ABSTRACT
We present evidence of a strong circular photon drag effect (PDE) in topological insulators (TIs) through the observation of helicity-dependent topological photocurrents with threefold rotational symmetry using THz spectroscopy in epitaxially-grown Bi2Se3 with reduced crystallographic twinning. We establish how twinned domains introduce competing nonlinear optical (NLO) responses inherent to the crystal structure that obscure geometry-sensitive optical processes through the introduction of a spurious mirror symmetry. Minimizing the twinning defect reveals strong NLO response currents whose magnitude and direction depend on the alignment of the excitation to the crystal axes and follow the threefold rotational symmetry of the crystal. Notably, photocurrents arising from helical light reverse direction for left/right circular polarizations and maintain a strong azimuthal dependence-a result uniquely attributable to the circular PDE, where the photon momentum acts as an applied in-plane field stationary in the laboratory frame. Our results demonstrate new levels of control over the magnitude and direction of photocurrents in TIs and that the study of single-domain films is crucial to reveal hidden phenomena that couple topological order and crystal symmetries.
ABSTRACT
SERRATE (SE) is a core protein for microRNA (miRNA) biogenesis as well as for mRNA alternative splicing. Investigating the regulatory mechanism of SE expression is hence critical to understanding its detailed function in diverse biological processes. However, little about the control of SE expression has been clarified, especially through long noncoding RNA (lncRNA). Here, we identified an antisense intragenic lncRNA transcribed from the 3' end of SE, named SEAIRa. SEAIRa repressed SE expression, which in turn led to serrated leaves. SEAIRa recruited plant U-box proteins PUB25/26 with unreported RNA binding ability and a ubiquitin-like protein related to ubiquitin 1 (RUB1) for H2A monoubiquitination (H2Aub) at exon 11 of SE. In addition, PUB25/26 helped cleave SEAIRa and release the 5' domain fragment, which recruited the PRC2 complex for H3 lysine 27 trimethylation (H3K27me3) deposition at the first exon of SE. The distinct modifications of H2Aub and H3K27me3 at different sites of the SE locus cooperatively suppressed SE expression. Collectively, our results uncover an epigenetic mechanism mediated by the lncRNA SEAIRa that modulates SE expression, which is indispensable for plant growth and development.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Epigenetic Repression , RNA, Long Noncoding , RNA-Binding Proteins , Epigenesis, Genetic , Histones , RNA, Long Noncoding/genetics , Arabidopsis Proteins/genetics , RNA-Binding Proteins/geneticsABSTRACT
Aldehydes fixation was accidentally discovered in the early 20th century and soon became a widely adopted practice in the histological field, due to an excellent staining enhancement in tissues imaging. However, the fixation process itself entails cell proteins denaturation and crosslinking. The possible presence of artifacts, that depends on the specific system under observation, must therefore be considered to avoid data misinterpretation. This contribution takes advantage of scanning electron assisted-dielectric microscopy (SE-ADM) and Raman 2D imaging to reveal the possible presence and the nature of artifacts in unstained, and paraformldehyde, PFA, fixed MNT-1 cells. The high resolution of the innovative SE-ADM technique allowed the identification of globular protein clusters in the cell cytoplasm, formed after protein denaturation and crosslinking. Concurrently, SE-ADM images showed a preferential melanosome adsorption on the cluster's outer surface. The micron-sized aggregates were discernible in Raman 2D images, as the melanosomes signal, extracted through 2D principal component analysis, unequivocally mapped their location and distribution within the cells, appearing randomly distributed in the cytoplasm. Protein clusters were not observed in living MNT-1 cells. In this case, mature melanosomes accumulate preferentially at the cell periphery and are more closely packed than in fixed cells. Our results show that, although PFA does not affect the melanin structure, it disrupts melanosome distribution within the cells. Proteins secondary structure, conversely, is partially lost, as shown by the Raman signals related to α-helix, ß-sheets, and specific amino acids that significantly decrease after the PFA treatment.
Subject(s)
Melanins , Melanosomes , Microscopy, Electron, Scanning , Melanosomes/metabolism , Melanins/metabolismABSTRACT
Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.
Subject(s)
Polymorphism, Genetic , Receptors, Calcium-Sensing , Animals , Humans , Mice , Calcium , Phenotype , Receptors, Calcium-Sensing/genetics , Selection, GeneticABSTRACT
Non-coding RNA (ncRNA) plays a critical role in biology. ncRNAs from the same family usually have similar functions, as a result, it is essential to predict ncRNA families before identifying their functions. There are two primary methods for predicting ncRNA families, namely, traditional biological methods and computational methods. In traditional biological methods, a lot of manpower and resources are required to predict ncRNA families. Therefore, this paper proposed a new ncRNA family prediction method called MFPred based on computational methods. MFPred identified ncRNA families by extracting sequence features of ncRNAs, and it possessed three primary modules, including (1) four ncRNA sequences encoding and feature extraction module, which encoded ncRNA sequences and extracted four different features of ncRNA sequences, (2) dynamic Bi_GRU and feature fusion module, which extracted contextual information features of the ncRNA sequence and (3) ResNet_SE module that extracted local information features of the ncRNA sequence. In this study, MFPred was compared with the previously proposed ncRNA family prediction methods using two frequently used public ncRNA datasets, NCY and nRC. The results showed that MFPred outperformed other prediction methods in the two datasets.
Subject(s)
Computational Biology , RNA, Untranslated , Humans , Computational Biology/methods , RNA, Untranslated/geneticsABSTRACT
Se-methylselenocysteine (MSC) is recognized for its potential in cancer prevention, yet the specific effects and underlying processes it initiates within non-small cell lung cancer (NSCLC) remain to be fully delineated. Employing a comprehensive array of assays, including CCK-8, colony formation, flow cytometry, MitoSOX Red staining, wound healing, transwell, and TUNEL staining, we evaluated MSC's effects on A549 and 95D cell lines. Our investigation extended to the ROS-mediated NF-κB signaling pathway, utilizing Western blot analysis, P65 overexpression, and the application of IκB-α inhibitor (BAY11-7082) or N-acetyl-cysteine (NAC) to elucidate MSC's mechanism of action. In vivo studies involving subcutaneous xenografts in mice further confirmed MSC's inhibitory effect on tumor growth. Our findings indicated that MSC inhibited the proliferation of A549 and 95D cells, arresting cell cycle G0/G1 phase and reducing migration and invasion, while also inducing apoptosis and increasing intracellular ROS levels. This was accompanied by modulation of key proteins, including the upregulation of p21, p53, E-cadherin, Bax, cleaved caspase-3, cleaved-PARP, and downregulation of CDK4, SOD2, GPX-1. MSC was found to inhibit the NF-κB pathway, as evidenced by decreased levels of P-P65 and P-IκBα. Notably, overexpression of P65 and modulation of ROS levels with NAC could attenuate MSC's effects on cellular proliferation and metastasis. Moreover, MSC significantly curtailed tumor growth in vivo and disrupted the NF-κB signaling pathway. In conclusion, our research demonstrates that MSC exhibits anticancer effects against NSCLC by modulating the ROS/NF-κB signaling pathway, suggesting its potential as a therapeutic agent in NSCLC treatment.
Subject(s)
Apoptosis , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Lung Neoplasms , NF-kappa B , Reactive Oxygen Species , Selenocysteine , Signal Transduction , Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Animals , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , NF-kappa B/metabolism , Selenocysteine/analogs & derivatives , Selenocysteine/pharmacology , Cell Proliferation/drug effects , Mice , Apoptosis/drug effects , Cell Movement/drug effects , Mice, Nude , Xenograft Model Antitumor Assays , Cell Line, Tumor , A549 Cells , Organoselenium Compounds/pharmacology , Mice, Inbred BALB CABSTRACT
Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are undoubtedly the ideal modality for overcoming drug resistance. Herein, we precisely engineered the surface chemistry of selenium nanoparticles (SeNPs) using neutral (polyvinylpyrrolidone-PVP), anionic (letinan-LET) and cationic (chitosan-CS) surfactants. It was found that surface chemistry greatly influenced the bioactivities of functionalized SeNPs, their interactions with methicillin-resistant Staphylococcus aureus (MRSA), immune cells and metabolisms. LET-functionalized SeNPs with distinct metabolisms exhibited the best inhibitory efficacy compared to other kinds of SeNPs against MRSA through inducing robust ROS generation and damaging bacterial cell wall. Meanwhile, only LET-SeNPs could effectively activate natural kill (NK) cells, and enhance the phagocytic capability of macrophages and its killing activity against bacteria. Furthermore, in vivo studies suggested that LET-SeNPs treatment highly effectively combated MRSA infection and promoted wound healing by triggering much more mouse NK cells, CD8+ and CD4+ T lymphocytes infiltrating into the infected area at the early stage to efficiently eliminate MRSA in the mouse model. This study demonstrates that the novel functionalized SeNP with dual functions could serve as an effective antibacterial agent and could guide the development of next generation antibacterial agents.
Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Selenium , Staphylococcal Infections , Methicillin-Resistant Staphylococcus aureus/drug effects , Animals , Selenium/chemistry , Selenium/pharmacology , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Staphylococcal Infections/drug therapy , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Nanoparticles/chemistry , Killer Cells, Natural/immunology , Killer Cells, Natural/drug effects , Macrophages/drug effects , Macrophages/immunology , Macrophages/microbiology , Humans , Disease Models, Animal , Surface Properties , Microbial Sensitivity TestsABSTRACT
Recently, radioresistance has become a major obstacle in the radiotherapy of cervical cancer. To demonstrate enhanced radiosensitization against radioresistant cervical cancer, radioresistant cervical cancer cell line was developed and the mechanism of radioresistance was explored. Due to the overexpression of (death receptor 5, DR5) in cervical cancer, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressed cervical cancer cell membrane-camouflaged Cu2-xSe nanomedicine (CCMT) was designed. Since the CCMT was encapsulated with TRAIL-modified cell membrane, it represented high target to cervical cancer cell and immune evasion. Furthermore, Cu2-xSe had the ability to scavenge glutathione (GSH) and produce ·OH with excess H2O2 in the tumor microenvironment. The presence of CCMT combined with radiation therapy could effectively increase the 1O2 produced by X-rays. In vitro and in vivo studies elaborated that CCMT exhibited excellent radiosensitization properties to reverse radiotolerance by scavenging GSH and promoting DNA damage, apoptosis, mitochondrial membrane potential damage and metabolic disruption. Collectively, this study suggested that the development of TRAIL-overexpressed cell membrane-camouflaged Cu2-xSe nanomedicine could advance future cervical cancer treatment and minimize the disadvantages associated with radiation treatment.
Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Hydrogen Peroxide , Ligands , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , TNF-Related Apoptosis-Inducing Ligand/metabolism , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Apoptosis , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
MicroRNAs (miRNAs) play an essential role in plant growth and development, and as such, their biogenesis is fine-tuned via regulation of the core microprocessor components. Here, we report that Arabidopsis AAR2, a homolog of a U5 snRNP assembly factor in yeast and humans, not only acts in splicing but also promotes miRNA biogenesis. AAR2 interacts with the microprocessor component hyponastic leaves 1 (HYL1) in the cytoplasm, nucleus, and dicing bodies. In aar2 mutants, abundance of nonphosphorylated HYL1, the active form of HYL1, and the number of HYL1-labeled dicing bodies are reduced. Primary miRNA (pri-miRNA) accumulation is compromised despite normal promoter activities of MIR genes in aar2 mutants. RNA decay assays show that the aar2-1 mutation leads to faster degradation of pri-miRNAs in a HYL1-dependent manner, which reveals a previously unknown and negative role of HYL1 in miRNA biogenesis. Taken together, our findings reveal a dual role of AAR2 in miRNA biogenesis and pre-messenger RNA splicing.
Subject(s)
Arabidopsis Proteins , Arabidopsis , MicroRNAs , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Eukaryota/genetics , Gene Expression Regulation, Plant , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA Processing, Post-Transcriptional , RNA Splicing Factors/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Ribonucleoprotein, U5 Small Nuclear/geneticsABSTRACT
Two-dimensional materials (2DMs) have exhibited remarkably tunable optical characteristics, which have been applied for significant applications in communications, sensing, and computing. However, the reported tunable optical properties of 2DMs are almost volatile, impeding them in the applications of multifarious emerging frameworks such as programmable operation and neuromorphic computing. In this work, nonvolatile electro-optic response is developed by the graphene-Al2O3-In2Se3 heterostructure integrating with microring resonators (MRRs). In such compact devices, the optical absorption coefficient of graphene is substantially tuned by the out-of-plane ferroelectric polarization in α-In2Se3, resulting in a nonvolatile optical transmission in MRRs. This work demonstrates that integrating graphene with ferroelectric materials paves the way to develop nonvolatile devices in photonic circuits for emerging applications such as optical neural networks.
ABSTRACT
Ultrathin topological insulator membranes are building blocks of exotic quantum matter. However, traditional epitaxy of these materials does not facilitate stacking in arbitrary orders, while mechanical exfoliation from bulk crystals is also challenging due to the non-negligible interlayer coupling therein. Here we liberate millimeter-scale films of the topological insulator Bi2Se3, grown by molecular beam epitaxy, down to 3 quintuple layers. We characterize the preservation of the topological surface states and quantum well states in transferred Bi2Se3 films using angle-resolved photoemission spectroscopy. Leveraging the photon-energy-dependent surface sensitivity, the photoemission spectra taken with 6 and 21.2 eV photons reveal a transfer-induced migration of the topological surface states from the top to the inner layers. By establishing clear electronic structures of the transferred films and unveiling the wave function relocation of the topological surface states, our work lays the physics foundation crucial for the future fabrication of artificially stacked topological materials with single-layer precision.
ABSTRACT
Flexible shortwave infrared detectors play a crucial role in wearable devices, bioimaging, automatic control, etc. Commercial shortwave infrared detectors face challenges in achieving flexibility due to the high fabrication temperature and rigid material properties. Herein, we develop a high-performance flexible Te0.7Se0.3 photodetector, resulting from the unique 1D crystal structure and small elastic modulus of Te-Se alloying. The flexible photodetector exhibits a broad-spectrum response ranging from 365 to 1650 nm, a fast response time of 6 µs, a broad linear dynamic range of 76 dB, and a specific detectivity of 4.8 × 1010 Jones at room temperature. The responsivity of the flexible detector remains at 93% of its initial value after bending with a small curvature of 3 mm. Based on the optimized flexible detector, we demonstrate its application in shortwave infrared imaging. These results showcase the great potential of Te0.7Se0.3 photodetectors for flexible electronics.
ABSTRACT
The gate-all-around (GAA) field-effect transistor (FET) holds great potential to support next-generation integrated circuits. Nanowires such as carbon nanotubes (CNTs) are one important category of channel materials in GAA FETs. Based on first-principles investigations, we propose that SiX2 (X = S, Se) nanowires are promising channel materials that can significantly elevate the performance of GAA FETs. The sub-5 nm SiX2 (X = S, Se) nanowire GAA FETs exhibit excellent ballistic transport properties that meet the requirements of the 2013 International Technology Roadmap for Semiconductors (ITRS). Compared to CNTs, they are also advantageous or at least comparable in terms of gate controllability, device dimensions, etc. Importantly, SiSe2 GAA FETs show superb gate controllability due to the ultralow minimum subthreshold swing (SSmin) that breaks "Boltzmann's tyranny". Moreover, the energy-delay product (EDP) of SiX2 GAA FETs is significantly lower than that of the CNT FETs. These features make SiX2 nanowires ideal channel material in the sub-5 nm GAA FET devices.
ABSTRACT
Neutrophilic superhalide-anion-triggered chalcogen conversion-based Zn batteries, despite latent high-energy merit, usually suffer from a short lifespan caused by dendrite growth and shuttle effect. Here, a superhalide-anion-motivator reforming strategy is initiated to simultaneously manipulate the anode interface and Se conversion intermediates, realizing a bipolar regulation toward longevous energy-type Zn batteries. With ZnF2 chaotropic additives, the original large-radii superhalide zincate anion species in ionic liquid (IL) electrolytes are split into small F-containing species, boosting the formation of robust solid electrolyte interphases (SEI) for Zn dendrite inhibition. Simultaneously, ion radius reduced multiple F-containing Se conversion intermediates form, enhancing the interion interaction of charged products to suppress the shuttle effect. Consequently, Zn||Se batteries deliver a ca. 20-fold prolonged lifespan (2000 cycles) at 1 A g-1 and high energy/power density of 416.7 Wh kgSe-1/1.89 kW kgSe-1, outperforming those in F-free counterparts. Pouch cells with distinct plateaus and durable cyclability further substantiate the practicality of this design.
ABSTRACT
Impaired airway epithelial barrier and decreased expression of E-cadherin are key features of severe asthma. As a gatekeeper of the mucosa, E-cadherin can be cleaved from the cell surface and released into the apical lumen as a soluble form (sE-cadherin).This study was aimed to investigate the role of sE-cadherin in severe asthma.Induced sputum was obtained from healthy subjects and patients with asthma. Two murine models of severe asthma were established using either TDI (toluene diisocyanate) or OVA (ovalbumin)/CFA (complete Freund's adjuvants). The role of sE-cadherin in severe asthma was evaluated by intraperitoneal injection of DECMA-1, a neutralizing antibody against sE-cadherin. Mice or THP-1-derived macrophages were treated with recombinant sE-cadherin to explore the pro-inflammatory mechanism of sE-cadherin.Severe asthma patients had a significantly higher sputum sE-cadherin level than the health subjects with mild to moderate asthma, which were positively correlated with sputum HMGB1 level and glucocorticoid dosage required for daily control. Allergen exposure markedly increased sE-cadherin level in the bronchoalveolar lavage fluid in mice. Treatment of DECMA-1 significantly attenuated allergen-induced airway inflammation and hyperresponsivenes in both models of severe asthma. While exposure to recombinant sE-cadherin dramatically up-regulated VEGF expression in THP-1-derived macrophages, and increased neutophlil and eosinophil infiltration into the airway as well as the release of VEGF and IL-6 in mice, both of which can be suppressed by pharmacological inhibition of ERK signaling.Taken together, our data indicated that sE-cadherin contributed to the airway inflammation of severe asthma in an ERK-depedent pathway.
ABSTRACT
The Type III secretion effectors (T3SEs) are bacterial proteins synthesized by Gram-negative pathogens and delivered into host cells via the Type III secretion system (T3SS). These effectors usually play a pivotal role in the interactions between bacteria and hosts. Hence, the precise identification of T3SEs aids researchers in exploring the pathogenic mechanisms of bacterial infections. Since the diversity and complexity of T3SE sequences often make traditional experimental methods time-consuming, it is imperative to explore more efficient and convenient computational approaches for T3SE prediction. Inspired by the promising potential exhibited by pre-trained language models in protein recognition tasks, we proposed a method called PLM-T3SE that utilizes protein language models (PLMs) for effective recognition of T3SEs. First, we utilized PLM embeddings and evolutionary features from the position-specific scoring matrix (PSSM) profiles to transform protein sequences into fixed-length vectors for model training. Second, we employed the extreme gradient boosting (XGBoost) algorithm to rank these features based on their importance. Finally, a MLP neural network model was used to predict T3SEs based on the selected optimal feature set. Experimental results from the cross-validation and independent test demonstrated that our model exhibited superior performance compared to the existing models. Specifically, our model achieved an accuracy of 98.1%, which is 1.8%-42.4% higher than the state-of-the-art predictors based on the same independent data set test. These findings highlight the superiority of the PLM-T3SE and the remarkable characterization ability of PLM embeddings for T3SE prediction.
ABSTRACT
Japan is a country with an approximate 10% prevalence rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Currently, a comprehensive overview of the genotype and phenotype patterns of CRPA in Japan is lacking. Herein, we conducted genome sequencing and quantitative antimicrobial susceptibility testing for 382 meropenem-resistant CRPA isolates that were collected from 78 hospitals across Japan from 2019 to 2020. CRPA exhibited susceptibility rates of 52.9%, 26.4%, and 88.0% against piperacillin-tazobactam, ciprofloxacin, and amikacin, respectively, whereas 27.7% of CRPA isolates was classified as difficult-to-treat resistance P. aeruginosa. Of the 148 sequence types detected, ST274 (9.7%) was predominant, followed by ST235 (7.6%). The proportion of urine isolates in ST235 was higher than that in other STs (P = 0.0056, χ2 test). Only 4.1% of CRPA isolates carried the carbapenemase genes: blaGES (2) and blaIMP (13). One ST235 isolate carried the novel blaIMP variant blaIMP-98 in the chromosome. Regarding chromosomal mutations, 87.1% of CRPA isolates possessed inactivating or other resistance mutations in oprD, and 28.8% showed mutations in the regulatory genes (mexR, nalC, and nalD) for the MexAB-OprM efflux pump. Additionally, 4.7% of CRPA isolates carried a resistance mutation in the PBP3-encoding gene ftsI. The findings from this study and other surveillance studies collectively demonstrate that CRPA exhibits marked genetic diversity and that its multidrug resistance in Japan is less prevailed than in other regions. This study contributes a valuable data set that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions.
Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Carbapenems , Microbial Sensitivity Tests , Pseudomonas Infections , Pseudomonas aeruginosa , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Japan/epidemiology , Carbapenems/pharmacology , Anti-Bacterial Agents/pharmacology , Humans , Bacterial Proteins/genetics , Pseudomonas Infections/microbiology , Pseudomonas Infections/epidemiology , Pseudomonas Infections/drug therapy , beta-Lactamases/genetics , Genome, Bacterial/genetics , Piperacillin, Tazobactam Drug Combination/therapeutic use , Piperacillin, Tazobactam Drug Combination/pharmacology , Whole Genome Sequencing , Meropenem/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Amikacin/pharmacologyABSTRACT
BACKGROUND: Lipid peroxidation is a characteristic metabolic manifestation of diabetic retinopathy (DR) that causes inflammation, eventually leading to severe retinal vascular abnormalities. Selenium (Se) can directly or indirectly scavenge intracellular free radicals. Due to the narrow distinction between Se's effective and toxic doses, porous Se@SiO2 nanospheres have been developed to control the release of Se. They exert strong antioxidant and anti-inflammatory effects. METHODS: The effect of anti-lipid peroxidation and anti-inflammatory effects of porous Se@SiO2 nanospheres on diabetic mice were assessed by detecting the level of Malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), decreased reduced/oxidized glutathione (GSH/GSSG) ratio, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL) -1ß of the retina. To further examine the protective effect of porous Se@SiO2 nanospheres on the retinal vasculopathy of diabetic mice, retinal acellular capillary, the expression of tight junction proteins, and blood-retinal barrier destruction was observed. Finally, we validated the GPX4 as the target of porous Se@SiO2 nanospheres via decreased expression of GPX4 and detected the level of MDA, GSH/GSSG, TNF-α, IFN-γ, IL -1ß, wound healing assay, and tube formation in high glucose (HG) cultured Human retinal microvascular endothelial cells (HRMECs). RESULTS: The porous Se@SiO2 nanospheres reduced the level of MDA, TNF-α, IFN-γ, and IL -1ß, while increasing the level of GPX4 and GSH/GSSG in diabetic mice. Therefore, porous Se@SiO2 nanospheres reduced the number of retinal acellular capillaries, depletion of tight junction proteins, and vascular leakage in diabetic mice. Further, we identified GPX4 as the target of porous Se@SiO2 nanospheres as GPX4 inhibition reduced the repression effect of anti-lipid peroxidation, anti-inflammatory, and protective effects of endothelial cell dysfunction of porous Se@SiO2 nanospheres in HG-cultured HRMECs. CONCLUSION: Porous Se@SiO2 nanospheres effectively attenuated retinal vasculopathy in diabetic mice via inhibiting excess lipid peroxidation and inflammation by target GPX4, suggesting their potential as therapeutic agents for DR.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Nanospheres , Selenium , Humans , Mice , Animals , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/metabolism , Selenium/metabolism , Selenium/pharmacology , Selenium/therapeutic use , Silicon Dioxide/metabolism , Silicon Dioxide/pharmacology , Silicon Dioxide/therapeutic use , Diabetes Mellitus, Experimental/metabolism , Endothelial Cells/metabolism , Lipid Peroxidation , Porosity , Tumor Necrosis Factor-alpha/metabolism , Glutathione Disulfide/metabolism , Glutathione Disulfide/pharmacology , Glutathione Disulfide/therapeutic use , Inflammation/metabolism , Anti-Inflammatory Agents/therapeutic use , Tight Junction Proteins/metabolismABSTRACT
Selenium@zinc nanoparticles, or Se@Zn NPs, are extensively employed in various environmental, industrial and biological domains. However, the biological potential of Se@Zn NPs has not been thoroughly investigated. This study focused on fabricating Se@Zn NPs from algae using an aqueous extract of Champia parvula seaweed. Analytical techniques were used to describe the successfully synthesized Se@Zn NPs. In addition, a biological function analysis of the Se@Zn NPs was conducted. The Ultraviolet-visible spectroscopy (UV-vis) spectrum showed a specific absorbance peak for the Se@Zn NPs at 350-400 nm. The biomolecules involved in forming Se@Zn NPs were identified by their potential functional groups, as revealed by Fourier transform infrared spectroscopy (FTIR). By scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Se@Zn NPs were shown to be spherical and to have a diameter range of 100-200 nm. NPs with a crystallite diameter of 54.8 nm and chemical compositions of zinc and selenium (1:1.5 ratio) were revealed by X-ray diffraction analysis (XRD) and energy dispersive x-ray spectroscopy (EDS). IC50 values were determined for the anticancer activity against A549, MCF-7 and HeLa cells. Cell morphological changes in fluorescence microscopy and apoptosis mechanisms by flow cytometry analysis were investigated, which show that Se@Zn NPs induced apoptosis in various cancer cells. DNA fragmentation and ROS levels were studied by fluorescence microscopy. In conclusion, conditions required for therapeutic and preventative applications may be met by the green synthesis of Se@Zn NPs.
ABSTRACT
BACKGROUND: The Polygonaceae is a family well-known for its weeds, and edible plants, Fagopyrum (buckwheat) and Rheum (rhubarb), which are primarily herbaceous and temperate in distribution. Yet, the family also contains a number of lineages that are principally distributed in the tropics and subtropics. Notably, these lineages are woody, unlike their temperate relatives. To date, full-genome sequencing has focused on the temperate and herbaceous taxa. In an effort to increase breadth of genetic knowledge of the Polygonaceae, we here present six fully assembled and annotated chloroplast genomes from six of the tropical, woody genera: Coccoloba rugosa (a narrow and endangered Puerto Rican endemic), Gymnopodium floribundum, Neomillspaughia emarginata, Podopterus mexicanus, Ruprechtia coriacea, and Triplaris cumingiana. RESULTS: These assemblies represent the first publicly-available assembled and annotated plastomes for the genera Podopterus, Gymnopodium, and Neomillspaughia, and the first assembled and annotated plastomes for the species Coccoloba rugosa, Ruprechtia coriacea, and Triplaris cumingiana. We found the assembled chloroplast genomes to be above the median size of Polygonaceae plastomes, but otherwise exhibit features typical of the family. The features of greatest sequence variation are found among the ndh genes and in the small single copy (SSC) region of the plastome. The inverted repeats show high GC content and little sequence variation across genera. When placed in a phylogenetic context, our sequences were resolved within the Eriogonoideae. CONCLUSIONS: These six plastomes from among the tropical woody Polygonaceae appear typical within the family. The plastome assembly of Ruprechtia coriacea presented here calls into question the sequence identity of a previously published plastome assembly of R. albida.