bluuebunny/crossref_metadata_2025 huggingface dataset:
Sono‐Triggered Biomimetically Nanoantibiotics Mediate Precise Sequential Therapy of MRSA‐Induced Lung Infection
Authors: Ding Linyu , Liang Xiaoliu , Ma Jiaxin , Liu Xue , Zhang Yang , Long Qiuyue , Wen Zihao , Teng Zihao , Jiang Lai , Liu Gang
Published: September 2024

Bacterial‐induced lower respiratory tract infections are a growing global health concern, exacerbated by the inefficacy of conventional antibiotics and delivery methods to effectively target the lower respiratory tract, leading to suboptimal therapeutic outcomes. To address this challenge, this work engineers PBP2a antibody‐presenting membrane nanovesicles (AMVs) specifically designed to target the penicillin‐binding protein variant on the surface of methicillin‐resistant Staphylococcus aureus (MRSA). Concurrently, this work develops pure ciprofloxacin nanoparticles (NanoCip) that, for the first time, exhibits exceptional self‐generated sonodynamic properties, attributed to hydrogen‐bond‐driven self‐assembly, while maintaining their inherent pharmacological efficacy. These NanoCip particles are integrated with AMVs to create a novel biomimetic nanomedicine, AMV@NanoCip. This formulation demonstrated remarkable MRSA‐targeting affinity in both in vitro and in vivo models, significantly enhancing antibacterial activity. Upon ultrasound stimulation, AMV@NanoCip achieves over 99.99% sterilization of MRSA in vitro, with a reduction exceeding 5.14 Log CFU. Prokaryotic transcriptomic analysis further elucidates the synergistic mechanisms by which AMV@NanoCip, coupled with ultrasound, disrupts the MRSA exoskeleton. In a MRSA‐induced pneumonia animal model, AMV@NanoCip+US results in a substantial bacterial load reduction in the lungs (99.99%, 4.02 Log CFU). This sequential treatment strategy (adhesion‐membrane disruption‐synergistic therapy) offers significant promise as an innovative therapeutic approach for combating bacterial infections.
An Intelligent Intestine‐on‐a‐Chip for Rapid Screening of Probiotics with Relief‐Enteritis Function
Authors: Wu Jing , Zhang Bowei , Liu Xiaoxia , Gu Wentao , Xu Fupei , Wang Jin , Liu Qisijing , Wang Ruican , Hu Yaozhong , Liu Jingmin , Ji Xuemeng , Lv Huan , Li Xinyang , Peng Lijun , Li Xiang , Zhang Yan , Wang Shuo
Published: September 2024

Screening probiotics with specific functions is essential for advancing probiotic research. Current screening methods primarily use animal studies or clinical trials, which are inefficient and costly in terms of time, money, and labor. An intelligent intestine‐on‐a‐chip integrating machine learning (ML) is developed to screen relief‐enteritis functional probiotics. A high‐throughput microfluidic chip combined with environment control systems provides a standardized and scalable intestinal microenvironment for multiple probiotic cocultures. An unsupervised ML‐based score analyzer is constructed to accurately, comprehensively, and efficiently evaluate interactions between 12 Bifidobacterium strains and host cells of the colitis model in the intestine‐on‐a‐chips. The most effective contender, Bifidobacterium longum 3–14, is discovered to relieve intestinal inflammation and enhance epithelial barrier function in vitro and in vivo. A distinct advantage of this strategy is that it can intelligently differentiate small therapeutic variations in probiotic strains and prioritize their efficacies, allowing for economical, efficient, accurate functional probiotics screening.
Topological Synthesis of 2D High‐Entropy Multimetallic (Oxy)hydroxide for Enhanced Lattice Oxygen Oxidation Mechanism
Authors: Liu Sijia , Jia Baorui , Wang Yong , Zhao Yongzhi , Liu Luan , Fan Fengsong , Qin Yunpu , Liu Jianfang , Jiang Yirui , Liu Hongru , Zhao Hong , Li Hao , Zhou Wenxiang , Wu Haoyang , Zhang Deyin , Qu Xuanhui , Qin Mingli
Published: September 2024

Owing to sluggish reaction kinetics and high potential, oxygen evolution reaction (OER) electrocatalysts face a trade‐off between activity and stability. Herein, an innovative topological strategy is presented for preparing 2D multimetallic (oxy)hydroxide, including ternary CoFeZn, quaternary CoFeMnZn, and high‐entropy CoFeMnCuZn. The key to the synthesis lies in using Ca‐rich brownmillerite oxide as a precursor, which possesses inherent structural flexibility enabling tailored elemental adjustments and topologically transforms from a point‐shared structure of metal‐oxygen octahedrons into an edge‐shared structure under alkaline conditions. The presence of Zn in the catalysts causes a shift in the center of the O2p band toward the Fermi level, resulting in more Co4+ species, which drive holes into oxygen ligands to promote intramolecular oxygen coupling. The triggered lattice oxidation mechanism is identified by detecting peroxo‐like (O22−) negative species using tetramethylammonium chemical probe, along with 18O isotope labeling experiments. As a result, the catalyst demonstrates an overpotential of 267 mV at 10 mA cm−2, ranking it among the top‐performing non‐Ni‐based catalysts. Importantly, the catalysts also show high Fe‐leaching resistance during OER compared to conventional NiFe and CoFe hydroxides/(oxy)hydroxides. The assembled zinc‐air battery enables stable operation for over 225 h at a low charging voltage of 1.93 V.
Fiber Optic‐Mediated Type I Photodynamic Therapy of Brain Glioblastoma Based on an Aggregation‐Induced Emission Photosensitizer
Authors: Zhang Wenguang , Kang Miaomiao , Li Xue , Pan Yinzhen , Li Zhuorong , Zhang Yibin , Liao Changrui , Xu Gaixia , Zhang Zhijun , Tang Ben Zhong , Xu Zhourui , Wang Dong
Published: September 2024

Glioblastoma (GBM) is one of the most lethal human malignancies. The current standard‐of‐care is highly invasive with strong toxic side effects, leading to poor prognosis and high mortality. As a safe and effective clinical approach, photodynamic therapy (PDT) has emerged as a suitable option for GBM. Nevertheless, its implementation is significantly impeded by the limits of light penetration depth and the firm reliance on oxygen. To overcome these challenges, herein, a promising strategy that harnesses a modified optical fiber and less oxygen‐dependent Type I aggregation‐induced emission (AIE) photosensitizer (PS) is developed for the first time to realize in vivo GBM treatments. The proposed AIE PS, namely TTTMN, characterized by a highly twisted molecular architecture and a bulky spacer, exhibits enhanced near‐infrared emission and strong production of hydroxyl and superoxide radicals at the aggregated state, thus affording efficient fluorescence imaging‐guided PDT once formulated into nanoparticles. The inhibition of orthotopic and subcutaneous GBM xenografts provides compelling evidence of the treatment efficacy of Type I PDT irradiated through a tumor‐inserted optical fiber. These findings highlight the substantially improved therapeutic outcomes achieved through fiber optic‐mediated Type I PDT, positioning it as a promising therapeutic modality for GBM.
Interface/Dipole Polarized Antibiotics‐Loaded Fe3O4/PB Nanoparticles for Non‐Invasive Therapy of Osteomyelitis Under Medical Microwave Irradiation
Authors: Jin Liguo , Liu Hanpeng , Wang Chaofeng , Mao Congyang , Wu Shuilin , Zhang Yu , Li Zhaoyang , Zhu Shengli , Jiang Hui , Cui Zhenduo , Zheng Yufeng , Liu Xiangmei
Published: September 2024

Due to their poor light penetration, photothermal therapy and photodynamic therapy are ineffective in treating deep tissue infections, such as osteomyelitis caused by Staphylococcus aureus (S. aureus). Here, a microwave (MW)‐responsive magnetic targeting composite system consisting of ferric oxide (Fe3O4)/Prussian blue (PB) nanoparticles, gentamicin (Gent), and biodegradable poly(lactic‐co‐glycolic acid) (PLGA) is reported. The PLGA/Fe3O4/PB/Gent complex is used in combination with MW thermal therapy (MTT), MW dynamic therapy (MDT), and chemotherapy (CT) to treat acute osteomyelitis infected with S. aureus‐infected. The powerful antibacterial effect of the PLGA/Fe3O4/PB/Gent is determined by the synergistic effects of heat and reactive oxygen species (ROS) generation by the Fe3O4/PB nanoparticles under MW irradiation and the effective release of Gent at the infection site via magnetic targeting. The antibacterial mechanism of the PLGA/Fe3O4/PB/Gent under MW irradiation is analyzed using bacterial transcriptome RNA sequencing. The MW heat and ROS reduce the activity of the protein transporters on the bacterial membrane, along with the transport of various ions and the acceleration of phosphate metabolism, which can lead to increased permeability of the bacterial membrane, damage the ribosome and DNA, and accompany the internal protein efflux of the bacteria, thus effectively killing the bacteria.
Emerging Zinc‐Ion Capacitor Science: Compatible Principle, Design Paradigm, and Frontier Applications
Authors: Zhu Jianhui , Tai Jie , Liu Tao , Wang Yanyi , Li Yinyin , Yang Ming , Ma Dingtao , Deng Libo , Luo Jingting , Zhang Peixin
Published: September 2024

The development of high energy/power density and long lifespan device is always the frontier direction and attracts great research attention in the energy storage fields. Zinc‐ion capacitors (ZICs), as an integration of zinc‐ion batteries and supercapacitors, have been widely regarded as one of the viable future options for energy storage, owing to their variable system assembly method and potential performance improvement. However, the research of ZICs still locate at initial stage until now, and how to construct the suitable systems for different condition is still challenging. Herein, the recent advance in the rational design of ZICs is reviewed in order to construct related theory including compatible principle and design paradigm. It starts with a systematically summary of the fundamental theory as well as the motivation. Then, the electrode materials are classified into capacitor‐type and battery‐type based on the storage mechanism, and the design strategies and progress of these two‐type candidates are comprehensively discussed, aiming to reveal the inherent relationship between the performance of devices and the component as well as architecture of electrode materials. Beyond that, the future perspectives in this emerging field are also given, expecting to guide the construction of high‐performance ZICs for practical applications and boost its development.
Synthesis of Doped g‐C3N4 Photonic Crystals for Enhanced Light‐Driven Hydrogen Production from Catalytic Water‐Splitting
Authors: Djoko T. Simon Y. , Kwon Sunil , Das Prasenjit , Weigelt Vincent , Tahir Warisha , Radhakrishnan Babu , Schwarzburg Klaus , Thomas Arne , Schwarze Michael , Schomäcker Reinhard
Published: September 2024

Dopants are frequently used to improve graphitic carbon nitride (gCN) photoactivity. As a doping source, phosphomolybdic acid (PMA) can activate doping sites inside the gCN lattice, resulting in 2D Mo:P‐gCN porous material. However, the gradual loading of the PMA fraction has no systematic improvement in the Mo:P‐gCN photoactivity. For improving the optoelectronic properties of Mo:P‐gCN, its textural geometry is a controllable parameter that can provide enhanced photonic properties, achievable by shaping its morphology through a crystalline template structure, namely, photonic crystals (PCs). Herein, a doped PC material is made of Mo:P‐gCN and PCs and labeled as Mo:P‐gCN/PCs. The impact of PCs is highlighted in the structural, electronic, and optical performances of Mo:P‐gCN. A well‐defined 3D crystalline network is evidenced by microscopic measurements (scanning electron microscopy, AFM, focused ion beam). Mo:P‐gCN/PCs shows a hydrogen production rate (750 μmol g−1 h−1) one time higher than Mo:P‐gCN and 6 times higher than pure gCN. The synthesis strategy proposed in this work leads simultaneously to the Mo:P codoping effect provided by PMA and the slow photon effect due to the PC structure, offering a novel strategy to improve the gCN photoactivity by simultaneously applying polyoxometalates as modifiers and polystyrene opals as templates.
DeepSLM: Speckle‐Licensed Modulation via Deep Adversarial Learning for Authorized Optical Encryption and Decryption
Authors: Huang Haofan , Zhao Qi , Li Huanhao , Zheng Yuandong , Yu Zhipeng , Zhong Tianting , Cheng Shengfu , Woo Chi Man , Gao Yi , Liu Honglin , Zheng Yuanjin , Tian Jie , Lai Puxiang
Published: September 2024

Optical encryption is pivotal in information security, offering parallel processing, speed, and robust security. The simplicity and compatibility of speckle‐based cryptosystems have garnered considerable attention. Yet, the predictable statistical distribution of speckle optical fields’ characteristics can invite statistical attacks, undermining these encryption methods. The proposed solution, a deep adversarial learning‐based speckle modulation network (DeepSLM), disrupts the strong intercorrelation of speckle grains. Utilizing the unique encoding properties of speckle patterns, DeepSLM facilitates license editing within the modulation phase, pioneering a layered authentication encryption system. Our empirical studies confirm DeepSLM's superior performance on key metrics. Notably, the testing dataset reveals an average Pearson correlation coefficient above 0.97 between decrypted images and their original counterparts for intricate subjects like human faces, attesting to the method's high fidelity. This innovation marries adjustable modification, optical encryption, and deep learning to enforce tiered data access control, charting new paths for creating user‐specific access protocols.
Wasserstoffaktivierung mit Phenylradikal durch Protium‐ und Deuteriumtunneln
Authors: Bhagat Virinder , Meisner Jan , Wagner J. Philipp
Published: September 2024

Die Aktivierung von molekularem Wasserstoff, H2, ist eine herausfordernde Aufgabe, die vorwiegend mithilfe von Übergangsmetallzentren in Angriff genommen wird. Reine Hauptgruppenverbindungen, die dazu in der Lage sind, wurden erst in den letzten Jahrzehnten entwickelt. Solche Verbindungen nutzen synergistische Donor‐Akzeptor‐Wechselwirkungen mit dem antibindenden σ*‐ und dem bindenden σ‐Orbital von H2. Eine alternative, radikalvermittelte Aktivierung ist problematisch, da die H−H‐Bindung stärker ist (104,2 kcal mol−1) als die meisten C−H‐Bindungen. Hier nutzen wir das Phenylradikal, um dieses Problem zu lösen, wobei Benzol mit einer C−H‐Bindungsenergie von 112,9 kcal mol−1 entsteht, wodurch eine thermodynamische Triebkraft erzeugt wird. Bei der Photolyse von Iodbenzol in einer H2‐dotierten Neonmatrix bei 4,4 K beobachten wir trotz einer Reaktionsbarriere von 7,6 kcal mol−1 hauptsächlich die Bildung eines Benzol‐HI‐Komplexes, während im Fall des schwereren D2‐Isotopologs das Phenylradikal entsteht. Wenn die D2‐Moleküle diffundieren können, bildet sich monodeuteriertes Benzol innerhalb von Stunden. Pfadintegralbasierte Instanton‐ Rechnungen ergeben, dass sich bei der Reaktion vorwiegend das transferierte Wasserstoffatom bewegt, was die Tunnelwahrscheinlichkeit stark erhöht. In guter Übereinstimmung mit dem Experiment sagen wir signifikante Reaktionsgeschwindigkeiten für beide Isotope, H2 und D2, voraus sowie einen ausgeprägten kinetischen Isotopeneffekt von bis zu vier Größenordnungen bei tiefsten Temperaturen.
Constructing Tandem Fenton‐like Reaction Systems Based on Structure Adaption to Boost Water Contaminant Mineralization Efficiency
Authors: Chen Min , Yang Tian , Lei Qiuxia , Gan Xue , Mao Shun , Zhao Hongying
Published: September 2024

Mineralization of emerging contaminants by using advanced oxidation processes (AOPs) is a desirable option to ensure water safety, but still challenged by the excessive chemical and/or energy input. Here, we conceptually proposed the tandem reaction system (TRS) of different reactive oxygen species (ROS) based on structure adaption of target contaminants. To construct a model TRS, we first realized highly selective generation of three classical ROS (1O2, HO⋅ and SO4⋅−) by peroxymonosulfate activation in an electrochemical Fenton‐like system, where three replaceable Fe‐centered cathodes were rationally designed as electronic mediator. The 1O2+SO4⋅−‐TRS exhibited nearly 100 % mineralization of sulfamethoxazole (SMX), whereas only 34.2 %, 56.2 % and 60.8 % for each of the single 1O2/HO⋅/SO4⋅−‐AOP systems. Mechanism exploration of SMX degradation in TRS evidenced that the initial reaction with 1O2 selectively destructed the sulfonamide bridge of SMX to form p‐aminobenzenesulfonic acid, which will be vulnerable to sequent SO4⋅− attack to facilitate mineralization. Successful extendibility of 1O2+SO4⋅−‐TRS to other sulfonamide antibiotics and 1O2+HO⋅‐TRS to phenolic and arylcarboxylic compounds, as well as the demonstration of 1O2+SO4⋅−‐TRS in treatment of three actual pharmaceutical wastewaters strongly support that TRS is a powerful and sustainable strategy to enhance the mineralization of emerging contaminants in water.
Comprehensive Profiling of Roquin Binding Preferences for RNA Stem‐Loops
Authors: Oberstrass Lasse , Tants Jan‐Niklas , Lichtenthaeler Chiara , Ali Sara E. , Koch Louisa , Mathews David H. , Schlundt Andreas , Weigand Julia E.
Published: September 2024

The cellular levels of mRNAs are controlled post‐transcriptionally by cis‐regulatory elements located in the 3’‐untranslated region. These linear or structured elements are recognized by RNA‐binding proteins (RBPs) to modulate mRNA stability. The Roquin‐1 and −2 proteins specifically recognize RNA stem‐loop motifs, the trinucleotide loop‐containing constitutive decay elements (CDEs) and the hexanucleotide loop‐containing alternative decay elements (ADEs), with their unique ROQ domain to initiate mRNA degradation. However, the RNA‐binding capacity of Roquin towards different classes of stem‐loops has not been rigorously characterized, leaving its exact binding preferences unclear. Here, we map the RNA‐binding preference of the ROQ domain at nucleotide resolution introducing sRBNS (structured RNA Bind‐n‐Seq), a customized RBNS workflow with pre‐structured RNA libraries. We found a clear preference of Roquin towards specific loop sizes and extended the consensus motifs for CDEs and ADEs. The newly identified motifs are recognized with nanomolar affinity through the canonical RNA‐ROQ interface. Using these new stem‐loop variants as blueprints, we predicted novel Roquin target mRNAs and verified the expanded target space in cells. The study demonstrates the power of high‐throughput assays including RNA structure formation for the systematic investigation of (structural) RNA‐binding preferences to comprehensively identify mRNA targets and elucidate the biological function of RBPs.
Phenyl Radical Activates Molecular Hydrogen Through Protium and Deuterium Tunneling
Authors: Bhagat Virinder , Meisner Jan , Wagner Jan Philipp
Published: September 2024

Activating dihydrogen, H2, is a challenging endeavor typically achieved using transition metal centers. Pure main‐group compounds capable of this are rare and have emerged in recent decades. These systems rely on synergistic donor‐acceptor interactions with H2’s antibonding σ* and bonding σ orbital. An alternative (hydrocarbon) radical‐mediated activation is problematic because the H−H bond is stronger (104.2 kcal mol−1) than most C−H bonds. Here, we explore using the phenyl radical to tackle this, forming benzene with a C−H bond energy (112.9 kcal mol−1) that provides a thermodynamic driving force. We mainly observe a benzene‐HI complex upon photolysis of iodobenzene in an H2‐doped neon matrix at 4.4 K despite a barrier of 7.6 kcal mol−1, while phenyl radical forms in case of the heavier D2 isotopologue. When D2 molecules are allowed to diffuse, mono‐deuterated benzene accumulates within hours. Computations using path integral‐based instanton theory highlight that primarily the transferred hydrogen atom is moving during the reaction which greatly increases the tunneling probability. In excellent agreement with the experimental results, we predict significant tunneling rate constants for both isotopologues, H2 and D2, featuring a strong kinetic isotope effect of up to four orders of magnitude at the lowest temperatures.
Establishing the Comprehensive Structure−Activity Relationship of the Natural Antibiotic Kibdelomycin/Amycolamicin
Authors: Chen Chenglong , Yin Yuyao , Lu Panrui , Han Ting , Wang Hui , Li Chao
Published: September 2024

Kibdelomycin (KBD) and amycolamicin (AMM) are potent natural antibiotics effective against antibiotic‐resistant Gram‐positive pathogens, including vancomycin‐intermediate Staphylococcus aureus (S. aureus, VISA), methicillin‐resistant S. aureus (MRSA), and quinolone‐resistant S. aureus (QRSA). Their antibacterial activity stems from an unprecedented dual mechanism: the lower binding sites occupy the adenosine triphosphate (ATP) binding pocket of bacterial type II topoisomerases, while the upper binding sites disrupt the enzyme dimer interface. This dual action, combined with their unique chemical structures, positions KBD and AMM as promising scaffolds for developing new antibiotics. However, the structure–activity relationship (SAR) of KBD/AMM remains underexplored due to their highly complex chemical structures. In this study, we utilized total synthesis to produce KBD/AMM analogs with various site modifications and evaluated their antimicrobial activities. Our findings establish the first comprehensive SAR for KBD/AMM, paving the way for the development of novel KBD/AMM‐based antibiotics.
Novel hydrazide‐hydrazone containing 1,2,4‐triazole as potent inhibitors of antiapoptotic protein Bcl‐xL: Synthesis, biological evaluation, and docking studies
Authors: Kuran Ebru Didem , Uner Burcu , Cam Muhammet Emin , Ulusoy‐Guzeldemirci Nuray
Published: September 2024

This study describes the synthesis and characterization of a series of novel hydrazide‐hydrazone derivatives containing a 1,2,4‐triazole ring. The compounds were characterized using various spectroscopic techniques, such as FT‐IR, 1H‐NMR, 13C‐NMR, HRMS, and elemental analysis. The antiproliferative activity of the synthesized compounds was evaluated against a panel of human cancer cell lines (HCT‐116, HepG‐2, KLN205, LTPA, U138, and SW620) and healthy cell lines (HSkMC and iPSCs). Among the compounds tested, compounds 4, 5p, 5r, and 5s showed the highest effectiveness in inhibiting the growth of cancer cells with Bcl‐xL inhibitory concentration (IC50) values. These compounds further demonstrated selective cytotoxicity against the Bcl‐xL‐dependent lymphoma cell line (DBs). Molecular docking studies were also performed to investigate the potential binding interactions of compounds 4, 5p, 5r, and 5s with the active site of Bcl‐xL (PDB ID: 7LH7, 1.4 Å). Mechanistic studies revealed that compounds 4, 5r, and 5s induced apoptosis predominantly through the intrinsic mitochondrial pathway, while compound 5p exhibited a distinct cell cycle arrest profile, impacting both the S and G2/M phases. Western blot analysis suggested that these compounds may downregulate cyclin expression, thereby blocking its association with Bcl‐xL. Overall, these results demonstrate the potential of these novel hydrazide‐hydrazone derivatives as anticancer agents with activity comparable or superior to doxorubicin and 5‐fluorouracil.
A sustainable RP‐HPLC method for concurrent estimation of capecitabine and celecoxib in liposomal formulation: Greenness and whiteness appraisal
Authors: Shewale Rushikesh Sanjay , Gomte Shyam Sudhakar , Jain Aakanchha
Published: September 2024

Liposomes have been reported for combination therapy due to their ability to carry both hydrophilic and lipophilic drugs together. The current investigation aims to develop a novel, eco‐friendly, and sustainable reverse‐phase high‐performance liquid chromatography (RP‐HPLC) method for the simultaneous quantification of capecitabine and celecoxib co‐encapsulated in liposomes. The method reported herein uses a C18 column (4.6 × 250 mm2, 5 μm) and a mobile phase consisting of water, and acetonitrile/methanol in a ratio of 60:40, containing 0.1% formic acid in both the phases. The flow rate is maintained at 1 mL/min, with an injection volume of 10 μL in the gradient mode. Detection is set at λmax = 240 nm for capecitabine and 252 nm for celecoxib. The developed liposomes are mono‐disperse with a surface potential of −6.93 mV. The average size of the liposomes is 142 nm. The percentage entrapment efficiency for capecitabine is 52.39 ± 0.94%, and for celecoxib, it is 77.13 ± 0.74%. The Analytical Greenness Metric of 0.61 and Analytical Eco‐Scale Score of 75 signify the greenness of the developed method. Also, the Red‐Green‐Blue model shows excellent whiteness, with a score of 83.2. Thus, the developed method offers a reliable, accurate, precise, buffer‐free, and environment‐friendly RP‐HPLC approach for the simultaneous analysis of capecitabine and celecoxib co‐encapsulated in liposomes.
Impact of IgG Fc Glycosylation on Disease Dynamics in Patients With Primary Sjögren Disease
Authors: Achten Helena , Meuris Leander , Deroo Liselotte , Jarlborg Matthias , Decruy Tine , Deprez Joke , Dumas Emilie , De Boeck Kristel , Genbrugge Eva , Bauters Wouter , Dochy Frederick , Creytens David , Roels Dimitri , Callewaert Nico , Elewaut Dirk , Peene Isabelle
Published: September 2024

Objective

Glycans attached to the Fc region of IgG antibodies influence their pro‐ or anti‐inflammatory effector function. We aimed to explore the interrelation of the Fc glycosylation profile and disease transition, disease activity, and outcome in patients with suspected and confirmed primary Sjögren disease (SjD).

Methods

IgG Fc sialylation and IgG Fc galactosylation serum levels were determined in 300 patients from the Belgian Sjögren's Syndrome Transition Trial. This cohort includes both suspected and confirmed patients with SjD meeting the 2016 American College of Rheumatology/EULAR criteria. Salivary gland involvement was evaluated through ultrasonography (Hocevar score 0–48) and histopathology (focus score). The relative amount of sialylated and galactosylated IgG was determined by capillary electrophoresis after using the endoglycosidase S‐based assay.

Results

Patients with SjD exhibited significantly lower sialylation and galactosylation levels versus asymptomatic carriers of anti‐SSA and patients with sicca. Lower sialylation and galactosylation levels were significantly associated with an increase in B cell activation markers and distinct autoantibody profiles, particularly with multiple autoantibody reactivities. They were also linked to histopathological salivary gland alterations, higher Hocevar scores, and, importantly, risk factors for non‐Hodgkin lymphoma (NHL) development. In contrast, patients with SjD who were mono‐anti‐Ro60 positive and those who were anti‐SSA negative had normal IgG Fc glycosylation.

Conclusion

This study points to a novel role of IgG Fc glycosylation in patients with SjD in predicting disease transition, monitoring disease activity, and stratifying risk of NHL development.

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Therapeutic potential of Shaoyao Gancao Decoction in mitigating anti‐tuberculosis drug‐induced liver injury through Nrf‐2/HO‐1/NF‐κB signaling
Authors: Zhang Huan , Ma Lihua , Li Sisi , Ding Qiaoyan , Zhang Yu , Zhou Ming
Published: September 2024

Tuberculosis (TB) is a persistent global health issue, evidenced by an increasing number of cases. Although anti‐TB drugs have proven efficacy, they are often associated with severe liver injury (ATB‐DILI). The objective of this research was to uncover the mechanisms through which Shaoyao Gancao Decoction (SGD) mitigates ATB‐DILI, emphasizing the role of the Nrf‐2/HO‐1/NF‐κB signaling pathway. We prepared SGD granules and subjected them to HPLC‐MS/MS for analysis. An ATB‐DILI rat model was then developed and administered SGD. We evaluated liver injury markers, the extent of oxidative stress, inflammation, and the principal proteins involved in the Nrf‐2/HO‐1/NF‐κB pathway. Additionally, network pharmacology techniques were utilized to discern potential SGD targets and their associated pathways. Administering SGD had a notable effect in counteracting the elevation of liver injury markers and pathological alterations induced by ATB‐DILI. Moreover, there was a marked reduction in oxidative stress and inflammation in the treated rats. We identified 12 active compounds in SGD, with 88 shared targets between SGD and ATB‐DILI. Subsequent KEGG analysis brought attention to pathways like MAPK, NF‐κB, and IL‐17 signaling. Our findings pave the way for more in‐depth studies into the application of SGD in treating drug‐induced liver injuries.
Monocyte‐to‐Albumin Ratio Is Associated With Hematoma Expansion in Spontaneous Intracerebral Hemorrhage
Authors: Fu Jie , Xu Yilin , Chen Xiu , Li Jinglun , Peng Lilei
Published: September 2024

Background

Hematoma expansion (HE) after spontaneous intracerebral hemorrhage (ICH) is a severe complication that independently predicts poor prognosis. In this study, we aimed to investigate whether monocyte‐to‐albumin ratio (MAR), a novel marker of systemic inflammation, could predict HE in patients with ICH.

Methods

We retrospectively assessed the data of patients with ICH. The clinical, imaging, and laboratory test data including, the MAR on admission, were analyzed. A multivariate logistic regression analysis was carried out to explore the relationship between MAR and hematoma growth. The receiver operating characteristic (ROC) curve was employed to investigate the predictive value of MAR for HE after ICH.

Results

A total of 246 patients were included in the present study. Multivariate logistic regression analysis demonstrated that the MAR was associated with HE (odds ratio [OR] = 1.179; 95% confidence interval, 1.093–1.272; p = 0.000). ROC curve analysis showed that MAR could predict HE, with an area under the curve of 0.802 (95% CI: 0.744–0.859, p < 0.001). The optimal predictive cutoff value of MAR for HE was 10.01 (sensitivity: 72.43%, specificity: 77.05%).

Conclusions

Our results suggested that a high MAR on admission was associated with an increased risk of HE in ICH patients, and MAR can become an independent predictor of HE in ICH patients.
Diagnostic Value of Serum Apolipoprotein B100 Combined With Hippocampal Volume in Alzheimer's Disease
Authors: Zhang Dandan , Wu Jing , Ren Guoqiang , Wang Yi , Xu Hang , Chen Siyuan , Li Xuezhong , Chen Xiaopeng
Published: September 2024

Purpose

To explore the diagnostic value of serum apolipoprotein B100 (Apo B100) combined with hippocampal volume in Alzheimer's disease (AD).

Methods

A total of 59 AD patients and 59 healthy subjects were selected. The Mini‐Mental State Examination (MMSE) was used for neuropsychological assessment. Blood glucose and serum lipid levels were detected by biochemical analyzer. Polymerase chain reaction (PCR) was used to detect apolipoprotein E (Apo E) ε3/ε4 genotypes in the plasma. Hippocampal volume was calculated using Slicer software. Independent‐sample t test or Mann–Whitney U test were used to compare the levels of various indicators between the two groups. Spearman's correlation analysis was used to analyze the correlation between each level. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to compare the diagnostic efficacy of individual and combined detection of serum Apo B100 levels and hippocampal volume in AD.

Results

Compared with the healthy control group, the levels of serum total cholesterol (TC), low‐density lipoprotein (LDL), Apo B100, and plasma Apo E ε3/ε4 were higher in the AD group, and serum high‐density lipoprotein (HDL) level was lower in the AD group (both p < 0.05). The hippocampal volume in the AD group was lower than in the control group (p < 0.01). The serum Apo B100 level was negatively correlated with MMSE score (r = −0.646), whereas hippocampal volume was positively correlated with MMSE score (r = 0.630). ROC curve analysis showed that the AUC of the combined serum Apo B100 level and hippocampal volume for AD was higher than that of either alone (AUC = 0.821, p < 0.01).

Conclusion

Serum Apo B100 level is elevated, and the hippocampal volume is reduced in AD patients. The combined detection of the two has a higher diagnostic efficiency for AD than other alone and has the potential to become an important indicator for the diagnosis of AD in the future.
Sustainability‐based value creation within a multi‐stakeholder network: Balancing expectation conflicts within the Amazon context
Authors: Dias Gabriela Nobre , Hamza Kavita Miadaira , Lievens Annouk , Moons Ingrid
Published: September 2024

The current paper reports on ways to better co‐create sustainability‐based value in multi‐stakeholder networks by focusing on stakeholder expectations, their resulting conflicts, and feasible interventions. Indeed, the literature review reveals a growing research focus on multi‐stakeholder networks involving non‐governmental organizations, traditional communities, and companies operating in vulnerable natural environments. This research interest is driven by the growing need for forest preservation and its impact on creating a more sustainable ecosystem. Our study uses the case of Origens Brasil, a multi‐stakeholder network promoting ethical trade and protection of the Amazon Forest, and involves 47 interviews, and observational data. We contribute by identifying stakeholder expectations and shedding light on the unique conflicts that emerge from differences in these expectations. Furthermore, we developed a framework for sustainability‐based value creation derived from expectation conflict intervening.
Application of MS Excel and FastTest PlugIn to automatically evaluate the students' performance in structural engineering courses
Authors: Huerta‐Gomez‐Merodio M. , Requena‐Garcia‐Cruz M. V.
Published: September 2024

Background

In recent years, the method of assessment in universities has been rapidly changing, shifting from entirely in‐person evaluations to a blended evaluation approach (b‐Learning).

Purpose

To effectively implement this type of assessment, it is necessary to create numerous similar problems with different data sets. In structural engineering courses, this entails a significant amount of work for the lecturers. Therefore, this work introduces a novel teaching and evaluation strategy leveraging technology to automate tasks, aiming to enhance student monitoring and alleviate lecturer workload.

Method

The digital platform Moodle has been used combined with the FastTest PlugIn to create computer coding to develop different problems. These problems, maintaining consistent structures but varying data, served both instructional and evaluative purposes in two structural engineering courses. As a novelty, these problems are automatically evaluated and created following the coding routine created. Some drawbacks have been identified while applying the method. Scientifically validated quizzes have been used to assess the efficacy of the method in engaging students and enhancing their confidence and satisfaction.

Results

Findings suggest that while initial setup requires additional time, the investment pays off in the grading efficiency, benefiting educators and students alike. The method has facilitated the creation of additional exercises for practice, and the inclusion of automatically corrected diagrams was appreciated by students. The results have indicated that this method has improved the motivation, attention, and confidence among students, leading to significant enhancements in academic performance, up to 40%.

Conclusions

This methodology has achieved positive responses from students. Hence, it is concluded that the time invested in developing structural engineering problems using MS Excel and the FastTest PlugIn in Moodle is worthwhile, as it motivates students to improve their academic performance. Furthermore, as the main outcome, it is shown that the time invested by the lecturer in developing the problems is amortized in subsequent academic years since the problems are graded automatically. For courses with many students, it is amortized sooner.
Reflections from LGBTQIA+ individuals of their past experiences of psychotherapy and counselling and the use of creative therapy—A qualitative study
Authors: Crummy Mark , Hansford Suzy
Published: September 2024

Background

Previous literature tends to suggest that the LGBTQIA+ community face higher rates of mental disorders and illnesses. This appears to be due to minority stress as a result of the discrimination and hostility towards the community from society. In relation to psychotherapy and/or counselling, affirmative therapy has been found to be helpful; however, it is clear from the literature that the LGBTQIA+ population do not feel accepted or understood when accessing mental health support.

Method

Participants were invited to take part in an interview consisting of open‐ended questions relating to the topic of interest. Following this, a thematic analysis was completed.

Findings

The thematic analysis revealed four main themes: these were ‘sexuality and gender within the therapeutic relationship’, ‘desirable characteristics and attributes in a therapist’, ‘undesirable characteristics and attributes in a therapist’ and ‘creative therapy’.

Implications for Practice

The results could be used to inform mental health practitioners of the importance of cultural competency in relation to the LGBTQIA+ community, as well as helping aid how to approach sexuality and/or gender in a therapeutic space. The conclusions also highlight the need for practitioners to explore context with LGBTQIA+ clients rather than solely emotion focus.

Conclusion

This study indicated that the LGBTQIA+ community prefer working with LGBTQIA+ therapists due to a shared lived experience and perceived baseline understanding of each other. It was also found that context was important for them in therapy, rather than emotion focus, and creative therapy was also shown to be useful for the community.
Deregulation of Melatonin Receptors and Differential Modulation of After‐Hyperpolarization and Ih Currents Using Melatonin Treatment Due to Amyloid‐β‐Induced Neurotoxicity in the Hippocampus
Authors: Eslamizade Mohammad J. , Saffarzadeh Fatemeh , Khatami Sanaz , Davoudi Shima , Soleimani Zahra , Anajafi Sara , Khoshnazar Amineh , Mehdizadeh Mehdi , Mohammadi‐Yeganeh Samira , Janahmadi Mahyar
Published: September 2024

Treatment with melatonin is routinely prescribed for its potent antioxidant and cognitive‐promoting effects, nevertheless, it has yet to find neuromodulatory effects in normal and disease conditions. Therefore, to investigate its neuromodulatory mechanisms, melatonin was systemically administered over 10 consecutive days to both intracortical normal saline‐ and amyloid‐β 1‐42 (Aβ) peptide‐injected rats. At the behavioral level, treatment with melatonin was associated with reduced efficacy in restoring Aβ‐induced deficit in passive‐avoidance memory. Whole‐cell patch‐clamp recordings from CA1 pyramidal neurons revealed that melatonin treatment reduced spontaneous and evoked intrinsic excitability in control rats while exerting a reduction of spontaneous, but not evoked activity, in the Aβ‐injected group. Interestingly, treatment with melatonin enhances after‐hyperpolarization in control, but not Aβ‐injected rats. In contrast, our voltage‐clamp study showed that Ih current is significantly enhanced by Aβ injection, and this effect is further strengthened by treatment with melatonin in Aβ‐injected rats. Finally, we discovered that the transcription of melatonin receptors 1 (MT1) and 2 (MT2) is significantly upregulated in the hippocampi of Aβ‐injected rats. Collectively, our study demonstrates that systemic treatment with melatonin has differential neuromodulation on CA1 neuronal excitability, at least in part, via differential effects on after‐hyperpolarization and Ih currents due to Aβ‐induced neurotoxicity.
Expanding the “Terpenome”: Applications of Unspecific Peroxygenases (UPOs) in Oxidations of Unnatural Terpenoids
Authors: Struwe Henry , Grimm Christopher , Dräger Gerald , Beutel Sascha , Alcalde Miguel , Kirschning Andreas , Kara Selin
Published: September 2024

An unnatural tricyclic oxaterpenoid, obtained by treatment of the sesquiterpene synthase presilphiperfolan‐8β‐ol synthase (BcBOT2) with an unnatural farnesyl pyrophosphate ether derivative, itself obtained by chemical synthesis, was converted in oxidation studies as part of a broad screening program by selected unspecific peroxygenases (UPOs). Product analysis revealed that Agrocybe aegerita UPO, its mutant PaDa‐I, and two commercial ones, UPO54 and UPO49, provided new oxidation products with sufficient efficiency for subsequent upscaling that allowed product isolation and structure elucidation. As such new terpene‐based oxiranes and hemiacetals were formed by UPO‐mediated epoxidations and CH‐activation. The structure elucidation was further supported by comparison with products generated by chemical oxidation.
A Reusable Polystyrene Support for Sustainable yet Cost‐effective Octreotide Synthesis
Authors: Kushwaha Priyanka , Madhavan Nandita
Published: September 2024

The synthesis of peptide drugs has become facile with the use of supports that enable easy separation of the growing peptide. Peptide synthesis on insoluble supports typically employs excess reagents to enhance reaction efficiency and faces challenges during intramolecular cyclization. A non‐crosslinked soluble polystyrene support is reported herein that improves cyclization efficiency on the support by using spacers. The support efficiency is illustrated by synthesizing octreotide drug in a scalable manner by on‐support cyclization. The methodology drastically reduces the reagent waste, raw‐material cost, and solvent requirement. The support can also be recovered and re‐used up to 3 times making this a very sustainable method.
Die Zukunft des Recyclings gestalten
Authors: Krause Lars
Published: September 2024

Die ambitionierten Recyclingziele der EU und die wachsenden Anforderungen an die chemische Industrie sowie die Markenhersteller erhöhen den Druck auf den Recyclingsektor. Gleichzeitig steigt die Nachfrage nach erneuerbaren Rohstoffen für Chemikalien und Materialien, was die Frage aufwirft, welche Recyclingtechnologien am besten geeignet sind. Die Advanced Recycling Conference beleuchtet spartenübergreifende Lösungen, während eine neue Studie einen globalen überblick über die Kapazitäten von Advanced Recycling‐Technologien bietet.
A review of multiscale numerical modeling of rock mechanics and rock engineering
Authors: Wei Xindong , Li Zhe , Zhao Gaofeng
Published: September 2024

Rock is geometrically and mechanically multiscale in nature, and the traditional phenomenological laws at the macroscale cannot render a quantitative relationship between microscopic damage of rocks and overall rock structural degradation. This may lead to problems in the evaluation of rock structure stability and safe life. Multiscale numerical modeling is regarded as an effective way to gain insight into factors affecting rock properties from a cross‐scale view. This study compiles the history of theoretical developments and numerical techniques related to rock multiscale issues according to different modeling architectures, that is, the homogenization theory, the hierarchical approach, and the concurrent approach. For these approaches, their benefits, drawbacks, and application scope are underlined. Despite the considerable attempts that have been made, some key issues still result in multiple challenges. Therefore, this study points out the perspectives of rock multiscale issues so as to provide a research direction for the future. The review results show that, in addition to numerical techniques, for example, high‐performance computing, more attention should be paid to the development of an advanced constitutive model with consideration of fine geometrical descriptions of rock to facilitate solutions to multiscale problems in rock mechanics and rock engineering.
Recent advances in functionalized separator for dendrites‐free and stable lithium metal batteries
Authors: Zhang Xiaojuan , Wu Yu , Yu Bo , Hu Kunpeng , Zhang Ping , Ding Fei , Zhang Lin , Chen Yuanfu , Ou Jian Zhen , Zhang Zhigang
Published: September 2024

Lithium (Li) metal anode is considered the “Holy grail” for the most promising next‐generation rechargeable lithium metal batteries (LMBs) because of ultra‐high theoretical specific capacity, ultra‐low reduction potential and small density. However, uncontrolled lithium dendrite growth and inevitable side reaction seriously hindered the application of practical LMBs because of the deteriorating electrochemical performances and exacerbating the safety issues of LMBs. Thus, improving the electrochemical performances of LMBs by constructed of functionalized separator is promising for overcoming the above‐mentioned challenges due to its' significantly advantages, such as enhancing mechanical and thermal stability, regulating the diffusion and migration of Li ions, homogenizing Li ion flux, forming protective layer on Li anode surfaces, etc. The relational investigations have significantly increased since 2020, while the comprehensive reviews on this research direction are relatively rare, especially in the detailed mechanism aspects. In this review, an overview in functionalized separator for stable LMBs is discussed in detail. Firstly, the current issues of LMBs are in‐depth discussion and the general strategies are summarized. Subsequently, the requirements and limitations of separator, as well as the advantages of functionalized separator are summarized and reviewed. Most importantly, the protection mechanisms and research advances of advanced functionalized separator are comprehensively discussed and summarized. Furthermore, the applications of functionalized separator in rechargeable lithium metal‐based full cells are reviewed. Finally, the challenges and potential opportunities for the future development and rational design of functionalized separator are highlighted in rechargeable LMBs to obtain future research directions related to the significant strategy of constructing dendrite‐free and stable LMBs.
Summer primary production of Arctic kelp communities is more affected by duration than magnitude of simulated marine heatwaves
Authors: Miller Cale A. , Gazeau Frédéric , Lebrun Anaïs , Alliouane Samir , Urrutti Pierre , Schlegel Robert W. , Gattuso Jean‐Pierre , Comeau Steeve
Published: September 2024

Fjord systems in the Norwegian Arctic are experiencing an increasing frequency and magnitude of marine heatwaves. These episodic heat stress events can have varying degrees of acute impacts on primary production and nutrient uptake of mixed kelp communities, as well as modifying the biogeochemical cycling in nearshore systems where vast areas of kelp create structural habitat. To assess the impact of future marine heatwaves on kelp communities, we conducted a 23 day mesocosm experiment exposing mixed kelp communities to warming and heatwave scenarios projected for the year 2100. Three treatments were considered: a constant warming (+1.8°C from the control), a medium magnitude and long duration heatwave event (+2.8°C from the control for 13 days), and two short‐term, more intense, heatwaves(5 day long scenarios with temperature peaks at +3.9°C from the control). The results show that both marine heatwave treatments reduced net community production, whereas the constant warm temperature treatment displayed no difference from the control. The long marine heatwave scenario resulted in reduced accumulated net community production, indicating that prolonged exposure had a greater severity than two high magnitude, short‐term heatwave events. We estimated an 11°C temperature threshold at which negative effects to primary production appeared present. We highlight that marine heatwaves can induce sublethal effects on kelp communities by depressing net community production. These results are placed in the context of potential physiological resilience of kelp communities and implications of reduced net community production to future Arctic fjord environmental conditions.