bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial DNA Activates Endothelial Cells and Promotes Neutrophil Adherence through TLR9 Signaling
Authors: El Kebir Driss , József Levente , Pan Wanling , Wang Lili , Filep János G.
Published: March 2009

TLR9 detects bacterial DNA (CpG DNA) and elicits both innate and adoptive immunity. Recent evidence indicates that TLR9 is expressed in more diverse cell types than initially thought. In this study, we report that HUVECs constitutively express TLR9 and selectively recognize unmethylated CpG motifs in bacterial DNA and synthetic immune stimulatory CpG oligodeoxynucleotides. HUVECs respond to CpG DNA with rapid phosphorylation of IκB-α and NF-κB-mediated gene transcription and surface expression of the adhesion molecules ICAM-1 and E-selectin independent of MAPK signaling. The telomere-derived TLR9 inhibitory oligonucleotide 5′-TTT AGG GTT AGG GTT AGG G-3′, agents that block endosomal acidification such as chloroquine and bafilomycin A, and NF-κB inhibitors abrogated CpG DNA-induced signaling. HUVEC activation by CpG DNA led to markedly enhanced neutrophil adhesion under nonstatic conditions that was further enhanced when neutrophils were stimulated with CpG DNA. The adhesive interactions were blocked by Abs against CD18 and, to a lesser degree, by anti-E-selectin and anti-L-selectin Abs. Our findings demonstrate that bacterial DNA promotes β2 integrin and E-selectin-mediated HUVEC-neutrophil adherence, and indicate the ability of CpG DNA to initiate and/or maintain the inflammatory response.
TLR3 Ligand Induces NF-κB Activation and Various Fates of Multiple Myeloma Cells Depending on IFN-α Production
Authors: Chiron David , Pellat-Deceunynck Catherine , Amiot Martine , Bataille Régis , Jego Gaëtan
Published: March 2009

Multiple myeloma (MM) cells express TLR. It has been shown that TLR ligands induce the proliferation, survival, and immune surveillance escape of MM cells through MyD88-TLR pathways. Deciphering TLR function in MM cells will help in understanding the mechanisms of tumor cell growth. In this study, we examined the response of MM cells to the MyD88-independent/TIR-domain-containing adapter-inducing IFN-β-dependent TLR3. Deregulation of NF-κB pathway is a feature of MM cells, and we wondered whether TLR3 activation could mobilize the NF-κB pathway. We show that five of seven human myeloma cell line (HMCL) cells expressed TLR3. In the presence of the synthetic TLR3 ligand (poly(I:C)), activation of NF-κB pathway was observed in three of five selected TLR3+ HMCL, NCI-H929, RPMI 8226, and KMM1. In agreement with NF-κB activation, only these three HMCL responded to poly(I:C), although by either an increase (KMM1) or a decrease (NCI-H929, RPMI 8226) of proliferation. We show that KMM1 increase of proliferation was prevented by NF-κB inhibitor. In contrast, inhibition of proliferation in both NCI-H929 and RPMI 8226 was due to IFN-α-induced apoptosis. We next demonstrated that p38 MAPK pathway controlled both IFN-α secretion and IFN-α-mediated cell death. Moreover, cell death also involved activation of ERK1/2 pathway. In conclusion, our results show that TLR3 ligand induces NF-κB pathway activation in MM and support a switching function of type I IFN in the functional outcome of TLR3 triggering in tumor cells.
Interactions between Human NK Cells and Macrophages in Response to Salmonella Infection
Authors: Lapaque Nicolas , Walzer Thierry , Méresse Stéphane , Vivier Eric , Trowsdale John
Published: March 2009

NK cells play a key role in host resistance to a range of pathogenic microorganisms, particularly during the initial stages of infection. NK cell interactions with cells infected with viruses and parasites have been studied extensively, but human bacterial infections have not been given the same attention. We studied crosstalk between human NK cells and macrophages infected with intracellular Salmonella. These macrophages activated NK cells, resulting in secretion of IFN-γ and degranulation. Reciprocally, NK cell activation led to a dramatic reduction in numbers of intramacrophagic live bacteria. We identified three elements in the interaction of NK cells with infected macrophages. First, communication between NK cells and infected macrophages was contact-dependent. The second requirement was IL-2- and/or IL-15-dependent priming of NK cells to produce IFN-γ. The third was activation of NK cells by IL-12 and IL-18, which were secreted by the Salmonella-infected macrophages. Adhesion molecules and IL-12Rβ2 were enriched in the contact zone between NK cells and macrophages, consistent with contact- and IL-12/IL-18-dependent NK activation. Our results suggest that, in humans, bacterial clearance is consistent with a model invoking a “ménage à trois” involving NK cells, IL-2/IL-15-secreting cells, and infected macrophages.
Identification and Characterization of a Human CD5+ Pre-Naive B Cell Population
Authors: Lee Jisoo , Kuchen Stefan , Fischer Randy , Chang Sooghee , Lipsky Peter E.
Published: March 2009

We have identified a distinct pre-naive B cell population circulating in human peripheral blood that exhibits an intermediate phenotype between transitional and naive B cells. Like human transitional B cells, these cells express CD5 but have intermediate densities of CD38, CD10, CD9, and the ABCB1 transporter compared with transitional and naive B cells. These pre-naive B cells account for a majority of circulating human CD5+ B cells. Importantly, CD5+ pre-naive B cells could be induced to differentiate into cells with a naive phenotype in vitro. CD5+ pre-naive B cells show only partial responses to BCR stimulation and CD40 ligation and undergo more spontaneous apoptosis and cell death than do naive B cells, whereas BAFF/BLyS (B cell-activating factor belonging to the TNF family) did not enhance their survival compared with naive B cells. In contrast, CD5+ pre-naive B cells carry out certain functions comparable to naive B cells, including the capacity to differentiate into plasma cells and the ability to function as APCs. Notably, an increased proportion of CD5+ pre-naive B cells were found in peripheral blood of patients with systemic lupus erythematosus. These results have identified a unique intermediate in human naive B cell development within the peripheral blood and derangements of its homeostasis in patients with systemic lupus erythematosus.
Early NK Cell-Derived IFN-γ Is Essential to Host Defense in Neutropenic Invasive Aspergillosis
Authors: Park Stacy J. , Hughes Molly A. , Burdick Marie , Strieter Robert M. , Mehrad Borna
Published: March 2009

Invasive aspergillosis is among the most common human fungal infections and occurs in patients with severe and complex defects in immune responses. NK cells have previously been found to be important in host defense against this infection, but the mechanism of this effect is not known. We hypothesized that NK cells mediate their protective effect in invasive aspergillosis by acting as the major source of IFN-γ during early infection. We found that, in the lungs of neutropenic mice with invasive aspergillosis, NK cells were the major population of cells capable of generating IFN-γ during early infection. Depletion of NK cells resulted in reduced lung IFN-γ levels and increased lung fungal load that was independent of T and B cell subsets. Depletion of NK cells and absence of IFN-γ resulted in a similar increase in susceptibility to the infection, but depletion of NK cells in IFN-γ-deficient hosts did not result in further increase in severity of the infection. NK cell-derived IFN-γ caused enhanced macrophage antimicrobial effects in vitro and also resulted in greater expression of IFN-inducible chemokines in the lungs. Finally, transfer of activated NK cells from wild-type, but not IFN-γ-deficient hosts, resulted in greater pathogen clearance from the lungs of both IFN-γ-deficient and wild-type recipients. Taken together, these data indicate that NK cells are the main source of early IFN-γ in the lungs in neutropenic invasive aspergillosis, and this is an important mechanism in the defense against this infection.
Protective Antigen-Independent CD8 T Cell Memory Is Maintained during γ-Herpesvirus Persistence
Authors: Cush Stephanie S. , Flaño Emilio
Published: March 2009

Ag persistence during high-titer chronic viral infections induces CD8 T cell dysfunction and lack of Ag-independent CD8 T cell memory formation. However, we have a poor understanding of the generation and maintenance of CD8 T cell memory during asymptomatic persistent viral infections, particularly γ-herpesvirus infections. In this study, we demonstrate that the continuous presence of cognate Ag in the host is not required for the maintenance of CD8 T cell memory during a persistent γ-herpesvirus infection. Importantly, the Ag-independent CD8 T cell memory that is maintained during γ-herpesvirus persistence has the capacity to survive long-term under homeostatic conditions and to mount a protective recall response to a secondary encounter with the pathogen. These data highlight the ability of the immune system to maintain a population of protective memory CD8 T cells with capacity for long-term Ag-independent survival in the presence of systemic virus persistence.
Isoforms of Vitamin E Have Opposing Immunoregulatory Functions during Inflammation by Regulating Leukocyte Recruitment
Authors: Berdnikovs Sergejs , Abdala-Valencia Hiam , McCary Christine , Somand Michelle , Cole Rokeisha , Garcia Alex , Bryce Paul , Cook-Mills Joan M.
Published: March 2009

Reports indicate contradictory outcomes for anti-inflammatory functions of the α-tocopherol isoform of vitamin E in clinical studies of asthma and atherosclerosis. These seemingly disparate clinical results are consistent with novel unrecognized properties of isoforms of vitamin E reported in this study. We demonstrate that the isoform d-γ-tocopherol elevates inflammation in experimental asthma. Moreover, d-γ-tocopherol, at as little as 10% the concentration of d-α-tocopherol, ablates the anti-inflammatory benefit of the d-α-tocopherol isoform. A mechanism for these opposing immunoregulatory functions of purified tocopherols at physiological concentrations is not through modulation of expression of several cytokines, chemokines, or adhesion molecules, but is, at least in part, by regulation of endothelial cell signals during leukocyte recruitment. These opposing regulatory functions of vitamin E isoforms have impact on interpretations of vitamin E studies. In summary, our studies with purified tocopherol isoforms alter our understanding of vitamin E regulation of vascular function and asthma.
Human IgG4 Binds to IgG4 and Conformationally Altered IgG1 via Fc-Fc Interactions
Authors: Rispens Theo , Ooievaar-De Heer Pleuni , Vermeulen Ellen , Schuurman Janine , van der Neut Kolfschoten Marijn , Aalberse Rob C.
Published: March 2009

The Fc fragment of IgG4 can interact with the Fc fragment of another IgG molecule. This interaction is a confounding factor when measuring IgG4 rheumatoid factor levels. Recently, we demonstrated that half-molecules of IgG4 can exchange to form a bispecific Ab. We expected these two phenomena to be related and investigated the physicochemical aspects of IgG4 Fc-Fc interactions. We found that IgG4 is >99% monomeric by size-exclusion chromatography; therefore, IgG4 Fc-Fc interactions in the fluid phase (if any) would be short-lived. However, 125I-labeled IgG4 does bind to IgG1 and IgG4 coupled to a solid phase. By contrast, IgG1 does not bind to coupled IgG4. Furthermore, conditions that induce partial unfolding/dissociation of the CH3 domains enhance IgG4 Fc binding, suggesting that Fc binding is primarily CH3 mediated. IgG4 slowly associates with both IgG4 and IgG1 coupled to a biosensor chip. Remarkably, subsequent dissociation was much faster for IgG4 than for IgG1. Moreover, after binding of an IgG4 mAb to Sepharose-coupled Ag, we observed additional binding of IgG4 with irrelevant specificity, whereas similar binding was not observed with Ag-bound IgG1. We propose that the IgG4-IgG4 Fc interaction resembles an intermediate of the Fab-arm (half-molecule) exchange reaction that is stabilized because one of the IgG4 molecules is coupled to a solid phase. By contrast, IgG4 Fc recognizes IgG1 only after a conformational change that renders CH3(IgG1) accessible to an interaction with the CH3(IgG4). Such Fc interactions may enhance Ag binding of IgG4 in vivo.
TLR-Induced Local Metabolism of Vitamin D3 Plays an Important Role in the Diversification of Adaptive Immune Responses
Authors: Enioutina Elena Yu , Bareyan Diana , Daynes Raymond A.
Published: March 2009

The addition of monophosphoryl lipid A, a minimally toxic derivative of LPS, to nonmucosally administered vaccines induced both systemic and mucosal immune responses to coadministered Ags. This was dependent on an up-regulated expression of 1α-hydroxylase (CYP27B1, 1αOHase), the enzyme that converts 25-hydroxycholecalciferol, a circulating inactive metabolite of vitamin D3, into 1,25(OH)2D3 (calcitriol). In response to locally produced calcitriol, myeloid dendritic cells (DCs) migrated from cutaneous vaccination sites into multiple secondary lymphoid organs, including classical inductive sites of mucosal immunity, where they effectively stimulated B and T cell immune responses. The endogenous production of calcitriol by monophosphoryl lipid A-stimulated DCs appeared to be Toll-IL-1R domain-containing adapter-inducing IFN-β-dependent, mediated through a type 1 IFN-induced expression of 1αOHase. Responsiveness to calcitriol was essential to promote the trafficking of mobilized DCs to nondraining lymphoid organs. Collectively, these studies help to expand our understanding of the physiologically important roles played by locally metabolized vitamin D3 in the initiation and diversification of adaptive immune responses. The influences of locally produced calcitriol on the migration of activated DCs from sites of vaccination/infection into both draining and nondraining lymphoid organs create a condition whereby Ag-responsive B and T cells residing in multiple lymphoid organs are able to simultaneously engage in the induction of adaptive immune responses to peripherally administered Ags as if they were responding to an infection of peripheral or mucosal tissues they were designed to protect.
Cyclic Failure of a Cr–Au Bilayer on Polyimide: In Situ Transmission Electron Microscopy Observations of Interfacial Dislocation Mechanisms
Authors: Gebhart David D. , Krapf Anna , Schretter Lukas , Lassnig Alice , Merle Benoit , Cordill Megan J. , Gammer Christoph
Published: April 2024

This work presents in situ transmission electron microscopy observations of dislocation activities and associated fatigue properties in a cross‐sectional sample of a Cr–Au bilayer on a polyimide substrate under cyclic loading. Dislocation structures in the Au layer are observed to evolve into a geometrically necessary boundary parallel to the Cr–Au interface, which significantly impedes dislocation motion and plays a crucial role in enhancing the fatigue resistance of the studied sample. While a comparison to the damage in a conventional blanket film testing geometry reveals some differences in the accumulation of plastic flow, the findings can provide insights into the underlying mechanisms governing fatigue in nanostructured multilayer materials on polymer substrates.
Multipurpose On‐the‐Spot Peptide‐Based Hydrogels for Skin, Cornea, and Heart Repair
Authors: Ross Alex , Guo Xixi , Salazar German A. Mercado , Schejtman Sergio David Garcia , El‐Hage Jinane , Comtois‐Bona Maxime , Macadam Aidan , Guzman‐Soto Irene , Takaya Hiroki , Hu Kevin , Liu Bryan , Tu Ryan , Siddiqi Bilal , Anderson Erica , Muñoz Marcelo , Briones‐Rebolledo Patricio , Ning Tianqin , Griffith May , Rotsein Benjamin , Poblete Horacio , Li Jianyu , Ruel Marc , Suuronen Erik J. , Alarcon Emilio I.
Published: April 2024

Bioinspired synthetic materials can be designed as reliable, cost‐effective, and fully controlled alternatives to natural biomaterials for treating damaged tissues and organs. However, several hurdles need to be overcome for clinical translation, particularly for biomaterials gelled in situ. These include the potential toxicity of chemical crosslinkers used in the materials' assembly or breakdown products they generate and the challenges of fine‐tuning the mechanical properties of the materials. Here, a minimalistic, adhesive soft material is developed by screening hundreds of potential formulations of self‐assembling, custom‐designed collagen‐like peptide sequences for the in situ formation of tissue‐bonding 3D hydrogels. Nine promising formulations for tissue repair are identified using a low‐volume and rapid combinatory screening approach. It is shown that simply varying the ratio of the two key components promotes adhesion and fine‐tunes the material's mechanical properties. The materials' skin and heart repair capabilities are assessed in vitro and clinically relevant animal models. The materials are also tested for corneal applications using ex vivo pig cornea models complemented by in vitro cell compatibility assays.
Deep Learning Prediction of Triplet–Triplet Annihilation Parameters in Blue Fluorescent Organic Light‐Emitting Diodes
Authors: Lim Junseop , Kim Jae‐Min , Lee Jun Yeob
Published: April 2024

The triplet–triplet annihilation (TTA) ratio and the rate coefficient (kTT) of TTA are key factors in estimating the contribution of triplet excitons to radiative singlet excitons in fluorescent TTA organic light‐emitting diodes. In this study, deep learning models are implemented to predict key factors from transient electroluminescence (trEL) data using new numerical equations. A new TTA model is developed that considers both polaron and exciton dynamics, enabling the distinction between prompt and delayed singlet decays with a fundamental understanding of the mechanism. In addition, deep learning models for predicting the kinetic coefficients and TTA ratio are established. After comprehensive optimization inspired by photophysics, determination coefficient values of 0.992 and 0.999 are achieved in the prediction of kTT and TTA ratio, respectively, indicating a nearly perfect prediction. The contribution of each kinetic parameter of polaron and exciton dynamics to the trEL curve is discussed using various deep‐learning models.
Boosting Contact Electrification by Amorphous Polyvinyl Alcohol Endowing Improved Contact Adhesion and Electrochemical Capacitance
Authors: Serairi Lisa , Santillo Chiara , Basset Philippe , Lavorgna Marino , Pace Giuseppina
Published: April 2024

Ion conductive hydrogels are relevant components in wearable, biocompatible, and biodegradable electronics. Polyvinyl‐alcohol (PVA) homopolymer is often the favored choice for integration into supercapacitors and energy harvesters as in sustainable triboelectric nanogenerators (TENGs). However, to further improve hydrogel‐based TENGs, a deeper understanding of the impact of their composition and structure on devices performance is necessary. Here, it is shown how ionic hydrogels based on an amorphous‐PVA (a‐PVA) allow to fabricate TENGs that outperform the one based on the homopolymer. When used as tribomaterial, the Li‐doped a‐PVA allows to achieve a twofold higher pressure sensitivity compared to PVA, and to develop a conformable e‐skin. When used as an ionic conductor encased in an elastomeric tribomaterial, 100 mW cm−2 average power is obtained, providing 25% power increase compared to PVA. At the origin of such enhancement is the increased softness, stronger adhesive contact, higher ionic mobility (> 3,5‐fold increase), and long‐term stability achieved with Li‐doped a‐PVA. These improvements are attributed to the high density of hydroxyl groups and amorphous structure present in the a‐PVA, enabling a strong binding to water molecules. This work discloses novel insights on those parameters allowing to develop easy‐processable, stable, and highly conductive hydrogels for integration in conformable, soft, and biocompatible TENGs.
Regioselective C6‐Arylation of Thieno[3,2‐c]pyrazole Heterocycles with Aryl Iodides
Authors: Ait Lfakir Noura , Jismy Badr , Guillaumet Gérald , Akssira Mohamed , El Hakmaoui Ahmed , Guillot Régis , Tikad Abdellatif , Abarbri Mohamed
Published: April 2024

Regioselective C6‐arylation of thieno[3,2‐c]pyrazoles with aryl iodides as coupling partners has been developed. This strategy was performed in the presence of Pd(OAc)2 as catalyst in combination with AgOTf as an oxidant and TFA in dimethylacetamide. In all experiments, only the C6‐arylated thieno[3,2‐c]pyrazole was isolated since its C5‐regioisomer was not observed, indicating the high regioselectivity of this approach. The catalytic system used is compatible with a variety of 3‐functionalized thieno[3,2‐c]pyrazoles and iodoaryl electrophiles, providing access to 3,6‐disubstituted thieno[3,2‐c]pyrazoles in yields ranging from 49% to 94%.
I2‐Promoted Oxidative Annulation of Deoxybenzoin‐Chalcone Adduct: Temperature‐Controlled Access to Tetrasubstituted 2,3‐trans‐Dihydrofurans and Furans
Authors: Thanh Nhan Vu Thi , Ngoc Trinh Thu , Trang Pham Thu , Tu Ha Minh , Hung Mac Dinh , Retailleau Pascal , Binh Nguyen Thanh
Published: April 2024

Tetrasubstituted 2,3‐trans‐dihydrofuran and furan are important heterocyclic scaffolds in natural product, bioorganic and medicinal chemistry as well as in material science. The synthesis of both of these heterocycles starting from common and readily available starting materials are challenging. We found that in situ generated deoxybenzoin‐chalcone Michael adducts underwent oxidative annulation upon heating with molecular iodine in DMSO to provide selectively 2,3‐trans‐dihydrofurans at 80 °C and furans at 120 °C.
A Ratiometric Fluorescent Detection Platform Using G‐CDs@[Ru(bpy)3]2+ for the Specific Detection of Hypochlorite and Live Cell Imaging
Authors: Rong Mingcong , He Zheng , Wang Danru , Zeng Jiahao , Liu Qian , Niu Li
Published: April 2024

Hypochlorite (ClO−), an essential reactive oxygen species (ROS) in physiological processes, is identified to be closely connected with oxidative stress and related diseases. Meanwhile, ClO− is a commonly‐used disinfector for water treatment, and in public places, under acidic conditions, it's easily decomposed into hypertoxic chlorine gas. Since the strong oxidizing property of ClO−, many oxidizing agents may disturb the ClO− detection. Specific and accurate detection of ClO− with superior sensitivity is a challenge. In this work, a sensing platform for rapid, sensitive, and specific ClO− detection is constructed using green fluorescent carbon dots (G‐CDs), with a linear detection range of 0.5–11 µm and a detection limit of 0.233 µm. Moreover, introducing a red fluorescent tripyridinium ruthenium ([Ru(bpy)3]2+) as a reference, a ratiometric fluorescence nanoprobe G‐CDs@[Ru(bpy)3]2+ is prepared and shows favorable intracellular imaging of exogenous and endogenous ClO−. With G‐CDs@[Ru(bpy)3]2+‐based test paper microarrays and a color recognition APP, a smartphone‐based sensing system for point‐of‐care testing of ClO− is also fabricated. In summary, this work proposed a versatile and economical smartphone‐based sensing system that featured reliability and simplicity, and suggested its potential applications in environmental water quality monitoring and live cell imaging.
Facile Generation of Heterotelechelic Poly(2‐Oxazoline)s Towards Accelerated Exploration of Poly(2‐Oxazoline)‐Based Nanomedicine
Authors: Van Guyse Joachim F. R. , Abbasi Saed , Toh Kazuko , Nagorna Zlata , Li Junjie , Dirisala Anjaneyulu , Quader Sabina , Uchida Satoshi , Kataoka Kazunori
Published: April 2024

Controlling the end‐groups of biocompatible polymers is crucial for enabling polymer‐based therapeutics and nanomedicine. Typically, end‐group diversification is a challenging and time‐consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end‐group diversification approach for poly(2‐oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation. The approach relies on the careful tuning of reaction parameters to establish differential reactivity of a pentafluorobenzyl initiator fragment and the living oxazolinium chain‐end, allowing the selective introduction of N‐, S‐, O‐nucleophiles via the termination of the polymerization, and a consecutive nucleophilic para‐fluoro substitution. The value of this approach for the accelerated development of nanomedicine is demonstrated through the synthesis of well‐defined lipid‐polymer conjugates and POx‐polypeptide block‐copolymers, which are well‐suited for drug and gene delivery. Furthermore, we investigated the application of a lipid‐POx conjugate for the formulation and delivery of mRNA‐loaded lipid nanoparticles for immunization against the SARS‐COV‐2 virus, underscoring the value of POx as a biocompatible polymer platform.
Improving flame retardancy in BADGE epoxy via novel phosphorus‐functionalized epoxy integration
Authors: Toan Mai , Kwon Kiok , Shin Seunghan
Published: April 2024

A novel epoxy resin, DPHP, was synthesized from diphenolic acid, which contains biobased levulinic acid, with triethylphosphite, to improve the flame retardancy of bisphenol‐A diglycidyl ether (BADGE) epoxy. Curing experiments were conducted using isophorone diamine as a curing agent for BADGE and DPHP mixtures. Variations in cure kinetics, mechanical properties, and flame retardancy were evaluated across different DPHP contents. The introduction of phosphorus functional groups into DPHP affected the polarization of epoxide CO bonds, resulting in reduced apparent activation energy for epoxy curing reactions. However, the higher epoxy equivalent weight of DPHP compared with that of BADGE led to a decrease in the tensile strength and the glass transition temperature of the cured material with increasing DPHP content. A significant increase in char yield for combustion of the epoxy blend was observed, ranging from 8.3% at 0 wt% DPHP to 20.1% at 50 wt% DPHP. Additionally, cone calorimeter measurements showed significant reductions in heat release rate and total heat release, leading to a decrease in fire spread from 1.07 MJm−2 s−1 at 0 wt% DPHP to 0.43 MJm−2 s−1 at 50 wt% DPHP. These results show that the flame retardancy of the cured material improved significantly as the DPHP content increased.
Deinococcus wulumuqiensis R12 synthesized silver nanoparticles with peroxidase‐like activity for synergistic antibacterial application
Authors: Liu Jingjia , Zhang Nan , Shen Bowen , Zhang Liling , Zhang Zhidong , Zhu Liying , Jiang Ling
Published: April 2024

The use of a combination of several antibacterial agents for therapy holds great promise in reducing the dosage and side effects of these agents, improving their efficiency, and inducing potential synergistic therapeutic effects. Herein, this study provides an innovative antibacterial treatment strategy by synergistically combining R12‐AgNPs with H2O2 therapy. R12‐AgNPs were simply produced with the supernatant of an ionizing radiation‐tolerant bacterium Deinococcus wulumuqiensis R12 by one‐step under room temperature. In comparison with chemically synthesized AgNPs, the biosynthesized AgNPs presented fascinating antibacterial activity and peroxidase‐like properties, which endowed it with the capability to catalyze the decomposition of H2O2 to generate hydroxyl radical. After the combination of R12‐AgNPs and H2O2, an excellent synergistic bacteriostatic activity was observed for both Escherichia coli and Staphylococcus aureus, especially at low concentrations. In addition, in vitro cytotoxicity tests showed R12‐AgNPs had good biocompatibility. Thus, this work presents a novel antibacterial agent that exhibits favorable synergistic antibacterial activity and low toxicity, without the use of antibiotics or a complicated synthesis process.
Development of an efficient liposomal DOX delivery formulation for HCC therapy by targeting CK2α
Authors: Zhao Ruixia , Cheng Sinan , Bai Xue , Zhang Danying , Fang Hongming , Che Wanlin , Zhang Wenxuan , Zhou Yujuan , Duan Wei , Liang Qiumin , Xiao Li , Nie Guochao , Hou Yingchun
Published: April 2024

Hepatocellular carcinoma (HCC) is a digestive tract cancer with high mortality and poor prognosis, especially in China. Current chemotherapeutic drugs lead to poor prognosis, low efficacy, and high side effects due to weak targeting specificity and rapidly formed multidrug resistance (MDR). Based on the previous studies on the doxorubicin (DOX) formulation for cancer targeting therapy, we developed a novel DOX delivery formulation for the targeting chemotherapy of HCC and DOX resistant HCC. HCSP4 was previously screened and casein kinase 2α (CK2α) was predicted as its specific target on HCC cells in our lab. In the study, miR125a‐5p was firstly predicted as an MDR inhibiting miRNA, and then CK2α was validated as the target of HCSP4 and miR125a‐5p using CK2α‐/‐HepG2 cells. Based on the above, an HCC targeting and MDR inhibiting DOX delivery liposomal formulation, HCSP4/Lipo‐DOX/miR125a‐5p was synthesized and tested for its HCC therapeutic efficacy in vitro. The results showed that the liposomal DOX delivery formulation targeted to HCC cells specifically and sensitively, and presented the satisfied therapeutic efficacy for HCC, particularly for DOX resistant HCC. The potential therapeutic mechanism of the DOX delivery formulation was explored, and the formulation inhibited the expression of MDR‐relevant genes including ATP‐binding cassette subfamily B member 1 (ABCB1, also known as P‐glycoprotein), ATP‐binding cassette subfamily C member 5 (ABCC5), enhancer of zeste homolog 2 (EZH2), and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). Our study presents a novel targeting chemotherapeutic drug formulation for the therapy of HCC, especially for drug resistant HCC, although it is primarily and needs further study in vivo, but provided a new strategy for the development of novel anticancer drugs.
Serum and urine metabolomics based on UPLC–QTOF/MS reveal the effect and potential mechanism of “schisandra–evodia” herb pair in the treatment of Alzheimer's disease
Authors: Pang Chengguo , Wang Ruijiao , Liu Kemeng , Yuan Xu , Ni Jiating , Cao Qingyu , Chen Yuanjin , Dong Pei Liang , Han Hua
Published: April 2024

The “schisandra–evodia” herb pair (S–E) is a herbal preparation to treat Alzheimer's disease (AD). This study aims to investigate the therapeutic efficacy and potential mechanism of S–E in AD rats, utilizing pharmacodynamic assessments and serum‐ and urine‐based metabolomic analyses. Pharmacodynamic assessments included Morris water maze test, hematoxylin–eosin staining and immunohistochemistry experiments. The results of the study showed that the AD model was successful; the S–E significantly enhanced long‐term memory and spatial learning in AD rats. Meanwhile, S–E notably ameliorated Aβ25–35‐induced cognitive impairment, improved hippocampal neuron morphology, decreased Aβ deposition in the hippocampus and mitigated inflammatory damage. We then analyzed serum and urine samples using UPLC–MS/MS to identify potential biomarkers and metabolic pathways. Metabolomic analysis revealed alterations in 40 serum metabolites and 38 urine metabolites following S–E treatment, predominantly affecting pathways related to taurine and hypotaurine metabolism, linoleic acid metabolism, α‐linolenic acid metabolism, glycerophospholipid metabolism and arachidonic acid metabolism. This study elucidates the biochemical mechanism underlying AD and the metabolic pathway influenced by S–E, laying the groundwork for future clinical applications.
Stakeholder pressure and circular supply chain practices: Moderating roles of environmental information exchange capability and circular innovation orientation
Authors: Agyabeng‐Mensah Yaw , Afum Ebenezer , Baah Charles
Published: April 2024

This study deploys institutional theory and Resource orchestration theory (ROT) to examine the roles supply chain stakeholder pressure, circular innovation orientation (CIO) and environmental information exchange capability (EIEC) play in adopting Circular supply chain (CSC) practices. This study uses a partial least square structural equation modelling (PLS‐SEM) to analyse survey data gathered from 290 managers of manufacturing Small and medium enterprises (SMEs) in Ghana. This study finds that pressure from supply chain stakeholders substantially drives manufacturing SMEs' CSC practices. This study confirms that EIEC negatively moderates the relationship between supply chain stakeholder pressure and CSC practices. Finally, this study confirms the complementarity between CIO and EIEC through moderating effects between supply chain stakeholder pressure and CSC practices. This study advances circular supply chain management (CSCM) literature by testing a research framework that examines important but rarely studied roles of CIO and EIEC in SMEs' CSC practices adoption under supply chain stakeholder pressure through institutional and resource orchestration perspectives.
Flow cytometric minimal residual disease measurement accounting for cytogenetics in children with non‐high‐risk acute lymphoblastic leukemia treated according to the ALL‐MB 2008 protocol
Authors: Popov Alexander , Henze Guenter , Tsaur Grigory , Budanov Oleg , Roumiantseva Julia , Belevtsev Mikhail , Verzhbitskaya Tatiana , Movchan Liudmila , Lagoyko Svetlana , Zharikova Liudmila , Olshanskaya Yulia , Riger Tatiana , Valochnik Alena , Miakova Natalia , Litvinov Dmitry , Khlebnikova Olga , Streneva Olga , Stolyarova Elena , Ponomareva Natalia , Novichkova Galina , Aleinikova Olga , Fechina Larisa , Karachunskiy Alexander
Published: April 2024

Background

Quantitative measurement of minimal residual disease (MRD) is the “gold standard” for estimating the response to therapy in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). Nevertheless, the speed of the MRD response differs for different cytogenetic subgroups. Here we present results of MRD measurement in children with BCP‐ALL, in terms of genetic subgroups with relation to clinically defined risk groups.

Methods

A total of 485 children with non‐high‐risk BCP‐ALL with available cytogenetic data and MRD studied at the end‐of‐induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard‐risk (SR) of intermediate‐risk (ImR) regimens of “ALL‐MB 2008” reduced‐intensity protocol.

Results and Discussion

Among all study group patients, 203 were found to have low‐risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC‐MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC‐MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low‐(0.03%) and intermediate (0.01%) cytogenetic risk groups.

Conclusion

Our data show that combining clinical risk factors with MFC‐MRD measurement is the most useful tool for risk group stratification of children with BCP‐ALL in the reduced‐intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.
Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view
Authors: Nuyts Sandra , Bollen Heleen , Eisbruch Avrahram , Strojan Primoz , Mendenhall William M. , Ng Sweet Ping , Ferlito Alfio
Published: April 2024

Background

Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution.

Methods

This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice.

Results and Conclusion

Although based on mainly non‐randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well‐designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART.
Electrophotocatalysis Versus Indirect Electrolysis: Electrochemical Selenocyclization of 3‐Aza‐1,5‐dienes Facilitated by Energy Transfer, Direct Photolysis or N‐Hydroxyphthalimide
Authors: Wang Dongyin , Zeng Li , Shi Jifu , Gao Shulin , Shi Lou , Sun Shaoguang , Liang Deqiang
Published: April 2024

Three hybrid electrochemical protocols, which involve the energy transfer, direct photolysis and N‐hydroxyphthalimide catalyst, respectively, are presented for the selenylation/cyclization of the fragile substrates of 3‐aza‐1,5‐dienes with diorganyl diselenides to afford 3‐selenomethyl‐4‐pyrrolin‐2‐ones. The two electrophotocatalytic reactions and the indirect electrolysis one are both regioselective and external‐oxidant‐ and transition‐metal‐free, and are associated with a broad substrate scope and high Se‐economy, and all three methods are amenable to gram‐scale syntheses, late‐stage functionalizations, sunlight‐induced experiments and all‐solar‐driven syntheses.
Detection and Characterization of Hydride Ligands in Copper Complexes by Hard X‐Ray Spectroscopy
Authors: Fritsch Lorena , Rehsies Pia , Barakat Wael , Estes Deven P. , Bauer Matthias
Published: April 2024

Transition metal complexes, particularly copper hydrides, play an important role in various catalytic processes and molecular inorganic chemistry. This study employs synchrotron hard X‐ray spectroscopy to gain insights into the geometric and electronic properties of copper hydrides as potential catalysts for CO2 hydrogenation. The potential of high energy resolution X‐ray absorption near‐edge structure (HERFD‐XANES) and valence‐to‐core X‐ray emission (VtC‐XES) is demonstrated with measurement on Stryker's reagent (Cu6H6) and [Cu3(μ3‐H)(dpmppe)2](PF6)2 (Cu3H), alongside a non‐hydride copper compound ICu(dtbppOH) (Cuy−I). The XANES analysis reveals that coordination geometries strongly influence the spectra, providing only indirect details about hydride coordination. The VtC‐XES analysis exhibits a distinct signal around 8975 eV, offering a diagnostic tool to identify hydride ligands. Theoretical calculations support and extend these findings by comparing hydride‐containing complexes with their hydride‐free counterparts.
Asymmetric 1,4‐Addition of Diarylphosphine Oxides to α, β‐Unsaturated 2‐Acyl Imidazoles
Authors: Chen Lirong , Wang Guiyong , Nong Xiufei , Shao Wendi , Li Jiuling , Guo Yafei , Fan Baomin
Published: April 2024

Here we introduce a metal‐free, catalytic and enantioselective strategy from α,β‐unsaturated 2‐acyl imidazoles to the chiral phosphorous 2‐acyl imidazoles. Interestingly, this methodology was catalyzed by the classical and commercial oxazaborolidine under mild conditions. This strategy features a wide range of substrates scope with good yields and excellent enantioselectivities. The possible mechanism further suggests the key of this reaction through the cleavage of diarylphosphine oxides using Frustrated Lewis Pairs theory.
Research progress of hydrogen production and CO2 fixation in molten slag cooling process
Authors: Zhou Chaogang , Li Jinyue , Meng Xianguang , Chen Qinggong , Yan Zhanhui , Li Juncheng , Gao Xu , Ueda Shigeru , Wang Shuhuan , Ai Liqun , Lin Lu
Published: April 2024

Steel slag is a waste discharged from the iron and steel smelting process, which has the characteristics of large output, high temperature, complex chemical composition and poor stability. The application of steel slag in hydrogen production and CO2 fixation is of great significance for reducing energy consumption, obtaining renewable energy and fixing CO2 in the air. In this paper, the research progress of high‐temperature sensible heat of steel slag used for hydrogen production and CO2 fixation at medium and low temperature is introduced, the reaction mechanism of different hydrogen production methods and the treatment path and direction of high‐efficiency hydrogen production in the future are deeply analyzed, and the steel slag used for CO2 fixation is discussed and summarized from the theory, effect and treatment mode of CO2 fixation. In the future, the research on the economic benefits of hydrogen production and CO2 fixation from steel slag is a major focus, which can achieve economic benefits while utilizing steel slag resources.
Phase Transition in Silicon from Machine Learning Informed Metadynamics
Authors: Bhullar Mangladeep , Bai Zihao , Akinpelu Akinwumi , Yao Yansun
Published: April 2024

Investigating reconstructive phase transitions in large‐sized systems requires a highly efficient computational framework with computational cost proportional to the system size. Traditionally, widely used frameworks such as density functional theory (DFT) have been prohibitively expensive for extensive simulations on large systems that require long‐time scales. To address this challenge, this study employed well‐trained machine learning potential to simulate phase transitions in a large‐size system. This work integrates the metadynamics simulation approach with machine learning potential, specifically deep potential, to enhance computational efficiency and accelerate the study of phase transition and consequent development of grains and dislocation defects in a system. The new method is demonstrated using the phase transitions of bulk silicon under high pressure. This approach has revealed the transition path and formation of polycrystalline silicon systems under specific stress conditions, demonstrating the effectiveness of deep potential‐driven metadynamics simulations in gaining insights into complex material behaviors in large‐sized systems.
Characterizing cognitive profiles in diverse middle‐aged and older Hispanics/Latinos: Study of Latinos‐Investigation of Neurocognitive Aging (HCHS/SOL)
Authors: Graves Lisa V. , Tarraf Wassim , Gonzalez Kevin , Bondi Mark W. , Gallo Linda C. , Isasi Carmen R. , Daviglus Martha , Lamar Melissa , Zeng Donglin , Cai Jianwen , González Hector M.
Published: April 2024

Introduction

We investigated cognitive profiles among diverse, middle‐aged and older Hispanic/Latino adults in the Study of Latinos–Investigation of Neurocognitive Aging (SOL‐INCA) cohort using a cross‐sectional observational study design.

Methods

Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL‐INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function.

Results

Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average‐to‐high‐average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average‐to‐low‐average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low‐average‐to‐mildly impaired across all cognitive/IADL tests (12.1%).

Discussion

Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community‐dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos.

Highlights

The present study characterized cognitive profiles among diverse middle‐aged and older Hispanic/Latino adults.

Latent profile analysis of neurocognitive test scores was the primary analysis conducted.

The target population consists of middle‐aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos ‐ Investigation of Neurocognitive Aging.
A case report of loss of thyroid transcription factor 1 expression in lung adenocarcinoma EBUS FNA
Authors: Mathew Hitesh , Bartle‐Jones Ros
Published: April 2024

We present a case report of a 76‐year‐old male with a histologically confirmed KRAS mutated, thyroid transcription factor 1 (TTF1) positive, grade 1, mucinous adenocarcinoma with cytologically difficult to interpret lymph node metastasis showing loss of TTF1 expression and overlapping features with goblet cell hyperplasia. The case highlights the importance of molecular testing in aiding diagnosis and guiding treatment of non‐small cell lung carcinomas (NSCLC).
Intersection of coral molecular responses to a localized mortality event and ex situ deoxygenation
Authors: Strader Marie E. , Wright Rachel M. , Pezner Ariel K. , Nuttall Marissa F. , Aichelman Hannah E. , Davies Sarah W.
Published: April 2024

In July 2016, East Bank of Flower Garden Banks (FGB) National Marine Sanctuary experienced a localized mortality event (LME) of multiple invertebrate species that ultimately led to reductions in coral cover. Abiotic data taken directly after the event suggested that acute deoxygenation contributed to the mortality. Despite the large impact of this event on the coral community, there was no direct evidence that this LME was driven by acute deoxygenation, and thus we explored whether gene expression responses of corals to the LME would indicate what abiotic factors may have contributed to the LME. Gene expression of affected and unaffected corals sampled during the mortality event revealed evidence of the physiological consequences of the LME on coral hosts and their algal symbionts from two congeneric species (Orbicella franksi and Orbicella faveolata). Affected colonies of both species differentially regulated genes involved in mitochondrial regulation and oxidative stress. To further test the hypothesis that deoxygenation led to the LME, we measured coral host and algal symbiont gene expression in response to ex situ experimental deoxygenation (control = 6.9 ± 0.08 mg L−1, anoxic = 0.083 ± 0.017 mg L−1) in healthy O. faveolata colonies from the FGB. However, this deoxygenation experiment revealed divergent gene expression patterns compared to the corals sampled during the LME and was more similar to a generalized coral environmental stress response. It is therefore likely that while the LME was connected to low oxygen, it was a series of interconnected stressors that elicited the unique gene expression responses observed here. These in situ and ex situ data highlight how field responses to stressors are unique from those in controlled laboratory conditions, and that the complexities of deoxygenation events in the field likely arise from interactions between multiple environmental factors simultaneously.