods , FoodABSTRACT
Food protein-derived peptides have garnered considerable attention due to their potential bioactivities and functional properties. However, the limited activity poses a challenge in effective utilization aspects. To overcome this hurdle, various methods have been explored to enhance the activity of these peptides. This comprehensive review offers an extensive overview of pretreatment, preparation methods, and modification strategies employed to augment the activity of food protein-derived peptides. Additionally, it encompasses a discussion on the current status and future prospects of bioactive peptide applications. The review also addresses the standardization of mass production processes and safety considerations for bioactive peptides while examining the future challenges and opportunities associated with these compounds. This comprehensive review serves as a valuable guide for researchers in the food industry, offering insights and recommendations to optimize the production process of bioactive peptides.
Subject(s)
Food , Peptides , Peptides/chemistryABSTRACT
BACKGROUND: This study is to evaluate and compare the improvement of upper airway morphology and hyoid bone position in children with Class II mandibular retrusion treated with Invisalign mandibular advancement (MA) and Twin-Block (TB) appliances, utilizing cone beam computed tomography (CBCT). METHODS: 32 children aged between 8 and 11.5 years old were included in this study, with an average age of 10.2 years old. These children were divided into two groups, MA and TB, with 16 children in each group. Changes in upper airway morphology and hyoid bone position before and after treatment were analyzed using CBCT. RESULTS: (1) Changes in upper airway before and after treatment: the oropharynx volume (Or-V), the oropharynx minimum cross-sectional area (Or-mCSA), the hypopharynx volume (Hy-V), and the hypopharynx minimum cross-sectional area (Hy-mCSA) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05) compared to pre-treatment status. (2) Changes in hyoid bone position before and after treatment: The distances between H point and third cervical vertebra (H-C3), H point and pogonion (H-RGN), H point and mandibular plane (H-MP), H point and Frankfort horizontal plane (H-FH), H and S point (H-S), and H point and palatal plane (H-PP) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05). CONCLUSION: Both MA and TB appliances effectively improved the structural narrowness of the upper airway and reduced respiratory resistance, thus improving breath quality. However, MA showed more effectiveness in improving the narrowest part of the hypopharynx compared to TB. Both appliances also promoted anterior downward movement of the hyoid bone, which opens the upper airway of the oropharynx and hypopharynx and helps the upper airway morphology return to normal range.