Dual Roles Research Articles

Abstract 5448: Malignant RNA editing by inflammation-responsive RNA editase ADAR1 drives T-cell leukemia relapse via attenuating dsRNA sensing

Abstract Leukemia-initiating cells (LICs) play a crucial role in leukemia research and treatment, being considered the source of relapse and resistance, posing a substantial challenge for successful management of the disease. It's crucial to identify the key factors that drive LIC self-renewal to develop targeted methods for eliminating LICs and preventing relapse. In this study, we demonstrate that the RNA editing enzyme ADAR1 plays a vital role as a determinant of stemness, promoting LIC self-renewal by reducing the detection of abnormal double-stranded RNA (dsRNA). As a result, ADAR1-knockdown significantly impairs the ability of LICs to self-renew and extends survival in T-ALL PDX models. We performed RNA-seq studies on enriched T-ALL LICs (CD34+Lin-). The lentivirus-to-cell ratio was optimized to achieve a 50% reduction in ADAR1, resulting in differential expression of 661 genes, with downregulation of critical self-renewal genes in ADAR1-deficient leukemia-initiating cells. Importantly, additional data indicated that ADAR1 likely influences self-renewal gene expression independently of A-to-I RNA editing, revealing novel regulatory mechanisms in leukemia. Knockdown of MDA5 and ADAR1 in patient-derived xenograft (PDX) T-ALL leukemia-initiating cells (LICs) revealed diverse rescue effects on self-renewal in different PDX models. The differential response was associated with variations in gene expression patterns in Rig-I-Like signaling and cytosolic sensing pathways, suggesting intrinsic differences in IFN signaling properties among patients. Moreover, the study proposes a patient-specific reliance on the ADAR1 p150-MDA5 axis for promoting self-renewal, as evidenced by differential rescue effects and varying expression levels of ADAR1 isoforms and MDA5 in T-ALL patient samples and cell lines. ADAR1, beyond its role in RNA editing, acts as a dsRNA binding protein, exerting RNA editing-independent functions to suppress aberrant IFN signaling and promote cancer progression. Using Jurkat cells with high intrinsic MDA5 levels, an ADAR1 knockout (KO) was generated, revealing that ADAR1 is upregulated by IFN treatment, predominantly the p150 isoform. We explored the dual roles of ADAR1—RNA editing-dependent and -independent—in suppressing IFN-induced apoptosis, demonstrating the necessity of both for optimal function. Additionally, ADAR1 was found to suppress cytoplasmic dsRNA sensing pathways, such as RIG-I and PKR, and its RNA editing-independent activity contributes significantly to the suppression of interferon-stimulated gene (ISG) expression in T-ALL. In summary, our findings reveal that ADAR1 acts as a factor that promotes self-renewal while limiting the recognition of naturally occurring dsRNA. Therefore, targeting ADAR1 emerges as a safe and effective therapeutic approach for eradicating LICs in T-ALL. Citation Format: Maria Dolores Rivera, Haoran Zhang, Qingchen Zhou, Jessica Pham, Jane Isquith, Roman Sasik, Adam Mark, Sabina Enlund, Frida Holm, Ma Wenxue, Kathleen Fisch, Dennis Kuo, Catriona Jamieson, Qingfei Jiang. Malignant RNA editing by inflammation-responsive RNA editase ADAR1 drives T-cell leukemia relapse via attenuating dsRNA sensing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5448.

Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high-grade serous ovarian cancer cells.

No data are currently available on the functional role of small conductance Ca2+ -activated K+ channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non-cell-permeant SK2 inhibitor Lei-Dab7, we identified functional SK2 channels at the plasma membrane, regulating store-operated Ca2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei-Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei-Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro-migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression-free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination.

Performance Enhancement of Tin-Based Perovskite Photodetectors through Bifunctional Cesium Fluoride Engineering.

Tin halide perovskites are rising as promising candidates for next-generation optoelectronic materials due to their good optoelectronic properties and relatively low toxicity. However, the high defect density and the easy oxidation of Sn2+ have limited their optoelectronic performance. Herein, we report the treatment of the FASnI3 (formamidinium tin, FA) perovskite film by a bifunctional cesium fluoride (CsF) additive, which improves the film quality and significantly enhances the photoelectric performance. The responsivity of the perovskite-based photodetector (PD) with an optimal CsF concentration of 15% is over 60 times larger than that of the PD without CsF. It indicates that both the Cs substitution and the fluoride anion additive from CsF inhibit the oxidation of Sn2+, optimize the crystal growth, and passivate the defects, demonstrating the dual roles of the CsF additive in improving the photoelectric performance. This work offers valuable insights into the additive selection for developing high-quality tin-based perovskite films and devices.

NHC-Au-Catalyzed Isomerization of Propargylic B(MIDA)s to Allenes and Double Isomerization of Alkynes to 1,3-Dienes.

The synthesis of allenyl boronates is an important yet challenging topic in organic synthesis. Reported herein is an NHC-gold-catalyzed 1,3-H shift toward allenyl boronates synthesis from simple propargylic B(MIDA)s. Mechanistic studies suggest dual roles of the boryl moiety in the reaction: to activate the substrate for isomerization and at the same time, to prevent the allene product from further isomerization. These effects should be a result of α-anion stabilization and α-cation destabilization conferred by the B(MIDA) moiety, respectively. The NHC-Au catalyst, which is commercially available, is also found to be reactive in alkyne-to-1,3-diene isomerization reactions in an atom-economic and base-free manner.

Neutrophils in cancer: dual roles through intercellular interactions.

Neutrophils, the most abundant immune cells in human blood, play crucial and diverse roles in tumor development. In the tumor microenvironment (TME), cancer cells regulate the recruitment and behaviors of neutrophils, transforming some of them into a pro-tumor phenotype. Pro-tumor neutrophils interact with cancer cells in various ways to promote cancer initiation, growth, and metastasis, while anti-tumor neutrophils interact with cancer cells to induce senescence and death. Neutrophils can also interact with other cells in TME, including T cells, macrophages, stromal cells, etc. to exert anti- or pro-tumor functions. In this review, we will analyze the anti- and pro-tumor intercellular interactions mediated by neutrophils, with a focus on generalizing the mechanisms underlying the interaction of neutrophils with tumor cells and T cells. Furthermore, we will provide an overview of cancer treatment strategies targeting neutrophil-mediated cellular interactions.

CaIAA2-CaARF9 module mediates the trade-off between pepper growth and immunity.

To challenge the invasion of various pathogens, plants re-direct their resources from plant growth to an innate immune defence system. However, the underlying mechanism that coordinates the induction of the host immune response and the suppression of plant growth remains unclear. Here we demonstrate that an auxin response factor, CaARF9, has dual roles in enhancing the immune resistance to Ralstonia solanacearum infection and in retarding plant growth by repressing the expression of its target genes as exemplified by Casmc4, CaLBD37, CaAPK1b and CaRROP1. The expression of these target genes not only stimulates plant growth but also negatively impacts pepper resistance to R. solanacearum. Under normal conditions, the expression of Casmc4, CaLBD37, CaAPK1b and CaRROP1 is active when promoter-bound CaARF9 is complexed with CaIAA2. Under R. solanacearum infection, however, degradation of CaIAA2 is triggered by SA and JA-mediated signalling defence by the ubiquitin-proteasome system, which enables CaARF9 in the absence of CaIAA2 to repress the expression of Casmc4, CaLBD37, CaAPK1b and CaRROP1 and, in turn, impeding plant growth while facilitating plant defence to R. solanacearum infection. Our findings uncover an exquisite mechanism underlying the trade-off between plant growth and immunity mediated by the transcriptional repressor CaARF9 and its deactivation when complexed with CaIAA2.

Photocatalyst-Free Activation of Sulfamoyl Chlorides for Regioselective Sulfamoyl-Oximation of Alkenes via Hydrogen Atom Transfer (HAT) and Halogen-Atom Transfer (XAT) Relay Strategy.

The use of readily available and diverse sulfamoyl chlorides for synthesizing sulfonamide compounds presents an intriguing, yet significantly underexplored strategy. Activating sulfamoyl chlorides via single-electron reduction poses challenges due to their high reduction potential. Alternatively, the SO2-Cl bond in sulfamoyl chlorides could be readily cleaved by XAT. However, the existing methodologies have been limited to either the use of photocatalyst or the monofunctionalization of activated alkenes. Here, we report a regioselective sulfamoyl-oximation of alkenes by involving the activation of sulfamoyl chlorides through a HAT and XAT relay strategy in a photocatalyst-free way. The key to this success lies in the dual roles of tert-butyl nitrite (TBN), which not only serves as the source of oximes but also acts as the HAT reagent to generate the crucial XAT reactive species. The exclusion of metal catalysts or photosensitizers for utilizing light energy renders this protocol versatile and universally applicable for synthesizing a broad range of structurally diverse oxime-containing alkyl sulfonamides.

N2 -Acetylornithine deacetylase functions as a Cys-Gly dipeptidase in the cytosolic glutathione degradation pathway in Arabidopsis thaliana.

Glutathione (GSH) is required for various physiological processes in plants, including redox regulation and detoxification of harmful compounds. GSH also functions as a repository for assimilated sulfur and is actively catabolized in plants. In Arabidopsis, GSH is mainly degraded initially by cytosolic enzymes, γ-glutamyl cyclotransferase, and γ-glutamyl peptidase, which release cysteinylglycine (Cys-Gly). However, the subsequent enzyme responsible for catabolizing this dipeptide has not been identified to date. In the present study, we identified At4g17830 as a Cys-Gly dipeptidase, namely cysteinylglycine peptidase 1 (CGP1). CGP1 complemented the phenotype of the yeast mutant that cannot degrade Cys-Gly. The Arabidopsis cgp1 mutant had lower Cys-Gly degradation activity than the wild type and showed perturbed concentrations of thiol compounds. Recombinant CGP1 showed reasonable Cys-Gly degradation activity in vitro. Metabolomic analysis revealed that cgp1 exhibited signs of severe sulfur deficiency, such as elevated accumulation of O-acetylserine (OAS) and the decrease in sulfur-containing metabolites. Morphological changes observed in cgp1, including longer primary roots of germinating seeds, were also likely associated with sulfur starvation. Notably, At4g17830 has previously been reported to encode an N2 -acetylornithine deacetylase (NAOD) that functions in the ornithine biosynthesis. The cgp1 mutant did not show a decrease in ornithine content, whereas the analysis of CGP1 structure did not rule out the possibility that CGP1 has Cys-Gly dipeptidase and NAOD activities. Therefore, we propose that CGP1 is a Cys-Gly dipeptidase that functions in the cytosolic GSH degradation pathway and may play dual roles in GSH and ornithine metabolism.

Meiotic prophase length modulates Tel1-dependent DNA double-strand break interference.

During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we provide evidence that DSB clustering is abolished when meiotic prophase timing is extended via deletion of the NDT80 transcription factor. We propose that extension of meiotic prophase enables most cells, and therefore most chromosomal domains within them, to reach an equilibrium state of similar Spo11-DSB potential, reducing the impact that priming has on estimates of coincident DSB formation. Consistent with this view, when Tel1 is absent but Ndt80 is present and thus cells are able to rapidly exit meiotic prophase, genome-wide maps of Spo11-DSB formation are skewed towards pericentromeric regions and regions that load pro-DSB factors early-revealing regions of preferential priming-but this effect is abolished when NDT80 is deleted. Our work highlights how the stochastic nature of Spo11-DSB formation in individual cells within the limited temporal window of meiotic prophase can cause localised DSB clustering-a phenomenon that is exacerbated in tel1Δ cells due to the dual roles that Tel1 has in DSB interference and meiotic prophase checkpoint control.

Synthesis of Polar-functionalized Isotactic Polypropylenes Using Commercial Heterogeneous Ziegler-Natta Catalyst.

The efficient synthesis of polar-functionalized polypropylenes with high molecular weight and high stereoregularity represents a challenging task. This challenge becomes even more daunting when pursuing an industrially preferred heterogeneous process. This study demonstrated the realization of these goals through the use of commercial heterogeneous Ziegler-Natta catalysts in the copolymerization of propylene with ionic cluster polar monomers. The results revealed high copolymerization activity (∼1.1 × 107 g mol-1 h-1), moderate polar monomer incorporation ratios (∼4.9 mol %), high copolymer molecular weight (Mw > 105 g mol-1), high stereoregularity ([mmmm] ∼ 96%), and high melting temperature range (150-162 °C). The utilization of ionic cluster polar monomers improved the thermal stability as well as stereoselectivity of the catalyst. Moreover, the Ziegler-Natta catalyst can homopolymerize ionic cluster polar monomers with high activities (>104 g mol-1 h-1). The resulting polar-functionalized isotactic polypropylenes (iPP) exhibited superior tensile strength, impact strength, creep resistance, transparency, and crystallinity compared with nonpolar iPP. This enhancement was attributable to the dual roles of the ionic cluster polar monomer unit, serving as both a transparent nucleating agent and a dynamic cross-linking functionality. Furthermore, the polar-functionalized iPP exhibited improved compatibility with polar materials, offering benefits for applications in composites, recycling of mixed plastic wastes, 3D printing, and other fields. This study offered a comprehensive solution for the future industrial production of polar-functionalized iPP via copolymerization, bridging the gap between an efficient and practical copolymerization process from a synthetic chemistry perspective and enhanced material properties from an application perspective.

Feeding two birds with one scone: The dual roles of SMARCAL1 in antitumor immunity

In a recent issue of Cell, Leuzzi etal.1 report the identification of the DNA translocase SMARCAL1 as a novel factor that dampens immune responses against tumor cells through two distinct mechanisms.

Innate immunity in diabetic nephropathy: Pathogenic mechanisms and therapeutic targets

AbstractDiabetic nephropathy (DN) represents a prevalent chronic microvascular complication of diabetes mellitus (DM) and is a major cause of end‐stage renal disease. The anfractuous surrounding of DN pathogenesis and the intricate nature of this metabolic disorder often pose challenges in both the diagnosis and treatment of DN compared to other kidney diseases. Hyperglycaemia in DM predispose vulnerable renal cells into microenvironmental disequilibrium and thereby results in innate immunocytes infiltration including neutrophils, macrophages, myeloid‐derived suppressor cells, dendritic cells, and so forth. These immune cells play dual roles in kidney injury and closely correlated with the degree of proteinuria in DN patients. Additionally, innate immune signaling cascades, initiated by altered metabolic and hemodynamic in diabetic context, are crucial in instigating and perpetuating renal inflammation, which detrimentally contribute to DN pathogenesis. As such, anti‐inflammatory therapies, particularly those targeting innate immunity, hold renoprotective promise in DN. In this article, we reviewed the origin and feature of the above four prominent kidney innate immune cells, analyze their pathogenic role in DN, and discuss potential targeted‐therapeutic strategies, aiming to enhance the current understanding of renal innate immunity and hence help to discover promising therapeutic approaches for DN.

Towards theorizing from the Arab non-periphery: Hyphenated identities and the boundless security field

Across the Middle East, military professionals, private militias, and other security actors often play a central role in the management of urban planning, public administration, and other state affairs. However, security studies scholarship offers few theoretical tools for understanding this deep and overt inter-twinement of security and governance, framing it as an outcome of authoritarian practices of coup-proofing or a symptom of ‘weak’ states. This article analyzes spatial planning and land management practices in Egypt and Lebanon to propose two concepts, ‘hyphenated identities’ and the ‘boundless security field’, as alternative theoretical tools for thinking about security. I argue that security logics are deeply enmeshed with the identity of the nation, its histories of conflict, and its experiences of state formation, creating a security field that is boundless and non-discrete. Within this field are a set of ‘hyphenated identities’, or categories of actors who perform dual roles as managers of security and managers of other governance matters. The influence of these actors on governance practices illustrates the extent to which security logics can be imbedded in the structures of the state and its modus operandi, thereby reinforcing the boundlessness of the security field.

Coping Strategies for Work-Family Conflict among Working Housewives in Cipatujah Village, Tasikmalaya Regency, Indonesia

This research addresses the escalating phenomenon of working mothers in Indonesia, particularly in Cipatujah Village, Tasikmalaya Regency. With nearly 30 percent of married women engaged in employment, the study focuses on the work-family conflict experienced by these working housewives and aims to uncover their coping strategies. The literature review emphasizes the scarcity of research on coping efforts from the perspective of working women, particularly in developing country contexts like Indonesia. Using a qualitative approach, the study explores the experiences of six working homemakers managing dual roles through observation, interviews, and document analysis. The findings reveal diverse types of work-family conflict, including time-based, strain-based, and behavior-based conflicts. The coping strategies employed by these housewives vary, encompassing problem-focused coping, emotion-focused coping, and a combination of both. This research contributes to the existing literature by providing nuanced insights into the challenges faced by working housewives in a specific rural context. The variations in coping strategies underscore the importance of recognizing individual differences and the complexity of work and family contexts. The study advocates for tailored support systems and policies, considering cultural values and grassroots-level experiences. In conclusion, this research contributes to a comprehensive understanding of coping mechanisms for work-family conflict among working mothers in Indonesia, offering valuable implications for policymakers and future research endeavors.

Hybridization and gene expression: Beyond differentially expressed genes.

Gene expression has a key role in reproductive isolation, and studies of hybrid gene expression have identified mechanisms causing hybrid sterility. Here, we review the evidence for altered gene expression following hybridization and outline the mechanisms shown to contribute to altered gene expression in hybrids. Transgressive gene expression, transcending that of both parental species, is pervasive in early generation sterile hybrids, but also frequently observed in viable, fertile hybrids. We highlight studies showing that hybridization can result in transgressive gene expression, also in established hybrid lineages or species. Such extreme patterns of gene expression in stabilized hybrid taxa suggest that altered hybrid gene expression may result in hybridization-derived evolutionary novelty. We also conclude that while patterns of misexpression in hybrids are well documented, the understanding of the mechanisms causing misexpression is lagging. We argue that jointly assessing differences in cell composition and cell-specific changes in gene expression in hybrids, in addition to assessing changes in chromatin and methylation, will significantly advance our understanding of the basis of altered gene expression. Moreover, uncovering to what extent evolution of gene expression results in altered expression for individual genes, or entire networks of genes, will advance our understanding of how selection moulds gene expression. Finally, we argue that jointly studying the dual roles of altered hybrid gene expression, serving both as a mechanism for reproductive isolation and as a substrate for hybrid ecological adaptation, will lead to significant advances in our understanding of the evolution of gene expression.

PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche.

Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH's role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH-catabolic and anabolic-on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH's multifaceted influence on bone health.

Legionella pneumophila usurps host cell lipids for vacuole expansion and bacterial growth.

Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria growth. Conversely, when exogenous lipids are limited, the decrease in host lipid availability restricts expansion of the replication vacuole membrane, resulting in a higher density of bacteria within the vacuole. Modifying the architecture of the vacuole prioritizes bacterial growth by allowing the greatest number of bacteria to remain protected by the vacuole membrane despite limited resources for its expansion. However, this trade-off is not without risk, as it can lead to vacuole destabilization, which is detrimental to the pathogen. However, when host lipid resources become extremely scarce, for example by inhibiting host lipid scavenging, de novo biosynthetic pathways, and/or diverting host fatty acids to storage compartments, bacterial replication becomes severely impaired, indicating that host cell fatty acid availability also directly regulates L. pneumophila growth. Collectively, these data demonstrate dual roles for host cell fatty acids in replication vacuole expansion and bacterial proliferation, revealing the central functions for these molecules and their metabolic pathways in L. pneumophila pathogenesis.

Deep-Learning Uncovers certain CCM Isoforms as Transcription Factors.

Cerebral Cavernous Malformations (CCMs) are brain vascular abnormalities associated with an increased risk of hemorrhagic strokes. Familial CCMs result from autosomal dominant inheritance involving three genes: KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). CCM1 and CCM3 form the CCM Signal Complex (CSC) by binding to CCM2. Both CCM1 and CCM2 exhibit cellular heterogeneity through multiple alternative spliced isoforms, where exons from the same gene combine in diverse ways, leading to varied mRNA transcripts. Additionally, both demonstrate nucleocytoplasmic shuttling between the nucleus and cytoplasm, suggesting their potential role in gene expression regulation as transcription factors (TFs). Due to the accumulated data indicating the cellular localization of CSC proteins in the nucleus and their interaction with progesterone receptors, which serve dual roles as both cellular signaling components and TFs, a question has arisen regarding whether CCMs could also function in both capacities like progesterone receptors. To investigate this potential, we employed our proprietary deep-learning (DL)-based algorithm, specifically utilizing a biased-Support Vector Machine (SVM) model, to explore the plausible cellular function of any of the CSC proteins, particularly focusing on CCM gene isoforms with nucleocytoplasmic shuttling, acting as TFs in gene expression regulation. Through a comparative DL-based predictive analysis, we have effectively discerned a collective of 11 isoforms across all CCM proteins (CCM1-3). Additionally, we have substantiated the TF functionality of 8 isoforms derived from CCM1 and CCM2 proteins, marking the inaugural identification of CCM isoforms in the role of TFs. This groundbreaking discovery directly challenges the prevailing paradigm, which predominantly emphasizes the involvement of CSC solely in endothelial cellular functions amid various potential cellular signal cascades during angiogenesis.

A Fluorescent Probe with Zwitterionic ESIPT Feature for Ratiometric Monitoring of Peroxynitrite In Vitro and In Vivo.

Peroxynitrite (ONOO-), as a short-term reactive biological oxidant, could lead to a series of effects in various physiological and pathological processes due to its subtle concentration changes. In vivo monitoring of ONOO- and relevant physiological processes is urgently required. Herein, we describe a novel fluorescent probe termed HBT-Fl-BnB for the ratiometric detection of ONOO- in vitro and in vivo. The probe consists of an HBT core with Fl groups at the ortho and para positions responding to the zwitterionic excited-state intramolecular proton-transfer (zwitterionic ESIPT) process and a boronic acid pinacol ester with dual roles that block the zwitterionic ESIPT and recognize ONOO-. Thanks to the specificity as well as low cytotoxicity, success in imaging of endogenous and exogenous ONOO- in living cells by HBT-Fl-BnB was obtained. Additionally, the applicability of HBT-Fl-BnB to tracking the abnormal expression of ONOO- in vivo induced by inactivated Escherichia coli was also explored. This is the first report of a fluorescent probe for ONOO- sensing via a zwitterionic ESIPT mechanism.

Reliable data transmission for a VANET-IoIT architecture: A DNN approach

The challenges and resilience of vehicular ad hoc network (VANET) and deep neural network (DNN) hybrid architectures in terms of reliability in smart cities have attracted much global interest stemming from the rollout of the next generation of intelligent networks. In this paper, we propose a novel distributed DNN (D-DNN) scheme with blockchain to support the Internet of Intelligent Things (IoIT) infrastructure in the VANET environment of the future. In particular, because the communication links between edge nodes are very unstable in VANETs, a new neuro-fuzzy server that serves the dual roles of finding reliable links between edge nodes and performing optimal routing path selection is proposed. Next, a blockchain layer is employed at the edge nodes, which are initially scrutinized before establishing communication links to ensure reliability during data transfer. Then, the proposed D-DNN (PD-DNN) scheme is applied to enhance the performance of the VANET-IoIT architecture by improving the data flow and convergence rate and mitigating erratic variations in output. To address reliability concerns, the coverage probability (CP) metric is investigated as a measure of network connectivity. Furthermore, we present an analysis of the PD-DNN scheme in comparison with the traditional DNN (T-DNN) scheme. Finally, simulation results for VANET-IoIT scenarios show that, subject to data protection and privacy constraints, the CP values corresponding to different communication links are improved to a greater extent under our scheme than under the traditional scheme, demonstrating the feasibility of the proposed scheme.