Broad Functions Research Articles

Role of CD14 in human disease.

The cell surface antigen CD14 is primarily understood to act as a co-receptor for toll-like receptors (TLRs) to activate innate immunity responses to pathogens and tissue injury in macrophages and monocytes. However, roles for CD14 are increasingly being uncovered in disease responses in epithelial and endothelial cells. Consistent with these broader functions, CD14 expression is altered in a variety of non-immune cell types in response to a several of disease states. Moreover, soluble CD14 activated by factors from both pathogens and tissue damage may initiate signalling in a variety of non-immune cells. This review examined the current understanding CD14 in innate immunity as well as its potential functions in nonimmune cells and associated human diseases.

The selection of copiotrophs may complicate biodiversity-ecosystem functioning relationships in microbial dilution-to-extinction experiments

The relationships between biodiversity-ecosystem functioning (BEF) for microbial communities are poorly understood despite the important roles of microbes acting in natural ecosystems. Dilution-to-extinction (DTE), a method to manipulate microbial diversity, helps to fill the knowledge gap of microbial BEF relationships and has recently become more popular with the development of high-throughput sequencing techniques. However, the pattern of community assembly processes in DTE experiments is less explored and blocks our further understanding of BEF relationships in DTE studies. Here, a microcosm study and a meta-analysis of DTE studies were carried out to explore the dominant community assembly processes and their potential effect on exploring BEF relationships. While stochastic processes were dominant at low dilution levels due to the high number of rare species, the deterministic processes became stronger at a higher dilution level because the microbial copiotrophs were selected during the regrowth phase and rare species were lost. From the view of microbial functional performances, specialized functions, commonly carried by rare species, are more likely to be impaired in DTE experiments while the broad functions seem to be less impacted due to the good performance of copiotrophs. Our study indicated that shifts in the prokaryotic community and its assembly processes induced by dilutions result in more complex BEF relationships in DTE experiments. Specialized microbial functions could be better used for defining BEF. Our findings may be helpful for future studies to design, explore, and interpret microbial BEF relationships using DTE.

The role of PIWIL4 and piRNAs in the development of choroidal neovascularization

Wet age-related macular degeneration (wAMD) is the leading cause of blindness among the elderly in industrialized nations. Anti-vascular epidermal growth factor (VEGF) therapy via intravitreal injection is the most effective clinical treatment for wAMD due to high concentrations of VEGF that promote choroidal neovascularization. While PIWI proteins participate in various biological processes, their function in AMD remains unclear. In this study, we discovered that PIWIL4 expression is elevated in a laser-induced choroidal neovascularization (CNV) model and that it regulates angiogenesis in vitro and in vivo. Differentially expressed piwi-interacting RNAs (piRNAs) were identified in a CNV model and were shown to potentially regulate angiogenesis via bioinformatics analysis. PIWIL4 knockdown inhibits VEGF secretion and VEGFR2 phosphorylation. Overall, PIWIL4 may serve as a novel target to block pathological choroidal neovascularization, and the study of the PIWI-piRNAs pathway in wAMD highlights its broad function in somatic cells.

Visible-Light-Induced Regioselective C-H Sulfenylation of Pyrazolo[1,5-a]pyrimidines via Cross-Dehydrogenative Coupling.

A visible-light-induced cross-dehydrogenative methodology has been developed for the regioselective sulfenylation of pyrazolo[1,5-a]pyrimidine derivatives. Rose bengal, blue LEDs, KI, K2S2O8, and DMSO are all essential for this photocatalytic transformation. The protocol is applicable for the synthesis of a library of 3-(aryl/heteroaryl thio)pyrazolo[1,5-a]pyrimidine derivatives with broad functionalities. The selectivity and scalability of the methodology have been also demonstrated. Moreover, the efficiency of this strategy for sulfenylation of pyrazoles, indole, imidazoheterocycles, and 4-hydroxy coumarin has been proven. The mechanistic investigation revealed the radical-based mechanism and formation of diaryl disulfide as a key intermediate for this cross-dehydrogenative coupling reaction.

A compact multi-functional model of the rabbit atrioventricular node with dual pathways.

The atrioventricular node (AVN) is considered a "black box", and the functioning of its dual pathways remains controversial and not fully understood. In contrast to numerous clinical studies, there are only a few mathematical models of the node. In this paper, we present a compact, computationally lightweight multi-functional rabbit AVN model based on the Aliev-Panfilov two-variable cardiac cell model. The one-dimensional AVN model includes fast (FP) and slow (SP) pathways, primary pacemaking in the sinoatrial node, and subsidiary pacemaking in the SP. To obtain the direction-dependent conduction properties of the AVN, together with gradients of intercellular coupling and cell refractoriness, we implemented the asymmetry of coupling between model cells. We hypothesized that the asymmetry can reflect some effects related to the complexity of the real 3D structure of AVN. In addition, the model is accompanied by a visualization of electrical conduction in the AVN, revealing the interaction between SP and FP in the form of ladder diagrams. The AVN model demonstrates broad functionality, including normal sinus rhythm, AVN automaticity, filtering of high-rate atrial rhythms during atrial fibrillation and atrial flutter with Wenckebach periodicity, direction-dependent properties, and realistic anterograde and retrograde conduction curves in the control case and the cases of FP and SP ablation. To show the validity of the proposed model, we compare the simulation results with the available experimental data. Despite its simplicity, the proposed model can be used both as a stand-alone module and as a part of complex three-dimensional atrial or whole heart simulation systems, and can help to understand some puzzling functions of AVN.

The ion channel CALHM6 controls bacterial infection‐induced cellular cross‐talk at the immunological synapse

Membrane ion channels of the calcium homeostasis modulator (CALHM) family promote cell–cell crosstalk at neuronal synapses via ATP release, where ATP acts as a neurotransmitter. CALHM6, the only CALHM highly expressed in immune cells, has been linked to the induction of natural killer (NK) cell anti‐tumour activity. However, its mechanism of action and broader functions in the immune system remain unclear. Here, we generated Calhm6−/− mice and report that CALHM6 is important for the regulation of the early innate control of Listeria monocytogenes infection in vivo. We find that CALHM6 is upregulated in macrophages by pathogen‐derived signals and that it relocates from the intracellular compartment to the macrophage‐NK cell synapse, facilitating ATP release and controlling the kinetics of NK cell activation. Anti‐inflammatory cytokines terminate CALHM6 expression. CALHM6 forms an ion channel when expressed in the plasma membrane of Xenopus oocytes, where channel opening is controlled by a conserved acidic residue, E119. In mammalian cells, CALHM6 is localised to intracellular compartments. Our results contribute to the understanding of neurotransmitter‐like signal exchange between immune cells that fine‐tunes the timing of innate immune responses.

Studies on Cistanches Herba: A Bibliometric Analysis

As a famous tonic herb, Cistanches Herba is known for its broad medicinal functions, especially its hormone balancing, anti-aging, anti-dementia, anti-tumor, anti-oxidative, neuroprotective, and hepatoprotective effects. This study aims to provide a comprehensive bibliometric analysis of studies on Cistanche and to identify research hotspots and frontier topics on the genus. Based on the metrological analysis software CiteSpace, 443 Cistanche related papers were quantitatively reviewed. The results indicate that 330 institutions from 46 countries have publications in this field. China was the leading country in terms of research importance and number of publication (335 articles). In the past decades, studies on Cistanche have mainly focused on its rich active substances and pharmacological effects. Although the research trend shows that Cistanche has grown from an endangered species to an important industrial plant, its breeding and cultivation continue to be important areas for research. In the future, the application of Cistanche species as functional foods may be a new research trend. In addition, active collaborations among researchers, institutions, and countries are expected.

Resveratrol alleviated neuroinflammation induced by pseudorabies virus infection through regulating microglial M1/M2 polarization

BackgroundPseudorabies virus (PRV) infections in susceptible non-porcine species trigger uncontrolled inflammations and eventually fatal encephalitis. Resveratrol (Res) has broad pharmacological functions including anti-virus, anti-inflammation, and neuroprotective. PurposeWe attempted to investigate the potential of Res in ameliorating PRV infection pathology in mice and decipher the mechanism of Res in treating PRV. MethodsThe mice were infected by PRV to investigate the protective effect of Res. Blood-brain barrier (BBB) permeability, H&E/Nissl/TUNEL staining, Real-time PCR and ELISA analyses were performed. Primary microglia and neuron were isolated from mice and cultured. The co-culture model of microglia and neuron was established by transwell. Immunofluorescence assay and flow cytometry were used. ResultsIn this study, we showed that Res ameliorated brain damage by reducing BBB permeability in PRV-infected mice, and diminished the expressions of MMP-2, MMP-9 and ZO-1 in the cortex. Pathological changes of neurons by H&E/Nissl/TUNEL staining suggested that Res could alleviate neuronal lesions. Moreover, Res inhibited the expressions of pro-inflammatory factors (IL-6, TNF-α) and chemokines (CCL3, CXCL10, MCP-1), but increased the expressions of anti-inflammatory factors (IL-4, IL-10) and neurotrophic factor (TGF-β, NGF and GDNF) in brain. In vitro cultured microglia cells, Res could suppress M1 microglia polarization and activate M2 microglia polarization. Co-culture of PRV-infected microglia with neuron cells by transwell system indicated that Res alleviated inflammatory response and neuronal apoptosis. ConclusionThis study provided evidence that Res could protect mice from PRV-induced encephalitis through regulation of microglia polarization and neuronal apoptosis suggesting the potential for treatment of viral encephalitis.

Modular Access to Quaternary α-Hydroxyl Acetates by Catalytic Cross-Coupling of Alcohols

Quaternary α-hydroxyl acids and their derivatives have attracted considerable attention because of their unique and broad functionalities. Herein, we successfully established a selective and modular protocol to access quaternary α-hydroxyl acetates via dehydrogenative cross-coupling of 1,2-diols and primary alcohols by using tris-N-heterocyclic carbene iridium (tris-NHC-Ir, 0.05 mol %) complexes as catalysts and Ba(OH)2 as the base, along with the generation of byproducts water and hydrogen gas. A plausible mechanism involving dehydrogenation of alcohols, aldol-condensation, and 1,2-alkyl rearrangement reactions was proposed, in which 1,2-alkyl rearrangement was responsible for the construction of the quaternary carbon center.

Bacterial community structure of electrogenic biofilm developed on modified graphite anode in microbial fuel cell

Formation of electrogenic microbial biofilm on the electrode is critical for harvesting electrical power from wastewater in microbial biofuel cells (MFCs). Although the knowledge of bacterial community structures in the biofilm is vital for the rational design of MFC electrodes, an in-depth study on the subject is still awaiting. Herein, we attempt to address this issue by creating electrogenic biofilm on modified graphite anodes assembled in an air–cathode MFC. The modification was performed with reduced graphene oxide (rGO), polyaniline (PANI), and carbon nanotube (CNTs) separately. To accelerate the growth of the biofilm, soybean-potato composite (plant) powder was blended with these conductive materials during the fabrication of the anodes. The MFC fabricated with PANI-based anode delivered the current density of 324.2 mA cm−2, followed by CNTs (248.75 mA cm−2), rGO (193 mA cm−2), and blank (without coating) (151 mA cm−2) graphite electrodes. Likewise, the PANI-based anode supported a robust biofilm growth containing maximum bacterial cell densities with diverse shapes and sizes of the cells and broad metabolic functionality. The alpha diversity of the biofilm developed over the anode coated with PANI was the loftiest operational taxonomic unit (2058 OUT) and Shannon index (7.56), as disclosed from the high-throughput 16S rRNA sequence analysis. Further, within these taxonomic units, exoelectrogenic phyla comprising Proteobacteria, Firmicutes, and Bacteroidetes were maximum with their corresponding level (%) 45.5, 36.2, and 9.8. The relative abundance of Gammaproteobacteria, Clostridia, and Bacilli at the class level, while Pseudomonas, Clostridium, Enterococcus, and Bifidobacterium at the genus level were comparatively higher in the PANI-based anode.

Genome-Wide Identification of BTB Domain-Containing Gene Family in Grapevine (Vitis vinifera L.)

BTB (broad-complex, tram track and bric-a-brac) proteins have broad functions in different growth processes and biotic and abiotic stresses. However, the biological role of these proteins has not yet been explored in grapevine, which draws our attention towards the BTB gene family. Herein, we identified 69 BTB genes (VvBTB) in the Vitis vinifera genome and performed comprehensive in silico analysis. Phylogenetic analysis classified VvBTB proteins into five groups, and further domain analysis revealed the presence of other additional functional domains. The majority of BTB proteins were localized in the nucleus. We also performed differential expression analysis by harnessing RNA- seq data of 10 developmental stages and different biotic and abiotic stresses. Our findings revealed the plausible roles of the BTB gene family in developmental stages; Fifty VvBTB were differentially expressed at different developmental stages. In addition, 47 and 16 VvBTB were responsive towards abiotic and biotic stresses, respectively. Interestingly, 13 VvBTB genes exhibited differential expression in at least one of the developmental stages and biotic and abiotic stresses. Further, miRNA target prediction of 13 VvBTB genes revealed that vvi-miR482 targets VvBTB56, and multiple miRNAs, such as vvi-miR172, vvi-miR169 and vvi-miR399, target VvBTB24, which provides an insight into the essential role of the BTB family in the grapevine. Our study provides the first comprehensive analysis and essential information that can potentially be used for further functional investigation of BTB genes in this economically important fruit crop.

Molecular dynamics simulations depict structural motions of the whole human aryl hydrocarbon receptor influencing its binding of ligands and HSP90

The aryl hydrocarbon receptor (AhR) has broad biological functions when its ligands activate it; the non-binding interactions with AhR have not been fully elucidated due to the absence of a complete tridimensional (3D) structure. Therefore, utilization of the whole 3D structure from Homo sapiens AhR by in silico studies will allow us to better study and analyze the binding mode of its full and partial agonists, and antagonists, as well as its interaction with the HSP90 chaperone. The 3D AhR structure was obtained from I-TASSER and subjected to molecular dynamics (MD) simulations to obtain different structural conformations and determine the most populated AhR conformer by clustering analyses. The AhR-3D structures selected from MD simulations and those from clustering analyses were used to achieve docking studies with some of its ligands and protein–protein docking with HSP90. Once the AhR-3D structure was built, its Ramachandran maps and energy showed a well-qualified 3D model. MD simulations showed that the per-Arnt-Sim homology (PAS) PAS A, PAS B, and Q domains underwent conformational changes, identifying the conformation when agonists were binding also, and HSP90 was binding near the PAS A, PAS B, and Q domains. However, when antagonists are binding, HSP90 does not bind near the PAS A, PAS B, and Q domains. These studies show that the complex agonist-AhR-HSP90 can be formed, but this complex is not formed when an antagonist is binding. Knowing the conformations when the ligands bind to AHR and the behavior of HSP90 allows for an understanding of its activity. Communicated by Ramaswamy H. Sarma

Molecular cloning and expression analysis of Myxovirus resistance gene in Yangzhou goose (Anser cygnoides domesticus)

ABSTRACT 1. Myxovirus resistance (Mx) is a protein produced by the interferon-induced natural immune response with broad spectrum antiviral function. However, the role and expression characteristics of the Mx gene in immune defence against viral infection in goose have not yet been reported. 2. This study found a 2576 bp genomic sequence and a 2112 bp mRNA sequence for Mx, encoding 703 amino acids. Multiple sequence alignments of the amino acid sequences showed that the Yangzhou goose Mx (goMx) had 86.99% similarity to the mallard duck (Anas platyrhynchos). 3. Tissue-specific expression profiling revealed that the expression of goMx was highest in the lung and spleen. Both poly (I:C) and GPV were found to elevate the expression of goMx. The upregulated expression of goMx was associated with interferon pathway-related genes IRF7, JAK1, STAT1, and STAT2. Furthermore, overexpression of goMx significantly activated the transcription of poly (I:C) induced TNF-α, IL-1β, IL-6, and IL-18. 4. The findings of this study suggest that the goMx modulation of the antiviral response is mediated by the interferon pathway.

A universal metasurface transfer technique for heterogeneous integration.

Metasurfaces offer a versatile platform for engineering the wavefront of light using nanostructures with subwavelength dimensions and hold great promise for dramatically miniaturizing conventional optical elements due to their small footprint and broad functionality. However, metasurfaces so far have been mainly demonstrated on bulky and planar substrates that are often orders of magnitude thicker than the metasurface itself. Conventional substrates not only nullify the reduced footprint advantage of metasurfaces, but also limit their application scenarios. The bulk substrate also determines the metasurface dielectric environment, with potentially undesired optical effects that undermine the optical performance. Here we develop a universal polymer-assisted transfer technique to tackle this challenge by decoupling the substrate employed on the fabrication of metasurfaces from that used for the target application. As an example, Huygens' metasurfaces with 120 nm thickness in the visible range (532 nm) are demonstrated to be transferred onto a 100 nm thick freestanding SiNx membrane while maintaining excellent structural integrity and optical performance of diffraction-limited focusing. This transfer method not only enables the thinnest dielectric metalens to the best of our knowledge, but also opens up new opportunities in integrating cascaded and multilayer metasurfaces, as well as the heterogeneous integration with nonconventional substrates and various electronic/photonic devices.

Genome-wide characterization, chromosome localization, and expression profile analysis of poplar non-specific lipid transfer proteins

Plant non-specific lipid transfer proteins (nsLTPs) are small and have a broad biological function involved in reproductive development and abiotic stress resistance. Although a small part of plant nsLTPs have been identified, these proteins have not been characterized in poplar at the genomic level. A genome-wide characterization and expression identification of poplar nsLTP members were performed in this study. A total of 42 poplar nsLTP genes were identified from the poplar genome. A comprehensive analysis of poplar nsLTPs was conducted by a phylogenetic tree, duplication events, gene structures, and conserved motifs. The cis-elements of poplar nsLTPs were predicted to respond to light, hormone, and abiotic stress. Many transcription factors (TFs) were identified to interact with poplar nsLTP cis-elements. The tested poplar nsLTPs were expressed in leaves, stems, and roots, but their expression levels differed among tested tissues. Most poplar nsLTP expression levels were changed by abiotic stress, implying that poplar nsLTP may be involved in abiotic stress resistance. Network analysis showed that poplar nsLTPs are putative genes involved in fatty acid (FA) metabolism. This research provides sight into the further study to explain the regulatory mechanism of the poplar nsLTPs.

The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors

An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents.

Tandem Denitrogenation Oxidative Coupling Reaction of Phenyl Vinyl Azides and Cyclic Ethers Under Metal‐Free Conditions

AbstractAn efficient synthesis of α‐oxoalkyl ketones is described. The current method is the coupling reaction of phenyl vinyl azides and cyclic ethers under metal‐free conditions. The reaction is conducted with KI as the additive and TBHP (70 % solution in water) as the oxidant at 60 °C for 12 h. A wide range of α‐oxyalkylated ketones with broad functionalities has been synthesized in moderate to good yields.

Enhancing electrochemical performance and stabilizing zinc anode in mild acidic electrolyte using combined additive

Rechargeable zinc-based batteries having aqueous electrolytes are renowned as promising alternatives for large scale energy storage systems (ESSs). However, in mild acidic electrolytes, zinc anodes pose several issues that have yet to be overcome. For tackling the major difficulties of zinc anodes, electrolyte engineering is the most practical and cost-effective strategy. Notwithstanding the broad variety of mechanisms associated with different electrolyte additives, the function of a single additive is straightforward. Finding combined additives with broader functionalities and greater efficacy is crucial. In this work, the combination of ionic liquid (IL) 1-butyl-1-methylpyrrolidinium dicyanamide ([BMPY][DCN]) and ethylene glycol (EG) as additives in an aqueous electrolyte 3 M ZnSO4 proves to be an effective strategy for simultaneously enhancing both zinc dissolution and deposition. IL significantly enhances zinc (Zn) dissolution and deposition while EG plays an important role in suppressing hydrogen evolution reaction (HER)and corrosion. Thus, 13.50 % improvement in capacity is achieved by the mixed additive EG + IL/ZnSO4 compared with the 3 M ZnSO4 electrolyte. In the Zn//Zn symmetrical system at 2 mA cm−2, the mixed additive greatly augments the cyclability of zinc, reaching over 400 h while maintaining excellent coulombic efficiency (CE). In-situ XAS and FT-EXAFS analyses confirm the high activities of both zinc oxidation/reduction in the mixed additive electrolyte. Results demonstrate that EG + IL/ZnSO4 can be applied to increase the cyclability of aqueous zinc-based batteries while sustaining high performance.

Селективные свойства двухрезонаторных структур и высокоизбирательные фильтры на их основе

An increase in the frequency selectivity of microstrip filters is traditionally achieved by forming transient response zeros at final frequencies. In this case, the specified requirements for the selectivity of filters are provided with a smaller number of resonators, and, consequently, lower loss es in the passband are achieved in more compact structures. Thus, the effectiveness of this approach to the synthesis of microstrip filters is determined by the number of transient response zeros that can potentially be formed in various structures. One way to form damping transient response zeros is to introduce additional cross-couplings between non-adjacent resonators. However, when synthesizing highly selective filters based on such widely used N-resonator structures, a limited number of transient response zeros equal to N-2 is formed. At the same time, two-resonator structures are known in which a much larger number of transient response zeros is formed, which is several times greater than the number of resonators in them. However, each of these structures has its own specific frequency-selective properties, which limits the scope of their wide application as universal links. The aim of this work is the synthesis of highly selective two-cavity structures with various types of frequency characteristics, which expands the scope of such structures. The frequency properties of microstrip two-resonator structures of a new type, which have broad functionality and increased frequency selectivity, are studied. It is shown that in multistage structures on two half-wave hairpin resonators, under certain conditions, a significant number of transient response zeros is formed, which is two to three times greater than the number of resonators in the filter, and parasitic transmission bands also degenerate. Depending on the ratio of the coefficients of electromagnetic interaction in different sections of the length of the coupled resonators, they acquire the properties of both single-band and multi-band bandpass filters, as well as low-pass filters. The noted features predetermine the possibility of wide application of these structures as both independent compact filters and basic units as part of higher-order filters with a significantly limited number of resonators. The results of electrodynamic 3D modeling and experimental studies of the proposed structures are presented, which are in good agreement.

Русская идея и китежская тема: «Сказание о невидимом граде Китеже...» Н. А. Римского-Корсакова как вершина истории русской духовности

The article is devoted to the consideration of the «Russian idea» in the projection on the broad historical functioning of the legend of the city of Kitezh, which received artistic embodiment in the work of the opera «The Legend of the Invisible City of Kitezh and the Virgin Fevronia». The author emphasizes the fundamental essential aspects of the «Russian idea», relying on the works of F. M. Dostoevsky, V. S. Solovyov, N. A. Berdyaev. A special series of Russian wanderers is being built, aspiring to metaphorical Russia in search of truth: Kitezhans — non-possessors — netovtsy — wanderers — schismatics — Masons — intellectuals — cosmists. Walking into the invisible city in the finale of Rimsky-Korsakov's opera is the final abandonment of the present imperfect Russia by persecuted schismatic idealists. Russian cosmism appears as a universal construct for the musical embodiment of the myth of the saved city at the peak stage of Rimsky-Korsakov's creativity. The metaphor of «Kitezh» is a reflection of the composer's sad conviction that a new period of Russian historical drama is inevitable.