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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3

Charge Density Wave Order and Electronic Phase Transitions in a Dilute d ‐Band Semiconductor

Abstract As one of the most fundamental physical phenomena, charge density wave (CDW) order predominantly occurs in metallic systems such as quasi‐1D metals, doped cuprates, and transition metal dichalcogenides, where it is well understood in terms of Fermi surface nesting and electron–phonon coupling mechanisms. On the other hand, CDW phenomena in semiconducting systems, particularly at the low carrier concentration limit, are less common and feature intricate characteristics, which often necessitate the exploration of novel mechanisms, such as electron–hole coupling or Mott physics, to explain. In this study, an approach combining electrical transport, synchrotron X‐ray diffraction, and density‐functional theory calculations is used to investigate CDW order and a series of hysteretic phase transitions in a dilute d ‐band semiconductor, BaTiS 3 . These experimental and theoretical findings suggest that the observed CDW order and phase transitions in BaTiS 3 may be attributed to both electron–phonon coupling and non‐negligible electron–electron interactions in the system. This work highlights BaTiS 3 as a unique platform to explore CDW physics and novel electronic phases in the dilute filling limit and opens new opportunities for developing novel electronic devices.

36 MATERIALS SCIENCE↗

Spectroscopic evidence for the direct involvement of local moments in the pairing process of the heavy-fermion superconductor CeCoIn 5

The microscopic mechanism for electron pairing in heavy-fermion superconductors remains a major challenge in quantum materials. Some form of magnetic mediation is widely accepted with spin fluctuations as a prime candidate. A novel mechanism, “composite pairing” based on the cooperative two-channel Kondo effect directly involving the f -electron moments, has also been proposed for some heavy-fermion compounds including CeCoIn 5 . The origin of the spin-resonance peak observed in neutron-scattering measurements on CeCoIn 5 is still controversial and the corresponding hump-dip structure in the tunneling conductance is missing. This is in contrast to the cuprate and Fe-based high-temperature superconductors, where both characteristic signatures are observed, indicating spin fluctuations are likely involved in the pairing process. In this study, we report results from planar tunneling spectroscopy along three major crystallographic orientations of CeCoIn 5 over wide ranges of temperature and magnetic field. The pairing gap opens at T p ~ 5 K , well above the bulk T c = 2.3 K , and its directional dependence is consistent with d x 2 – y 2 symmetry. With increasing magnetic field, this pairing gap is suppressed as expected but, intriguingly, a gaplike structure emerges smoothly, increasing linearly up to the highest field applied. This field-induced gaplike feature is only observed below T p . The concomitant appearance of the pairing gap and the field-induced gaplike feature, along with its linear increase with field, indicates that the f -electron local moments are directly involved in the pairing process in CeCoIn 5 .

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition

Cbl-b is a RING-type E3 ubiquitin ligase that is expressed in several immune cell lineages, where it negatively regulates the activity of immune cells. Cbl-b has specifically been identified as an attractive target for cancer immunotherapy due to its role in promoting an immunosuppressive tumor environment. A Cbl-b inhibitor, Nx-1607, is currently in phase I clinical trials for advanced solid tumor malignancies. Using a suite of biophysical and cellular assays, we confirm potent binding of C7683 (an analogue of Nx-1607) to the full-length Cbl-b and its N-terminal fragment containing the TKBD-LHR-RING domains. To further elucidate its mechanism of inhibition, we determined the co-crystal structure of Cbl-b with C7683, revealing the compound’s interaction with both the TKBD and LHR, but not the RING domain. Here, we provide structural insights into a novel mechanism of Cbl-b inhibition by a small-molecule inhibitor that locks the protein in an inactive conformation by acting as an intramolecular glue.

59 BASIC BIOLOGICAL SCIENCES↗

Telomere-to-telomere assemblies of chromosome 10 reveal complex adaptive variation of 3-ketoacyl-CoA-synthases in Populus trichocarpa likely driven by Helitrons

The model woody plant Populus trichocarpa displays an atypical alkene-diverse wax cuticle likely driven by copy number variation (CNV) of 3-ketoacyl-CoA synthases ( KCS ), which has been difficult to confirm with short-read assemblies. Long-read sequencing enables the development of telomere-to-telomere resources to detect cryptic variation, including CNVs, which are currently missed. Integrating this information can improve genomic prediction for breeding and provide insights into the evolutionary basis of important traits. Our analysis of 78 long-read haplotypes from chromosome 10 identified more than twice as many KCS genes as previously reported, and numerous intragenic non-synonymous substitutions. Random Forest predictive models highlighted the importance of Potri.010G079500 in producing very long chain alkenes; however, its absence did not predict previously reported alkene-deficient phenotypes. Instead, alkene levels are best predicted by the combinations of KCS copies. Additionally, amino acid substitutions clustered around ligand and donor binding pockets, suggesting they contribute to differing wax cuticle composition. Finally, each KCS gene and copy was linked to a Helitron transposon. A phylogenetic analysis suggests Helitrons are the evolutionary mechanism for generating KCS tandem arrays. Long-read generated telomere-to-telomere assemblies of P. trichocarpa chromosome 10 revealed large-effect loci critical to genetic studies that are unattainable from short-reads. This new resource produced novel insights into genome structure and function, and a novel mechanism for generating tandem gene duplication. Our results highlight that, given current challenges in annotation and assembly, detailed and focused long-read sequences are key to interpreting complex genomic regions that contain tandem copy number variants.

09 BIOMASS FUELS↗

Influence of Tibetan Plateau sensible heat on pre-monsoon dust burdens over South Asia: Observational and modeling evidence

Tibetan Plateau sensible heating (TPSH) effect is recognized as a key driver of the South Asian climate; however its role in regulating the regional dust burdens over South Asia during the pre-monsoon season remains unclear. Using long-term reanalysis and/or observational dust and TPSH data, we show that the dust optical depth at 550 nm (DOD 550 ) over South Asia is significantly positively correlated with TPSH at the interannual scale. DOD 550 over South Asia increases (decreases) by 20 % (12 %) in the strongest (weakest) TPSH years. The phenomenon of TPSH-dust relationships is reinforced by sensitivity experiments by altering TPSH from global climate models. Further mechanism analysis reveals that TPSH perturbation induces regional circulation anomalies over South Asia, which features a low-tropospheric cyclonic response around the Tibetan Plateau. This cyclonic anomaly strengthens the prevailing northwesterly winds, increasing regional dust emissions and transportation over South Asia. This novel mechanism helps understand the South Asian dust change.

54 ENVIRONMENTAL SCIENCES↗

A Modular Mechanism for Downhole Weight-on-Bit and Torque Reaction in Small Diameter Boreholes

Drilling systems that use downhole rotation must react torque either through the drill-string or near the motor to achieve effective drilling performance. Problems with drill-string loading such as buckling, friction, and twist become more severe as hole diameter decreases. Therefore, for small holes, reacting torque downhole without interfering with the application of weight-on-bit, is preferred. In this paper, we present a novel mechanism that enables effective and controllable downhole weight on bit transmission and torque reaction. This scalable design achieves its unique performance through four key features: (1) mechanical advantage based on geometry, (2) direction dependent behavior using rolling and sliding contact, (3) modular scalability by combining modules in series, and (4) torque reaction and weight on bit that are proportional to applied axial force. As a result, simple mechanical devices can be used to react large torques while allowing controlled force to be transmitted to the drill bit. We outline our design, provide theoretical predictions of performance, and validate the results using full-scale testing. The experimental results include laboratory studies as well as limited field testing using a percussive hammer. These results demonstrate effective torque reaction, axial force transmission, favorable scaling with multiple modules, and predictable performance that is proportional to applied force.

15 GEOTHERMAL ENERGY↗

Chain Formation as a Mechanism for Mass-Independent Fractionation of Sulfur Isotopes in the Archean Atmosphere

The anomalous abundances of sulfur isotopes in ancient sediments provide the strongest evidence for an anoxic atmosphere prior to ∼2.45 Ga, but the mechanism for producing this 'mass-independent' fractionation pattern remains in question. The prevailing hypothesis has been that it is created by differences in the UV photolysis rates of different SO2 isotopologues. We investigate here a recently proposed additional source of fractionation during gas-phase formation of elemental sulfur (S4 and S8). Because two minor S isotopes rarely occur in the same chain, the longer S4 and S8 chains should be strongly, and roughly equally, depleted in all minor isotopes. This gives rise to negative ∆(sup 33) S values and positive ∆(sub 36) S values in elemental sulfur-just the opposite of (and much larger than) what is predicted from SO2 photolysis itself. Back-reactions during chain formation, specifically photolysis of S2 and S3, pass sulfur having the opposite fractionation back to atomic S, and thence to other sulfur species, causing H2S, SO2, sulfate, and short-chain elemental sulfur to have positive ∆(sup 33) S and negative ∆(sup 36) S. Positive ∆(sup 33) S values in elemental sulfur produced in laboratory SO2 photolysis experiments could be caused by the initial fractionation during photolysis, combined with rapid condensation of short-chain sulfur species on the walls of the reaction chamber, along with a scarcity of back-reactions. The simulated fractionations produced by the chain formation mechanism do not directly match fractionations from the rock record. The mismatch might be explained if the isotopic signals leaving the atmosphere were significantly modulated by life, by uncertainties in the rates of reactions of both major and minor isotopic sulfur species, or by the relatively large potential range of atmospheric parameters. Further work is needed to better constrain these uncertainties, but this novel mechanism suggests new avenues to explore in our search for a explanation for the S-MIF record.

Great Oxidation Event↗

Chain Formation as a Mechanism for Mass-Independent Fractionation of Sulfur Isotopes in the Archean Atmosphere

The anomalous abundances of sulfur isotopes in ancient sediments provide the strongest evidence for an anoxic atmosphere prior to ∼2.45 Ga, but the mechanism for producing this ‘mass-independent’ fractionation pattern remains in question. The prevailing hypothesis has been that it is created by differences in the UV photolysis rates of different SO2 isotopologues. We investigate here a recently proposed additional source of fractionation during gas-phase formation of elemental sulfur (S4 and S8). Because two minor S isotopes rarely occur in the same chain, the longer S4 and S8 chains should be strongly, and roughly equally, depleted in all minor isotopes. This gives rise to negative Δ(exp 33)S values and positive Δ(exp 33)S values in elemental sulfur—just the opposite of (and much larger than) what is predicted from SO2 photolysis itself. Back-reactions during chain formation, specifically photolysis of S2 and S3, pass sulfur having the opposite fractionation back to atomic S, and thence to other sulfur species, causing H2S, SO2, sulfate, and short-chain elemental sulfur to have positive Δ(exp 33)S and negative Δ(exp 33)S. Positive Δ(exp 33)S values in elemental sulfur produced in laboratory SO2 photolysis experiments could be caused by the initial fractionation during photolysis, combined with rapid condensation of short-chain sulfur species on the walls of the reaction chamber, along with a scarcity of back-reactions. The simulated fractionations produced by the chain formation mechanism do not directly match fractionations from the rock record. The mismatch might be explained if the isotopic signals leaving the atmosphere were significantly modulated by life, by uncertainties in the rates of reactions of both major and minor isotopic sulfur species, or by the relatively large potential range of atmospheric parameters. Further work is needed to better constrain these uncertainties, but this novel mechanism suggests new avenues to explore in our search for a explanation for the S-MIF record.

C. E. Harman↗

A flavor of SO(10) unification with a spinor Higgs

We investigate Higgs Parity unification — a realization of SO(10) grand unification based on the Higgs Parity mechanism in which the Standard Model (SM) Higgs resides in a spinor representation. The theory has an intermediate left-right symmetric stage where the SU(2)R symmetry breaking scale is fixed by the vanishing of the SM Higgs quartic coupling. The strong CP problem is solved by parity. Gauge coupling unification successfully predicts αs(MZ) to within 1%. The spinor Higgs naturally leads to a seesaw origin for SM flavor observables. We identify a novel mechanism where large mixing of third generation fermions with additional heavy vector-like fermions accounts for the anarchical nature of the PMNS matrix and the lack of hierarchy in the neutrino mass spectrum, relative to the up-quarks. A fit to quark and lepton masses and mixings, with a minimal parameter set, predicts 1) A testable relation between the top quark mass and αs(MZ) which is about (1 – 2)σ from current best fit values, 2) The order of magnitude of the baryon asymmetry of the universe, via leptogenesis from second-generation right-handed neutrino decays. 3) The proton decay and the neutron EDM are likely observable in next generation experiments, and 4) A normal ordered neutrino mass spectrum where 0νββ decay and the mass of the lightest neutrino are out of reach of next generation experiments.

Baryo-and Leptogenesis↗

T-Cell Shenanigans: The Impact of MHC Pathway & Lipid Metabolism Genes on T-Cell Differentiation in the Thymus

Astronaut health and proper immune function are key to the success and sustainability of long term missions in space. While previous studies have observed adaptive immune dysfunction such as diminished WBC counts and cytokine production during spaceflight, the underlying mechanisms behind why immune function worsens are poorly understood. Using transcriptomic data analyzed from mouse thymus tissues available from the GLDS-421 experiment on the Rodent Research-9 mission, we used the GeneLab standardized RNA-Seq pipeline and identified four genes that were largely dysregulated (p<0.05): lipid metabolic genes Hpgd and Pgr and cell cycle regulator genes Cenpe and Kif11. We analyzed how these genes regulate the MHC-TCR interaction, and used this understanding to propose a novel mechanism for alterations to T-cell differentiation. In our experimental methodology, we propose to use 36 transgenic CD4-CD8 mice and 12 wild-type mice from the Jackson Lab to create a microgravity-simulating hindlimb unloading model and test our hypothesis. By silencing the aforementioned genes using custom siRNA based primers, we will use flow cytometry and RNA-Seq to quantify Treg counts in comparison to naive CD4+ cells, Alamar Blue assay for observing the metabolic activity in T-cells, and Enzyme-Linked Immunosorbent Assay (ELISA) to observe the general immune response in terms of T-cell differentiation. We hope this methodology will improve our knowledge of MHC-TCR interaction, contribute to a better understanding of the mechanisms of autoimmune diseases such as lupus, and improve the success rate of newer cancer treatments such as CAR-T cell therapy.

GL4HS↗

Two-dimensional ruthenium boride: a Dirac nodal loop quantum electrocatalyst for efficient hydrogen evolution reaction

Catalysts with high carrier mobility, high activity, and an active basal plane have been highly sought for the hydrogen evolution reaction (HER). However, combining these advantages into one single material is a grand challenge. Herein, using first principles computations, we predicted that a two-dimensional (2D) Dirac nodal loop semimetal, namely the RuB 4 monolayer, is promising as a superior catalyst for the HER. Our systematic computations showed that the single layer RuB 4 is thermodynamically, dynamically, mechanically, and thermally stable and presents multiple Ru and B sites for the HER on the basal plane. The estimated Gibbs free energy for hydrogen adsorption at a Ru site is approaching zero (–8.8 meV), suggesting its excellent HER performance. The RuB 4 monolayer is a Dirac nodal loop semimetal with high Fermi velocities, which can accelerate charge transfer between catalysts and reaction intermediates. The RuB 4 monolayer is an auxetic material with an out-of-plane negative Poisson's ratio, implying its novel mechanical properties. Finally, this work provides an example of using a Dirac nodal loop semimetal for high-performance HER catalysts, which is a promising alternative to the known catalysts with trivial metallic properties.

30 DIRECT ENERGY CONVERSION↗

Control of Vibration Systems with Mechanical Motion Rectifier and their Applications to Vehicle Suspension and Ocean Energy Harvester

Vibration control is a large branch in control research, because all moving systems may induce desired or undesired vibration. Due to the limitation of passive system’s adaptability and changing excitation input, vibration control brings the solution to change system dynamic with desired behavior to fulfill control targets. According to preference, vibration control can be separated into two categories: vibration reduction and vibration amplification. Lots of research papers only examine one aspect in vibration control. The thesis investigates the control development for both control targets with two different control applications: vehicle suspension and ocean wave energy converter. It develops control methods for both systems with simplified modeling setup, then followed by the application of a novel mechanical motion rectifier (MMR) gearbox that uses mechanical one-way clutches in both systems. The flow is from the control for common system to the control design for a specifically designed system. In the thesis, active (model predictive control: MPC), semi-active (Skyhook, skyhook-power driven damper: SHPDD, hybrid model predictive control: HMPC), and passive control (Latching Control) methods are developed for different applications or control performance comparison on single system. The thesis also studies about new type of system with switching mechanism, in which other papers do not talk too much and possible control research direction to deal with such complicated system in vibration control. The state-space modeling for both systems are provided in the thesis with detailed model of the MMR gearbox. From the simulation, it can be shown that in the vehicle suspension application, the controlled MMR gearbox can be effective in improving vehicle ride comfort by 29.2% compared to that of the traditional hydraulic suspension. In the ocean wave energy converter, the controlled MMR WEC with simple latching control can improve the power generation by 57% compared to the passive MMR WEC. Besides, the passive MMR WEC also shows its advantage on the passive direct drive WEC in power generation improvement. From the control development flow for the MMR system, the limitation of the MMR gearbox is also identified, which introduces the future work in developing active-MMR gearbox by using an electromagnetic clutch. Some possible control development directions on the active-MMR is also mentioned at the end of the thesis to provide reference for future works.

16 TIDAL AND WAVE POWER↗

Center for Gas Separations (CGS)

The total energy consumption in the U.S. has been rising steadily for decades, and it currently amounts to ~98,000 TBtu/yr, with approximately 30% of this total attributable to the industrial sector. Reasonable estimates indicate that 45–55% of total industry energy consumption derives from chemical separations, and for example, over 120 TBtu/yr alone is used in carrying out olefin/paraffin separations via energy-intensive cryogenic distillation. Therefore, the pursuit of new, even radically different approaches to some of the most energy-intensive industrial separations processes is an imperative scientific pursuit for reducing energy consumption toward a more sustainable future. Adsorbent and membrane-based separations can require a fraction of the energy needed for distillation methods, and as such are considered promising solutions for balancing increasing energy demand in the U.S. with the need for a massive reduction in energy consumption. Although considerable research effort has been devoted to the design of materials capable of carrying out various gas separations, usually operating through size-selective, chemisorptive, or physisorptive mechanisms, it remains a great challenge to design materials that function adequately for real-world applications. Indeed, the chemical and physical differences between molecules in gas mixtures of interest are often small, and therefore it is necessary, through the use of nanoscience and synthetic chemistry, to engineer unprecedented molecular-level control in adsorbate–adsorbent interactions. The overarching mission of the Center for Gas Separations (CGS) was to discover fundamental innovations that have the potential to dramatically reduce the energy associated with critical gas separations. In particular, the CGS developed novel synthetic routes, guided by molecular chemistry principles, as well as advanced characterization and computational methods, that have enabled the discovery of new materials and membranes tailor-made to exhibit exceptional performance for a range of gas separations processes, as required in the clean use of fossil fuels and in reducing CO 2 emissions from industry. A challenge of this magnitude required the collaboration and synergy of a large team of researchers with expertise in materials synthesis, characterization, and computations. During the 11-year project period, the CGS created a range of new materials within the family of highly-tunable, porous solids known as metal–organic frameworks (MOFs). These new frameworks demonstrate novel mechanisms for key industrial gas separations, including revolutionary new cooperative adsorption processes that enable low-energy CO 2 and CO capture, and are capable of efficiently separating olefins from paraffins, O 2 from air, and the shape-selective separation of alkane isomers. In addition, the CGS developed new strategies for incorporating these materials into composite membranes toward highly efficient and selective membrane-based separations. As a testament to the success of the CGS, two start-up companies, Mosaic Materials,4 Inc. and Flux Technology, Inc., grew out of these research efforts, and these companies are seeking to commercialize MOF and composite membranes materials for key separations in industry, including large-scale CO 2 capture and hydrocarbon separations, respectively. Another company, framergy, Inc., licensed IP resulting from CGS research toward the commercialization of adsorbents for various energy-relevant applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Overcoming the Damping–Elasticity Paradox via 3D‐Printed NiTiSn Nanocomposite

Abstract Developing high damping alloys (HDAs) with large elastic strain has attracted growing attention due to the increasing demand for energy absorption with overload reliability and reusability. However, damping capacity inherently conflicts with elasticity, because the former requires a liable movement of crystal defects while the latter opposite. To deal with the damping‐elasticity paradox, the advantage of pseudobinary eutectic reaction and rapid cooling of laser powder bed fusion is taken to fabricate a bulk NiTiSn nanocomposite with a two‐level hierarchical structure. The first‐level architecture is composed of martensitic NiTi nanolamellae and reinforced Ti 3 Sn nanolamellae. In addition to lattice strain matching and lamellar boundary strengthening, a novel mechanism of martensite reorientation mediated by reversible stress‐induced detwinning‐twinning is activated to generate large elastic strain. A high density of nanotwins and nanodomains within NiTi nanolamellae constitute the second‐level architecture, which provides pronounced internal friction for high damping capacity. As a result, our NiTiSn nanocomposite exhibits a record‐high integration of damping capacity (tanδ > 0.10) and elastic strain (exceeding 4.5%), as well as superb stability under cyclic overload. This research not only represents a major breakthrough in achieving HDAs with outstanding damping and elastic strain but also offers a novel paradigm for high‐performance functional and structural materials.

Chemistry↗

Dislocation line tension model to improve understanding of the effects of hydrogen on the deformation of structural materials

Decarbonization efforts highlight hydrogen as an attractive alternative to fossil fuels, but its tendency to embrittle structural metals demands careful consideration when designing hydrogen infrastructure. Moreover, the mechanisms by which hydrogen degrades these materials are still being elucidated. The current work develops new computational tools to quantify the different contributions of hydrogen to the energy barrier of cross-slip, a key deformation mechanism. Novel features are implemented to a line tension model, which include the use of non-singular dislocation interactions, character-dependent dislocation energies and simulations of the constriction configurations. A new molecular dynamics technique is developed to calculate the interaction energy between the partials of a dissociated dislocation via fixing the centers of mass of the regions below and above the Shockley partials and performing time-averaged calculations. Hydrogen is found to impact the stacking fault width of dislocations in different ways depending on their characters: it decreases for dislocations with a character θ > 30°, remains unchanged for θ = 30° and increases for θ < 30°. The latter regime is a newly identified mechanism by which hydrogen inhibits cross-slip. Moreover, formation of nano-hydrides is predicted to occur around screw dislocations for high hydrogen concentrations, a phenomenon previously identified only in dislocations with an edge component. If nano-hydrides develop, their influence extending the equilibrium stacking fault width and increasing both the constriction and cross-slip energy barriers dominate over all other hydrogen contributions. The theory and tools developed will pave the way towards a comprehensive understanding of hydrogen-dislocation interactions in structural metals.

08 HYDROGEN↗

Permeability of the HIV-1 capsid to metabolites modulates viral DNA synthesis

Reverse transcription, an essential event in the HIV-1 life cycle, requires deoxynucleotide triphosphates (dNTPs) to fuel DNA synthesis, thus requiring penetration of dNTPs into the viral capsid. The central cavity of the capsid protein (CA) hexamer reveals itself as a plausible channel that allows the passage of dNTPs into assembled capsids. Nevertheless, the molecular mechanism of nucleotide import into the capsid remains unknown. Employing all-atom molecular dynamics (MD) simulations, we established that cooperative binding between nucleotides inside a CA hexamer cavity results in energetically favorable conditions for passive translocation of dNTPs into the HIV-1 capsid. Furthermore, binding of the host cell metabolite inositol hexakisphosphate (IP 6 ) enhances dNTP import, while binding of synthesized molecules like benzenehexacarboxylic acid (BHC) inhibits it. The enhancing effect on reverse transcription by IP 6 and the consequences of interactions between CA and nucleotides were corroborated using atomic force microscopy, transmission electron microscopy, and virological assays. Collectively, our results provide an atomistic description of the permeability of the HIV-1 capsid to small molecules and reveal a novel mechanism for the involvement of metabolites in HIV-1 capsid stabilization, nucleotide import, and reverse transcription.

60 APPLIED LIFE SCIENCES↗

Serum Neutralizing and Enhancing Effects on African Swine Fever Virus Infectivity in Adherent Pig PBMC

African swine fever virus (ASFV) causes hemorrhagic fever with mortality rates of up to 100% in domestic pigs. Currently, there are no commercial vaccines for the disease. Only some live-attenuated viruses have been able to protect pigs from ASFV infection. The immune mechanisms involved in the protection are unclear. Immune sera can neutralize ASFV but incompletely. The mechanisms involved are not fully understood. Currently, there is no standardized protocol for ASFV neutralization assays. In this study, a flow cytometry-based ASFV neutralization assay was developed and tested in pig adherent PBMC using a virulent ASFV containing a fluorescent protein gene as a substrate for neutralization. As with previous studies, the percentage of infected macrophages was approximately five time higher than that of infected monocytes, and nearly all infected cells displayed no staining with anti-CD16 antibodies. Sera from naïve pigs and pigs immunized with a live-attenuated ASFV and fully protected against parental virus were used in the assay. The sera displayed incomplete neutralization with MOI-dependent neutralizing efficacies. Extracellular, but not intracellular, virions suspended in naïve serum were more infectious than those in the culture medium, as reported for some enveloped viruses, suggesting a novel mechanism of ASFV infection in macrophages. Both the intracellular and extracellular virions could not be completely neutralized.

59 BASIC BIOLOGICAL SCIENCES↗

Aberrant FBXW7-mediated ubiquitination and degradation of ZMYND8 enhances tumor progression and stemness in bladder cancer

ZMYND8, an epigenetic regulator, was identified as a common oncogene across various tumors. However, little was reported about the association between ZMYND8 and bladder cancer. Besides, aberrant mechanisms that contribute to abnormal ZMYND8 expressions still remain unclear. In the current study, we first found that ZMYND8 protein levels were significantly elevated in Bca samples versus normal tissues, but not the mRNA levels. We then utilized the Cell Counting Kit-8 (CCK-8) assay, clone formation assay and transwell analysis to confirm that ZMYND8 could remarkably promote the tumor progression in vitro, including growth capacity and migration. Bioinformatic predictive analysis revealed that E3 ubiquitin ligase FBXW7 interacts directly with ZMYND8 and degrades ZMYND8 in a polyubiquitination manner. Low FBXW7 was a hazard factor for promoting and depending on accumulated ZMYND8 proteins to promote Bca progression. Gene set enrichment analysis (GSEA) further indicated that ZMYND8 was notably associated with stemness process, which was well functionally validated. Lastly, ZMYND8 deficiency was observed to inhibit tumor growth of Bca in vivo, revealing a promising translational significance in Bca treatment. In conclusion, our study for the first time provided evidence for a novel mechanism of FBXW7/ZMYND8 axis in Bca, providing therapeutic vulnerability for individualized cancer treatment.

60 APPLIED LIFE SCIENCES↗