bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Gate‐Tunable Hot‐Carrier Photocurrent from Perovskite Multiple Quantum Wells
Authors: Wang Chenhao , Wei Qi , Ren Hui , Wong Kin Long , Liu Qi , Zhou Luwei , Wang Pengzhi , Cai Songhua , Yin Jun , Li Mingjie
Published: December 2024

Hot‐carrier relaxation above the bandgap results in significant energy losses, making the extraction of hot carriers a critical challenge for efficient hot‐carrier photocurrent generation in devices. In this study, we observe long‐lived hot carriers in the metal‐halide perovskite multiple quantum wells, (BA)2(MA)n−1PbnI3n+1 (n = 3), and demonstrate effective hot‐hole photocurrent generation using 2D MoS₂ as an extraction layer. A high external quantum efficiency of short‐circuit hot‐carrier photocurrent of up to 35.4% is achieved. Further enhancement in photocurrent efficiency and open‐circuit photovoltage is achieved when a gate electric field is applied, resulting in an external quantum efficiency of up to 61.9%. Evidence of hot‐hole extraction is validated through operando transient reflection measurements on the working devices, with studies that depend on wavelength, carrier density, and gate voltage. DFT calculations on the heterostructure devices under different bias voltages further elucidate the mechanism of hot‐hole extraction enhancement. These findings underscore the potential of perovskite multiple quantum wells as long‐lived hot‐carrier generators and highlight the role of 2D transition metal dichalcogenide semiconductors as efficient hot‐carrier extraction electrodes for low‐power optoelectronics.
Isolation of Biomolecules Using MXenes
Authors: Vojoudi Hossein , Soroush Masoud
Published: December 2024

Biomolecule isolation is a crucial process in diverse biomedical and biochemical applications, including diagnostics, therapeutics, research, and manufacturing. Recently, MXenes, a novel class of two‐dimensional nanomaterials, have emerged as promising adsorbents for this purpose due to their unique physicochemical properties. These biocompatible and antibacterial nanomaterials feature a high aspect ratio, excellent conductivity, and versatile surface chemistry. This timely review explores the potential of MXenes for isolating a wide range of biomolecules, such as proteins, nucleic acids, and small molecules, while highlighting key future research trends and innovative applications poised to transform the field. This review provides an in‐depth discussion of various synthesis methods and functionalization techniques that enhance the specificity and efficiency of MXenes in biomolecule isolation. In addition, the mechanisms by which MXenes interact with biomolecules are elucidated, offering insights into their selective adsorption and customized separation capabilities. This review also addresses recent advancements, identifies existing challenges, and examines emerging trends that may drive the next wave of innovation in this rapidly evolving area.
AI‐Powered Multimodal Modeling of Personalized Hemodynamics in Aortic Stenosis
Authors: Ozturk Caglar , Pak Daniel H. , Rosalia Luca , Goswami Debkalpa , Robakowski Mary E. , McKay Raymond , Nguyen Christopher T. , Duncan James S. , Roche Ellen T.
Published: December 2024

Aortic stenosis (AS) is the most common valvular heart disease in developed countries. High‐fidelity preclinical models can improve AS management by enabling therapeutic innovation, early diagnosis, and tailored treatment planning. However, their use is currently limited by complex workflows necessitating lengthy expert‐driven manual operations. Here, we propose an AI‐powered computational framework for accelerated and democratized patient‐specific modeling of AS hemodynamics from computed tomography (CT). First, we demonstrate that the automated meshing algorithms can generate task‐ready geometries for both computational and benchtop simulations with higher accuracy and 100 times faster than existing approaches. Then, we show that the approach can be integrated with fluid‐structure interaction and soft robotics models to accurately recapitulate a broad spectrum of clinical hemodynamic measurements of diverse AS patients. The efficiency and reliability of these algorithms make them an ideal complementary tool for personalized high‐fidelity modeling of AS biomechanics, hemodynamics, and treatment planning.
Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease
Authors: Zhang Yuan , Jia Cuiping , Guo Manli , Chen Qian , Wen Ying , Wang Ting , Xie Yinyin , Fan Xuejiao , Gao Jingwen , Yarovinsky Timur O. , Liu Renjing , Jiang Zhiyong , Wang Mengmeng , Zhou Jin , Che Di , Fu Lanyan , Edelson Richard , Gu Xiaoqiong , Hwa John , Tang Wai Ho
Published: December 2024

Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inflammation and vasculopathy in KD remains unclear. A cytokine‐mediated positive feedback loop between KD platelets and monocytes is identified. KD platelet–monocyte aggregates (MPAs) are mediated by an initial interaction of P‐selectin (cluster of differentiation 62P, CD62p) and its glycoprotein ligand 1 (PSGL‐1). This is followed by a coordinated interaction of platelet glycoprotein (GP)Ibα with monocyte CD11b. Monocyte‐activated platelets initiate transforming growth factor (TGF)β1 release, which results in nuclear localization of nuclear factor kappaB in monocytes, therefore, driving the phenotypic conversion of classical monocytes (CD14+CD16−) into proinflammatory monocytes (CD14+CD16+). The platelet‐activated monocytes release interleukin‐1 and tissue necrotic factor‐α, which promote further platelet activation. KD‐induced inflammation and vasculopathy are prevented by inhibiting the components of this positive feedback loop. Notably, mice deficient in platelet TGFβ1 show less MPA and CD14+CD16+ monocytes, along with reduced inflammation and vasculopathy. These findings reveal that platelet–monocyte interactive proteins (CD62p/PSGL‐1 and (GP)Ibα/CD11b) and cytokine mediators (platelet TGFβ1) are potential biomarkers and therapeutic targets for KD vasculopathy.
Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis
Authors: Liu Bonnie Hei Man , Lin Yuezhen , Long Xi , Hung Sze Wan , Gaponova Anna , Ren Feng , Zhavoronkov Alex , Pun Frank W. , Wang Chi Chiu
Published: December 2024

Endometriosis affects over 190 million women globally, and effective therapies are urgently needed to address the burden of endometriosis on women's health. Using an artificial intelligence (AI)‐driven target discovery platform, two unreported therapeutic targets, guanylate‐binding protein 2 (GBP2) and hematopoietic cell kinase (HCK) are identified, along with a drug repurposing target, integrin beta 2 (ITGB2) for the treatment of endometriosis. GBP2, HCK, and ITGB2 are upregulated in human endometriotic specimens. siRNA‐mediated knockdown of GBP2 and HCK significantly reduced cell viability and proliferation while stimulating apoptosis in endometrial stromal cells. In subcutaneous and intraperitoneal endometriosis mouse models, siRNAs targeting GBP2 and HCK notably reduced lesion volume and weight, with decreased proliferation and increased apoptosis within lesions. Both subcutaneous and intraperitoneal administration of Lifitegrast, an approved ITGB2 antagonist, effectively suppresses lesion growth. Collectively, these data present Lifitegrast as a previously unappreciated intervention for endometriosis treatment and identify GBP2 and HCK as novel druggable targets in endometriosis treatment. This study underscores AI's potential to accelerate the discovery of novel drug targets and facilitate the repurposing of treatment modalities for endometriosis.
TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques
Authors: Zhai Ming , Lei Zhijun , Shi Yefei , Shi Jiayun , Zeng Yanxi , Gong Shiyu , Jian Weixia , Zhuang Jianhui , Yu Qing , Feinberg Mark W. , Peng Wenhui
Published: December 2024

Atherosclerotic plaque rupture mainly contributes to acute coronary syndrome (ACS). Insufficient repair of these plaques leads to thrombosis and subsequent ACS. Central to this process is the modulation of vascular smooth muscle cells (VSMCs) phenotypes, emphasizing their pivotal role in atherosclerotic plaque stability and healing post‐disruption. Here, an expansion of FSP1+ cells in a tandem stenosis (TS) model of atherosclerotic mice is unveiled, predominantly originating from VSMCs through single‐cell RNA sequencing (scRNA‐seq) analyses and VSMC lineage tracing studies. Further investigation identified TEA domain transcription factor 1 (TEAD1) as the key transcription factor driving the trans‐differentiation of VSMCs into fibroblast‐like cells. In vivo experiments using a TS model of plaque rupture demonstrated that TEAD1 played a crucial role in promoting plaque stability and healing post‐rupture through pharmacological or TEAD1‐AAV treatments. Mechanistically, it is found that TEAD1 promoted the expression of fibroblast markers through the Wnt4/β‐Catenin pathway, facilitating the trans‐differentiation. Thus, this study illustrated that TEAD1 played a critical role in promoting the trans‐differentiation of VSMCs into fibroblast‐like cells and subsequent extracellular matrix production through the Wnt4/β‐Catenin pathway. Consequently, this process enhanced the healing mechanisms following plaque rupture, elucidating potential therapeutic avenues for managing atherosclerotic instability.
Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy
Authors: Wu Hangyi , Lu Xiaoyu , Hu Yuhan , Baatarbolat J. , Zhang Zhihao , Liang Yiping , Zhang Youwen , Liu Ye , Lv Huixia , Jin Xin
Published: December 2024

Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and disrupt intracellular Cu homeostasis. Extra intracellular Cu induces cuproptosis and chemodynamic therapy (CDT), which further cascades immunogenic cell death (ICD) and activates antitumor immune responses. However, the tumor immunosuppressive microenvironment (TIM) attenuates the efficiency of the immune response. Herein, a biomimic nanodrug (ECNM) is fabricated, of which ES, Cu2+ and NLG919 (an IDO1 inhibitor) are integrated via a self‐assembly process and subsequently coated with 4T1 cell membrane. ECNM can overcome the typical drawbacks of ES, ameliorating the stability and half‐life of ES by membrane‐coating and enhancing its tumor accumulation and internalization via homotypic targeting. It is worth mentioning that, the addition of NLG919 is also beneficial to the system circulation stability of ES and reduces the non‐specific ES release. After internalization, ECNM dissociates via the glutathione‐responsive process and exhibits comprehensive antitumor capabilities, including cuproptosis, CDT and TIM reversing, thereby eliciting ICD and optimizing the antitumor immune response. Furthermore, ECNM not only accelerates tumor regression but also gains a strong abscopal effect and displays the potential of tumor vaccination. Overall, ECNM can activate antitumor immunity via cuproptosis and CDT, together with TIM reversing, for cancer treatment.
Microglia Process α‐Synuclein Fibrils and Enhance their Pathogenicity in a TREM2‐Dependent Manner
Authors: Xiong Min , Xia Danhao , Yu Honglu , Meng Lanxia , Zhang Xingyu , Chen Jiehui , Tian Ye , Yuan Xin , Niu Xuan , Nie Shuke , Zhang Zhaohui , Liu Chaoyang , Chen Qiang , Ye Keqiang , Zhang Zhentao
Published: December 2024

Parkinson's disease (PD) is characterized by the deposition of misfolded α‐synuclein (α‐syn) in the brain. Converging evidence indicates that the intracellular transmission and subsequent templated amplification of α‐syn are involved in the onset and progression of PD. However, the molecular mechanisms underlying the cell‐to‐cell transmission of pathological α‐syn remain poorly understood. Microglia is highly activated in the brains of PD patients. Here, it is shown that depletion of microglia slows the spread of pathological α‐syn pathology in mice injected with α‐syn fibrils. Microglia phagocytose α‐syn fibrils and transform them into more toxic species. The phagocytosis of α‐syn fibrils by microglia is partially mediated by triggering a receptor expressed on myeloid cells 2 (TREM2), a transmembrane protein expressed on the surface of microglia. The endocytosed α‐syn fibrils are then cleaved by the lysosomal proteinase asparagine endopeptidase (AEP) to generate truncated α‐syn 1–103 fibrils with enhanced seeding activity. Knockout of TREM2 and AEP impedes the endocytosis and cleavage of α‐syn fibrils, respectively. The results demonstrate that TREM2‐mediated phagocytosis of α‐syn fibrils by microglia and subsequent AEP‐mediated cleavage of α‐syn fibrils contribute to the spread of α‐syn in the brain. Blocking either of these two steps attenuates the progression of α‐syn pathology.
Giant Nonlinear Hall Effect Induced Ultrahigh Rectification in a Weyl Semiconductor
Authors: Liu Hao , Lim Ting Yong , Tian Shijia , Zhai Jinfeng , Xiang Du , Liu Tao , Chang Tay‐Rong , He Pan , Shen Jian
Published: December 2024

Conventional diode‐based rectifiers suffer from limited applicability in low‐power electronics and high‐frequency wireless networks due to their inherent junction structures. Recent studies have demonstrated that the nonlinear Hall effect (NHE) in non‐centrosymmetric quantum materials can enable diode‐free rectification with advantages such as large active area, low power threshold, and high cutoff frequency. Here, a giant NHE is reported in a chiral semiconductor hosting Weyl nodes, achieving a voltage responsivity of up to 1.4×107 V W−1 at low temperature and 1.7×106 V W−1 at room temperature. This represents orders of magnitude improvement over existing NHE rectifiers and commercial Schottky diodes. This ultrahigh rectification is attributed to the significant contributions of Weyl nodes at the conduction band edge. Moreover, the device exhibits remarkable tunability through electrostatic gate voltages. The findings establish Weyl semiconductors as a promising platform for developing highly sensitive NHE rectifiers for low‐power and high‐frequency applications.
Sc(OTf)3‐Catalyzed Tunable Thio‐(3+3) Annulation Reactions of Indoline‐2‐thiones with α‐Benzylidene‐β‐tetralones
Authors: Jiang Yan , Ma Hao‐Jie , Zhai Chen‐Ying , Wang Xue‐Long , Yang Yi
Published: December 2024

A Sc(OTf)3‐catalyzed tunable thio‐Michael addition/nucleophilic addition/dehydration reaction of indoline‐2‐thiones with α‐benzylidene‐β‐tetralones was realized, leading to biologically important tetrahydrobenzo[7,8]isothiochromeno[3,4‐b]indoles and thiazino[3,2‐a]indoles in moderate to good yields. Moreover, by extending the reaction time, the dehydrogenated cycloadducts dihydrobenzo[7,8]isothiochromeno[3,4‐b]indoles were also obtained from the reaction of indoline‐2‐thiones with α‐benzylidene‐β‐tetralones.
Group 8 Organometallic Photochromic Compounds: Strategies and Applications
Authors: Bag Sayan Kumar , Ghosh Swapnamoy , Roy Subha , Jana Subhendu , Thakur Arunabha
Published: December 2024

Stimuli‐responsive photochromic units have emerged as one of the key components in the development of multi‐responsive switches, optoelectronics, biomedical sciences and many more. The photoswitchability of such compounds depends greatly on the molecular structure, where association of metallic species is found to produce fascinating results. This review is a comprehensive report of all such photoswitchable metal‐bounded molecules with group 8 metals within a span of last six years (2018‐2024). Apart from the regular photoswitching phenomenon, this review focusses on the enhanced tunability, structural flexibility and perturbation in the photophysical properties of the group 8 metal‐based photoswitches. Previous reviews in this field have either focused on some specific applications or have been general with the type of metal incorporations. Herein, we have constructed the review with group 8 organometallic photochromic compounds that possess a wide range of real‐life applications. Designing strategies, structure‐property relationships and application‐oriented approach of the photochromic organometallic compounds have been elucidated categorically for building up a comprehensive idea about this modern developing field of research.
Redox‐Active Triphenylamine‐Triazine Covalent Organic Framework: A High Surface Area Microporous Material for Electrochromism and Electrofluorochromism
Authors: Nandre Bhushan Kishor , Halder Sayan , Chakraborty Chanchal
Published: December 2024

Porous covalent organic frameworks (COFs) offer significant advantages in electrochromic (EC) applications due to their high surface area and porosity, which facilitate faradaic redox‐mediated diffusion‐controlled processes. However, COFs remain underexplored as EC materials due to challenges such as limited solubility and poor film‐forming ability. In this study, we synthesized a redox‐active triphenylamine‐containing COF (TPA‐TCIF) on ITO glass via a solvothermal method tailored for electrochromism and electrofluorochromism. The COF, formed through the condensation of tris(4‐formyl phenyl)amine and 2,4,6‐tris‐(4‐aminophenyl)‐1,3,5‐triazine, features a high surface area of 1136.8 m2/g and a pore diameter of 1.18 nm. This structure promotes efficient ion transport, reducing switching times and enhancing coloration efficiency (CE). Reversible redox reactions induce a color change from yellow to red, with an optical contrast (ΔT) of 37 % and a CE of 47.7 cm2/C. The film exhibited stable electrofluorochromic (EFC) behavior, switching from yellow emissive to dark black upon voltage application, with stability over 40 cycles. A quasi‐solid‐state electrochromic device (ECD) based on TPA‐TCIF demonstrated reversible color transitions, showcasing its potential for future display technologies and highlighting the promise of COFs in advanced EC applications.
Phagocytosis by the retinal pigment epithelium: New insights into polarized cell mechanics
Authors: Zihni Ceniz
Published: December 2024

The retinal pigment epithelium (RPE) is a specialized epithelium at the back of the eye that carries out a variety of functions essential for visual health. Recent studies have advanced our molecular understanding of one of the major functions of the RPE; phagocytosis of spent photoreceptor outer segments (POS). Notably, a mechanical link, formed between apical integrins bound to extracellular POS and the intracellular actomyosin cytoskeleton, is proposed to drive the internalization of POS. The process may involve a “nibbling” action, as an initial step, to sever outer segment tips. These insights have led us to hypothesize an “integrin adhesome‐like” network, atypically assembled at apical membrane RPE‐POS contacts. I propose that this hypothetical network orchestrates the complex membrane remodeling events required for particle internalization. Therefore, its analysis and characterization will likely lead to a more comprehensive understanding of the molecular mechanisms that control POS phagocytosis.
Overexpression of the Global Transcriptional Regulator LaeA Leads to Production of Cyclic Lipopeptides in Marine‐Derived Aspergillus niger L14
Authors: Zhou Wenjuan , Li Mengshi , Wang Wei , Bai Xuelian , Zhang Huawei
Published: December 2024

Overexpression of a global transcriptional regulator LaeA was performed to awaken cryptic biosynthetic gene clusters (BGCs) in a marine sponge‐derived fungus, Aspergillus niger L14, to obtain secondary metabolites (SMs), and resulted in the production of five previously undiscovered SMs in the wild‐type strain, including three cyclic lipopeptides aspochracin (1), JBIR‐15 (2) sclerotiotide C (3), kojic acid (4) and penicillic acid (5). Bioassays revealed that compound 2 displayed promising antimicrobial effects on Candida albicans with a minimum inhibitory concentration value of 32 µg/mL and 4 exhibited significant antioxidant activity with a similar half‐maximal inhibitory concentration value (5 µg/mL) to that of ascorbic acid. Transcriptome analysis results indicated that the overexpression of LaeA in strain L14 remarkably enhanced the expression of genes involved in polyketide synthase–non‐ribosomal peptide synthetase hybrids and amino acid metabolism, demonstrating an effective approach for the production of cyclic lipopeptides.
Extracellular fluid volume as a key indicator in home‐care management of chronic heart failure: The role of nutritional and exercise therapy
Authors: Shida Junko , Watanabe Ryosuke , Kazama Itsuro , Wanezaki Masahiro , Misawa Hiromi , Uno Chisaki , Matsuda Yumi
Published: December 2024

Key Clinical Message

Extracellular fluid volume, rather than body weight, should guide chronic heart failure management in home‐care patients. Enhancing muscle mass through pharmacotherapy, nutrition, and exercise is essential to prevent heart failure exacerbation.
New Concept on the Generation and Regulation of Circularly Polarized Luminescence
Authors: Zhang Gong , Zhang Wei
Published: December 2024

Circularly polarized luminescence (CPL) has attracted tremendous attention because of its significant application prospect across multiple fields of three‐dimensional display, data storage, and information encryption. Chirality and luminescence are two necessary prerequisites for the generation of CPL. However, controlling these two factors simultaneously in a rational manner remains a challenge. Herein, we highlight the recent advances on the rational generation and regulation of CPL through the new concept, named matching rules, mainly including fluorescence‐selective absorption, circularly polarized fluorescence energy transfer, and chiral communication between excited state and ground state. An important commonality among these strategies is that they need a good overlap of the corresponding spectra between the luminescent part (fluorescence, phosphorescence, or CPL) and the chiral part (organic, inorganic, or organic‐inorganic hybrid materials), which can be contactless and separate. Different from most previous studies, no covalent or noncovalent interactions between the two parts are required, which makes them more facile and convenient. Finally, we summarize the main advantages of these strategies and the current challenges. We expect this concept to offer insightful and novel understanding and inspiration on CPL generation and regulation.
Rationale and Design of a Study to Assess the Engagement and Usefulness of the Care4Today Connect Digital Health Application for Disease Management in Coronary Artery Disease and Peripheral Artery Disease (iPACE‐CVD Study)
Authors: Lakkireddy Dhanunjaya , Angiolillo Dominick J. , Charlton‐Ouw Kristofer , Jefferson Brian , Peeran Syed , Bisharat Mohannad , Ortega‐Paz Luis , Harxhi Ante , Kaul Simrati , Michaud Evelyne , Juan Stephanie , Woods Breeana , Damaraju CV , Fontana Gregory , Bonaca Marc P.
Published: December 2024

Introduction

Coronary artery disease (CAD) and peripheral artery disease (PAD) increase the risks of cardiovascular events and death. Digital health technologies are rapidly expanding to improve healthcare quality and access. The Care4Today Connect (C4T CAD‐PAD) mobile application is designed to help patients with CAD and/or PAD improve medication adherence, learn about their disease, make lifestyle modifications, and enhance healthcare provider (HCP) connection via an HCP‐facing portal.

Hypothesis & Methods

The prospective, single‐arm, multicenter, noninterventional iPACE‐CVD (innovative Patient compAnion impaCting health outcomEs: a CardioVascular Digital health program) study (ClinicalTrials.gov identifier: NCT06052319) is evaluating engagement and usefulness of the application for patients with CAD and/or PAD in clinical settings. Application access is provided with a code from patients' HCPs. Key features include medication and health experience tracking. The application is available in English and Spanish and for iOS and Android devices. Engagement is defined as the proportion of patients who use the application for ≥ 10 weeks during the 3‐month study period. Application use is defined as the number of patients using ≥ 1 application feature(s) each week. Usefulness is determined by the percentage of engaged patients who complete the My Feedback Matters survey with a satisfaction response score of > 2 (on a 5‐point scale, where 1 = strongly disagree and 5 = strongly agree) for at least three of the six questions.

Results

A total of 271 participants were enrolled between November 29, 2023, and May 15, 2024. The study concluded on August 15, 2024.

Conclusion

This study will help enhance the application for subsequent studies. Trial Registration: NCT06052319
On the usefulness of genomic selection for rice ratoon performance in early breeding stages
Authors: Borges Karina Lima Reis , Montiel Maria Guadalupe , Cerioli Tommaso , Angira Brijesh , Famoso Adam , Fritsche‐Neto Roberto
Published: December 2024

Rice (Oryza sativa L.) ratooning, a sustainable production system involves regrowing a second rice crop and it is a very common practice in southwest United States. Employing modern tools such as genomic selection (GS) can enhance breeding efficiency by enabling early selection. The Louisiana State University Rice Breeding Program has traditionally focused on developing superior varieties for the Louisiana's rice industry, however ratoon (RT) performance has typically been considered only in the late breeding stages, when there is little genetic variability available, and all the previous selections were made based on other qualitative and quantitative traits. Therefore, we aimed to verify if our pipeline for variety development is efficient in simultaneously selecting top grain yield performance lines for both harvest seasons: the main crop (H1) and the RT. In this context, we tested the following approaches: 1) Selection index, 2) Indirect selection, and 3) GS. Grain yield data evaluated over three years and three locations from the MP6‐8 population was used in this study. The results highlighted the genetic potential to be explored and the reliability of the data quality. Despite the low phenotypic and genotypic correlations between the first and second harvests (0.11 and 0.12, respectively), the plant response indices proved inefficient for dual‐season selection. Consequently, genotype ranking changed between harvest seasons, suggesting their relative independence. In simpler terms, the genotype that yields the highest productivity for H1 may not necessarily be the same for RT. Our study highlights the feasibility of using GS tools to perform early selections for RT and underscores it as a target trait in the breeding decision‐making process.
Dual Activation‐Induced Marker Combinations Efficiently Identify and Discern Antigen‐Specific and Bystander‐Activated Human CD4+ T Cells
Authors: Ceraolo Maria Grazia , Leccese Maristella , Cassotta Antonino , Triolo Sara , Bombaci Mauro , Coluccio Elena , Prati Daniele , Ungaro Riccardo , Abrignani Sergio , Bandera Alessandra , Sallusto Federica , Lanzavecchia Antonio , Notarbartolo Samuele
Published: December 2024

Identifying activated T lymphocytes and differentiating antigen‐specific from bystander T cells is crucial for understanding adaptive immune responses. This study investigates the efficacy of activation‐induced markers (AIMs) in distinguishing these cell populations. We measured the expression of commonly used AIMs (CD25, CD38, CD40L, CD69, CD137, HLA‐DR, ICOS, and OX40) in an in vitro T‐cell activation system and evaluated their sensitivity, specificity, and positive predictive value.

We demonstrated that individual AIMs, while specific in detecting activated CD4+ T cells, poorly discriminate between antigen‐specific and bystander activation, as assessed by a discriminative capacity (DC) score we developed. Our analysis revealed that dual AIM combinations significantly enhanced the ability to distinguish antigen‐specific from bystander‐activated T cells, achieving DC scores above 90%. These combinations also improved positive predictive value and specificity with a modest reduction in sensitivity. The CD25hi/ICOShi combination emerged as the most efficient, with an average sensitivity of 84.35%, specificity of 99.7%, and DC score of 90.12%. Validation through T‐cell cloning and antigen re‐stimulation confirmed the robustness of our predictions.

This study provides a practical framework for researchers to optimize strategies for identifying and isolating antigen‐specific human CD4+ T lymphocytes and studying their phenotype, function, and T‐cell receptor repertoire.
Real‐Time Energy Management Strategy for Fuel Cell/Battery Plug‐In Hybrid Electric Buses Based on Deep Reinforcement Learning and State of Charge Descent Curve Trajectory Control
Authors: Lian Jing , Li Deyao , Li Linhui
Published: December 2024

In order to reduce the energy consumption of fuel cell/battery plug‐in hybrid electric buses and prolong the service life of fuel cell and power battery, this article proposes a multiobjective real‐time energy management strategy (EMS) based on deep reinforcement learning and state of charge (SOC) descent curve trajectory control. First, the demand curve based on power is derived from the operational data collected from a bus in Dalian, and a set of SOC reference decline curves based on mileage is formulated. Second, a multiobjective cost function is constructed to consider hydrogen consumption cost, power consumption cost, fuel cell lifespan, and power battery lifespan. Finally, a comprehensive dynamic decision Q network (CDDQN) framework based on double deep Q network (DDQN) is established, a series of deep reinforcement learning EMS that integrate CDDQN with SOC trajectory control are designed, and they are validated through experimental analysis. The results demonstrate that this strategy exhibits excellent real‐time performance and economic efficiency. Compared with the comparison algorithms rule algorithm, equivalent consumption minimization strategy, finite‐step dynamic programming (DP), and DDQN proposed herein, the economy is increased by 15.08, 13.48, 8.81, and 3.07%, respectively, and reaches 94.00% of the economy of the ideal optimal solution DP.
Experimental Investigation on the Seismic Behavior of RC Double‐Column Medium‐Height Bents Retrofitted With SCEB‐Us
Authors: Dong Huihui , Hu Xiao , Bi Kaiming , Han Qiang , Entezami Alireza , Du Xiuli
Published: December 2024

Two columns of RC double‐column medium‐height bents (DCMBs) are normally connected by link beams to enhance the lateral stability. Serious damage and/or large residual displacement were repeatedly observed in the DCMBs after major earthquakes, which may make the bridges lose traffic functionality or even be demolished and rebuilt. To enhance the seismic performance of bridge structures with DCMB with link beams, the self‐centering energy dissipation braces (SCEBs) were applied to the DCMB in the “K”‐shaped arrangement scenario to replace the traditional link beams in this study. To this end, the design philosophies of the SCEBs in the DCMB were first developed based on the configuration and force analysis of the DCMB with SCEBs. Then, 1:4 scaled RC DCMB and DCMB with link beams specimens were designed. Based on the design philosophies and the hysteretic performance of the DCMB, a novel SCEB with U‐shaped steel plates (SCEB‐U) was developed and tested, and the test results showed that the SCEB‐U exhibited a typical flag‐shaped hysteretic behavior with great deformation capacity. Subsequently, the quasi‐static cyclic loading test of the DCMB with SCEBs specimen was carried out, and a DCMB with link beams and a DCMB with energy dissipation braces (EDBs) with U‐shaped steel plates (DCMB with EDB‐Us) were also tested for comparison. The experimental results showed that the DCMBs with braces suffered the least damage compared with the DCMB with link beams, and there was no obvious damage in the column‐brace connection regions. The DCMB with SCEB‐Us exhibited excellent flag‐type hysteresis behavior with large carrying capacity, stable energy dissipation, and satisfactory self‐centering ability.
Field EPSPs of Dentate Gyrus Granule Cells Studied by Selective Optogenetic Activation of Hilar Mossy Cells in Hippocampal Slices
Authors: Bernstein Hannah L. , Lu Yi‐Ling , Botterill Justin J. , Duffy Áine M. , LaFrancois John J. , Scharfman Helen E.
Published: December 2024

Glutamatergic dentate gyrus (DG) mossy cells (MCs) innervate the primary DG cell type, granule cells (GCs). Numerous MC synapses are on GC proximal dendrites in the inner molecular layer (IML). However, field recordings of the GC excitatory postsynaptic potential (fEPSPs) have not been used to study this pathway selectively. Here we describe methods to selectively activate MC axons in the IML using mice with Cre recombinase expressed in MCs. Slices were made after injecting adeno‐associated virus (AAV) encoding channelrhodopsin (ChR2) in the DG. In these slices, we show that fEPSPs could be recorded reliably in the IML in response to optogenetic stimulation of MC axons. Furthermore, fEPSPs were widespread across the septotemporal axis. However, fEPSPs were relatively weak because they were small in amplitude and did not elicit a significant population spike in GCs. They also showed little paired pulse facilitation. We confirmed the extracellular findings with patch clamp recordings of GCs despite different recording chambers and other differences in methods. Together the results provide a simple method for studying MC activation of GCs and add to the evidence that this input is normally weak but widespread across the GC population.
Behavioural Interventions for Problematic Infant Sleeping and Cry/Fuss Behaviour: A Systematic Review and Meta‐Analyses
Authors: Stanzel Karin , Honda Tomoko , Tran Thach , Fisher Jane
Published: December 2024

This systematic review and meta‐analyses aim to synthesise evidence about behavioural interventions to address dysregulated sleeping and cry/fuss behaviour in infants aged up to 12 months and the effects on infant behaviour and maternal mental health. A systematic literature search of English‐language publications was performed in November 2020 and updated in May 2023 using Medline, Embase, PsychInfo and Cinahl Plus. Twenty‐two papers reporting twenty studies met inclusion criteria of these sixteen papers reported both maternal and infant outcomes. Although, there is heterogeneity of the investigations, their results are broadly consistent. Parents who attended a behavioural intervention program for unsettled behaviours in infants reported improvement of their mental health and parenting confidence, and unsettled infant behaviours were improved including a reduction of night waking and cry/fuss behaviour. This review and meta‐analyse provides evidence that behavioural interventions show a mild to moderate improvement in unsettled infant behaviour and maternal mental health.
Validating social reinforcer classes for low‐severity challenging behavior identified by sensitivity tests
Authors: Melanson Isaac J. , Fahmie Tara A. , Ferris Emily L. , Rahaman Javid A.
Published: December 2024

Behavior analysts typically assess and treat challenging behavior after it occurs regularly and at high severity. Although effective, this reactive approach is quite costly and resource intensive. A growing literature supports an alternative preventive approach; the first step involves conducting sensitivity tests to screen the topographies and functions of low‐severity behavior evoked by establishing operations commonly included in challenging behavior research (e.g., Fahmie et al., 2020). Despite the potential value of sensitivity tests, their correspondence with functional analyses has yet to be established. This study measured the correspondence between social reinforcer classes nominated by sensitivity tests and social reinforcer classes verified by traditional functional analysis outcomes of the same behaviors. Participants included 10 young autistic learners who were reported to exhibit low‐severity challenging behavior. Data showed generally high correspondence between both assessment outcomes for challenging behavior but not for appropriate requests.
The β‐Chain Mutation p.Arg17Stop Impairs Fibrinogen Synthesis and Secretion: A Nonsense Mutation Associated With Hypofibrinogenemia
Authors: Qian Chen , Huang Chaoyu , Luo Qinghui , Qin Kaili , Wu Yangyang , Liao Lin , Zhang Qian , Xiang Liqun , Yan Jie
Published: December 2024

Background

Congenital hypofibrinogenemia, a quantitative fibrinogen disorder, is characterized by abnormally low levels of both functional and antigen fibrinogen. We identified a heterozygous nonsense mutation, p.Arg17Stop, in the fibrinogen Bβ chain of a three‐month‐old female infant.

Methods

Coagulation testing, gene analysis, in vitro plasmid construction, and functional analyses were conducted to investigate the underlying pathogenic mechanisms.

Results

Plasma fibrinogen levels showed decrease in the proband. DNA sequencing of the proband revealed a heterozygous point mutation (c.139C>T) in exon 2 of the FGB gene causing Arg → Stop substitution. Human Arg17 was found to be highly conserved. In vitro expression analyses indicated that the mutation impacts both the transcription and translation of the FGB gene, subsequently affecting the synthesis and secretion of fibrinogen.

Conclusions

The p.Arg17Stop mutation in the fibrinogen Bβ chain disrupts fibrinogen production and secretion, contributing to hypofibrinogenemia.
Characterization of Spirulina‐derived extracellular vesicles and their potential as a vaccine adjuvant
Authors: Sharifpour Mohammad Farouq , Sikder Suchandan , Wong Yide , Koifman Na'ama , Thomas Tamara , Courtney Robert , Seymour Jamie , Loukas Alex
Published: December 2024

Spirulina is an edible cyanobacterium that increasingly gaining recognition for it untapped potential in the biomanufacturing of pharmaceuticals. Despite the rapidly accumulating information on extracellular vesicles (EVs) from most other bacteria, nothing is known about Spirulina extracellular vesicles (SPEVs). This study reports the successful isolation, characterization and visualization of SPEVs for the first time and it further investigates the potential therapeutic benefits of SPEVs using a mouse model. SPEVs were isolated using ultracentrifugation and size‐exclusion‐chromatography. Cryo‐Transmission Electron Microscopy revealed pleomorphic outer‐membrane‐vesicles and outer‐inner‐membrane‐vesicles displaying diverse shapes, sizes and corona densities. To assess short‐ and long‐term immune responses, mice were injected intraperitoneally with SPEVs, which demonstrated a significant increase in neutrophils and M1 macrophages at the injection site, indicating a pro‐inflammatory effect induced by SPEVs without clinical signs of toxicity or hypersensitivity. Furthermore, SPEVs demonstrated potent adjuvanticity by enhancing antigen‐specific IgG responses in mice by over 100‐fold compared to an unadjuvanted model vaccine antigen. Mass‐spectrometry identified 54 proteins within SPEVs, including three protein superfamily members linked to the observed pro‐inflammatory effects. Our findings highlight the potential of SPEVs as a new class of vaccine adjuvant and warrant additional studies to further characterize the nature of the immune response.
Health‐related quality of life determinants in Spanish children with eosinophilic esophagitis
Authors: García‐Martínez de Bartolomé Ruth , Barrio‐Torres Josefa , Sebastián‐Viana Tomás , Vila‐Miravet Víctor , La Orden‐Izquierdo Enrique , Fernández‐Fernández Sonia , Herrero‐Álvarez Myriam , Soria‐López Marta , Botija‐Arcos Gonzalo , Rodríguez‐Martínez Alejandro , Galicia‐Poblet Gonzalo , García‐Díaz Alejandro , Herreros‐Sáenz Marta , Blasco‐Alonso Javier , Rodrigo‐García Gloria , Alonso‐Pérez Natalia , de Valderrama‐Rodríguez Ana Fernández , Oppenau‐López Noel , Pérez‐Moneo Begoña , Feo‐Ortega Sara , Vecino‐López Raquel , Donado‐Palencia Paloma , Alberto‐Alonso José Ramón , Revenga‐Parra Margarita , Lorenzo‐Garrido Helena , Carro‐Rodríguez Miguel Ángel , Grande‐Herrero Luis , Vicente‐Santamaría Saioa , Balmaseda‐Serrano Elena , Miranda‐Cid María Carmen , Martín‐González Jessica , García‐Romero Ruth , García‐Tirado Diana , Rizo‐Pascual Jana , Alonso‐López Pedro , Blanco‐Rodríguez Miriam , Rendo‐Vázquez Alicia , Millán‐Jiménez Antonio , Castro‐Millán Ana , Bastida‐Ratera Eduard , Cilleruelo‐Pascual M. Luz
Published: December 2024

Objectives

To study the health‐related quality of life (HRQoL) and its possible determinant factors in Spanish children with eosinophilic esophagitis (EoE) and their parents.

Methods

Multicenter observational cross‐sectional study. The Spanish version of the Pediatric Quality of Life Eosinophilic Esophagitis Module was filled out by EoE patients aged 8–18 and their parents. Demographic, psychosocial, and clinical variables were studied. Multiple linear regression was performed to identify related factors of HRQoL.

Results

A total of 279 children and their parents participated (72.7% males). 39.1% received swallowed corticosteroids, 35.5% proton pump inhibitors and 16.8% diet. 1.1% received other treatments and 7.5% received no treatment. Poor compliance to treatment was observed in 11.5% and 6.5% of patients were referred to mental health.

The Total Scale Scores were 72.71 ± 17.50 and 75.62 ± 16.73 for children and parents, respectively. “Communication” was the dimension with the highest scores (82.14 ± 21.65 and 81.59 ± 24.13) while “Food and Eating” (48.92 ± 32.94 and 62.85 ± 28.78), and “Food Feelings” (53.55 ± 29.96 and 53.95 ± 27.78) had the lower scores. Patients and parents under dietary treatment showed lower scores than those under pharmacological treatment, 65.77 ± 16.96 versus 74.28 ± 16.96, p = 0.001 and 68.33 ± 17.32 versus 77.24 ± 15.97, p = 0.001, respectively. Factors associated with worse HRQoL scores were symptom frequency, diet, food allergies, and the need for mental health assistance.

Conclusions

The HRQoL of children and their parents was “good.” However, diet, frequency of symptoms, food allergies, and the need for mental health care were the factors that had a negative impact on HRQoL of children with EoE.
Designing a Heteroleptic Tetrahedral Group with an Ultrahigh Polarizability Anisotropy by Optimizing the Bonding Electrons Activity and Their Distribution
Authors: Sha Hongyuan , Yang Dongling , Li Qinghe , Yang Lilin , Wang Zujian , Su Rongbing , He Chao , Su Bin , Yang Xiaoming , Long Xifa
Published: December 2024

In contrast to regular tetrahedral groups, which struggle to induce a sufficient birefringence to satisfy the phase‐matching condition, heteroleptic tetrahedral ones with higher polarizability anisotropy are perfect functional building units for short‐wave UV nonlinear optical crystals. However, the intrinsic origin of their properties remains unclear. Here, the high polarizability anisotropy in groups is deconstructed to the large anisotropy of numerical density and confined force of the electron, which corresponds to the optimization of bonding electrons activity and their distribution in the tetrahedral group. It can be perfectly achieved in heteroleptic tetrahedral groups. Then, an elegant hetero‐two‐site heteroleptic tetrahedral group, [SO2NH2Cl], with a high polarizability anisotropy is found, which is inducive to generate a large optical anisotropy as confirmed by the experimental birefringence of 0.085 @ 546 nm and the excellent phase‐matching ability in SO2NH2Cl crystals. Therefore, this work illuminates a new horizon for the design of heteroleptic tetrahedron‐based short‐wave UV nonlinear optical materials.
Inhibition of Selenoprotein I promotes ferroptosis and reverses resistance to platinum chemotherapy by impairing Akt phosphorylation in ovarian cancer
Authors: Li Jing , Chen Mimi , Huang Dingwen , Li Ziyin , Chen Yu , Huang Jinhua , Chen Yuanqun , Zhou Zhili , Yu Zhiying
Published: December 2024

Ovarian cancer (OV) ranks among the deadliest gynecological cancer, known for its high risk of relapse and metastasis, and a general resistance to conventional platinum‐based chemotherapy. Selenoprotein I (SELENOI) is a crucial mediator implicated in human hereditary spastic paraplegia. However, its role in human tumors remains poorly elucidated. Here, we comprehensively analyzed SELENOI expression patterns, functions, and clinical implications across various malignancies through the integration of bulk transcriptomics, cancer databases, and in vitro and in vivo experiments. Pan‐cancer analysis indicated upregulated SELENOI expression across various cancers, correlating with augmented malignancy, suppressed tumor immunity and poor prognosis. Knockdown of SELENOI caused G0/G1‐phase cell cycle arrest and diminished aggressive cancer phenotypes in OV cells. Moreover, SELENOI inhibition augments ferroptosis and reverses the cisplatin resistance in OV cells by modulating Akt phosphorylation. Conversely, overexpression of SELENOI in OV cells enhanced therapeutic sensitivity to cisplatin by upregulating Akt phosphorylation. Importantly, in vivo studies demonstrated that SELENOI inhibition suppressed ovarian tumor growth and enhanced cisplatin's anticancer effects. These findings highlight the significant role of SELENOI in OV by modulating ferroptosis and chemotherapy resistance. Targeting SELENOI represents a promising therapeutic approach to promote the efficacy of platinum‐based chemotherapy in OV, particularly in cases of resistance.
Service Guarantee Decision of Online Service Providers and Market Implications
Authors: Lu Aijun , Chen Fuzan , Wu Harris
Published: December 2024

Online services face quality uncertainties. To address user concerns, Online Service Providers (OSPs) sometimes provide service guarantees, compensating users if quality falls below a predefined threshold. This paper analyzes how OSPs use service guarantees to navigate market competition and enhance revenue through game theory and queuing theory models. Key findings include the following: offering guarantees enable OSPs to increase prices; in monopolistic markets, guarantees are offered only if the service guarantee strength is sufficient, whereas in competitive markets, decisions depend on relative strengths and competitor actions. Surprisingly, slower response times under service guarantees can boost profits, especially when resource costs are high.