bluuebunny/crossref_metadata_2025 huggingface dataset:
A Molecular‐Targeting Photosensitizer to Inhibit DNA Damage Repair System and Induce cGAS‐STING Pathway Activation for Photo‐Immunotherapy of Ovarian Cancer
Authors: Fan Lianfeng , Zhang Peng , Gan Yuxuan , Li Ling , Wang Li , Wang Minjia , Liu Xianglong , Ma Jing , Liu Bin , Shi Leilei
Published: November 2024

Poly(ADP‐ribose) polymerase (PARP) inhibitors are commonly utilized in the clinical management of patients with platinum‐sensitive recurrent and late‐stage ovarian cancer, which constitutes a significant proportion of gynecological cancer‐related mortality. Nonetheless, the constraints of their monofunctional properties and limited therapeutic efficacy observed in advanced cancer cases necessitate the exploration of more potent therapeutic strategies for the management of ovarian cancer. The present study describes the development of QTABI, a PARP‐targeting photosensitizer capable of producing reactive oxygen species with light irradiation. Simultaneously, it exhibits significant inhibition of PARP activity, induction of deoxyribonucleic acid (DNA) damage, and consequent synthetic lethality. Furthermore, QTABI can effectively promote the accumulation of cytosolic DNA and activate the cyclicGMP‐AMP synthase (cGAS)‐stimulator of interferon gene (STING) pathway under light irradiation, thereby eliciting potent anti‐tumor immune responses and ultimately boosting anti‐cancer efficacy. Collectively, these findings suggest that QTABI is a multi‐functional photosensitizer, which targets the DNA‐damaging repair system and activates the cGAS‐STING pathway, offering a promising combination photo‐immunotherapy strategy for treating ovarian cancer.
Antitumor Activity of a Bispecific Chimera Targeting EGFR and Met in Gefitinib‐Resistant Non‐Small Cell Lung Cancer
Authors: Wang Ya , Zhang Guixi , Zhou Zhilan , Zhang Ning , Jiang Hang , Liu Yichang , Fu Ting , Zhu Yingdi , Li Juan
Published: November 2024

Non‐small cell lung cancers (NSCLC) frequently acquire resistance to tyrosine kinase inhibitors (TKI) due to epidermal growth factor receptor (EGFR) mutation or activation of the bypass pathway involving mesenchymal‐epithelial transition factor (Met). To address this challenge, a bispecific nanobody‐aptamer chimera is designed to target mutated EGFR and Met simultaneously to block their cross‐talk in NSCLC. The EGFR‐Met chimera is cost‐effectively engineered using microbial transglutaminase and click chemistry strategies. With enhanced binding affinity toward the target proteins, the as‐developed chimera inhibits efficiently the cross‐talk between signaling pathways associated with EGFR and Met. This inhibition leads to the suppression of downstream pathways, such as Erk and Akt, and induces upregulation of cell cycle arrest‐related proteins, including Rb, p21, and p27. Additionally, the chimera activates the caspase‐dependent apoptotic signaling pathway. Consequently, it inhibits cell migration, induces cell death, and causes cell cycle arrest in vitro. Moreover, the chimera exhibits significant antitumor efficacy in drug‐resistant xenograft mouse models, showcasing improved tissue penetration and low toxicity. This study accentuates the potential of the bispecific EGFR‐Met chimera as a promising therapeutic option for NSCLC resistant to EGFR TKIs.
How the Versatile Self‐Assembly in Drug Delivery System to Afford Multimodal Cancer Therapy?
Authors: Cao Yuqi , Zhao Xiaomin , Miao Yuhang , Wang Xin , Deng Dawei
Published: November 2024

The rapid development of self‐assembly technology during the past few decades has effectively addressed plenty of the issues associated with carrier‐based drug delivery systems, such as low loading efficiency, complex fabrication processes, and inherent toxicity of carriers. The integration of nanoscale delivery systems with self‐assembly techniques has enabled efficient and targeted self‐administration of drugs, enhanced bioavailability, prolonged circulation time, and controllable drug release. Concurrently, the limitations of single‐mode cancer treatment, including low bioavailability, poor therapeutic outcomes, and significant side effects, have highlighted the urgent need for multimodal combined antitumor therapies. Set against the backdrop of multimodal cancer therapy, this review summarizes the research progress and applications of a large number of self‐assembled drug delivery platforms, including natural small molecule self‐assembled, carrier‐free self‐assembled, amphiphilic polymer‐based self‐assembled, peptide‐based self‐assembled, and metal‐based self‐assembled nano drug delivery systems. This review particularly analyzes the latest advances in the application of self‐assembled nano drug delivery platforms in combined antitumor therapies mediated by chemotherapy, phototherapy, radiotherapy, sonodynamic therapy, and immunotherapy, providing innovative research insights for further optimization and expansion of self‐assembled nano drug delivery systems in the clinical translation and development of antitumor combined therapy.
Sustainable Lithography Paradigm Enabled by Mechanically Peelable Resists
Authors: Chen Lei , Liang Huikang , Liu Peng , Liu Cuihong , Feng Bo , Shu Zhiwen , Chen Yiqin , Dong Xiaoqian , Xie Jianfei , Ji Ming , Duan Huigao
Published: November 2024

Lithography is critical in micro‐ and nanofabrication processes, enabling the development of integrated circuits, semiconductor devices, and various advanced electronic and photonic systems. However, there are challenges related to sustainability, efficiency, and yield, as well as compatibility with transient electronics. This work introduces a sustainable lithography paradigm employing mechanically peelable resists compatible with existing cleanroom processes. The resists exhibit near‐zero adhesion to various substrates, facilitating efficient, cost‐effective, environmentally friendly, and chemical‐free mechanical stripping without observable particulate residues. The mechanical lift‐off process enables scalable and 100%‐yield pattern transfer using commercially available tape within seconds. Furthermore, the new paradigm supports distributed and in situ conformal manufacturing using the peelable resist as a “transferable stencil mask” to fabricate various functional devices on flexible and nonplanar surfaces, as well as ultra‐thin biodegradable substrates. Overall, this work expands the potential for using lift‐off as a standard process in the pan‐semiconductor industry and opens new avenues for lithographic procedures aimed at the reliable mass production of transient electronics and integrated biodegradable devices, addressing growing sustainability issues caused by electronic waste.
Joule‐Heated Interfacial Catalysis for Advanced Electrified Esterification with High Conversion and Energy Efficiency
Authors: Zhang Jifang , Zhang Xinyuan , Shen Yue , Fu Bo , Wu Yijin , Kang Jian , Chen Shan , Wang Guozhong , Zhang Haimin , Yin Huajie , Zhao Huijun
Published: November 2024

Esterification reactions are crucial in industries such as chemicals, fragrances, and pharmaceuticals but often face limitations due to high reversibility and low reactivity, leading to restricted yields. In this work, an electrified esterification pathway utilizing a Joule‐heated interfacial catalysis (JIC) system is proposed, where a hydrophilic, sulfonic acid‐functionalized covalent organic framework grown on carbon felt (COF─SO3H@CF) acts as the interfacial catalyst, and the carbon felt serves as the electric heat source. This approach achieves an acetic acid conversion of 80.5% at a heating power density of 0.49 W cm−3, without additional reagents by vaporizing reaction products, surpassing the theoretical equilibrium limit of 62.5% by 1.29 times. Comprehensive analysis indicates that the intimate contact between the electric heat source and the COF─SO3H catalyst enables efficient, localized Joule heating directly at catalytic sites, minimizing thermal losses and allowing precise control over reaction interfaces. This finding demonstrates that this JIC system not only enhances esterification efficiency but may also offer a sustainable, energy‐efficient pathway for high‐yield chemical processes.
A Building‐Integrated Hybrid Photovoltaic‐Thermal (PV‐T) Window for Synergistic Light Management, Electricity and Heat Generation
Authors: Polito Francesco , Huang Gan , Markides Christos N.
Published: November 2024

The installation of common solar panels and collectors in the built environment requires access to significant roof space, which is limited. This motivates the development of high‐efficiency, building‐integrated technologies that can maximize space utilization and energy provision. In this work, a building‐integrated hybrid photovoltaic‐thermal window (PVTW) is fabricated and tested, composed of a semi‐transparent photovoltaic (PV) layer and a selectively absorptive liquid‐based thermal absorber. It is demonstrated that, at 30° inclination, the PVTW can simultaneously generate electricity, with an electrical efficiency of 3.6%, and provide ≈50 °C water, with a thermal efficiency of 10.7%, in the middle of a typical summer day (20th July) in London (maximum ambient temperature ≈34 °C, solar irradiance ≈1100 W m−2 at midday). The water temperature decreases by ≈7 °C, whilst thermal efficiency improves to 17.6% as the inclination angle increases to 90° (vertical); the electrical efficiency reduces marginally (3.3%). Compared to a liquid‐based solar‐thermal window (STW), the PVTW can generate hot water at ≈10 °C higher temperature and with 10% absolute increase in thermal efficiency when the inclination angle is 60°, plus electricity. The wider uptake of this technology in glass‐based urban spaces has the potential to generate significant energy while reducing building temperature management costs.
A Purely Biomanufactured System for Delivering Nanoparticles and STING Agonists
Authors: Li Yu‐an , Feng Yi , Li Wenjing , Zhang Yuqin , Sun Yanni , Wang Shifeng , Curtiss Roy , Shi Huoying
Published: November 2024

Nanovaccines have significantly contributed in the prevention and treatment of diseases. However, most of these technologies rely on chemical or hybrid semibiological synthesis methods, which limit the manufacturing performance advantages and improved inoculation outcomes compared with traditional vaccines. Herein, a universal and purely biological nanovaccine system is reported. This system integrates three modules: (1) self‐assembling nanoparticles, (2) self‐catalyzed synthesis of small‐molecule stimulator of interferon gene (STING) agonists, and (3) delivery vectors that target the cytosolic surveillance system. Various nanoparticles are efficiently self‐assembled using this system. After confirming the excellent immunostimulatory and lymph node targeting of this system, its broad‐spectrum antiviral efficacy is further demonstrated. By leveraging the comprehensive biosynthetic capabilities of bacterial cells, this system can efficiently combine various adjuvant‐active modular components and antigenic cargo, thereby providing a highly diversified and potent vaccine platform.
Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment
Authors: Rui Min , Mao Jiannan , Wu Hongshuai , Hui Yujian , Shen Hao , Yang Yilin , Ma Tao , Ren Kewei , Wang Juan , Cui Wenguo , Shi Qin , Yang Huilin
Published: November 2024

Hypoxia and reactive oxygen species (ROS) overaccumulation cause persistent oxidative stress and impair intrinsic regenerative potential upon tissue injury. For local tissue injury with hypoxia, such as bone fracture and defects, a localized‐sufficient oxygen supply is highly desirable but remains challenging. Therefore, to explore a strategy and its intrinsic mechanism for supplying oxygen locally and remodeling the regenerative microenvironment, an innovative oxygenating hydrogel microsphere system with sustained oxygenation and antioxidant properties is introduced by loading CaO2@SiO2@PDA (CSP) nanoparticles. Specifically, the CSP nanoparticles exhibited broad‐spectrum free radicals scavenging ability, along with prolonged controlled‐release of oxygen once integrated into the gelatin methacrylate anhydride (GelMA) microspheres (CSP‐GM). The CSP‐GM with extra cellular matrix (ECM)‐mimicking structures reconstructed living niches, promoting the adhesion and proliferation of bone marrow stromal cells (BMSCs). As a multifaceted microenvironment regulator, CSP‐GM remodeled the regenerative microenvironment by synergistically producing oxygen and scavenging ROS, recovering mitochondrial homeostasis and antioxidant defenses of BMSCs, promoting angiogenesis and osteogenesis under hypoxia conditions via precisely modulating the Nrf2/HO‐1 signaling pathway. The multiple pro‐regenerative effects of the implantable functionalized micro‐oxygen reservoir on bone repair are further corroborated by the enhanced vascularized bone formation in rat femoral defects, presenting a comprehensive and promising strategy for tissue repair.
Metamaterial‐Enabled Hybrid Receive Coil for Enhanced Magnetic Resonance Imaging Capabilities
Authors: Zhu Xia , Wu Ke , Anderson Stephan W. , Zhang Xin
Published: November 2024

Magnetic resonance imaging (MRI) relies on high‐performance receive coils to achieve optimal signal‐to‐noise ratio (SNR), but conventional designs are often bulky and complex. Recent advancements in metamaterial technology have led to the development of metamaterial‐inspired receive coils that enhance imaging capabilities and offer design flexibility. However, these configurations typically face challenges related to reduced adaptability and increased physical footprint. This study introduces a hybrid receive coil design that integrates an array of capacitively‐loaded ring resonators directly onto the same plane as the coil, preserving its 2D layout without increasing its size. Both the coil and metamaterial are individually non‐resonant at the targeted Larmor frequency, but their mutual coupling induces a resonance shift, achieving a frequency match and forming a hybrid structure with enhanced SNR. Experimental validation on a 3.0 T MRI platform shows that this design allows for adjustable trade‐offs between peak SNR and penetration depth, making it adaptable for various clinical imaging scenarios.
Mechanical Activation of cPLA2 Impedes Fatty Acid β‐Oxidation in Vein Grafts
Authors: Fan Linwei , Tang Yuanjun , Liu Jian , Liu Yueqi , Xu Yiwei , Liu Jiayu , Liu Han , Pang Wei , Guo Yuxuan , Yao Weijuan , Zhang Tao , Peng Qin , Zhou Jing
Published: November 2024

High‐magnitude cyclic stretch from arterial blood pressure significantly contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMCs), leading to neointima formation in vein grafts. However, the molecular mechanisms remain unclear. This study highlights the critical role of cytosolic Phospholipase A2 (cPLA2)/ Yin Yang 1 (YY1)/ carnitine palmitoyltransferase 1b (CPT1B) signaling in coordinating VSMC mechanical activation by inhibiting fatty acid β‐oxidation. Metabolomic analysis showed that a 15%–1 Hz arterial cyclic stretch, compared to a 5%–1 Hz venous stretch, increased long‐chain fatty acids in VSMCs. cPLA2, identified as a mechanoresponsive molecule, produces excessive arachidonic acid (ArAc) under the 15%–1 Hz stretch, inhibiting CPT1B expression, a key enzyme in fatty acid β‐oxidation. ArAc promotes transcription factor YY1 degradation, downregulating CPT1B. Inadequate fatty acid oxidation caused by knockdown of CPT1B or YY1, or etomoxir treatment, increased nuclear membrane tension, orchestrating the activation of cPLA2. Overexpressing CPT1B or inhibiting cPLA2 reduced VSMC proliferation and migration in vein grafts, decreasing neointimal hyperplasia. This study uncovers a novel mechanism in lipid metabolic reprogramming in vein grafts, suggesting a new therapeutic target for vein graft hyperplasia.
Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies
Authors: Wan Hongping , Zhong Xinyi , Yang Shinong , Deng Jiarong , Song Xu , Liu Yong , Li Yuanfeng , Yin Zhongqiong , Zhao Xinghong
Published: November 2024

The rise of antibiotic resistance, coupled with a dwindling antibiotic pipeline, presents a significant threat to public health. Consequently, there is an urgent need for novel therapeutics targeting antibiotic‐resistant pathogens. Nisin, a promising peptide antibiotic, exhibits potent bactericidal activity through a mechanism distinct from that of clinically used antibiotics. However, its cationic nature leads to hemolysis and cytotoxicity, which has limited its clinical application. Here, nanodelivery systems have been developed by mimicking the mechanisms bacteriophages use to deliver their genomes to host bacteria. These systems utilize bacteriophage receptor‐binding proteins conjugated to loading modules, enabling efficient targeting of bacterial pathogens. Peptide antibiotics are loaded via dynamic covalent bonds, allowing for infection microenvironment‐responsive payload release. These nanodelivery systems demonstrate remarkable specificity against target pathogens and effectively localize to bacteria‐infected lungs in vivo. Notably, they significantly reduce the acute toxicity of nisin, rendering it suitable for intravenous administration. Additionally, these bacteriophage‐mimicking nanomedicines exhibit excellent therapeutic efficacy in a mouse model of MRSA‐induced pneumonia. The facile synthesis, potent antimicrobial performance, and favorable biocompatibility of these nanomedicines highlight their potential as alternative therapeutics for combating antibiotic‐resistant pathogens. This study underscores the effectiveness of bacteriophage mimicry as a strategy for transforming peptide antibiotics into viable therapeutics.
Modulating the Interactions of Peptide‐Polyphenol for Supramolecular Assembly Coatings with Controllable Kinetics and Multifunctionalities
Authors: Huo Kaiyuan , Liu Wenjie , Shou Zeyu , Wang Hongxiang , Liu Hao , Chen Yang , Zan Xingjie , Wang Qing , Li Na
Published: November 2024

Polyphenols and peptides represent two fundamental building blocks in the kingdom of supramolecular assembly (SA) coatings, which have recently attracted considerable interest. Regulating the assembly kinetics of SA coatings is critical to controlling the performance of SA coatings, but this area is still in its infancy, especially in the SA coating of peptide‐polyphenol. Herein, a library of oligopeptides with rich diversity, numerous polyphenols, and modulators are explored to reveal their roles in the formation and regulation of SA coating. Citric acid (CA) is an effective regulator of interaction between the polyphenols and peptides to produce peptide‐polyphenol coatings, TCP. The electrostatic interaction between tannic acid (TA) and cationic peptide drives the formation of TCP, while the multiple hydrogen bonds between CA and TA and peptide dominate the assembly kinetics. With optimized assembly pH and the mass ratio of TA, CA, and peptide, the thickness of TCP coating deposits onto diverse substrates (glass, silica, titanium, polystyrene) is ≈400 nm with controllable kinetics. The multifunctional TCP coatings are endowed via peptide‐coupled functional units, including enhanced cellular adhesion, elevated osteogenic capacity, anti‐protein adsorption, and antimicrobial. This work contributes to the understanding of the assembly kinetics and functionalization of peptide‐polyphenol coatings.
Boosting Li‐Metal Anode Performance with Lithiophilic Li–Zn Seeds in a 2D Reduced Graphene Oxide Scaffold
Authors: Zhou Xiaoze , Wang Shuaiqi , Li Yaru , Yang Yi , Xiao Xiao , Chen Gang
Published: November 2024

The substitution of conventional graphite with Li metal as an anode material has garnered significant interest due to its exceptionally high theoretical energy density. However, the direct application of Li metal as an anode in batteries faces formidable challenges, including dendrite growth and interphase instability. Herein, a high‐performance composite anode (LZ‐rGO) that integrates a reduced graphene oxide (rGO) scaffold with lithiophilic Li–Zn alloy nanoparticles is presented. The Li–Zn seeds embedded in the structure lower the initial nucleation barrier and facilitate uniform Li deposition. Furthermore, the rGO scaffold, possessing a large specific surface area, enables the LZ‐rGO anode to significantly reduce voltage hysteresis and prevents the deactivation of metallic Li during the plating/stripping processes. As a result, the symmetric cell demonstrates stability over 1200 h at a current density of 1 mA cm−2, with negligible voltage fluctuation. When paired with a LiFePO4 cathode, the full cell achieves stable cycling for 1000 cycles with a high‐capacity retention, demonstrating exceptional interface stability and cycling efficiency.
Boosting electrocatalytic alcohol oxidation: Efficient d–π interaction with modified TEMPO and bioinspired structure
Authors: Chen Ying , Wang Shibin , Xu Zaixiang , Wang Yuhang , He Jiahui , Li Kai , Wang Jieyu , Liu Lihao , Ren Linhan , Li Suiqin , Zhang Zhengbin , Zhong Xing , Wang Jianguo
Published: November 2024

Aminoxyl radicals electrocatalysis presents a sustainable method for oxidizing alcohols into high‐value products. Nonetheless, the requirement for high doses of aminoxyl radicals diminishes product purity and economic viability. This study synthesized methylimidazole‐functionalized 4‐acetylamino‐2,2,6,6‐tetramethylpiperidine‐N‐oxyl derivative (MIAcNH‐TEMPO) with a strongly electron‐withdrawing imidazole group and combined it with bioinspired nickel‐supported carbonaceous octopus tentacles for effective electrooxidation of alcohols, achieving high current density of 200 mA cm−2, selectivity of 99%, and turnover frequency of 26,490 h−1. In situ experiments and theoretical calculations indicated that the synergistic effect of Ni‐3dxz orbitals on the tentacle surface interacting with the π orbitals of MIAcNH‐TEMPO creates a strong d–π interaction, which effectively facilitating the creation of a locally intermediate‐enriched microenvironment, decreased the required quantity of aminoxyl radicals. Moreover, the high aqueous solubility of MIAcNH‐TEMPO reduces the difficulty of separation process. Scale‐up experiments conducted in a continuous flow electrolyzer showcased the potential of this strategy for practical applications.
Doping Si/O to enhance interfacial occupancy of demulsifiers for low‐carbon breaking of water‐in‐heavy oil emulsions
Authors: Tian Ying , He Changqing , Zhang Xincheng , He Lin , Xu Zhenghe , Sui Hong , Li Xingang
Published: November 2024

Separating water‐in‐heavy oil (W/HO) emulsions at low (room) temperature is challenging when exploiting heavy oil. We propose an adaptable strategy for constructing Si/O‐doped demulsifiers. A nonionic demulsifier (APBMP) has been synthesized based on polysiloxane modified by allyl polyether and butyl acrylate. APBMP achieves 95.97% dehydration within 5 min for W/HO emulsions at 288.15 K and complete dehydration in 15 min at 323.15 K. Mechanistic studies found that doping Si/O into the demulsifier molecules increases the number of hydrogen bond sites, which enables the demulsifiers to quickly disperse natural stabilizers (e.g., asphaltenes) and replace them at the oil–water interfacial film. The demulsifiers prefer to occupy the interfacial sites rather than dissolve into the bulk oil or water phases. Driven by hydrogen‐bond‐dominated noncovalent interactions, the oil–water interfacial film is softened, reconstructed, and broken. These findings provide insights into developing novel materials for oil–water separations in a low‐carbon way.
The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI)
Authors: Mormino Elizabeth C. , Biber Sarah A. , Rahman‐Filipiak Annalise , Arfanakis Konstantinos , Clark Lindsay , Dage Jeffrey L. , Detre John A. , Dickerson Bradford C. , Donohue Michael C. , Kecskemeti Steven , Hohman Timothy J. , Jagust William J. , Keene Dirk C. , Kukull Walter , Levendovszky Swati R. , Rosen Howie , Thompson Paul M. , Villemagne Victor L. , Wolk David A. , Okonkwo Ozioma C. , Rabinvovici Gil D. , Rivera‐Mindt Monica , Foroud Tatiana , Johnson Sterling C.
Published: November 2024

The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap. The ADRCs longitudinally follow ≈ 17,000 participants, ranging from cognitively unimpaired to dementia, arising from Alzheimer's disease (AD) and related dementias (ADRD; e.g., AD, Lewy body disorders, vascular). Motivated by the Alzheimer's Disease Neuroimaging Initiative's (ADNI) impact, the ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) was formed. Leveraging existing ADRC infrastructure, CLARiTI will integrate standardized imaging and plasma collection to characterize mixed pathologies and use community‐engaged research methods to ensure that ≥ 25% of the sample is from underrepresented populations (e.g., ethnoculturally minoritized, low education). The resulting ADRD profiles, within a more diverse sample, will provide key resources for ADRCs and an unprecedented, more generalizable publicly available imaging‐plasma dataset.

Highlights

In vivo detection of mixed pathologies is critical for Alzheimer's disease and related dementias research.

The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address gaps related to mixed pathologies.

The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will enhance this national program by adding standardized imaging and plasma collection to existing ADRC infrastructure.

This effort will provide key resources for ADRCs and an unprecedented publicly available imaging–plasma–neuropath dataset.
Elevated locus coeruleus metabolism provides resilience against cognitive decline in preclinical Alzheimer's disease
Authors: Koops Elouise A. , Dutta Joyita , Hanseeuw Bernard J. , Becker J. Alex , Van Egroo Maxime , Prokopiou Prokopis C. , Price Julie C. , Arnold Steven E. , Sperling Reisa A. , Johnson Keith A. , Jacobs Heidi I. L. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: November 2024

INTRODUCTION

Alterations in locus coeruleus’ (LC) metabolic turnover are associated with Alzheimer's disease (AD)‐pathology and cognitive impairment. However, the evolution of these changes across disease stages and their functional relevance remains unknown.

METHODS

We examined associations of [18F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET) ‐derived LC metabolism with clinical diagnostic status, cerebrospinal fluid (CSF) ‐based AD biomarkers of AD pathology, and cognitive decline in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (n = 604).

RESULTS

FDG‐PET‐derived LC metabolism was elevated in the earliest preclinical stages and lower in later disease stages. Higher LC metabolism was associated with attenuated memory decline in preclinical stages, particularly in those with low CSF Aβ42, but not in AD patients with cognitive impairment.

DISCUSSION

Higher locus coeruleus [18F]‐FDG‐PET‐derived signal in the early preclinical stages of AD can confer cognitive resilience and may reflect increased metabolic activity, whereas later stages are characterized by lower LC FDG‐PET‐derived signal, possibly due to neurodegeneration.

Highlights

LC FDG‐PET signal is lower in Alzheimer's disease (AD) patients.

LC FDG‐PET signal is higher in the preclinical stage of AD.

We observed less memory decline in those with higher LC FDG‐PET signal.

Higher LC FDG‐PET signal conferred cognitive resilience in preclinical AD.
An Yb(OTf)₃‐Mediated Indirect Activation Strategy for the Stereoselective Synthesis of α‐Sialosides from 2‐Fluorosialyl Donors
Authors: Ruan Bo‐Chang , Li Cheng‐Hsu , Chang Huai‐En , Li Pei‐Jhen
Published: November 2024

Most of chemical sialylation reactions are conducted at extremely low temperatures to achieve the formation of challenging sialic acid linkages with high stereoselectivities. Performing chemical sialylation at room temperature independent of enzymatic methods represents an effective approach, particularly significant in biological and biochemical research. Our study aims to develop a convenient method of providing α‐sialyl glycosides. Herein, we carry out sialyation using Yb(OTf)3 as an activating promoter at room temperature in tetrahydrofurane and obtain excellent stereoselectivities when reacting the N‐acetyl‐5‐N,4‐O‐carbonyl‐2‐fluorosialyl donor with galacto‐ or glucopyranosides. The advantages of this method include an over eight‐month shelf life of the sialyl donors and minimal formation of the hydrolyzed or eliminated side‐products. Sialylation of the C3 hydroxyl group in galactosides affords exclusive α‐selectivities, and a one‐pot synthesis of trisaccharide is accomplished by application of this method. Finally, we anticipate that this sialylation strategy can compensate for the limitations of the current enzymatic synthesis of complex glycans.
Dual (oxy)hydroxide Cocatalyst Synergistically Boosts Solar Water Splitting of BiVO4 Photoanode
Authors: Su Youyi , Du Yian , Yan Ruyu , Wang Haohua , Zhang Ming , Pang Xiangui , Peng Pai , Yang Pingping , Lu Xinxin , Xie Jiale
Published: November 2024

Bismuth oxide (BiVO4) is considered one of the most promising semiconductors for photoelectrochemical (PEC) water splitting due to its highly theoretical photocurrent of 7.5 mA cm−2. However, its sluggish kinetics and severe photocorrosion still hinder the real application of a large‐area BiVO4 photoanode. Herein, a room‐temperature immersion method has been used to fabricate a dual cocatalyst‐coated BiVO4 film, namely the BiVO4/FeOOH/Co(OH)2 photoanode. This composite photoanode delivers a photocurrent density of 2.56 mA cm−2, which is 2.7 times that of pure BiVO4. After a long‐term testing of 10 h, its retention rate of photocurrent reaches 71.63 %, which is 4.6 times that of BiVO4. The kinetic studies illustrate that dual cocatalyst can significantly lower the charge transfer resistance, improve the charge injection efficiency, and reduce the Tafel slope. Specifically, FeOOH plays a role in transporting photogenerated holes, while Co(OH)2 facilitates water oxidation reactions. In addition, the dual cocatalyst coating can slow down vanadium ion dissolution and improve PEC stability. This immersion method can easily be applied to large‐area photoelectrodes.
Prescribing Agreement Improves Judgments and Decisions
Authors: Voinov Pavel V. , Knoblich Günther
Published: November 2024

We investigated whether prescribing agreement improves the quality of judgments and decisions. Participants were first asked to provide judgments or decisions individually. Then, they either revised their initial judgments and decisions based on a partners' response, or they provided a joint judgment agreed upon with their partner. In the latter condition, we allowed for a minimal communication protocol restricted to acceptance and rejection responses to each other's proposals. In the Agreement condition, participants improved both in a cognitive (Experiment 1a) and a perceptual decision task (Experiment 1b). The cognitive task agreement allowed participants to improve above the level of accuracy achieved with revision. Surprisingly, the prescribing agreement improved the quality of the initial independent decisions. In a judgment task (Experiment 2), the prescribing agreement led to more accurate judgments because partners weighed each other's judgments more equally than in the Revision condition where they gave higher weight to their own judgments. We conclude that prescribing agreement reduces egocentric discounting bias and motivates individuals to be more accurate. These results not only demonstrate that collective benefits in judgment and decision making can be accrued without verbal communication but also suggest potential limitations of this approach.
Fluorescence Turn‐Off‐On Sensing Strategy for the Detection of Pb2+ and Metalaxyl Fungicide Using Yellow Fluorescent Carbon Dots From Cordia dichotoma Fruits
Authors: Vadia Foziya Yusuf , Malek Naved I. , Park Tae Jung , Kailasa Suresh Kumar
Published: November 2024

In this work, a facile and rapid fluorescence turn‐off‐on sensing method was developed for the detection of Pb2+ and metalaxyl fungicide in environmental samples using yellow carbon dots (CDs) from Cordia dichotoma fruits. The prepared C. dichotoma‐CDs showed the emission band (𝜆Em) at 535 nm under 448 nm of excitation wavelength. The fluorescence intensity of C. dichotoma‐CDs quenches by Pb2+ ion and then restores by metalaxyl fungicide, favoring to develop a fluorescence turn‐off‐on sensing strategy. The intensity ratios (I0/I and I/I0) are linear against Pb2+ (0.01–50 μM) and metalaxyl fungicide (0.025–10 μM) concentrations, offering the detection limits of 0.0054 and 0.0087 μM for Pb2+ and metalaxyl fungicide, respectively. Additionally, the potential application of C. dichotoma‐CD‐based fluorescence turn‐off‐on sensing approach was effectively demonstrated for Pb2+ and metalaxyl fungicide assays in real samples, which confirms that C. dichotoma‐CDs act as “turn‐off‐on” fluorescent probe for assaying of Pb2+ and metalaxyl fungicide, respectively.
Sequence and Configuration of a Novel Bispecific Antibody Format Impacts Its Production Using Chinese Hamster Ovary (CHO) Cells
Authors: Hussain Hirra , Ozanne Angelica M. S. , Patel Tulshi , Vito Davide , Ellis Mark , Hinchliffe Matthew , Humphreys David P. , Stephens Paul E. , Sweeney Bernie , White James , Dickson Alan J. , Smales C. Mark
Published: November 2024

There are a number of new format antibody‐inspired molecules with multiple antigen binding capabilities in development and clinical evaluation. Here, we describe the impact of the sequence and configuration of a unique bispecific antibody format (termed BYbe) using a panel of four BYbe's and the three IgG1s from which they were derived on their production in a Chinese hamster ovary (CHO) cell expression system. Following transfection and selection, one bispecific antibody format yielded fewer mini‐pools in comparison to the other bispecific cell pools. When the top 12 expressing stable mini‐pools of all BYbe configurations and sequences were evaluated, both the dsscFv sequence and antibody chain configuration or placement directly impacted productivity. The cell‐specific productivity (qP, pg/cell/day) was lower in all BYbe cell pools compared to the IgG1 cell lines. However, when the actual molecules/cell/day produced were considered, three of the four bispecific cell pools outproduced the parental IgG1 cell pools. While gene copy number did not correlate to productivity, mRNA analysis showed that for specific BYbe formats there was a strong correlation with productivity. In summary, we describe how bispecific antibody format configuration impacts the cell line construction process and yield of product from CHO cells.
Development of a Microphysiological System to Model Human Cancer Metastasis From the Colon to the Liver
Authors: Miller Paula G. , Huang Emina , Fisher Robert , Shuler Michael L.
Published: November 2024

We describe a novel device to mimic the metastasis of cancer cells from the colon into the liver in a human model. The colon mimic is connected to the liver model by a gravity‐driven recirculating unidirectional flow of a blood surrogate and can mimic the five steps of the metastatic cascade: invasion in the colon, intravasation into the bloodstream, systemic transportation, extravasation into the liver, and colonization in the liver. The colon mimic uses established normal colon epithelial organoid cells (NL) and human umbilical vein endothelial cells (HUVEC) plated on opposite sides of a membrane. To better mimic the colon structure the NL side of the membrane is exposed to air to establish an air‐liquid interface. The liver mimic consists of human liver sinusoidal endothelial cells (HHSEC) and epithelial hepatic cells (HepG2 C3A) plated in Matrigel on opposite sides of a membrane. Labeled colorectal cancer cells/clusters (CA) from organoids are introduced into an established normal colon epithelial cell (NL) layer from the same patient before assembly of the system or alternatively NL organoids and fluorescently labeled CA organoids from the same patient were prepared as a ratio of 10:1 NL:CA and established together before assembly of the system. Cell viability is greater than 85% in this system. We demonstrate that over 5 days of operation that the five steps of the metastatic cascade are replicated. This novel device allows an in vitro estimate of metastatic capability (as measured by using percentages of the labeled areas per device through ImageJ) in response to selected variables. In this study, the metastatic capability depends on the source of cancer cells (e.g., the patient), the clumping of cancer cells, glucose concentration, and oxygen levels (hypoxia). For the first time, this new in vitro system mimics all five steps of the metastatic cascade in a single device and provides a new device to probe and observe the process of metastasis in a human‐based model in only 5 days. The rapid observation is due to the use of a high concentration of cancer cells in the colon (e.g. 10%) and the absence of the immune system. Our device makes it possible to probe aspects of each step of metastasis and interactions between steps.
Circulating serum miRNAs predict response to platinum chemotherapy in high‐grade serous ovarian cancer
Authors: Suzuki Kazuhiro , Yokoi Akira , Matsuzaki Juntaro , Yoshida Kosuke , Yamamoto Yusuke , Kato Tomoyasu , Ishikawa Mitsuya , Ochiya Takahiro , Kajiyama Hiroaki
Published: November 2024

Background

Platinum chemotherapy is the cornerstone of treatment for high‐grade serous ovarian cancer (HGSOC); however, validated biomarkers that can accurately predict platinum response are lacking. Based on their roles in the underlying pathophysiology, circulating microRNAs are potential, noninvasive biomarkers in cancer. In the present study, we aimed to evaluate the circulating miRNA profiles of patients with HGSOC and to assess their potential utility as biomarkers to predict platinum response.

Methods

Pretreatment serum samples collected from patients who received platinum chemotherapy for Stage III–IV HGSOC between 2008 and 2016 were analyzed using miRNA microarray. LASSO logistic regression analysis was used to construct predictive models for treatment‐free interval of platinum (TFIp).

Results

The median follow‐up was 54.6 (range, 3.5–144.1) months. The comprehensive analysis of 2588 miRNAs was performed in serum samples of 153 eligible patients, and predictive models were constructed using a combination of circulating miRNAs with an area under the receiver operating characteristic curve of 0.944 for TFIp >1 month, 0.637 for TFIp ≥6 months, 0.705 for TFIp ≥12 months, and 0.938 for TFIp ≥36 months. Each predictive model provided a significant TFIp classification (p = 0.001 in TFIp >1 month, p = 0.013 in TFIp ≥6 months, p < 0.001 in TFIp ≥12 months, and p < 0.001 in TFIp ≥36 months).

Conclusion

Circulating miRNA profiles has potential utility in predicting platinum response in patients with HGSOC and can aid clinicians in choosing appropriate treatment strategies.
Confinement Effects of Coordination Cages on the Synthesis and Application of Polyoxometalates
Authors: Liu Cui‐Lian , Kalandia Givi , Reek Joost N. H. , Parac‐Vogt Tatjana N.
Published: November 2024

The confinement effects within coordination cages present powerful tools in modern chemistry, particularly for the synthesis and manipulation of complex molecules. This concept article reviews the use of coordination cages to stabilize and tune the properties of polyoxometalates (POMs), a class of nano‐sized metallic clusters, expanding the focus beyond traditional organic reactions. The article provides a brief overview of coordination cages, POM chemistry and discusses the encapsulation of POMs in coordination cages, highlighting how these cages provide a confinement effect that enhances the stability and reactivity of POMs. Additionally, the concept of cavity‐directed synthesis is explored as a method for creating labile POMs, which are often unstable in aqueous conditions, underlining its implications for supramolecular catalysis. Future research will focus on expanding the structures and applications of encapsulated POMs, as well as improving cage designs to unlock new cluster architectures.
Rationale and Design of Dual Antiplatelet Therapy in Patients with Coronary Multi‐Vessel Disease (DAPT‐MVD): A Multicenter, Randomized, Controlled Trial
Authors: Tian Jinwei , Wang Zhuozhong , Wang Yan , Wang Fan , Wang Yini , Zhao Peng , Hou Xinyu , Peng Xiang , Tian Maoyi , Wang Duolao , Yu Bo
Published: November 2024

Background

The optimal duration of dual antiplatelet therapy (DAPT) for patients with coronary multi‐vessel disease (MVD) who have received drug‐eluting stents (DES) remains unclear.

Hypothesis and Methods

The Dual Antiplatelet Therapy in Patients with Coronary Multi‐Vessel Disease (DAPT‐MVD) study is a multicenter, open‐label, randomized controlled trial designed to assess the efficacy and safety of extended DAPT in MVD patients 12 months following DES implantation. We plan to enroll 8250 patients across approximately 100 sites in China. Participants will be randomized in a 1:1 ratio to receive either extended DAPT (75 mg clopidogrel plus 75–150 mg aspirin daily) or monotherapy (75–150 mg aspirin daily) beyond 12 months post‐DES implantation. The follow‐up period will last at least 12 months, with all potential endpoints adjudicated by a blinded Clinical Events Committee. The primary endpoint is major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.

Results

As of April 2024, a total of 8250 participants have been enrolled in the study. The mean age of the enrolled patients was 60.5 ± 8.8years, with 5753 (69.7%) being men.

Conclusions

The DAPT‐MVD study is the first large‐scale trial to evaluate the efficacy and safety of prolonged DAPT with clopidogrel plus aspirin beyond 12 months after DES implantation in MVD patients. The trial will provide novel insights into the optimal duration of DAPT for MVD patients (ClinicalTrials. gov ID: NCT04624854. Registered on 10/27/2020).
Coordination Compounds as Antivirals against Neglected Tropical Diseases
Authors: Rezende Wallace S. , Neto Antonio Marçal , Corbi Juliano J. , Corbi Pedro P. , de Paiva Raphael E. F. , Bergamini Fernando R. G.
Published: November 2024

Neglected tropical viral diseases are a burden to social and economic welfare being responsible for higher pathogen‐related mortality rates and chronic debilitating patient conditions. Climatic changes have widened up the infectibility ratio of such diseases, with autochthonous transmission in formerly temperate‐to‐cold environments. The slow‐paced development of potential vaccines followed by the inexistence of antiviral drugs for such diseases considerably worsens the situation. Coordination compounds are a class of molecules that have been extensively explored as antiviral drugs for viruses such as poliovirus, HIV and, more recently, SARS‐CoV‐2, figuring as potential molecules to be explored and capitalized as antivirals against neglected viral strains. In this review the current efforts from the inorganic medicinal chemistry to address viral neglected tropical diseases, with emphasis to coordination compounds, is presented. Since many of neglected viruses are also arthropod‐borne viruses, relying on a vector for transmission, coordination entities able to mitigate vectors are also presented as a parallel strategy to prevent and control such diseases.
Considerations in screening for asymptomatic carotid artery stenosis in irradiated head and neck cancer survivors
Authors: Day Andrew T. , Mitchell Dalia N. , Eary Rebecca L. , Jones Erica , Pinho Marco C. , Zaha Vlad G. , Yang Eric H. , Sher David J.
Published: November 2024

Carpenter et al. add to the body of evidence demonstrating that irradiated head and neck cancer survivors are at high risk for carotid artery stenosis. In this editorial, the concept of screening for asymptomatic carotid artery stenosis in this subpopulation is explored.
Pharmacokinetics and Bioequivalence Evaluation of Trazodone Hydrochloride Sustained‐Release Tablets in Healthy Chinese Volunteers
Authors: Wang Jingyan , Xu Yuan , Zhao Zhicheng , Meng Tian , Zou Yang , Lan Yi
Published: November 2024

The aim of this study was to investigate the pharmacokinetics, bioequivalence, and safety of generic trazodone hydrochloride sustained‐release tablet and its reference listed product in healthy Chinese subjects. An open, randomized, single‐dose, and 2‐period crossover study was involved under fasting and fed conditions, with a 7‐day washout period. A single oral dose of 150 mg of 2 trazodone hydrochloride sustained‐release tablets was administered to 84 healthy volunteers, with 36 in the fasting group and 48 consuming a high‐fat diet, respectively. The plasma concentrations of trazodone were analyzed using a liquid chromatography‐tandem mass spectrometry method, and pharmacokinetic parameters were obtained from concentration‐time profiles. The geometric mean ratio with 90% confidence intervals of the maximum trazodone concentration, area under the plasma concentration‐time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the bioequivalence acceptance criteria (80%‐125%) under fasting and fed conditions, which indicated that the test and reference formulations were bioequivalent. Compared with the fasting study, the concomitant administration of trazodone with a high‐fat diet had a negligible influence on the drug pharmacokinetic behavior. Adverse events were recorded, and no serious adverse events were observed during either fasting or fed conditions. Trazodone has proven to have an acceptable safety profile in the Chinese population, with bioequivalence successfully established under both fasting and fed conditions.
Interactions Between [PdX4]2− (X=Cl, Br) Dianions in Presence of Counterions
Authors: Trzęsowska Natasza , Wysokiński Rafał , Hajlaoui Fadhel , Zouari Nabil , Michalczyk Mariusz , Scheiner Steve , Zierkiewicz Wiktor
Published: November 2024

The interaction between two square palladium (II) dianions PdX42− (X=Cl, Br) is evaluated by crystal study and analyzed by quantum chemical means. The arrangement within the crystal between each pair of PdX42− neighbors is suggestive of a Pd⋅⋅⋅X noncovalent bond, which is verified by a battery of computational protocols. While the potential between these two bare dianions is computed to be highly repulsive, the introduction of even just two counterions makes this interaction attractive, as does the presence of a constellation of point charges. It is concluded that there is indeed a stabilizing Pd⋅⋅⋅X bond, but it is incapable of overcoming the strong coulombic repulsive force between two dianions. While the QTAIM, NBO, and NCI tools can indicate the presence of a noncovalent bond, they are unable to distinguish an attractive from a repulsive interaction.