Breakthrough Strategy Research Articles

Crystallization Control of Blade‐Coated Wide Bandgap FACs‐Based Perovskite

AbstractTransforming perovskite solar cells into commercial production requires advanced scalable deposition technology. However, the deposition of high‐quality perovskite thin films using the blade coating method presents challenges, especially in controlling the nucleation and crystallization of perovskite. In this work, an effective approach is proposed for controlling nucleation and crystallization by simultaneously incorporating two kinds of ionic liquid, namely 1H‐imidazole acetate (IMAc), and 1‐buty‐3‐methylimidazolium tetrafluoroborate (BMIMBF4), into the precursor solution. This innovative strategy initiates π–π interactions between IM and BMIM cations, thereby enhancing the interaction between cations and the Pb‐I framework. The competitive mechanism of interaction with Pb‐I framework effectively suppresses the formation of unfavorable mesophase, thereby enabling a single crystallization pathway from NMP + PbI2 to α‐perovskite. Consequently, this method effectively reduces defects and enhances the crystal quality of α‐perovskite film. Based on this strategy, the power conversion efficiency of the p‐i‐n wide bandgap perovskite device prepared by the blade coating method, is increased to 21.31%, representing one of the highest efficiencies achieved with this technology for 1.68 eV bandgap FACs‐based perovskites. Thus, this approach emerges as a feasible breakthrough strategy that may unleash the full potential of perovskite solar cells.

Microneedle-based arrays – Breakthrough strategy for the treatment of bacterial and fungal skin infections

Currently, fungal and bacterial skin infections rank among the most challenging public health problems due to the increasing prevalence of microorganisms and the development of resistance to available drugs. A major issue in treating these infections with conventional topical medications is the poor penetration through the stratum corneum, the outermost layer of the skin. The concept of microneedles seems to be a future-proof approach for delivering drugs directly into deeper tissues. By bypassing the skin barrier, microneedle systems allow therapeutic substances to reach deeper layers more efficiently, significantly improving treatment outcomes. Nonetheless, the primary challenges regarding the effectiveness of microneedles involve selecting the appropriate size and shape, along with polymer composition and fabrication technology, to enable controlled and efficient drug release. This review offers a comprehensive overview of the latest knowledge on microneedle types and manufacturing techniques, highlighting their potential effectiveness in treating bacterial and fungal skin infections. It includes updated statistics on infection prevalence and provides a detailed examination of common bacterial and fungal diseases, focusing on their symptoms, causative species, and treatment methods. Additionally, the review addresses safety considerations, regulatory aspects, and future perspectives for microneedle-based therapeutic systems. It also underscores the importance of industrialization and clinical translation efforts, emphasizing the significant potential of microneedle technology for advancing medical applications.

Revolutionizing cancer treatment: The role of radiopharmaceuticals in modern cancer therapy

AbstractRadiopharmaceutical therapy (RPT) is a precision medicine approach that involves the targeted delivery of radioactive atoms to tumor cells, representing a breakthrough strategy for cancer treatment. Radiopharmaceuticals typically consist of a small amount of radioactive material, a radionuclide, paired with a chemical that specifically targets the cell. Some radionuclides naturally target specific cells or biological processes without the need for modification. RPT is a novel cancer treatment method that offers various advantages over current traditional treatment approaches. One of the primary advantages of RPT is its ability to target cancer cells, including those in metastatic areas. Another key advantage of RPT is that radiation can be delivered systemically, locally, or physiologically to specific cells internally rather than being applied externally. Moreover, radiotracer imaging can be utilized to determine radiopharmaceutical absorption in target tissues before providing a therapeutic dose. Compared to all other cancer treatment approaches, RPT has demonstrated high efficacy with minimal toxicity. The recent approval of multiple RPT medicines by the US Food and Drug Administration highlights the tremendous potential of this treatment. This article provides a detailed review of RPT, including insights into manufacturing procedures, safety measures, and its applications in cancer therapy.

Interfacial and Vacancy Engineering on 3D-Interlocked Anode Catalyst Layer for Achieving Ultralow Voltage in Anion Exchange Membrane Water Electrolyzer.

Developing a high-efficiency and stable anode catalyst layer (CL) is crucial for promoting the practical applications of anion exchange membrane (AEM) water electrolyzers. Herein, a hierarchical nanosheet array composed of oxygen vacancy-enriched CoCrOx nanosheets and dispersed FeNi layered double hydroxide (LDH) is proposed to regulate the electronic structure and increase the electrical conductivity for improving the intrinsic activity of the oxygen evolution reaction (OER). The CoCrOx/NiFe LDH electrodes require an overpotential of 205 mV to achieve a current density of 100 mA cm-2, and they exhibit long-term stability at 1000 mA cm-2 over 7000 h. Notably, a breakthrough strategy is introduced in membrane electrode assembly (MEA) fabrication by transferring CoCrOx/NiFe LDH to the surface of an AEM, forming a 3D-interlocked anode CL, significantly reducing the overall cell resistance and enhancing the liquid/gas mass transfer. In AEM water electrolysis, it exhibits an ultralow cell voltage of 1.55 Vcell to achieve a current density of 1.0 A cm-2 in 1 M KOH, outperforming the state-of-the-art Pt/C//IrO2. This work provides a valuable approach to designing high-efficiency electrocatalysts at the single-cell level for advanced alkaline water electrolysis technologies.

DIRECTIONS AND MECHANISM FOR STRATEGIC DEVELOPMENT OF GRAIN PRODUCTION IN NIZHNY NOVGOROD REGION

The strategic development of grain production is a very relevant area, since in order to remain competitive in the long term, it must be transformed into a high-tech branch of the national economy. The purpose of the study: justification of directions and development of a mechanism for strategic development of grain production in the Nizhny Novgorod region. Within the framework of this goal, a critical analysis of studies on this problem was carried out. Based on the use of methodological tools such as SWOT analysis and the BSC method, the directions of strategic development of grain production in the Lower Rod region were scientifically substantiated, and thanks to the empirical modeling method, the Ministry of Management of Strategic Development of Grain Production in this region was developed. As a result, the author highlighted and specified the following areas of strategic development of grain production: a breakthrough strategy, strategies aimed at qualitative renewal of production technologies in conditions of production instability and a survival strategy. The directions were drawn up in the form of a map of the strategic development of grain production in the Nizhny Novgorod region. The mechanism proposed by the author to manage the strategic development of grain production in the region includes such subsystems as goal setting, strategy, control and implementation of the developed areas of strategic development. As a result, the implementation of the proposed directions on the basis of the mechanism for strategic development of grain production will contribute to its transformation into a high-tech industry.

Engineering Magnetic Extracellular Vesicles Mimetics for Enhanced Targeting Chemodynamic Therapy to Overcome Ovary Cancer.

Chemodynamic therapy (CDT), employing metal ions to transform endogenous H2O2 into lethal hydroxyl radicals (•OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and β-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective H2O2 generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H2O2 into •OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.

State-Of-The-Art Advancements on Cancer Vaccines and Biomarkers.

The origins of cancer vaccines date back to the 1800s. Since then, there have been significant efforts to generate vaccines against solid and hematologic malignancies using a variety of platforms. To date, these efforts have generally been met with minimal success. However, in the era of improved methods and technological advancements, supported by compelling preclinical and clinical data, a wave of renewed interest in the field offers the promise of discovering field-changing paradigms in the management of established and resected disease using cancer vaccines. These include novel approaches to personalized neoantigen vaccine development, as well as innovative immune-modulatory vaccines (IMVs) that facilitate activation of antiregulatory T cells to limit immunosuppression caused by regulatory immune cells. This article will introduce some of the limitations that have affected cancer vaccine development over the past several decades, followed by an introduction to the latest advancements in neoantigen vaccine and IMV therapy, and then conclude with a discussion of some of the newest technologies and progress that are occurring across the cancer vaccine space. Cancer vaccines are among the most promising frontiers for breakthrough innovations and strategies poised to make a measurable impact in the ongoing fight against cancer.

Fabrication of Large‐Area Multi‐Stimulus Responsive Thin Films via Interfacially Confined Irreversible Katritzky Reaction

AbstractFabrication of large‐area thin films through irreversible reactions remains a formidable task. This study reports a breakthrough strategy for in situ synthesis of large‐area, free‐standing, robust and multi‐stimulus responsive thin films through a catalyst‐free and irreversible Katritzky reaction at a liquid–liquid interface. The as resulted films are featured with adjustable thickness of 1–3 μm and an area up to 50 cm2. The thin films exhibit fast photo‐mechanical motions (a response time of ca 0.1 s), vapor‐mechanical motions, as well as photo‐chromic and solvato‐chromic behaviors. It was revealed that the reason behind the observable motions is proton transfer from the imine groups to the carbonyl structures within the film induced by photo‐ and/or dimethyl sulfoxide‐stimulus. In addition, the films can harvest anionic radicals and the radicals as captured can be efficiently degraded under UV light illumination. This study provides a new strategy for fabricating smart thin films via interfacially confined irreversible Katritzky reaction.

Fabrication of Large-Area Multi-Stimulus Responsive Thin Films via Interfacially Confined Irreversible Katritzky Reaction.

Fabrication of large-area thin films through irreversible reactions remains a formidable task. This study reports a breakthrough strategy for in situ synthesis of large-area, free-standing, robust and multi-stimulus responsive thin films through a catalyst-free and irreversible Katritzky reaction at a liquid-liquid interface. The as resulted films are featured with adjustable thickness of 1-3 μm and an area up to 50 cm2. The thin films exhibit fast photo-mechanical motions (a response time of ca 0.1 s), vapor-mechanical motions, as well as photo-chromic and solvato-chromic behaviors. It was revealed that the reason behind the observable motions is proton transfer from the imine groups to the carbonyl structures within the film induced by photo- and/or dimethyl sulfoxide-stimulus. In addition, the films can harvest anionic radicals and the radicals as captured can be efficiently degraded under UV light illumination. This study provides a new strategy for fabricating smart thin films via interfacially confined irreversible Katritzky reaction.

Digital economy and education in China: globalisation and cyber sovereignty

The article studies the socio-cultural specifics of digitalisation of public administration system, economy, and education of China. With the help of historical and philosophical, comparative, and hermeneutic methods alongside with the analysis of secondary sources and statistical information, the authors examine the socio- cultural features of Chinese strategy of digital breakthrough and the impact this strategy may have on the global world. The following problematic areas of digitalisation have been identified: transparency of public administration system that is relevant to the Zeitgeist and demanded by the population versus strict state control over various spheres of life; the global Internet versus cyber sovereignty; maintaining a balance between internationalisation and localisation of Chinese education. Several potential spheres of influence on the international community have been highlighted: world-class standardisation; demand for Chinese education (including education in the field of public administration) in the global market for educational services; development of artificial intelligence due to national peculiarities of China (a huge volume of domestic data, the possibility of mass implementation of developments, financial capabilities of the country). Special attention is given to the problem of cyber sovereignty. Within its framework, three main types of security that the Chinese information sphere concentrates on are analysed: computer, cognitive, information and psychological

Abstract 7593: Photodynamic therapy improves therapeutic management of glioblastoma

Abstract Glioblastoma (GBM) remains a formidable challenge in the realm of oncology, primarily due to the limitations of the standard of care therapies. Photodynamic therapy (PDT), which exploits the light-activated potential of 5-aminolevulinic acid (5-ALA), emerges as a promising avenue to combat GBM. In this study, primary patient-derived cell lines, Ox5 core, and G7, served as critical subjects, exposed to light excitation at wavelengths of 410 nm, 528 nm, and 810 nm, both with and without 5-ALA (protoporphyrin IX). The central objective was to rigorously assess the efficacy of PDT, either with or without 5-ALA, in reducing cell viability and curtailing clonogenic expansion. This evaluation was performed within the context of the existing standard of care for GBM, encompassing Temozolomide (TMZ) and Radiotherapy. Our results unveiled striking insights into the potential of PDT as an innovative therapeutic strategy. Notably, Ox5 cells exhibited a remarkable reduction in viability, exceeding 70%, following exposure to PDT with 410 nm light and 5-ALA at a concentration of 50μM. A similar, albeit slightly less profound, effect was observed in G7 cells, with a viability decrease of more than 53%. These outcomes, meticulously quantified through the MTT viability assay (n=4), were reinforced by statistical significance, as indicated by p-values falling below 0.05 and, lower 0.001. Furthermore, clonogenic assays employing G7 cells provided an additional layer of evidence, demonstrating a substantial inhibition of clonogenic potential following PDT treatment with 410 nm light and 5-ALA. Immunohistochemistry techniques, particularly focusing on the cleaved caspase-3 marker, in both Ox5 core and G7 cells, underscoring the mechanistic basis of the observed cell death. In stark contrast, the conventional standard of care, involving TMZ monotherapy, was tested, and the results across four biological replicates were less significant. The relative viability of Ox5 and G7 cells exhibited no statistical significance, with p-values exceeding 0.05, implying a limited impact of this regimen on cell viability. Moreover, clonogenic assays conducted under the standard of care protocol (TMZ+/-Radiotherapy) unveiled the persistence of colonies, even at higher radiation doses of 4 and 6 Gy.In summary, PDT, specifically when implemented with 410 nm light and 5-ALA, represents a breakthrough strategy that leads to substantial cell death in both Ox5 and G7 cells. This compelling alternative therapy shines a hopeful light on the horizon of GBM treatment, providing a potentially transformative approach that can augment the current standard of care. Citation Format: Nazar Vasyliv, Karin Williams. Photodynamic therapy improves therapeutic management of glioblastoma [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 7593.

Blue-Emissive ZnSeTe Quantum Dots and Their Electroluminescent Devices.

Over the last two decades, quantum-dot light-emitting diodes (QLEDs), also known as quantum dot (QD) electroluminescent devices, have gained prominence in next-generation display technologies, positioning them as potential alternatives to organic light-emitting diodes. Nonetheless, challenges persist in enhancing key device performances such as efficiency and lifetime, while those of blue QLEDs lag behind compared with green and red counterparts. In this Perspective, we discuss key factors affecting the photoluminescence characteristics of environmentally benign blue-emissive ternary ZnSeTe QDs, including composition, core/shell heterostructure, and surface ligand. Notably, we highlight the recent progress in breakthrough strategies to enhance blue QLED performance, examining the effects of the ZnSeTe QD attribute and device architecture on device performance. This Perspective offers insights into integrated aspects of QD material and device structure in overcoming challenges toward a high-performance blue ZnSeTe QLED.

Characterization of GABAergic marker expression in prefrontal cortex in dexamethasone induced depression/anxiety model.

The pivotal responsibility of GABAergic interneurons is inhibitory neurotransmission; in this way, their significance lies in regulating the maintenance of excitation/inhibition (E/I) balance in cortical circuits. An abundance of glucocorticoids (GCs) exposure results in a disorder of GABAergic interneurons in the prefrontal cortex (PFC); the relationship between this status and an enhanced vulnerability to neuropsychiatric ailments, like depression and anxiety, has been identified, but this connection is still poorly understood because systematic and comprehensive research is lacking. Here, we aim to investigate the impact of dexamethasone (DEX, a GC receptor agonist) on GABAergic interneurons in the PFC of eight-week-old adult male mice. A double-blind study was conducted where thirty-two mice were treated subcutaneously either saline or DEX (0.2 mg/10 ml per kg of body weight) dissolved in saline daily for 21 days. Weight measurements were taken at five-day intervals to assess the emotional changes in mice as well as the response to DEX treatment. Following the 21-day regimen of DEX injections, mice underwent examinations for depression/anxiety-like behaviours and GABAergic marker expression in PFC. In a depression/anxiety model generated by chronic DEX treatment, we found that our DEX procedure did trigger depression/anxiety-like behaviors in mice. Furthermore, DEX treatment reduced the expression levels of a GABA-synthesizing enzyme (GAD67), Reelin, calcium-binding proteins (parvalbumin and calretinin) and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y and vasoactive intestinal peptide) in the PFC were reduced after 21 days of DEX treatment; these reductions were accompanied by decreases in brain size and cerebral cortex thickness. Our results indicate that a reduction in the number of GABAergic interneurons may result in deficiencies in cortical inhibitory neurotransmission, potentially causing an E/I imbalance in the PFC; this insight suggests a potential breakthrough strategy for the treatment of depression and anxiety.

Microglia in Neuropathic Pain.

Neuropathic pain (NP) is pain resulting from lesions or disease of the somatosensory system. A cardinal feature of NP is tactile allodynia (a painful response to normally innocuous stimulation). In 2003, a breakthrough strategy for inducing NP was proposed in which microglia of the spinal dorsal horn (SDH) are activated after peripheral nerve injury (PNI) to overexpress P2X4 receptor (P2X4R) and play an important role in inducing tactile allodynia. In 2005, it was reported that stimulation of microglial P2X4Rs evokes the release of brain-derived neurotrophic factor (BDNF), which causes a depolarizing shift of the anion reversal potential (Eanion) of secondary sensory neurons. These findings and other facts suggest the mechanism by which innocuous touch stimuli cause severe pain and the important role of microglia in the mechanism.

The Integration Innovation and Breakthrough Strategy of Radio Drama in the New Media Context

The Integration Innovation and Breakthrough Strategy of Radio Drama in the New Media Context

The Value Connotation, Problem Review, and Breakthrough Strategies of Ideological and Political Construction in Primary and Secondary School Physical Education Curriculum under the Perspective of “Fostering Virtue to Build Character”

The Value Connotation, Problem Review, and Breakthrough Strategies of Ideological and Political Construction in Primary and Secondary School Physical Education Curriculum under the Perspective of “Fostering Virtue to Build Character”

СУЧАСНІ ТРАНСФОРМАЦІЇ В РЕГІОНІ САХЕЛЮ В КОНТЕКСТІ ФОРМУВАННЯ БАГАТОПОЛЯРНОГО СВІТУ

The problem of the article highlights the poorly researched problem of the formation of regional cen- ters of influence in the process of creating a multipolar world. It is emphasized that the traditional coordinate system of the world system is experiencing significant changes, new centers and centers of influence are being formed. It has been established that the African continent is of great interest to individual states, organizations, and corpo- rations, and its importance for ensuring global stability and predictability of development is becoming decisive. It is noted that in recent years the continent is going through a period of political and economic transformations with a rejection of mono-export specialization and a focus on diversified breakthrough strategies. This is accompanied by the final destruction of the remnants of economic colonialism. As an example, the multifaceted processes taking place in the Sahel zone, a zone of priority influence of France, were considered. It is shown how the latter gradually loses its cementing influence on African countries, which not only get rid of its political dictates, but also try to form alternative economic enclaves with their own currency. At the same time, the processes of intensifying the cooperation of the Sahel countries with the G20, BRICS, etc. were considered. A certain problem of breaking traditional contacts with the metropolis for the region has also been identified and further transformations in the near future have been predicted. It is shown that the recent political transformations in a number of leading countries of the Sahel have determined new vectors for the development of the region, which today is becoming one of the key priorities of the investment policy of India, China and others. Among the key countries of the region, Niger and Gabon are analyzed, which, becoming the path of final decolonization, largely determine the agenda and undermine the European monopoly. At the same time, this significantly affects the stability of both Africa and the EU. It was determined that the latter still retains the monetary union of African countries as the last source of influence, while simultaneously losing military and political. At the same time, African countries are faced with the task of the fastest search for optimal cooperation both on the continent and outside it.

Programmed Co-delivery of tamoxifen and docetaxel using lipid-coated mesoporous silica nanoparticles for overcoming CYP3A4-mediated resistance in triple-negative breast cancer treatment

PurposeThis study aims to revolutionize the treatment of aggressive triple-negative breast cancer (TNBC), notorious for its resistance to standard therapies. By ingeniously combining Tamoxifen (TMX) and Docetaxel (DTX) within a lipid-coated mesoporous silica nanoparticle (LP-MSN) delivery system, we intend to enhance therapeutic efficacy while circumventing DTX resistance mediated by CYP3A4 expression. MethodsWe rigorously tested TNBC cell lines to confirm the responsiveness to Docetaxel (DTX) and Tamoxifen (TMX). We adeptly engineered LP-MSN nanoparticles and conducted a thorough examination of the optimal drug release strategy, evaluating the LP-MSN system's ability to mitigate the impact of CYP3A4 on DTX. Additionally, we comprehensively analyzed its pharmacological performance. ResultsOur innovative approach utilizing TMX and DTX within LP-MSN showcased remarkable efficacy. Sequential drug release from the lipid layer and mesoporous core curbed CYP3A4-mediated metabolism, substantially enhancing cytotoxic effects on TNBC cells without harming normal cells. ConclusionThis pioneering research introduces a breakthrough strategy for tackling TNBC. By capitalizing on synergistic TMX and DTX effects via LP-MSN, we surmount drug resistance mediated by CYP3A4. This advancement holds immense potential for transforming TNBC treatment, warranting further clinical validation.

Artificial Breakthrough of Cell Membrane Barrier for Transmembrane Substance Exchange: A Review of Recent Progress

AbstractCell membrane composed of lipid bilayer is a selectively permeable membrane that only allows specific molecules to pass through. While such selectivity is essential for the survival and function of cells, there exist instances when it is necessary to overcome the cell membrane barrier. Study on the artificial cell membrane barrier breakthrough strategies is of great significance for the development of drug delivery systems and the understanding of cellular behaviors. Herein, the advancements in the development of strategies for opening cell membrane barriers over the past decade are summarized. The main transmembrane mechanisms are elucidated and then divided into three categories, i.e., cell perforation via microinjection/external physical fields, cell endocytosis‐assisted construction of artificial transmembrane channels, and untethered micro/nanomachines. Next, the potential applications after opening the cell membrane are discussed, which mainly focus on the transmembrane cargo delivery into the cell and endogenous substance extraction out from the cell. Finally, this review outlines the current challenges that impede the realization of practical applications and presents an outlook of future opportunities to promote further development. Through overcoming the challenges, it is anticipated that artificial cell membrane breakthrough strategies will provide a revolutionized tool in the near future to advance the field of biomedicine and biotechnology.

9.1 Healing Through Justice: A Community-Led Breakthrough Strategy for Healing-Centered Communities

9.1 Healing Through Justice: A Community-Led Breakthrough Strategy for Healing-Centered Communities