bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antiviral Efficacy and Safety of Azvudine in Hospitalized SARS‐CoV‐2 Infected Patients with Liver Diseases Based on a Multicenter, Retrospective Cohort Study
Authors: Sun Junyi , Yang Mengzhao , Su Guanyue , Wang Ling , Hu Xiaobo , Zhou Yongjian , Cui Guangying , Qian Guowu , Yuan Yiqiang , Hu Xinjun , Li Silin , Luo Hong , Zhang Shixi , Li Guangming , Zhang Donghua , Li Guotao , Cheng Ming , Yu Zujiang , Ren Zhigang
Published: February 2025

Despite azvudine being prioritized for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, its effectiveness and safety remain inadequately substantiated in hospitalized SARS‐CoV‐2 infected patients with liver diseases. A retrospective nine‐center cohort study along with an independent validation cohort is conducted to examine the efficacy of azvudine (Clinical Trial Registration Number: NCT06349655). The primary outcome is all‐cause mortality and the secondary outcome is composite disease progression. Efficacy is assessed via Kaplan–Meier analysis and Cox regression, with subgroup and sensitivity analyses for further validation. Among 32 864 hospitalized SARS‐CoV‐2 infected patients, 1022 eligible azvudine recipients, and 1022 controls are included through propensity score match. Kaplan–Meier analysis reveals that azvudine treatment is associated with a lower risk of all‐cause mortality and composite disease progression (both p<0.0001). Cox regression analysis suggests azvudine recipients could have a 39% lower risk of all‐cause mortality than controls (95% confidence interval [CI]: 0.468–0.795, p<0.001), but with no notable significance in composite disease progression (hazard ratio: 0.85, 95% CI: 0.686‐1.061, p = 0.154). Subgroup analysis suggests that azvudine has a greater benefit for both all‐cause mortality and composite disease progression in patients with kidney diseases or without autoimmune diseases. Three sensitivity analyses and validation cohorts confirm the robustness of the findings. Safety analysis observes few adverse events in azvudine recipients. Within 15 days after azvudine administration, no significant difference in liver function indexes and kidney function indexes is observed between the two groups except for a few time points. These findings demonstrate that azvudine shows potential clinical efficacy in improving all‐cause mortality in hospitalized SARS‐CoV‐2 infected patients with liver diseases, with acceptable adverse effects.
UFMylation of NLRP3 Prevents Its Autophagic Degradation and Facilitates Inflammasome Activation
Authors: Jing Jiongjie , Yang Fan , Wang Ke , Cui Mintian , Kong Ni , Wang Shixi , Qiao Xiaoyue , Kong Fanyu , Zhao Dongyang , Ji Jinlu , Tang Lunxian , Gao Jiaxin , Cong Yu‐Sheng , Ding Deqiang , Chen Kun
Published: February 2025

NLRP3 (NOD, LRR and pyrin domain‐containing protein 3) inflammasome is important for host defense against infections and maintaining homeostasis. Aberrant activation of NLRP3 inflammasome is closely related to various inflammatory diseases. Post‐translational modifications are critical for NLRP3 inflammasome regulation. However, the mechanism of NLRP3 inflammasome activation remains incompletely understood. Here, it is demonstrated that the Ufm1 E3 ligase Ufl1 mediated UFMylation is essential for NLRP3 inflammasome activation. Mechanistically, Ufl1 binds and UFMylates NLRP3 in the priming stage of NLRP3 activation, thereby sustaining the stability of NLRP3 by preventing NLRP3 K63‐linked ubiquitination and the subsequent autophagic degradation. It is further demonstrated that myeloid cell‐specific Ufl1 or Ufm1 deficiency in mice significantly alleviated inflammatory responses and tissue damage following lipopolysaccharide (LPS)‐induced endotoxemia and alum‐induced peritonitis. Thus, the findings offer new insights into potential therapeutic targets for NLRP3 inflammasome‐related diseases by targeting the UFMylation system.
GABP Promotes Mesangial Cell Proliferation and Renal Fibrosis Through GLI1 in Diabetic Nephropathy
Authors: Du Lei , Liu Sijie , Lu Yinfei , Ren Dongxue , Yu Xiujuan , Hu Yue , Yang Tingting , Yang Qun , Ming Jingxian , Zhang Jiawei , Yin Xiaoxing , Lu Qian
Published: February 2025

Abnormal proliferation of mesangial cells is a hallmark of diabetic nephropathy (DN). However, the cellular signaling mechanisms that regulate this proliferation remain poorly understood. In this study, it is demonstrated that GA‐binding protein (GABP), a member of the ETS family of transcription factors composed of GABPα and GABPβ, plays a significant role in the development of renal fibrosis by modulating mesangial cell proliferation. Notably, the deficiency of GABP in mesangial cells inhibits hyperglycemia‐induced proliferation and mitigates renal fibrosis in a murine model of type 2 diabetes mellitus (T2DM). RNA sequencing analysis identifies GLI Family Zinc Finger 1 (GLI1) as the principal downstream effector of GABP in diabetic mice, serving as a crucial regulator of the G1/S transition within the cell cycle. Subsequent investigations have demonstrated that GABP interacts with the GLI1 promoter, facilitating mesangial cell proliferation via GLI1‐dependent pathways. This is evidenced by the fact that GLI1 knockdown abrogates the proliferation of mesangial cells with GABP overexpression. Consequently, GABP emerges as a pivotal regulator of renal fibrosis and represents a promising therapeutic target for the treatment of diabetic nephropathy.
Acoustic Rayleigh Wave Turbulence in Soft Viscoelastic Matter
Authors: Kharbedia Mikheil , López‐Menéndez Horacio , García Basilio Javier , Velarde Manuel G. , Monroy Francisco
Published: February 2025

Evidence of discrete acoustic Rayleigh wave turbulence (DARWT) is reported on the free surface of complex viscoelastic materials under monochromatic excitation. These surface elastic non‐linear Rayleigh waves exhibit dispersionless dynamics governed by bulk shear rigidity at coexistence with dispersive capillary waves supported by surface tension. Using Laser Doppler Vibrometry (LDV), the discrete Kolmogorov–Zakharov (KZ) spectrum is measured, characterized by a power‐law envelope in an inertial cascade of discrete harmonics. When shear rigidity dominates, KZ‐spectrum characterized by an ω−5/2 acoustic fingerprint is observed as a conservative solid‐like scaling, theoretically predicted from the exact three‐wave dispersionless resonance. Conversely, when surface tension dominates over bulk stresses, dispersive CW behavior under the usual ω−17/6 liquid‐like scaling is recovered. These findings support a unique theoretical framework for understanding conservative DARWT and advance the field of surface wave turbulence in viscoelastic media with markedly non‐Newtonian rheology. Acoustic Rayleigh wave turbulence represents a conservative mechanism for dispersionless energy transport through weakly nonlinear wave interactions across scales, with relevance to various physics fields, from soft matter and biological systems up to geophysical flows.
Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis
Authors: Wu Xiaoping , Zhang Zixuan , Li Jingjing , Zong Jiuyu , Yuan Lufengzi , Shu Lingling , Cheong Lai Yee , Huang Xiaowen , Jiang Mengxue , Ping Zhihui , Xu Aimin , Hoo Ruby L.C.
Published: February 2025

Dysregulation of adipose tissue (AT) homeostasis in obesity contributes to metabolic stress and disorders. Here, we identified that Coiled‐coil‐helix‐coiled‐coil‐helix domain containing 10 (Chchd10) is a novel regulator of AT remodeling upon excess energy intake. Chchd10 is significantly reduced in the white adipose tissue (WAT) of mice in response to high‐fat diet (HFD) feeding. AT‐Chchd10 deficiency accelerates adipogenesis predominantly in subcutaneous AT of mice to store excess energy in response to short‐term HFD feeding while upregulates glutathione S‐transferase A4 (GSTA4) to facilitate 4‐HNE clearance mainly in visceral AT to prevent protein carbonylation‐induced cell dysfunction after long‐term HFD feeding. Hence, Chchd10 deficiency attenuates diet‐induced obesity and related metabolic disorders in mice. Mechanistically, Chchd10 deficiency enhances adipogenesis and GSTA4 expression by activating TDP43/Raptor/p62/Keap1/NRF2 axis. Notably, the beneficial effect of Chchd10 deficiency is eliminated in hypertrophic adipocytes, where p62 is strikingly reduced. Collectively, Chchd10 is a metabolic sensor maintaining AT homeostasis, and the loss of p62 in adipose tissue under obese conditions impairs Chchd10‐mediated AT remodeling.
3‐D Sustained‐Release Culture Carrier Alleviates Rat Intervertebral Disc Degeneration by Targeting STING in Transplanted Skeletal Stem Cells
Authors: Luo Liwen , Zhang Shiyu , Gong Junfeng , Zhang Ji , Xie Peng , Yin Jun , Zhang MengJie , Zhang Cong , Chen Hong , Liu Yao , Ni Bing , Li Changqing , Tian Zhiqiang
Published: February 2025

The hypoxic and high‐pressure microenvironment of the intervertebral discs poses a major challenge to the survival and therapeutic efficiency of exogenous stem cells. Therefore, improving the utilization efficiency and therapeutic effect of exogenous stem cells to delay intervertebral disc degeneration (IVDD) is of great importance. Here, hypoxic induction studies are conducted in vivo and in vitro using rat costal cartilage‐derived skeletal stem cells (SSCs) and find that hypoxia activates the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and increased reactive oxygen species (ROS) accumulation, triggering ferroptosis in SSCs through hypoxia‐inducible factor‐1 alpha‐dependent mitophagy. Progressive hypoxia preconditioning reduce STING expression and ROS accumulation, inducing SSCs differentiation into nucleus pulposus‐like cells via the Wnt signaling pathway. Considering this, a 3‐D sustained‐release culture carrier is generated by mixing SSCs with methacrylated hyaluronic acid and polydopamine nanoparticles coated with the STING inhibitor C‐176 and evaluated its inhibitory effect on IVDD. This carrier is demonstrated to inhibit the cGAS/STING pathway and prevent ROS accumulation by continuously releasing C‐176‐coated polydopamine nanoparticles, thereby reducing ferroptosis, promoting differentiation, and ultimately attenuating IVDD, suggesting its potential as a novel treatment strategy.
An Anti‐CD147 Antibody−Drug Conjugate Mehozumab‐DM1 is Efficacious Against Hepatocellular Carcinoma in Cynomolgus Monkey
Authors: Huang Wan , Zhong Liping , Shi Ying , Ma Qingzhi , Yang Xiangmin , Zhang Hongmei , Zhang Jing , Wang Ling , Wang Kun , Li Jingzhuo , Zou Jie , Yang Xu , Yang Liu , Zeng Qingmei , Jing Lin , Chen Zhi‐Nan , Zhao Yongxiang
Published: February 2025

Effective treatment strategies are urgently needed for hepatocellular carcinoma (HCC) patients due to frequent therapeutic resistance and recurrence. Antibody‐drug conjugate (ADC) is a specific antibody‐drug conjugated with small molecular compounds, which has potent killing activity against cancer cells. However, few ADC candidates for HCC are undergoing clinical evaluation. CD147 is a tumor‐associated antigen that is highly expressed on the surface of tumor cells. Here CD147 is found significantly upregulated in tumor tissues of HCC. Mehozumab‐DM1, a humanized anti‐CD147 monoclonal antibody conjugated with Mertansine (DM1) is developed. Mehozumab‐DM1 is effectively internalized by cancer cells and demonstrated potent antitumor efficacy in HCC cells. In vivo evaluation of Mehozumab‐DM1 is conducted in a CRISPR‐mediated PTEN and TP53 mutation cynomolgus monkey liver cancer model, which is poorly responsive to sorafenib treatment. Mehozumab‐DM1 demonstrated potent tumor inhibitory efficacy at doses of 0.2 and 1.0 mg kg−1 treatment groups in cynomolgus monkey. No treatment‐related adverse reactions or body weight loss are observed. Interestingly, Mehozumab‐DM1 treatment induced RIPK‐dependent tumor cell necroptosis through inhibiting IκB kinase/NF‐κB pathway. In conclusion, Mehozumab‐DM1 potently inhibits hepatoma through effective internalization to release payload and inducing cell necroptosis to enhance the bystander effect, which is a promising treatment for refractory HCC.
Pepticombisomes: Biomimetic Vesicles Crafted From Recombinant Supercharged Polypeptides with Uniformly Distributed Side‐Chains
Authors: Söder Dominik , Schadt Melina , Petrovskii Vladislav S. , Haraszti Tamás , Rahimi Khosrow , Potemkin Igor I. , Kostina Nina Yu. , Rodriguez‐Emmenegger Cesar , Herrmann Andreas
Published: February 2025

Cell membranes play a key role in bottom‐up synthetic biology, as they enable interaction control, transport, and other essential functions. These ultra‐thin, flexible, yet stable structures form through the self‐assembly of lipids and proteins. While liposomes are common mimics, their synthetic membranes often fail to replicate natural properties due to poor structural control. To address this, pepticombs are introduced, a new family of supramolecular building blocks. They are synthesized by regularly appending anionic surfactants with lipid‐long alkyl tails to cationic amino acid residues of recombinant elastin‐like supercharged unfolded polypeptides (SUPs). Using microscopy techniques and molecular dynamics simulations, the formation of giant unilamellar vesicles, termed pepticombisomes, is demonstrated and their membrane properties are characterized. The molecular topology of pepticombs allows for precise mimicry of membrane thickness and flexibility, beyond classic polymersomes. Unlike the previously introduced ionically‐linked comb polymers, all pepticombs exhibit a uniform degree of polymerization, composition, sequence, and spontaneous curvature. This uniformity ensures consistent hydrophobic tail distribution, facilitating intermolecular hydrogen bonding within the backbone. This generates elastic heterogeneities and the concomitant formation of non‐icosahedral faceted vesicles, as previously predicted. Additionally, pepticombisomes can incorporate functional lipids, enhancing design flexibility.
CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages
Authors: Xiong Jiaqiang , Huang Juyuan , Xu Hanxiao , Wu Qiuji , Zhao Jiahui , Chen Yurou , Fan Guanlan , Guan Haotong , Xiao Rourou , He Zhaojin , Wu Siqi , Ouyang Wenliang , Wang Shixuan , Zhang Lu , Xia Peng , Zhang Wei , Wu Meng
Published: February 2025

CpG oligodeoxynucleotides (CpG), as an immunoadjuvant, can facilitate the transformation of tumor‐associated macrophages (TAMs)into tumoricidal M1 macrophages. However, the accumulation of free CpG in tumor tissues remains a substantial challenge. To address this, a nanovaccine (PLGA‐CpG@ID8‐M) is engineered by encapsulating CpG within PLGA using ID8 ovarian cancer cell membranes (ID8‐M). This nanovaccine demonstrates remarkable efficacy in reprogramming TAMs in ovarian cancer and significantly extends survival in ID8‐bearing mice. Notably, these findings indicate that the nanovaccine can also mitigate chemotherapy‐induced immunosuppression by increasing the proportion of M1‐like TAMs and reducing the expression of CD47 on tumor cells, thereby achieving a synergistic effect in tumor immunotherapy. Mechanistically, through transcriptome sequencing (RNA‐seq), single‐cell RNA sequencing (scRNA‐seq), and mass spectrometry‐based proteomics, it is elucidated that the nanovaccine enhances the expression of Gbp2 and promotes the recruitment of Pin1, which activates the NFκB signaling pathway, leading to the M1 polarization of TAMs. Furthermore, macrophages with elevated Gbp2 expression significantly inhibit tumor growth in both ID8 ovarian cancer and 4T1 breast cancer models. Conversely, targeting Gbp2 diminishes the antitumor efficacy of the nanovaccine in vivo. This study offers an innovative approach to immunotherapy and elucidates a novel mechanism (Gbp2‐Pin1‐NFκB pathway) for remodeling TAMs.
Hybrid EMT Phenotype and Cell Membrane Tension Promote Colorectal Cancer Resistance to Ferroptosis
Authors: Wei Xiaowei , Ge Yutong , Zheng Yaolin , Zhao Sunyan , Zhou Yuhan , Chang Yuhan , Wang Nuofan , Wang Xiumei , Zhang Juan , Zhang Xuanchang , Hu Liqiao , Tan Youhua , Jia Qiong
Published: February 2025

Intratumoral heterogeneity, including epithelial–mesenchymal transition (EMT), is one major cause of therapeutic resistance. The induction of ferroptosis, an iron‐dependent death, has the potential in overcoming this resistance to traditional treatment modalities. However, the roles of distinct EMT phenotypes in ferroptosis remain an enigma. This study reports that 3D soft fibrin microenvironment confers colorectal cancer (CRC) cells hybrid EMT phenotype and high level of resistance to ferroptosis. The activation of histone acetylation and WNT/β‐catenin signaling drives this EMT phenotypic transition, which promotes the defense of 3D CRCs against ferroptosis via glutathione peroxidases/ferritin signaling axis. Unexpectedly, E‐cadherin knockout in 3D but not 2D CRCs mediates an integrin β3 marked‐late hybrid EMT state and further enhances the resistance to ferroptosis via integrin‐mediated tension and mitochondrial reprogramming. The inhibition of integrin αvβ3‐mediated tension and WNT/β‐catenin‐mediated hybrid EMT sensitizes 3D CRCs with and without E‐cadherin deficiency to ferroptosis in vivo, respectively. Further, the EMT phenotype of patient‐derived tumoroids is associated with CRC therapeutic resistance. In summary, this study uncovers previously unappreciated roles of hybrid EMT and cell membrane tension in ferroptosis, which not only predict the treatment efficacy but also potentiate the development of new ferroptosis‐based targeted therapeutic strategies.
A Methionine Allocation Nanoregulator for the Suppression of Cancer Stem Cells and Support to the Immune Cells by Epigenetic Regulation
Authors: Su Boyu , Chen Qinjun , Li Xuwen , Fang Mingzhu , Wang Yu , Song Haolin , You Haoyu , Zhou Zheng , Wu Yuxing , Zhao Zhenhao , Chen Yun , Fan Hongrui , Li Chufeng , Jiang Chen , Sun Tao
Published: February 2025

Epigenetic dysregulation is prevalent in human cancers, affecting gene expression and metabolic patterns to meet the demands of malignant evolution and abnormal epigenetic processes, and resulting in a protumor immune microenvironment. Tumors require a steady supply of methionine for maintaining epigenetic flexibility, which is the only exogenous precursor of methyl donor S‐adenosylmethionine for methylation, crucial for their resistance to therapies and survival in a nutrient‐deficient microenvironment. Thus, tumor cells upregulate the Lat4 transporter to compete and deprive methionine in the microenvironment, sustaining their malignant phenotypes and also impairing immune cell functions. Addressing this methionine addiction is the key to overcoming drug resistance and improving immune response. Despite the challenge of lacking specific Lat4 inhibitors, an oxaliplatin prodrug crosslinked fluorinated polycation/anti‐Lat4 small interfering RNA complex nanoregulator (AS‐F‐NP) has been designed and developed here. This nanoregulator restricted the greedy methionine uptake of tumor cells by knocking down Lat4, which in turn inhibited the malignant evolution of the tumor while restoring the viability and function of tumor‐infiltrating immune cells.
Fundamentals and Applications of Dual‐Frequency Magnetic Particle Spectroscopy: Review for Biomedicine and Materials Characterization
Authors: Krause Hans‐Joachim , Engelmann Ulrich M.
Published: February 2025

Superparamagnetic nanoparticles (MNP) offer exciting applications for engineering and biomedicine in imaging, diagnostics, and therapy upon magnetic excitation. Specifically, if excited at two distinct frequencies f1 and f2, MNP responds with magnetic intermodulation frequencies m·f1 ± n·f2 caused by their nonlinear magnetization. These mixing frequencies are highly specific for MNP properties, uniquely characterizing their presence. In this review, the fundamentals of frequency mixing magnetic detection (FMMD) as a special case of magnetic particle spectroscopy (MPS) are reviewed, elaborating its functional principle that enables a large dynamic range of detection of MNP. Mathematical descriptions derived from Langevin modeling and micromagnetic Monte‐Carlo simulations show matching predictions. The latest applications of FMMD in nanomaterials characterization as well as diagnostic and therapeutic biomedicine are highlighted: analysis of the phase of the FMMD signal characterizes the magnetic relaxation of MNP, allowing to determine hydrodynamic size and binding state. Variation of excitation amplitudes or magnetic offset fields enables determining the size distribution of the particles’ magnetic cores. This permits multiplex detection of polydisperse MNP in magnetic immunoassays, realized successfully for various biomolecular targets such as viruses, bacteria, proteins, and toxins. A portable magnetic reader enables portable immunodetection at point‐of‐care. Future applications toward theranostics are summarized and elaborated.
Achieving High‐Performance Organic Long Persistent Luminescence Materials via Manipulation of Radical Cation Stability
Authors: Gao Hongxin , Wang Guangming , Wang Tengyue , Ye Zi , Yan Qianqian , Chong Qianhui , Chan Chin‐Yiu , Wang Biaobing , Zhang Kaka
Published: February 2025

Organic long persistent luminescence (OLPL) materials, with their hour‐long afterglow, hold great promise across numerous applications, yet their performance lags behind that of inorganic counterparts. A deeper understanding of the underlying photophysical mechanisms, particularly the effective control of radical intermediates, is essential for developing high‐performance OLPL materials; while systematic studies on the intrinsic stability of radical intermediates and their impact on OLPL performance remain scarce. Here biphenyl groups is introduced into a luminophore‐matrix‐donor three‐component OLPL system. By varying substituents at the ortho‐position of the biphenyl groups, the stability of radical cations is systematically modulated, and their influence on OLPL properties is investigated. Combined experimental results and theoretical calculations reveal that increased flexibility of the biphenyl bond and adjustable conformations lead to higher stability of radical cations, thereby significantly enhancing OLPL performance. Based on this understanding, a luminophore with two biphenyl groups is designed to successfully achieve remarkable afterglow brightness close to inorganic Sr2Al14O25/Eu2+, Dy3+ materials. Furthermore, these OLPL materials exhibit time‐encoded afterglow properties and promising applications in advanced anti‐counterfeiting, as well as background‐independent bioimaging functions. This work not only provides a novel strategy for constructing high‐performance OLPL materials but also lays a foundation for their widespread application in various fields.
Enhanced Photoredox Activity in Nitrogen‐Doped Carbon Nitride for Heterogeneous Nitrogen and Oxygen Radical Reactions
Authors: Qin Lan , Liu Huan , Wei Yi , Chen Lian‐Qing , Hu Xiao‐Qiang
Published: February 2025

A nitrogen‐doped carbon nitride (NCN) has been synthesized and utilized for the sustainable generation of reactive nitrogen and oxygen radicals under mild photocatalytic conditions. This material exhibits a significant improvement in the separation and transfer of photoexcited charge carriers, which facilitates the direct activation of N─H and O─H bonds to achieve a variety of radical carboamination, oxyamination and deoxygenation reactions. The NCN catalyst has further demonstrated its robust photoredox activity through several successful applications, including the aerobic oxidation of boronic acids and the controllable oxidation of alcohols to aldehydes and carboxylic acids. Moreover, the NCN catalyst maintains its reactivity and efficiency even after multiple cycles of use, showcasing its durability and potential for practical applications in sustainable chemistry.
2D ferroelectric AgInP2Se6 for Ultra‐Steep Slope Transistor with SS Below 10 mV Decade−1
Authors: Yang Yujue , Liu Zihao , Liu Xueting , Dong Huafeng , Zhang Xin , Yang Juehan , Wu Fugen , Li Jingbo , Huo Nengjie
Published: February 2025

Along with continuous size shrinking, conventional silicon based transistors face the the challenges of both manufacture complexity and physical limitations. The negative capacitance transistors (NC‐FETs) using 2D ferroelectric materials as dielectric insulators are emerging as reliable solutions owing to their advantages of breaking the Boltzmann limitation and Complementary Metal‐Oxide Semiconductor (CMOS) compatibility. Here, the room temperature ferroelectricity of 2D AgInP2Se6 is discovered which is further integrated with MoS2 channel into ultra‐steep NC‐FETs for low‐power electronic applications. Due to the negative capacitance effect of AgInP2Se6 during the polarization reversal process, the transistor breaks the Boltzmann limitation with a subthreshold swing (SS) of less than 10 mV decade−1. By optimizing the thickness of AgInP2Se6, superior transistor performance with a minimum SS of 7.75 mV dec−1 and a high on/off ratio of up to 5.88 × 104 can be achieved. This work develops a new 2D ferroelectric AgInP2Se6 with room temperature ferroelectricity, providing promising material platforms for small‐size, ultra‐steep, and low‐power electronics.
A study of online monitoring for two‐phase flow patterns in a microchannel based on deep learning
Authors: Wang Zhenlun , Wang Yuhan , Chen Pengli , Xin Zhiling , Shang Minjing , Su Yuanhai
Published: February 2025

A low‐cost, low‐noise, high‐frequency microchannel photoelectric detection device based on a photodiode was developed. Based on this device, photoelectric waveforms of gas–liquid and liquid–liquid two‐phase flows in a microchannel were collected, and then online flow pattern detection was realized by using artificial intelligence algorithms. Light intensity distribution characteristics of slug flow were simulated using COMSOL software, and detailed analyses were conducted to examine the relationship between waveform variations and slug flow morphology. After denoising the collected data with wavelet analysis filtering, artificial intelligence algorithms were employed to identify flow patterns for gas–liquid and liquid–liquid two‐phase flows. It was found that the recognition accuracy of the Convolutional Neural Networks algorithm in a variety of fluid systems reaches 100%. Based on this work, a general automatic gas–liquid/liquid–liquid flow pattern recognition platform was developed, which can automatically and quickly identify flow patterns and generate flow pattern graphs from the collected data.
Role of tau versus TDP‐43 pathology on medial temporal lobe atrophy in aging and Alzheimer's disease
Authors: Wisse Laura E. M. , Wuestefeld Anika , Murray Melissa E. , Jagust William , La Joie Renaud
Published: February 2025

Hippocampal atrophy on magnetic resonance imaging is an important biomarker in Alzheimer's disease (AD). While hippocampal atrophy was thought to result from tau tangles in AD, different neuropathologies can lead to hippocampal atrophy, especially TAR DNA‐binding protein 43 (TDP‐43) pathology. In this narrative review, we evaluate existing studies on the relative contribution of tau and TDP‐43 pathology to medial temporal lobe (MTL) atrophy. We report a clear association of both tau and TDP‐43 neuropathology with MTL atrophy, even after correcting for other neuropathologies. Next, we discuss a potential synergism between tau and TDP‐43 and the relative timing of the effects of both neuropathologies. Finally, avenues for future research will be discussed. A better understanding of the interplay between tau and TDP‐43 neuropathologies and their effect on atrophy will help with the development of more specific biomarkers for limbic‐predominant age‐related TDP‐43 encephalopathy and pinpointing of the optimal timing for testing anti‐tau and anti‐TDP‐43 treatments in trials.

Highlights

Both tau and TAR DNA‐binding protein 43 (TDP‐43) pathology contribute to medial temporal lobe atrophy.

There is a positive association between tau and TDP‐43 and potentially a synergism.

It is unclear if tau and TDP‐43 have an additive or synergistic effect on atrophy.

The relative timing of the tau and TDP‐43 effects on atrophy remains unclear.

Clarifying the interplay between tau and TDP‐43 will help improve magnetic resonance imaging biomarkers.
Machine learning prediction of tau‐PET in Alzheimer's disease using plasma, MRI, and clinical data
Authors: Karlsson Linda , Vogel Jacob , Arvidsson Ida , Åström Kalle , Strandberg Olof , Seidlitz Jakob , Bethlehem Richard A. I. , Stomrud Erik , Ossenkoppele Rik , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Palmqvist Sebastian , Smith Ruben , Janelidze Shorena , La Joie Renaud , Rabinovici Gil D. , Binette Alexa Pichet , Mattsson‐Carlgren Niklas , Hansson Oskar
Published: February 2025

INTRODUCTION

Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, but its routine clinical use is limited by cost and accessibility barriers.

METHODS

We thoroughly investigated the ability of various machine learning models to predict clinically useful tau‐PET composites (load and laterality index) from low‐cost and non‐invasive features, for example, clinical variables, plasma biomarkers, and structural magnetic resonance imaging (MRI).

RESULTS

Models including plasma biomarkers yielded the most accurate predictions of tau‐PET burden (best model: R‐squared = 0.66–0.69), with especially high contribution from plasma phosphorylated tau‐217 (p‐tau217). MRI variables were the best predictors of asymmetric tau load between the two hemispheres (best model: R‐squared = 0.28–0.42). The models showed high generalizability to external test cohorts with data collected at multiple sites. Through a proof‐of‐concept two‐step classification workflow, we also demonstrated possible model translations to a clinical setting.

DISCUSSION

This study highlights the promising and limiting aspects of using machine learning to predict tau‐PET from scalable cost‐effective variables, with findings relevant for clinical settings and future research.

Highlights

Accessible variables showed potential in estimating tau tangle load and distribution.

Plasma phosphorylated tau‐217 (p‐tau217) and magnetic resonance imaging (MRI) were the best predictors of different tau‐PET (positron emission tomography) composites.

Machine learning models demonstrated high generalizability across AD cohorts.
Setup and Characterization of a Fiber Brillouin Amplifier Module for Optical Frequency Transfer Over Interferometric Fiber Links
Authors: Kuhl Alexander , Koke Sebastian , Koczwara Andreas , Waterholter Thomas , Grosche Gesine
Published: February 2025

The details of fiber Brillouin amplifier modules developed for optical frequency dissemination and installed on the fiber link between Braunschweig and Strasbourg for performing optical clock comparisons are described and documented. The performance of these fiber Brillouin amplification modules is characterized in terms of gain, one‐way phase shift, and signal‐to‐noise ratio across a wide parameter space of signal and pump powers. Finally, upper estimates are derived for the frequency transfer uncertainty contributions resulting from the non‐reciprocity induced by the fiber Brillouin amplifier modules based on the characterized one‐way phase shift.
Photoexcited Transition‐Metal Catalyzed Carbon‐Halogen Bond Formation
Authors: Arora Ramon , Samokhin Philip , Lautens Mark
Published: February 2025

Transition‐metal catalysis has proven useful in facilitating carbon‐halogen (C–X) bond formation. Despite the vast number of methodologies reported to furnish these bonds, limitations have remained, warranting continued development. The recent surge of metallaphotoredox‐based transformations has provided a novel gateway to bypass these limitations. Through the use of photoexcited species, the formation of C‐X bonds arise through new mechanistic pathways, finding alternatives to high reaction temperatures and stoichiometric additives. The discovery of this novel strategy has provided access to molecular space that has not been previously attainable. Herein, we report the recent advances on transition‐metal photocatalyzed C–X bond formation, in hopes to ease the synthetic endeavors for chemists in industrial and academic laboratories.
A Dual Biomarker Approach to Stress: Hair and Salivary Cortisol Measurement in Students via LC‐MS/MS
Authors: Hakeem Muhammad K. , Sallabi Sundas , Ahmed Raghda , Hamdan Hana , Mameri Amel , Alkaabi Mariam , Alsereidi Asmaa , Elangovan Sampath K. , Shah Iltaf
Published: February 2025

Stress is a significant issue among students, affecting both their mental and physical health. In this study, we investigated cortisol levels, a key biomarker for stress, in students at the United Arab Emirates University (UAEU) during their exam period. Using a sensitive liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) methodology we measured cortisol concentrations in hair and saliva samples and explored the potential correlation between exam‐induced stress and cortisol levels. The results revealed an increase in cortisol levels during the exam period, with male students showing an average hair cortisol concentration of 150.625 pg/mg and female students displaying an average of 77.756 pg/mg. Salivary cortisol levels ranged from 0.002 to 9.189 ng/mL, with an overall average of 4.505 ng/mL. Statistical analysis revealed significant differences in cortisol levels between male and female students, underscoring the impact of exam‐related stress on both acute and chronic stress markers. This study underscores the importance of addressing academic stress and suggests targeted strategies to mitigate its impact on student health ultimately fostering an environment encouraging both academic success and psychological well‐being within the student community. Future research directions include exploring additional clinical parameters and expanding the study population to further understand the long‐term effects of academic stress.
Prerequisite Relations Annotation Tool: Annotation and analysis of educational relations in texts
Authors: Alzetta Chiara , Torre Ilaria
Published: February 2025

Relations between terms in texts have long been studied in linguistics and specialized knowledge domains, especially when occurring in educational materials like textbooks, where they play a crucial role in guiding instructional design and learning. Prerequisite relations (PR), which determine the sequence of presentation of domain terms, are particularly crucial for effective learning. Therefore, the authors consider them carefully when writing instructional texts. The reverse process of identifying PR within texts aims to extract the inherent knowledge structure they are based on and is a key task in the field of corpora annotation for educational knowledge modeling. Although there are tools for manual annotation, there is a need for specialized tools tailored to the unique properties of PR, enabling easy creation, analysis, and sharing of annotated datasets. In this paper, we introduce Prerequisite Relations Annotation Tool (PRAT), a novel tool designed for annotating PR based on a validated protocol. PRAT simplifies the process of capturing, analyzing, and visualizing prerequisite structures in educational texts. We outline PRAT's architecture and functionalities, emphasizing its unique features compared to existing corpora annotation tools. Through a user study involving users with diverse backgrounds, we show PRAT's effectiveness in real‐world scenarios.
Concise Total Synthesis of Phenylethanoid Glycoside Acteoside
Authors: Judeh Zaher M. A. , Thinh Khong Duc , Marlow Hannah
Published: February 2025

Acteoside is a prominent phenylethanoid glycoside (PhG) with diverse pharmacological activities. However, its chemical synthesis has been challenging due to the reliance on extensive protection/deprotection strategies, leading to lengthy routes and low overall yields. Herein, we present a streamlined and efficient synthetic approach that minimizes synthetic complexity while improving overall efficiency. The strategy, which gave acteoside in 18.6% overall yield over just 6 steps, employs key regio‐ and chemoselective transformations, including β‐glycosylation, selective caffeoylation, regioselective silylation, α‐rhamnosylation, and a one‐pot global deprotection. By exploiting the inherent differences in hydroxyl reactivity, this method significantly reduces the need for protecting groups, ensuring a more direct synthetic pathway. Importantly, the approach prevents E:Z isomerization of the caffeoyl moiety, preserving the structural integrity of the final product. This methodology can be extended to a broader class of phenylethanoid glycosides, facilitating access to these bioactive natural products for further applications.
Unboxing the intersections between self‐esteem and academic mindfulness with test emotions, psychological wellness and academic achievement in artificial intelligence‐supported learning environments: Evidence from English as a foreign language learners
Authors: Hou Lin
Published: February 2025

The integration of artificial intelligence (AI) into language education is rapidly transforming English as a foreign language (EFL) learning environments, presenting both opportunities and challenges. While AI‐supported tools offer potential benefits, they can also trigger complex test‐related emotions that may impact learners’ psychological and academic well‐being. Therefore, understanding the interplay between internal resources like self‐esteem and academic mindfulness, alongside these emotions, becomes crucial. This study investigated the correlations between self‐esteem and academic mindfulness with test emotions, psychological well‐being and academic achievement among EFL learners in AI‐supported contexts in China. To meet this purpose, a quantitative approach was employed, using data collected from a sample of 305 EFL university students (155 males and 150 females) in China selected through stratified random sampling. The analysis was conducted via confirmatory factor analysis and structural equation modelling using SMART PLS software. The results indicated that self‐esteem and academic mindfulness were strong predictors of test emotions, psychological wellness and academic achievement. Higher levels of academic self‐esteem and academic mindfulness were linked to higher test emotions, psychological well‐being and academic achievement. These findings stress the necessity of incorporating socio‐emotional skills into AI‐enhanced EFL learning, considering students’ psychological well‐being when deploying AI tools and designing interventions to address emotional challenges within AI‐supported environments.
Right Ventricular Systolic Dysfunction Predicts Recovery of Left Ventricular Systolic Function and Reduced Quality of Life in Patients With Arrhythmia‐Induced Cardiomyopathy
Authors: Körtl Thomas , Mühleck Franziska , Baum Paul , Resch Markus , Meindl Christine , Üçer Ekrem , Maier Lars S. , Wachter Rolf , Sossalla Samuel , Schach Christian
Published: February 2025

Introduction

Arrhythmia‐induced cardiomyopathy (AIC) is an underrecognized condition resulting in left ventricular systolic dysfunction (LVSD) that is primarily caused by atrial fibrillation (AFib). The relationship between AIC, right ventricular (RV) function, and quality of life (QoL) has not been well studied.

Methods

We performed a post‐hoc analysis of our AIC trial in which we prospectively screened for patients with tachyarrhythmia and newly diagnosed, otherwise unexplained LVSD. Following rhythm restoration, patients were followed up at 2, 4, and 6 months. Only patients with persistent sinus rhythm were analyzed. RV function was assessed via echocardiography (tricuspid annular plane systolic excursion [TASPE] and fractional area change [FAC]) and QoL by the Minnesota Living with Heart Failure Questionnaire.

Results

Of a total of 50 patients recovering from LVSD, 41 were diagnosed with AIC and 9 with non‐AIC. Initially, RV function was reduced in the AIC group and recovered after rhythm restoration, whereas no relevant changes were noted in the non‐AIC group. QoL was reduced in both groups and also improved after rhythm restoration. Regression analysis identified low TAPSE as a predictive parameter for AIC diagnosis and worse QoL in AIC patients.

Conclusion

We demonstrated that RV function and QoL are impaired in patients with AIC. Six months after rhythm restoration, TAPSE may serve as an early indicator of AIC while also correlating with QoL. This underscores the importance of detailed echocardiographic evaluation with a focus on RV function in patients with concomitant tachyarrhythmia and LVSD.
The Neutrophil‐to‐Lymphocyte Ratio Is an Independent Inflammatory Biomarker for Adverse Events in Patients With Atrial Fibrillation: Insights From the Murcia AF Project II (MAFP‐II) Cohort Study
Authors: Soler‐Espejo Eva , Marín Francisco , López‐Gálvez Raquel , Ramos‐Bratos María Pilar , Sánchez‐Villalobos María , Esteve‐Pastor María Asunción , Lip Gregory Y. H. , Rivera‐Caravaca José Miguel , Roldán Vanessa
Published: February 2025

Background

Systemic inflammation plays a central role in atrial fibrillation (AF). The neutrophil‐to‐lymphocyte ratio (NLR) is a simple hematological index that has been shown to be associated with prognosis in different pathologies.

Hypothesis

The NLR is associated with an increased risk of adverse events in patients with AF.

Methods

We included a prospective cohort of AF patients who started vitamin K antagonists (VKAs) therapy between July 2016 and June 2018. NLR was assessed at baseline and classified into three categories: low (< 3), moderate (3–5), and high (> 5). During a 2‐year follow‐up period, all cardiovascular deaths, all‐cause deaths, and net clinical outcomes (NCO; either ischemic stroke/transient ischemic attack, major bleeding or all‐cause death), were recorded.

Results

A total of 1050 patients were included (51.4% women; median age 77 years). NLR was available in 936 patients: 507 (54.2%) had low NLR (< 3), 239 (25.5%) had moderate NLR (3–5), and 190 (20.3%) had high NLR (> 5). The primary endpoint was significantly increased in the high NLR category (p = 0.002 for cardiovascular death; p < 0.001 for all‐cause mortality, and p < 0.001 for NCO), with higher IRRs (all p < 0.001). Multivariate Cox regression analyses showed that high NLR was independently associated with an increased risk of cardiovascular death (aHR: 2.02; 95% CI: 1.04–3.92), all‐cause mortality (aHR: 2.51; 95% CI: 1.58–3.97), and NCO (aHR: 1.99; 95% CI: 1.37–2.87), compared to low NLR.

Conclusions

In this prospective AF cohort receiving VKAs, elevated NLR was significantly associated with an increased risk of adverse clinical outcomes. NLR has independent prognostic value beyond other classical risk factors.
Recent Advances in the Development of Efficient Tin Halide Perovskite Solar Cells: Interface Engineering, Crystallization Kinetics, and Stability Optimization
Authors: Zhang Shiwei , Abdel-Shakour Muhammad , Pan Yongle , Wang Junfang , Wang Xu , Meng Xiangyue
Published: February 2025

Tin halide perovskite solar cells (Sn‐PSCs) are gaining increasing attention from the research community as a promising renewable and green energy source. Recently, numerous strategies have been explored for the development of efficient Sn‐PSCs. This review article highlights the potential of Sn‐PSCs as eco‐friendly alternatives and discusses recent advances in this field. The discussion focuses on the exceptional properties of tin perovskite materials, and the challenges in optimization of device performance. The article provides an overview of controlling crystallization kinetics of tin halide perovskites and interface engineering to enhance device performance of Sn‐PSCs. Furthermore, the stability challenges of Sn‐PSCs have been discussed, and perspective on future developments has been included.
Barium Oxide Thin Films Designed as Electro‐Optical Gigahertz/Terahertz Filters
Authors: Alharbi Seham R. , Qasrawi A. F. , Gaabour Laila H.
Published: February 2025

Herein barium oxide thin films are studied as a promising electro‐optical system. The deposited films exhibited a polycrystalline tetragonal structure and are composed of a mixture of BaO and BaO2. The p‐type films are highly transparent (80%) with an energy band gap of 3.55 eV containing exponential band tails of widths of 1.22 eV. Analyses using the Drude‐Lorentz model demonstrated the films suitability for nonlinear optical applications, with optical conductivity parameters revealing a scattering time constant in the range of 0.4–1.8 fs, a free hole concentration of 1018−1019 cm−3 and drift mobility values of 0.70–3.16 cm2 Vs−1. Terahertz cutoff frequency spectra calculations indicated the films capability as efficient terahertz band filters with a cutoff frequency range of 3.2–193.0 THz. Additionally, the nonlinear third‐order optical susceptibility increased with decreasing incident photon energy. Applying an AC signal with a driving frequency of 0.01–1.40 GHz across the terminals of Yb/BaO/Ag devices revealed a high cutoff frequency (≈9 GHz) in the microwave frequency domain. These properties highlight the potential of BaO films as nonlinear optical filters and microwave waveguides, positioning them as candidates for gigahertz/terahertz technology applications.
Stable isotopes of saproxylic beetles reveal low differences among trophic guilds and suggest a high dependence on fungi
Authors: Kozel Petr , Lejeune Benjamin , Lepoint Gilles , Drag Lukas , Cizek Lukas , Sebek Pavel
Published: February 2025

Deadwood stores about 8% of global carbon stock, and its decomposition is a key factor in forest ecosystems. Deadwood‐associated (saproxylic) organisms constitute a food web that sustains a substantial part of biodiversity globally. After fungi, saproxylic beetles are the most prominent agents of structural deadwood decomposition in forests. They are often classified according to their presumed link to the deadwood decomposition gradient, generally as feeding on fresh wood, decayed wood, fungi, or predators. These classifications are, however, based on ecomorphological characters (e.g., trophic morphology, habitat use) while information on their diet is globally limited. Carbon (δ13C) and nitrogen (δ15N) stable isotope ratios represent potential useful tracers to improve knowledge on the trophic ecology of this model group and the whole decomposition food web. We performed stable isotope analysis on 121 beetle species (530 samples) from a mixed‐deciduous forest in Central Europe in order to (1) characterize drivers of saproxylic beetles' isotopic variability with respect to potential food sources along the wood decomposition gradient and in relation to the potentially key intrinsic factors such as phylogeny and body size and (2) to assess how isotope information matches with two trophic guild classifications based on ecomorphological characters which are commonly used in ecological studies. The analysis revealed a clear pattern of δ13C increase and simultaneous C:N ratio decrease across potential food sources along the gradient from fresh to decayed deadwood and fungi. Beetle phylogeny and body size explained a significant part of their isotope variability, with values of δ13C being lower in smaller species. After filtering out these effects, the δ13C values reflected the position of beetle species on the decomposition gradient only loosely. Fungi‐feeding guilds had higher δ13C values than the guilds dependent on fresher deadwood, but otherwise the guilds were indistinguishable. Deadwood consumers did not differ from predators. The isotopic niches of different feeding guilds largely overlapped, and the large observed variation suggests that not only fungi feeders but species from most guilds may depend considerably on fungi and that mixed trophic strategies may be more common in the decomposition food web than currently acknowledged.