bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in Promoting Bone Regeneration in Type 2 Diabetes Using Drug Delivery Vehicles and Vehicle‐Free Therapeutics
Authors: Pesaran Afsharian Yasamin , Rahimnejad Mostafa , Rabiee Sayed Mahmood , Feizi Farideh , Seitz Hermann
Published: January 2025

The incidence of type 2 diabetes (T2DM) increases significantly worldwide. Due to consistent hyperglycemia, insulin resistance, and chronic inflammation, T2DM patients encounter osteoporosis and induced osteoporotic fracture risks. Antidiabetic drugs have been traditional therapies that seek to control blood glucose, balance bone metabolism, and favor systemic immunosuppression. However, such drugs impact bone quality and its nano‐scale features in the long‐term. Today, biomedical experts are continuously advancing drug delivery tools for local delivery of osteo‐immunomodulatory agents in T2DM. It is demonstrated that bioavailability and release profile determine osteo‐immunomodulatory and osteoconductivity outcomes of such therapeutics. This review focuses on introducing currently used local drug delivery vehicles in T2DM. The fabrication techniques of such biomaterial‐based systems are thoroughly examined. Furthermore, the feasibility and the potential factors contributing to consistent release of bioactive agents are surveyed. Furthermore, the extent of in vivo responses is described in the context of current research examples. Targeted signaling mechanisms are also assessed in detail to elucidate the activated healing routes.
The Primary Cilia are Associated with the Axon Initial Segment in Neurons
Authors: Wang Han , Li Yu , Li Xin , Sun Zehui , Yu Fengdan , Pashang Abolghasem , Kulasiri Don , Li Hung Wing , Chen Huan , Hou Hongwei , Zhang Yan
Published: January 2025

The primary cilia serve as pivotal mediators of environmental signals and play crucial roles in neuronal responses. Disruption of ciliary function has been implicated in neuronal circuit disorders and aberrant neuronal excitability. However, the precise mechanisms remain elusive. To study the link between the primary cilia and neuronal excitability, manipulation of somatostatin receptor 3 (SSTR3) is investigated, as an example of how alterations in ciliary signaling may affect neuronal activity. It is found that aberrant SSTR3 expression perturbed not only ciliary morphology but also disrupted ciliary signaling cascades. Genetic deletion of SSTR3 resulted in perturbed spatial memory and synaptic plasticity. The axon initial segment (AIS) is a specialized region in the axon where action potentials are initiated. Interestingly, loss of ciliary SSTR3 led to decrease of Akt‐dependent cyclic AMP‐response element binding protein (CREB)‐mediated transcription at the AIS, specifically downregulating AIS master organizer adaptor protein ankyrin G (AnkG) expression. In addition, alterations of other ciliary proteins serotonin 6 receptor (5‐HT6R)and intraflagellar transport protein 88 (IFT88) also induced length changes of the AIS. The findings elucidate a specific interaction between the primary cilia and AIS, providing insight into the impact of the primary cilia on neuronal excitability and circuit integrity.
Achieving Balanced Performance and Safety for Manufacturing All‐Solid‐State Lithium Metal Batteries by Polymer Base Adjustment
Authors: Yi Xiaoping , Yang Yang , Xiao Kaishan , Zhang Sidong , Wang Bitong , Wu Nan , Cao Bowei , Zhou Kun , Zhao Xiaolong , Leong Kee Wah , Wang Xuelong , Pan Wending , Li Hong
Published: January 2025

Organic–inorganic composite solid electrolytes (CSEs) have aroused intensive attention due to their balanced performance and environmental adaptability. However, their high performance, e.g., the high ionic conductivity, wide electrochemical window, and excellent interfacial compatibility, is achieved by sacrificing their mechanical strength, which increases the possibility of short circuits and thus poses serious safety hazards. Herein, a high‐performance and rigid‐flexible PM polymer matrix is synthesized by a simple process of polymerization addition reaction between polyethylene oxide (PEO) and methylene diphenyl diisocyanate (MDI), where PM‐based CSEs (denoted as PMPS@LATP‐NF) is also prepared through a porous non‐woven fabric (NF) dense filling process. The effect of PM polymer on the mechanical properties, ionic transport, and interactions of CSEs is elucidated by the combined experimental and theoretical methods, where functional groups (─C─O─C, ─NCO, ─NH) contribute to the dissociation of lithium salts, self‐healing, and interfacial compatibility. Besides, PMPS@LATP‐NF can further mechanically regulate lithium dendrites and demonstrates ultra‐high thermal stability. Moreover, PMPS@LATP‐NF exhibits significantly enhanced cycling performance and rate capability in all‐solid‐state Li/LiFePO4 cells. This work emphasizes the pivotal role of the mechanical properties of CSEs in electrolyte modification, cycling stability, and lifespan of all‐solid‐state lithium metal batteries, and provides inspiration for the development of practical solid electrolytes.
Pd(II)‐Catalyzed Tandem Intramolecular Oxidative Heck Reaction/ C–H Arylation Sequence: One‐Pot Synthesis of 3‐Nitro‐2‐Aryl‐Indoles
Authors: Das Parthasarathi , Tiwari Mohit , Saini Muskan
Published: January 2025

The present article describes a Pd(II)‐catalyzed cascade methodology that proceeds in a one‐step sequence via intramolecular oxidative Heck‐type C–C coupling and NO2‐directed selective C‐2 arylation of in‐situ formed 3‐nitroindoles with haloarenes. Importantly, this highly efficient and atom‐economical cascade protocol utilizes the same catalyst system and affords a diverse library of privileged C‐2‐aryl‐nitroindole scaffolds (5a‐5aa) in a single step with good to excellent yields. Mechanistic investigations, including radical trapping, control, competition experiments and studies on the effects of EDGs and EWGs, strongly suggest the involvement of σ‐bond metathesis or a base accelerated proton abstraction, followed by the formation of a key intermediate i.e., a highly reactive Ar‐Pd‐C‐2‐nitroindole complex, which further signifies the vital role of the NO2 group in leading the efficiency and regioselectivity of the protocol. In addition, this cascade protocol is applicable in the ‘one pot’ synthesis of architecturally complex C‐5 functionalized (‐F/‐Cl/‐Me/‐OMe) C‐2‐aryl‐nitroindoles and offers great potential in terms of biological and pharmaceutical fields.
Buffered Hydroxyl Radical for Photocatalytic Non‐Oxidative Methane Coupling
Authors: Wang Xueyuan , Xin Xueshang , Xiong Lunqiao , Yang Jianlong , Wang Tieou , Yang Yang , Huang Zhipeng , Luo Nengchao , Tang Junwang , Wang Feng
Published: January 2025

Hydroxy radical (⋅OH) is a prestigious oxidant that allows the cleavage of strong chemical bonds of methane but is untamed, leading to over‐oxidation of methane and waste of oxidants, especially at high methane conversion. Here, we managed to buffer ⋅OH in an aqueous solution of photo‐irradiated Fe3+, where ⋅OH almost participates in methane oxidation. Due to the interaction between Fe3+ and SO42−, the electron transfer from OH− to excited‐state Fe3+ for ⋅OH generation is retarded, while excessive ⋅OH is consumed by generated Fe2+ to restore Fe3+. When combined with a Ru/SrTiO3:Rh photocatalyst, the buffered ⋅OH converts methane to C2+ hydrocarbons and H2 with formation rates of 246 and 418 μmol h−1, respectively. The apparent quantum efficiency reaches 13.0±0.2 %, along with 10.2 % methane conversion and 81 % C2+ selectivity after 80 hours of reaction. Overall, this work presents a strategy for controlling active radicals for selective and efficient photocatalysis.
Strained Dehydro‐[2,2]‐paracyclophane Enabled Planar Chirality Construction and [2.2]Paracyclophane Functionalization
Authors: Zhang Xue , Zhou Yi , Yu Zhi‐Xiang , Tung Chen‐Ho , Xu Zhenghu
Published: January 2025

Planar chirality found tremendous use in many fields, such as chemistry, optics, and materials science. In particular, planar chiral [2.2]paracyclophanes (PCPs) are a type of structurally interesting and practically useful chiral compounds bearing unique electronic and photophysical properties and thus have been widely used in π‐stacking polymers, organic luminescent materials, and as a valuable toolbox for developing chiral ligands or organocatalysts. However, the synthesis of chiral PCP derivatives remains a longstanding challenge. Current synthetic methods primarily rely on chiral preparative liquid chromatography separation or chemical and kinetic resolution reactions. Here, we report an enantioconvergent alkynylation of an in situ‐formed dehydro‐[2,2]‐paracyclophane intermediate by asymmetric copper(I) catalysis. This approach enables the efficient synthesis of valuable planar chiral PCP building blocks and heterocycles with good yields and excellent enantioselectivity. The success of this reaction lies in the development of a practical route to access strained dehydro‐[2,2]‐paracyclophane intermediates, which can also be utilized in various strain‐release nucleophilic or cycloaddition reactions to synthesize diverse functionalized PCPs. DFT calculations of this reaction suggest that the enantioselectivity is determined by the aryne complexation with chiral copper(I) acetylide and the subsequent insertion reaction.
Molecular Design for Dual Circularity: Polyester with Complementary Mechanical and Chemical Recyclability under Mild Conditions
Authors: Han Yue , Zhang Pingxia , Zhou Heng , Zhao Tong , Odelius Karin , Hakkarainen Minna
Published: January 2025

The plastic waste accumulation requires facile yet effective solutions. Currently mechanical recycling typically leads to downcycling, while the environmental footprint of chemical recycling is often unacceptable. Here, we introduce a dual circularity concept, where rational molecular design paves the way for complementary closed‐loop mechanical and chemical recyclability under mild conditions. Very small changes in macromolecular structures, thermal and mechanical properties were observed, after as many as six repeated mechanical recycling cycles, showing that a wide processing window could be the key for closing the mechanical recycling loop. Facile, time and energy efficient closed‐loop chemical recycling into products with identical performance to original ones was also realized, thanks to the abundant free volume and accessible ester‐functionalities. With these design criteria at hand, dual circulation in recyclability can be realized; proceeding with mechanical recycling when we can, and switching to chemical recycling when we must.
Selective Hydrogen Isotope Exchange Catalysed by Simple Alkali‐Metal Bases in DMSO
Authors: Tschopp Melina S. , Tortajada Andreu , Hevia Eva
Published: January 2025

Isotope Exchange processes are becoming the preferred way to prepare isotopically labelled molecules, avoiding the redesign of multistep synthetic protocols. In the case of deuterium incorporation, the most used strategy has employed transition metals, that offer high reactivity under mild reaction conditions. Despite their success, the trade‐off is that these metals are precious, so expensive, and often exhibit high toxicity. Therefore, alternative transition‐metal‐free protocols would be a welcome addition to this field. In this report we show how the simple bases NaHMDS (HMDS=hexamethyldisilazide) and NaCH2SiMe3 can efficiently and selectively promote deuteration of a wide range of C(sp2)−H and C(sp3)−H bonds in DMSO‐d6, providing an easy and direct access to deuterated compounds. Heterocycles, fluoroarenes, N‐heterocyclic carbenes, amides and other aromatic molecules could be deuterated under mild conditions using catalytic amounts of base. Mechanistic studies along with the isolation and characterisation of reaction intermediates have flagged up the importance of the metalated substrate and metalated solvent in solution, establishing an equilibrium between these compounds is crucial for the success of this approach. An alkali‐metal effect was observed, with heavier alkali‐metal amides being more reactive at room temperature, but their lower stability at higher temperatures made sodium bases the optimal reagents for Hydrogen Isotope Exchange.
Chiral Nanofibers of Camptothecin Trigger Pyroptosis for Enhanced Immunotherapy
Authors: Gao Fengli , Qiu Xiaxin , Baddi Sravan , He Sijia , Wang Shuting , Zhao Changli , Dou Xiaoqiu , Feng Chuanliang
Published: January 2025

Camptothecin (CPT), a chemotherapeutic agent, demonstrates significant potential in cancer therapy. However, as a drug, CPT molecule suffers from poor water solubility, limited bioavailability, and insufficient immune response. Herein, we construct CPT nanofibers (CNF) with a right‐handed chiral property via supramolecular self‐assembly, which significantly overcomes the solubility barriers associated with bioavailability and improves tumor immune prognosis. The CNF exhibits high chiral asymmetry factor (gabs) (~0.11) and remarkable structure stability under pH 6.5 condition. By formulating chiral CNF with mitochondrial‐targeted DSPE‐PEG‐TPP, CNF accumulates specifically in the mitochondria of cancer cells, leading to mitochondrial dysfunction and a 3.42‐fold increase in reactive oxygen species (ROS) generation compared to the CPT molecule. This ROS amplification activates the caspase‐1/gasdermin D (GSDMD) pathway, inducing pyroptosis that promotes M1 macrophage polarization and enhances CD8+ T‐cell‐dependent antitumor immunity. Consequently, CNF achieves 1.8‐fold greater growth inhibition of distant tumor and reduces tumor metastasis compared to the CPT molecule. Our innovative platform, assembling CPT molecules into chiral CNF structure, is highly anticipated to overcome the current clinical limitations of CPT molecules and offer a new direction for the development of next‐generation immunotherapy strategies.
Developing Orthogonal Fluorescent RNAs for Photoactive Dual‐Color Imaging of RNAs in Live Cells
Authors: Yin Peng , Huang Chunzheng , Zhang Li , Li Zhenzhen , Zhong Caijun , Kuang Shi , Lei Chunyang , Huang Yan , Nie Zhou
Published: January 2025

Fluorogenic RNA aptamers have revolutionized the visualization of RNAs within complex cellular processes. A representative category of them employs the derivatives of green fluorescent protein chromophore, 4‐hydroxybenzlidene imidazolinone (HBI), as chromophores. However, the structural homogeneity of their chromophoric backbones causes severe cross‐reactivity with other homologous chromophores. This limitation impairs their multiplexing capabilities, which are essential for the simultaneous visualization of multiple RNA species in live cells. Herein, we rationally designed a series of red‐shifted chromophores and employed SELEX‐independent engineering to develop a novel fluorogenic RNA aptamer, mSquash. mSquash displays specific and intense fluorescence upon binding with our red‐shifted chromophore DFHBFPD (Ex/Em=501/624 nm). The mSquash/DFHBFPD allows orthogonal imaging of selected RNA targets alongside the established Broccoli/DFHBI‐1T (Ex/Em=472/501 nm), facilitating multiplexed live cell imaging of various targets. Moreover, we expanded the application of fluorescent RNA to photoactive imaging by constructing two genetically encoded photoactivatable fluorescent RNAs for the first time. This innovative approach allows photoactivatable control of fluorescent RNAs via specific light wavelengths (365 nm and 450 nm), enabling spatiotemporal dual‐color imaging of RNAs in live cells. Our findings represent a significant advancement in fluorescent RNA‐based orthogonal imaging and spatiotemporal analysis of RNAs.
Digital and Tunable Genetically Encoded Tension Sensors Based on Engineered Coiled‐Coils
Authors: Liu Shuhong , Liu Jinchan , Foote Alexander , Ogasawara Hiroaki , Al Abdullatif Sarah , Batista Victor S. , Salaita Khalid
Published: January 2025

Genetically encoded tension sensors (GETSs) allow for quantifying forces experienced by intracellular proteins involved in mechanotransduction. The vast majority of GETSs are comprised of a FRET pair flanking an elastic “spring‐like” domain that gradually extends in response to force. Because of ensemble averaging, the FRET signal generated by such analog sensors conceals forces that deviate from the average, and hence it is unknown if a subset of proteins experience greater magnitudes of force. We address this problem by developing digital GETSs comprised of coiled‐coils (CCs) with tunable mechanical thresholds. We validate the mechanical response of CC digital probes using thermodynamic stability prediction, AlphaFold2 modeling, steered molecular dynamics simulations, and single‐molecule force spectroscopy. Live cell measurements using optimized CC tension sensors that are inserted into vinculin demonstrate that 13 % of this mechanosensor experiences forces >9.9 pN within focal adhesions. This reveals greater magnitudes of vinculin force than had previously been reported and demonstrates that CC tension sensors enable more facile and precise tension measurements in living systems.
Organoboron‐Functionalized Metal‐Organic Nanosheets for Highly Efficient CO2 Fixation Mediated by Frustrated Lewis Pairs
Authors: Chen Cheng‐Xia , Wang Haiping , Rabaâ Hassan , Xiong Yang‐Yang , VanNatta Peter , Wei Zhang‐Wen , Al‐Enizi Abdullah M. , Nafady Ayman , Ma Shengqian
Published: January 2025

Converting CO2 to high‐value fine chemicals represents one of the most promising approaches to combat global warming and subsequently achieve a sustainable carbon cycle. Herein, we contribute an organoboron functionalized ultra‐thin metal‐organic nanosheet (MON), termed TCPB‐Zr‐NS, featuring an abundance of exposed Lewis acidic B and formate sites, which can effectively promote CO2 conversion upon the addition of Lewis basic o‐phenylenediamines. Compared with the prototypical 3D analogue TCPB‐Zr‐3D, the resultant TCPB‐Zr‐NS showcases dramatically improved catalytic activity for the cyclization of o‐phenylenediamine as a result of the highly exposed active sites and efficient substrates/products diffusion. Strikingly, the incorporation of Lewis acidic B sites into ultra‐thin Zr‐based MON (Zr‐MON) not only promotes the highly efficient CO2 conversion, but also enhances the recyclability/durability of catalysts. Additionally, the underlying catalytic mechanism has been well established by the comprehensive experiments and theoretical calculations, unveiling a formate‐assisted frustrated Lewis pairs (FLP) mediated catalytic pathway. This work opens up a new avenue to heterogeneous FLP‐based catalysts for small molecule activation and beyond.
Regularly Arranged Heterogeneous Pores in Gas Separation Membranes Constructed by Cocrystallization of Porous Organic Molecules
Authors: Yu Saisai , Yang Siyuan , Yang Miao , Yang Ju , Song Ziye , Hu Dingyue , Ji Heng , Jia Zhe , Liu Ming
Published: January 2025

Integrating two or more materials to construct membranes with heterogeneous pore structures is an effective strategy for enhancing separation performance. Regularly arranging these heterogeneous pores can significantly optimize the combined effect of the introduced components. Porous Organic Cages (POCs), an emerging subclass of porous materials composed of discrete molecules, assemble to form interconnected pores and exhibit permanent porosity in the solid state. A unique feature of POCs is their modularity, enabling a “mix and match” approach to create co‐crystal structures driven by the intermolecular interactions. Herein, we adopted the cocrystallization strategy for fabricating gas separation membranes. We prepared membranes from a series of [4+6] imine cage pairs, which vary in cavity sizes and include cages with fluorescence properties. By optimizing the cocrystalization conditions, we successfully fabricated continuous, defect‐free gas membranes, benefiting from chiral recognition interactions. By introducing regularly alternating small and large pores, we addressed challenges such as the trade‐off between permeability and selectivity in gas separation membrane. Moreover, the cocrystallization strategy has been proven effective for other molecular systems besides POCs, such as macrocycles, for the preparation of co‐crystal membranes. This method broadens the scope for fabricating high‐performance gas separation membranes with ordered heterogeneous pores.
Bioinspired Photo‐Thermal Catalytic System Using Covalent Organic Framework‐Based Aerogel for Synchronous Seawater Desalination and H2O2 Production
Authors: Xu Yaning , Ai Shiyan , Wu Tiantian , Zhou Chengxu , Huang Qing , Li Baiyan , Tian Dan , Bu Xian‐He
Published: January 2025

Efficient utilization of solar energy is widely regarded as a crucial solution to addressing the energy crisis and reducing reliance on fossil fuels. Coupling photothermal and photochemical conversion can effectively improve solar energy utilization yet remains challenging. Here, inspired by the photosynthesis system in green plants, we report herein an artificial solar energy converter (ASEC) composed of light‐harvesting units as solar collector and oriented ionic hydrophilic channels as reactors and transporters. Based on such architecture, the obtained ASEC (namely ASEC‐NJFU‐1) can efficiently realize parallel production of freshwater and H2O2 from natural seawater under natural light. The total solar energy conversion (SEC) of ASEC‐NJFU‐1 reaches up to 8047 kJ m−2 h−1, corresponding to production rates of freshwater and H2O2 are 3.56 kg m−2−1 h−1 and 19 mM m−2 h−1, respectively, which is a record‐high value among all photothermal‐photocatalytic systems reported to date. Mechanism investigation of combining spectrum and experimental studies indicated that the high SEC performance for ASEC‐NJFU‐1 was attributed to the presence of plant bioinspired architecture with carbon nanotubes as solar‐harvestor and COF‐based oriented aerogel as reactors and transporters. Our work thus establishes a novel artificial photosynthesis system for highly efficient solar energy utilization.
A Low‐Symmetry Copper Benzenehexathiol Coordination Polymer with In‐Plane Electrical Anisotropy
Authors: Wang Zhiyong , Un Hio‐Ieng , Liu Tsai‐Jung , Liang Baokun , Polozij Miroslav , Hambsch Mike , Pöhls Jonas F. , Weitz R. Thomas , Mannsfeld Stefan C. B. , Kaiser Ute , Heine Thomas , Sirringhaus Henning , Feng Xinliang , Dong Renhao
Published: January 2025

Electrically conductive coordination polymers (ECCPs), particularly those incorporating benzenehexathiol (BHT) ligands, are emerging as a distinctive class of electronic materials with tunable semiconducting and metallic properties. However, the exploration of novel ECCPs with low‐symmetry structures and electrical anisotropy remains under development. Here, we report the on‐water surface synthesis of a novel ECCP, namely Cu5BHT, which exhibits a low‐symmetry structure and unique in‐plane electrical anisotropy that differs from the well‐known Cu3BHT phase. Utilizing imaging and diffraction techniques, we elucidate the unit cell and crystal structure of Cu5BHT, revealing an asymmetric arrangement of the kagome resembling lattice connected by two different secondary building units: square planar CuS4 and non‐planar Cu2S4. Theoretical studies indicate that Cu5BHT is metallic and exhibits in‐plane electrical anisotropy due to the structure arranged in interconnected well‐conducting CuS4 chains and less‐conducting Cu2S4 slabs oriented along single crystal direction. Single‐crystal electrical measurements confirm a metallic character characterized by the increase of conductance upon cooling. Notably, the measured conductance along different crystal directions within the ab plane unambiguously reveals a significant anisotropy, with an anisotropic factor reaching ~8. This work demonstrates a novel low‐symmetry ECCP and highlights its potential for achieving in‐plane electrical anisotropy.
Porous Organic Polymers Incorporating Shape‐Persistent Cyclobenzoin Macrocycles for Organic Solvent Separation
Authors: Ashirov Timur , Lim Jay , Robles Alexandra , Puangsamlee Thamon , Fritz Patrick W. , Crochet Aurelien , Wang Xiqu , Hewson Connor , Iacomi Paul , Miljanić Ognjen Š. , Coskun Ali
Published: January 2025

The recovery and separation of organic solvents is highly important for the chemical industry and environmental protection. In this context, porous organic polymers (POPs) have significant potential owing to the possibility of integrating shape‐persistent macrocyclic units with high guest selectivity. Here, we report the synthesis of a macrocyclic porous organic polymer (np‐POP) and the corresponding model compound by reacting the cyclotetrabenzil naphthalene octaketone macrocycle with 1,2,4,5‐tetraaminobenzene and 1,2‐diaminobenzene, respectively, under solvothermal conditions. Co‐crystallization of the macrocycle and the model compound with various solvent molecules revealed their size‐selective inclusion within the macrocycle. Building on this finding, the np‐POP with a hierarchical pore structure and a surface area of 579 m2 g−1 showed solvent uptake strongly correlated with their kinetic diameters. Solvents with kinetic diameters below 0.6 nm – such as acetonitrile and dichloromethane – showed high uptake capacities exceeding 7 mmol g−1. Xylene separation tests revealed a high overall uptake (~34 wt %), with o‐xylene displaying a significantly lower uptake (~10 wt % less than other isomers), demonstrating the possibility of size and shape selective separation of organic solvents.
Design, Preparation, Characterization, Density Functional Theory, and HOMO‐LUMO Perspective of Fe3O4@SiO2‐Pr‐NH‐IC as a New Nanomagnetic Chemosensor
Authors: Zamiran Fatemeh , Mohammadi Ziarani Ghodsi , Feizi‐Dehnayebi Mehran , Mirhosseyni Marziesadat , Badiei Alireza , Abu‐Dief Ahmed M.
Published: January 2025

In this research, the Fe3O4@SiO2‐Pr‐NH‐IC magnetic nanoparticles (MNPs) were synthesized based on Fe3O4 nanoparticles. Initially, Fe3O4 was coated with tetraethylorthosilicate (TEOS) to produce Fe3O4@SiO2, which was functionalized by the reaction with 3‐aminopropyl three‐methoxy silane (APTMS) to yield Fe3O4@SiO2‐Pr‐NH2, followed by the treatment with indole‐3‐carbaldehyde (IC) to obtain Fe3O4@SiO2‐Pr‐NH‐IC as target hybrid organic and inorganic material. The Fe3O4@SiO2‐Pr‐NH‐IC was analyzed using photoluminescence spectroscopy. It was shown that this compound can selectively detect Al3+ ions in aqueous media among various cations, with a limit of detection (LOD) of 2.47 × 10−6 M. Comprehensive DFT calculations were carried out utilizing the B3LYP functional in conjunction with the 6‐311g (d,p) and LANL2DZ basis sets to analyze the ground state of the system. To elucidate the interaction mechanism, the MEP map was generated, and a full geometry optimization was performed. Additionally, the electronic properties and chemical reactivity were examined through a HOMO‐LUMO analysis at the same computational level. The findings revealed that the incorporation of the Al3+ ion significantly enhances the reactivity of the Pr‐NH‐IC + Al3+ complex in comparison to the free Pr‐NH‐IC structure. These findings suggest that Fe3O4@SiO2‐Pr‐NH‐IC has significant potential for the development of advanced sensor systems for the selective detection of Al3+ ions in aqueous environments. Future research could focus on the modification of the nanostructure to enhance its sensitivity and selectivity toward other environmentally and biologically relevant metal ions. Additionally, the integration of this material into portable sensing devices or the development of a real‐time detection system could pave the way for practical applications in environmental monitoring and water quality assessment.
Polypyrrole/CoFe2O4 Nanocomposite for the Removal of Basic Blue 3 Dye From Wastewater: Kinetic, Adsorption Isotherm, and Thermodynamic Study
Authors: Goswami Madhav Krishn , Srivastava Abhishek
Published: January 2025

Water contamination constitutes a substantial global issue that affects the environment. Adsorption materials have demonstrated huge potential in wastewater treatment. For the efficient removal of a cationic dye, basic blue 3 (BB3), a polypyrrole‐coated cobalt ferrite (PPy@CoFe2O4) magnetic nanosorbent is prepared via in situ polymerization of pyrrole on CoFe2O4 nanoparticles. Scanning electron microscopy (SEM) analysis demonstrated spherical nanoparticles with sizes around 50 nm, which was further supported by XRD data. Zeta‐potential study showed that the surface charge of PPy@CoFe2O4 is negative in alkaline media and positive in acidic media. The adsorption system adhered to a pseudo‐second‐order kinetic model, with the equilibrium time being determined at 50 min. The Langmuir model accurately simulated the adsorption isotherms. Under optimal conditions (pH—8.0, volume—30 mL, adsorbent dose—0.67 g/L, and at 303 K temperature), the maximum monolayer adsorption capacity of PPy/CoFe2O4 is 130.1 mg g−1. Even after five desorption–adsorption cycles, the removal efficiency remained above 92%. Negative ΔG° and ΔH° indicate spontaneous BB3 adsorption onto PPy/CoFe2O4, decreasing with temperature. These findings demonstrate that the PPy/CoFe2O4 composite is a highly effective adsorbent with broad potential applications for treating wastewater containing cationic dye.
Phenolic Hydroxyl‐Activated Lignin for Preparation of Extreme Environments Adaptive Adhesives
Authors: Zhang Shuang , Zheng Jianhua , Zheng Shunji , Song Mizhao
Published: January 2025

Epoxy resins is widely applied in various industrial production. Lignin exhibits enormous potential as an alternate for health‐risk compound, bisphenol A, in the preparation of epoxy resin adhesives. However, the complicated structures and low reactivity limit the further utilization of lignin. In this study, a green deep eutectic solvent (DES) was utilized to enhance the phenolic hydroxyl content of hard wood organic lignin, from 3.63 to 5.63 mmol/g, to promote the reactivity of lignin during the preparation process of epoxy resin adhesives. Enabling by the DES induced lignin activation, the prepared lignin‐based epoxy resin exhibited excellent epoxy‐value (0.41 mol/100 g) and the as‐prepared adhesives possessed remarkable mechanical properties (tensile stress up to 50.86 MPa). Even after exposure to extreme conditions (freezing or soaking for 48 h), the adhesives maintained over 70% mechanical strength. This work contributes to the broader effort towards sustainable lignin‐based adhesives in industrial applications.
Immune Aging in Rheumatoid Arthritis
Authors: Weyand Cornelia M. , Goronzy Jörg J.
Published: January 2025

Rheumatoid arthritis (RA) is a life‐long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self‐tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals >65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with autodestructive immunity in affected patients, including the process of immune aging. Patients with RA have a signature of premature immune aging, best understood for CD4+ T cells, which function as pathogenic effectors in this HLA class II–associated disease. Premature immune aging is present in healthy HLA–DRB1*04+ individuals, placing accelerated immune aging before joint inflammation. Aging‐related molecular abnormalities directly implicated in turning RA CD4+ T cells into proinflammatory effector cells are linked to malfunction of subcellular organelles, such as mitochondria, lysosomes, lipid droplets, and the endoplasmic reticulum. Resulting changes in T cell behavior include cellular hypermobility, tissue invasiveness, unopposed mammalian target of rapamycin complex (mTORC)1 activation, excessive release of tumor necrosis factor, lysosomal failure, clonal expansion, and immunogenic cell death. Aged and metabolically reprogrammed T cells in patients with RA are accompanied by age‐associated B cells, which specialize in autoantibody production. Clonal hematopoiesis drives myeloid cell aging by producing aged monocytes and hypermetabolic macrophages, which sustain the process of inflammaging. Here, we synthesize insights into the relationship of RA risk and immune aging and discuss mechanisms through which immune aging can cause autoimmunity.

image
Associations of Fire Smoke and Other Pollutants With Incident Rheumatoid Arthritis and Rheumatoid Arthritis–Associated Interstitial Lung Disease
Authors: Kronzer Vanessa L. , Yang Yangyuna , Roul Punyasha , Crooks James L. , Crowson Cynthia S. , Davis John M. , Sparks Jeffrey A. , Pierce Jeffrey R. , O'Dell Katelyn , Sauer Brian C. , Cannon Grant W. , Baker Joshua F. , Mikuls Ted R. , England Bryant R.
Published: January 2025

Objective

The aim of this study was to determine whether pollutants such as fire smoke–related particulate matter <2.5 μm (PM2.5) are associated with incident rheumatoid arthritis (RA) and RA‐associated interstitial lung disease (RA‐ILD).

Methods

This patient–control study used Veterans Affairs (VA) data from October 1, 2009, to December 31, 2018. We identified patients with incident RA and RA‐ILD using validated algorithms, matching each patient to ≤10 controls on age, sex, and VA enrollment year. We obtained pollutants including fire smoke PM2.5, carbon monoxide, nitrogen oxides (NOx), ozone, overall PM2.5, PM10, and sulfur dioxide (SO2) at least one year before the index date. We fit conditional logistic regression models to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for incident RA and RA‐ILD, adjusted for confounders.

Results

We identified 9,701 patients with incident RA (mean age 65 years, 86% male), including 531 patients with RA‐ILD (mean age 69 years, 91% male), and 68,852 matched controls. Fire smoke PM2.5 was not associated with RA (aOR 1.07, 95% CI 0.92–1.23) but was associated with RA‐ILD (aOR 1.98, 95% CI 1.08–3.62, per 1 μg/m3). Increased levels of NOx were associated with RA (aOR 1.16, 95% CI 1.06–1.27, highest vs lowest quartile). The highest quartiles of ozone (aOR 1.19, 95% CI 1.06–1.34) and PM10 (aOR 1.25, 95% CI 1.10–1.43) were associated with seronegative RA. Carbon monoxide, overall PM2.5, and SO2 were not, or negatively, associated with RA and RA‐ILD.

Conclusion

Increased fire smoke PM2.5 was associated with RA‐ILD, whereas NOx, ozone, and PM10 were associated with RA risk. Thus, air pollution may increase the risk of RA and RA‐ILD.

image
Hot‐Exciton Mechanism with Diphenyl Anthracene Core Unit: A Detailed Theoretical Study
Authors: Sivasakthi Pandiyan , Samanta Pralok K.
Published: January 2025

Hot‐exciton materials, among all kinds of organic light‐emitting diode (OLED) emitters, have better exciton utilization efficiency and efficiency roll‐off, making them possible for their practical applications. We studied the photophysical properties of a few hot‐exciton molecules based on an anthracene core unit to efficiently harvest all triplet excitons to the lowest excited singlet state. The conversion of triplet exciton to singlet exciton utilizing hRISC can be enhanced due to the 1ππ*←3nπ* transition channel. The energy gap between the excited singlet and triplet excited states, spin‐orbit coupling interaction, nature of excited states, rate constants of reverse intersystem crossing, and radiative process were calculated and analyzed to gain more insights into the hot‐exciton mechanism. Additionally, we extended our study by substituting groups in the diphenyl anthracene core unit to find improved performance. We found that the combinations of triphenylamine (TPA) or 9‐phenyl‐9H‐carbazole (CZP) acting as the electron donor, benzophenone as the acceptor, and the anthracene as the π‐bridge is the most efficient hot‐exciton emitter for improved OLED lighting application technology.
The development of legal rights for intersex persons: Part II: Advancement
Authors: Felthous Alan R. , Kahlon Chanchal
Published: January 2025

Having addressed the nature and complexity of intersexuality including commonalities with and differences from the transgender condition, we now address major legal challenges to the bisexual status quo through the legal advancement of rights for intersexual persons. Identified here are four domains in which the rights of intersex individuals are being advanced through litigation and legislation: (a) Sex assignment at birth and in early childhood, including the individual's right to consent and self‐determination and to be spared from surgery that is not needed for medical reasons; (b) the right to change one's legal sex on legal documents such as birth certificates and passports, (c) the right of intersex persons to marry, and (d) the right not to be discriminated against. Within this legal framework, we identify commonalities with and differences from the struggle for rights within the transgender community.
Evaluation of the Interaction Between Menthol and Camphor, Major Compounds of Clinopodium nepeta Essential Oil: Antioxidant, Anti‐inflammatory and Anticancer Activities Against Breast Cancer Cell Lines
Authors: Taibi Mohamed , Elbouzidi Amine , Haddou Mounir , Baraich Abdellah , Gharsallaoui Adem , Mothana Ramzi A. , Alqahtani Abdulaziz M. , Asehraou Abdeslam , Bellaouchi Reda , Addi Mohamed , El Guerrouj Bouchra , Chaabane Khalid
Published: January 2025

This study evaluates the antioxidant, anti‐inflammatory, and anticancer activities of camphor, menthol, and their equimolar combination. In silico toxicity analysis confirmed the absence of toxic effects for both compounds. Antioxidant activity, assessed by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) assays, revealed a synergistic effect of the equimolar combination with half‐maximal inhibitory concentration (IC50) values of 10.3 µg/mL (DPPH) and 8.9 µg/mL (ABTS), surpassing the efficacy of ascorbic acid (IC50 = 12.4 µg/mL). Evaluation of anti‐inflammatory activity showed that the combination more effectively inhibited 5‐lipoxygenase (72.5% vs. 48.3% for camphor and 52.9% for menthol) and COX‐1 and COX‐2 cyclooxygenases (78.1% and 79.4% respectively, vs. 60.4% and 62.7% for camphor, 64.2% and 66.3% for menthol). Anticancer activity, tested on MCF‐7, MDA‐MB‐231, and MDA‐MB‐436 breast cancer lines, revealed that the equimolar combination exhibited IC50 of 27.6, 31.2, and 36.5 µg/mL, respectively, with an IC50 of 52.3 µg/mL on normal cells, demonstrating remarkable selectivity for cancer cells. These results suggest that the camphor‐menthol combination represents a promising therapeutic approach against pathologies associated with oxidative stress, inflammation, and carcinogenesis.
Evaluation of Multispecific Drugs Based on Patient‐Derived Immunocompetent Tumor Organoids
Authors: Zhao Zihan , Wu Xiangyu , Zhang Tianyang , Zhou Meng , Liu Siyang , Yang Rong , Li Jie P.
Published: January 2025

The evolution of antitumor drug development has transitioned from single‐agent chemotherapy to targeted therapy, immunotherapy, and more recently, multispecific drugs. These innovative drugs target multiple cellular or molecular pathways simultaneously, offering a more comprehensive anticancer approach and addressing some of the limitations inherent in traditional monotherapies. However, preclinical assessment of multispecific drugs remains challenging, as conventional tumor models often lack the necessary complexity to accurately reflect the interactions between various cell types and targets. Patient‐derived immunocompetent tumor organoids (PDITOs), which incorporate both tumor cells and immune cells, present a promising platform for the evaluation of these drugs. Beyond their use in drug evaluation, PDITOs can also be utilized in personalized drug screening and predicting patient‐specific treatment outcomes, thus advancing both multispecific drug development and precision medicine. This perspective discusses the current landscape of multispecific drug development and the methodologies for constructing PDITOs. It also addresses the associated challenges and introduces the concept of employing these organoids to optimize the evaluation and rational design of multispecific drug therapies.
Pacemaker Implantation in a Patient With Isolated Persistent Left Superior Vena Cava: A Novel Approach
Authors: Shahi Shayan , Nematollahi Soroush , Vasheghani‐Farahani Ali
Published: January 2025

Implanting pacemakers in patients with isolated persistent left superior vena cava (PLSVC) present unique challenges. Recognizing venous anomalies and adapting lead placement techniques are crucial for successful outcomes and stable pacemaker function.
Atrial Septal Defect and Percutaneous Closure: Healing the Heart From Within
Authors: Acharya Rikesh , Shah Prashant , Pradhan Ayurda , Khan Sajjad Ahmed , Yadav Udip , Neupane Sudhan , Panthi Madhav
Published: January 2025

Early diagnosis and percutaneous closure of symptomatic adult atrial septal defects can enhance cardiac function and relieve symptoms. Thorough pre‐procedural evaluation and diligent follow‐up care are essential for achieving the best outcomes and ensuring long‐term success.
Catalytic Guaiacol Hydrodeoxygenation in Supercritical Fluids: A Review
Authors: Valizadeh Soheil , Valizadeh Behzad , Lee Jechan , Park Young‐Kwon
Published: January 2025

Upgrading bio‐oil is crucial for the use of renewable fuels in the transportation sector. Hydrodeoxygenation (HDO) is a key technology for upgrading bio‐oil and removing oxygen in the form of water, typically under pressurized hydrogen. However, the use of high‐pressure hydrogen is limited by several factors (e.g., storage safety issues). This review primarily discusses the substantial advantages of catalytic HDO in supercritical fluids, which overcome the need for external H2 while providing a wider range of products. In particular, this study focuses on ethanol and methanol as effective H‐donor solvents for HDO processes due to their ability to provide active hydrogen under relatively mild conditions, along with their multifunctionality as both solvents and H‐donors and their potential to enhance mass‐ and heat‐transfer efficiencies. Guaiacol was chosen as the HDO feedstock because it can be found abundantly in bio‐oil. Furthermore, the effects of the catalyst properties (e.g., pore size, acidity, and acidic and metallic site distribution) and reaction conditions on the reaction efficiency and product distribution are discussed. This review also describes technical challenges, proposes solutions, and outlines future research directions for advancing the supercritical HDO processes with the aim of guiding future studies toward more effective and sustainable HDO‐based biofuel‐upgrading technologies.
Can using the Cochrane RCT classifier in EPPI‐Reviewer help speed up study selection in qualitative evidence syntheses? A retrospective evaluation
Authors: Ames Heather Melanie R. , Hestevik Christine Hillestad , Jardim Patricia Sofia Jacobsen , Larsen Martin Smådal , Langøien Lars Jørun , Bergsund Hans Bugge , Borge Tiril Cecilie
Published: January 2025

Introduction

Using machine learning functions, such as study design classifiers, to automatically identify studies that do not meet the inclusion criteria, is one way to speed up the systematic review screening process. As a qualitative study design classifier is yet to be developed, using the Cochrane randomized controlled trial (RCT) classifier in reverse is one possible way to speed up the identification of primary qualitative studies during screening. The objective of this study was to evaluate whether the Cochrane RCT classifier can be used to speed up the study selection process for qualitative evidence synthesis (QES).

Methods

We performed a retrospective evaluation where we first identified QES. We then extracted the bibliographic information of the included primary qualitative studies in each QES, and uploaded the references into our data management tool, EPPI‐Reviewer. We then ran the Cochrane RCT classifier on each group of included studies for each QES.

Results

Eighty‐two QES with 2828 unique primary studies were included in the analysis. 56% of the primary studies were classified as unlikely to be an RCT and 40% as being 0–9% likely to be an RCT. 4% were classified as being 10% or more likely to be an RCT. Of these, only 1.7% were classified as being 50% or more likely to be an RCT.

Conclusions

The Cochrane RCT classifier could be a useful tool to identify primary studies with qualitative study designs to speed up study selection in a QES. However, it is possible that mixed methods studies or qualitative studies conducted as part of a clinical trial may be missed. Further evaluations using the Cochrane RCT classifier on all the references retrieved from the complete literature search is needed to investigate time‐ and resource savings.
Gold(I)‐Catalyzed Nucleophilic Propargylation of Azinium Ions via Hydroxydihydroazine Intermediates
Authors: Smithson Jack , O'Brien Luke , Jones Kieran D. , Argent Stephen P. , Wheelhouse Katherine M. , Woodward Simon , Ermanis Kristaps , Lam Hon Wai
Published: January 2025

The nucleophilic propargylation of azinium ions with a propargylboronate proceeds efficiently under gold(I) catalysis. A range of N‐alkylated pyridinium, quinolinium, and pyrazinium ions undergo propargylation with good yields and high regioselectivities to give various functionalized 1,4‐dihydropyridines, 1,2‐dihydropyridines, 1,4‐dihydroquinolines, 1,2‐dihydroquinolines, and 4,5‐dihydropyrazines. No allenylation side‐products are observed. Density functional theory (DFT) calculations provided insight into the mechanisms of these reactions. Hydroxydihydroazine intermediates formed by the addition of LiOH to the azinium ions were found to be the reactive electrophiles in these reactions.
APH Inhibitors that Reverse Aminoglycoside Resistance in Enterococcus casseliflavus
Authors: Kaplan Elise , Chaloin Laurent , Guichou Jean‐François , Berrou Kévin , Rahimova Rahila , Labesse Gilles , Lionne Corinne
Published: January 2025

Aminoglycoside‐phosphotransferases (APHs) are a class of bacterial enzymes that mediate acquired resistance to aminoglycoside antibiotics. Here we report the identification of small molecules counteracting aminoglycoside resistance in Enterococcus casseliflavus. Molecular dynamics simulations were performed to identify an allosteric pocket in three APH enzymes belonging to 3′ and 2′′ subfamilies in which we then screened, in silico, 12,000 small molecules. From a subset of only 14 high‐scored molecules tested in vitro, we identified a compound, named here EK3, able to non‐competitively inhibit the APH(2′′)‐IVa, an enzyme mediating clinical gentamicin resistance. Structure‐activity relationship (SAR) exploration of this hit compound allowed us to identify a molecule with improved enzymatic inhibition. By measuring bacterial sensitivity, we found that the three best compounds in this series restored bactericidal activity of various aminoglycosides, including gentamicin, without exhibiting toxicity to HeLa cells. This work not only provides a basis to fight aminoglycoside resistance but also highlights a proof‐of‐concept for the search of allosteric modulators by using in silico methods.