ABSTRACT
Telomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating. We measured the telomere length and telomerase activity of mouse cardiomyocytes (CMs) at different days of age, and the results showed that they were negatively correlated with age. Overexpressed Tert could enhance telomerase activity and lengthen telomeres, thereby repairing the DNA damage induced by ROS and promoting CM proliferation in vitro. The in vivo results indicated that enhanced Tert could significantly improve cardiac function and prognosis by alleviating CM DNA damage and promoting angiogenesis post-MI. In terms of mechanism, DNA pulldown assay was used to identify that nuclear ribonucleoprotein A2B1 (hnRNPA2B1) could be an upstream regulator of Tert in CMs. Overexpressed Tert could activate the NF-κB signaling pathway in CMs and bind to the VEGF promoter in the endothelium to increase the VEGF level. Further immunoblotting showed that Tert protected DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking the Chk1/p53/p21 pathway activation. HnRNPA2B1-activated Tert could repair the ROS-induced telomeric DNA damage to induce the cell cycle re-entry in CMs and enhance the interaction between CMs and endothelium, thus achieving cardiac regenerative repair after MI.
ABSTRACT
In this paper, we explore the distribution of the orbital angular momentum (OAM) in the coaxial vortex superposition states based on the independent propagation principle of light in this interference process. We find that in this case, some specific singular points exist in the spatial intensity distribution. The first type of singular point is located at the center point of the spatial intensity distribution. The second type of specific singular point is at the critical location of the overlapping area in angular direction. By analogy with the angular momentum superposition of two axially rotating homogeneous disks with different radius in rigid body, We present a suggestion: the center point is located at the overlapping area of all the superposed components. Therefore, the topological charge value in the center point should be doubled by the actual number of superposition field components. The singular point at the critical location of the overlapping area in angular direction should also be co-owned by the superposition components outside the position of the ring (including the corresponding component of the ring). The total OAM is exactly equal to the sum of those two types contained in the superposition states, which is equal to the input OAM of the superposition state components. The conservation of the OAM in the coaxial interference process is demonstrated.
ABSTRACT
We theoretically propose and demonstrate topological parabolic umbilic beams (PUBs) with high-dimensional caustic by mapping catastrophe theory into optics. The PUBs are first experimentally observed via dimensionality reduction. Due to the high-dimensionality, such light beams exhibit rich caustic structures characterized by optical singularities where the high-intensity gradient appears. Further, we propose an improved caustic approach to artificially tailored structured beams which exhibit significant intensity gradient and phase gradient. The properties can trap and drive particles to move along the predesigned trajectory, respectively. The advantages for structured caustic beams likely enable new applications in flexible particle manipulation, light-sheet microscopy, and micromachining.
ABSTRACT
The abnormal aggregation of Aß has been considered one of the primary causative factors for Alzheimer's disease. Diverse molecular entities have been developed to mitigate the formation of toxic Aß aggregates within the brain by inhibiting Aß aggregation. Recognizing that many FDA-approved drugs are derived from natural products, we present a summary of recent discoveries involving natural product molecules with inhibitory effects on Aß aggregation. By consolidating these findings, our review offers researchers a concise overview of the latest advancements in natural product-based interventions for Alzheimer's disease.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biological Products , Protein Aggregates , Biological Products/chemistry , Biological Products/pharmacology , Biological Products/chemical synthesis , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Protein Aggregates/drug effects , Molecular StructureABSTRACT
INTRODUCTION: Sympathetic hyperinnervation plays an important role in modulating the vascular smooth muscle cell (VSMC) phenotype and vascular diseases, but its role in abdominal aortic aneurysm (AAA) is still unknown. OBJECTIVES: This study aimed to investigate the role of sympathetic hyperinnervation in promoting AAA development and the underlying mechanism involved. METHODS: Western blotting and immunochemical staining were used to detect sympathetic hyperinnervation. We performed sympathetic denervation through coeliac ganglionectomy (CGX) and 6-OHDA administration to understand the role of sympathetic hyperinnervation in AAA and investigated the underlying mechanisms through transcriptome and functional studies. Sema4D knockout (Sema4D-/-) mice were utilized to determine the involvement of Sema4D in inducing sympathetic hyperinnervation and AAA development. RESULTS: We observed sympathetic hyperinnervation, the most important form of sympathetic neural remodeling, in both mouse AAA models and AAA patients. Elimination of sympathetic hyperinnervation by CGX or 6-OHDA significantly inhibited AAA development and progression. We further revealed that sympathetic hyperinnervation promoted VSMC phenotypic switching in AAA by releasing extracellular ATP (eATP) and activating eATP-P2rx4-p38 signaling. Moreover, single-cell RNA sequencing revealed that Sema4D secreted by osteoclast-like cells induces sympathetic nerve diffusion and hyperinnervation through binding to Plxnb1. We consistently observed that AAA progression was significantly ameliorated in Sema4D-deficient mice. CONCLUSIONS: Sympathetic hyperinnervation driven by osteoclast-like cell-derived Sema4D promotes VSMC phenotypic switching and accelerates pathological aneurysm progression by activating the eATP/P2rx4/p38 pathway. Inhibition of sympathetic hyperinnervation emerges as a potential novel therapeutic strategy for preventing and treating AAA.
ABSTRACT
Optical vortex (OV) modulation is a powerful technique for enhancing the intrinsic degrees-of-freedom in structured light applications. Particularly, the lattices involving multiple OVs have garnered significant academic interest owing to their wide applicability in optical tweezers and condensed matter physics. However, all OVs in a lattice possess the same order, which cannot be modulated individually, limiting its versatile application. Herein, we propose, to our knowledge, a novel concept, called the hot-swap method, to design a switchable hybrid-order OV lattice, in which each OV is easily replaced by arbitrary orders. We experimentally generated the switchable hybrid-order OV lattice and studied its characteristics, including interferograms, retrieved phase, energy flow, and orbital angular momentum. Furthermore, the significant advantages of the switchable hybrid-order OV lattice are demonstrated through the independent manipulation of multiple yeast cells. This study provides a novel scheme for accurate control and modulation of OV lattices, which greatly facilitates the diverse applications of optical manipulation and particle trapping and control.
ABSTRACT
Optical vortex arrays (OVAs) are complex light fields with versatile structures that have been widely studied in large-capacity optical communications, optical tweezers, and optical measurements. However, generating OVAs with arbitrary structures without explicit analytical expressions remains a challenge. To address this issue, we propose an alternative scheme for customizing OVAs with arbitrary structures using an epicycle model and vortex localization techniques. This method can accurately generate an OVA with an arbitrary structure by pre-designing the positions of each vortex. The influence of the number and coordinates of the locating points on customized OVAs is discussed. Finally, the structures of the OVA and each vortex are individually shaped into specifically formed fractal shapes by combining cross-phase techniques. This unique OVA will open up novel potential applications, such as the complex manipulation of multiparticle systems and optical communication based on optical angular momentum.
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Peptide toxins found in sea anemones venom have diverse properties that make them important research subjects in the fields of pharmacology, neuroscience and biotechnology. This study used high-throughput sequencing technology to systematically analyze the venom components of the tentacles, column, and mesenterial filaments of sea anemone Heteractis crispa, revealing the diversity and complexity of sea anemone toxins in different tissues. A total of 1049 transcripts were identified and categorized into 60 families, of which 91.0% were proteins and 9.0% were peptides. Of those 1049 transcripts, 416, 291, and 307 putative proteins and peptide precursors were identified from tentacles, column, and mesenterial filaments respectively, while 428 were identified when the datasets were combined. Of these putative toxin sequences, 42 were detected in all three tissues, including 33 proteins and 9 peptides, with the majority of peptides being ShKT domain, ß-defensin, and Kunitz-type. In addition, this study applied bioinformatics approaches to predict the family classification, 3D structures, and functional annotation of these representative peptides, as well as the evolutionary relationships between peptides, laying the foundation for the next step of peptide pharmacological activity research.
Subject(s)
Cnidarian Venoms , Sea Anemones , Animals , Humans , Sea Anemones/metabolism , Peptides/chemistry , Gene Expression Profiling , Cnidarian Venoms/chemistryABSTRACT
Stellera chamaejasme (S. chamaejasme) is an important medicinal plant with heat-clearing, detoxifying, swelling and anti-inflammatory effects. At the same time, it is also one of the iconic plants of natural grassland degradation in northwest China, playing a key role in the invasion process. Plant endophytes live in healthy plant tissues and can synthesize substances needed for plant growth, induce disease resistance in host plants, and enhance plant resistance to environmental stress. Therefore, studying the root endophytes of S. chamaejasme is of great significance for mining beneficial microbial resources and biological prevention and control of S. chamaejasme. This study used Illumina MiSeq high-throughput sequencing technology to analyze the composition and diversity of endophytes in the roots of S. chamaejasme in different alpine grasslands (BGC, NMC and XGYZ) in Tibet. Research results show that the main phylum of endophytic fungi in the roots of S. chamaejasme in different regions is Ascomycota, and the main phyla of endophytic bacteria are Actinobacteria, Proteobacteria and Firmicutes (Bacteroidota). Overall, the endophyte diversity of the NMC samples was significantly higher than that of the other two sample sites. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) results showed significant differences in the composition of endophytic bacterial and fungal communities among BGC, NMC and XGYZ samples. Co-occurrence network analysis of endophytes showed that there were positive correlations between fungi and some negative correlations between bacteria, and the co-occurrence network of bacteria was more complex than that of fungi. In short, this study provides a vital reference for further exploring and utilizing the endophyte resources of S. chamaejasme and an in-depth understanding of the ecological functions of S. chamaejasme endophytes.
Subject(s)
Actinobacteria , Thymelaeaceae , Endophytes/genetics , High-Throughput Nucleotide Sequencing , Thymelaeaceae/genetics , Analysis of VarianceABSTRACT
Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.
Subject(s)
Interleukin-10 , Myocardial Infarction , Adult , Humans , Interleukin-10/genetics , Optogenetics , Myocardial Infarction/therapy , Vagus Nerve , Myocytes, CardiacABSTRACT
The Meconopsis species are widely distributed in the Qinghai-Tibet Plateau, Himalayas, and Hengduan Mountains in China, and have high medicinal and ornamental value. The high diversity of plant morphology in this genus poses significant challenges for species identification, given their propensity for highland dwelling, which makes it a question worth exploring how they cope with the harsh surroundings. In this study, we recently generated chloroplast (cp) genomes of two Meconopsis species, Meconopsis paniculata (M. paniculata) and M. pinnatifolia, and compared them with those of ten Meconopsis cp genomes to comprehend cp genomic features, their phylogenetic relationships, and what part they might play in plateau adaptation. These cp genomes shared a great deal of similarities in terms of genome size, structure, gene content, GC content, and codon usage patterns. The cp genomes were between 151,864 bp and 154,997 bp in length, and contain 133 predictive genes. Through sequence divergence analysis, we identified three highly variable regions (trnD-psbD, ccsA-ndhD, and ycf1 genes), which could be used as potential markers or DNA barcodes for phylogenetic analysis. Between 22 and 38 SSRs and some long repeat sequences were identified from 12 Meconopsis species. Our phylogenetic analysis confirmed that 12 species of Meconopsis clustered into a monophyletic clade in Papaveraceae, which corroborated their intrageneric relationships. The results indicated that M. pinnatifolia and M. paniculata are sister species in the phylogenetic tree. In addition, the atpA and ycf2 genes were positively selected in high-altitude species. The functions of these two genes might be involved in adaptation to the extreme environment in the cold and low CO2 concentration conditions at the plateau.
Subject(s)
Genome, Chloroplast , Papaveraceae , Sequence Analysis, DNA , Phylogeny , Genomics/methods , Papaveraceae/genetics , Evolution, MolecularABSTRACT
Meconopsis bella Prain 1894 (M. bella) is a rare herb within the family Papaveraceae of which unique and gorgeous purple flowers are blooming in the flowering phase. In this study, we reported the complete chloroplast (cp) genome of M. bella, which was mainly distributed on the Qinghai-Tibet plateau. The complete chloroplast genome sequence of M. bella was 153,073 bp in size and was characterized by a typical quadripartite structure consisting of a large single-copy (LSC) region of 83,562 bp, a small single-copy (SSC) region of 178,33 bp and two identical inverted repeats (IR) regions of 25,839 bp. The genome contained 133 genes, including 88 protein-encoding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. Phylogenetic analysis based on the maximum-likelihood (ML) method showed that M. bella was closely related to M. paniculate and M. pinnatifolia within the genus Meconopsis.
ABSTRACT
Background: Pulsed-field ablation using annular or petal-shaped catheters had been proven to be effective for achieving electrical isolation of pulmonary veins in patients with atrial fibrillation. However, the utilization of linear pulse-field power for treating atrial flutter has yet to been documented. Case summary: In this report, we present a case involving the successful treatment of tricuspid isthmus-dependent atrial flutter treated with a linear pulsed-field catheter. The patient, a 71-year-old male, presents with an electrocardiogram indicating atrial flutter. Subsequent electrophysiological examination reveals typical atrial flutter that is dependent on the cavo-tricuspid isthmus (CTI). This condition is successfully terminated through the application of linear pulsed-field ablation. Discussion: This case represents a pioneering instance of CTI-dependent atrial flutter ablation utilizing linear pulse-field power. The innovative approach not only effectively treats the patient but also serves as a valuable reference for future applications of linear treatment with pulsed-field ablation.
ABSTRACT
In clinical practice, it is frequently observed that cardiac and psychological disorders frequently co-occur, leading to the emergence of a field known as cardiovascular disease with depression. Depression, in particular, poses a remarkable risk for the evolution of cardiovascular disease and intimately relates to adverse cardiovascular outcomes and mortality. Moreover, individuals who are depressed exhibit a higher susceptibility to developing cardiovascular disease compared to those in good health. Patients diagnosed with cardiovascular disease with depression disease face a heightened risk of mortality within a 5-year timeframe, and their prognosis remains unsatisfactory even after receiving treatment targeting a single disorder, with a notable recurrence rate. Psychological interventions in conjunction with medications are commonly employed in clinical settings for treating patients with cardiovascular disease and depression diseases, albeit with limited effectiveness and unfavorable prognosis. Traditional Chinese medicine (TCM), such as Shuangxinfang, Chaihujialonggumuli, and Yixin Ningshen Tablet, etc., have been reported and have Therapeutic effects in patients with cardiovascular disease combined with depression. Despite numerous articles documenting a notable association between heart disease and depression, there exists a dearth of studies elucidating the precise pathogenesis and target of action for cardiovascular disease with depression diseases. This article endeavors to consolidate the epidemiological data, potential pathogenic mechanisms, and available treatment modalities for cardiovascular disease with depression diseases. Its primary objective is to unveil plausible co-morbid mechanisms and suitable treatment approaches, thereby offering novel insights for the prevention, diagnosis, and management of cardiovascular disease with depression diseases.
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The optical spin-orbit Hall effect manifests the separation of the spin angular momentum (SAM) and the orbital angular momentum (OAM), yet it can be obtained for the radially polarized light and well controlled by the initial phase of the polarization state which leads to the twist of its distribution. In this paper, we introduce the polarization helicity to characterize the effect of the initial phase of the polarization states in the optical spin-orbit Hall effect. We find the polarization helicity of the radial polarization state can be modulated by changing its initial phase, and the polarization helicity of the high-order polarization state always is zero. We show that the separation magnitude of the SAM and the OAM reach the maximum value when the initial phase of the radial polarization state equals π/4 (or -π/4). The sign of the SAM and the OAM are determined by the polarization helicity of incident light and the anisotropy of uniaxial crystal, and its evolution follows a sinusoidal function. Furthermore, the polarization state of the incident radially polarized light will evolve into the left-handed (or right-handed) elliptical polarization state as the change of the polarization helicity of incident light. Our studies further deepen the understanding of the spin-orbit coupling of the vector beams, and provide a potential technique for modulating the polarization state of the light in uniaxial crystal.
ABSTRACT
BACKGROUND: SMARTTOUCH SURROUNDFLOW (STSF) catheter is the new generation of SMARTTOUCH (ST) catheter with an upgraded irrigation system for radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF). METHODS: This systematic literature review searched the major English and Chinese bibliographic databases from 2016 to 2022 for any original clinical studies assessing the STSF catheter for RFCA in AF patients. Meta-analysis with a random effects model was used for evidence synthesis. RESULTS: Pooled outcomes from 19 included studies indicated that STSF catheter was associated with a significantly shorter procedure time (weighted mean difference (WMD): -17.4 min, p<0.001), shorter ablation time (WMD: -6.6 min, p<0.001) and lower catheter irrigation fluid volume (WMD: -492.7 mL, p<0.001) than ST catheter. Pooled outcomes from four included studies with paroxysmal AF patients reported that using the STSF catheter for RFCA was associated with a significantly shorter ablation time (WMD: -5.7 min, p<0.001) and a lower risk of 1-year postablation arrhythmia recurrence (rate ratio: 0.504, p<0.001) than the SURROUNDFLOW (SF) catheter. Significant reductions in procedure time and ablation time associated with the STSF catheter were also reported in the other four studies using non-ST/SF catheters as the control. Overall complications of STSF catheter and control catheters were comparable. CONCLUSIONS: Using the STSF catheter was superior to using the ST catheter to conduct RFCA for AF by significantly reducing procedure time, ablation time, fluoroscopy time and irrigation fluid volume. The superiority of the STSF catheter over the SF catheter and other non-ST/SF catheters for RFCA needs further confirmation.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/etiology , Treatment Outcome , Catheters , Catheter Ablation/methods , Time Factors , RecurrenceABSTRACT
The fast and accurate solution of integer ambiguity is the key to achieve GNSS high-precision positioning. Based on the lattice theory of high-dimensional ambiguity solving, the reduction time consumption is much larger than the search time consumption, and it is especially important to improve the efficiency of the lattice basis reduction algorithm. The Householder QR decomposition with minimal column pivoting is utilized to pre-sort the basis vectors and reduce the number of basis vector exchanges during the reduction process by partial size reduction and relaxing the basis vector exchange condition to improve the reduction efficiency of the LLL algorithm. The improved algorithm is validated using simulated and measured data, respectively, and the performance advantages and disadvantages of the improved algorithm are evaluated from the perspectives of the extent of reduction basis orthogonality and the quality of reduction basis size reduction. The results show that the improved LLL algorithm can significantly reduce the number of basis vector exchanges and the reduction time consumption. The HSLLL and PSLLL algorithms with the Siegel condition as the basis vector exchange condition have a better reduction effect, but are slightly less stable. The PLLLR algorithm significantly improves the search ambiguity resolution efficiency, which is conducive to the rapid realization of ambiguity resolution.
ABSTRACT
As the population ages, neurodegenerative diseases are becoming more prevalent, making it crucial to comprehend the underlying disease mechanisms and identify biomarkers to allow for early diagnosis and effective screening for clinical trials. Thanks to advancements in gene expression profiling, it is now possible to search for disease biomarkers on an unprecedented scale.Here we applied a selection of five machine learning (ML) approaches to identify blood-based biomarkers for Alzheimer's (AD) and Parkinson's disease (PD) with the application of multiple feature selection methods. Based on ROC AUC performance, one optimal random forest (RF) model was discovered for AD with 159 gene markers (ROC-AUC = 0.886), while one optimal RF model was discovered for PD (ROC-AUC = 0.743). Additionally, in comparison to traditional ML approaches, deep learning approaches were applied to evaluate their potential applications in future works. We demonstrated that convolutional neural networks perform consistently well across both the Alzheimer's (ROC AUC = 0.810) and Parkinson's (ROC AUC = 0.715) datasets, suggesting its potential in gene expression biomarker detection with increased tuning of their architecture.
Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Parkinson Disease , Humans , Neurodegenerative Diseases/diagnosis , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Machine Learning , Biomarkers , Neural Networks, Computer , Parkinson Disease/diagnosis , Parkinson Disease/geneticsABSTRACT
We introduce a class of twisted sinc-correlation partially coherent array sources, by applying the construction theory of correlation function. Spectral density of such novel focused beam propagating in free space is analyzed. It is shown that the intensity distribution presents a good twisted effect and splitting phenomenon upon propagation. The array dimension, the intensity distribution and spatial distribution of the lobes can be flexibly regulated by altering the source parameters. We also explore the spatial evolution of multiple correlation singularities of this light field, where the phase distribution appears as a rotational spiral windmill profile during propagation. Furthermore, the coherence orbital angular momentum of the twisted source beam is investigated. These findings could be useful in the particle manipulation and free-space optical communication.