High Synergy Research Articles

PROBABILISTIC LEARNING OF TREATMENT TREES IN CANCER.

Accurate identification of synergistic treatment combinations and their underlying biological mechanisms is critical across many disease domains, especially cancer. In translational oncology research, preclinical systems such as patient-derived xenografts (PDX) have emerged as a unique study design evaluating multiple treatments administered to samples from the same human tumor implanted into genetically identical mice. In this paper, we propose a novel Bayesian probabilistic tree-based framework for PDX data to investigate the hierarchical relationships between treatments by inferring treatment cluster trees, referred to as treatment trees (Rx-tree). The framework motivates a new metric of mechanistic similarity between two or more treatments accounting for inherent uncertainty in tree estimation; treatments with a high estimated similarity have potentially high mechanistic synergy. Building upon Dirichlet Diffusion Trees, we derive a closed-form marginal likelihood encoding the tree structure, which facilitates computationally efficient posterior inference via a new two-stage algorithm. Simulation studies demonstrate superior performance of the proposed method in recovering the tree structure and treatment similarities. Our analyses of a recently collated PDX dataset produce treatment similarity estimates that show a high degree of concordance with known biological mechanisms across treatments in five different cancers. More importantly, we uncover new and potentially effective combination therapies that confer synergistic regulation of specific downstream biological pathways for future clinical investigations. Our accompanying code, data, and shiny application for visualization of results are available at: https://github.com/bayesrx/RxTree.

Tailoring surface defects in Plasma Electrolytic Oxidation (PEO) treated 2-D black TiO2: Post-treatment role, and intensification by peroxymonosulfate activation in visible light-driven photocatalysis

Herein, we have developed a visible light-responsive black TiO2 photocatalytic coating with controlled formation of oxygen vacancies (OV) and Ti3+ species, crucial for enhancing photocatalytic reactions. The rational control of these semiconductor defects was achieved through plasma electrolytic oxidation (PEO), followed by NaOH post-treatment. The coating's effectiveness was evaluated by tetracycline (TC) degradation. The surface defects function as traps, reducing electron/hole recombination and forming mid-gap/localized-donor states, narrowing the band gap. Rigorous material characterization confirmed unaffected morphology and PEO coating phases, while increasing the density of OVs and Ti3+ species. As a result, TC photo-degradation was ∼3.5 times higher compared to plain PEO coatings. The material demonstrated exceptional stability and efficiency, while it was successfully intensified via peroxymonosulfate (PMS) activation, leading to high synergies (2.10). Scavenger tests revealed the existence of both radical/non-radical pathways, indicating the prevailing photocatalytic mechanism and the key differences achieved through this novel process.

A novel ligand protection strategy based on lacunary polyoxometalate to precisely construct CoMoS active sites for hydrodesulfurization

Efficient CoMoS catalysts with intimate bimetallic synergy are derived from cobalt-substituted phosphomolybdate and exhibited excellent hydrodesulfurization (HDS) activity. Based on ligand protection strategy, the introduction of pyridine ligands onto the vacancies of the trivacant polyoxometalates (POMs) successfully overcame their low stability and isomerization behavior in solution. Subsequently, Co2+ was anchored in the molecular skeleton of [A-α-PMo9O31(py)3]3− (PMo9-py) to form CoxPMo9-py precursors with high Co/Mo ratios, which enhanced the reducibility of Mo species and transformed them to abundant CoMoS active phase during sulfidation process. The quenching effect of pyridine molecules on the acidic sites of support and carbon deposition generated in the high temperature sulfidation weakened the strong metal-support interactions (SMSI) while improving the dispersion and sulfidation of active metals. Due to the unique structure of CoxPMo9-py, the CoMoS phase with high dispersion, efficient synergy and high concentration was obtained. The combination of POMs precursors and pyridine ligands enabled the S-CoxPMo9-py/Al2O3 catalyst to achieve up to 99.5% conversion of dibenzothiophene (DBT).

A facile method for access to high efficient piezo-photocatalytic synergy of Ba0.85Sr0.15TiO3 through tuning grain size, Curie temperature and energy band gap

Piezo-catalysis represents a promising and environmentally-friendly technology for dye degradation, but the commonly used BaTiO3 piezoelectric material still face bottleneck of relative low piezo-catalytic activity. Enhancement of its catalytic activity via diversified means is crucial for improving the degradation efficiency and implementation of water treatment. In this study, we synthesized Ba1-xSrxTiO3 nanoparticles utilizing the sol-gel method. The highest catalytic performance for degrading rhodamine B is at x = 0.15 through the piezo-photocatalytic synergy, displaying a degradation rate of 92.66 % within 18 min and an impressive reaction rate of 14.26 × 10−2 min−1, surpassing most of other BaTiO3-based materials. Importantly, the nanoparticles exhibited excellent catalytic degradation performance for a variety of pollutants under different environments. In addition, it is confirmed that Sr2+ doping can enhance the catalytic efficiency via three pathways, i.e. modifying energy band gap, modulating grain size as well as Curie temperature. This work provides a convenient strategy for the rational regulation of catalytic performance in BaTiO3-based piezoelectric materials.

Synergies and scaling of use case combinations in the field of asset logging and labeling

The digitalization of the energy sector enables a broad range of new digital use cases and business models. For instance, blockchain-technology can be used for the verification of tamper-resistant storage of asset data (asset logging) or manipulation-resistant guarantees of origin for electricity (labeling). Yet, it is associated with high implementation and operating effort. But many of these use cases require similar players, interfaces, data sets and data processing, so that synergies can result from a joint implementation. We thus evaluate these synergies in implementation and operating effort for use cases in the field of asset logging and labeling using a bottom-up evaluation of the components based on a methodology of Dossow (Energies 16:2424, 2022). Additionally, we extend this methodology to analyze the scalability of the use cases by assessing the relative effort reduction for an increasing number of players involved. The analysis already shows substantial synergies for combinations of two use cases. Yet, especially for combinations of three or more use cases a high effort reduction potential is derived. The highest synergies are obtained among the asset logging use cases, while a combination of asset logging and labeling use cases shows lower synergies in comparison. The analysis of the scaling of the use cases demonstrates that for labeling use cases the main effort driver is the number of consumers, while for asset logging use cases the number of asset operators shows to be more relevant. Thus, scaling effects outweigh the effort reduction potential of use case combinations especially for combinations of asset logging and labeling cases.

Simultaneously enhancing the strength and ductility of as-extruded AlN/AZ91 composites via nano-precipitation and pyramidal slip

Age hardening is often used to optimize the mechanical properties of as-deformed Mg-based materials in industry, whereas the improvement of strength is usually accompanied by the significant loss of ductility, which hinders the application of Mg-based materials in structural components. In the present work, high strength-ductility synergy (the yield strength of 263 ± 9 MPa, ultimate tensile strength of 398 ± 7 MPa and elongation to fracture of 34% ± 1%) was realized in as-extruded AlN/AZ91 composites after optimizing aging processes. Microstructural characterization shows that AlN particles induced a large number of geometrically necessary dislocations around the AlN/Mg interface during extrusion, which decreased the nucleation barrier and provided more heterogeneous nucleation sites for γ-Mg17Al12 continuous precipitation. Meanwhile, 95% of residual dislocations in as-extruded AlN/AZ91 composites were annihilated during peak-aging, suppressing the growth and coarsening of continuous precipitates. Therefore, high density of nano-sized γ-Mg17Al12 continuous precipitates was produced in as-extruded AlN/AZ91 composites after peak-aging. During tension, gliding dislocations bypassed spherical γ-Mg17Al12 nano-precipitates by Orowan looping rather than cutting mechanism, which induced a strong block on dislocation motion. So high yield strength was mainly attributed to the high density of non-shearable γ-Mg17Al12 nano-precipitates with spherical morphology, which was different from other Mg-Al-based systems. The results of texture evolution and slip trace analysis demonstrated that the suppression of extension twinning and less basal slip was due to the enhanced activity of pyramidal 〈c + a〉 slip in as-extruded AlN/AZ91 composites after peak-aging during the room temperature tension, meanwhile, the dislocation density of as-extruded AlN/AZ91 composites was significantly decreased during peak-aging, then higher elongation to fracture was achieved.

Superior strength-ductility synergy by microstructural heterogeneities in pure titanium

Optimizing strength and ductility by uniting microstructural heterogeneity and profitable crystallographic orientation is a challenge due to processing difficulties. Here, we synthesize a new kind of highly-oriented heterostructure (HOH) in pure titanium (Ti) by controlling hot extrusion, cold swaging, and annealing processing. The processed microstructure is characterized by (i) obvious grain size heterogeneity and (ii) highly-preferred crystallographic orientation with the c-axis of most grains perpendicular to the rolling direction (RD). The HOH Ti exhibits superior strength-ductility synergy in the RD, while higher strength but lower ductility in the transverse direction (TD). When the sample is stretched along the RD, obvious geometrically necessary dislocation accumulation and strain gradients near grain boundaries in a soft zone are experimentally verified, inducing extraordinary strengthening/hardening by producing hetero-deformation-induced stress and promoting dislocation storage. In the TD, {10–12} twins are observed in a hard zone while no plastic deformation occurs in the soft zone. It is further revealed that both the hard and soft zones exhibit high Schmid factors (m) for the prismatic, pyramidal <a> slip and pyr1/pyr2 <c + a> slip in the RD, indicating a soft slip mode. On the other hand, the soft zone becomes “hard” due to very low m values for the prismatic <a> slip in the TD, resulting in fewer slip systems in the soft zone. These observations suggest that the heterostructure design with profitable crystallographic orientation is an effective approach to achieving high strength-ductility synergy.

Improving strain hardening capacity of high-strength Ti–6Al–4V alloy by a dual harmonic structure

By TiH2/Al60V40 powder processing, in-situ dehydrogenation, and powder compact extrusion, we successfully fabricate a Ti–6Al–4V (wt.%) alloy with a dual harmonic structure. Such multilevel structural heterogeneity is attained by suppressing the stabilization effect of the residual hydrogen on β-Ti phase, through controlling the prior β grain sizes and interstitial element contents. It is demonstrated that this dual harmonic structure is beneficial in alleviating mechanical mismatch between hetero-domains and fully exploiting the hetero-deformation induced hardening, thereby leading to a high strain hardening rate and large uniform elongation. As a result, the material exhibits a better strength-ductility synergy (an ultimate tensile strength of 1338 MPa and a uniform elongation of 7.7%) than both the one-level harmonic and homogeneously structured materials. The present ‘tailoring structural heterogeneity through manipulating hydrogen-enabled eutectoid transformation’ strategy offers a different pathway to design and fabricate novel heterogeneously structured titanium alloys with a high strength-ductility synergy.

Universal Piezo-Photocatalytic Wastewater Treatment on Realistic Pollutant Feedstocks by Bi4TaO8Cl: Origin of High Efficiency and Adjustable Synergy.

Clean water is a fundamental human right but millions struggle for it daily. Herein, we demonstrate a new piezo-photocatalyst with immense structural diversity for universal wastewater decontamination. Single-crystalline Bi4TaO8Cl nanoplates with exposed piezoelectric facets exhibit visible-light response, piezoelectric behavior with coercive voltages of ±5 V yielding 0.35% crystal deformation, and pressure-induced band-bending of >2.5 eV. Using five common contaminants of textile and pharmaceutical industries, we show that the nanoplates can mineralize them in all piezocatalytic, photocatalytic, and piezo-photocatalytic approaches with efficiencies higher than most catalysts developed for just one contaminant. Their efficiencies for feedstocks differing over 2 orders of magnitude in concentrations, the highest to date, are also demonstrated to simulate real-life situations. These extensive studies established that combining piezocatalytic and photocatalytic approaches can lead to a tremendous synergy exceeding >45%. The origin of synergy has been illustrated for the first time using band-bending models and improved charge transfer from valence and conduction band electronic surfaces. We further quantified synergy across reactants, concentrations, and ultrasonic frequency and power to demonstrate their versatility and unpredictability. Finally, seven parameters that contribute to synergy but create unpredictability have been identified for the rational design of piezo-photocatalysts for wastewater treatment.

Dynamic precipitation and deformation behaviors of a bimodal-grained WE43 alloy with enhanced mechanical properties

Achieving a high strength-ductility synergy in rolled Mg alloys remains a major challenge, especially for Mg alloys with high contents of rare earth (RE) elements, which are hard-to-deform and exhibit poor formability. In the present work, a bimodal grain structure consisting of fine grains (FGs) and coarse grains (CGs) has been achieved in a novel WE43 alloy sheet prepared by the hard-plate rolling (HPR) technique, which breaks the strength-ductility trade-off dilemma of the conventional WE43 alloy. Notably, the yield strength (YS) reaches as high as ∼312 MPa, presenting a remarkable improvement of YS (∼60 MPa) in comparison to conventionally rolled counterparts. Meanwhile, the ultimate tensile strength (UTS) and elongation-to-failure (EF) are ∼332 MPa and ∼11.8%, respectively, much higher than those of the wrought WE43 alloy reported in literature. Specifically, the disparate dislocation slips and dynamic precipitation behaviors in FGs and CGs have been studied in detail by combining EBSD and TEM analysis. The discrepancy of dynamic precipitation behavior in FGs and CGs is originated from the heterogeneous dislocation slip-dominated deformation behavior during HPR, related to initial grain orientations. It reveals that basal slips are dominant in the FG area, where equilibrium β-Mg14Nd2Y phase has precipitated along grain boundaries. In contrast, non-basal slips are prevalent and the metastable short rod-shaped β1 phase has formed within CGs. The enhanced YS of the present HPRed WE43 alloy sheet is mainly attributed to the formation of large amounts of extremely fine grains with an average size of ∼0.94 μm. The enhanced Orowan strengthening comes from the interaction between short rod-shaped β1 particles and non-basal dislocations (prismatic <a>, pyramidal <c + a> and pyramidal <a> dislocations) in CGs. In particular, the interactions between β1 particles and pyramidal <a> dislocations dominate the Orowan strengthening, leading to an increase of ∼34 MPa in the YS. Basal to basal slip transfers have been observed in FGs while non-basal slips are prevalent in CGs, which could be helpful for release the stress concentration near GBs. It is beneficial for preventing earlier fracture and thus enhancing the tensile strength combined with decent ductility.

Dislocation loop assisted precipitation of Cu-rich particles: A phase-field study

In order to better understand thermal aging mechanism of reactor pressure vessel steels with the action of dislocation loop, the hardening behavior and microstructure evolution of Fe-10at. %Cu-3at. %Mn-1.5at. %Ni-1.5at. %Al alloy is investigated using phase-field method. The results showed that the precipitation includes spinodal decomposition of Cu-rich precipitates (Cu/Ni (Al, Mn) core–shell structure) assisted by dislocation loops, spinodal decomposition assisted by new dislocations, and nucleation and growth induced by thermal aging. Ultimately, a gradient of Cu-rich nanoprecipitates is formed, which can result in high strength-ductility synergy. Phase-field method provides better details for predicting the morphology, distribution, and size of Cu-rich precipitates in Fe-Cu-Mn-Ni-Al alloy with dislocation loops. The simulation results are introduced into the hardening model of copper-rich precipitates to achieve a closed-loop of process → microstructure → performance.

Achieving ultrahigh strength and ductility in high-entropy alloys via dual precipitation

The strength-ductility trade-off has been a longstanding dilemma in metallic materials. Here we report an innovative approach to achieve a high strength-ductility synergy via dual precipitation of sheared and bypassed precipitates. (Ni2Co2FeCr)96–xAl4Nbx (at.%) alloys strengthened by nanoscale L12 particles and Laves precipitates were selected as a model for this study, and their precipitate microstructures and mechanical properties were thoroughly investigated. The dual-precipitation-strengthened alloys exhibit a yield strength of more than 1400 MPa, an ultimate tensile strength of over 1800 MPa, and a uniform elongation of 18%, thus achieving a high strength-ductility synergy. Our analysis reveals that the nanoscale L12 precipitates contribute to the strength via the particle shearing mechanism, whereas the Laves phase provides the strengthening through the Orowan bypass mechanism. The study of deformation microstructures shows that the L12 precipitates are sheared by stacking faults, which facilitates long-range dislocation gliding through the matrix. As a result, deformation induces the formation of hierarchical stacking fault networks and immobile Lomer–Cottrell locks, which effectively enhance the work hardening capability and plastic stability, thereby resulting in a high ductility at high strength levels. Dislocations are piled-up against the interface between the Laves precipitates and matrix, which increases the work hardening capability at the early stages of plastic deformation but causes stress concentrations. The dual precipitation strategy may be useful for many other alloys for achieving superior mechanical properties for technological applications.

Improving mechanical properties of Mg-Sn alloys by co-addition of Li and Al

In this work, a novel low-alloyed Mg-Sn-Li-Al alloy with high-strength has been developed. The addition of ∼1 ​wt% Li into the Mg-2Sn wt.% binary alloy can change the type of strengthening phases in Mg-2Sn-1Li sample (TL21), involving the formation of both Li2MgSn and Mg2Sn phases. The co-addition of ∼1 ​wt% Al and ∼1 ​wt% Li can further induce the higher density of both micron-sized phases and nano-precipitations in the Mg-2Sn-1Li-1Al sample (TLA211). The nano-precipitations can inhibit the grain growth, which thus lead to the fine grain size of ∼1.38 ​μm in TLA211 sample, and ∼1.59 ​μm in the TL21 sample. Besides, the profuse nano-phases would improve the yield strength via Orowan hardening effect. Consequently, the TL21 sample can exhibit the high yield strength of ∼204 ​MPa, and elongation of ∼6.6%. The TLA211 sample exhibits the much higher yield strength of ∼250 ​MPa, ultimate tensile strength of ∼291 ​MPa, and also high elongation of ∼9.0%. The high strength-ductility synergy, together with the low-Sn content, make the present Mg-Sn based alloy to be potential for the wider industrial applications.

A Comprehensive Investigation on the Direct-Ammonia Thin-Film Solid Oxide Fuel Cells (TF-SOFCs) and the Effect of Porosity-Control of the Anode Support Layer

Ammonia is highly regarded as a hydrogen storage and transportation medium due to its various advantages. Solid oxide fuel cells (SOFCs) can achieve high synergy by using ammonia directly as fuel without the ammonia decomposition reactor and filtration devices. We confirmed the distribution of hydrogen produced by the decomposition of ammonia through 2D multi-physics numerical modeling and predicted the decomposition rate and maximum current density according to the tortuosity. Based on the results, we adjusted the pore volume of the anode-support layer using PMMA to reduce tortuosity and facilitate hydrogen supply and produced anode support layer-anode functional layer substrate. We then manufactured a Thin-film SOFC and tested using hydrogen and ammonia fuel, and achieved high performance of 1897 and 1357 mW/cm2 at 650 °C.

Synergistic enhancement of high temperature strength and ductility with a novel γ/ε dual-phase hetero-nanostructure in NiCoCr-based alloys

In most γ"-strengthened superalloys, the γ"→δ stabilization is generally considered as an unfavorable transformation process due to the incapability of δ phase on conferring high-temperature strengthening. While recent studies in multi-component alloys indicate that another stabilized γ" phase (ε phase with D019 structure) has been found and proven to be beneficial to mechanical properties. This work shows that the precipitation of ε phase could be tailored in such a way, that it is accompanied by the formation of nano-twins in low stacking fault energy NiCoCr-based multi-component alloys, establishing a unique matrix/(nano-twin/ε/nano-twin)/matrix double-stacked-sandwich heterogeneous nanostructure. This novel ε-plate/nano-twin structure has been found to provide satisfying high temperature strength-ductility synergy and structural stability after aging, thereby leading to a yield-strength enhancement of ∼120% at 25 °C and ∼98% at 700 °C, respectively, while still maintaining sound ductilities. This unique self-organized, heterogeneous, lamellar nanostructure opens up new avenues for further development of hierarchically-nanostructured, high-temperature structural materials.

Computational design and experimental realization of Zn substitution in Cr-poisoning resistant LaNi0.6Fe0.4O3-δ solid oxide fuel cell cathode for enhanced performance and durability

Chromium poisoning rapidly degrades the performance of solid oxide fuel cell (SOFC) cathode materials with superior oxygen reduction kinetics, such as La0·6Sr0·4Co0·2Fe0·8O3 and La0·6Sr0·4CoO3. Previously, LaNi0.6Fe0.4O3 (LNF) demonstrated excellent resistance to chromium poisoning; however, it has relatively low electrocatalytic activity. Here, we investigate the effect of Zn substitution on the B-site of LNF cathode and deliver La(Ni0·6Fe0.4)1-xZnxO3-δ cathode materials with enhanced electrical and electrochemical properties. The ab initio first-principles calculations showed charged oxygen-vacancy defect formation energies of Zn-doped LNF (2.07 eV for La8Ni5Fe2Zn1O24 and 1.83 eV for La8Ni4Fe3Zn1O24) are lower than those of undoped LNF (2.92 eV for La8Ni5Fe3O24). Various Zn-doped LNF materials are synthesized and tested for experimental validation of the DFT results. Electrical conductivity relaxation, temperature-programmed oxygen desorption, and electrochemical impedance spectroscopy analysis indicate enhanced oxygen reduction kinetics for LNFZ3 (La(Ni0·6Fe0.4)0.97Zn0·03O3-δ). At 700 °C, LNFZ3 has 25.4% less polarization resistance and 52.3% higher maximum power density of an anode-supported SOFC than LNF. Moreover, LNFZ3 has the lowest polarization resistance compared with various studies reporting LNF cathode material. Furthermore, LNFZ3 shows highly robust operation under accelerated chromium-poisoning conditions at 700 °C. The high performance and durability synergy makes the newly developed LNFZ3 a promising cathode material for further commercial validation studies.

Development and characteristics of a low rare-earth containing magnesium alloy with high strength-ductility synergy

In this study, we successfully developed a low RE containing Mg-3Y-2Gd-1Nd-0.5Zr (wt%) alloy with high strength-ductility synergy by combined processes of hot extrusion, hot rolling and ageing. This alloy exhibits an excellent strength-ductility balance (UTS of 345 ± 2.0 MPa, TYS of 301 ± 5.0 MPa and EL of 9.2 ± 1.9%), which is better than that of many Mg-RE wrought alloys with higher RE concentration and even comparable to that of 6061 Al wrought alloy. A long-range chain-like structure consisting of β′ phase, β H phase, β M phase and zig-zag atomic columns is observed for the first time in the studied alloy. The combined process of hot extrusion and hot rolling boosts the formation of deformed grains and low angle grain boundaries, and makes the deformed grains dominate in the alloy strengthening. Under this circumstance, the following ageing generates a novel heterogeneous structure comprising the long-range chain-like structure with broad interparticle spacing and the spacious precipitate-free zones in the deformed grains, which plays a key role in the concurrent strengthening and toughening of the alloy. The present study demonstrates that the deformed grains with long-range chain-like structures and precipitate-free zones is desirable microstructure for the low RE containing Mg alloys to achieve high strength-ductility synergy.

Synergies and trade-offs of climate-smart agriculture (CSA) practices selected by smallholder farmers in Geshy watershed, Southwest Ethiopia

Studies on mainstreaming climate-smart agriculture (CSA) practices can increase smallholder farmers’ capacity and awareness to improve food security and establish sustainable livelihoods through resilient agricultural systems, while achieving adaptation and mitigation benefits. Hence, valuable insights can be obtained from smallholder farmers in responding to present and forthcoming challenges of climate change impacts. However, there is little research work on trade-off and synergy assessments. Taking Geshy watershed in Southwest Ethiopia as a case study area, both quantitative and qualitative data analysis were undertaken in this study. The data were collected from 15 key informant interviews, 6 focus group discussions, and 384 households to answer the following questions: (1) what are the top 5 preferred CSA practices for smallholder farmers in Geshy watershed when coping with the impacts of climate change? (2) What is the performance of the preferred CSA practices? And (3) which trade-offs and synergies are experienced upon the implementation of CSA practices? The study came up with the most preferred CSA practices such as the use of improved crop varieties, small-scale irrigation, improved animal husbandry, the use of efficient inorganic fertilizers, and crop rotation with legumes. The selected CSA practices showed that the productivity goal exhibit the best synergy, while the mitigation goal has trade-offs. The study also has shown that the use of improved crop varieties causes high synergies in all 3 goals of CSA practices; small-scale irrigation provides a medium synergy on productivity goal but high synergy for adaptation and mitigation goals; improved animal husbandry shows a high synergy with the adaptation goal, a relatively lower synergy with the productivity goal, and a trade-off with the mitigation goal; the use of efficient inorganic fertilizers shows maximum synergy for the productivity and adaptation goals; and crop rotation with legumes exhibits high synergy with the productivity and mitigation goals but a relatively lower synergy with the adaptation goal. These results can provide evidence to various stakeholder farmers in the value chain that the impacts of climate change can be addressed by the adoption of CSA practices. In general, CSA practices are considered indispensable. Smallholder farmers prefer CSA practices that help to increase crop productivity and household resilience to climate change impacts. The results generate a vital foundation for recommendations to smallholder farming decision-makers. It also sensitizes actions for innovative and sustainable methods that are able to upscale the preferred CSA practices in the agricultural system in Geshy watershed of Southwest Ethiopia and other regions.

Synergistic interactions in multispecies biofilm combinations of bacterial isolates recovered from diverse food processing industries.

Most biofilms within the food industry are formed by multiple bacterial species which co-exist on surfaces as a result of interspecies interactions. These ecological interactions often make these communities tolerant against antimicrobials. Our previous work led to the identification of a large number (327) of highly diverse bacterial species on food contact surfaces of the dairy, meat, and egg industries after routine cleaning and disinfection (C&D) regimes. In the current study, biofilm-forming ability of 92 bacterial strains belonging to 26 genera and 42 species was assessed and synergistic interactions in biofilm formation were investigated by coculturing species in all possible four-species combinations. Out of the total 455 four-species biofilm combinations, greater biofilm mass production, compared to the sum of biofilm masses of individual species in monoculture, was observed in 34 combinations. Around half of the combinations showed synergy in biofilm mass > 1.5-fold and most of the combinations belonged to dairy strains. The highest synergy (3.13-fold) was shown by a combination of dairy strains comprising Stenotrophomonas rhizophila, Bacillus licheniformis, Microbacterium lacticum, and Calidifontibacter indicus. The observed synergy in mixed biofilms turned out to be strain-specific rather than species-dependent. All biofilm combinations showing remarkable synergy appeared to have certain common species in all combinations which shows there are keystone industry-specific bacterial species which stimulate synergy or antagonism and this may have implication for biofilm control in the concerned food industries.

Abstract 1638: Validation of a novel pan-Ras inhibitor, ADT-007, against lethal variants of prostate cancer

Abstract Metastatic prostate cancer is the second leading cause of cancer deaths in US men. Most early-stage PCa are dependent on overexpression of the androgen receptor (AR) and are therefore sensitive to androgen deprivation therapies. However, eventual resistance to standard medical castration and secondary chemotherapies including next-generation AR-targeting agents like abiraterone or enzalutamide and taxanes (Docetaxel or cabazitaxel) is nearly universal. Further, neuroendocrine PCa or NEPC, a poorly differentiated aggressive variant of PCa that lacks AR expression, and the presence of cancer stem-like cells with self-renewal and differentiation (epithelial to mesenchymal trans-differentiation or EMT) capacities significantly contribute to the development of clinically most aggressive and lethal variants of PCa. Endogenous Ras/ERK/MAPK signaling is known to drive prostate tumor formation, cancer progression, cell migration, and the acquisition of mesenchymal phenotype (EMT) in metastatic prostate cancers. Ras family members are responsible for modulating the function of most of the receptors upregulated in advanced PCa, including AR, so that AR can be functional even in the absence of physiologic levels of androgen. Previous studies have reported that the NSAID, sulindac, inhibits Ras-induced transformation and directly binds Ras. In this study, we show that a non-COX inhibitory sulindac derivative, ADT-007, is a potent drug candidate against lethal PCa. First, we performed single-cell RNA sequencing as a biomarker-based drug screen and showed that chemo-resistant, drug-tolerant, stem-cell-like PCa cell clusters had high expression of Ras genes, indicating that the Ras inhibitor, ADT-007, may be effective in targeting these aggressive subclones. Next, using several cell-based assays on a large panel of lethal PCa cell lines representing metastatic castration-resistant PCa (mCRPC), NEPC as well as African American ancestry, we showed that ADT-007 is highly effective as a single-agent and in combination with taxanes. Combination index values were &amp;lt;0.7, and BLISS scores were &amp;gt;10, indicating very high synergy. Finally, using pre-vs-post-treatment bulk RNAseq, we demonstrated that ADT-007 is indeed effective in downregulating KRas and NRas in a dose-dependent manner. In addition, ingenuity pathway analysis (IPA) predicted significant downregulation of cell cycle, DNA replication, CCND1, AR, and the lncRNA ELDR, and upregulation of autophagy and interferon pathway genes, and the microRNA miR-96. Finally, using PCa patient datasets, we showed that ADT-007 is potentially capable of reversing the expression of several genes associated with biochemical recurrence. Thus, our results show that ADT-007 is a novel drug candidate that circumvents subclonal aggressiveness, drug resistance, and stemness in lethal PCa through simultaneous inhibition of multiple oncogenic factors/pathways. Citation Format: Taraswi Mitra Ghosh, Adam B. Keeton, Xi Chen, Salsabil Ahmed, Razan S. Waliagha, Gary A. Piazza, Amit K. Mitra. Validation of a novel pan-Ras inhibitor, ADT-007, against lethal variants of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1638.