bluuebunny/crossref_metadata_2025 huggingface dataset:
Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy
Authors: Lu Sheng , Li Yifan , Yu Yingjie
Published: June 2024

Cuproptosis is a novel copper‐dependent programmed cell death. The efficacy of cuproptosis is highly dependent on intracellular copper accumulation and counteracted by a high level of glutathione (GSH) in tumor cells. Here, this work develops a self‐amplified cuproptosis nanoparticles (Cel‐Cu NP) using celastrol (Cel), a natural product isolated from medical plant. In Cel‐Cu NP, Cel serves as a versatile copper ionophore, exhibiting an ideal coordination capacity toward copper ions without compromising the cuproptosis induction. Notably, Cel can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, this self‐amplified cuproptosis further activates immunogenic cell death (ICD) to elicit robust immune response. Combining with immune checkpoint blockade, Cel‐Cu NP effectively eradicates metastatic tumors in a mouse lung metastasis model. This study provides an efficient nanomedicine by inducing self‐amplified cuproptosis for robust immunotherapy.
Cooperative In Situ Impregnation of PEG and Au Nanoparticles into Expanded CNT Network Toward Composite Phase Change Fibers with High Storage Capacity and Photothermal Conversion
Authors: Liao Tanqian , Li Wenya , Zhao Jingna , Yang Xiaoyu , Zhang Wentao , Zou Jingyun , Zhao Bing , Zhang Xiaohua , Li Qingwen
Published: June 2024

Phase change fibers with multifunctionalities are a promising material for thermal management applications, however, it is still challenging to simultaneously give the fiber high energy conversion and storage capacity. Here, a cooperative in situ impregnation strategy is reported, to introduce Au nanoparticles (NPs) and polyethylene glycol (PEG) together into carbon nanotube (CNT) network during the expansion process, resulting in a CNT/Au/PEG composite phase change fiber. The obtained composite fiber have the characteristics of high loading (up to 88.0–98.6%) and uniform distribution of Au NPs, and thus exhibits superior mechanical, electrical, and thermal properties. The presence of Au NPs plays more important role in not only improving the PEG crystallinity and phase change enthalpy, but also enhancing the photothermal conversion efficiency (up to 88.2%). There is also a new feature of precise regulation of the phase change temperatures, e.g., from 9.5 to 20.5 °C for the solidification temperature. More importantly, due to the strong confinement of PEG and Au NPs inside the CNT network, the composite fiber also shows excellent thermal stabilities, including the anti‐leakage behavior and cycling phase change ability.
Hypermultiplexed Off‐Chip Hologram by On‐Chip Integrated Metasurface
Authors: Liu Xianjin , Ma Zhanying , Zhang Dasen , Bao Qiwen , Liu Zhenzhen , Xiao Jun‐Jun
Published: June 2024

The waveguide‐integrated metasurface introduces a novel photonic chip capable of converting guided modes into free‐space light. This enables functions such as off‐chip beam focusing, steering, and imaging. The challenge lies in achieving hyper‐multiplexing across diverse parameters, including guided‐wave mode type, direction, polarization, and notably, multiple wavelengths. Here, a comprehensive end‐to‐end inverse design framework is introduced, rooted in a physical model, for the multifunctional design of on‐chip metasurfaces. This framework allows for metasurface optimization through a target‐field‐driven iteration process. A hypermultiplexed on‐chip metasurface capable of generating red‐green‐blue holograms at multiple target planes is demonstrated, with both independent and cooperative control over guided‐wave direction. Significantly, the proposed method streamlines the design process utilizing only the positions of meta‐atoms as the design variable. Nine independent holographic channels are demonstrated through a combination of wavelength and distance multiplexing. Moreover, by incorporating the excitation direction into the design, the metasurface produces a total of 36 distinct holograms. The robustness of these results against fabrication discrepancies is validated through 3D full‐wave electromagnetic simulations, aligning well with advanced manufacturing techniques. The research presents a universal design framework for the development of multifunctional on‐chip metasurfaces, opening up new avenues for a wide range of applications.
Quantum‐Dots‐In‐Double‐Perovskite for High‐Gain Short‐Wave Infrared Photodetector
Authors: Jhang An‐Ting , Tsai Po‐Cheng , Tsai Yi‐Ting , Lin Shih‐Yen , Fang Mu‐Huai
Published: June 2024

Short‐wave infrared (SWIR) photodetectors utilizing quantum dot (QD) material systems, harnessed through the quantum confinement effect to tune the absorption wavelength, offer an attractive avenue for the development of cost‐effective and solution‐processed photodetectors compared to the relatively expensive compound semiconductor photodetectors. However, the pores between the QDs and poor chemical stability after surface modification have impeded the practical application of quantum‐dot‐based photodetectors. In this study, high‐gain SWIR photodetector is demonstrated and achieved by incorporating PbS QD into the Cs2AgBiBr6 halide‐based double perovskite matrix, as confirmed by X‐ray diffraction, transmission electron microscope, and energy dispersive spectrometer. The thin film structure and detailed local structure are revealed by 2D grazing‐incidence wide and small‐angle X‐ray scattering. The resulting PbS@Cs2AgBiBr6‐based SWIR photodetector exhibits remarkable performance with a responsivity and detectivity of 15000 A W−1 and 1.31 × 1012 cm Hz1/2 W−1, respectively. This study offers valuable insights into the design of composite materials for high‐gain SWIR photodetectors.
Phase‐Shifted Bragg Gratings from High Refractive Index Chalcogenide Hybrid Inorganic/Polymers: Fabrication and Thermo‐Optic Characterization
Authors: Nishant Abhinav , Kim Kyung‐Jo , Himmelhuber Roland , Lee Taeheon , Kleine Tristan S. , Pyun Jeffrey , Norwood Robert A
Published: June 2024

In this study, the first fabrication of phase‐shifted Bragg gratings utilizing chalcogenide hybrid inorganic/organic polymers (CHIPs) is presented based on poly(sulfur‐random‐(1,3‐isopropenylbenzene) to measure the thermo‐optic coefficient (TOC) of this new class of optical polymers. The unique properties of CHIPs, such as high index contrast and low optical losses, are leveraged to fabricate Bragg gratings that enable precise determination of the TOC and glass transition temperature (Tg) of these polymers. The optical measurement introduces a novel technique to measure the TOC and Tg of optical polymers which can be difficult to determine using traditional methods such as differential scanning calorimetry (DSC) after fabrication into photonic device constructs. The findings demonstrate that CHIPs exhibit low thermo‐optic (TO) effects, making them exceptionally well‐suited for the development of thermally stable photonic integrated circuits.
Electrochemical α‐Functionalization of N‐Aryl‐Activated Tertiary Amines
Authors: Wang Feijun , Frankowski Kevin J.
Published: June 2024

Numerous appropriately substituted pyridyl or phenyl groups serve as a particularly advantageous activation motif for the electrochemical oxidation of amines. Such groups enable a general, mild method for the electrochemical α‐functionalization of tertiary amines across numerous activating groups and amine scaffolds. Notably, the method accommodates an unprecedented range of nucleophile classes, allowing for the introduction of diverse functional groups to the readily prepared amine substrates. The utility of this method is then demonstrated through applications to unsymmetrical bisfunctionalization, site‐selective functionalization of N‐pyridyl amines vs. other activated amines, a formal synthesis of ivosidenib and the diversification of FDA‐approved drugs or natural product substrates.
Controlled Delivery of Paclitaxel via Stable Synthetic Protein Nanoparticles
Authors: Mauser Ava , Waibel Isabel , Banerjee Kaushik , Mujeeb Anzar A. , Gan Jingyao , Lee Sophia , Brown William , Lang Nigel , Gregory Jason , Raymond Jeffery , Franzeb Matthias , Schwendeman Anna , Castro Maria G. , Lahann Joerg
Published: June 2024

Despite decades of intense research, glioma remains a disease for which no adequate clinical treatment exists. Given the ongoing therapeutic failures of conventional treatment approaches, nanomedicine may offer alternative options because it can increase the bioavailability of drugs and alter their pharmacokinetics. Here, a new type of synthetic protein nanoparticles (SPNPs) is reported that allow for effective loading and controlled release of the potent cancer drug, paclitaxel (PTX) – a drug that so far has been unsuccessful in glioma treatment due to hydrophobicity, low solubility, and associated delivery challenges. SPNPs are prepared by electrohydrodynamic (EHD) jetting of dilute solutions of PTX‐loaded albumin made by high‐pressure homogenization. After EHD jetting, PTX SPNPs possess a dry diameter of 165 ± 44 nm, hydrated diameter of 297 ± 102 nm, and a zeta potential of −19 ± 8 mV in water. For the SPNP formulation with a total PTX loading of 9.4%, the loading efficiency is 94%, and controlled release of PTX is observed over two weeks (6% burst release). PTX SPNPs are more potent (68% lethality) than free PTX (45% lethality using 0.2% dimethyl sulfoxide). PTX SPNPs in combination with IR show a significant survival benefit in glioma‐bearing mouse models, avoid adverse liver toxicity, and maintain a normal brain architecture. Immunohistochemistry reveals a dramatic tumor size reduction including 40% long‐term survivors without discernible signs of tumor. Using flexibly engineered SPNPs, this work outlines an efficient strategy for the delivery of hydrophobic drugs that are otherwise notoriously hard to deliver.
Near‐Complete Suppression of NIR‐II Luminescence Quenching in Halide Double Perovskites for Surface Functionalization Through Facet Engineering
Authors: Duan Qiudong , Xu Yusheng , Zha Yu , Meng Fanju , Wang Qi , Wen Yugeng , Qiu Jianbei
Published: June 2024

Lanthanide‐based NIR‐II‐emitting materials (1000–1700 nm) show promise for optoelectronic devices, phototherapy, and bioimaging. However, one major bottleneck to prevent their widespread use lies in low quantum efficiencies, which are significantly constrained by various quenching effects. Here, a highly oriented (222) facet is achieved via facet engineering for Cs2NaErCl6 double perovskites, enabling near‐complete suppression of NIR‐II luminescence quenching. The optimally (222)‐oriented Cs2Ag0.10Na0.90ErCl6 microcrystals emit Er3+ 1540 nm light with unprecedented high quantum efficiencies of 90 ± 6% under 379 nm UV excitation (ultralarge Stokes shift >1000 nm), and a record near‐unity quantum yield of 98.6% is also obtained for (222)‐based Cs2NaYb0.40Er0.60Cl6 microcrystallites under 980 nm excitation. With combined experimental and theoretical studies, the underlying mechanism of facet‐dependent Er3+ 1540 nm emissions is revealed, which can contribute to surface asymmetry‐induced breakdown of parity‐forbidden transition and suppression of undesired non‐radiative processes. Further, the role of surface quenching is reexamined by molecular dynamics based on two facets, highlighting the drastic two‐phonon coupling effect of a hydroxyl group to 4I13/2 level of Er3+. Surface‐functionalized facets will provide new insights for tunable luminescence in double perovskites, and open up a new avenue for developing highly efficient NIR‐II emitters toward broad applications.
Iridium Single Atoms to Nanoparticles: Nurturing the Local Synergy with Cobalt‐Oxide Supported Palladium Nanoparticles for Oxygen Reduction Reaction
Authors: Bhalothia Dinesh , Yan Che , Hiraoka Nozomu , Ishii Hirofumi , Liao Yen‑Fa , Dai Sheng , Chen Po‐Chun , Chen Tsan‐Yao
Published: June 2024

A ternary catalyst comprising Iridium (Ir) single‐atoms (SA)s decorated on the Co‐oxide supported palladium (Pd) nanoparticles (denoted as CPI‐SA) is developed in this work. The CPI‐SA with 1 wt.% of Ir exhibits unprecedented high mass activity (MA) of 7173 and 770 mA mgIr−1, respectively, at 0.85 and 0.90 V versus RHE in alkaline ORR (0.1 m KOH), outperforming the commercial Johnson Matthey Pt catalyst (J.M.‐Pt/C; 20 wt.% Pt) by 107‐folds. More importantly, the high structural reliability of the Ir single‐atoms endows the CPI‐SA with outstanding durability, where it shows progressively increasing MA of 13 342 and 1372 mA mgIr−1, respectively, at 0.85 and 0.90 V versus RHE up to 69 000 cycles (3 months) in the accelerated degradation test (ADT). Evidence from the in situ partial fluorescence yield X‐ray absorption spectroscopy (PFY‐XAS) and the electrochemical analysis indicate that the Ir single‐atoms and adjacent Pd domains synergistically promote the O2 splitting and subsequent desorption of hydroxide ions (OH−), respectively. Whereas the Co‐atoms underneath serve as electron injectors to boost the ORR activity of the Ir single‐atoms. Besides, a progressive and sharp drop in the ORR performance is observed when Ir‐clusters and Ir nanoparticles are decorated on the Co‐oxide‐supported Pd nanoparticles.
Cabazitaxel‐Loaded Thermosensitive Hydrogel System for Suppressed Orthotopic Colorectal Cancer and Liver Metastasis
Authors: Chen Yu , Dai Liqun , Shi Kun , Pan Meng , Yuan Liping , Qian Zhiyong
Published: June 2024

The treatment of colorectal cancer is always a major challenge in the field of cancer research. The number of estimated new cases of colorectal cancer worldwide in 2020 is 1 148 515, and the estimated number of deaths is 576 858, revealing that mortality accounted for approximately half of the disease incidence. The development of new drugs and strategies for colorectal cancer treatment is urgently needed. Thermosensitive injectable hydrogel PDLLA‐PEG‐PDLLA (PLEL) loaded with cabazitaxel (CTX) is used to explore its anti‐tumor effect on mice with orthotopic colorectal cancer. CTX/PLEL is characterized by a solution state at room temperature and a hydrogel state at physiologic temperature. The excipients MPEG‐PCL and PDLLA‐PEG‐PDLLA have good biocompatibility and biodegradability. The simple material synthesis and preparation process renders this system cost‐effective and more conducive to clinical transformation. An orthotopic colorectal cancer model is established by transplantation subcutaneous tumors onto the cecum of mice. According to the results of experiments in vivo, CTX/PLEL significantly inhibits orthotopic colorectal cancer and liver metastasis in mice. The results indicate that CTX/PLEL nanoparticle preparations have high security and excellent anti‐tumor effects, and have great application potential in colorectal cancer therapy.
3D Printing of Customizable Transient Bioelectronics and Sensors
Authors: Fumeaux Nicolas , Briand Danick
Published: June 2024

Transient electronics have emerged as a new category of devices that can degrade after their functional lifetime, offering tremendous potential as disposable sensors, actuators, wearables, and implants. Additive manufacturing methods represent a promising approach for patterning transient materials, yet examples of fully printed bioelectronic devices are scarce. This study introduces a fully digital 3D printing approach enabling the prototyping and customization of soft bioelectronics made of transient materials. The direct ink writing of poly(octamethylene maleate (anhydride) citrate) (POMaC) as an elastomeric matrix and of a shellac‐carbon ink as a conductor is investigated. Precise and repeatable deposition of both structural and conductive features is achieved by optimizing printing parameters, i.e., the dispense gap, printing speed, and inlet pressure. Multi‐material 3D printing enables the fabrication of functional transient devices. Notably, pressure and strain sensors are shown to operate in ranges relevant to implanted biomechanical monitoring. 3D‐printed transient electrodes are demonstrated to be comparable to state‐of‐the‐art devices in terms of impedance behavior. Finally, physical degradation of the materials is confirmed at physiological conditions. These fully digital additive manufacturing processes enable the monolithic fabrication of customizable transient bioelectronics with adaptable functions and geometries.
Digital Twin‐Assisted Degradation Diagnosis and Quantification of NMC Battery Aging Effects During Fast Charging
Authors: Guo Wendi , Sun Zhongchao , Guo Jia , Li Yaqi , Vilsen Søren Byg , Stroe Daniel Ioan
Published: June 2024

A comprehensive understanding of aging mechanisms and degradation diagnosis under fast charging in battery electric vehicles is needed. However, there is a lack of tools to capture both macroscopic and microscopic parameters, still focusing on experiment results analysis. To get a comprehensive degradation insight for improved service life, this study explores aging mechanisms in LiNi0.5Co0.2Mn0.3O2 graphite batteries under different fast charging conditions (0.6C to 2C) for up to 1000 equivalent full cycles (EFCs). An improved digital twin is used to quantify aging effects and identify aging modes, combining electrochemical techniques with post‐mortem analysis for assessing chemical and structural degradation. After 1000 EFCs, the dominant aging modes are loss of active material (LAM) in the negative electrode and loss of lithium inventory (LLI), surpassing LAM in the positive electrode. Compared to constant current charging, multistep fast charging effectively mitigates Li plating effects and graphite cracking, resulting in a 13% reduction in LAM. Additionally, optimizing the depth of discharge leads to at least 4% reductions in LLI and 16% in LAMpos. This study proves the electrochemical digital twin's potential for quantifying aging effects and serves as a basis for future physics‐informed machine learning to predict aging behavior and modes.
Preoperative geniohyoid muscle mass in esophageal cancer patients is associated with swallowing function after esophagectomy
Authors: Kawata Sanshiro , Hiramatsu Yoshihiro , Honke Junko , Murakami Tomohiro , Booka Eisuke , Matsumoto Tomohiro , Morita Yoshifumi , Kikuchi Hirotoshi , Yamauchi Katsuya , Takeuchi Hiroya
Published: June 2024

Aim

Dysphagia often develops after esophagectomy. The geniohyoid muscle is involved in swallowing movements, but its significance in esophagectomy patients remains unclear. We investigated the relationship of preoperative geniohyoid muscle mass with post‐esophagectomy swallowing function.

Methods

We retrospectively analyzed 114 patients who underwent esophagectomy and gastric conduit reconstruction for esophageal malignancy. We evaluated preoperative geniohyoid muscle sagittal cross‐sectional areas (cm2) using computed tomography. Median values for each sex were considered as cutoff values. Dysphagia severity was assessed using the Penetration–Aspiration Scale (PAS) during video‐fluoroscopic swallowing studies performed 7–10 days postoperatively.

Results

The cross‐sectional area was significantly larger in males than in females (3.2 ± 0.7 vs. 2.4 ± 0.5, p < 0.01: median in males: 3.2 cm2, and in females: 2.3 cm2). These values were used to define high and low cross‐sectional area groups. The cross‐sectional area correlated positively with grip strength (correlation coefficient (CC) = 0.530) and skeletal muscle index (CC = 0.541). Transthyretin levels (22.4 ± 6.8 vs. 25.4 ± 5.5, p = 0.03) and cross‐sectional area (2.6 ± 0.7 vs. 3.2 ± 0.8, p < 0.01) were significantly lower in patients with (PAS score ≥6; 20%) than in those without aspiration during fluoroscopic swallowing studies. Recurrent laryngeal nerve palsy was significantly more frequent in those with than in those without aspiration during fluoroscopic studies (22% vs. 5%, p = 0.03). In the multivariate analysis, low cross‐sectional area and recurrent laryngeal nerve palsy were both independent risk factors for aspiration during swallowing studies (odds ratio = 3.6, p = 0.03 and odds ratio = 6.6, p = 0.02, respectively).

Conclusion

Preoperative geniohyoid muscle mass, evaluated using neck computed tomography, can predict dysphagia after esophagectomy.
Hereditary chronic neutrophilic leukemia in a four‐generation family without transformation to acute leukemia
Authors: Lance Amanda , Chiad Zane , Seegers Sara L. , Paschall Sarah‐Catherine , Drummond Kendra , Steuerwald Nury M. , Yang Hsih‐Te , Chen Jenny , Voorhees Peter M. , Avalos Belinda R. , Druhan Lawrence J.
Published: June 2024

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by peripheral blood neutrophilia, marrow granulocyte hyperplasia, hepatosplenomegaly, and driver mutations in the colony‐stimulating factor 3 receptor (CSF3R). Designation of activating CSF3R mutations as a defining genomic abnormality for CNL has led to increased recognition of the disease. However, the natural history of CNL remains poorly understood with most patients reported being of older age, lacking germline data, and having poor survival, in part due to transformation to acute leukemia. CSF3R driver mutations in most patients with CNL have been reported to be acquired, although rare cases of germline mutations have been described. Here, we report the largest pedigree to date with familial CNL, spanning four generations with affected family members ranging in age from 4 to 53 years, none of whom have transformed to acute leukemia. A heterozygous T618I CSF3R mutation was identified in peripheral blood and mesenchymal stromal cells from the proband and in all affected living family members, while the unaffected family members tested were homozygous wild type. We show that the T618I mutation also confers a survival advantage to neutrophils in an MCL1‐dependent manner. Collectively, these data provide additional insights into the natural history of familial CNL arising from T618I CSF3R mutations and suggest that enhanced neutrophil survival also contributes to the high neutrophil count observed in patients with CNL.
An open‐label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid‐dependent/steroid‐resistant chronic GVHD
Authors: Inamoto Yoshihiro , Kato Koji , Kawakita Toshiro , Onishi Yasushi , Matsuoka Ken‐ichi , Shiratori Soichi , Ikegame Kazuhiro , Hiramoto Nobuhiro , Toyosaki Masako , Katayama Yuta , Murayama Shun , Sasagawa Yuji , Maeda Yoshinobu , Hatake Kiyohiko , Teshima Takanori
Published: June 2024

Belumosudil mesylate is a selective Rho‐associated coiled‐coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open‐label, single‐arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid‐dependent/steroid‐resistant chronic graft‐versus‐host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7–97.0), and the lower limit of the 95% CI exceeded the pre‐defined threshold of 25%. The Kaplan–Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46–90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90–8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0–51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure‐free and overall survival were not reached. Treatment‐emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug‐related. There were no drug‐related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid‐dependent/steroid‐resistant cGVHD was effective, with no new safety concerns.
A Quantum‐Chemical Study of the Mechanism of 1‐Azadienes Formation from Aldimines and Arylacetylenes in the KOtBu/DMSO Superbasic Medium
Authors: Orel Vladimir B. , Zubarev Andrey A. , Vitkovskaya Nadezhda M. , Schmidt Elena Yu. , Trofimov Boris A.
Published: June 2024

The mechanism of 1‐azadienes formation from aldimines and arylacetylenes in the KOtBu/DMSO superbasic medium has been explored theoretically using a DFT approach [B2PLYP(D2)/6‐311+G(d,p)//B3LYP/6‐31+G(d)] and a sophisticated model taking the potassium tert‐butoxide and the nearest solvation shell of the potassium cation explicitly into account. The main focus is placed on (i) a detailed analysis of the kinetic and thermodynamic characteristics of the isomerization of intermediate propargylamine into 1‐azadienes, and (ii) the factors determining the isomeric composition of 1‐azadienes with different substituents in the starting arylaldimines and arylacetylenes. Our findings clearly indicate that the mild experimental conditions of 1‐azadienes formation are accounted for by the relatively small activation barrier (ΔG≠≤16.2 kcal/mol) of the limiting step (ethynylation of aldimine with arylacetylenes). The rapid isomerization of propargylamine to 1‐azadiene is found to be due to low activation barriers (ΔG≠≤9.1 kcal/mol) related to the protons transfer. The isomeric composition in the case of various substituted 1‐azadienes is determined solely by the difference in the thermodynamic stability of the 1E,2E‐ and 1Z,2E‐forms.
Contemporary practice patterns for chronic rhinosinusitis with nasal polyps
Authors: Ayoub Noel F. , Sbeih Firas , Bleier Benjamin S.
Published: June 2024

Key points

Data on current practice patterns for the management of chronic rhinosinusitis with nasal polyps, including which medications are deemed by otolaryngologists to better manage patient symptoms, are limited.

This study demonstrated that contemporary practice patterns are largely consistent with published clinical consensus statements.

Off‐label nasal steroid irrigations and dupilumab are the most commonly used topical and systemic therapies for chronic rhinosinusitis with nasal polyps, respectively.
Suppression of eEF2 phosphorylation alleviates synaptic failure and cognitive deficits in mouse models of Down syndrome
Authors: Wang Xin , Yang Qian , Zhou Xueyan , Keene C. Dirk , Ryazanov Alexey G. , Ma Tao
Published: June 2024

INTRODUCTION

Cognitive impairment is a core feature of Down syndrome (DS), and the underlying neurobiological mechanisms remain unclear. Translation dysregulation is linked to multiple neurological disorders characterized by cognitive impairments. Phosphorylation of the translational factor eukaryotic elongation factor 2 (eEF2) by its kinase eEF2K results in inhibition of general protein synthesis.

METHODS

We used genetic and pharmacological methods to suppress eEF2K in two lines of DS mouse models. We further applied multiple approaches to evaluate the effects of eEF2K inhibition on DS pathophysiology.

RESULTS

We found that eEF2K signaling was overactive in the brain of patients with DS and DS mouse models. Inhibition of eEF2 phosphorylation through suppression of eEF2K in DS model mice improved multiple aspects of DS‐associated pathophysiology including de novo protein synthesis deficiency, synaptic morphological defects, long‐term synaptic plasticity failure, and cognitive impairments.

DISCUSSION

Our data suggested that eEF2K signaling dysregulation mediates DS‐associated synaptic and cognitive impairments.

Highlights

Phosphorylation of the translational factor eukaryotic elongation factor 2 (eEF2) is increased in the Down syndrome (DS) brain.

Suppression of the eEF2 kinase (eEF2K) alleviates cognitive deficits in DS models.

Suppression of eEF2K improves synaptic dysregulation in DS models.

Cognitive and synaptic impairments in DS models are rescued by eEF2K inhibitors.
Allenamides as a Powerful Tool to Incorporate Diversity: Thia‐Michael Lipidation of Semisynthetic Peptides and Access to β‐Keto Amides
Authors: Na Tae‐Ung , Sander Veronika , Davidson Alan J. , Lin Rolland , Hermant Yann O. , Hardie Boys Madeleine T. , Pletzer Daniel , Campbell Georgia , Ferguson Scott A. , Cook Gregory M. , Allison Jane R. , Brimble Margaret A. , Northrop Brian H. , Cameron Alan J.
Published: June 2024

Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more efficient strategy for late‐stage structural derivatisation of a peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non‐native moieties. Utilising an allenamide, we report the first semisynthesis of antimicrobial lipopeptides leveraging a highly efficient thia‐Michael addition of chemically diverse lipophilic thiols. Using chemoenzymatically prepared polymyxin B nonapeptide (PMBN) as a model scaffold, an optimised allenamide‐mediated thia‐Michael addition effected rapid and near quantitative lipidation, affording vinyl sulfide‐linked lipopeptide derivatives. Harnessing the utility of this new methodology, 22 lipophilic thiols of unprecedented chemical diversity were introduced to the PMBN framework. These included alkyl thiols, substituted aromatic thiols, heterocyclic thiols and those bearing additional functional groups (e.g., amines), ultimately yielding analogues with potent Gram‐negative antimicrobial activity and substantially attenuated nephrotoxicity. Furthermore, we report facile routes to transform the allenamide into a β‐keto amide on unprotected peptides, offering a powerful “jack‐of‐all‐trades” synthetic intermediate to enable further peptide modification.
Interface Engineering via Manipulating Solvation Chemistry for Liquid Lithium‐Ion Batteries Operated≥100 °C
Authors: Gao Hongjing , Chen Yufang , Teng Tao , Yun Xiaoru , Lu Di , Zhou Guangmin , Zhao Yun , Li Baohua , Zhou Xing , Zheng Chunman , Xiao Peitao
Published: June 2024

High‐performance and temperature‐resistant lithium‐ion batteries (LIBs), which are able to operate at elevated temperatures (i.e., >60 °C) are highly demanded in various fields, especially in military or aerospace exploration. However, their applications were largely impeded by the poor electrochemical performance and unsatisfying safety issues, which were induced by the severe side reactions between electrolytes and electrodes at high temperatures. Herein, with the synergetic effects of solvation chemistry and functional additive in the elaborately designed weakly solvating electrolyte, a unique robust organic/inorganic hetero‐interphase, composed of gradient F, B‐rich inorganic components and homogeneously distributed Si‐rich organic components, was successfully constructed on both cathodes and anodes, which would effectively inhibit the constant decomposition of electrolytes and dissolution of transition metal ions, thus highly enhancing the high‐temperature electrochemical performance. As a result, both cathodes and anodes, without compromising their low‐temperature performance, can operate at temperatures ≥100 °C, with excellent capacity retentions of 96.1 % after 500 cycles and 93.5 % after ≥200 cycles, respectively, at 80 °C. Ah‐level LiCoO2||graphite full cells with a cut‐off voltage of 4.3 V also exhibited superior temperature‐resistance with a capacity retention of 89.9 % at temperature as high as 120 °C. Moreover, the fully charged pouch cells exhibited highly enhanced safety, demonstrating their potentials in practical applications at ultrahigh temperatures.
Aggregation of One‐Dimensional Wires: The Case of Long Oligoynes
Authors: Gordillo‐Gámez Fernando , Gao Yueze , Aragó Juan , Ortí Enrique , Aranda Daniel , Kertesz Miklos , Tykwinski Rik R. , Casado Juan
Published: June 2024

We show an unexpected aggregation phenomenon of a long oligoyne (Py[16]) with 16 contiguous triple bonds and endcapped with bulky 3,5‐bi(3,5‐bis‐tert‐butylphenyl)pyridine groups. Aggregation of 1D π‐conjugated oligoyne chains is rare given the minimal π–π intermolecular interactions as well as its flexibility that works against self‐assembly. In dilute solutions, the reversible aggregation of Py[16] initiates at low temperature in the range of 140–180 K, and is not observed for shorter oligoynes in this series. Cryogenic UV/Vis electronic absorption spectra and vibrational Raman spectra with different laser wavelength lines tuning from in‐resonance to off‐resonance conditions have been used to extract the vibrational features characterizing the monomer and aggregate species. Theoretical calculations complement the spectroscopic findings.
Function Switch of a Fungal Sesterterpene Synthase through Molecular Dynamics Simulation Assisted Alteration of an Aromatic Residue Cluster in the Active Pocket of PfNS
Authors: Zhang Weiyan , Wang Xinye , Zhu Guoliang , Zhu Bin , Peng Kaitong , Hsiang Tom , Zhang Lixin , Liu Xueting
Published: June 2024

Terpene synthases (TPSs) play pivotal roles in generating diverse terpenoids through complex cyclization pathways. Protein engineering of TPSs offers a crucial approach to expanding terpene diversity. However, significant potential remains untapped due to limited understanding of the structure‐function relationships of TPSs. In this investigation, using a joint approach of molecular dynamics simulations‐assisted engineering and site‐directed mutagenesis, we manipulated the aromatic residue cluster (ARC) of a bifunctional terpene synthase (BFTPS), Pestalotiopsis fici nigtetraene synthase (PfNS). This led to the discovery of previously unreported catalytic functions yielding different cyclization patterns of sesterterpenes. Specifically, a quadruple variant (F89A/Y113F/W193L/T194W) completely altered PfNS′s function, converting it from producing the bicyclic sesterterpene nigtetraene to the tricyclic ophiobolin F. Additionally, analysis of catalytic profiles by double, triple, and quadruple variants demonstrated that the ARC functions as a switch, unprecedently redirecting the production of 5/11 bicyclic (Type B) sesterterpenes to 5/15 bicyclic (Type A) ones. Molecular dynamics simulations and theozyme calculations further elucidated that, in addition to cation‐π interactions, C−H⋅⋅⋅π interactions also play a key role in the cyclization patterns. This study offers a feasible strategy in protein engineering of TPSs for various industrial applications.
Accelerating the Discovery of Oxygen Reduction Electrocatalysts: High‐Throughput Screening of Element Combinations in Pt‐Based High‐Entropy Alloys
Authors: Pan Yiyang , Shan Xiangyi , Cai Furong , Gao Han , Xu Jianan , Zhou Min
Published: June 2024

The vast number of element combinations and the explosive growth of composition space pose significant challenges to the development of high‐entropy alloys (HEAs). Here, we propose a procedural research method aimed at accelerating the discovery of efficient electrocatalysts for oxygen reduction reaction (ORR) based on Pt‐based quinary HEAs. The method begins with an element library provided by a large language model (LLM), combined with microscale precursor printing and pulse high‐temperature synthesis techniques to prepare multi‐element combination HEA array in one step. Through high‐throughput measurement using scanning electrochemical cell microscopy (SECCM), precise identification of highly active HEA element combinations and exploration of composition space for a specific combination are achieved. Advantageous element combinations are further validated in practical electrocatalytic evaluations. The contributions of individual element sites and the synergistic effects among elements of such HEAs in enhancing reaction activity are elucidated via density functional theory (DFT) calculations. This method integrates high‐throughput experiments, practical catalyst validation, and DFT calculations, providing a new pathway for accelerating the discovery of efficient multi‐element materials in the field of energy catalysis.
exo‐6b2‐Methyl‐Substituted Pentabenzocorannulene: Synthesis, Structural Analysis, and Properties
Authors: Wu Guan‐Yi , Huang Chun‐Lin , Kang Hao‐Wen , Ou Wei‐Ting , Ho Yeu‐Shiuan , Cheng Mu‐Jeng , Wu Yao‐Ting
Published: June 2024

exo‐6b2‐Methyl‐substituted pentabenzocorannulene (exo‐PBC‐Me) was synthesized by the palladium‐catalyzed cyclization of 1,2,3‐triaryl‐1H‐cyclopenta[l]phenanthrene. Its bowl‐shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X‐ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen‐doped analogs with intact π‐conjugated backbones (see the main text), exo‐PBC‐Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250–620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO–LUMO gap (2.01 eV). exo‐PBC‐Me formed polar crystals where all bowl‐in‐bowl stacking with close π ⋅ ⋅ ⋅ π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.
Cucurbit[8]uril‐Mediated Supramolecular Heterodimerisation and Photoinduced [2+2] Heterocycloaddition to Generate Unexpected [2]Rotaxanes
Authors: Zhang Shu , Zhang Liyan , Chen Aocheng , An Yi , Chen Xu‐Man , Yang Hong , Li Quan
Published: June 2024

In contrast to the self‐assembly of homosupramolecules, the self‐assembly of heterosupramolecules is more challenging and significant in various fields. Herein, we design and investigate a cucurbit[8]uril‐mediated heterodimerisation based on an arene‐fluoroarene strategy. Furthermore, the heteroternary complex is found to be able to undergo a photoinduced [2+2] heterocycloaddition, resulting in the formation of an unexpected [2]rotaxane. This work demonstrates a novel supramolecular heterodimerisation system that not only contributes to the development of photoisomerisation systems, but also enriches synthetic methods for mechanically interlocked molecules.
5‐(4′‐carboxylphenoxy) isophthalic acid and 1, 4‐bis(1‐imidazolyl)benzene appended Co(II)‐based MOF as efficient photocatalyst for nitrofurantoin degradation
Authors: Wang Jia‐Jia , Pu Cui‐Ying , Lu Lu , Muddassir Mohd. , Srivastava Shreya , Jayswal Madhav Raj , Wang Xiaoxiong , Kumar Abhinav
Published: June 2024

A new Cobalt(II)‐based metal–organic framework (MOF) with composition [Co2(μ2‐OH)(L)(bib)·H2O·2DMA]n (1) (H3L = 5‐[4′‐carboxylphenoxy] isophthalic acid, bib = 1, 4‐bis[1‐imidazolyl]benzene, DMA = dimethylacetamide) has been solvothermally synthesized and characterized. The MOF exhibits unprecedented topology with Schläfli symbol (43)2(4.66.1686) and display optical band gap of 3.68 eV and hence utilized as photocatalyst to photodegrade antibiotics such as metronidazole, tinidazole, nitrofurantoin, and dimetridazole. Among these antibiotics, it displays exceptional photocatalytic degradation of nitrofurantoin. Additional studies suggest that at pH 5 and 5 mg/L dosage of 1, 99.66% of nitrofurantoin decomposes at its 40 ppm concentration. Further, mechanistic pathway for light‐driven nitrofurantoin decomposition has been explored by utilizing experimental, namely, radical trapping experiments and computational techniques employing density of states and Hirshfeld surface analyses.
Enhanced antibacterial activity of poly(vinyl alcohol)‐graphene composites via graphene oxide surfactancy
Authors: Jung Jae Gu , Kim Jin Hee , Moon Juhyung , Kang Jun Hyeok , Kim Yu Jin , Park Ho Bum
Published: June 2024

The escalating threat of bacterial infections to human health necessitates innovative antibacterial strategies and materials. Despite this need, there is still a significant demand for materials that combine high mechanical and thermal properties with biocompatibility. To address these urgent issues, our study investigates the development of poly(vinyl alcohol) (PVA) composite with graphene flakes (GF) as fillers. The aim is to strengthen the unique properties of graphene to enhance antibacterial activity. Graphene oxide (GO) was used as a surfactant to achieve stable graphene dispersion in water, preserving its inherent properties while avoiding the drawbacks associated with common surfactants, such as property reduction and complex removal processes. In this study, the mechanical and thermal properties of PVA composites containing GO and GF are superior to those of pristine PVA. Especially, the PVA‐2 composite exhibited a notable enhancement in both tensile strength and elongation at break compared with the PVA composite, with increases of 7.8% and 15% respectively. Moreover, PVA‐2, 4, and 6 composites exhibit significant antibacterial efficacy, achieving 4.8 and 4.9 log CFU/cm2 for Staphylococcus aureus and Escherichia coli, respectively. These results indicate that the enhanced oxidative stress induced by GO as a surfactant, combined with the physical damage caused by the increased GF nanostructures. This study highlights the potential of PVA/GF/GO composites in biomedical and tissue engineering applications, providing a promising pathway for the development of new antibacterial materials.
Preparation and rheological properties of organic zirconium crosslinked KGM/HPAM gel
Authors: Li Jie , Jiang Qiyun , Gao Shanjun , Shen Chunhui
Published: June 2024

Konjac glucomannan (KGM) and partially hydrolyzed polyacrylamide (HPAM) have good application prospects in the field of petroleum fracturing field, but few studies on the rheological properties of KGM and HPAM double polymer gel systems have been reported. Optimal conditions for the high temperature and shear resistant organozirconium crosslinked double polymer gel system for petroleum fracturing were explored through optimization experiments. The thickener contained a mass ratio of 2:1 of KGM to HPAM, while the organic zirconium crosslinking agent had controlled molar ratios of 1:4:3:3 of zirconium butoxide to ligand acetylacetone, triethanolamine, and glycerol. This work presents a systematic analysis of the chemical structure, microstructure, delayed crosslinking performance, temperature resistance, and shear resistance of the gel system. The study found that the crosslinking ratio of 100:2 resulted in a controllable delayed crosslinking time of the gel formed by the organic zirconium crosslinking agent and 4.0 g/L KGM/HPAM thickener within 5–25 min at room temperature. The viscosity remained above 81 mPa·s even after shearing for 100 min at 140°C and 170 s−1. These findings provide a useful reference for the application of organic zirconium crosslinked KGM/HPAM gel system in the petroleum fracturing field.
Application of Object Detection Algorithm for Efficient Damages Identification of the Conservation of Heritage Buildings
Authors: Tang Huadu , Feng Yalin , Wang Ding , Zhu Ruiguang , Wang Liwei , Hao Shengwang , Xu Shan
Published: June 2024

Heritage buildings are crucial for any area's cultural and political aspects. Proper maintenance and monitoring are essential for the conservation of these buildings. However, manual inspections are time‐consuming and expensive. We propose a deep learning–based detection framework to identify the damages on the ancient architectural wall. The algorithm applied in this study is YOLOv5. Comparing its five different versions, it was decided to use YOLOv5m as the most accurate detection algorithm with a mAP of 0.801. The damage types identified are physical weathering and visitors' scratches. High‐resolution images were selected for the experiment and effectively identified image. In addition, the applied algorithm allows real‐time detection and the identification of seasonal sources of disruption, which is proved by the video test in this study. The findings contribute to the development of an intelligent tool for health monitoring with the goal of fast and remote damage detection in the routine maintenance of heritage buildings.
Caffeine Inhibits Both Basal and Insulin‐Activated Urate Transport
Authors: Mandal Asim K. , Merriman Tony R. , Choi Hyon K. , Mount David B.
Published: June 2024

Objective

Caffeine, an adenosine receptor antagonist, is a potent central nervous system stimulant that also impairs insulin signaling. Recent studies have suggested that coffee consumption lowers serum urate (SU) and protects against gout by unknown mechanisms. We hypothesized that caffeine lowers SU by affecting activity of urate transporters.

Methods

We examined the effect of caffeine and adenosine on basal and insulin stimulation of net 14C‐urate uptake in the human renal proximal tubule cell line PTC‐05 and on individual urate transporters expressed in Xenopus laevis oocytes.

Results

We found that caffeine and adenosine efficiently inhibited both basal and insulin stimulation of net 14C‐urate uptake mediated by endogenous urate transporters in PTC‐05 cells. In oocytes expressing individual urate transporters, caffeine (>0.2 mM) more efficiently inhibited the basal urate transport activity of GLUT9 isoforms, OAT4, OAT1, OAT3, NPT1, ABCG2, and ABCC4 than did adenosine without significantly affecting URAT1 and OAT10. However, unlike adenosine, caffeine at lower concentrations (<0.2 mM) very effectively inhibited insulin activation of urate transport activity of GLUT9, OAT10, OAT1, OAT3, NPT1, ABCG2, and ABCC4 by blocking activation of Akt and extracellular signal–regulated kinase.

Conclusion

We postulate that inhibition of urate transport activity of the re‐absorptive transporters GLUT9, OAT10, and OAT4 by caffeine is a key mechanism in its urate‐lowering effects. Additionally, the ability of caffeine to block insulin‐activated urate transport by GLUT9a and OAT10 suggests greater relative inhibition of these transporters in hyperinsulinemia.
Early developmental milestone clusters of autistic children based on electronic health records
Authors: Ben‐Sasson Ayelet , Guedalia Joshua , Ilan Keren , Shefer Galit , Cohen Roe , Gabis Lidia V.
Published: June 2024

Autistic children vary in symptoms, co‐morbidities, and response to interventions. This study aimed to identify clusters of autistic children with a distinct pattern of attaining early developmental milestones (EDMs). The clustering of 5836 autistic children was based on the attainment of 43 gross motor, fine motor, language, and social developmental milestones during the first 3 years of life as recorded in baby wellness visits. K‐means cluster analysis detected four EDM clusters: mild (n = 1686); moderate (n = 1691); severe (n = 2265); and global (n = 194). The most prominent cluster differences were in the language domain. The global cluster showed earlier and greater developmental delay across domains, unique early gross motor delays, and more were born preterm via cesarean section. The severe cluster had poor language development prominently in the second year of life, and later fine motor delays. Moderate cluster had mainly language delays in the third year of life. The mild cluster mostly passed milestones. EDM clusters differed demographically, with higher socioeconomic status in mild cluster and lowest in global cluster. However, the severe cluster had more immigrant and non‐Jewish mothers followed by the moderate cluster. The rates of parental concerns and provider developmental referrals were significantly higher in the global, followed by the severe, moderate, and mild EDM clusters. Autistic children's language and motor delay in the first 3 years can be grouped by common magnitude and onset profiles as distinct groups that may link to specific etiologies (like prematurity or genetics) and specific intervention programs. Early autism screening should be tailored to these different developmental profiles.