bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystatin A promotes the antitumor activity of T helper type 1 cells and dendritic cells in murine models of pancreatic cancer
Authors: Nasti Alessandro , Inagaki Shingo , Ho Tuyen Thuy Bich , Seki Akihiro , Yoshida Keiko , Satomura Kosuke , Sakai Yoshio , Kaneko Shuichi , Yamashita Taro
Published: January 2025

Pancreatic ductal adenocarcinoma (PDAC) is a disease with poor prognosis due to diagnostic and therapeutic limitations. We previously identified cystatin A (CSTA) as a PDAC biomarker and have conducted the present study to investigate the antitumor effects of CSTA. PDAC murine models were established with genetically modified PAN02 tumor cell lines to evaluate the antitumor immune response. PDAC mouse survival was significantly longer with CSTA, and its antitumor effect was mediated mainly by CD4+ cells and partly by CD8+ cells. We also observed an increased infiltration of CD4+ and CD8+ cells in tumors of mice overexpressing CSTA. Phenotypically, we confirmed higher T helper type 1 (Th1) cell activity and increased frequency and activity of M1 macrophages and dendritic cells (DCs) in CSTA‐overexpressing mice. Gene expression analysis highlighted pathways related to interferon gamma (IFN‐γ) induction and Th1 lymphocyte activation that were induced by CSTA. Macrophages and DCs shifted toward proinflammatory antitumor phenotypes. Furthermore, activated splenocytes of PDAC model mice expressing CSTA had increased proapoptotic activity. CSTA also promoted the selective migration of CD4+ and CD11c+ immune cells in an in vitro migration assay. In conclusion, CSTA exerts antitumor effects by enhancing Th1‐mediated antitumor effects through promotion of DC and M1 macrophage activity, thereby increasing immune cell chemotaxis. CSTA could be a novel therapeutic candidate for PDAC.
MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats
Authors: Chen Xiao , Gan Yeting , Zhang Kaiqi , Wu Yuhan , Li Ye , Lan Tian , Zhuang Xianghua , Chen Shihong , Yu Shuyan
Published: January 2025

Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR‐204‐5p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression. Knockdown of miR‐204‐5p in the vmPFC of normal rats results in depression and anxiety‐like behaviors accompanied with the activation of microglia, elevated levels of pro‐inflammatory cytokines, and increased numbers of neural apoptotic cells, effects which appear to be mediated by activation of the JAK2/STAT3 signaling pathway. Electrophysiological recordings further demonstrate that knockdown of miR‐204‐5p induces abnormal excitability of pyramidal neurons. In contrast, upregulation of miR‐204‐5p in the vmPFC of CUMS rats significantly causes inhibition of JAK2/STAT3 signaling pathway, improvements in neuronal impairments, and an abolition of the depression and anxiety‐like behaviors. Moreover, pharmacological blocking of the JAK2/STAT3 signaling pathway significantly ameliorates abnormal behaviors resulting from miR‐204‐5p deficiency within the vmPFC. Collectively, these results provide robust evidence that the miR‐204‐5p/JAK2/STAT3 pathway may critically involve in the pathogenesis of depression, which may serve as potentially critical therapeutic target in the treatment of MDD.
Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair
Authors: Wei Yi , Zhou Xiaolin , Li Zhenhua , Liu Qing , Ding Han , Zhou Yunlong , Yin Ruo‐feng , Zheng Lifei
Published: January 2025

Protein self‐assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single‐component self‐assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair is demonstrated. Gelation is achieved by the physical entanglement of CsgA nanofibrils, resulting in a self‐supporting hydrogel at low concentrations (≥5 mg mL−1). By leveraging the programmability of the CsgA gene sequence, the bioactive hydrogel is enhanced by fusing functional peptide GHK. GHK is recognized for its anti‐inflammatory, antioxidant, and neurotrophic factor‐stimulating properties, making it a valuable addition to the hydrogel for spinal cord injury repair applications. In vitro experiments demonstrate that the CsgA‐GHK hydrogel can modulate microglial M2 polarization, promote neuronal differentiation of neural stem cells, and inhibit astrocyte differentiation. Additionally, the hydrogel shows efficacy in alleviating inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery in a rat model with compression injury spinal cord cavity. These findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in tissue repair applications.
Supramolecular Engineering of Nanoceria for Management and Amelioration of Age‐Related Macular Degeneration via the Two‐Level Blocking of Oxidative Stress and Inflammation
Authors: Xu Mingyu , Zhou Yifan , Xu Yufeng , Shao An , Han Haijie , Ye Juan
Published: January 2025

Age‐related macular degeneration (AMD), characterized by choroidal neovascularization (CNV), is the global leading cause of irreversible blindness. Current first‐line therapeutics, vascular endothelial growth factor (VEGF) antagonists, often yield incomplete and suboptimal vision improvement, necessitating the exploration of novel and efficacious therapeutic approaches. Herein, a supramolecular engineering strategy to construct moringin (MOR) loaded α‐cyclodextrin (α‐CD) coated nanoceria (M@CCNP) is constructed, where the hydroxy and newly formed carbonyl groups of α‐CD interact with the nanoceria surface via O─Ce conjunction and the isothiocyanate group of MOR inserts deeply into the α‐CD cavity via host–guest interaction. By exploiting the recycling reactive oxygen species (ROS) scavenging capability of nanoceria and the anti‐inflammation properties of MOR, the two‐level strike during AMD pathogenesis can be precisely blocked by M@CCNP. Remarkably, excellent therapeutic efficacy to CNV is observed in vivo, achieving over 80% reduction in neovascularization and over 60% reduction in leakage area. In summary, the supramolecular engineered nanoceria provides an efficient approach for amelioration of AMD by blocking the two‐level strike, and presents significant potential as an exceptional drug delivery platform, particularly for ROS‐related diseases.
ROS‐Responsive Microneedle Patches Enable Peri‐Lacrimal Gland Therapeutic Administration for Long‐Acting Therapy of Sjögren's Syndrome‐Related Dry Eye
Authors: Mu Jingqing , Ding Xiangyu , Song Yapeng , Mi Baoyue , Fang Xiaolong , Chen Baihua , Yao Bin , Sun Xuguang , Yuan Xiaoyong , Guo Shutao , Hua Xia
Published: January 2025

Sjögren's syndrome‐related dry eye (SSDE) is a severe dry eye subtype characterized by significant immune cell attacks on the lacrimal gland. However, delivering immunosuppressive drugs to the lacrimal glands for SSDE therapy safely and sustainably poses significant challenges in clinical practice. Herein, a ROS‐responsive microneedle patch with detachable functionality (CE‐MN) is developed to enable straightforward and minimally invasive administration to the lacrimal gland area by penetrating the periocular skin. CE‐MN is loaded with immunosuppressive cyclosporin A and anti‐inflammatory drug epigallocatechin gallate, the latter also serving as a cross‐linker for the microneedle matrix. Poly(N‐isopropylacrylamide‐co‐butylacrylate), a temperature‐sensitive polymer is utilized to fabricate separable layers that allow controlled detachment of the base from the needle, reducing patient discomfort. CE‐MN is capable of modulating drug release by responding to ROS, facilitating on‐demand release, and drug accumulation to the lacrimal gland. Compared to traditional eye drops, the CE‐MN patch facilitated long‐acting drug delivery to the lacrimal gland for more than 48 h, demonstrating potent anti‐inflammatory and immunosuppressive effects in an SSDE mouse model by scavenging ROS and inhibiting the proliferation of Th1, Th17 cells, and macrophages. Overall, this long‐acting microneedle patch potentially offers a novel clinical approach for treating SSDE and other ocular chronic diseases.
Novel Leech Antimicrobial Peptides, Hirunipins: Real‐Time 3D Monitoring of Antimicrobial and Antibiofilm Mechanisms Using Optical Diffraction Tomography
Authors: Kumar S. Dinesh , Park Jeongwon , Radhakrishnan Naveen Kumar , Aryal Yam Prasad , Jeong Geon‐Hwi , Pyo In‐Hyeok , Ganbaatar Byambasuren , Lee Chul Won , Yang Sungtae , Shin Younhee , Subramaniyam Sathiyamoorthy , Lim Yu‐jin , Kim Sung‐Hak , Lee Seongsoo , Shin Song Yub , Cho Sung‐Jin
Published: January 2025

Antimicrobial peptides (AMPs) are promising agents for treating antibiotic‐resistant bacterial infections. Although discovering novel AMPs is crucial for combating multidrug‐resistant bacteria and biofilm‐related infections, their clinical potential relies on precise, real‐time evaluation of efficacy, toxicity, and mechanisms. Optical diffraction tomography (ODT), a label‐free imaging technology, enables real‐time visualization of bacterial morphological changes, membrane damage, and biofilm formation over time. Here, a computational analysis of the leech transcriptome using an advanced AI‐based peptide screening strategy with ODT to identify potential AMPs is employed. Among the 19 potential AMPs identified, hirunipin 2 demonstrates potent antibacterial activity, low mammalian cytotoxicity, and minimal hemolytic effects. It demonstrates efficacy comparable to melittin, resistance to physiological salts and human serum, and a low likelihood of inducing bacterial resistance. Microscopy and 3D‐ODT confirm its disruption of bacterial membranes and intracellular aggregation, leading to cell death. Notably, hirunipin 2 effectively inhibits biofilm formation, eradicates preformed biofilms, and synergizes with antibiotics against multidrug‐resistant Acinetobacter baumannii (MDRAB) by enhancing membrane permeability. Additionally, hirunipin 2 significantly suppresses pro‐inflammatory cytokine expression in LPS‐stimulated macrophages, highlighting its anti‐inflammatory properties. These findings highlight hirunipin 2 as a strong candidate for developing novel antibacterial, anti‐inflammatory, and antibiofilm therapies, particularly against multidrug‐resistant bacterial infections.
Toward Large‐Scale Photonic Chips Using Low‐Anisotropy Thin‐Film Lithium‐Tantalate
Authors: Huang Fei , Shen Xiaowan , Wang Siyuan , Xu Haochen , Liu Hongxuan , Wang Zexu , Gao He , Yao Xinmin , Cao Hengzhen , Chen Bin , Wang Xijie , Zhang Jizhi , Wu Zhile , Zhu Mingyu , Xiong Hongzhi , Zhao Weike , Li Huan , Yu Zejie , Liu Liu , Shi Yaocheng , Dai Daoxin
Published: January 2025

Photonic manipulation of large‐capacity data with the advantages of high speed and low power consumption is a promising solution for explosive growth demands in the era of post‐Moore. A well‐developed lithium‐niobate‐on‐insulator (LNOI) platform has been widely explored for high‐performance electro‐optic (EO) modulators to bridge electrical and optical signals. However, the photonic waveguides on the x‐cut LNOI platform suffer serious polarization‐mode conversion/coupling issues because of strong birefringence, making it hard to realize large‐scale integration. Here, low‐birefringence photonic integrated circuits (PICs) based on lithium‐tantalate‐on‐insulator (LTOI) are proposed and demonstrated, which enables high‐performance passive photonic devices as well as EO modulators, showing great potential for large‐scale photonic chips. Analysis of mode conversion and evolution behaviors with both low‐ and high‐birefringence shows undesired mode hybridizations can be effectively suppressed. A simple and universal fabrication process is developed and various representative passive photonic devices are demonstrated with impressive performances. Finally, a wavelength‐division‐multiplexed optical transmitter is developed with a data rate of 1.6 Tbps by monolithically integrating 8 EO modulators and an 8‐channel arrayed waveguide grating. Therefore, the demonstrated low‐birefringence LTOI platform shows strong ability in both passively and actively controlling photon behaviors on a chip, indicating great potential for ultrafast processing and communicating large‐capacity data.
Co‐Atomic Interface Minimizing Charge Transfer Barrier in Polytypic Perovskites for CO2 Photoreduction
Authors: Zhong Fengyi , Sheng Jianping , Du Chenyu , He Ye , Zhang Fengying , Sun Yanjuan , Zhou Ying , Dong Fan
Published: January 2025

Heterojunctions, known for their decent separation of photo‐generated electrons and holes, are promising for photocatalytic CO2 reduction. However, a significant obstacle in traditional post‐assembled heterojunctions is the high interfacial barrier for charge transfer caused by atomic lattice mismatch at multiphase interfaces. Here, as research prototypes, the study creates a lattice‐matched co‐atomic interface within CsPbBr3‐CsPb2Br5 polytypic nanocrystals (113‐125 PNs) through the proposed in situ hybrid strategy to elucidate the underlying charge transfer mechanism within this unique interface. Compared to CsPbBr3 nanocrystals, the 113–125 PNs exhibit a remarkable 3.6‐fold increase in photocatalytic CO2 reduction activity (173.3 µmol−1 g−1 within 5 h). Furthermore, Kelvin probe force microscopy results reveal an increase in the built‐in electric field within this lattice‐matched co‐atomic interface from 43.5 to 68.7 mV, providing a stronger driving force for charge separation and directional migration. Additionally, ultrafast transient absorption spectroscopy uncovers the additional charge carrier transfer pathways across this lattice‐matched co‐atomic interface. Thus, this unique co‐atomic interface significantly promotes the interfacial electronic coupling and mitigates the charge transfer barrier, thus facilitating efficient charge separation and transfer. These insights underscore the importance of interfacial structure in heterojunction design and comprehending the intricate interplay between interface and carrier dynamics.
Sequential Targeting Chondroitin Sulfate‐Bilirubin Nanomedicine Attenuates Osteoarthritis via Reprogramming Lipid Metabolism in M1 Macrophages
Authors: Deng Caifeng , Xiao Yongbing , Zhao Xuan , Li Hui , Chen Yuxiao , Ai Kelong , Jiang Ting , Wei Jie , Chen Xiaoyuan , Lei Guanghua , Zeng Chao
Published: January 2025

The infiltration and excessive polarization of M1 macrophages contribute to the induction and persistence of low‐grade inflammation in joint‐related degenerative diseases such as osteoarthritis (OA). The lipid metabolism dysregulation promotes M1 macrophage polarization by coordinating the compensatory pathways of the inflammatory and oxidative stress responses. Here, a self‐assembling, licofelone‐loaded nanoparticle (termed LCF‐CSBN), comprising chondroitin sulfate and bilirubin joined by an ethylenediamine linker, is developed to selectively reprogram lipid metabolism in macrophage activation. LCF‐CSBN is internalized by M1 macrophages via CD44‐mediated endocytosis and targets the Golgi apparatus accompanied with the reactive oxygen species‐responsive release of licofelone (LCF, dual inhibitor of arachidonic acid metabolism). LCF‐CSBN effectively promotes M1 to M2 macrophage transition by reprogramming the Golgi apparatus‐related sphingolipid metabolism and arachidonic acid metabolism. Intra‐articularly injected LCF‐CSBN retains in the joint for up to 28 days and accumulates into M1 macrophages. Moreover, LCF‐CSBN can effectively attenuate joint inflammation, oxidative stress, and cartilage degeneration in OA model rats. These findings indicate the promising potential of lipid‐metabolism‐reprogramming LCF‐CSBN in the targeted therapy of OA.
Skin‐Integrated Electrogenetic Regulation of Vasculature for Accelerated Wound Healing
Authors: Guha Ray Preetam , Rajasekaran Ragavi , Pratihar Bitan , De Sirshendu , Dhara Santanu , Fussenegger Martin
Published: January 2025

Neo‐vascularization plays a key role in achieving long‐term viability of engineered cells contained in medical implants used in precision medicine. Moreover, strategies to promote neo‐vascularization around medical implants may also be useful to promote the healing of deep wounds. In this context, a biocompatible, electroconductive borophene–poly(ε‐caprolactone) (PCL) 3D platform is developed, which is called VOLT, to support designer cells engineered with a direct‐current (DC) voltage‐controlled gene circuit that drives secretion of vascular endothelial growth factor A (VEGFA). The VOLT platform consists of a 3D‐printed borophene‐PCL honeycomb‐shaped matrix decorated with borophene‐PCL nanofibers by electrospinning. The honeycomb structure provides mechanical stability, while the nanofibers facilitate the adhesion, migration, and proliferation of the engineered cells. The cells incorporate a DC‐powered reactive oxygen species (ROS)‐sensing gene circuit wired to an engineered synthetic promoter that triggers secretion of VEGFA to promote vascularization in the adjacent extracellular matrix. Cells engineered with this gene circuit and enclosed in the VOLT matrix, termed the VOLTVEGFA system, can be simply triggered using off‐the‐shelf AA batteries, utilizing the established ability of a brief DC bias to generate non‐cytotoxic levels of ROS. For proof‐of‐concept, a subcutaneous wound‐healing model in rats is chosen. Electrostimulation of a VOLTVEGFA implant (5 V, 20 s per day) induced secretion of VEGFA, and significantly accelerated neovascularization and granulation tissue formation, resulting in faster wound closure compared with non‐stimulated controls. Complete re‐epithelialization and dermal regeneration are observed within 15 days of application.
Radiative Warming Glass for High‐Latitude Cold Regions
Authors: Zhou Zhengui , Liu Rong , Huang Zhen , Hu Bin , Long Yi
Published: January 2025

Traditional window glazing, with inherently adverse energy‐efficient optical properties, leads to colossal energy losses. Energy‐saving glass requires a customized optical design for different climate zones. Compared with the widely researched radiative cooling technology which is preferable to be used in low‐altitude hot regions; conversely in high‐latitude cold regions, high solar transmittance (Tsol) and low mid‐infrared thermal emissivity (εMIR) are the key characteristics of high‐performance radiative warming window glass, while the current low‐emissivity (low‐e) glass is far from ideal. To address this issue, Drude's theory is used to numerically design a near‐ideal film with specified electron density (ne) and electron mobility (µe). The fabricated hydrogen‐doped indium oxide (IHO) could achieve high Tsol (0.836) and low εMIR (0.117). Energy‐saving simulations further reveal a substantial decrease in annual heating energy consumption up to 6.6% across high‐latitude regions (climate zones 6 to 8), translating to a corresponding reduction in CO2 emissions (20.0 kg m−2), outperforming 1165 high performance commercial low‐e glass. This radiative warming glass holds the promise of making a significant contribution to sustainable building energy savings specifically for high‐latitude cold regions, advancing the goal of carbon neutrality.
Cell‐Type Specific miRNA Regulatory Network Responses to ABA Stress Revealed by Time Series Transcriptional Atlases in Arabidopsis
Authors: Gao Zhaoxu , Su Yanning , Jiao Guanzhong , Lou Zhiying , Chang Le , Yu Renbo , Xu Chao , Han Xue , Wang Zejia , Li Jian , Deng Xing Wang , He Hang
Published: January 2025

In plants, microRNAs (miRNAs) participate in complex gene regulatory networks together with the transcription factors (TFs) in response to biotic and abiotic stresses. To date, analyses of miRNAs‐induced transcriptome remodeling are at the whole plant or tissue levels. Here, Arabidopsis’s ABA‐induced single‐cell RNA‐seq (scRNA‐seq) is performed at different stages of time points–early, middle, and late. Single‐cell level primary miRNAs (pri‐miRNAs) atlas supported the rapid, dynamic, and cell‐type specific miRNA responses under ABA treatment. MiRNAs respond rapidly and prior to target gene expression dynamics, and these rapid response miRNAs are highly cell‐type specific, especially in mesophyll and vascular cells. MiRNA‐TF‐mRNA regulation modules are identified by identifying miRNA‐contained feed‐forward loops (M‐FFLs) in the regulatory network, and regulatory networks with M‐FFLs have higher co‐expression and clustering coefficient (CC) values than those without M‐FFLs, suggesting the hub role of miRNAs in regulatory networks. The cell‐type‐specific M‐FFLs are regulated by these hub miRNAs rather than TFs through sc‐RNA‐seq network analysis. MiR858a‐FBH3‐MYB module inhibited the expression of MYB63 and MYB20, which related to the formation of plant secondary wall and the production of lignin, through M‐FFL specifically in vascular. These results can provide prominent insights into miRNAs' dynamic and cell‐type‐specific roles in plant development and stress responses.
Machine Learning‐Driven Prediction, Preparation, and Evaluation of Functional Nanomedicines Via Drug–Drug Self‐Assembly
Authors: Zhang Chengyuan , Yuan Yuchuan , Xia Qiong , Wang Junjie , Xu Kangkang , Gong Zhiwei , Lou Jie , Li Gen , Wang Lu , Zhou Li , Liu Zhirui , Luo Kui , Zhou Xing
Published: January 2025

Small molecules as nanomedicine carriers offer advantages in drug loading and preparation. Selecting effective small molecules for stable nanomedicines is challenging. This study used artificial intelligence (AI) to screen drug combinations for self‐assembling nanomedicines, employing physiochemical parameters to predict formation via machine learning. Non‐Steroidal Anti‐Inflammatory Drugs (NSAIDs) are identified as effective carriers for antineoplastic drugs, with high drug loading. Nanomedicines, PEG‐coated indomethacin/paclitaxel nanomedicine (PiPTX), and laminarin‐modified indomethacin/paclitaxel nanomedicine (LiDOX), are developed with extended circulation and active targeting functions. Indomethacin/paclitaxel nanomedicine iDOX exhibits pH‐responsive drug release in the tumor microenvironment. These nanomedicines enhance anti‐tumor effects and reduce side effects, offering a rapid approach to clinical nanomedicine development.
Synergetic Contributions of High Quenching Concentration and Tuned Square Antiprism Geometry Boosting Far‐Red Emission of Eu3+ with Near‐Unit Efficiency
Authors: Li Hong , Haider Asif Ali , Xie Zhi , Liu Conglin , Zhang Hongzhi , Jiang Hongming , Li Junpeng , Zhu Jing
Published: January 2025

Far‐red phosphors have emerged as a desirable research hotspot owing to their critical role in promoting plant growth. Especially, Eu3+ ions typically present the 5D0→7FJ (J = 0, 1, 2, 3, 4) transitions, which overlap with the far‐red light required for plant photosynthesis. However, achieving high‐efficiency far‐red emission of Eu3+ remains challenging due to weak 5D0→7F4 transition and concentration quenching. The study constructs two anomalously efficient far‐red garnet phosphors A3Sc2C3O12 (A = Y3+, Gd3+. C = Al3+, Ga3+):Eu3+. A high‐resolution STEM measurement equipped with an aberration corrector provides the direct proofs for both the [EuO8] configuration‐dependent strong 5D0→7F4 and the origin of high quenching concentration. Excitedly, a two‐component substitution (replacing Y3+‐Al3+ with Gd3+‐Ga3+) triggers a near‐unity internal quantum efficiency (IQE = 99.01%) and high external quantum efficiency (EQE = 38.73%) in Gd3Sc2Ga3O12:60%Eu3+, resulting from the effective modulation of 5D0→7F4/7F2 transitions. A far‐red LEDs device based on Gd3Sc2Ga3O12:60%Eu3+ exhibits an output power of 113 mW at 300 mA. Subsequently, practical applications for promoting plant growth underscore the significance of these findings. This work opens a new path for the development of highly efficient far‐red phosphors via the synergistic effect of Eu3+ square antiprism configuration and high quenching concentration.
Network congestion games with player failures for charging problem of EVs via matrix approach
Authors: Liu Shuqi , Ma Lijun , Wang Jinhuan
Published: January 2025

With the increasing popularity of electric vehicles (EVs), the congestion problem encountered during EV charging has become a new challenge that needs to be addressed. In this paper, the congestion problem of EV charging is investigated within the framework of network congestion games. It takes into account congestion during both travelling and charging stages. Initially, for the scenario where no player fails, the EV charging problem is modeled as a network congestion game, which is proven to be a potential game. Secondly, two types of games with player failures are considered. The game with player failures on roads is verified a weighted potential game, drawing support from the semi‐tensor product (STP) of matrices. The game in which players only fail at charging stations, rather than on roads, is not a (weighted) potential game but admits at least one Nash equilibrium (NE). Thirdly, the effect of player failures on NEs is discussed, and the condition that keeps the NE of the original game unchanged is provided. Finally, the theoretical results are validated through examples.
Synthesis and Characterization of Brucine Gold Nanoparticles for Targeted Breast Cancer Therapy: Mechanistic Insights Into Apoptosis and Antioxidant Disruption in MCF‐7 Cells
Authors: Alamelu Saravanan , Venkatesan Kamalesh Balakumar , Srinivasan Manoj Kumar , Pachaiappan Pugalendhi
Published: January 2025

Globally, breast cancer continues to be the leading type of cancer affecting women, with rising mortality rates projected by 2030. This highlights the importance of developing new, affordable treatments, like drug delivery systems that use nanoparticles. Gold nanoparticles (AuNPs), including their exceptional optical and physical attributes, make them an attractive vehicle for targeted treatment, allowing for accurate and focused delivery of medication directly to cancerous cells while reducing harmful side effect. This study focuses on the synthesis and characterization of brucine‐gold nanoparticles (BRU‐AuNPs) for targeted breast cancer therapy by evaluating their antioxidant and apoptotic mechanism. BRU‐AuNPs were synthesized and characterized (UV–Vis spectroscopy, Fourier transform infrared [FTIR], scanning electron microscopy [SEM], x‐ray diffraction [XRD], dynamic light scattering [DLS], and zeta potential) to confirm successful synthesis, size, and stability. In vitro studies were assessed using MCF‐7 breast cancer cell lines to evaluate cell cytotoxicity, antioxidant balance, reactive oxygen species (ROS) generation, mitochondrial membrane potential, apoptosis induction, cell migration, and pro‐apoptotic gene expression. Characterization results confirmed the successful synthesis of BRU‐AuNPs with an average crystal size of 85.40 nm and stable surface charge. Results demonstrated that BRU‐AuNPs reduced MCF‐7 cell viability in a dose‐dependent manner, with an IC50 value of 11.47 µg/mL. Treatment with BRU‐AuNPs altered the antioxidant balance, increased ROS generation, depolarized mitochondrial membranes, and induced apoptosis. Additionally, BRU‐AuNPs inhibited cell migration and upregulated pro‐apoptotic gene expression. The synthesized BRU‐AuNPs exhibit potential as a highly effective targeted delivery system for breast cancer treatment. Their ability to directly deliver BRU to tumor cells while reducing side effects and enhancing therapeutic efficacy underscores their promise in advancing breast cancer therapy. Further studies are warranted to explore their clinical potential and optimize therapeutic outcomes.
The Legitimacy–Commitment Paradox in Corporate Sustainability Strategy Formulation
Authors: Albertsen Rikke Rønholt
Published: January 2025

Researchers have long problematised the gap between corporations' formulated sustainability strategies and their actual contributions to sustainability. This study draws on 24 months of real‐time observations in a multinational company to explore the origins of this gap in the formulation phase of corporate sustainability (CS) strategy. The findings show that contradictory logics and processes related to (a) gaining external legitimacy and (b) mobilising internal commitment impose paradoxical demands on the formulation process. Strategy makers tackled these tensions through rhetorical ambiguity and temporal separation. However, while these paradox management strategies facilitated coping with conflicting demands and avoiding deadlocks in the formulation process, they also created a commitment vacuum that undermined implementation. This study highlights the role of the formulation phase as an overlooked origin of implementation failure. The findings nuance our understanding of defensive and proactive paradox responses and call for further examination of the unintended outcomes of paradox responses.
Small Molecule X‐ray Crystal Structures at a Crossroads
Authors: Hill Nathan D. D. , Boeré René T.
Published: January 2025

Refinement of ‘small molecule’ crystal structures from X‐ray diffraction benefits from advances in methods derived from quantum crystallography. After outlining some pertinent principles and reasons for needed improvements in the theoretical structure model, the author′s experience in implementing Hirshfeld Atom Refinement using the NoSpherA2 option in the popular Olex2 crystallographic GUI is outlined. The method allows the placement of hydrogen atoms with accuracy comparable to neutron diffraction. Moreover, the average precisions of bonds involving light atoms is found to improve in most cases, with the degree of improvement correlating strongly with the overall quality of the diffraction data and the refinement model. A suggested workflow for HAR with NoSpherA2 is provided. A call is made for wide‐spread adoption, along with a community‐wide development of ‘standard protocols for the use of aspherical form factors in chemical crystallography’.
Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board DNA Sequencing Data: Workflow and Estimated Costs
Authors: Koo Hyunwoo , Smith Tayler B. , Callaghan John T. , Osei Wilberforce , Bray Steven M. , Tillman Emma M. , Tran Mya T. , Fausel Christopher A. , Schneider Bryan P. , Shugg Tyler , Skaar Todd C.
Published: January 2025

Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncology practice; these include sequencing of pharmacogenes, but the germline pharmacogenetic variants are rarely included in the clinical reports, despite many being clinically actionable. We established an informatics workflow to evaluate the clinical sequencing results for pharmacogenetic variants. We used the Aldy computational tool, which we have previously shown to determine the variant alleles in 14 pharmacogenes in clinical sequencing data with >99% accuracy, to identify pharmacogenetic variants in the clinical whole exome sequencing from our molecular tumor board. Patients with genetic variants that are clinically actionable for their individual therapy programs, including both treatment and supportive care, are referred to a clinical pharmacogenetics testing laboratory for confirmation. Through an evaluation of our weekly informatics workflow, we determined it took approximately 3.25 hours to complete the analysis of the sequencing data from approximately 20 patients. Using a United States pharmacist's median salary, we estimated the incremental added cost of the process to be only ~$15 per patient. This adds only a minor increase to the patient's cost of testing and has the potential to improve the safety and efficacy of their treatment.
Current and future burden of female breast cancer in the Middle East and North Africa region using estimates from GLOBOCAN 2022
Authors: Zahwe Mariam , Bendahhou Karima , Eser Sultan , Mukherji Deborah , Fouad Heba , Fadhil Ibtihal , Soerjomataram Isabelle , Znaor Ariana
Published: January 2025

Breast cancer is the most diagnosed female cancer and the most common cause of cancer death in women in the Middle East and North Africa (MENA) region. In this study, we aimed to describe the current patterns of breast cancer among women in the MENA region and estimate the burden for the year 2050. We used the estimates of the breast cancer incidence and mortality from the GLOBOCAN 2022 database and predicted the burden of breast cancer in 2050 according to different scenarios. With 118,200 new breast cancer cases and 41,000 deaths, breast cancer contributed to 25% of cancer incidence and almost 20% of cancer mortality among women in MENA. The highest incidence rates were in Algeria and Iraq (≥60/100,000) and the lowest rates in Saudi Arabia and Yemen (<30/100,000). The highest mortality rates were in Iraq, Syrian Arab Republic, Algeria, and Sudan (>20/100,000), and the lowest in Saudi Arabia (7.6/100,000). While the incidence rates were low compared to other world regions, the mortality rates (16.9/100,000) were higher than in any other world region except Sub‐Saharan Africa. The incidence rates for women <50 years in MENA were 5.5 times lower than in women aged ≥50 years, and lower than for women <50 years in Western countries. By 2050, the burden of breast cancer is estimated to increase to 219,000 new cases and to 88,900 deaths (86% and 117%, respectively). Scaling up cancer control to curb the rising burden alongside improved surveillance is vital to develop targeted interventions and improving outcomes.
The Resilience of Green Bonds During Market Turmoil: Implications for Investors and Policymakers
Authors: Meo Muhammad Saeed , Afshan Sahar , Zaied Younes Ben , Staniewski Marcin
Published: January 2025

Despite significant growth, green bonds comprise less than 1% of the conventional bonds market, and more research is needed to determine their role as diversifiers, hedges or safe havens. In compliance. This study examines the co‐movement between green bonds and various financial markets (stocks, commodities, digital currencies, bonds and foreign exchange) before and during COVID‐19, using daily data from 28/11/2008 to 21/3/2022 and using quantile‐based analysis. The findings based on quantile‐on‐quantile regression confirm an asymmetric/non‐linear association between green bonds and other financial markets before COVID‐19, with the association varying depending on market conditions, such as bearish, normal and bullish. During the COVID‐19 period, a robust negative correlation is identified between green bonds and other financial markets, affirming the safe‐haven role of green bonds against broader financial markets. These findings have important policy implications for investors, fund managers and policymakers. For increased diversification, investors in conventional and Islamic equities, commodities, conventional bonds, Sukuk markets, virtual and foreign currency markets can find it advantageous to include green bonds as a protection to downside risk.
Results on Existence, Uniqueness, and Stability of an Impulsive Caputo–Katugampola Hybrid FDE With p$$ p $$‐Laplacian Operator
Authors: Devi Darshana , Borah Jayanta
Published: January 2025

The article deals with a second kind of hybrid noninstantaneous impulsive fractional differential equation with ‐Laplacian operator involving Caputo–Katugampola fractional derivatives. The rudimentary concept of this article is to establish the existence, uniqueness, Hyers–Ulam stability, and Hyers–Ulam–Rassias stability. The fixed point approach is the basis for establishing the results of solution to the considered problem. An example is also given to highlight the main findings.
Joint k‐b space diffusion‐weighted image reconstruction and apparent diffusion coefficient fitting for diffusion‐weighted turbo‐spin‐echo imaging
Authors: Dai Yan , Jia Xun , Liu Jiaen , Liao Yen‐Peng , Deng Jie
Published: January 2025

Background

Diffusion‐weighted (DW) turbo‐spin‐echo (TSE) imaging offers improved geometric fidelity compared to single‐shot echo‐planar‐imaging (EPI). However, it suffers from low signal‐to‐noise ratio (SNR) and prolonged acquisition times, thereby restricting its applications in diagnosis and MRI‐guided radiotherapy (MRgRT).

Purpose

To develop a joint k‐b space reconstruction algorithm for concurrent reconstruction of DW‐TSE images and the apparent diffusion coefficient (ADC) map with enhanced image quality and more accurate quantitative measurements.

Methods

The joint k‐b reconstruction model was formulated as an optimization problem subject to a self‐consistency condition comprising the exponential decay relationship between DW images and the ADC map. The objective function included a data fidelity term confirming an agreement between the reconstructed images and measured k‐space data, incorporating the mono‐exponential decay relationship between DW images and ADC map as a constraint, along with spatial regularization terms on both amplitude and phase images. The optimization problem was solved using the alternating‐direction method of multipliers (ADMM). We evaluated the performance of the joint reconstruction (JR) algorithm for DW‐TSE in a phantom study and patient studies on five brain and head/neck cancer patients. Image distortion, accuracy, and repeatability of ADC measurements were assessed and compared with those from conventional Fourier‐transformed (FFT)‐based reconstruction and magnitude‐based ADC fitting methods, as well as with the clinically used DW‐EPI technique.

Results

The proposed joint k‐b reconstruction method demonstrated improved SNR and enhanced accuracy of ADC measurements in DW‐TSE compared to the conventional method. Additionally, JR‐DW‐TSE with fewer averages at high b‐values provided better image quality than the conventional FFT‐reconstructed DW‐TSE with full averages.

Conclusion

The proposed joint k‐b reconstruction method for DW‐TSE has the potential to deliver distortion‐robust diffusion‐weighted MRI (DWI) for clinical applications, which is particularly crucial for MRgRT.
Presenting Symptoms Define Time to Diagnosis in Degenerative Cervical Myelopathy: Process Mapping From a Musculoskeletal Triage Unit in the UK
Authors: Foulds Stephanie , Henshaw Lorraine , Davies Benjamin M.
Published: January 2025

Study Design

Retrospective cohort study.

Objective

Tackling delayed diagnosis in degenerative cervical myelopathy (DCM) is a global research priority. On average, it takes 2–5 years, leading to worse outcomes from surgery and greater disability. Many countries in the UK use interface triage units run by specialist physiotherapists that sit between primary and secondary care termed musculoskeletal services. Their role in the efficient diagnosis of DCM is unknown. The aim of this study was to map the journey of the patient in the musculoskeletal service and to establish the presenting signs and symptoms.

Methods

A retrospective review of 2.5 years of clinical notes was performed in a musculoskeletal service. Process mapping was utilised to visualise the patient's journey and identify delays to diagnosis and presenting signs and symptoms.

Results

Twenty‐seven cases were reviewed. Patients spent an average of three months in the service. There was a wide variety of presenting symptoms. DCM was more often suspected if patients had both upper limb symptoms and gait disturbance or pathological reflexes. Delays occurred when patients had no gait disturbance or a normal or incomplete neurological assessment. Longest delays occurred when patients received electrophysiology tests for differential diagnosis of peripheral neuropathies. Delays were also seen with incorrect triaging of MRI results.

Conclusions

Where DCM is the principal differential diagnosis, diagnosis was faster. Incomplete examination, misinterpretation of MRI findings or delays in other investigations contributed to delays. Improved awareness and protocols of care within musculoskeletal services represent an opportunity to accelerate diagnosis in DCM.
Reliability and Validity of the Japanese Version of the Internet Gaming Disorder Scale for Children (IGDS‐C)
Authors: Ono Koki , Tokushige Makoto , Hiratani Nanami , Kaneko Kyosuke , Hamamura Toshitaka , Miyamoto Yuki , Tateno Masaru , Ito Masaya , Takano Ayumi
Published: January 2025

Aim

The Internet Gaming Disorder Scale is a 9‐item screening instrument developed based on the diagnostic criteria for Internet Gaming Disorder (IGD) in the DSM‐5. This study aimed to examine the reliability and validity of the Internet Gaming Disorder Scale for children (IGDS‐C) in Japanese clinical and nonclinical populations.

Methods

The study included clinical outpatients aged 9–29 with problematic game use and nonclinical adolescents aged 12–18 who played online games at least once a week. Reliability was examined by calculating internal consistency and test–retest reliability. Validity was assessed using Spearman's correlation and Confirmatory Factor Analysis (CFA).

Results

A total of 746 participants (93 clinical, 653 nonclinical) were eligible for statistical analysis. Reliability results revealed acceptable internal consistency (Cronbach's α = 0.87) and test–retest reliability (intraclass correlation coefficient = 0.62). CFA results (Comparative Fit Index = 0.92, Tucker–Lewis Index = 0.90, root mean square error of approximation = 0.10, standardized root mean square residual = 0.05, factor loadings = 0.59–0.71) and significant correlations with the GAMES test, psychological distress, and gaming hours verified the validity of the IGDS‐C.

Conclusion

The study verified the reliability and validity of the IGDS‐C in Japanese clinical and nonclinical participants, suggesting that it generally reflects the severity of IGD well.
Clinical and Electromyographic Characteristics of Pediatric Laryngeal Dyskinesia
Authors: Alobida Nasser W. , Binnasser Ameen , King Aleksandra , Isaac Andre , El‐Hakim Hamdy
Published: January 2025

Objective

To report the clinical and laryngeal electromyographic (LEMG) parameters of children with laryngeal dyskinesia (LD) and its prevalence among laryngeal mobility disorder (LMD) requiring full airway examination.

Study Design

Retrospective uncontrolled study.

Setting

Tertiary pediatric center.

Methods

Eligible children (<17 years old) were stridulous patients suspected of LMD (16 years period). We included those diagnosed with LD according to previously described criteria by Denoyelle et al, followed up for at least 3 months, who were assessed endoscopically and LEMG. Primary outcome: LEMG scores, and the prevalence of LD in all LMD who required airway exam under anesthesia. Secondary outcomes: clinical resolution, McGill scores, and instrumental swallowing test.

Results

A total of 44 patients (<17 years) were identified. Of these, 29 were included (25 boys; median age: 9.83 months [0.42‐116.58]). LD constituted 18.58% of all patients during the study period. Asymmetry of movement and LEMG between the 2 sides was noted (the right side was more affected). Seventeen had swallowing difficulties (13 abnormal instrumental tests), and 27 snored (mean McGill score 3). The median follow up was 49.96 months (range: 5.25‐243.25). Symptoms improved in all patients, but one, by the last follow‐up date.

Conclusion

LD is prevalent among LMD and is mostly self‐limiting. We noted asymmetry of LEMG grades between the 2 sides of the larynx, male predominance, and functional deficits in sleep and swallowing. The diagnosis requires a complete endoscopic exam with LEMG. Conflating this entity with bilateral laryngeal paralysis has likely impacted the documented epidemiology and natural history.
Diagnosis of Leptomeningeal Disease in Diffuse Midline Gliomas by Detection of H3F3A K27M Mutation in Circulating Tumor DNA of Cerebrospinal Fluid
Authors: Shibuma Satoshi , On Jotaro , Natsumeda Manabu , Koyama Akihide , Takahashi Haruhiko , Watanabe Jun , Mitobe Masaki , Nakata Satoshi , Tanaka Yuki , Tsukamoto Yoshihiro , Okada Masayasu , Yoshimura Junichi , Tada Mari , Shimizu Hiroshi , Oya Soichi , Murai Junko , Okamoto Kouichirou , Kawashima Hiroyuki , Kakita Akiyoshi , Oishi Makoto
Published: January 2025

Introduction

Leptomeningeal disease (LMD) in diffuse midline gliomas (DMGs) can lead to devastating symptoms such as severe pain, urinary incontinence, and tetraparesis, with limited treatment options. We determined whether detecting H3F3A K27M‐mutant droplets in cerebrospinal fluid (CSF) circulating tumor deoxyribonucleic acid (ctDNA) could be a biomarker for detecting LMD in DMGs.

Methods

Twenty‐five CSF samples were obtained from 22 DMG patients. Histological confirmation of H3F3A K27M mutation was obtained in 10 (45.5%) cases. ctDNA was extracted from CSF, and H3F3A K27M‐mutant and wildtype droplets were detected using digital droplet polymerase chain reaction (ddPCR). LMD was diagnosed by CSF cytology and pre‐ and post‐contrast head and spine magnetic resonance (MR) imaging.

Results

The number of H3F3A K27M‐mutant droplets (median 27 [range: 1–379] vs. median 0 [range: 0–1]; p < 0.0001) and variant allele frequency (VAF) (median 48.9% [range: 7.5%–87.5%] vs. median 0.0% [range: 0.0%–50.0%]; p < 0.0001) were significantly higher in the LMD/early‐LMD group compared to no‐LMD group. In two cases (Cases 4 and 11) without clinical evidence of LMD, multiple H3F3A K27M‐mutant droplets were detected in CSF ctDNA. In those cases, extensive spinal dissemination was detected 6 months after the initial liquid biopsy. One case (Case 15) with high Schlafen11 (SLFN11) expression responded well to treatment for LMD and survived for 532 days after the diagnosis of LMD.

Conclusion

This study provides evidence that detecting H3F3A K27M‐mutant droplets in CSF ctDNA is diagnostic for LMD and is more sensitive than traditional methods such as CSF cytology and MR imaging.
Characterization of Potassium Titanate Whisker and UHMWPE‐reinforced Polyethersulfone/Short Carbon Fiber composites: Mechanical, thermal, and structural insights
Authors: Bettegowda Harshavardhan , Mahesh Vishwas , Mahesh Vinyas , Dixit Arun C.
Published: January 2025

Thermoplastics and their composites have advanced significantly, with ongoing efforts to meet complex engineering demands. This study focuses on polyethersulfone (PES) composites reinforced with 25 wt.% short carbon fibers (SCF), investigating the effects of potassium titanate whiskers (PTW) and ultra‐high‐molecular‐weight polyethylene (UHMWPE) fillers on their properties. Using extrusion and injection molding, PES/SCF composites were developed and modified with 2.5 and 5 wt.% of PTW and UHMWPE fillers. Mechanical tests, including tensile, flexural, and impact assessments, were conducted per ASTM standards. The addition of 25 wt.% SCF improved tensile strength (62.28 MPa) and flexural strength (55.4 MPa), though it decreased notched impact strength (nIS) to 2.1 kJ/m2. Incorporating 5 wt.% PTW further enhanced flexural strength (25 MPa) and marginally increased tensile strength (3.61 MPa) but reduced nIS by 0.7 kJ/m2. Conversely, 5 wt.% UHMWPE decreased tensile and flexural strengths by 12.07 and 3.4 MPa, respectively, while improving nIS by 1.2 kJ/m2. These results suggest that PES/SCF composites tailored with PTW and UHMWPE fillers offer promising potential for secondary structural applications in aerospace and automotive industries, where strength and impact resistance are critical.

Highlights

PTW and UHMWPE fillers enhance mechanical properties, elevating PES/SCF composite performance for structural use.

Thermal analysis (TGA, DSC) confirms increased high‐temperature resilience.

SEM imaging shows uniform PTW and UHMWPE distribution, enhancing load transfer and fracture resistance.

Higher storage modulus and lower damping indicate enhanced stiffness, durability, and energy dissipation.