bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an automated CBCT‐based simulation‐free platform for expedited palliative radiotherapy on a conventional linear accelerator
Authors: Tegtmeier Riley C. , Clouser Edward L. , Chen Quan , Buckey Courtney R. , Chungbin Suzanne J. , Kutyreff Christopher J. , Aguilar Jose S. , Labbe Amber L. , Horning Brooke L. , Rule William G. , Vora Sujay A. , Rong Yi
Published: December 2024

Background

Conventional approaches for emergent or expedited palliative radiotherapy (RT) involve the application of cumbersome vendor‐provided solutions and/or multiple patient appointments to complete the RT workflow within a compressed timeframe.

Purpose

This report delineates the clinical development of an in‐house, semi‐automated Cone‐beam computed tomography (CBCT)‐based simulation‐free platform for expedited palliative RT on conventional linacs, intended to supplant existing techniques employed at this institution.

Methods

The internal software, termed SimFree Wizard (SFW), was engineered utilizing a C#‐based application programming interface integrated within the treatment planning system (TPS). Generated scripts were compiled as stand‐alone executables, with a graphical user interface (GUI) customized via an integrated development environment. The platform was conceived as a framework for accelerated CBCT‐based RT, bypassing the requirement for standard simulation imaging. SFW employs full automation where feasible to minimize user intervention, supplemented by graphical instructions for tasks requiring manual execution. During development, relevant temporal metrics from 10 end‐to‐end tests for palliative spine RT were quantified. User feedback was solicited via a simple questionnaire assessing the overall platform usability. Automated in‐house secondary verification software was developed for validation of the TPS‐calculated monitor units (MUs).

Results

The mean duration for workflow execution was 41:42 ± 3:18 [mm:ss] (range ∼37–46 min). SFW satisfactorily generated simple, multi‐field CBCT‐based 3D treatment plans within seconds following delineation of the desired treatment area. User feedback indicated enhanced usability compared to previously employed solutions. Validation of the secondary verification software demonstrated accurate results for palliative spine RT and other simple cases wherein the dose calculation point resides in a predominantly homogenous medium.

Conclusion

A novel in‐house solution for expedited CBCT‐based RT was successfully developed, facilitating completion of the entire workflow within approximately 1‐hour or less for simple palliative/emergent scenarios. Overall, this application is expected to improve the quality and safety of palliative RT while greatly reducing workflow duration, thereby improving access to palliative care.
Comparative Wear and Friction Analysis of Sliding Surface Materials for Hydrostatic Bearing under Oil Supply Failure Conditions
Authors: Michalec Michal , Daněk Lukáš , Foltýn Jan , Svoboda Petr , Gachot Carsten , Hartl Martin , Křupka Ivan
Published: December 2024

Hydrostatic bearings are commonly used in high‐precision applications due to their excellent performance across a wide range of sizes, from millimeters to tens of meters. However, their operation is dependent on a continuous external supply. If this supply fails or the pad alignment is improper, collisions or damage to sliding surfaces can occur, compromising machine precision or even causing malfunction. This study presents an experimental assessment of selected material combinations for sliding surfaces to minimize damage in large‐scale hydrostatic bearings under critical conditions. The research aims to identify the most suitable material combinations that ensure a reliable and efficient operation of hydrostatic bearings, even in the case of oil supply failure or pad misalignment. The experimental methodology focuses on the influence of material properties on friction and wear. According to the results, the most suitable materials to combine with structural steel are tin, polytetrafluoroethylene, and leaded compositions. On the other hand, aluminum bronze, structural steel, and galvanized steel are the least suitable combinations. These findings offer valuable insights into selecting the most appropriate conformal sliding surface material combination for large‐scale hydrostatic bearings based on multiple criteria, which can contribute to improved safety and durability.
Deformation Behavior of La2O3‐Doped Copper during Equal Channel Angular Pressing
Authors: Kunčická Lenka , Walek Josef , Kocich Radim
Published: December 2024

Pure copper has a very low strength of not more than 20 MPa. Nevertheless, its mechanical properties can be enhanced by (micro)alloying, additions of strengthening particles/elements, or imparting structure modifications/grain refinement via (severe) shear strain. The presented study proposes a way of strengthening commercially pure copper by combining 5 wt% addition of La2O3 particles and deformation processing. The composite is vacuum induction cast and subsequently processed by the equal channel angular pressing (ECAP) severe plastic deformation method. Single‐pass ECAP through a die with 110° angle is selected to observe the effect of La2O3 addition on the development of substructure at the beginning of plastic deformation. The results show that the addition of oxide particles not only enhances the microhardness, but also efficiently supports the development of subgrains and shear bands during deformation, which finally results in an increase in the microhardness of the composite to more than double the original copper value. Although the presence of La2O3 particles slightly decreases the electric conductivity, the subsequent ECAP processing provides the final composite with a conductivity of 97.9% IACS (International Annealed Copper Standard), as it promotes the alignment of the strengthening particles along the developed shear bands.
A Stemness‐Enhanced Eye Drop Stimulates Corneal Regeneration via Sustained Release of Versican and Providing Lubricated Substrate
Authors: Li Shiding , Zhang Siyi , Fang Fei , Bai Jinjie , Sun Hao , Chen Liangbo , Fu Yao
Published: December 2024

Stem cells are vital for tissue regeneration, and their dysfunction can lead to diseases like aplastic anemia and Alzheimer's disease. Limbal epithelial stem cells (LESCs) maintain corneal transparency as the sole source of corneal epithelium. Dysfunction or deficiency of LESCs causes corneal opacity, neovascularization or corneal blindness, known as limbal stem cell deficiency (LSCD). Current LSCD treatment mainly relies on stem cell transplantation, which faces challenges like limited cell sources and immune rejection, making therapy challenging and often ineffective. This study introduces a cell‐free, stemness‐enhanced eye drop (SEED@) to stimulate autologous LESCs regeneration. SEED@, a thermosensitive Pluronic F‐127 hydrogel loaded with versican, can promote LESCs proliferation, chemotaxis, and migration while maintaining their stemness via the Wnt/β‐catenin signaling pathway. In vivo, Pluronic F‐127 alone can lubricate the cornea and promote corneal epithelial repair in mouse corneal alkali burn model. In addition, SEED@ forms a thin, transparent layer on the ocular surface, enabling sustained versican release for up to 24 h. Notably, twice‐daily application of SEED@ significantly accelerated corneal regeneration in a rabbit LSCD model, achieving approximately 95% corneal epithelial repair by day 14. Collectively, SEED@ shows great potential for treating LSCD and offers a promising drug delivery platform for ocular diseases.
Ultrathin Graphene Oxide Nanoribbon Networks as Architects of Enhanced Performance in Polyamide‐Based Nanofiltration Membranes
Authors: Zarshenas Kiyoumars , Habibpour Saeed , Salestan Saeed Khoshhal , Dou Haozhen , Sadrzadeh Mohtada , Rahimpour Ahmad , Pope Michael A. , Yu Aiping , Chen Zhongwei
Published: December 2024

Customized architecture and chemistry play a pivotal role in conferring exceptional permeability and selectivity to polyamide (PA) membranes for desalination and ionic separation. Herein, a new interfacial polymerization (IP) template, the ultrathin graphene oxide nanoribbon (GONR) networks, is developed to meet the need for minimizing the funnel effect and mediating the IP reaction toward a highly permeable and selective membrane. The coated GONR template efficiently represents the gutter layer role and regulates the adsorption and transport of amine monomers at the GONR interface, which is studied by molecular simulation as well. The structure, electrostatic interaction, capillary rise, and nanoconfinement of the IP template are manipulated by different GONR loadings to optimize the membrane structure. The optimized GONR loading at 0.02 g m−2 results in a hybrid layered GONR/PA‐thin‐film‐composite nanofiltration membrane with nanostrip crumpled structure beyond the PA context, ultrathin 15 nm PA nanofilm, 80% cross‐linking degree, and narrow pore size distribution. The membrane passes the upper bound trade‐off with a permeance of 21.3 L m−2 h−1 bar−1 and a remarkable rejection of 98% for Na2SO4. This research offers a fresh perspective on comprehensively understanding the role of the IP template in creating a desired membrane for efficient desalination and ionic separation.
Direct Crystallographic Observation of Obvious Structural Deformation in a Lead Halide Framework Induced by Host–Guest Interactions
Authors: Chen Xinfeng , Deng Quanzheng , Wang Shi , Chen Yichong , Li Yukong , Dan Wenyan , Liu Yang , Wu Yi‐nan , Han Lu , Fei Honghan
Published: December 2024

Host–guest chemistry represents a prominent field within many inorganic solids, where the host entity typically retains its original lattice. The hybrid composition and soft lattice of organolead halides make their structural changes and optical properties highly sensitive to host–guest interactions, distinguishing them from conventional inorganic solids. Herein, 3D electron diffraction tomography, an advanced crystallographic technique, is employed to observe the pronounced structural deformation of the lead bromide layers upon the cleavage of coordinated solvent molecules, which renders a coordination unsaturated side for the activated Pb2+ sites. Moreover, the structural transmutation induced by this process leads to a significant enhancement and red‐shift in self‐trapped emission, which is analyzed in‐depth using a variety of photophysical studies. More importantly, the activated Pb2+ centers are able to re‐coordinate with the environmental N,N‐dimethylformamide vapors in a selective and reversible manner, highlighting high application potentials in multilevel information encryption and anti‐counterfeiting.
Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra‐Articular Space
Authors: Crastin Ana , Martin Claire S. , Suresh Sai , Davies Scott P. , Kearns Daniel , Parlak Ahsen , Adcock Holly , Filer Andrew , Jones Simon W. , Raza Karim , Moakes Richard JA , Grover Liam M. , Hardy Rowan S.
Published: December 2024

Intra‐articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra‐articular application – capable of shear thinning under force but restructuring at rest to enhance residence. This study examined GSHs for extended intra‐articular glucocorticoid delivery of prednisolone (10 mg mL−1); demonstrating links between material mechanics, steroid release, and preclinical assessment of efficacy in synoviocyte culture and transgenic(TNF)197Gkl (TNFtg) murine model of arthritis. GSHs demonstrated sustained release, with typical Fickian profiles over 18 days. Moreover, systems showed good stability under extended culture, with inherent cell‐compatibility and suppression of inflammatory synoviocyte activation. In TNFtg animals, GSHs suppressed synovitis (70.08%, p < 0.05), pannus formation (45.01%, p < 0.05), and increased articular cartilage (82.23%, p < 0.05) relative to vehicle controls. The extended profile of steroid release from injectable GSH formulations holds promise in the treatment and management of inflammatory arthritides such as rheumatoid and osteoarthritis, representing a step‐change in intra‐articular drug delivery to suppress long‐term joint inflammation.
Rethinking Biomedical Titanium Alloy Design: A Review of Challenges from Biological and Manufacturing Perspectives
Authors: Rabbitt Daisy , Villapún Victor M. , Carter Luke N. , Man Kenny , Lowther Morgan , O'Kelly Paraic , Knowles Alexander J. , Mottura Alessandro , Tang Yuanbo T. , Luerti Lorenzo , Reed Roger C. , Cox Sophie C.
Published: December 2024

Current biomedical titanium alloys have been repurposed from other industries, which has contributed to several biologically driven implant failure mechanisms. This review highlights the added value that may be gained by building an appreciation of implant biological responses at the onset of alloy design. Specifically, the fundamental mechanisms associated with immune response, angiogenesis, osseointegration and the potential threat of infection are discussed, including how elemental selection can modulate these pivotal systems. With a view to expedite inclusion of these interactions in alloy design criteria, methods to analyze these performance characteristics are also summarized. While machine learning techniques are being increasingly used to unearth complex relationships between alloying elements and material properties, much is still unknown about the correlation between composition and some bio‐related properties. To bridge this gap, high‐throughput methods are also reviewed to validate biological response along with cutting edge manufacturing approaches that may support rapid discovery. Taken together, this review encourages the alloy development community to rethink their approach to enable a new generation of biomedical implants intrinsically designed for a life in the body, including functionality to tackle biological challenges thereby offering improved patient outcomes.
Scintillating Glass Fiber Arrays Enable Remote Radiation Detection and Pixelated Imaging
Authors: Huang Xiongjian , Le Yakun , Zhang Hao , Yin Bozhao , Guo Qianyi , Xiao Xiudi , Liu Xiaofeng , Xia Zhiguo , Qiu Jianrong , Yang Zhongmin , Dong Guoping
Published: December 2024

The emerging metal halide perovskites are challenging the traditional scintillators in the field of radiation detection and radiography. However, they lack the capability for remote and real‐time radiation monitoring and imaging in confined and hostile conditions. To address this issue, details on an inorganic scintillating glass fiber incorporating perovskite quantum dots (QDs) as highly efficient pixelated radiation emitters are reported, while the glass fibers themselves serve at the same time as low‐loss waveguides, enabling long‐distance and underwater X‐ray detection. The multi‐color emissions and controllable radiation sensitivities endow CsPbX3 (X = Cl, Br, I) QD scintillating glass fibers with the potential as wearable and visualized radiation indicators. Furthermore, these scintillating glass fibers can be regularly arranged into a fiber array plate with a thickness of 7.5 mm to enhance X‐ray absorption for X‐ray imaging. Leveraging the light‐guiding character of glass fibers, a 5 × 5 fiber array with fiber lengths up to 11 cm has demonstrated the potential of remote pixelated X‐ray imaging. This study offers a novel platform for the development of remote detectors and imagers for X‐ray radiation.
HClO‐Activated Near‐Infrared Chemiluminescent Probes with a Malononitrile Group for In‐Vivo Imaging
Authors: Cao Yalei , Gu Juqing , Chen Zhijian , Gao Jucai , Yang Jie , Wu Wenbo , Fang Manman , Li Qianqian , Liu Bin , Li Zhen
Published: December 2024

Chemiluminescence (CL) imaging has emerged as a powerful approach to molecular imaging that allows exceptional sensitivity with virtually no background interference because of its unique capacity to emit photons without an external excitation source. Despite its high potential, the application of this nascent technique faces challenges because the current chemiluminescent agents have limited reactive sites, require complex synthesis, are insufficiently bright, and lack near‐infrared emission. Herein, a series of HClO‐activated chemiluminescent probes that exhibit robust near‐infrared emission are studied. Specifically engineered to respond to HClO, a known biomarker of acute inflammation, these probes achieve high‐contrast in vivo imaging by eliminating the need for constant external excitation. Comprehensive experimental and theoretical investigations demonstrate that the CL of the probes depends on the reactivity of the vinylene bonds, following a concerted decomposition of the oxidized chemiluminescent molecule. The application of these chemiluminescent nanoparticles in vivo facilitates high‐contrast imaging of acute inflammation, providing real‐time, high‐contrast visualization of inflammatory conditions. This advancement signifies a leap forward for chemiluminescent nanoplatforms in biomedical imaging and expands the available methodologies in this field.
Tough Polyurethane Hydrogels with a Multiple Hydrogen‐Bond Interlocked Bicontinuous Phase Structure Prepared by In Situ Water‐Induced Microphase Separation
Authors: Wang Ruyue , Xu Ting , Yang Yuxuan , Zhang Mengyuan , Xie Ruilin , Cheng Yilong , Zhang Yanfeng
Published: December 2024

Hydrogels with mechanical performances similar to load‐bearing tissues are in demand for in vivo applications. In this work, inspired by the self‐assembly behavior of amphiphilic polymers, polyurethane‐based tough hydrogels with a multiple hydrogen‐bond interlocked bicontinuous phase structure through in situ water‐induced microphase separation strategy are developed, in which poly(ethylene glycol)‐based polyurethane (PEG‐PU, hydrophilic) and poly(ε‐caprolactone)‐based polyurethane (PCL‐PU, hydrophobic) are blended to form dry films followed by water swelling. A multiple hydrogen bonding factor, imidazolidinyl urea, is introduced into the synthesis of the two polyurethanes, and the formation of multiple hydrogen bonds between PEG‐PU and PCL‐PU can promote homogeneous microphase separation for the construction of bicontinuous phase structures in the hydrogel network, by which the hydrogel features break strength of 12.9 MPa, fracture energy of 2435 J m−2, and toughness of 48.2 MJ m−3. As a biomedical patch, the outstanding mechanical performances can withstand abdominal pressure to prevent hernia formation in the abdominal wall defect model. Compared to the commercial PP mesh, hydrogel can prevent tissue/organ adhesion to reduce inflammatory responses and promote angiogenesis, thereby accelerating the repair of abdominal wall defects. This work may provide useful inspiration for researchers to design different gel materials through solvent‐induced microphase separation.
Popularizing Holistic High‐Index Crystal Plane via Nonepitaxial Electrodeposition Toward Hydrogen‐Embrittlement‐Relieved Zn Anode
Authors: Zou Yuhan , Mu Yongbiao , Xu Liang , Qiao Changpeng , Chen Ziang , Guo Wenyi , Gu Jiaxi , Su Yiwen , Zeng Lin , Cheng Tao , Sun Jingyu
Published: December 2024

Electrodeposition is promising to fabricate Zn electrodes affording nonepitaxial single‐crystal textures. Previous research endeavors focus on achieving Zn(002) faceted deposition, nevertheless, the popularization of a high‐index Zn plane with favorable electrochemical activity remains poorly explored. There also exists a deficiency in the assessment of the electrodeposited quality of Zn. Here, a straightforward strategy to address such concerns by cultivating predominant Zn(112) texture via a potentiostatic electrodeposition mode is reported. By precisely identifying the “limiting” conditions for electrodeposition, a striking balance between improved deposition quality, tailored deposition kinetics, and suppressed hydrogen evolution is found. (002) Faceted Zn electrode is shown that be indeed produced, yet the rampant hydrodynamic convection and hydrogen embrittlement issue under such “over‐limiting” preparation conditions pose challenges in the electrode lifespan. In contrast, an optimized deposition minimizes hydrodynamic disturbances and mitigates the hydrogen embrittlement effect, where the thus‐generated high‐index (112)‐textured Zn electrode manifests impressive deposition quality and demonstrates holistic cycling stability. The pouch cell by pairing a ZnxV2O5 (ZnVO) cathode manages a reversible capacity of ≈130 mAh and a capacity retention of 98.42%. This study offers guidance for the development of dendrite‐free and hydrogen‐embrittlement‐relieved Zn anodes, unleashing the potential of high‐index plane textures for advanced Zn batteries.
Creating Single‐Crystalline β‐CaSiO3 for High‐Performance Electronic Packaging Substrate
Authors: Jia Qingchao , Wang Wenzhi , Zhang Hujun , Chen Chunyu , Li Ao , Chen Chen , Yu Hang , Zhang Liangzhu , Tao Haizheng , Zeng Huidan , Luo Xiongke , Yue Yuanzheng
Published: December 2024

β‐CaSiO3 based glass‐ceramics are among the most reliable materials for electronic packaging. However, developing a CaSiO3 glass‐ceramic substrate with both high strength (>230 MPa) and low dielectric constant (<5) remains challenging due to its polycrystalline nature. The present work has succeeded in synthesizing single‐crystalline β‐CaSiO3 for a high‐performance glass‐ceramic substrate. This is accomplished by introducing Al3+ into the CaO‐B2O3‐SiO2 glass system, and by optimizing the sintering condition. Al3+ doping facilitates a heterogeneous network structure that energetically favors the precipitation of polycrystalline particles, including nanosized β‐CaSiO3 crystals and sub‐nanosized α‐CaSiO3 crystals. As the sintering temperature increases, the nano α‐CaSiO3 crystals (2–10 nm) are gradually absorbed by the β‐CaSiO3 crystals. Through atomic rearrangement, α‐CaSiO3 crystals transform into micrometer‐sized single crystal β‐CaSiO3 (1–2 µm) with layered structure. The low temperature co‐fired β‐CaSiO3 glass‐ceramics exhibit exceptional properties, including a low dielectric constant of 4.04, a low dielectric loss of 3.15 × 10−3 at 15 GHz, and a high flexural strength of 256 MPa. This work provides a new strategy for fabricating high‐performance single‐crystalline glass‐ceramics for electronic packaging and other applications.
Matching P‐ and N‐type Organic Electrochemical Transistor Performance Enables a Record High‐gain Complementary Inverter
Authors: Kuang Yazhuo , Yao Tangqing , Deng Sihui , Dong Jingjin , Ye Gang , Zhang Linlong , Shao Shuyan , Zhu Zhongjie , Liu Jun , Liu Jian
Published: December 2024

The charge transport of channel materials in n‐type organic electrochemical transistors (OECTs) is greatly limited by the adverse effects of electrochemical doping, posing a long‐standing puzzle for the community. Herein, an n‐type conjugated polymer with glycolated side chains (n‐PT3) is introduced. This polymer can adapt to electrochemical doping and create more organized nanostructures, mitigating the adverse effects of electrochemical doping. This unique characteristic gives n‐PT3 excellent charge transport in the doped state and reversible ion storage, making it highly suitable as an n‐type organic mixed ionic‐electronic conducting (OMIEC) material. n‐PT3 exhibits a high electron mobility of µ ≈ 1.0 cm2 V−1 s−1 and a figure of merit value of µC* ≈ 100 F cm−1 V−1 s−1, representing one of the best results for n‐type OMIEC materials. A new p‐type OMIEC polymer has been synthesized as the channel material for constructing a complementary inverter to match the n‐type OECT channel layer based on n‐PT3. As a result, a voltage gain value of up to 307 VV−1 has been achieved, which is a record value for sub−1 V complementary inverters based on OECTs. This work offers valuable insights into designing electrochemical doping adaptive n‐type OMIEC materials and fabricating high‐gain organic complementary inverters.
Manipulation Study of Bubble‐Propelled Hydrogel Microbots
Authors: Li Mingliang , Wang Ping , Zhang Hui , Liu Ping , Liu Guangli , Sui Cong , Yang Runhuai , Luo Tingting
Published: December 2024

Microbots have shown considerable potential in the biomedical field. Their capability to target specific areas for diagnosis, treatment, and other applications with minimal invasiveness is particularly advantageous. However, complex application environments and harsh driving conditions greatly limit the locomotion behaviors of microbots, and therefore the locomotion mode of microbots deserves more exploration and research. This study focuses on a near‐infrared light‐driven bubble‐propelled microbot. The photothermally responsive materials used in the design are modified to enhance bubble generation properties. Additionally, the controlled 3D printing preparation process can indirectly influence the bubble aggregation pathway by altering the microbot's micro‐nanostructured porous structure. Ultimately, by adjusting the laser parameters, the microbot can be controlled to achieve a variety of locomotion modes. Furthermore, the experimental observations and theoretical analysis of the microbot's locomotion modes are summarized. A preliminary digital description is provided, which verifies the feasibility of controlling these locomotion modes. This lays the foundation for the precise control of microbots in future applications.
Copper‐Catalyzed Reductive Coupling of Nitroalkanes with Aliphatic Grignard/Cerium and Organozinc Reagents for Synthesis of Functionalized Nitrones
Authors: Hata Takeshi , Nishi Koki , Yamaguchi Koki , Tatsumi Yuta , Tanaka Naomi , Shigeta Masayuki , Urabe Hirokazu
Published: December 2024

This study aims to develop a more efficient, functional‐group‐tolerant approach using stable nitroalkanes and reductive coupling reactions with aliphatic Grignard/cerium and organozinc reagents. The treatment of nitroalkanes with aliphatic Grignard reagents in the presence of a catalytic amount of CuF2 and stoichiometric amount of CeCl3 affords various nitrones in good yields as single isomers. The reaction of tertiary nitroalkanes with organozinc reagents affords various functionalized nitrones without CuF2 or CeCl3. These reductive coupling reactions proceed without the loss of functional groups such as alkene, alkyne, benzyl ether, chlorine, ester, and nitrile moieties. Nitrones can also be used as precursors for [3+2] cyclizations with electron‐withdrawing alkenes and alkynes.
Copper and DMAP Relay‐Catalyzed Three‐Component coupling of Terminal Alkynes, Anthranils and Alcohols for the Modular Synthesis of 2‐alkoxy Quinolines
Authors: Li Haixia , Gao Yang , Zhong Xiongwei , Huo Yanping , Li Xianwei , Chen Qian
Published: December 2024

A copper and DMAP relay‐catalyzed strategy has been achieved for the modular synthesis of 2‐alkoxy quinolines from a three‐component coupling of terminal alkynes, anthranils, and alcohols. In this protocol, a novel quinoline pyridine salt is formed and serves as a key intermediate in the formation of 2‐alkoxy quinolines. The reaction has a broad substrate scope of each reaction partners, affording diversified 2‐alkoxy quinoline products in generally good yields.
Statistical, Bottom‐Up Model for Chemical Diffusion Based on Atomic Vacancy Sublattice Configurations in Layered Lithium Nickel Oxide Cathode Materials
Authors: Olou'ou Guifo Stéphane B. , Mueller Jonathan E. , Markus Torsten
Published: December 2024

To investigate the influence of the local environment on Li‐ion diffusivity in layered lithium nickel oxide (LixNiO2) cathodes, a bottom‐up, multiscale‐modeling approach is applied, utilizing density functional theory (DFT) with corrected Coulomb and van der Waals interactions to describe the energy‐structure relationship of LixNiO2 (x = 0 – 1) in good agreement with previous experiments. The UNiversal CLuster Expansion (UNCLE) is employed to construct high‐probability Li–vacancy configurations and the Nudged Elastic Band (NEB) method to compute energy barriers for representative Li diffusion mechanisms. By fitting a cluster expansion model to these barriers, diffusion barriers are determined for all possible Li–vacancy configurations within a nearest‐neighbor approximation. Based on this description, Li‐concentration‐dependent diffusion coefficients are predicted for the entire Li‐concentration range. For the LixNiO2 crystal lattice, the computed Li chemical diffusivities well lie within experimental ranges, namely 10−11 – 10−8 cm2 s−1, at room temperature with activation energies around 37.9 kJ mol−1. The maximum diffusivity of 4.23 × 10−8 cm2 s−1 is identified at x = 0.63. The new analytical, self‐consistent approach here relies on configurational samplings of individual atomistic mechanisms and can be applied to investigate diffusion properties in further dilute and concentrated alloy systems more efficiently than common numerical procedures.
Revealing the Effect of Solvent Additive Selectivity on Morphology and Formation Kinetics in Printed Non‐fullerene Organic Solar Cells at Ambient Conditions
Authors: Zhang Jinsheng , Li Zerui , Jiang Xinyu , Xie Lin , Pan Guangjiu , Buyan‐Arivjikh Altantulga , Baier Thomas , Tu Suo , Li Lixing , Schwartzkopf Matthias , Vayalil Sarathlal Koyiloth , Roth Stephan V. , Ge Ziyi , Müller‐Buschbaum Peter
Published: December 2024

Solvent additives enable the efficient modification of the morphology to improve the power conversion efficiency (PCE) of organic solar cells. However, the impact of solvent additive selectivity on the film morphology and formation kinetics is still unclarified. Herein, this work investigates two solvent additives, 1‐chloronaphthalene (1‐CN) and tetralin, characterized by their varying selectivity for the polymer donor (PBDB‐T‐2F) and the non‐fullerene small molecule acceptor (BTP‐C3‐4F). Specifically, 1‐CN exhibits superior solubility for BTP‐C3‐4F over PBDB‐T‐2F, whereas tetralin shows the opposite trend. The blend films with and without solvent additives are fabricated with the slot‐die coating at ambient conditions. Both solvent additives can promote larger phase separation and increase the size of crystals of the selectively dissolved component. In situ grazing‐incidence wide‐angle X‐ray scattering and UV–vis absorption spectra during printing unveil two distinct kinetic processes induced by 1‐CN and tetralin, leading to large‐sized crystals. 1‐CN can prolong the liquid‐solid phase separation to provide sufficient time for the BTP‐C3‐4F crystal growth but suppress the crystal growth of PBDB‐T‐2F. Tetralin can swell PBDB‐T‐2F and break down BTP‐C3‐4F crystals at the same time. Upon thermal annealing, the oversized crystals triggered by both solvent additives can be optimized to an appropriate size, resulting in an enhanced PCE.
A Deep Intronic Splice Variant in COL1A1 Causing Osteogenesis Imperfecta Type II
Authors: Schouw Mackenna E. , Ruivenkamp Claudia A. L. , Koopmann Tamara T. , Santen Gijs W. E. , Nikkels Peter G. J. , van der Tuin Karin
Published: December 2024

Osteogenesis imperfecta (OI) is a rare disease, hallmarked by bone fragility, multiple fractures, and deformities, and is commonly caused by pathogenic variants in the genes encoding type I collagen. Type II OI is the most severe form and is lethal in the perinatal period. Here, we report recurrence of perinatal lethal OI in two fetuses due to parental mosaicism for a deep intronic pathogenic variant at c.2451 + 77C > T in intron 35 of COL1A1, which resulted in aberrant splicing and the in‐frame addition of 75 nucleotides into the mRNA. These patients highlight the importance of considering deep intronic variants in type 1 collagen genes in patients with high suspicion of OI, which may be missed with conventional genetic analysis.
Oxirane‐Driven Cascade Transformations of 5‐Arylidene‐Thiazolidine‐2,4‐Diones
Authors: Simonov Alexander Yu. , Panov Alexey A. , Churakov Andrei V. , Polshakov Vladimir I. , Levshin Igor B.
Published: December 2024

The reaction of thiazolidine‐2,4‐diones (TZDs) with oxiranes has been thoroughly investigated. For the first time, it has been observed that 5‐arylidene‐TZD derivatives can undergo transformation into 6‐substituted 1,4‐oxathian‐2‐ones. Additionally, it has been demonstrated that certain 3‐substituted 5‐arylidene‐TZDs can convert to 1,4‐oxathian‐2‐ones and oxazolidines upon reaction with oxiranes, confirming that the process follows a cascade mechanism. Several factors have been found to influence the reaction‘s outcome, including the amount of oxirane, the presence of a base, and solvent polarity. It has been determined that dimethylformamide (DMF) is essential for the reaction to proceed efficiently. Furthermore, the critical role of the benzylidene group in facilitating the reaction has been confirmed. An unusual hydrogen bond between the ortho‐hydrogens of the phenyl group and the sulfur atom of the thiazolidine ring, observed via NMR spectroscopy, highlights the sulfur atom‘s strong electron‐accepting properties, which play a key role in the observed transformations.
Co‐pathologies modify hippocampal protein accumulation patterns in neurodegenerative diseases
Authors: Yoshida Koji , Forrest Shelley L. , Ichimata Shojiro , Tanaka Hidetomo , Kon Tomoya , Kovacs Gabor G.
Published: December 2024

INTRODUCTION

Limited research has extensively analyzed neurodegenerative disease–related protein deposition patterns in the hippocampus.

METHODS

This study examined the distribution of proteins in hippocampal subregions across major neurodegenerative diseases and explored their relation to each other. The area density of phosphorylated tau (p‐tau), amyloid beta (Aβ), α‐synuclein, and phosphorylated TDP‐43 protein deposits together with pyramidal cell density in each hippocampal subregion, including CA1‐4, prosubiculum (ProS), and subiculum was assessed in 166 cases encompassing various neurodegenerative diseases.

RESULTS

Alzheimer's disease‐associated p‐tau predominated in ProS, Aβ in the CA1, and Lewy body–related α‐synuclein in the CA2. The area density of protein deposits increased with the pathological stage until a peak, then decreased in cases with high pathology stages along with pyramidal cell density. Comorbid protein pathology influenced protein deposition patterns.

DISCUSSION

This comprehensive evaluation reveals characteristic neurodegenerative disease–related protein accumulation patterns in hippocampal subregions modified by co‐pathologies.

Highlights

Alzheimer's disease–related phosphorylated tau predominates in the prosubiculum.

Amyloid beta predominates in the CA1 and Lewy body–related α‐synuclein in the CA2.

The area density of protein deposition increases with the disease stage up to a peak.

In the high pathology stage, protein deposition and pyramidal cell density decreases.

Comorbid protein pathology affects the pattern of protein accumulation.
Examination of MGMT as a risk gene for dementia in the Amish
Authors: Main Leighanne R. , Song Yeunjoo E. , Lynn Audrey , Laux Renee A. , Miskimen Kristy L. , Osterman Michael D. , Cuccaro Michael L. , Ogrocki Paula K. , Lerner Alan J. , Vance Jeffery M. , Fuzzell M. Denise , Fuzzell Sarada L. , Hochstetler Sherri D. , Dorfsman Daniel A. , Caywood Laura J. , Prough Michael B. , Adams Larry D. , Clouse Jason E. , Herington Sharlene D. , Scott William K. , Pericak‐Vance Margaret A. , Haines Jonathan L.
Published: December 2024

INTRODUCTION

Recently, the O‐6‐methylguanine‐DNA methyltransferase (MGMT) locus was proposed as influencing the risk of Alzheimer's disease (AD) in women who did not carry the apolipoprotein E ε4 allele. We examined an Amish founder population for any influence of genetic variation in and around the MGMT locus on the risk for dementia.

METHODS

Genetic association was performed for single nucleotide polymorphisms (SNPs) surrounding the MGMT locus. A total of 946 individuals of Amish descent between the ages of 76 and 95 who were classified as cognitively impaired or cognitively unimpaired were included. Multiple statistical models were applied to test for replication.

RESULTS

The results for the previously associated individual SNPs were not significant. However, a different SNP (rs7909468) generated significant results under a model different from the previous report.

DISCUSSION

The MGMT locus may influence the risk of AD, although its genetic mechanisms remain unclear and warrant further study.

Highlights

Association analyses around the O‐6‐methylguanine‐DNA methyltransferase (MGMT) locus showed a study‐significant single nucleotide polymorphism (SNP), rs7909468, in a female cognitively impaired group lacking the apolipoprotein E ε4 genotype.

Functional implications of rs7909468 are relatively unexplored, but in silico analyses indicate it may regulate MGMT expression.

rs7909468 was not in linkage disequilibrium with other SNPs found to be significant in this region and appears as a distinct novel association.
Proteomic signatures of Alzheimer's disease and Lewy body dementias: A comparative analysis
Authors: Canal‐Garcia Anna , Branca Rui M. , Francis Paul T. , Ballard Clive , Winblad Bengt , Lehtiö Janne , Nilsson Per , Aarsland Dag , Pereira Joana B. , Bereczki Erika
Published: December 2024

INTRODUCTION

We aimed to identify unique proteomic signatures of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD).

METHODS

We conducted a comparative proteomic analysis of 33 post mortem brains from AD, DLB, and PDD individuals without dementia focusing on prefrontal, cingulate, and parietal cortices, using weighted gene co‐expression network analyses with differential enrichment analysis.

RESULTS

Network modules revealed hub proteins common to all dementias. Lewy body dementias differed from AD by reduced levels of the autophagy protein p62 (SQSTM1), whereas DLB was distinguished from both AD and PDD by altered TRIM33 and cysteine/glutamate transporter (SLC7A11) across brain regions. An increase in mitochondrial and synaptic proteins was related to better cognition whereas enrichment in the extracellular matrix, complement system, and autophagy proteins was associated with greater cognitive impairment.

DISCUSSION

Our study offers valuable insights into the network‐based biomarker characterization of molecular signatures of AD, DLB, and PDD.

Highlights

Reduced levels of the autophagy protein p62 (SQSTM1) differentiated Lewy body dementias from Alzheimer's disease (AD) across multiple brain regions.

Dementia with Lewy bodies (DLB) was distinguished from both AD and Parkinson's disease dementia (PDD) by altered TRIM33 and cysteine/glutamate transporter (SLC7A11) levels across brain regions.

Key mitochondrial oxidative phosphorylation proteins (e.g., COX7A2, TOMM40L, NDUFV1), and synaptic proteins (e.g., GABRB3, GABRB2, GLUA3, GLUA4, SNAP47, dynamin1) were more abundant in preserved cognitive states.

Extracellular matrix proteins and members of the complement system (decorin, biglycan, C4A, C4B) showed a strong positive correlation with cognitive decline.
Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms
Authors: Falkon Kristian F. , Danford Liliana , Gutierrez Kuri Eduardo , Esquinca‐Moreno Paulina , Peña Señeriz Yaren L. , Smith Sabrina , Wickline Jessica L. , Louwrier Ariel , McPhail Jacob A. , Sayre Naomi L. , Hopp Sarah C.
Published: December 2024

INTRODUCTION

Alzheimer's disease (AD) and other tauopathies are characterized by intracellular aggregates of microtubule‐associated protein tau that are actively released and promote proteopathic spread. Microglia engulf pathological proteins, but how they endocytose tau is unknown.

METHODS

We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin‐mediated endocytosis (CME) or antagonism/genetic depletion of known tau receptors heparan‐sulfate proteoglycans (HSPGs) and low‐density lipoprotein receptor‐related protein 1 (LRP1).

RESULTS

Dynamin inhibition decreased microglial endocytosis of all tested tau species. Meanwhile, HSPG antagonism blocked only fibril uptake, and LRP1 antagonism or genetic depletion inconsistently inhibited the endocytosis of fibrils and monomers. Cre recombinase robustly enhanced tau uptake with partial selectivity for fibrils.

DISCUSSION

These data show that microglia take up both tau monomers and aggregates via a dynamin‐dependent form of endocytosis (eg, CME) but may differ in using HSPGs for entry depending on species.

Highlights

Microglial endocytosis of tau monomers and fibrils is dynamin‐dependent.

HSPG antagonism blocks microglial uptake of tau fibrils but not monomers.

LRP1 antagonism or knockdown inconsistently inhibits tau uptake.

TAT‐Cre stimulates semi‐selective uptake of fibrils over monomers.
Increased White Matter Aerobic Glycolysis in Multiple Sclerosis
Authors: Brier Matthew R , Judge Bradley , Ying Chunwei , Salter Amber , An Hongyu , Patel Aakash , Wang Qing , Wang Yong , Cross Anne H , Naismith Robert T , Benzinger Tammie LS , Goyal Manu S
Published: December 2024

Objective

Despite treatments which reduce relapses in multiple sclerosis (MS), many patients continue to experience progressive disability accumulation. MS is associated with metabolic disruptions and cerebral metabolic stress predisposes to tissue injury and possibly impaired remyelination. Additionally, myelin homeostasis is metabolically expensive and reliant on glycolysis. We investigated cerebral metabolic changes in MS and when in the disease course they occurred, and assessed their relationship with microstructural changes.

Methods

This study used combined fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) to measure cerebral metabolic rate of glucose and oxygen, thereby quantifying glycolysis. Twelve healthy controls, 20 patients with relapsing MS, and 13 patients with non‐relapsing MS were studied. Relapsing patients with MS were treatment naïve and scanned pre‐ and post‐initiation of high efficacy disease modifying therapy.

Results

In normal appearing white matter, we observed increased glucose utilization and reduced oxygen utilization in newly diagnosed MS, consistent with increased glycolysis. Increased glycolysis was greater in patients with a longer disease duration course and higher disability. Among newly diagnosed patients, different treatments had differential impacts on glucose utilization. Last, whereas hypermetabolism within lesions was clearly associated with inflammation, no such relationship was found within normal appearing white matter.

Interpretation

Increased white matter glycolysis is a prominent feature of cerebral metabolism in MS. It begins early in the disease course, increases with disease duration and is independent of microstructural evidence of inflammation in normal appearing white matter. Optimization of the metabolic environment may be an important component of therapies designed to reduce progressive disability. ANN NEUROL 2024
Air‐Mediated Biomimetic Synthesis of Polyhydroxyalkanoate with C4 Diol
Authors: Xie Huilin , Zhong Kaibin , Niu Shihao , Li Xiaoxu , Hu Zexu , Xiao Guang , Huang Yifu , Zhang Hongjie , Liu Yuan , Zhang Hefeng , Cai Qiuquan
Published: December 2024

Poly(4‐hydroxybutyrate) (P4HB) is a high‐performance, well‐recyclable, and biodegradable polyhydroxyalkanoate (PHA). However, conventional bioproduction of homopolymeric P4HB involves complex and costly processes with C4 feedstocks, particularly 1,4‐butanediol (BDO), and enzyme‐coenzyme systems in genetically engineered bacteria. An alternative extracellular chemical route utilizing aerial oxidation of BDO offers cost and energy benefits but struggle with conversion efficiency. Inspired by efficient intracellular oxidation of primary alcohols, we propose a ruthenium‐phosphine synergistic catalytic system that mimics enzyme‐coenzyme functionality. This system effectively catalyzed the air‐mediated, solvent‐free oxidation of BDO to produce γ‐butyrolactone (γ‐BL) and oligomeric P4HB, with a space‐time yield (10.37 g [γ‐BL unit] g−1 catalyst h−1) surpassing the values (<5.5) of previous approaches. The oligomer‐containing products were reversibly converted to γ‐BL and then to P4HB (28.9 kDa) via ring‐opening polymerization, exceeding reported values (<16 kDa). This study provides the potential for large‐scale synthesis of high‐value PHAs from diverse non‐grain‐based diols, offering economic and environmental advantages.
Borane‐Mediated Highly Secondary Selective Deoxyfluorination of Alcohols
Authors: Willcox Dominic R. , Cironis Nojus , Winfrey Laura , Kirschner Sven , Nichol Gary S. , Thomas Stephen P. , Ingleson Michael J.
Published: December 2024

Organofluorine compounds are vital across multiple sectors, hence highly selective methods to install fluorine are of considerable importance. The deoxyfluorination of alcohols is a key approach to prepare organofluorine compounds, however, a highly secondary (2°)‐selective deoxyfluorination of alcohols has not been realized to date. Herein, we report that borane‐mediated deoxyfluorination results in high 2°‐selectivity in inter‐ and intra‐molecular competition reactions versus primary (1°), tertiary (3°) and even benzylic (Bn) alcohols. This is an operationally simple method using only commercial reagents (e.g., Et3N ⋅ 3HF) that starts from the alcohol which is converted to the O‐alkyl‐N‐H‐isourea in situ. The origin of the high 2°‐selectivity was elucidated to be due to the relative barriers to carbodiimide elimination from the O‐alkyl‐N‐(BR2)‐isoureas. As the selectivity controlling step does not involve fluoride, this borane‐mediated approach can be applied to other nucleophiles, as demonstrated by 2°‐selective deoxychlorination using HCl occurring in preference to substitution of 1° and Bn analogues. This borane‐mediated nucleophilic substitution therefore provides a new approach to circumvent the selectivity limitations inherent in classical SN2 and SN1 type reactions.
Auf dem Weg zur Nutzung von CO2‐Quellen mit Niedriger Konzentration durch Direkte Selektive Elektrokatalytische Reduktion
Authors: Mahbub Muhammad Adib Abdillah , Das Debanjan , Wang Xin , Lu Guilong , Muhler Martin , Schuhmann Wolfgang
Published: December 2024

Die direkte CO2‐Reduktionsreaktion (CO2RR) aus Rauchgas mit verschiedenen CO2‐Konzentrationen könnte die zusätzliche Energie für Vorkonzentrationsprozesse zu hochkonzentriertem CO2 als Ausgangsmaterial minimieren. Wir untersuchen die Herausforderungen für die CO2RR, die durch niedrige CO2‐Konzentrationen verursacht werden, und stellen Strategien für den Einfluss des gewählten Elektrokatalysatormaterials und die Auswahl des Elektrolyten vor, um eine hohe CO‐Selektivität zu erreichen. Wir führen den Gasdiffusionselektroden in einem Modell‐Durchflusselektrolyseur kontinuierlich CO2 gemischt mit N2 (dem typischen Verdünnungsmittel im Rauchgas) in verschiedenen Verhältnissen zu. Der Betrieb der CO2RR bei niedrigeren CO2‐Konzentrationen führt zu einer Verschiebung des Überpotentials zu mehr kathodischen Werten. Wir zeigen, dass aktivere Katalysatoren eine hohe CO‐Selektivität bis hinunter zu 5 % CO2 aufrechterhalten können, indem Katalysatoren auf NiCu‐Basis verwendet werden. NiCu erreicht seine Grenze, wenn die CO2‐Konzentration auf 2 % gesenkt wird, was auf die geringe CO2‐Verfügbarkeit und die Konkurrenz der Carbonatbildung zurückzuführen ist. Durch den Einsatz von nahezu neutralen Elektrolyten mit einer hohen Pufferkapazität konnten wir eine hohe Faradaysche Effizienz bei niedrigen Überspannungen und eine höhere CO2‐Ausnutzung bei niedriger CO2‐Konzentration erzielen.