ABSTRACT
We aimed to develop an efficient detection platform that can identify a larger number of suspicious samples in a single test, saving time, manpower, and material costs, and providing vital support to the public health system in coping with the current challenging and dynamic bioterrorism threat landscape, particularly in regions of turmoil and conflict. We have successfully developed a high-throughput, multitarget fluorescent array detection platform by effectively combining integrating multiprobe amplification (MPA) with melting curve analysis. Specifically, we have established reliable laboratory testing methods for eight highly pathogenic bacteria, including Bacillus anthracis, Yersinia pestis, Brucella spp., Burkholderia pseudomallei, Francisella tularensis, Vibrio cholerae, Salmonella typhi, and Staphylococcus aureus. Our method achieves sensitive and specific simultaneous detection of eight target bacteria in one well by optimizing the reaction conditions of MPA. In the assessment of 192 simulated environmental samples, both positive and negative coincidence rates were 100.00%. Among 48 simulated clinical samples, the positive coincidence rate reached 97.73%, while maintaining a perfect negative coincidence rate of 100.00%. Moreover, the detection platform holds immense potential for attaining a more comprehensive bioterrorism screening, and its high cost-effectiveness enables the provision of diverse and adaptable diagnostic methods for public health quarantine in underdeveloped countries and regions.
Subject(s)
Bioterrorism , Nucleic Acid Amplification Techniques , Nucleic Acid Amplification Techniques/methods , Bacteria/genetics , Bacteria/isolation & purification , Cost-Benefit Analysis , Transition TemperatureABSTRACT
After coarse-graining a complex system, the dynamics of its macro-state may exhibit more pronounced causal effects than those of its micro-state. This phenomenon, known as causal emergence, is quantified by the indicator of effective information. However, two challenges confront this theory: the absence of well-developed frameworks in continuous stochastic dynamical systems and the reliance on coarse-graining methodologies. In this study, we introduce an exact theoretic framework for causal emergence within linear stochastic iteration systems featuring continuous state spaces and Gaussian noise. Building upon this foundation, we derive an analytical expression for effective information across general dynamics and identify optimal linear coarse-graining strategies that maximize the degree of causal emergence when the dimension averaged uncertainty eliminated by coarse-graining has an upper bound. Our investigation reveals that the maximal causal emergence and the optimal coarse-graining methods are primarily determined by the principal eigenvalues and eigenvectors of the dynamic system's parameter matrix, with the latter not being unique. To validate our propositions, we apply our analytical models to three simplified physical systems, comparing the outcomes with numerical simulations, and consistently achieve congruent results.
ABSTRACT
The fundamental differences in phospholipids between bacterial and mammalian cell membranes present remarkable opportunities for antimicrobial design. However, it is challenging to distinguish bacterial anionic phospholipid phosphatidylglycerol (PG) from mammalian anionic phosphatidylserine (PS) with the same net charge. Here, we report a class of radially amphiphilic α helix antimicrobial peptides (RAPs) that can selectively discriminate PG from PS, relying on the helix structure. The representative RAP, L10-MMBen, can direct the rearrangement of PG vesicles into a lamellar structure with its helix axis parallel to the PG membrane surface. The helical structure imparts both the thermodynamic and kinetic advantages of L10-MMBen/PG assembly, and the hiding of hydrophobic regions in RAPs is crucial for PG recognition. L10-MMBen exhibits high selectivity against bacteria depending on PG recognition, showing low in vivo toxicity and significant treatment efficacy in mice infection models. Our study introduces a helicity-direct bacterial phospholipid recognition paradigm for designing highly selective antimicrobial peptides.
Subject(s)
Antimicrobial Peptides , Phospholipids , Animals , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/pharmacology , Mice , Phospholipids/chemistry , Phospholipids/metabolism , Phosphatidylglycerols/chemistry , Bacteria/drug effects , Microbial Sensitivity Tests , Hydrophobic and Hydrophilic Interactions , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistryABSTRACT
The chemical modification of the achiral carbon nanohoops to break the symmetry will result in inherently chiral structures with interesting optical properties. Herein, we report two novel π-extended chiral macrocycles, cyclo[10]paraphenylene-pyrene ([10]CPP-2Pyrene) and cyclo[10]paraphenylene-hexa-peri-hexabenzocoronene ([10]CPP-2HBC). The large substituents on the nanohoop peripheries effectively prevented free rotation and the racemization process. The conformation of each enantiomer is stable enough to be resolved by recycling HPLC.
ABSTRACT
Peptide design and drug development offer a promising solution for combating serious diseases or infections. In this study, using an AI-human negotiation approach, we have designed a class of minimal model peptides against tuberculosis (TB), among which K7W6 exhibits potent efficacy attributed to its assembly-induced function. Comprising lysine and tryptophan with an amphiphilic α-helical structure, the K7W6 sequence exhibits robust activity against various infectious bacteria causing TB (including clinically isolated and drug-resistant strains) both in vitro and in vivo. Moreover, it synergistically enhances the effectiveness of the first-line antibiotic rifampicin while displaying low potential for inducing drug resistance and minimal toxicity toward mammalian cells. Biophysical experiments and simulations elucidate that K7W6's exceptional performance can be ascribed to its highly selective and efficient membrane permeabilization activity induced by its distinctive self-assembly behavior. Additionally, these assemblies regulate the interplay between enthalpy and entropy during K7W6-membrane interaction, leading to the peptide's two-step mechanism of membrane interaction. These findings provide valuable insights into rational design principles for developing advanced peptide-based drugs while uncovering the functional role played by assembly.
Subject(s)
Entropy , Humans , Peptides/chemistry , Peptides/pharmacology , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Rifampin/chemistry , Rifampin/pharmacology , AnimalsABSTRACT
Soil fungi are pivotal in alpine and arctic ecosystems that are vulnerable to climate changes. Previous studies have shown broad connections between soil fungi in the arctic and alpine regions, but most of these studies are mainly from Europe and North America, with more sporadic studies from East Asia. Currently, little is known about the biogeographic relationships between soil fungi in alpine meadows of southwestern China (AMSC) and other regions of the world. In addition, the regional-scale spatial patterns of fungal communities in the AMSC, as well as their driving factors and ecological processes, are also poorly understood. In this study, we collected roots and surrounding soils of two dominant ectomycorrhizal plants, Bistorta vivipara and B. macrophylla from the AMSC, and performed bioinformatic and statistical analyses based on high-throughput sequencing of ITS2 amplicons. We found that: (1) fungi from the AMSC were closely related with those from boreal forests and tundra, and saprotrophic fungi had higher dispersal potential than ectomycorrhizal fungi; (2) community compositions exhibited clear divergences among geographic regions and between root and soil samples; (3) climate was the predominant factor driving regional-scale spatial patterns but had less explanatory power for saprotrophic and total fungi from roots than those from soils; (4) homogeneous selection and drift were the key ecological processes governing community assembly, but in communities of saprotrophic and total fungi from soil samples, drift contributed less and its role was partially replaced by dispersal limitation. This study highlights the importance of climatic selection and stochastic processes on fungal community assembly in alpine regions, and emphasizes the significance of simultaneously investigating fungi with different trophic modes and from both roots and soils.
Subject(s)
Fungi , Grassland , Mycorrhizae , Soil Microbiology , China , Climate Change , Climate , Soil/chemistry , MycobiomeABSTRACT
BACKGROUND: Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. OBJECTIVES: This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). METHODS: Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. RESULTS: In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E - 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. CONCLUSIONS: The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.
Subject(s)
Bone Density , Genome-Wide Association Study , Intervertebral Disc Degeneration , Mendelian Randomization Analysis , Humans , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/epidemiology , Risk Factors , Male , Female , Multivariate AnalysisABSTRACT
Aberrant FGF2/FGFR signaling is implicated in lung squamous cell carcinoma (LSCC), posing treatment challenges due to the lack of targeted therapeutic options. Designing drugs that block FGF2 signaling presents a promising strategy different from traditional kinase inhibitors. We previously reported a ColVα1-derived fragment, HEPV (127AA), that inhibits FGF2-induced angiogenesis. However, its large size may limit therapeutic application. This study combines rational peptide design, molecular dynamics simulations, knowledge-based prediction, and GUV and FRET assays to identify smaller peptides with FGF2-blocking properties. We synthesized two novel peptides, HBS-P1 (45AA) and HBS-P2 (66AA), that retained the heparin-binding site. Both peptides demonstrated anti-LSCC and antiangiogenesis properties in cell viability and microvessel network induction assays. In two LSCC subcutaneous models, HBS-P1, with its affinity for FGF2 and enhanced penetration ability, demonstrated substantial therapeutic potential without apparent toxicities. Our study provides the first evidence supporting the development of collagen V-derived natural peptides as FGF2-blocking agents for LSCC treatment.
Subject(s)
Carcinoma, Squamous Cell , Drug Design , Fibroblast Growth Factor 2 , Lung Neoplasms , Peptides , Fibroblast Growth Factor 2/antagonists & inhibitors , Fibroblast Growth Factor 2/metabolism , Fibroblast Growth Factor 2/chemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Humans , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Animals , Peptides/pharmacology , Peptides/chemistry , Peptides/chemical synthesis , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Molecular Dynamics Simulation , Mice, NudeABSTRACT
Drug-eluting microspheres are commonly used as a local drug delivery system for interventional therapy. However, current drug-eluting microspheres have poor X-ray visibility, which can hinder tracking and postembolization evaluation. In the current study, X-ray-visible poly(acrylic acid) drug-eluting beads loaded with iodized oil (IO-PAA-DEBs) ranging from 100-300 µm were prepared and evaluated both in vitro and in vivo. Iodized oil served as the radiopaque agent, and X-ray and computed tomography scanning confirmed that the microspheres exhibited excellent X-ray-visible properties. The drug-loading capacities of bleomycin hydrochloride, doxorubicin hydrochloride, and oxaliplatin were also investigated. IO-PAA-DEBs exhibited sustained drug release properties, accompanied by a cumulative drug release rate that reached approximately 60% after 120 h. In vitro and in vivo experiments revealed that IO-PAA-DEBs had good biocompatibility. Collectively, these results demonstrated that IO-PAA-DEBs could facilitate transarterial embolization and sustained drug delivery.
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Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus ß-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.
ABSTRACT
Ecological security (ES) is a crucial indicator for assessing the sustainable development of a region. Currently, most studies on ES primarily focus on process analysis, and the integration of environmental variability into the development of tailored control strategies for regions with varying ecological quality is overlooked. Therefore, in this study, we identified regional ES change processes, employed an optimized system to calculate the ecological security index (ESI), and identified ecological corridors (ECs) through the Minimum Constrained Resource (MCR) model to determine zoning strategies for typical arid regions, using the Ningxia region in the Yellow River Basin of China as an example. The findings showed that (1) from 2006 to 2020, the ESI values of most regions were between 0.2 and 0.4, with small but consistent increases in the ESI values over the years. (2) The proportion of regions with high ES ratings increased by 9.08 % across all districts and counties, and the center of gravity of ES shifted in a north-south and east-west direction. (3) The ESI exhibited a strong positive spatial correlation, characterized by spatial diffusion and spillover effects in most regions. (4) The ECs were predominantly distributed in a north-south direction, involving a total of 20 districts and counties. Based on the principles of sustainable development, we developed a model for the dynamic identification and zoning control of regional ES, aiming to provide a practical framework for effective ecological restoration and protection measures. Additionally, the strategies and methodologies presented in this study serve as important references for similar regions worldwide to facilitate the zoning control of ES, highlighting the broader significance and applicability of the study.
ABSTRACT
Intervertebral disc degeneration (IVDD) severely affects the work and the quality of life of people. We previously demonstrated that silencing activation transcription factor 3 (ATF3) blocked the IVDD pathological process by regulating nucleus pulposus cell (NPC) ferroptosis, apoptosis, inflammation, and extracellular matrix (ECM) metabolism. Nevertheless, whether miR-874-3p mediated the IVDD pathological process by targeting ATF3 remains unclear. We performed single-cell RNA sequencing (scRNA-seq) and bioinformatics analysis to identify ATF3 as a key ferroptosis gene in IVDD. Then, Western blotting, flow cytometry, ELISA, and animal experiments were performed to validate the roles and regulatory mechanisms of miR-874-3p/ATF3 signalling axis in IVDD. ATF3 was highly expressed in IVDD patients and multiple cell types of IVDD rat, as revealed by scRNA-seq and bioinformatics analysis. GO analysis unveiled the involvement of ATF3 in regulating cell apoptosis and ECM metabolism. Furthermore, we verified that miR-874-3p might protect against IVDD by inhibiting NPC ferroptosis, apoptosis, ECM degradation, and inflammatory response by targeting ATF3. In vivo experiments displayed the protective effect of miR-874-3p/ATF3 axis on IVDD. These findings propose the potential of miR-874-3p and ATF3 as biomarkers of IVDD and suggest that targeting the miR-874-3p/ATF3 axis may be a therapeutic target for IVDD.
Subject(s)
Activating Transcription Factor 3 , Ferroptosis , Intervertebral Disc Degeneration , MicroRNAs , Nucleus Pulposus , Activating Transcription Factor 3/metabolism , Activating Transcription Factor 3/genetics , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Humans , Rats , Ferroptosis/genetics , Male , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Single-Cell Analysis/methods , Apoptosis/genetics , Signal Transduction , Female , Middle Aged , Rats, Sprague-Dawley , Sequence Analysis, RNA/methods , Extracellular Matrix/metabolism , Adult , Gene Expression Regulation , Disease Models, Animal , Computational Biology/methodsABSTRACT
Herein we report the construction of an inherently chiral carbon nanoring, cyclo[7]paraphenylene-2,9-rubicene ([7]CPPRu2,9), by combining rubicene with a C-shaped synthon through the Suzuki-Miyaura coupling reaction. The structure was fully confirmed by high-resolution mass spectroscopies (HR-MS) and various NMR techniques. The photophysical properties were investigated by UV-vis absorption and fluorescence spectroscopy as well as the time-resolved fluorescence decay. Moreover, two enantiomers (M)/(P)-[7]CPPRu2,9 were successfully resolved by recyclable HPLC and studied by CD and CPL spectra.
ABSTRACT
Ecosystem carbon storage (ECS) is a critical consideration in reducing the impact of global warming and tackling environmental challenges, positioning it at the forefront of contemporary research. Due to the significant differences in the influence of land usage patterns on ECS in various policy contexts and China's commitment to attaining a carbon-neutral status, a model simulating different scenarios is needed to analyze the spatiotemporal characteristics and evolutionary process of carbon storage in terrestrial ecosystems accurately. To address this challenge, this study established a coupling model of "Geographical analysis -Evolution analysis -Predicting (GEP)" for assessing ecosystem ECS and analyzing its spatial characteristics and evolutionary patterns and projecting the spatial distribution of ECS under various developmental scenarios, which analyzed variations in ECS across different levels of magnitude and delineated the changing areas across a range of varying scenarios in the future additionally. The outcomes suggested that the ECS decreased by 1.17 × 106 t from 1990 to 2020, which pertaining to the utilization transfer of land in the area, whose change in ECS levels with a positive trend. It is predicted that the ECS will grow by 1.15 × 106 t and 1.44 × 106 t, in 2030 and 2060 compared with 2020 within the framework of natural development scenario (NDS), while within the framework of ecological protection scene (EPS), ECS will increase significantly, increasing by 3.06 × 106 t and 4.44 × 106 t. There will be more areas where ECS increases within the framework of EPS, by comparing with the NDS. This study offers a comprehensive analysis of Hanzhong City's carbon storage trends, demonstrating its significant impact on climate change mitigation and serving as a predictive model for similar regions, which underscores the importance of localized carbon management strategies, offering valuable insights for local governments in formulating effective climate adaptation and mitigation policies.
Subject(s)
Ecosystem , China , Carbon , Carbon Sequestration , Models, Theoretical , Global WarmingABSTRACT
During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62â% for internal transcribed spacer (ITS), 98.66-99.10â% for ribosomal small subunit (nrSSU), and 96.36-98.22â% for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.
Subject(s)
Fatty Acids , Mucorales , Animals , Phylogeny , China , Sequence Analysis, DNA , Base Composition , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Bacterial Typing Techniques , Fatty Acids/chemistry , InvertebratesABSTRACT
AIMS: This study aimed to investigate the relationship between ulcerative colitis (UC) and anxiety and explore its central mechanisms using colitis mice. METHODS: Anxiety-like behavior was assessed in mice induced by 3% dextran sodium sulfate (DSS) using the elevated plus maze and open-field test. The spatial transcriptome of the hippocampus was analyzed to assess the distribution of excitatory and inhibitory synapses, and Toll-like receptor 4 (TLR4) inhibitor TAK-242 (10 mg/kg) and AAV virus interference were used to examine the role of peripheral inflammation and central molecules such as Glutamate Receptor Metabotropic 1 (GRM1) in mediating anxiety behavior in colitis mice. RESULTS: DSS-induced colitis increased anxiety-like behaviors, which was reduced by TAK-242. Spatial transcriptome analysis of the hippocampus showed an excitatory-inhibitory imbalance mediated by glutamatergic synapses, and GRM1 in hippocampus was identified as a critical mediator of anxiety behavior in colitis mice via differential gene screening and AAV virus interference. CONCLUSION: Our work suggests that the hippocampus plays an important role in brain anxiety caused by peripheral inflammation, and over-excitation of hippocampal glutamate synapses by GRM1 activation induces anxiety-like behavior in colitis mice. These findings provide new insights into the central mechanisms underlying anxiety in UC and may contribute to the development of novel therapeutic strategies for UC-associated anxiety.
Subject(s)
Anxiety , Hippocampus , Inflammation , Receptors, Metabotropic Glutamate , Animals , Male , Mice , Anxiety/metabolism , Colitis/chemically induced , Colitis/metabolism , Colitis/pathology , Dextran Sulfate , Hippocampus/metabolism , Inflammation/metabolism , Mice, Inbred C57BL , Receptors, Metabotropic Glutamate/metabolism , Receptors, Metabotropic Glutamate/geneticsABSTRACT
The cellular endocytosis of nanoparticles (NPs) is a fundamental biological process with significant potential in biomedical applications. However, a comprehensive understanding of the mechanistic aspects of endocytosis and the impact of particle properties on this process remains elusive. In this study, we investigated the membrane-wrapping behavior of soft NPs (SNPs) with varying rigidities using theoretical calculations. Our findings reveal that the membrane-wrapping process of SNPs involves a complex energy change including the possible existence of an energy barrier; moreover, it is found that the location and height of this barrier strongly depend on the mechanistic properties of the NPs and membranes. Additionally, by considering force balance in the membrane-wrapping process, we calculated the speed at which NP is internalized by the membrane, showing a nonmonotonic dependence on particle rigidity and/or wrapping degree. These phenomena can be attributed to competition between different energy components associated with NP-membrane binding, membrane tension, and deformations occurring during SNP-membrane interaction processes. Our results contribute to a deeper understanding of cellular-level endocytosis mechanisms and offer potential applications for soft NPs in biomedicine.
Subject(s)
Nanoparticles , Cell Membrane/chemistry , Nanoparticles/chemistry , Membranes , Endocytosis , Physical PhenomenaABSTRACT
It is a long-standing scientific controversy to achieve anti-Kasha-type multiple emissions by tuning the structures at a molecular level. Although it is known that some conjugated structures have excitation-dependent multiple emissions, no all-benzenoid molecules have yet been reported, the emissions of which originate from different excited states. Herein, we report the design of two symmetry-breaking heterogeneous carbon bisnanohoops that in solution become multiple fluorescent emitters with unusual anti-Kasha characteristics. This phenomenon can be spectroscopically and theoretically explained and will find applications in a wide range of sensing and imaging technologies.
ABSTRACT
The Greatwall-family protein kinase Rim15 is associated with the nutrient starvation response, whereas its role in oxidative stress responses remains unclear. Here, acetic acid and peroxide were used as two oxidative stress elicitors. The antioxidant indicator assay under acetic acid stress revealed the impaired growth in rim15Δ related to the regulation of antioxidant systems. Comparative transcriptome analysis revealed that differentially expressed genes (DEGs) are predicted to be mostly regulated by oxidative stress-responsive transcriptional factor Yap1. Among the DEGs, acetic acid stress-induced genes were found, and YAP1 disruption also inhibited their induction. The deletion of Rim15 or the Rim15 kinase domain in yap1Δ did not further decrease the gene expression, suggesting that Rim15 functions together with Yap1 in regulating acetic acid stress-induced genes, which requires Rim15 kinase activity. Additionally, Rim15 regulated H2O2 stress tolerance through partially similar but special mechanisms in that Rim15 kinase activity impacted acetic acid and H2O2 stress tolerance in different degrees, indicating the different mechanisms underlying Rim15-mediated redox regulation against different stressors. These results benefit the better understanding of stress signaling pathways related to Rim15. Given that Rim15 and some of its target genes are conserved across eukaryotes, these results also provide a basis for studies of oxidative stress-related processes in other organisms.
ABSTRACT
Two new termite-pathogenic species, Ophiocordycepsglobiperitheciata and O.longistipes, are described from Yunnan Province, China. Six-locus (ITS, nrSSU, nrLSU, tef-1α, rpb1 and rpb2) phylogenetic analyses in combination with morphological observations were employed to characterize these two species. Phylogenetically, O.globiperitheciata is most closely related to Hirsutellacryptosclerotium and O.communis, whereas O.longistipes shares a sister relationship with O.fusiformis. However, O.globiperitheciata differs from H.cryptosclerotium by parasitizing Blattodea and producing clavate, unbifurcated stromata. Ophiocordycepsglobiperitheciata is distinguished from O.communis by multiple stromata, shorter asci and ascospores. Ophiocordycepslongistipes differs from O.fusiformis in producing larger stromata, perithecia, asci and ascospores, as well as smaller citriform or oval conidia. Morphological descriptions of the two new species and a dichotomous key to the 19 termite-pathogenic Ophiocordyceps species are presented.