Dual Functional Role Research Articles

Bacterial seed endophytes promote barley growth and inhibits Fusarium graminearum in vitro

ObjectivesSeeds host microbes that function in plant growth and phytopathogen resistance. The aim of the work was to investigate total bacterial community in malting barley seeds and whether their bacterial seed endophytes have dual functional roles in plant growth-promotion and inhibition of Fusarium graminearum, the causative agent of Fusarium head blight (FHB) in barley. We used culture dependent and culture independent methods.ResultsPhylogenetic classification of seed endophytic bacteria based on sequencing data identified B. subtilis, B. licheniformis and B. pumilis as predominant subgroups. Location driven divergence in bacterial endophytic communities was evident based on a clear separation of the samples from Crookston and other location samples. The bio-primed seeds using one hundred and seventy bacterial isolates showed that 3.5% (6/170) of the bacterial isolates conferred greater than 10% increase in both root length (RL) and shoot length (SL), while 19.4% (33/170) and 26.5% (45/170) showed RL and SL specific growth effects, respectively, relative to controls. Among the six bacterial isolates that increased RL and SL, five (#29, #63, #109, #124 and #126) also significantly inhibit the growth of F. graminearum based on in vitro assays. This study identified novel seed bacterial endophytes that could be further exploited for promoting growth during seedling establishment and as biocontrol for combating the devastating scab disease.

GbHSP90 act as a dual functional role regulated in telomere stability in Ginkgo biloba

The heat shock protein 90 (HSP90) family members are not only widely involved in animal cellular immune response and signal transduction pathway regulation, but also play an important role in plant development and environmental stress response. Here,we identified a HSP90 family member in Ginkgo biloba, designated as GbHSP90, which performs a dual functional role to regulate telomere stability. GbHSP90 was screened by a yeast one-hybrid library using the Ginkgo biloba telomeric DNA (TTTAGGG)5. Fluorescence polarization, surface plasmon resonance(SPR) and EMSA technologyies revealed a specific interaction between GbHSP90 and the double-stranded telomeric DNA via its N-CR region, with no affinity for the single-stranded telomeric DNA or human double-stranded telomeric DNA. Furthermore, yeast two-hybrid system and Split-LUC assay demonstrated that GbHSP90 can interacts with two telomere end-binding proteins:the ginkgo telomerase reverse transcriptase (GbTERT) and the ginkgo Structural Maintenance of Chromosomes protein 1 (GbSMC1). Overexpression of GbHSP90 in human 293 T and HeLa cells increased cell growth rate, the content of telomerase reverse transcriptase (TERT), and promote cell division and inhibit cell apoptosis. Our results indicated GbHSP90 have dually functions: as a telomere-binding protein that binds specifically to double-stranded telomeric DNA and as a molecular chaperone that modulates cell differentiation and apoptosis by binding to telomere protein complexes in Ginkgo biloba. This study contributes to a significantly understanding of the unique telomere complex structure and regulatory mechanisms in Ginkgo biloba, a long-lived tree species.

Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring.

Due to the rise in overnutrition, the incidence of obesity-induced hepatocellular carcinoma (HCC) will continue to escalate; however, our understanding of the obesity to HCC developmental axis is limited. We constructed a single-cell atlas to interrogate the dynamic transcriptomic changes during hepatocarcinogenesis in mice. Here we identify fatty acid binding protein 5 (FABP5) as a driver of obesity-induced HCC. Analysis of transformed cells reveals that FABP5 inhibition and silencing predispose cancer cells to lipid peroxidation and ferroptosis-induced cell death. Pharmacological inhibition and genetic ablation of FABP5 ameliorates the HCC burden in male mice, corresponding to enhanced ferroptosis in the tumour. Moreover, FABP5 inhibition induces a pro-inflammatory tumour microenvironment characterized by tumour-associated macrophages with increased expression of the co-stimulatory molecules CD80 and CD86 and increased CD8+ T cell activation. Our work unravels the dual functional role of FABP5 in diet-induced HCC, inducing the transformation of hepatocytes and an immunosuppressive phenotype of tumour-associated macrophages and illustrates FABP5 inhibition as a potential therapeutic approach.

Dual-functional nano-photosensitizers: Eosin-Y decorated gold nanorods for plasmon-enhanced fluorescence and singlet oxygen generation.

Photosensitizer (PS) with enhanced fluorescence is attractive for image-guided photodynamic therapy (PDT) due to its dual functional role in Singlet Oxygen Generation (SOG) and producing high fluorescence signals. Here, Eosin-Y (Ey) decorated polymer coated gold nanorods (GNRs) of different aspect ratios are synthesized and introduced as novel plasmon-enhanced nano-photosensitizers for this purpose. We show, upon excitation at 519 nm, simultaneous enhancement in fluorescence and SOG was achieved for the hybrid nanostructure. The best enhancement factors of 110 and 18 for metal-enhanced fluorescence and metal-enhanced SOG, respectively, are obtained with GNRs of length 133 nm and width 45 nm, where Ey is positioned at 12.6 nm from the metal core using layer-by-layer assembly of oppositely charged polymers. The observed plasmonic effect is critically analysed by comparing the near field damping rate along with decay length, far field scattering and nonradiative energy transfer of the nanohybrids.

MR-TADF emitter as a dual-functional solid additive to extend exciton lifetime and optimize morphology for organic solar cells with ∼19% efficiency

Extending exciton lifetime and optimizing active-layer morphology simultaneously to advance power conversion efficiency (PCE) of organic solar cells (OSCs) still encounter great challenges by conventional additive strategies. Herein, to address these issues, a multiple-resonance thermally activated delayed fluorescence (MR-TADF) emitter of BNS-H1 containing heteroatom-embedded polycyclic aromatic hydrocarbon is innovatively served as a dual-functional solid additive (DFSA) in OSCs. The primary studies on the PM6:Y6 system indicate that BNS-H1 plays an exceptional dual-functional role in promoting π-π stacking of Y6 component and optimizing active-layer morphology. Meanwhile, the steady/transient photoluminescence spectra and transient photocurrent measurements further reveal that incorporating BNS-H1 with the system enhances emission of PM6 component, extend exciton lifetime and diffusion distance. Consequently, four types of binary OSCs demonstrate a notable improvement in PCE processed by 1.0 wt% BNS-H1. Specifically, the BNS-H1-treated OSCs with PM6:Y6 and PM6:BTP-eC9 systems achieve outstandingly increasing PCEs of 17.4% and 18.8% compared to their BNS-H1-free control devices, respectively. Furthermore, device stability of the BNS-H1-treated PM6:Y6 devices is significantly enhanced. Notably, the approaching 19% efficiency is one of the highest PCEs in the reported non-volatile additives treated binary OSCs. Our work highlights the significant potential of MR-TADF emitter as a DFSA in OSCs for boosting PCEs.

MiR-124-3p negatively impacts embryo implantation via suppressing uterine receptivity formation and embryo development

During embryo implantation, blastocyst interacts with the receptivity endometrium and the endometrial epithelium secretes nurturing fluid to support embryonic development. Interferon-λ (IFN-λ) is a novel, non-redundant regulator that participates in the fetal–maternal interaction; however, the precise molecular mechanism underlying its impact on uterine receptivity remains elusive. Here, microarray profiling revealed that 149 specific miRNAs were differentially expressed in the human endometrial cells following IFN-λ treatment. In particular, miR-124-3p expression was significantly reduced after IFN-λ treatment (p < 0.05). An in vivo mouse pregnancy model showed that miR-124-3p overexpression notably decreased embryo implantation rate and led to an aberrant epithelial phenotype. Furthermore, miR-124-3p negatively impacted the migration and proliferation of endometrial cells, and hindered embryonic developmental competence in terms of blastocyst formation and global DNA re-methylation. Downstream analysis showed that LIF, MUC1 and BCL2 are potential target genes for miR-124-3p, which was confirmed using western blotting and immunofluorescence assays. In conclusion, IFN-λ-driven downregulation of miR-124-3p during embryo implantation modulates uterine receptivity. The dual functional role of miR-124-3p suggests a cross-talk model wherein, maternal endometrial miRNA acts as a transcriptomic modifier of the peri-implantation endometrium and embryo development.

Phytochemicals-linked food safety and human health protective benefits of the selected food-based botanicals.

Phytochemicals-rich food-based botanicals including traditional or under-utilized plant-based ingredients can serve a dual functional role to help counter food contamination of bacterial origin, while also addressing the rise of diet-linked non-communicable chronic diseases (NCDs) such as type 2 diabetes, chronic hypertension and the associated oxidative stress. Hence the screening of these food-based botanicals for their phenolic content and profile, as well as antimicrobial, antioxidant, anti-hyperglycemic and anti-hypertensive properties has relevant merit. Using in vitro assay models, hot water extracts of different forms (slice, pickle, or powder) of amla (Phyllanthus emblica), clove (Syzygium aromaticum), kokum (Garcinia indica), and garlic (Allium sativum) were analyzed for their total soluble phenolic content (TSP) and phenolic profile as well as antimicrobial activity against strains of Salmonella Enteritidis, Listeria monocytogenes, and Escherichia coli that are associated with food-borne disease outbreaks. In addition, the antioxidant, anti-hyperglycemic and anti-hypertensive activity of the extracts were also determined using in vitro assay models, with the goal of establishing a dual functional role of the food safety and health protective benefits of these botanicals. A high baseline TSP content was observed in all the extracts and the major phenolic phytochemicals detected were gallic, cinnamic, ellagic, benzoic, dihydroxybenzoic, protocatechuic, and p-coumaric acid along with catechin and rutin. All extracts displayed significant antimicrobial activity against most of the bacterial strains tested and the antimicrobial activity was specific for each strain targeted in this study. Furthermore, significant antioxidant, anti-hyperglycemic and antihypertensive activity were observed among the botanical extracts, especially among the amla and kokum extracts. These results indicate that phytochemicals enriched botanicals, including amla and kokum, can be integrated into modern-day food preservation and dietary support strategies aimed at improving the food safety and health protective benefits of the food matrix.

The dual-functional role of carboxylate in a nickel-iron catalyst towards efficient oxygen evolution.

The efficiency of the oxygen evolution reaction (OER) is severely limited by the sluggish proton-coupled electron transfer processes and inadequate long-term stability. Herein, we introduce a carboxylate group (TPA) to modify NiFe layered double hydroxide (NiFe LDH@TPA), resulting in notable improvements in both activity and stability. A combination of spectroscopic and theoretical investigations reveals the dual-functional role of incorporated TPA. It facilitates the deprotonation of OER intermediates while strengthening the Fe-O bond and acting as a molecular fence, ensuring superior OER kinetics and anti-dissolution properties. NiFe LDH@TPA delivers a low overpotential of 200 mV at 10 mA cm-2 and an impressive long-term stability of 500 h at 150 mA cm-2, significantly outperforming its unmodified counterpart. Furthermore, operating in an anion exchange membrane water electrolyzer, it affords prolonged stability at an industrial-scale current density of 1 A cm-2, sustaining performance for over 120 hours. This strategy offers a promising avenue for the development of durable and efficient OER catalysts.

Dual functional roles of nutritional additives in nutritional fortification and safety of thermally processed food: Potential, limitations, and perspectives.

The Maillard reaction (MR) has been established to be a paramount contributor to the characteristic sensory property of thermally processed food products. Meanwhile, MR also gives rise to myriads of harmful byproducts (HMPs) (e.g., advanced glycation end products (AGEs) and acrylamide). Nutritional additives have attracted increasing attention in recent years owing to their potential to simultaneously improve nutritional quality and attenuate HMP formation. In this manuscript, a brief overview of various nutritional additives (vitamins, minerals, fatty acids, amino acids, dietary fibers, and miscellaneous micronutrients) in heat-processed food is provided, followed by a summary of the formation mechanisms of AGEs and acrylamide highlighting the potential crosstalk between them. The main body of the manuscript is on the capability of nutritional additives to modulate AGE and acrylamide formation besides their traditional roles as nutritional enhancers. Finally, limitations/concerns associated with their use to attenuate dietary exposure to HMPs and future perspectives are discussed. Literature data support that through careful control of the addition levels, certain nutritional additives possess promising potential for simultaneous improvement of nutritional value and reduction of AGE and acrylamide content via multiple action mechanisms. Nonetheless, there are some major concerns that may limit their wide applications for achieving such dual functions, including influence on sensory properties of food products, potential overestimation of nutrition enhancement, and introduction of hazardous alternative reaction products or derivatives. These could be overcome through comprehensive assay of dose-response relationships and systematic evaluation of the diverse combinations from the same and/or different categories of nutritional additives to establish synergistic mixtures.

Function of iron-stress-induced protein A in cyanobacterial cells with monomeric and trimeric photosystem I.

The acclimation of cyanobacteria to iron deficiency is crucial for their survival in natural environments. In response to iron deficiency, many cyanobacterial species induce the production of a pigment-protein complex called iron-stress-induced protein A (IsiA). IsiA proteins associate with photosystem I (PSI) and can function as light-harvesting antennas or dissipate excess energy. They may also serve as chlorophyll storage during iron limitation. In this study, we examined the functional role of IsiA in cells of Synechocystis sp. PCC 6803 grown under iron limitation conditions by measuring the cellular IsiA content and its capability to transfer energy to PSI. We specifically tested the effect of the oligomeric state of PSI by comparing wild-type (WT) Synechocystis sp. PCC 6803 with mutants lacking specific subunits of PSI, namely PsaL/PsaI (PSI subunits XI/VIII) and PsaF/PsaJ (PSI subunits III/IX). Time-resolved fluorescence spectroscopy revealed that IsiA formed functional PSI3-IsiA18 supercomplexes, wherein IsiA effectively transfers energy to PSI on a timescale of 10 ps at room temperature-measured in isolated complexes and in vivo-confirming the primary role of IsiA as an accessory light-harvesting antenna to PSI. However, a notable fraction (40%) remained unconnected to PSI, supporting the notion of a dual functional role of IsiA. Cells with monomeric PSI under iron deficiency contained, on average, only 3 to 4 IsiA complexes bound to PSI. These results show that IsiA can transfer energy to trimeric and monomeric PSI but to varying degrees and that the acclimatory production of IsiA under iron stress is controlled by its ability to perform its light-harvesting function.

A domestic pressure cooker mediated, facile autoclaving method for the synthesis of silver nanoparticles

As an alternative to an expensive hydrothermal reactor, in the current method a domestic pressure was used for the synthesis of silver nanoparticles (Ag NP) using tree gum, kondagogu as dual functional reductant and stabilizer by autoclaving. The formation of Ag NP was evaluated with colour transformation, UV-Visible spectroscopy (UV–Vis) and transmission electron microscopy. The formation of Ag NP by gum confirmed from the developed yellow coloration of the solution and the appearance of surface plasmon resonance peak at 408 nm in the UV–Vis. The produced NP were spherical, polydisperse, particle size ranged from 2.9–17.6 nm and the average particle size was 4.5 ± 3.1 nm. The developed method is useful for demonstration, gaining hands on experience and production of metal and metal oxide NP in resource limited small laboratories, rural colleges, startups etc.•Pressure cooker serves as an easily accessible, durable, inexpensive, electricity independent hydrothermal nanoparticle production vessel.•Autoclaving serves as a facile, ecofriendly, less energy consuming, one pot, green method with dual functional role of in situ nanoparticle synthesis and sterilization.•Production of intrinsically safe and sterile nanoparticles amenable for in vivo and in vitro biomedical applications.

TDCs - a distinct subset with dual functional and developmental roles.

tDCs - a distinct subset with dual functional and developmental roles.

Carbon neutral hydrogen storage and release cycles based on dual-functional roles of formamides

The development of alternative clean energy carriers is a key challenge for our society. Carbon-based hydrogen storage materials are well-suited to undergo reversible (de)hydrogenation reactions and the development of catalysts for the individual process steps is crucial. In the current state, noble metal-based catalysts still dominate this field. Here, a system for partially reversible and carbon-neutral hydrogen storage and release is reported. It is based on the dual-functional roles of formamides and uses a small molecule Fe-pincer complex as the catalyst, showing good stability and reusability with high productivity. Starting from formamides, quantitative production of CO-free hydrogen is achieved at high selectivity ( > 99.9%). This system works at modest temperatures of 90 °C, which can be easily supplied by the waste heat from e.g., proton-exchange membrane fuel cells. Employing such system, we achieve >70% H2 evolution efficiency and >99% H2 selectivity in 10 charge-discharge cycles, avoiding undesired carbon emission between cycles.

Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKCδ during Plasticity.

The activity-dependent plasticity of synapses is believed to be the cellular basis of learning. These synaptic changes are mediated through the coordination of local biochemical reactions in synapses and changes in gene transcription in the nucleus to modulate neuronal circuits and behavior. The protein kinase C (PKC) family of isozymes has long been established as critical for synaptic plasticity. However, because of a lack of suitable isozyme-specific tools, the role of the novel subfamily of PKC isozymes is largely unknown. Here, through the development of fluorescence lifetime imaging-fluorescence resonance energy transfer activity sensors, we investigate novel PKC isozymes in synaptic plasticity in CA1 pyramidal neurons of mice of either sex. We find that PKCδ is activated downstream of TrkB and DAG production, and that the spatiotemporal nature of its activation depends on the plasticity stimulation. In response to single-spine plasticity, PKCδ is activated primarily in the stimulated spine and is required for local expression of plasticity. However, in response to multispine stimulation, a long-lasting and spreading activation of PKCδ scales with the number of spines stimulated and, by regulating cAMP response-element binding protein activity, couples spine plasticity to transcription in the nucleus. Thus, PKCδ plays a dual functional role in facilitating synaptic plasticity.SIGNIFICANCE STATEMENT Synaptic plasticity, or the ability to change the strength of the connections between neurons, underlies learning and memory and is critical for brain health. The protein kinase C (PKC) family is central to this process. However, understanding how these kinases work to mediate plasticity has been limited by a lack of tools to visualize and perturb their activity. Here, we introduce and use new tools to reveal a dual role for PKCδ in facilitating local synaptic plasticity and stabilizing this plasticity through spine-to-nucleus signaling to regulate transcription. This work provides new tools to overcome limitations in studying isozyme-specific PKC function and provides insight into molecular mechanisms of synaptic plasticity.

Photocatalytic Defluoroalkylation of Trifluoroacetates with Alkenes using 4-(Acetamido)thiophenol

AbstractUnder mild irradiation conditions using violet light-emitting diodes, a catalytic amount of a thiolate of N-(4-mercaptophenyl)pivalamide promotes monoselective defluoroalkylation of trifluoroacetates with a variety of aliphatic alkenes in the presence of a formate salt. The reactions allow facile and low-cost synthesis of valuable α,α-difluoro substituted aliphatic carboxylate esters under mild conditions, and demonstrate the dual-functional role of arenethiolates in photocatalysis as both a strong photoreductant in a redox cycle and a hydrogen-atom-transfer catalyst.

Identification of Agents That Ameliorate Hyperphosphatemia-Suppressed Myogenin Expression Involved in the Nrf2/p62 Pathway in C2C12 Skeletal Muscle Cells.

Hyperphosphatemia can occur as a result of reduced phosphate (Pi) excretion in cases of kidney dysfunction, which can induce muscle wasting and suppress myogenic differentiation. Higher Pi suppresses myogenic differentiation and promotes muscle atrophy through canonical (oxidative stress-mediated) and noncanonical (p62-mediated) activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. However, the crosstalk between myogenin and Nrf2/p62 and potential drug(s) for the regulation of myogenin expression needed to be addressed. In this study, we further identified that myogenin may negatively regulate Nrf2 and p62 protein levels in the mouse C2C12 muscle cell line. In the drug screening analysis, we identified N-acetylcysteine, metformin, phenformin, berberine, 4-chloro-3-ethylphenol, cilostazol, and cilomilast as ameliorating the induction of Nrf2 and p62 expression and reduction in myogenin expression that occur due to high Pi. We further elucidated that doxorubicin and hydrogen peroxide reduced the amount of myogenin protein mediated through the Kelch-like ECH-associated protein 1/Nrf2 pathway, differently from the mechanism of high Pi. The dual functional roles of L-ascorbic acid (L-AA) were found to be dependent on the working concentration, where concentrations below 1 mM L-AA reversed the effect of high Pi on myogenin and those above 1 mM L-AA had a similar effect of high Pi on myogenin when used alone. L-AA exacerbated the effect of hydrogen peroxide on myogenin protein and had no further effect of doxorubicin on myogenin protein. In summary, our results further our understanding of the crosstalk between myogenin and Nrf2, with the identification and verification of several potential drugs that can be applied in rescuing the decline of myogenin due to high Pi in muscle cells.

Vascularized polypeptide hydrogel modulates macrophage polarization for wound healing

Wound repair involves a sophisticated process that includes angiogenesis, immunoregulation and collagen deposition. However, weak revascularization performance and the lack of biochemical cues to trigger immunomodulatory function currently limit biomaterial applications for skin regeneration and tissue engineering. Herein, we fabricate a new bioactive polypeptide hydrogel (QK-SF) constituted by silk fibroin (SF) and a vascular endothelial growth factor mimetic peptide KLTWQELYQLKYKGI (QK) for tissue regeneration by simultaneously promoting vascularization and macrophage polarization. Our results showed that this QK-SF hydrogel can be prepared via an easy manufacturing process, and exhibited good gel stability and low cytotoxicity to cultured human umbilical vein endothelial cells (HUVECs) via both live/dead and cell counting kit-8 assays. Importantly, this QK-SF hydrogel triggered macrophage polarization from M1 into M2, as exemplified by the enhanced expression of the M2 marker and decreased expression of the M1 marker in RAW264.7 cells. Furthermore, the QK-SF hydrogel showed high capacity for inducing endothelial growth, migration and angiogenesis, which were proved by increased expression of angiogenesis-related genes in HUVECs. Consistent with in vitro findings, in vivo data show that the QK-SF hydrogel promoted M2 polarization, keratinocyte differentiation, and collagen deposition in the mouse skin wound model in immunohistochemistry assay. Furthermore, this QK-SF hydrogel can reduce inflammation, induce angiogenesis and promote wound healing as exemplified by the increased vessel formation and decreased wound area in the mouse skin wound model. Altogether, these results indicate that the bioactive QK-SF hydrogel plays dual functional roles in promoting angiogenesis and immunoregulation for tissue regeneration. Statement of significanceThe QK-SF hydrogel plays dual functional roles in promoting angiogenesis and immunoregulation for tissue repair and wound healing. The QK-SF hydrogel can be prepared via an easy manufacturing process, and exhibited good gel stability and low cytotoxicity to cultured HUVECs. The QK-SF hydrogel triggered macrophage polarization from M1 into M2. The QK-SF hydrogel showed high capacity for inducing endothelial growth, migration and angiogenesis. The QK-SF hydrogel promoted M2 polarization, keratinocyte differentiation, and collagen deposition.

Dual functional roles of a novel bifunctional β-lactamase/esterase from Lactococcus garvieae

A novel bifunctional β-lactamase/esterase (LgLacI), which is capable of hydrolyzing β-lactam-containing antibiotics including ampicillin, oxacillin, and cefotaxime as well as synthesizing biodiesels, was cloned from Lactococcus garvieae. Unlike most bacterial esterases/lipases that have G-x-S-x-G motif, LgLacI, which contains S-x-x-K catalytic motif, has sequence similarities to bacterial family VIII esterase as well as β-lactamases. The catalytic properties of LgLacI were explored using a wide range of biochemical methods including spectroscopy, assays, structural modeling, mutagenesis, and chromatography. We confirmed the bifunctional property of LgLacI hydrolyzing both esters and β-lactam antibiotics. This study provides novel perspectives into a bifunctional enzyme from L. garvieae, which can degrade β-lactam antibiotics with high esterase activity.

Depicting the Implication of miR-378a in Cancers.

MicroRNA-378a (miR-378a), including miR-378a-3p and miR-378a-5p, are encoded in PPARGC1B gene. miR-378a is essential for tumorigenesis and is an independent prognostic biomarker for various malignant tumors. Aberrant expression of miR-378a affects several physiological and pathological processes, including proliferation, apoptosis, tumorigenesis, cancer invasion, metastasis, and therapeutic resistance. Interestingly, miR-378a has a dual functional role in either promoting or inhibiting tumorigenesis, independent of the cancer type. In this review, we comprehensively summarized the role and regulatory mechanisms of miR-378a in cancer development, hoping to provide a direction for its potential use in cancer therapy.

Carbon Neutral Hydrogen Storage and Release Cycles Based on Dual-Functional Role of Formamides

Carbon Neutral Hydrogen Storage and Release Cycles Based on Dual-Functional Role of Formamides