Synergistic Combination Research Articles

All-solution-processed perovskite-quantum-dot light-emitting diodes through effective synergistic combination of orthogonal solvent and electron transport material

Perovskite quantum dots (PQDs) have shown great promise for use in photovoltaic devices, due to their ability to offer advantages such as tunability of visible light and efficient light emission. This study demonstrates the successful utilization of a triazine-based PO-T2T (2,4,6-Tris[3(diphenylphosphenyl)phenyl]-1,3,5-triazine; PO-T2T) as the electron transport layer (ETL) through an all-solution process. To improve the structural and optical characterization of CsPbBr3 and CsPbI3 QDs, three organic solvents, namely chlorobenzene, methyl acetate, and ethyl acetate, were selected to find an effective orthogonal solvent for PO-T2T. The all-solution processed devices incorporating PO-T2T and Methyl acetate (MeOAc) demonstrated impressive external quantum efficiencies of 5.57% for CsPbBr3 and 1.60% for CsPbI3 QDs. Notably, these devices also achieved the highest maximum luminance among all-solution processed PQDs-LEDs, with values of 33334 cd m–2 for CsPbBr3 and 224 cd m–2 for CsPbI3 QDs.

An innovative microplastic extraction technique: the switchable calcium chloride density separation column tested for biodegradable polymers, polyethylene, and polyamide

Extracting microplastics from complex matrices poses challenges due to the potential impact of harsh chemical treatments on microplastic properties. For fate and hazard assessment reliable techniques are needed to not only quantify the particle number but also to assess the physicochemical properties of environmental microplastics with minimum changes induced by extraction. Here we present the method development for an innovative and non-destructive extraction protocol based on a switchable calcium chloride density separation column. In contrast to commonly reported extraction protocols, the presented technique is suitable for targeted microplastic property analysis (e.g., surface chemistry and texture) by keeping chemical treatments (such as oxidation and enzymatic digestion) to a minimum. By adjusting the temperature we can control the aggregate state of the highly concentrated salt solution, allowing to separate the microplastics from matrix by cutting of purified, solidified samples. Harsh chemical treatments are avoided, as well as obstruction of microplastic extraction by adsorption to matrix components when passing the tap at the bottom of traditional density separation funnels.The use of microplastics that were prelabeled with a fluorescence dye helped to solve difficulties observed during method development by visual inspection before measurement of extraction efficiency: We spiked a blank compost with low-density polyethylene (LDPE) and polyamide (PA). Additionally, UV aged LDPE was used to demonstrate applicability to more hydrophilic, more environmentally relevant microplastics. The obtained initial results show high recovery of both unaged and aged LDPE over 97 wt.-% and an efficient compost removal but a lower and less robust recovery (between 68 and 18 wt.-%) for PA particles that are more challenging to extract due to an unfortunate synergistic combination of smaller particle size and higher density. Method adaptation to other microplastic types may still be necessary. In short:A low-cost and simple approach without oxidation to extract (pre-aged) microplastics from compostMethod development by visual observation using fluorescent labelled microplastics and method validation by spike-recovery tests

In Vitro Evaluation of Synergistic Essential Oils Combination for Enhanced Antifungal Activity against Candida spp.

In recent years, a significant number of infections have been attributed to non-albicidal Candida species (NAC), mainly due to the increasing resistance of NAC to antifungal agents. As only a few antifungal agents are available (azoles, echinocandins, polyenes, allylamines and nucleoside analogues), it is very important to look for possible alternatives to inhibit resistant fungi. One possibility could be essential oils (EOs), which have been shown to have significant antifungal and antibacterial activity. Therefore, in this study, the efficacy of 12 EOs and their combinations was evaluated against four yeasts of the genus Candida (C. albicas, C. glabrata, C. tropicalis and C. parapsilosis). GC-MS and GC-MS FID techniques were used for the chemical analysis of all EOs. VITEK-2XL was used to determine the antifungal susceptibility of the tested Candida spp. strains. The agar disc diffusion method was used for primary screening of the efficacy of the tested EOs. The broth dilution method was used to determine the minimum inhibitory concentrations (MICs) of the most potent EOs. After MIC cultivation, the minimum fungicidal concentration (MFC) was determined on Petri dishes (60 mm). The synergistic effect of combined EOs was evaluated using the checkerboard method and expressed as a fractional inhibitory concentration index (FICI). The results showed that ginger > ho-sho > absinth > dill > fennel > star anise > and cardamom were the most effective EOs. For all Candida species tested, the synergy was mainly observed in these combinations: ginger/fennel for C. albicans FICI 0.25 and C. glabrata, C. tropicalis and C. parapsilosis FICI 0.5 and absinth/fennel for C. albicans FICI 0.3125, C. tropicalis FICI 0.3125 and C. parapsilosis FICI 0.375. Our results suggest that the resistance of fungal pathogens to available antifungals could be reduced by combining appropriate EOs.

Anti-Inflammatory and Anti-Arthritis Activity of Quercetin: A Comprehensive Review.

This comprehensive exploration delves into the multifaceted attributes of quercetin, a flavonoid with extensive health-promoting potential. The review navigates through its fundamental properties, encompassing its chemical structure, classification as a flavonoid, and its natural prevalence in various sources. Addressing solubility, stability, and bioavailability challenges, the investigation delves into innovative isolation techniques, including solvent extraction, solid-phase extraction, natural deep eutectic solvents, supercritical fluid extraction, microwave-assisted extraction, column chromatography, and high-performance thin-layer chromatography. Transitioning into pharmacological implications, the study unveils quercetin's roles in anti-inflammatory pathways, antioxidant effects, and immune modulation, reflecting its versatile significance in health management. The review highlights its impact on wound healing processes and its potential to mitigate arthritis, elucidating its holistic contributions. Culminating in an exploration of recent studies, the analysis underscores quercetin's remarkable anti-inflammatory and anti-arthritis activities, reflecting its substantial potential across various ailments. The review concludes by projecting future trajectories, emphasizing prospects for an advanced understanding of quercetin's mechanisms, sustainable extraction techniques, clinical integration, and exploration of synergistic combinations. Collectively, this review investigation underscores quercetin's dynamic role at the intersection of natural compounds and medicinal applications, offering profound implications for well- being and health enhancement.

Case Report: Treatment of akinetic mutism after unilateral anterior cerebral artery infarction with methylphenidate and levodopa/benserazide

Introduction: Akinetic mutism is a severe state of impaired volition that can result from a stroke. Its therapeutic evidence relies on single case reports that used atomoxetine or levodopa with variable latency and efficacy. Case presentation: We present the case of a 54-year-old woman who developed akinetic mutism after infarction in the territory of the right anterior cerebral artery, successfully treated with methylphenidate and levodopa/benserazide. Clinical examination showed a patient lacking any spontaneous speech and movement while opening her eyes and fixating. Suspecting akinetic mutism after a comprehensive diagnostic work-up, we started an individual therapy attempt with methylphenidate 10 mg and levodopa/benserazide 100/25 mg twice daily. Both drugs affect the dopaminergic and noradrenergic transmission in the frontal-subcortical circuit, compromised in akinetic mutism. We saw rapid and sustained improvement in her volitional actions, devoid of side effects. Finally, the patient was actively communicating and moving her limbs. Conclusion: We discuss the patient's favorable clinical course in response to the synergistic combination of methylphenidate and levodopa/benserazide, emerging as a promising treatment strategy, and provide a brief literature review of treatment options in akinetic mutism following stroke.

Fe3+-DOX-mediated self-assembled nanolipids for tumor microenvironment activated synergistic ferroptotic-chemo therapy assisted with MR-imaging

Chemotherapy is often plagued by side-effects, development of drug resistance, difficulty of targeted delivery, and limited effectiveness. Here, we tackle these issues by rationally designing a nanolipid system with the capabilities of selective accumulation in tumor tissues, responsiveness to tumor microenvironment (TME), synergistic combination of chemotherapy with ferroptosis, magnetic resonance (MR) imaging to monitor the uptake kinetics and therapeutic process. Specifically, a tumor-responsive nanolipid encapsulated with Fe3+-DOX nanocomplexes is devised. DOX is only released inside the tumor cells and subsequently induces apoptosis after the nanolipids are selectively accumulated in tumor tissues, readily uptaken by tumor cells, and finally disassembled by overexpressed glutathione (GSH). Free Fe2+ ions reduced from Fe3+ by GSH catalyze the excess H2O2 in tumor cells into cytotoxic ·OH radicals, which in turn cause lipid peroxidation and consequently ferroptosis. Intracellularly released Fe3+-DOX nanocomplexes emit strong MR signal, indicating successful internalization of the therapeutics and initiation of the ferroptotic-chemotherapy. Such MR imaging-monitored, highly targeted, synergistic therapy offers high therapeutic efficacy, low side-effects, and immunity to drug resistance.

State Identification Via Symbolic Time Series Analysis for Reinforcement Learning Control

Abstract This technical brief makes use of the concept of symbolic time-series analysis (STSA) for identifying discrete states from the nonlinear time response of a chaotic dynamical system for model-free reinforcement learning (RL) control. Along this line, a projection-based method is adopted to construct probabilistic finite state automata (PFSA) for identification of the current state (i.e., operational regime) of the Lorenz system; and a simple Q-map-based (and model-free) RL control strategy is formulated to reach the target state from the (identified) current state. A synergistic combination of PFSA-based state identification and RL control is demonstrated by the simulation of a numeric model of the Lorenz system, which yields very satisfactory performance to reach the target states from the current states in real-time.

Advancements in Telehealth: Enhancing Breast Cancer Detection and Health Automation through Smart Integration of IoT and CNN Deep Learning in Residential and Healthcare Settings

The rapid evolution of telehealth, or telemedicine, has spurred crucial technological advancements aimed at addressing the early stages of complex cancer conditions, where conventional diagnostic methods face challenges. This research introduces a cancer detection system that utilizes Internet of Things (IoT)-based patient records and machine learning. The primary objective is to automate real-time breast cancer monitoring and detection in residential institutions and smart hospitals, thus enhancing the delivery of quality cancer healthcare. Background: Traditional diagnostic methods, particularly physical inspection, exhibit inherent limitations in identifying breast cancer at early stages. This research responds to this challenge by leveraging innovative technologies, such as IoT and deep learning-based techniques, to overcome the constraints of conventional approaches. Objective: The primary goal of this study is to develop and implement a cancer detection system that integrates IoT-based patient records and machine learning for real-time breast cancer monitoring in residential and healthcare settings. Method: The research employs a synergistic combination of IoT technology for collecting images of residential users and Convolutional Neural Network (CNN), a deep learning technique, for early cancer prediction. The focus lies on contributing to the overall well-being of individuals who may unknowingly be living with cancer. Result: Simulated outcomes after 25 epochs are presented, emphasizing the training accuracy of the model and its validation accuracy using the proposed VGG16 classifier. Graphical representations of the results indicate consistent performance metrics, with both validation and training accuracy exceeding 99%. Specifically, the training accuracy measures at an impressive 99.64%, while the validation accuracy stands at 99.12%. Main Findings: The study demonstrates the effectiveness of the integrated IoT and deep learning techniques in achieving high accuracy rates for early breast cancer prediction. The findings affirm the potential of this approach to assist dermatologists in identifying breast malignancies at treatable stages. Conclusion: This research establishes a foundational framework for the integration of IoT and deep learning techniques, presenting a promising avenue for advancing early cancer detection in smart healthcare systems. The proposed cancer detection system holds significant potential for improving healthcare outcomes and contributing to the overall well-being of individuals at risk of breast cancer.

CASE-DFT Structure Elucidation of Proton-Deficient Chlorodepsidones from the Indonesian Lichen Teloschistes flavicans and Structure Revision of Flavicansone.

Biodiscovery efforts in Indonesia have aimed to explore the understudied chemical diversity of its rich lichen flora, seeking to find new products endowed with significant biological properties. The chemical screening of a Teloschistes flavicans extract led to selection of this species for further investigation. LC/MS and 1H NMR-based dereplication pinpointed six chlorodepsidones from the thallus of a sample of this lichen. This led to the streamlined isolation and the subsequent structure elucidation of the three new compounds norflavicansone 1, flavicansone 2, and isocaloploicin 3, along with the known chlorodepsidones 4-6, stictic acid 7, aurantiamide acetate 8, and parietin 9. The challenging structure elucidation of these proton-deficient metabolites benefited from a state-of-the-art workflow involving a synergistic combination of Computer-Assisted Structure Elucidation (CASE) and Density Functional Theory (DFT) calculations of the top-ranked candidates. This investigation also led to the revision of flavicansone's structure, previously described from this species. The three new molecules that are being reported here are remarkable in that they represent hybrid depsidones in which one of the aromatic rings is derived from orsellinic acid and the other is derived from β-orcinol, a rare structural feature for lichen depsidones.

Injectable Thermogelling Nanostructured Ink as Simultaneous Optical and Magnetic Resonance Imaging Contrast Agent for Image-Guided Surgery.

The development of efficient and biocompatible contrast agents is particularly urgent for modern clinical surgery. Nanostructured materials raised great interest as contrast agents for different imaging techniques, for which essential features are high contrasts, and in the case of precise clinical surgery, minimization of the signal spatial dispersion when embedded in biological tissues. This study deals with the development of a multimodal contrast agent based on an injectable hydrogel nanocomposite containing a lanthanide-activated layered double hydroxide coupled to a biocompatible dye (indocyanine green), emitting in the first biological window. This novel nanostructured thermogelling hydrogel behaves as an efficient tissue marker for optical and magnetic resonance imaging because the particular formulation strongly limits its spatial diffusion in biological tissue by exploiting a simple injection. The synergistic combination of these properties permits to employ the hydrogel ink simultaneously for both optical and magnetic resonance imaging, easy monitoring of the biological target, and, at the same time, increasing the spatial resolution during a clinical surgery. The biocompatibility and excellent performance as contrast agents are very promising for possible use in image-guided surgery, which is currently one of the most challenging topics in clinical research.

A two-symmetric electrode hydride supercapacitor developed from G-C3N4 decorated with poly-2-aminobenzenethiol

The incorporation of poly-2-aminobenzene thiol (P2ABT) onto 2D g-C3N4 sheets results in the formation of a P2ABT/g-C3N4 nanocomposite, exhibiting favorable morphological and electrical properties that position it as a promising candidate for a paste utilized in a two-symmetric electrode hydride supercapacitor. The decoration process involves the oxidation of 2-aminobenzene thiol with K2S2O8, leading to the polymer coating of the embedded 2D g-C3N4 materials, yielding a robust composite. Analysis via scanning electron microscopy (SEM) unveils the formation of 2D sheets of g-C3N4 with an average length, width, and thickness of 750 nm, 200 nm, and 15 nm, correspondingly. The composite establishes a sturdy network with a porous structure, indicative of the synergistic combination of the electrical characteristics of the polymer and g-C3N4. In the construction of the two-symmetric electrode supercapacitor, an impressive specific capacitance (CS) of 310 F g−1 is achieved at 0.2 A/g. The supercapacitor exhibits a promising energy density (E) of 26.8 W h kg−1 and maintains retention stability even after undergoing 1000 charge/discharge cycles. Notably, the retention rate remains high at 98% after 250 cycles and 96% after an extended cycling period of 1000 cycles. This exceptional performance positions the supercapacitor as a prospective candidate for applications in industrial settings and within batteries. Its advantages lie in its ease of fabrication, mass production capabilities, and cost-effective manufacturing techniques, opening new avenues for these materials in energy storage fields.

Accident black spot clustering oriented maritime search and rescue resource allocation and optimization

Efficient and rapid deployment of maritime search and rescue(MSAR) resources is a prerequisite for maritime emergency search and rescue, in order to improve the efficiency and accuracy of MSAR. This paper proposes an integrated approach for emergency resource allocation. The approach encompasses three main steps: identifying accident black spots, assessing high-risk areas, and optimizing the outcomes through a synergistic combination of an optimization algorithm and reinforcement learning. In the initial step, the paper introduces the iterative self-organizing data analysis technology (ISODATA) for identifying accident spots at sea. A comparative analysis is conducted with other clustering algorithms, highlighting the superiority of ISODATA in effectively conducting dense clustering. This can effectively carry out dense clustering, instead of the situation where the data spots are too dispersed or obvious anomalies that affect the clustering. Furthermore, this approach incorporates entropy weighting to reassess the significance of accident spots by considering both the distance and the frequency of accidents. This integrated approach enhances the allocation of search and rescue forces, ensuring more efficient resource utilization. To address the MSAR vessel scheduling problem at sea, the paper employs the non-dominated sorting genetic algorithm II combined with reinforcement learning (NSGAII-RL). Comparative evaluations against other optimization algorithms reveal that the proposed approach can save a minimum of 7% in search and rescue time, leading to enhanced stability and improved efficiency in large-scale MSAR operations. Overall, the integrated approach presented in this paper offers a robust solution to the ship scheduling problem in maritime search and rescue operations. Its effectiveness is demonstrated through improved resource allocation, enhanced timeliness, and higher efficiency in responding to maritime accidents.

Bandgap engineering of novel Cu-vanadate/g-C3N4 hierarchical nanoflowers for enhanced photodegradation and excellent biosensing capability

Copper vanadate and graphitic carbon nitride (g-C3N4) are pivotal materials in the realm of advanced materials science, owing to their distinctive optical and electronic conductive properties. In the context of environmental photocatalysis and biosensing applications, their synergistic combination holds significant promise. Copper vanadate, renowned for its optical and electronic properties, complements the unique architecture and optical conduction characteristics of g-C3N4. Together, these materials exhibit immense potential for driving advancements in environmental sustainability and diagnostic techniques. In this study, we report the synthesis of copper vanadate (Cu0.261V2O5) and its composite with graphitic carbon nitride. XRD confirms the synthesis of the novel phase, FESEM and TEM analysis reveals hierarchical nanoflowers and UV-Visible spectroscopy divulges the visible light activation of the synthesized material and aids in the calculation of the optical bandgap. Interfacial charge transfer was studied with the help of EIS and Mott-Schottky analysis was employed to reveal the semiconductor type (n or p type) and determine the band edges. The as-prepared material was tested for the photocatalytic removal of methylene blue (MB), followed by the study of reaction kinetics, cyclic stability and active radicals participating in the photocatalysis process. The synthesized heterojunction showed 100 % removal of MB within a tenure of 90 minutes. The results of the experiment revealed that Cu0.261V2O5 decorated with g-C3N4 displays 1.5 and 1.4 times better photocatalytic degradation capability than pure Cu0.261V2O5 and g-C3N4, respectively. Furthermore, the synthesized material was evaluated for electrochemical biosensing of ascorbic acid in PBS (pH 7) analyte using a 3-electrode system. Compared to the pure material, the heterojunctions drew 1.9 times more current and provided near unity correlation (R2). It is evident that Cu0.261V2O5 decorated with g-C3N4 can be implemented for commercial eco-remediation and electrochemical ascorbic acid sensing.

Abstract B012: BET inhibition sensitizes preclinical models of bladder cancer to DDR inhibitors

Abstract Background: Bladder cancer (BC) remains a common and deadly disease, with 83,190 cases and 32,350 deaths projected in the U.S. in 2024. We previously showed bromodomain and extra-terminal protein inhibitors (BETi) are potent in multiple preclinical models of BC. Our bulk RNA-seq and RT-qPCR data showed BETi significantly reduces expression of homologous recombination (HR) genes, such as RAD51 and RBBP8, which could activate alternative DNA repair pathways including non-homologous end joining (NHEJ) and theta-mediated end joining (TMEJ). Specifically, DNA breaks are repaired through TMEJ by polymerase theta (Polθ) utilizing microhomology templates. Recently published data revealed Polθ inhibition is synthetically lethal when other DDR genes are concomitantly lost or inhibited. Thus, in this study, we sought to elucidate whether BETi-induced HR gene repression impacts TMEJ and POLQ expression, and to identify combinations with BETi that best leverage Polθ-mediated synthetic lethality. Methods: 5637 and J82 BC cells were pretreated with birabresib for 24 h and then transfected via electroporation with a Cas9 ribonucleoprotein, a gRNA targeting LBR2 and a 996 bp HR donor. Transfected cells were treated with birabresib for 24H, and DDR pathway function was assessed by digital droplet PCR. BC cells were synchronized at the G1/S transition with 2 mM thymidine incubated with birabresib alone. After 48 h, cells were harvested, and changes to target gene expression (i.e., POLQ) was assessed by RT-qPCR. Next, the same cells were treated with 8 ascending doses of the BETi birabresib (0.1–100 μM) alone or in combination with either the PARP inhibitor olaparib, CtIP inhibitor triapene, or RAD51 inhibitor RI-1 (10 nM–200 μM). After 72-96 h, CellTiter-Glo™ measured cell viability, and Compusyn v1 calculated combination index (CI) scores where <1.0 indicated synergism and >1.0 indicated antagonism. RT-qPCR was conducted to evaluate expression changes to POLQ after combination treatment. Results: After 48 h, birabresib significantly reduced TMEJ in both 5637 and J82 BC cells (49% reduction, P=0.008 and 41% reduction, P=0.004 both n=3), but did not significantly impact HR or NHEJ. POLQ mRNA expression was most reduced in synchronized 5637 and J82 BC cells after treatment with birabresib alone (46% reduction, P=0.006, n=3, and 38% reduction, P=0.001, n=3). Birabresib combined with olaparib was the most synergistic combination in both 5637 and J82 BC cells (CI = 0.83 and 0.29), but birabresib combined with triapene was also synergistic (CI = 0.91 and 0.90). In J82 cells, birabresib significantly reduced POLQ expression (27% reduction, P=0.008, n=3), but olaparib did not. In both 5637 and J82 cells combined birabresib and olaparib increased POLQ expression (41% increase and 5% increase, ns, n=3). Combined birabresib and triapene displayed a similar trend (46% increase and 17% increase, ns, n=3). Conclusions: These preliminary data support further exploration of POLQ expression increases caused by combined BETi+DDRi treatment in preclinical models of BC. Citation Format: Ryan M. Kemper, Bhavika C. Chirumamilla, Dennis A. Simpson, Manfred Meng, Gaorav P. Gupta, Daniel J. Crona. BET inhibition sensitizes preclinical models of bladder cancer to DDR inhibitors [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B012.

Influence of Nickel on Microstructure and Mechanical Properties in Medium-Carbon Spring Steel.

The effects of adding nickel on the phase transition temperature, microstructure, and mechanical properties of medium-carbon spring steel have been investigated. The results show that adding nickel reduces the martensite start (Ms) temperature, improves hardenability, and refines the sub-microstructure of the martensite, thereby improving yield stress. The yield strength of martensitic steel increases by approximately 100 MPa due to a synergistic combination of grain refinement strengthening and dislocation strengthening, with an increase in the nickel content from 0 wt.% to 1 wt.%. The cryogenic impact toughness of martensitic steel also improved with a higher nickel content due to packet and block refinement and an increase in the proportion of high-angle grain boundaries (HAGBs).

Abstract B027: The MAT2A inhibitor IDE397: a novel combination backbone for urothelial cancer subjects with MTAP deficiency

Abstract Methylthioadenosine phosphorylase (MTAP) loss, due to focal homozygous deletions in chromosome 9 (9p21.3), occurs in over 25% of urothelial carcinoma and is an adverse prognostic factor for overall survival. Furthermore, MTAP-deleted tumors are associated with a “cold” tumor immune microenvironment and are resistant to immune checkpoint inhibitor therapy. Loss of MTAP confers a dependency on methionine adenosyltransferase 2A (MAT2A), which catalyzes the production of the primary methyl donor for all cellular methyltransferase reactions, S-adenosyl methionine (SAM). IDE397, a potent small molecule inhibitor of MAT2A, was developed to selectively exploit this synthetic lethal vulnerability in MTAP −/− tumors. The accumulation of the metabolite MTA in MTAP −/− tumors combined with a reduction of SAM by MAT2A inhibition results in selective inhibition of PRMT5, a methyltransferase that governs spliceosome fidelity. This triggers pre-mRNA splicing defects that may induce RNA polymerase stalling and can cause R-loop accumulation. Furthermore, due to essential roles in 1-carbon metabolism, MAT2A inhibition together with MTAP loss leads to depletion of metabolites required for both de novo and salvage nucleotide biosynthesis, thus preventing effective management of DNA replication and DNA damage repair. Notably, R-loops must be resolved by topoisomerase activity (TOP1) to prevent replication conflict and mitotic catastrophe. These combinatorial mechanistic relationships underpin a hypothesis that dual inhibition of MAT2A and TOP1 will fully capitalize on the synthetic lethal vulnerabilities associated with MTAP loss in urothelial cancers (replication stress, genomic instability). Consistent with this, IDE397 in combination with TOP1 inhibitors demonstrated synergistic combination benefit in MTAP −/− bladder cancer cell lines in vitro and in cell-line derived xenograft (CDX) models in vivo. IDE397 exposure was associated with heavily disordered methionine metabolism and accumulation of DNA damage response intermediates. In the ongoing Phase 1 dose escalation/expansion study of IDE397 in MTAP −/− solid tumors (NCT04794699), measurable tumor shrinkage has been observed in urothelial cancers (including a CR per RECIST 1.1) along with molecular responses on serial ctDNA measurements. Supported by our preclinical data, and the clinical observation that MTAP −/− urothelial cancers may be more sensitive to sacituzumab govitecan (SG); a TROP-2-targeting TOP1 ADC (UNITE study; JCO.2023.41.16_suppl.4572), a combination of SG+IDE397 could represent a novel early-line therapy for these patients with high unmet need. We plan to evaluate the combination of SG+IDE397 in MTAP-/- urothelial cancers in the next stage of the ongoing IDE397 trial (NCT04794699). Citation Format: Claire L. Neilan, Marcus M. Fischer, Damien Garbett, Arjun A. Rao, Mili Mandal, Michael A. White, Jasgit C. Sachdev. The MAT2A inhibitor IDE397: a novel combination backbone for urothelial cancer subjects with MTAP deficiency [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B027.

(Invited) CdS/Ti-Si-O Composite Photoanode for Photoelectrochemical Hydrogen Generation

Advancements in clean energy drive socio-economic development and foster a sustainable future by restructuring energy systems and promoting low-carbon development. In this paper, we presented a comprehensive investigation on the design and performance characterization of CdS/Ti-Si-O composite photoanodes for photoelectrochemical (PEC) hydrogen generation. Silicon-doped TiO2 nanotube arrays were fabricated through anodization of Ti-5Si alloy, followed by the deposition of CdS using the SILAR (successive ionic layer adsorption and reaction) process, resulting in nanostructured Ti-Si-O photoanodes modified with CdS. The composite photoanodes were characterized in terms of their composition, microstructure, optical properties and photoelectrochemical hydrogen production performance. The composite photoanodes revealed a notable enhancement in PEC hydrogen generation properties with a photocurrent density of 7.86 mA/cm2，which was 19.15 times and 9.59 times to those of the undoped TiO2 photoanode and Ti-Si-O photoanode, respectively. The Si-doping mechanism of the photoanodes was elucidated through Density Functional Theory (DFT) calculations. The synergistic combination of Si-doping and CdS modification represents a novel and promising approach for the design of efficient nanostructured photoanodes.

Enhanced Osteosarcoma Immunotherapy via CaCO3 Nanoparticles: Remodelling Tumour Acidic and Immune Microenvironment for Photodynamic Therapy.

Osteosarcoma (OS) is a "cold" tumour enriched in noninflammatory M2 phenotype tumour-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumour microenvironment (TME), generated by factors such as excess hydrogen (H+) ions and high lactate levels, activates immunosuppressive cells (e.g., M2 phenotype TAMs), further promoting a suppressive tumour immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO3)/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) was developed for the targeted codelivery of the photosensitizer Ce6 and shikonin (SHK) to OS tumours via the bone-targeting ability of alendronate sodium (ALN). CaCO3 nanoparticles were used to neutralize H+ ions and alleviate the suppressive TIME, and the loaded SHK not only synergized with photodynamic therapy (PDT) by promoting reactive oxygen species (ROS) generation and enhancing immunogenic cell death (ICD) but also inhibited lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumour suppression and comprehensive beneficial effects on antitumour immune responses, including the promotion of CD8+ T-cell infiltration and regulatory T-cell (Treg) suppression. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, showed a remarkable ability to eliminate distant tumours and promote long-term immune memory function to protect against rechallenged tumours. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME. This article is protected by copyright. All rights reserved.

Effective Video Summarization by Extracting Parameter-Free Motion Attention

Video summarization remains a challenging task despite increasing research efforts. Traditional methods focus solely on long-range temporal modeling of video frames, overlooking important local motion information that cannot be captured by frame-level video representations. In this article, we propose the Parameter-free Motion Attention Module (PMAM) to exploit the crucial motion clues potentially contained in adjacent video frames, using a multi-head attention architecture. The PMAM requires no additional training for model parameters, leading to an efficient and effective understanding of video dynamics. Moreover, we introduce the Multi-feature Motion Attention Network (MMAN), integrating the PMAM with local and global multi-head attention based on object-centric and scene-centric video representations. The synergistic combination of local motion information, extracted by the proposed PMAM, with long-range interactions modeled by the local and global multi-head attention mechanism, can significantly enhance the performance of video summarization. Extensive experimental results on the benchmark datasets, SumMe and TVSum, demonstrate that the proposed MMAN outperforms other state-of-the-art methods, resulting in remarkable performance gains.

A synergistic combination of 2D MXene and MoO3 nanoparticles for improved gas sensing at room temperature

MXene Ti3C2T x (30% HF-etched, named Ti3C2T x -30) plays a pivotal role in the substantial enhancement of the structural modification of molybdenum trioxide (MoO3). Additionally, as the surface MoO3 molecules come into contact with reducing gas moieties, they actively participate in gas sensing at room temperature. The percentage of Ti3C2T x -30 in the MoO3 matrix was varied at 10%, 20%, and 40%, denoted as MM-10, MM-20, and MM-40, respectively. Structural analysis confirmed the composition of the basic elements and evolution of TiO2 at a higher percentage of Ti3C2T x -30. Spectroscopy analysis showed the interactions between Ti3C2T x -30 and MoO3, showcasing work functions of 6.91 eV, 6.75 eV, and 7.21 eV for MM-10, MM-20, and MM-40, respectively, confirming MM-20 to be an optimum composition. When the samples were exposed to ammonia gas, MM-20 showed a high response (93% for 100 ppm) at room temperature, with a response time of ∼10 s. Compared to bare MoO3, these samples showed ten-fold improvement. The excess electrons on the surface of Ti3C2T x -30 facilitate the formation of O2− species, which also provides stability to the otherwise highly reactive MXene surface. These species actively react with ammonia molecules in the presence of adsorbed MoO3, thereby changing the resistance of the system. This can be a significant step towards imparting high gas sensitivity to metal oxides at room temperature via incorporation of an optimum percentage of optimized Ti3C2T x .