Multiple Cycles Research Articles

Facile production of ethyl furfuryl ether via reductive etherification of furfural over Rh nanoparticles supported red mud as a catalyst

Reducing reliance on fossil fuels and mitigating industrial waste are two strategies for clean environmental management. An active research topic within this framework is to convert abundant bio-derived compounds, like furfural (FF), into a petroleum blend by employing industrial waste, like red mud (RM), as catalyst support. Here, we demonstrate that furfural can be chemoselectively converted in a single step into ethyl furfuryl ethers (EFE), which significantly enhance the blended petroleum's octane number. This is achieved in the presence of a recyclable Rh-impregnated RM catalyst. In this context, a range of valuable metals (M = Rh, Ir, and Ru) are impregnated into the RM (M@RM) and extensively characterized by SEM, EDS, XRD, FT-IR, TEM, and XPS. The 1% Rh@RM composite,calcined at 400 °C (1% Rh@RM-400), produced 75 % EFE selectivity with the >99 % conversion of furfural. The prepared catalyst retains its stability for the multiple cycles of the furfural hydrogenation reactions.

Abstract 3800: Next generation of spatial biology: High-throughput multiplexed Imaging Mass Cytometry™ with whole slide modes

Abstract Gaining spatial insights into the cellular composition of tumor tissue has tremendous potential to inform clinical and translational researchers about mechanisms behind spatial predictors of immunotherapy success, disease etiology and progression. Imaging Mass Cytometry™ (IMC™) is a high-plex spatial biology imaging technique that enables deep characterization of the diversity and complexity of the tumor microenvironment (TME). IMC supports detailed assessment of cell phenotype and function using 40-plus metal-tagged antibodies simultaneously on a single slide without issues associated with fluorescence-based spectral overlap, tissue autofluorescence or implementation of multiple washing and acquisition cycles. Currently, IMC enables user-defined regions of interest (ROI) in tissues to evaluate cellular and structural composition. To enhance the IMC user experience, we developed two new whole slide imaging (WSI) modes which enable streamlined workflows using ultrafast preview mode (PM) and high-throughput tissue mode (TM). PM samples the entire tissue at predefined spacing to rapidly capture a low-resolution image of all expressed markers in the antibody panel. PM generates an image in minutes to enable informed ROI placements while leaving the stained tissue intact for higher-resolution imaging. PM and TM are designed so acquisitions can easily occur on the same slide without additional processing steps. TM rapidly acquires images of the whole tissue at lower resolution (7 μm pixel size) at a quality that can be used for quantitative analysis of the tissue spatial biology. Specifically designed for high-throughput applications, TM in combination with a newly available 40-slide loader for the Hyperion XTi™ Imaging System permits automated and continuous imaging of more than 40 large tissue samples (400 mm2 per tissue) per week. We showcase the application of WSI modes using the newly developed Maxpar® Human Immuno-Oncology IMC Panel Kit. The 31-marker panel was combined with catalog antibodies to create a 40-plus-marker panel that expands the ability to conduct comprehensive high-plex tumor and immune cell profiling. Tumor tissue microarrays (TMA) and whole tumor tissue sections were stained with the expanded panel. Single-cell analysis of selected ROIs, on whole tumor sections and TMAs, guided by PM data successfully provided quantitative analyses of spatial biology at single-cell resolution. In parallel, TM on whole tumor sections followed by pixel-based analysis provided a spatially resolved quantitative assessment of specific tumor and immune components of the TME. This work demonstrates the expanded capabilities of IMC and establishes it as a reliable high-plex spatial biology imaging platform with high-throughput imaging capabilities ideally suited for translational and clinical applications. For Research Use Only. Not for use in diagnostic procedures. Citation Format: Qanber Raza, Thomas D. Pfister, Jyh Yun Chwee, Liang Lim, David Howell, Nikesh Parsotam, David King, Christina Loh. Next generation of spatial biology: High-throughput multiplexed Imaging Mass Cytometry™ with whole slide modes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3800.

MgAl Oxide Coatings Modified with CeO2 Particles Formed by Plasma Electrolytic Oxidation of AZ31 Magnesium Alloy: Photoluminescent and Photocatalytic Properties

MgAl oxide coatings composed of MgO and MgAl2O4 phases were doped with CeO2 particles via plasma electrolytic oxidation (PEO) of AZ31 magnesium alloy in a 5 g/L NaAlO2 water solution. Subsequently, particles of CeO2 up to 8 g/L were added. Extensive investigations were conducted to examine the morphology, the chemical and phase compositions, and, most importantly, the photoluminescent (PL) properties and photocatalytic activity (PA) during the photodegradation of methyl orange. The number of CeO2 particles incorporated into MgAl oxide coatings depends on the concentration of CeO2 particles in the aluminate electrolyte. However, the CeO2 particles do not significantly affect the thickness, phase structure, or surface morphology of the coatings. The PL emission spectrum of MgAl oxide coatings is divided into two bands: one in the 350–600 nm range related to structural defects in MgO, and another much more intense band in the 600–775 nm range attributed to the F+ centres in MgAl2O4. The incorporated CeO2 particles do not have a significant effect on the PL intensity of the band in the red spectral region, but the PL intensity of the first band increases with the concentration of CeO2 particles. The PA of MgAl/CeO2 oxide coatings is higher than that of pure MgAl oxide coatings. The MgAl/CeO2 oxide coating developed in aluminate electrolyte with a concentration of 2 g/L CeO2 particles exhibited the highest PA. The MgAl/CeO2 oxide coatings remained chemically and physically stable across multiple cycles, indicating their potential for applications.

PD-L1 Immune Checkpoint Targeted Photoactivable Liposomes (iTPALs) Prime the Stroma of Pancreatic Tumors and Promote Self-Delivery.

Desmoplasia in pancreatic ductal adenocarcinoma (PDAC) limits the penetration and efficacy of therapies. It has been previously shown that photodynamic priming (PDP) using EGFR targeted photoactivable multi-inhibitor liposomes remediates desmoplasia in PDAC and doubles overall survival. Here, bifunctional PD-L1 immune checkpoint targeted photoactivable liposomes (iTPALs) that mediate both PDP and PD-L1 blockade are presented. iTPALs also improve phototoxicity in PDAC cells and induce immunogenic cell death. PDP using iTPALs reduces collagen density, thereby promoting self-delivery by 5.4-fold in collagen hydrogels, and by 2.4-fold in syngeneic CT1BA5 murine PDAC tumors. PDP also reduces tumor fibroblast content by 39.4%. Importantly, iTPALs also block the PD-1/PD-L1 immune checkpoint more efficiently than free α-PD-L1 antibodies. Only a single sub-curative priming dose using iTPALs provides 54.1% tumor growth inhibition and prolongs overall survival in mice by 42.9%. Overall survival directly correlates with the extent of tumor iTPAL self-delivery following PDP (Pearson's r = 0.670, p = 0.034), while no relationship is found for sham non-specific IgG constructs activated with light. When applied over multiple cycles, as is typical for immune checkpoint therapy, PDP using iTPALs promises to offer durable tumor growth delay and significant survival benefit in PDAC patients, especially when used to promote self-delivery of integrated chemo-immunotherapy regimens.

Color stability of pressed lithium disilicate ceramics under repeated firings evaluated by different methods.

The aim of this study was to determine and compare color differences of pressed lithium disilicate ceramic specimens after repeated firing cycles. An additional objective was to determine and evaluate correlation of CIEDE2000 values analyzed by X-Rite Color i5 Spectrophotometer, VITA EasyShade Advance 4.0 and Adobe Photoshop. Tile specimens (N=36) with 8 x 10 x 1.5mm dimensions were prepared by IPS e.max Press lithium disilicate MT Monochromatic ingots and IPS e.max Multi Press lithium disilicate Multichromatic ingots. Specimens were exposed to 7 repeated firing cycles. Color analysis was performed after the 1st, 2nd, 3rd, 5th, and 7th firing cycles. CIE L*a*b* values were measured by X-Rite Color i5 Spectrophotometer, VITA EasyShade Advance 4.0 and Adobe Photoshop. CIE DE*2000 (ΔE*00) was calculated to estimate color differences. Linear regression and multiple comparison analysis (Tukey's HSD test) showed a statistically significant (p<.001) color difference ΔE*00 after multiple firing cycles. Statistically significant differences (p<.05) were also noted in different shade groups and between different instruments used for shade evaluation. Moreover, significant differences (p<.05) were found in interactive effects between different shades tested by different instrument, different shades tested after multiple firing cycles and different instruments after multiple firing cycles. Lithium disilicate material shows significant color differences after repeated firing cycles tested by three color analysis instruments. Measuring instruments used to evaluate CIE L*a*b* color values showed significant differences in color values analysis, which may lead to altered level of interpretation, particularly to determine perceptibility and clinical acceptability thresholds.

Molecularly imprinted photopolymers combined with smartphone-based optical sensing for selective detection of bisphenol A in foods.

Bisphenol A (BPA), known for its endocrine-disrupting properties and potential to leach into food products, has led to significant food safety concerns. Therefore, the development of sensitive and selective BPA rapid detection methods is crucial. In this study, molecularly imprinted solid-phase extraction coupled to a colorimetric method was adopted for the smartphone-based determination of BPA. The molecularly imprinted polymer (MIP) was prepared via photopolymerization and used as a selective adsorbent material for SPE columns. The solid-phase extraction (SPE) columns with multiple cycles significantly reduced the extraction time to only 30 min. The developed method demonstrates useful sensitivity for BPA (LOD = 30 ppb). Furthermore, BPA migration from plastic packaging was evaluated under different storage conditions, revealing that microwave treatment for 5 min led to BPA release from polycarbonate packaging in juice and basic solutions. The MIP selective extraction/clean-up and smartphone-based optical sensor were successfully applied to BPA standard solutions and complex food samples (e.g., juice and tap water), resulting in reproducible and selective BPA determination (RSD ≤ 6%, n = 3). This rapid and cost-effective method of producing MIPs for BPA offers a promising solution for fast and low-cost sensing for on-site fresh food analysis.

Exosome Isolation Using Chitosan Oligosaccharide Lactate-1-Pyrenecarboxylic Acid-Based Self-Assembled Magnetic Nanoclusters.

Exosomes are small extracellular vesicles that play a crucial role in intercellular communication and offer significant potential for a wide range of biomedical applications. However, conventional methods for exosome isolation have limitations in terms of purity, scalability, and preservation of exosome structural integrity. To address these challenges, an exosome isolation platform using chitosan oligosaccharide lactate conjugated 1-pyrenecarboxylic acid (COL-Py) based self-assembled magnetic nanoclusters (CMNCs), is presented. CMNCs are characterized to optimize their size, stability, and interaction dynamics with exosomes. The efficiency of CMNCs in isolating exosomes is systematically evaluated using various analytical methods to demonstrate their ability to capture exosomes based on amphiphilic lipid bilayers. CMNC-based exosome isolation consistently yields exosomes with structural integrity and purity similar to those obtained using traditional methods. The reusability of CMNCs over multiple exosome isolation cycles underscores their scalability and offers an efficient solution for biomedical applications. These results are supported by western blot analysis, which demonstrated the superiority of CMNC-based isolation in terms of purity compared to conventional methods. By providing a scalable and efficient exosome isolation process that preserves both structural integrity and purity, CMNCs can constitute a new platform that can contribute to the field of exosome studies.

Dion-Jacobson Type Lead-Free Double Perovskite with Ultra-Narrow Aromatic Interlayer Spacing for Highly Sensitive and Stable X-ray Detection.

The low-toxic and environmentally friendly 2D lead-free perovskite has made significant progress in the exploration of "green" X-ray detectors. However, the gap in detection performance between them and their lead-based analogues remains a matter of concern that cannot be ignored. To reduce this gap, shortening the interlayer spacing to accelerate the migration and collection of X-ray carriers is a promising strategy. Herein, a Dion-Jacobson (DJ) lead-free double perovskite (4-AP)2 AgBiBr8 (1, 4-AP = 4-amidinopyridine) with an ultra-narrow interlayer spacing of 3.0Å, is constructed by utilizing π-conjugated aromatic spacers. Strikingly, the subsequent enhanced carrier transport and increased crystal density lead to X-ray detectors based on bulk single crystals of 1 with a high sensitivity of 1117.3µCGy-1 cm-2 , superior to the vast majority of similar double perovskites. In particular, the tight connection of the inorganic layers by the divalent cations enhances structural rigidity and stability, further endowing 1 detector with ultralow dark current drift (3.06×10-8 nAcm-1 s-1 V-1 , 80V), excellent multiple cycles switching X-ray irradiation stability, as well as long-term environmental stability (maintains over 94% photoresponse after 90 days). This work brings lead-free double perovskites one step closer to realizing efficient practical green applications.

Nature‐Inspired Directional Microneedle Structures for Reversible Gripping on Skin and Fibrous Materials

Plants such as Galium aparine show directional gripping to various surfaces because of their microscale hook structures. A bio‐inspired artificial version of microhooks holds potential as a bidirectional, reversible, and reusable dry adhesive for soft, wet, or fibrous substrates such as skin or textiles. However, current methods for fabricating 3D structures are often costly, time‐consuming, or require precise alignment steps. Herein, a facile, cost‐effective, scalable, and unconventional microfabrication technique is proposed using tilted photolithography on a rotary stage and shear molding to fabricate a soft polydimethylsiloxane polymer mold containing the inverse replica of directional microneedle structures. To demonstrate the proof‐of‐concept, polyurethane is then added to the mold to obtain directional microneedles, referred to as microhooks. Friction force measurements using a nanotribometer show anisotropic performance (strong attachment in one direction and easy detachment in the opposite direction over multiple cycles) similar to the natural microhooks. Tribological characterization of the microhooks shows a gripping force 2.25 times greater than the sliding force. The fabricated microhook structures also provide an adhesion force of ≈0.62 N cm−2 to artificial skin. This biomimetic approach promises precise adhesion control and material versatility for attaching wearable devices and patches to the skin in biomedical applications.

A phase-transition model of reprocessible thermadapt shape memory polymer

A new type of thermadapt shape memory polymer (SMP) has not only the processability of thermoplastic SMP, but also the excellent shape fixation of thermosetting SMP. To enhance the application of this thermadapt SMP within industrial sectors, a comprehensive constitutive model based on phase transition is being proposed as an indicative descriptor of the semi-crystalline thermadapt SMP’s salient features, predominantly related to its two-way shape memory effect (SME) and thermal reprocessability. The concept of cooling elongation is also introduced in this model for modeling the two-way SME during the crystallization process. The molecular mechanism of chain-packing has been studied and used to establish phenomenological formulas. In addition, to systematically assess the temperature-time dependence of the crystallization process, the Avrami equation is improved by incorporating the distribution of polymer chain segments. This strategy provides a detailed investigation into the evolving pattern of the crystallization process in response to various temperature and time conditions. Compared with the experimental results, it is found that our model can well capture mechanical behavior in multiple shape memory cycles, including the two-way SME and reshaping process caused by bond exchange reaction. Furthermore, the potential application of SMP in smart mandrels is explored because the cooling elongation feature is able to endow it with self-adaptive expansion ability.

Optical pH Sensor Based on a Long-Period Fiber Grating Coated with a Polymeric Layer-by-Layer Electrostatic Self-Assembled Nanofilm.

An optical fiber pH sensor based on a long-period fiber grating (LPFG) is reported. Two oppositely charged polymers, polyethylenimine (PEI) and polyacrylic acid (PAA), were alternately deposited on the sensing structure through a layer-by-layer (LbL) electrostatic self-assembly technique. Since the polymers are pH sensitive, their refractive index (RI) varies when the pH of the solution changes due to swelling/deswelling phenomena. The fabricated multilayer coating retained a similar property, enabling its use in pH-sensing applications. The pH of the PAA dipping solution was tuned so that a coated LPFG achieved a pH sensitivity of (6.3 ± 0.2) nm/pH in the 5.92-9.23 pH range. Only two bilayers of PEI/PAA were used as an overlay, which reduces the fabrication time and increases the reproducibility of the sensor, and its reversibility and repeatability were demonstrated by tracking the resonance band position throughout multiple cycles between different pH solutions. With simulation work and experimental results from a low-finesse Fabry-Perot (FP) cavity on a fiber tip, the coating properties were estimated. When saturated at low pH, it has a thickness of 200 nm and 1.53 ± 0.01 RI, expanding up to 310 nm with a 1.35 ± 0.01 RI at higher pH values, mostly due to the structural changes in the PAA.

Deep eutectic solvent‐assisted selective extraction of valuable metals from waste lithium‐ion batteries

AbstractA novel synergistic extractant consisting of a deep eutectic solvent (DES) and tri‐n‐butyl phosphate (TBP) is proposed for selective extraction of valuable metals from waste lithium‐ion batteries (LIBs). The extraction efficiencies of Ni2+, Co2+, and Mn2+ were 99.8%, 99.1%, and 95.9%, respectively, and high‐purity Li+ was enriched in the raffinate after the single‐stage extraction. Valuable metal salts, lithium carbonate (92.3 wt%) and cobalt oxalate (94.9 wt%), were obtained. The DES + TBP extractant retained its high extraction performance even after multiple regeneration cycles. The extraction process followed the so‐called “cation exchange mechanism” with thermodynamic properties of ΔH &lt; 0, ΔG &lt; 0, and ΔS &lt; 0. The molecular‐level extraction mechanism demonstrated that the extraction process was dominated by both electrostatic and coordination interactions between the metal ions and DES/TBP, based on quantum chemical calculations. This study aims to provide a new strategy for recycling valuable metals from waste LIBs.

Additive friction stir deposition of super duplex stainless steel: Microstructure and mechanical properties

Additive Friction Stir Deposition (AFSD) is an emerging solid-state metal additive manufacturing (AM) process that offers several key benefits, including high deposition rates and wrought-equivalent mechanical properties even in the as-deposited condition. The work presented is the first study to report on the development of microstructure and mechanical properties of AFSD-processed duplex stainless steel (DSS2507). The banded microstructure of the starting material was remarkably affected by AFSD processing; the austenite grains exhibited a refined and equiaxed morphology, while the ferrite grains appeared slightly larger and elongated. Microstructural observations revealed that the potential mechanism of microstructure evolution in austenite was discontinuous dynamic recrystallization (DDRX), while in ferrite, it was continuous dynamic recrystallization (CDRX). The occurrence of multiple thermal cycles during the AFSD process resulted in σ phase precipitation, which in turn led to considerable variation in mechanical properties with respect to the build direction. The top region of the as-built part with an insignificant σ phase fraction showed improved tensile strength and ductility combination compared to the as-received DSS2507 as well as other AM-processed DSS2507 alloys.

Mechanical recycling of PET containing mixtures of phosphorus flame retardants

Flame-retarded polymers, such as polyester textiles and sheets, are attracting attention with regard to their sustainability. Mechanical recycling is currently the most frequently used technique for improving the circularity of plastics. However, one complication of mechanical recycling is associated with the (still) inevitable mixtures of polymers and additives, which can influence material stability and significantly deteriorate the mechanical properties of recycled products. In this study, we aim to specifically investigate the interactions between mixtures of phosphorus flame retardants (FRs) in polyethylene terephthalate (PET) and evaluate their potential role in the mechanical recycling of melt-spun fibers. Two highly relevant commercial FRs, namely a DOPO-derivative (DOPO-PEPA or DP) and Aflammit PCO 900 (AF), are added to PET compounds as additives using a melt compounder. The melt stability of PET/FR compounds over extended processing time is assessed by chemical, thermal, and rheological measurements. DP shows a molecular lubrication effect, lowering the melt viscosity of PET, while AF promotes chemical changes (i.e., chain branching/crosslinking). Interestingly, a PET compound containing hybrid mixtures of DP/AF 20/80 (wt.%/wt.%) shows the most stable behavior at high temperatures under both nitrogen and air atmospheres, thus showing a synergistic effect. Most importantly, in a recycling scenario, the stabilization effect persists at diluted concentrations below the typical FR contents in PET. Multiple extrusion cycles are used to assess the repeated processing behavior of the compounds, and the mechanical properties and fire behavior of melt-spun fibers are compared before and after recycling. The results reveal that DP can maintain the mechanical performance of recycled PET/FR fibers, even if it is mixed (contaminated) with AF.

Enhanced selective adsorption of H2S from CO2 by incorporating methylated polyethyleneimine into a porous carbon matrix

In this study, a series of hybrid adsorbent materials (AC@mPEI) with superior selective separation properties of H2S and CO2 are prepared by taking advantage of the differences in reaction mechanisms between H2S and CO2, as well as tertiary amines. Using a straightforward impregnation method, the methylated polyethyleneimine (mPEI) is successfully introduced into the pores of the porous carbon to create the desired hybrid adsorbents. The strong interaction between the tertiary amine groups and H2S facilitates the selective separation of H2S and CO2 gases. Remarkably, the adsorbent (1:1)AC@mPEI exhibits a substantial H2S adsorption capacity of 5.83 mmol·g−1 at 298 K and 1.0 bar and a high separation selectivity of H2S to CO2 (133), which is approximately 16.6 times higher than that of the porous carbon supporter. Further investigations, involving adsorption thermodynamics, breakthrough experiments, and spectroscopy, confirm that the strong interaction between the hybrid materials and H2S plays a pivotal role in enhancing the separation selectivity of H2S. Additionally, the adsorbed H2S can be well desorbed through vacuum degassing, allowing for multiple cycles of the adsorbent. This strategy, which leverages differences in gas adsorption mechanisms to fabricate hybrid adsorbents, presents novel concepts for the development of functional adsorbent materials for selective separation of gases.

Dynamic Characteristics and Energy Consumption of Electromechanical Converter of High-Speed On/Off Valve Under Multiple Motion Cycles Considering Eddy Current and Hysteresis

Dynamic Characteristics and Energy Consumption of Electromechanical Converter of High-Speed On/Off Valve Under Multiple Motion Cycles Considering Eddy Current and Hysteresis

Li3V2(PO4)3 Cathode Material: Synthesis Method, High Lithium Diffusion Coefficient and Magnetic Inhomogeneity.

Li3V2(PO4)3 cathodes for Li-ion batteries (LIBs) were synthesized using a hydrothermal method with the subsequent annealing in an argon atmosphere to achieve optimal properties. The X-ray diffraction analysis confirmed the material's single-phase nature, while the scanning electron microscopy revealed a granular structure, indicating a uniform particle size distribution, beneficial for electrochemical performance. Magnetometry and electron spin resonance studies were conducted to investigate the magnetic properties, confirming the presence of the relatively low concentration and highly uniform distribution of tetravalent vanadium ions (V4+), which indicated low lithium deficiency values in the original structure and a high degree of magnetic homogeneity in the sample, an essential factor for consistent electrochemical behavior. For this pure phase Li3V2(PO4)3 sample, devoid of any impurities such as carbon or salts, extensive electrochemical property testing was performed. These tests resulted in the experimental discovery of a remarkably high lithium diffusion coefficient D = 1.07 × 10-10 cm2/s, indicating excellent ionic conductivity, and demonstrated impressive stability of the material with sustained performance over 1000 charge-discharge cycles. Additionally, relithiated Li3V2(PO4)3 (after multiple electrochemical cycling) samples were investigated using scanning electron microscopy, magnetometry and electron spin resonance methods to determine the extent of degradation. The combination of high lithium diffusion coefficients, a low degradation rate and remarkable cycling stability positions this Li3V2(PO4)3 material as a promising candidate for advanced energy storage applications.

Achieving synergistic improvement of wear and mechanical properties in Ti–6Al–4V alloy by multiple cryogenic treatment

Ti–6Al–4V alloy was subjected to cryogenic treatment at −196 °C followed by single and multiple treatment cycles. Compression tests revealed that, despite a decrease in yield strength, cryogenically treated samples (especially by multiple cryogenic treatment) exhibited noteworthy improvements, with a 10.2% failure strain and 9.4% rise in compressive strength compared to the as-received state. The cryogenically treated samples were further refined and exhibited a reduced β-phase volume fraction, showed higher dislocation density and microstrain in X-ray diffraction results. Remarkably, the surface hardness was significantly improved by the cryogenic treatment, leading to enhanced wear resistance with lower coefficients of friction. This was attributed to the formation of smaller wear debris and a decrease in abrasive wear under sliding conditions. Electron backscatter diffraction (EBSD) findings demonstrate that the friction-induced localized deformation layers exhibit the high density of low angle grain boundaries (LAGBs) with deformation-induced sub-grains. The synergistic improvement of wear resistance and mechanical properties is ascribed to the intricate microstructural alterations induced during cryogenic treatment, particularly accentuated in multiple cryogenic treatment. These findings highlight the efficacy of cryogenic treatment in improving both mechanical and wear properties of Ti–6Al–4V alloy.

BRD4-targeting PROTACs Synergize With Chemotherapeutics Against Osteosarcoma Cell Lines.

Osteosarcoma at an advanced stage has a poor outcome, and novel targeted therapies are needed, especially for metastatic disease. Bromodomain inhibitors (BETi) are epigenetic modulators that broadly impair the expression of oncogenic proteins and exert antitumor effects. BETi can be combined with chemotherapeutics to increase therapeutic responses with superior effects in the form of proteolysis targeting chimeras (PROTACs) that degrade proteins of interest (POI) in multiple cycles. This work aimed to investigate the efficacy of BETi, such as JQ1, dBET57, and MZ1 PROTACs in combination with cytotoxic drugs against osteosarcoma cell lines. Chemosensitivity of the osteosarcoma cell lines HOS, Saos-2, MG-63, and G292 were tested with BET-directed agents alone or in combination with cytotoxic drugs comprising cisplatin, doxorubicin, topotecan, and gemcitabine using cell viability assays. The BET degraders exhibited highest toxicity to HOS cells and showed synergistic activity in combination with the chemotherapeutics, except for the degrader - topotecan/gemcitabine combinations. Highest synergy between BET agents and chemotherapeutics were found for the more chemoresistant Saos-2 cells and potentiation of toxicity in MG-63 cells for the BET agents - doxorubicin combinations and the MZ1-topotecan pair. HOS and Saos-2 cell lines had reduced protein expression of AXL, BCL-X, e-cadherin, CAIX, EpCAM, ErbB2, and vimentin in response to JQ1, MZ1, and BET57. The study suggests that the application of novel BET PROTACs in combination with chemotherapeutics could represent a new therapeutic option to improve the therapy of osteosarcomas. First orally available PROTACs have reached clinical trials.

From High Discipline Referrals to High-Engagement Classrooms: A Design-Based Approach to Creating a Campus-Wide Culture of Positive Learning Support for At-Risk Student Populations through Transforming Educators’ Instructional Teaming Practices

Instructional leaders in many school districts throughout the United States are increasingly confronted with spiraling numbers of discipline referrals from teachers who are unable to manage the off-task behaviors and discipline infractions of the growing percentages of diverse, academically at-risk students populating their classrooms. Many of these at-risk students, who come from families that are economically disadvantaged and have culturally rich and linguistically diverse backgrounds, have become stigmatized and minoritized by an education system whose curricula are often woefully inadequate in being able to meet the unique social and academic support needs of these diverse learners. This article profiles how one high school principal and his instructional turnaround leadership task force colleagues working in a high diversity urban school district utilized multi-leveled data analysis investigative thinking and innovative professional learning program design strategies derived from the education improvement science literature to implement a comprehensive intervention program for ninth through twelfth grade teams of core content teachers and their instructional supervisors. The specific goals of the intervention program were to: 1) change educators’ entrenched pedagogical thinking and instructional planning mindsets regarding the motivation levels and learning capabilities of the high discipline referral students who regularly engage in off-task disruptive behaviors in their classrooms; and 2) transform teachers’ instructional data teaming practices to better serve the academic learning support needs of the campus’s minoritized students. The design-based approach to instructional improvement employed in the high school case study leveraged the use of multiple cycles of new knowledge and skills acquisition, critical self-reflection, and immersive professional learning to assist educators in exploring how to engage together in authentic data teaming and data analysis–informed differentiated instructional planning to craft high-engagement classroom learning environments and interactive instructional units to effectively address the academic development and support needs of the campus’s diverse, at-risk learners.