Elimination Mechanism Research Articles

On the mechanism of carboxylate elimination from carbohydrate monoester-derived radicals.

A computational study of the mechanism of hydrogen atom transfer-induced carboxylate elimination from monoacylated 1,2-diol groups in pyranosides is presented. A comprehensive analysis of the 1,2-migration, elimination and fragmentation pathways reveals that concerted elimination via a 7-membered, hydrogen-bonded transition state is favored. Relative rates of elimination inferred from an intramolecular competition experiment are consistent with the trends obtained from the calculations.

Neutrofilné extracelulárne pasce a ich vplyv v patogenéze vybraných ochorení

Neutrophil extracellular traps (NETs) are net-like extracellular structures extruded by activated neutrophils capable of trapping many pathogens, including Gram-positive and Gram-negative bacteria, fungi, protozoa, and viruses. NETs are composed of DNA strands, histones, and antimicrobial proteins derived from neutrophil granules and nuclei. Pathogens are immobilized in them and exposed to a local, high and lethal concentration of effector proteins. Excessive release of NETs or violation of their elimination mechanisms is associated with several disease states. Toxic products of NETs (histones, granule proteins) induce cell apoptosis, promote tissue damage and inflammation. Components of NETs can serve as autoantigens and initiate reactions important in the pathogenesis of several autoimmune diseases. The presence of an increased amount of circulating NETs can influence the progression of cancer disease, the formation of metastases and the failure of treatment. NETs also play an important role in coagulation and blood clot formation.

A Novel Tightly Coupled Solution for SINS/Polarized Navigation System/Odometer Integration Using Polarized and Installed Angle Errors Model

Precise and reliable autonomous navigation in a GPS-denied environment is critical to unmanned systems. The idea of combining SINS, the polarized navigation system (PNS), and the odometer (OD) inspired by desert ants has been proven to be effective for autonomous navigation. However, there are two major challenges for polarization navigation nowadays: inaccurate modeling and obtaining reliable heading information when some sensor channels are blocked. Aiming at these two problems, a tightly-coupled solution for SINS/PNS is proposed in this paper. To obtain a refined integrated navigation system model, the installation errors between the inertial units and PNS, and polarization angle calculation errors are analyzed and modeled for SINS/PNS. Then, to quickly gain the accurate state estimation, an improved iterative unscented filtering method is devised. In particular, the sigma-point updating step with the conditional distribution of high-dimensional Gaussian distribution random variables is developed, which employs partial states to sample in each iteration to reduce the calculation burden. Finally, a detection and elimination mechanism for the abnormal light channels is provided to enhance the reliability of the integration in the presence of a light blockage. The optical channels for navigation are chosen using this mechanism depending on the difference between the predicted and measured incident light intensities. The results in both simulations and outdoor experiments show that the proposed method provides a higher heading estimation accuracy than the traditional SINS/PNS navigation method. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —This article is motivated by the inaccurate modeling and obtaining reliable heading in the presence of light occlusion for the polarization navigation. Various integrated navigation algorithms based on polarized skylight have been widely developed. However, the complex environment and inaccurate modeling limit the application of the polarization navigation. This article gives a novel accurate modeling method and reliable navigation algorithm. Tightly-coupled model with installation errors and the polarization angle error aims to improve the accuracy of the polarization navigation model. The improved iterative unscented Kalman filter is utilized to quickly obtain accurate state estimation. And the light detection and elimination mechanism is used to select normal light channels to navigate in the presence of light blockage. This navigation method can also extend the application of the polarization navigation.

Molecular and cellular mechanisms of developmental synapse elimination in the cerebellum: Involvement of autism spectrum disorder-related genes

Molecular and cellular mechanisms of developmental synapse elimination in the cerebellum: Involvement of autism spectrum disorder-related genes

Analysis of resources applied to rationalize elimination mechanisms

This study aimed to analyze second-semester organic chemistry students’ problem-solving strategies, specifically focusing on the resources activated while solving problems on E2, E1, and E1cB elimination reactions. Using the theoretical framework by Elby and Hammer, we defined a resource as a unit of information used in the problem-solving process. The resources activated to solve elimination reaction problems were probed using a mixed-methods approach using survey assessments and think-aloud interviews. The data were analyzed quantitatively and qualitatively following a validated set of scoring criteria. The results align with existing findings that students focus on surface-level structural information and use resources that have been repetitively emphasized over multiple semesters. Resources related to acid–base chemistry were activated more often than reaction-specific resources, such as conformational analyses or carbocation rearrangements. Although acid–base resources aid students in successfully analyzing reaction mechanisms, additional resources must be activated to rationalize specific mechanisms and to explain the products formed. This calls for instructors to provide formative and summative assessments that evaluate the many resources required to elucidate elimination reaction mechanisms and product stereochemistry.

Interaction of α‐Cembrenediol with Human Serum Albumin Based on Spectroscopic and Computational Analyses

α‐Cembrenediol exhibits a wide range of biological activities, including antibacterial, antitumor, and neuroprotective effects. However, knowledge of the absorption, transport, and release of α‐cembrenediol in drug metabolism within the body is currently limited. Therefore, we aimed to gain a comprehensive understanding of the in vivo transport, distribution, and elimination mechanisms of α‐cembrenediol and investigate the interaction between α‐cembrenediol and HSA. To this end, we utilized various methods including UV absorption spectroscopy, steady‐state fluorescence analysis, circular dichroism measurements, molecular docking studies, and molecular dynamics simulations. The results of the UV and fluorescence spectra clearly demonstrated that HSA interacts with α‐cembrenediol. Specifically, the fluorescence spectra results showed that at a temperature of 310 K, the fluorescence quenching constant (KSV) and binding constant (Kb) between HSA and α‐cembrenediol were determined to be 1.28 × 103 Lmol−1 and 218.27 Lmol−1, respectively. As the temperature was decreased from 310 K to 293 K, both KSV and Kb values increased, indicating the presence of a static quenching mechanism throughout the interaction process. Moreover, the results indicated the presence of a singular, specific binding site for α‐cembrenediol on HSA, as evidenced by an approximate count of one binding site at all three temperatures. Additionally, this binding process occurred spontaneously (ΔG &lt; 0), with van der Waals interactions and hydrogen bonding as the primary driving forces (ΔH = −9.40 kJmol−1 and ΔS = −14.50 Jmol−1·K−1). The binding of α‐cembrenediol to Sudlow site I of HSA was confirmed through molecular docking, a combination of fluorescence probe substitution, and molecular dynamics simulation experiments. Moreover, the results demonstrated that α‐cembrenediol binding led to alterations in the structural conformation of HSA, as confirmed by three‐dimensional fluorescence, synchronous fluorescence, and circular dichroism spectra. This study offers crucial insights into the interaction between α‐cembrenediol and HSA, contributing to an improved understanding of the compound’s pharmacokinetic properties.

Application of Artificial Intelligence in Computer Neural Network Algorithm Technology in the Age of Big Data

Abstract The arrival of the big data era makes the amount of data explosive growth, which puts forward new challenges and demands for computer network technology, and the integration of big data and network technology has become an important trend. This paper uses the optimization strategy and the elimination mechanism of the genetic algorithm to optimize the inertia weight and particle position speed updating mechanism of the particle swarm algorithm and combines the searching method of the Tennessee whisker algorithm with the sharing mechanism of the particle swarm algorithm to achieve the optimal data searching ability. Finally, the improved artificial intelligence algorithm and MapReduce are combined to improve the performance of the computer neural network algorithm in big data processing. The average data redundancy rate of this paper’s algorithm for big data processing is only 1.18%, and the resource integration checking rate always exceeds 85%, according to simulation experiments. In addition, the algorithm also shows good performance in practical applications, and it can achieve accurate classification of big data labels in big data label classification tasks while maintaining a low energy overhead. Meanwhile, it can accurately recognize electronic medical record data in large medical databases. Big data processing can benefit greatly from the proposed neural network algorithm in this paper.

Transcriptional profiling of human peripheral blood mononuclear cells in household contacts of pulmonary tuberculosis patients provides insights into mechanisms of Mycobacterium tuberculosis control and elimination

ABSTRACT Household contacts (HHCs) of patients with active tuberculosis (ATB) are at higher risk of Mycobacterium tuberculosis (M. tuberculosis) infection. However, the immune factors responsible for different defense responses in HHCs are unknown. Hence, we aimed to evaluate transcriptome signatures in human peripheral blood mononuclear cells (PBMCs) of HHCs to aid risk stratification. We recruited 112 HHCs of ATB patients and followed them for 6 years. Among the HHCs, only 2 developed ATB, while the remaining HHCs were classified into three groups: (1) HHC-1 group (n = 23): HHCs with consistently positive T-SPOT.TB test, negative chest radiograph, and no clinical symptoms or evidence of ATB during the 6-year follow-up period; (2) HHC-2 group (n = 15): HHCs with an initial positive T-SPOT result that later became negative without evidence of ATB; (3) HHC-3 group (n = 14): HHCs with a consistently negative T-SPOT.TB test and no clinical or radiological evidence of ATB. HHC-2 and HHC-3 were combined as HHC-23 group for analysis. RNA sequencing (RNA-seq) in PBMCs, with and without purified protein derivative (PPD) stimulation, identified significant differences in gene signatures between HHC-1 and HHC-23. Gene ontology analysis revealed functions related to bacterial pathogens, leukocyte chemotaxis, and inflammatory and cytokine responses. Modules associated with clinical features in the HHC-23 group were linked to the IL-17 signaling pathway, ferroptosis, complement and coagulation cascades, and the TNF signaling pathway. Validation using real-time PCR confirmed key genes like ATG-7, CXCL-3, and TNFRSF1B associated with infection outcomes in HHCs. Our research enhances understanding of disease mechanisms in HHCs. HHCs with persistent latent tuberculosis infection (HHC-1) showed significantly different gene expression compared to HHCs with no M. tuberculosis infection (HHC-23). These findings can help identify HHCs at risk of developing ATB and guide targeted public health interventions.

Dual barrier system against xenomitochondrial contamination in mouse embryos

Heteroplasmic mammalian embryos between genetically distant species fail to develop to term, preventing transmission of xenomitochondrial DNA to progeny. However, there is no direct evidence indicating the mechanisms by which species specificity of the mitochondrial genome is ensured during mammalian development. Here, we have uncovered a two-step strategy underlying the prevention of xenomitochondrial DNA transmission in mouse embryos harboring bovine mitochondria (mtB-M embryos). First, mtB-M embryos showed metabolic disorder by transient increase of reactive oxygen species at the 4-cell stage, resulting in repressed development. Second, trophoblasts of mtB-M embryos led to implantation failure. Therefore, we tested cell aggregation with tetraploid embryos to compensate for the placentation of mtB-M embryos. The 14 mtB-M embryos harboring bovine mtDNAs developed to term at embryonic day 19.5. Taken together, our results show that contamination of bovine mtDNA is prohibited by embryonic lethality due to metabolic disruption and failure of placentation, suggesting these represent xenomitochondrial elimination mechanisms in mammalian embryos.

Nazarov reaction triggered by active lithium salts in cyclopentyl methyl ether

Abstract In this study, we developed a lithium-activated Nazarov reaction of highly activated divinyl ketones in the presence of mixed lithium salts by combining LiClO4 with either LiOMe or LiI in cyclopentyl methyl ether (CPME). This reaction produces LiOPh in the reaction mixture, exhibiting aspects of a Nazarov reaction in the presence of base. The additives LiOMe and LiI not only facilitated the dissolution of LiClO4 aggregates but also promoted the addition–elimination mechanism, thereby accelerating the reaction and preventing side reactions.

Intra-erythrocytic vacuoles in asplenic patients: elusive genesis and original clearance of unique organelles.

The spleen plays a dual role of immune response and the filtration of red blood cells (RBC), the latter function being performed within the unique microcirculatory architecture of the red pulp. The red pulp filters and eliminates senescent and pathological RBC and can expell intra-erythrocytic rigid bodies through the so-called pitting mechanism. The loss of splenic function increases the risk of infections, thromboembolism, and hematological malignancies. However, current diagnostic tests such as quantification of Howell-Jolly Bodies and splenic scintigraphy lack sensitivity or are logistically demanding. Although not widely available in medical practice, the quantification of RBC containing vacuoles, i.e., pocked RBC, is a highly sensitive and specific marker for hyposplenism. The peripheral blood of hypo/asplenic individuals contains up to 80% RBC with vacuoles, whereas these pocked RBC account for less than 4% of RBC in healthy subjects. Despite their value as a spleen function test, intraerythrocytic vacuoles have received relatively limited attention so far, and little is known about their origin, content, and clearance. We provide an overview of the current knowledge regarding possible origins and mechanisms of elimination, as well as the potential function of these unique and original organelles observed in otherwise "empty" mature RBC. We highlight the need for further research on pocked RBC, particularly regarding their potential function and specific markers for easy counting and sorting, which are prerequisites for functional studies and wider application in medical practice.

A novel triple capacitor multi-level submodule MMC topology with fault current clearing capability

In the high voltage direct current system based on modular multilevel converter (MMC-HVDC), the half-bridge submodule (HBSM) has become the preferred submodule for significant projects due to its convenient control and low cost. However, the DC short-circuit protection performance of MMC-HVDC will seriously restrict its development in areas such as overhead lines, high voltage, and large capacity. This article proposes a triple capacitor multi-level submodule (TCMSM) topology of modular multilevel converter with DC fault-blocking capability. It utilizes at least one-third of the module capacitance in the bridge arm to reverse to suppress DC fault current and turn off the diode. At the same time, the unidirectional conductivity of the diode can also prevent arc reignition at the fault point. The article also conducted in-depth research on the DC short-circuit fault elimination mechanism of this topology, and compared its performance with other topologies. Through analysis, it can be concluded that TCMSM reduces the initial investment and operating costs by reducing the number of devices inside the module while possessing the fault current blocking ability. Finally, MATLAB/Simulink was used to simulate and verify the proposed new topology, and its performance was analyzed.

A tale of two pollutants: The mutual promotion mechanism of synergistic catalytic elimination of Hg0 and chlorobenzene on V2O5–WO3/TiO2 catalyst

The co-benefit of Hg0 or chlorinated volatile organic compounds (CVOCs) oxidation can be achieved by using vanadium-based catalysts in the selective catalytic reduction (SCR) unit. However, there is no research on the synergistic catalytic elimination of Hg0 and chlorobenzene (CB) in vanadium-based catalysts. Herein, the reaction mechanism of catalytic elimination of Hg0 and CB on vanadium-based catalysts was systematically analyzed and discussed for the first time. It is surprisingly observed that there is a synergistic effect between chlorobenzene catalytic oxidation (CBCO) and Hg0 oxidation. That is, CB could enhance Hg0 oxidation by providing active chlorine species, while the presence of Hg0 could also promote CBCO and reduce the formation of polychlorinated byproducts due to the consumption of chlorine species in the Hg0 oxidation reaction according to Le Chatelier’s principle. This synergistic effect was conducive to maintaining the physical structure and electronic properties of the catalyst and weakening the deposition of elements chlorine and mercury on the catalyst surface, promoting the re-exposure of active centers. This work provides unique insights for synergistic catalytic elimination of Hg0 and CB, and is expected to guide the prospective application on vanadium-based catalysts for multipollutant control.

Granulocyte colony-stimulating factor induces the migration of non-resident cells to intracerebral hemorrhage

The aim of the study is to determine the effect of granulocyte colony-stimulating factor (rHuG-CSF) on the migration of non-resident cells into the region of intracerebral hemorrhage (ICH), which can potentially be considered as mesenchymal stem cells. Materials and methods. In the experiment, unilateral ICH was simulated in rats by injection of autologous blood into the right hemisphere. Immunohistochemical method was used to study perihematomal area on day 1, 3, 10, 30, and 60 after ICH modeling. The appearance of cells expressing CD44, CD68, and CD146 markers was evaluated on a 3-point scale after penetrating trauma (PT) of the brain, ICH, and ICH with the growth factor injection (ICH/rHuG-CSF). Results. In contrast to PT, ICH intensified the infiltration of CD44+ cells in the perihematomal area of the brain and caused the appearance of CD68+ and CD146+ cells in hemorrhage. The specific density of CD44+ cells was decreased on day 60 after ICH, and the effect of rHuG-CSF consisted in reducing the density of CD44+ cells on days 30 and 60. The appearance of CD68+ and CD146+ cells in the perihematomal area was seen after 10 days and further their detection was rare, while after the rHuG-CSF injection, the infiltration by cells with a similar immunophenotype was detected on day 3 ICH with a tendency to accumulate. Conclusions. Infiltration by cells expressing CD44, CD68, and CD146 into the perihematomal area of the rat brain was heterogeneous as to the time after brain injury. The appearance of cells with specified immunophenotype could be associated with hematoma elimination, angiogenesis processes, and other mechanisms of the perihematomal brain region remodeling, in which mesenchymal stem cells were involved. rHuG-CSF modulated the migration of CD68+ and CD146+ cells, which consisted in their earlier and more intense migration to the damaged area of the brain after ICH.

In situ growth of Ag2S quantum dots on cellulose nanocrystals and their near-infrared bioimaging performance

Elongated nanoparticles show distinct advantages over spherical nanoparticles in bioimaging because of surface area-to-volume, rate of clearance from the body and elimination mechanism. In this work, we investigated the fluorescence emission properties of the hybrid system by decorating silver sulfide quantum dots (Ag2S QDs) in situ on the surface of cellulose nanocrystal (CNC) with unique rod shape, modifiability and biocompatibility. This water-dispersible fluorescent probe has both absorption and fluorescence in near-infrared (NIR) region. By varying the amount of surface ligands, uniformly dispersed Ag2S QDs with different crystalline states but similar sizes were prepared due to the anchoring effect of CNC. The fluorescence quantum yield of fluorescent probes can be improved up to 109-fold (from 0.04 % to 4.36 %). In addition, the CNC-restricted interparticle spacing of Ag2S QDs (< 10 nm), in combination with the overlap of wide fluorescence emission and ultraviolet absorption, significantly enhanced the 1070 nm emission in the NIR-II region via fluorescence resonance energy transfer (FRET). Further conjugation of these CNC probes with folic acid-polyethylene glycol-amino (FA-PEG-NH2) enables in vitro bioimaging of Hela cells, which are potentially applicable for in vivo cancer detection system. The synthetic strategy provides a new way for one-pot preparation of fluorescent probes with both high NIR-I absorption and NIR-II fluorescence.

Вопросы методологии использования и применения международных налоговых договоров (часть 2)

In this article the author intends to develop and justify the uniform approach to utilisation and application of the provisions of the conventions on avoidance of double taxation which specify the regime of taxation of particular types of income and capital (property). Stemming from the factors giving rise to double (multiple) taxation, the author examines the mechanisms of elimination of double taxation contained therein and the legal technicalities employed to lay down such mechanisms in the tax treaties. Furthermore, the author elaborates on his vision regarding the possible commonly shared algorithm that could eliminate or minimise the errors in utilisation and application of the distributive rules of the double taxation treaties taking into account peculiarities of terminology and wording of the treaties as well as the systematic approach of treaty drafters to the formulation of distributive rules (rules establishing the specifics of the tax treatment of certain types of income and capital) contained therein.

Gold-Manganese Bimetallic Redox Coupling with Light.

The classical Au(I)/Au(III) redox couple chemistry has been limited to constructing C-C and C-X bonds, and thus, the exploration of the elementary reaction of gold redox coupling is very significant to enrich its organometallic features. Herein, we report the first visible-light-mediated, external oxidant-free Au(I)/Au(III) redox couple using commercially available Mn2(CO)10 to generate Mn-Au(III)-Mn intermediates for bimetallic redox coupling. A wide range of structurally diverse heterodinuclear and polynuclear L-Au(I)-Mn-L' complexes (19 examples, up to >99% yields) are readily constructed, providing a robust strategy for the concise construction of Au-Mn complexes under mild reaction conditions. The mechanistic studies together with DFT calculations support the radical oxidative addition of •Mn(CO)5 to gold and bimetallic reductive elimination mechanisms from highly active Mn-Au(III)-Mn species, representing an important step toward an elementary reaction in gold chemistry research. Furthermore, the resulting Au-Mn complexes exhibit unique catalytic activity, with which divergent reductive coupling of nitroarenes can readily afford azoxybenzenes, azobenzenes, and hydrazobenzenes in moderate to good yields.

Novel Therapeutics Targeting Acute Myeloid Leukemia (AML) Stem Cells Identified through High-Throughput Screening

Acute myeloid leukemia (AML) is an aggressive form of blood cancer. Despite the use of cytotoxic standard-of-care drugs, patients often succumb to the disease partially due to the inability of medically unfit patients to withstand the cytotoxic treatments, regrowth from minimal residual disease and the chemo-resistant nature of leukemic stem cells (LSCs). Hence, novel therapies should focus on targeting the unique biology of LSCs to eliminate and avoid reoccurrence. To overcome challenges inherent of screening rare LSCs in vitro such as culturing and expanding, we optimized the conditions for a 4-week in vitro large-scale expansion (&amp;gt;600 million bulk) and enrichment of the CD34+ LSC-containing fraction (&amp;gt;90% purity) for a primary human AML sample (OCI-AML-8227), functionally validated to be enriched for LSCs in long-term xenotransplant assays (Eppert et al., 2011). Next, we performed a high-throughput screen of 11,140 chemical molecules in 3 stages. First, the viability of AML CD34+ cells and healthy cord blood (CB) CD34+ cells was read out at 1-2 doses using a CellTiter-Glo® Luminescent assay. 61 compounds had &amp;gt;70% inhibition of 8227 CD34+ cells and &amp;lt;30% inhibition on CB CD34+ cells. Next, we determined the dose response and refined the hits to 33 potent compounds with LC50 &amp;lt; 1 μM, including novel compounds and classes previously shown to target bulk and leukemic stem cells in AML. We are now presenting the follow up hits identified from the third stage of validation where we determined the LC 50 specifically in the CD34- (blast) and CD34+CD38- (LSC-enriched) OCI-AML-8227 populations using flow cytometry. We identified 25 novel anti-LSC compounds with high efficacy against CD34+CD38- AML cells (LC 50 &amp;lt; 500 nM). Venetoclax was among the top hits, a compound that revolutionized treatment for poor prognosis AML patients due to its anti-LSC activities, providing internal validation of the screen. We then tested these candidates in a second LSC-enriched model with poor prognosis, OCI-AML-20, to ensure the response of compounds on LSCs is not exclusive to OCI-AML-8227 and to investigate the influence of the microenvironment on drug efficiency. A total of 5 hits have significant responses (&amp;gt;50% reduction in LSC enriched populations) and nontoxic to stroma. Furthermore, we refined our top candidates to 7 compounds based on their efficiencies in the two LSC-enriched models (OCI-AML-20 and 8227) and low toxicity on stroma. To gain insights on their mechanisms of action in LSCs, the two models were treated with the 7 candidates and cytarabine as a control for 3 days and apoptosis was measured by flow cytometry. Out of 7 candidates, 5 induced apoptosis in the LSC-enriched fractions, suggesting elimination of LSCs through apoptosis. The remaining compounds may eliminate LSCs through different mechanisms. From these results, we focused on the three leading compounds and validated them for toxicity on CD34+ hematopoetic stem and progenitor cord blood cells (HSPCs) vs CD34+CD38- (LSC-enriched) OCI-AML-8227 by flow cytometry. Although slight toxicity was observed in HSPCs at higher doses, the LC 50 for the stem cell vs LSC-enriched populations differ by ~6-40-fold, indicating that a significantly lower concentration can be used to eradicate LSCs while sparing HSPCs (LC 50 for CD34+ population CB vs 8227; Compound A: 1558 nM vs 83 nM, Compound B: &amp;gt;2000 nM vs 305 nM and Compound C: 612 nM vs 16 nM, respectively). To functionally validate if HSPCs proliferation and differentiation was impaired and if leukemic progenitors were eradicated, a colony forming unit assay was performed for 12 days after 6 days of treatment. Candidates were found to eliminate leukemic progenitors by 50% or more, reducing leukemia initiating potential and having minimal or no impact on CB progenitor functionality. Overall, compound A is a potential candidate to move forward due to its ability to target and eliminate LSCs through apoptosis in two LSC-enriched models, its low toxicity on stroma and normal cord blood cells. This candidate is classified as an indole, a class shown by Pabst et al., 2014 to reduce CD34+CD15- AML cells in a drug screen for aryl hydrocarbon modulators, suggesting a potential mechanism for LSC elimination through apoptosis. We now aim to examine LSC eradication in a panel of genetically defined primary AMLs to be able to determine the broad applicability of this compound and translate the preliminary results for clinical use.

A second-generation M1-polarized CAR macrophage with antitumor efficacy.

Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner. Here we engineered induced pluripotent stem cell-derived macrophages (iMACs) with toll-like receptor 4 intracellular toll/IL-1R (TIR) domain-containing CARs resulting in a markedly enhanced antitumor effect over first-generation CAR-macrophages. Moreover, the design of a tandem CD3ζ-TIR dual signaling CAR endows iMACs with both target engulfment capacity and antigen-dependent M1 polarization and M2 resistance in a nuclear factor kappa B (NF-κB)-dependent manner, as well as the capacity to modulate the tumor microenvironment. We also outline a mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we provide a second-generation CAR-iMAC with an ability for orthogonal phagocytosis and polarization and superior antitumor functions in treating solid tumors relative to first-generation CAR-macrophages.

Novel BaO-decorated carbon-tolerant Ni-YSZ anode fabricated by an efficient phase inversion-impregnation approach

In this study, an efficient phase inversion-impregnation approach is developed for fabricating BaO-decorated Ni-8 mol% yttria-stabilized zirconia (YSZ) anode-supported tubular solid oxide fuel cells (SOFCs) toward anti-coking. This technique involves a simple phase-inversion process, along with the saturated barium nitrate solution as coagulation bath. Experimental results show that BaO nanoislands with particle size of less than 100 nm have been successfully and uniformly introduced inside the Ni-YSZ anode. The corresponding peak power densities are determined to be 0.30 W cm−2 and 0.22 W cm−2 at 800 °C in wet hydrogen and methane fuel, respectively. The long-term stability in methane fuel with the BaO-decorated anode is significantly improved with respect to the pristine one. Density functional theory (DFT) calculations suggest that the loading of BaO nanoislands can efficiently capture and dissociate the H2O molecules to generate OH, which subsequently serves as effective carbon elimination medium. The OH diffusion from BaO to BaO/Ni interface coupling with the formation of COH is the key step involved in the carbon elimination mechanism. The as-proposed phase inversion-impregnation approach exhibits advantage in time and cost savings compared to traditional impregnation methods, providing a new route for fabricating anti-coking SOFC anodes.