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Ethnopharmacological Relevance: Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR), a traditional Chinese medicinal plant, plays an active role in neuroprotection. Clinical medication and modern pharmacological studies have proved the efficacy of UR against Parkinson's disease (PD), with alkaloids being recognized as the main bioactive components. But the therapeutic effect and mechanism of U. rhynchophylla alkaloid extract (URA) against PD need further exploration., Aim of Study: The study aimed to investigate the therapeutic effect and potential mechanism of URA on PD., Materials and Methods: LC-MS methodology was used to evaluate the chemical constituents of URA. The anti-PD activity of URA in vivo was measured on the mouse and rat models of PD. Neuroprotective effect of URA on PC12 cells was measured by MTT assay. Dopamine (DA) and its metabolites were detected by LC-MS for probing the protection ability on dopaminergic neurons. The differentially expressed proteins between model group and URA administrated group were analyzed by proteomics, suggesting oxidative phosphorylation as possible pathway of URA. Considering the critical role of mitochondria in oxidative phosphorylation, JC-1 staining, MitoSOX staining, transmission electron microscopy (TEM) observation and adenosine triphosphate (ATP) levels detection were used to analyze the effects of URA on mitochondrial morphology and function. Biolayer interferometry (BLI) was used to search for the possible UCHL1-bonding compounds in URA., Results: URA significantly mitigated the behavioural defects by improving coordination, shortening the time to climb down the whole pole (T-LA) and increasing the forelimbs' muscle strength of MPTP-induced PD mice and 6-OHDA-induced PD rats. In addition, URA improved tyrosine hydroxylase expression in dopaminergic neurons by immunohistochemistry (IHC) staining, and thus increased the neurotransmitter levels of DA and relevant metabolites. Furthermore, URA promoted mitophagy as reflected by a significant decrease in reactive oxygen species (ROS) generation, an increase in ATP levels and clearance of damaged mitochondria. Subsequently, Ubiquitin C-terminal hydrolase 1 (UCHL1), which is associated with the mitochondrial dysfunction in PD, is suggested to be a promising target based on the proteomics result, and proved by the blocked protective effects of URA by UCHL1 inhibitor. Furthermore, hirsuteine (HTE) was identified as a potential active compound of URA binding to UCHL1 by BLI, and the binding capacity and site were verified by surface plasmon resonance (SPR) and molecular docking., Conclusion: This work demonstrates that URA exerts effective neuroprotective activity against PD via activation of mitophagy with the involvement of UCHL1, and HTE may be a potential active compound of URA., Competing Interests: Declaration of competing interest The author is not an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for Journal of Ethnopharmacology and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We state that there is no commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Phenolic pollutants with high toxicity and low biodegradability can disrupt environmental balance and severely affect human health, whereas existing methods are difficult to implement the rapid and high-throughput detection of multiple phenolic pollutants., Results: Herein, we developed a four-dimensional colorimetric sensor array based on imidazole-modulated Cu@MOFs for distinguishing and determining phenolic pollutants. Wherein, four Cu@MOFs (ATP@Cu, ADP@Cu, AMP@Cu, and GMP@Cu) nanozyme with laccase-like activity were firstly prepared, and a novel strategy of imidazole-containing molecules-regulated was proposed to improve the laccase-like activity of Cu@MOFs nanozymes. Interestingly, imidazole (IM) exhibited the strongest enhancing effects on the laccase-like activity of the four Cu@MOFs by accelerating electron transfer on the surface of laccase nanozymes and producing more reactive oxygen species. Subsequently, by using Cu@MOFs@IM as the recognition elements of the sensor array, a colorimetric sensor array based on imidazole-modulated Cu@MOFs was developed, and differentiation and classification of phenolic pollutants were carried out using LDA and HCA methods. More importantly, the proposed sensor array could accomplish the identification of 6 phenolic pollutants and their mixtures., Significance: Additionally, the designed sensor array was applied to identify these phenolic pollutants in real water samples, further highlighting the potentials for assessing water pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Type III resistant starch (RS3) is an important functional food ingredient. In this study, RS3 was prepared by retrogradation of pea starch after acid hydrolysis and pullulanase debranching. Heat-moisture treatments, including annealing (90 °C, 40-70 % moisture content) and pressure heating (121 °C, 10-40 % moisture content), were employed to further enhance the RS content of pea RS3. The relationship between the structural changes and digestibility of pea RS3 was investigated. The results showed significant increases in relative crystallinity, particle size, gelatinization temperature, and RS content, while swelling power, pasting viscosity, and rapidly digestible starch content were markedly decreased after heat-moisture treatment. A strong positive correlation (r = 0.94*) was observed between relative crystallinity and RS content. The highest RS content of 85.6 % was achieved after pressure heating at 20 % moisture content, which was notably higher than the 45.6 % RS content before heat-moisture treatment. This study highlights the beneficial effects of annealing and pressure heating in enhancing RS content in pea RS3, providing valuable insights for developing RS3 with high RS content after cooking., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The lack of in vivo accurate human liver models hinders the investigation of liver-related diseases, injuries, and drug-related toxicity, posing challenges for both basic research and clinical applications. Traditional cellular and animal models, while widely used, have significant limitations in replicating the liver's complex responses to various stressors. Liver organoids derived from human pluripotent stem cells, adult stem cells primary cells, or tissues can mimic diverse liver cell types, major physiological functions, and architectural features. Recent advancements in the field have shown that some liver organoids have sufficient accuracy to replicate specific aspects of the human liver's complexity. This review highlights recent progress in liver organoid research, with a particular emphasis on their potential for toxicity assessment and disease modeling. The intrinsic advantages of liver organoids include higher sensitivity and suitability for long-term studies, which enhance the predictive value in drug and nanomaterial toxicity testing. The integration of liver organoids with microfluidic devices enables the simulation of the liver microenvironment and facilitates high-throughput drug screening. The liver organoids also serve as ideal platforms for studying liver diseases such as hepatitis, liver fibrosis, viral liver diseases, and monogenic diseases. Additionally, this review discusses the advantages and limitations of liver organoids along with potential avenues for future research., Competing Interests: Declarations. Consent for publication: All the authors give their consent for publication in Stem Cell Research & Therapy. Ethical approval: Not applicable. AI usage: The authors declare that they have used artificial intelligence to polish the grammar of the manuscript. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2025. The Author(s).)

Background: The incidence of Major Depressive Disorder (MDD) is high among adolescent females, and MDD is often accompanied by suicide attempts (SAs), which have a serious negative impact on health. However, changes in lipids, thyroid hormone, and brain metabolism among female adolescents with MDD and the relationships between these three markers and MDD with SA have yet to be elucidated., Methods: This study enrolled 71 MDD patients with SA (MDD+SA), 66 MDD patients without SA (MDD-SA), and 47 healthy controls (HCs). We analysed the lipid and thyroid hormone levels and magnetic resonance spectroscopy results of the subjects., Results: Low levels of social support, high levels of life stress, and high levels of suicidal ideation (SI) were risk factors for SA. In MDD patients, 1) thyroid stimulating hormone was positively correlated with triglyceride (TG) and N-acetyl aspartic acid (NAA)/creatinine in the prefrontal cortex (PFC) and negatively correlated with high-density lipoprotein and the choline/creatinine in the thalamus; 2) free thyroxine was negatively correlated with the choline/creatinine in the thalamus; 3) total cholesterol, TG, low-density lipoprotein, and choline/NAA in the PFC were positively correlated with the severity of SI and suicide risk; and 4) NAA/creatinine in the thalamus was negatively correlated with the severity of SI and suicide risk., Conclusion: In female adolescents with MDD, there are significant synergistic changes in lipids, thyroid hormones, and brain metabolism-related factors, and the changes in these indicators may be related to the pathological mechanism of SA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The CRISPR-Cas12a system has shown tremendous potential for developing efficient biosensors. Albeit important, current CRISPR-Cas system-based diagnostic technologies (CRISPR-DX) highly rely on an additional preamplification procedure to obtain high sensitivity, inevitably leading to issues such as complicated assay workflow, cross-contamination, etc. Herein, a spherical protospacer-adjacent motif (PAM)-antenna-enhanced CRISPR-Cas12a system is fabricated for universal amplification-free nucleic acid detection with a detection limit of subfemtomolar. Meanwhile, the clinical detection capability of this sensor was further verified using gold-standard real-time quantitative polymerase chain reaction through Mycobacterium tuberculosis measurement, which demonstrated its good reliability for practical applications. Importantly, its excellent sensitivity is mainly ascribed to high efficiency of target search induced by a localized PAM-enriched microenvironment and improved catalytic activity of Cas12a (up to 4 folds). Our strategy provides some new insights for rapid and sensitive detection of nucleic acids in an amplification-free fashion.

Background: Human responses and acclimation to the environmental stresses of high altitude and low oxygen are multifaceted and regulated by multiple genes. However, the mechanism of how the body adjusts in a low-oxygen environment is not yet clear., Results: Hence, we performed RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) to observe the changes of transcriptome and chromatin accessibility in the peripheral blood of eight individuals at 1 h post adaptation in a simulated plateau environment with 3500 m and 4500 m altitude, respectively. Differential expression analysis and the Boruta algorithm identified differentially expressed genes (DEGs) and differentially accessible regions (DARs) associated with hypoxia adaptation. Specifically, RNA-seq identified 93 and 7 DEGs after 1 h post adaptation with 3500 m altitude and 45 and 8 DEGs after 1 h adaptation with 4500 m. Additionally, ATAC-seq screened 12 and 4 DARs in 3500 m altitude adaption and 15 and 5 DARs in 4500 m altitude adaption. Moreover, the combined analysis of RNA-seq and ATAC-seq revealed that 10 hub genes were independently identified from the protein-protein interaction (PPI) network for each altitude. Gene enrichment analysis displayed that most hub genes were related with hypoxia pathways., Conclusions: Our results can provide the reference for the early response of the organism to hypoxic adaptation., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Biological and Medical Ethics Committee of Beijing University of Aeronautics and Astronautics (BM20210149). All participants were included after providing written informed consent. Consent for publication: We have obtained consent to publish from the participants to report their data. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Heterojunctions are sustainable solutions for the photocatalytic CO 2 reduction reaction (CO 2 RR) by regulating charge separation behavior at the interface. However, their efficiency and product selectivity are severely hindered by the inflexible and weak built-in electric field and the electronic structure of the two phases. Herein, ferroelectric-based heterojunctions between polarized bismuth ferrite (BFO(P)) and CdS are constructed to enhance the interfacial interactions and catalytic activity. The intrinsic polarization field depending on the ferroelectric state causes significant electrostatic potential difference and energy-band bending. This helps overcome the unsatisfactory redox potential that differs from the classical catalytic mechanism, and synergy from the heterostructure facilitates effective separation and transfer of photogenerated charges with an extended lifetime (>20 ns) and significantly enhanced photovoltage (1002 times that of BFO). The optimized charge carrier dynamics allow the heterojunction to achieve a much higher CO yield compared to state-of-the-art ferroelectric-based photocatalysts, and 85.46 and 23.47 times higher than those of pristine CdS and BFO, respectively. Moreover, it maintains an impressive 100% product selectivity together with excellent repeatability and cycling. This work not only sheds light on how a strong inherent polarity promotes the performance of heterojunction photocatalysts but also provides new insights for designing efficient photocatalytic CO 2 RR., (© 2025 Wiley‐VCH GmbH.)

The ubiquitin-proteasome system (UPS) is essential for cellular homeostasis, regulating the degradation of proteins involved in key processes such as cell cycle, apoptosis, and DNA repair. Dysregulation of the UPS is implicated in hepatocellular carcinoma (HCC), contributing to tumor progression and therapeutic resistance. The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide. However, the endogenous substrates of CRBN in solid tumors like HCC remain poorly characterized. Here, we identify MORF4L1, a member of the MRG family involved in chromatin remodeling and DNA damage response, as a substrate of CRBN. Using proteomic analysis, co-immunoprecipitation, and structural modeling, we demonstrate that CRBN promotes MORF4L1 degradation under physiological conditions, which is further enhanced by the modulator CC-885. Importantly, MORF4L1 is upregulated in multiple cancers, including HCC, suggesting a broader role in tumorigenesis. Our findings reveal MORF4L1 as a physiological CRBN substrate and highlight the therapeutic potential of targeting CRBN substrates in cancer., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Highly sensitive and portable pesticide residues detection are indispensable for safeguarding food safety and environmental health. Herein, we introduce a one-step vacuum filtration strategy for the scalable production of cobalt-based conjugated coordination polymers (CoCCPs) electrode arrays, utilizing carboxylated single-walled carbon nanotubes (c-SWNTs) as bonding bridges (CoCCPs@c-SWNTs). Due to their abundant active sites and high conductivity, the CoCCPs@c-SWNTs arrays exhibit superior electrochemical performance (e.g., active area, charge transfer capacity, adsorbed charge, etc.) and enhanced electrocatalytic activity for carbendazim (CBZ). Benefiting from the homogeneous and twining interface, the CoCCPs@c-SWNTs arrays also demonstrate good repeatability, reproducibility, and stability (relative standard deviations <5 %). The CoCCPs@c-SWNTs sensor, with a linear range of 0.01-4.0 μM and a detection limit of 1.9 nM, has been successfully employed in tea and strawberry samples. Overall, this novel sensor holds great potential for application in rapid on-site detection of pesticide residues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

China is currently facing a notable decline in fertility rates. This research introduces a novel perspective on the factors influencing fertility among women of reproductive age, representing the first attempt to examine the impact of peer grit on female fertility. Analyzing nationally representative panel data from China and leveraging plausibly exogenous variations in peer exposure across cohorts, we find that peer grit is associated with a reduction in fertility behavior and intentions. The negative effects of peer grit are robust across alternative measures of core metrics and estimation techniques addressing endogeneity concerns. Additionally, our findings suggest that the influence of peer grit on women's fertility behavior and intentions may be mediated by changes in educational attainment and employment stability, operating through a mechanism known as the demonstration effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Citrus fruits are highly susceptible to pathogenic fungal infections after harvesting, which causes serious economic losses. Therefore, it's necessary to develop new antifungal packaging. In this study, gamma-Decanolactone (DL) was successfully encapsulated in a polycaprolactone (PCL)/β-cyclodextrin (β-CD) composite system using electrostatic spinning technology. PCL/β-CD was compounded in different ratios, the ratio was screened through other indicators such as fiber morphologies and mechanical properties. Then, antifungal mats were prepared by adding different concentrations of DL to the PCL/β-CD solution. The results showed that when the mixture ratio of PCL/β-CD was 6:1 and loaded with 6 % DL, the antifungal felt had strong mechanical, significantly inhibiting the growth of three citrus pathogens (P. digitatum, P. italicum and G. candidum), released DL for up to 204 h and effectively reduced the morbidity rate of citrus fruits. Therefore, the antifungal pad prepared in this study has great potential in the field of citrus disease control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, the self-assembly mechanism of Zein/(-)-epigallocatechin-3-gallate/polyethylene glycol (Zein/EGCG/PEG) composite nanoparticles and their interface adsorption behavior at the oil-water interface were investigated by coarse-grained molecular dynamics simulation. Fourier transform infrared spectroscopy and conformation analysis demonstrated that there were electrostatic and hydrogen bond interactions between Zein and EGCG, physical entanglement between PEG and Zein, and hydrogen bond interaction between EGCG and PEG. The nanoparticles accumulated at the oil-water interface, and there was an obvious interface layer between oil phase and water phase, as indicated by confocal laser scanning microscope and scanning electron microscope. The adsorbing of Zein/EGCG/PEG nanoparticles at the oil-water interface was confirmed by coarse-grained molecular dynamics simulation. Further findings confirmed that Zein/EGCG/PEG nanoparticles could serve as stabilizers for oleogels with self-supporting structure, viscoelastic solid behavior and temperature response characteristics. The current research offered a novel approach to enhance protein interface characteristics and create food-grade emulsifiers and oleogelators., Competing Interests: Declaration of competing interest On behalf of all the authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Oleogels have attracted considerable attention due to their excellent viscoelasticity and high content of polyunsaturated fatty acid. This study explored the potential of Zein/(-)-epigallocatechin-3-gallate/Ca 2+ complexes oleogels loaded with lycopene as potential substitute for solid fats in biscuit formulations. Utilizing an emulsion-templated method, oleogels were prepared and characterized for visual appearance, droplet size, microstructure, and rheological properties. The incorporation of lycopene indicated a dose-dependent effect on these characteristics, achieving optimal properties at a concentration of 0.3 mg/mL. At this concentration, oleogels exhibited higher encapsulation efficiency (> 90 %), lower oil loss (< 2 %), and denser network structures. Rheological analysis highlighted the shear-thinning behavior, gel-like structure, and thixotropic recovery of oleogels. Substituting of margarine with lycopene-loaded oleogels in biscuits yielded products with regular appearance, uniform color, and potential health benefits, demonstrating the viability of these oleogels as a healthier alternative to traditional solid fats in baking., Competing Interests: Declaration of competing interest On behalf of all the authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Responsive hydrogels show obvious superiorities when being employed at detection owing to their polymeric networks and optical properties. Albeit important, the slow response of traditional hydrogels against targets limits their further applications, and enhancing the responsiveness of hydrogel is therefore imperative. Herein, a cryogel with hierarchical structures was designed through adjusting the hydrogel structure by the freezing process to improve the responsive properties, and fabricated for rapid analysis of 17β-estradiol (E2). The cryogel encapsulating the DNA hairpins rapidly adsorbed the complementary DNA isolated from the aptamer in the presence of E2 and activated an efficient hybridization chain reaction (HCR). After integration with a smartphone system, a portable colorimetric sensing platform was created for sensitive detection of E2 with a low detection limit of 0.5 nM. Our work provides a promising way for highly responsive hydrogel-based biosensor design, and broadens their applications in rapid and portable target detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: This study aimed to investigate the characteristics, diagnosis, and management of tuberculous longitudinally extensive transverse myelitis (TB-LETM), a rare manifestation of tuberculosis., Findings: We analyzed two rare cases of TB-LETM and discussed their clinical manifestations and imaging findings in the context of the relevant literature. Patient 1, a 23-year-old female, presented with quadriplegia and dysuria, and spinal magnetic resonance imaging (MRI) revealed lesions extending from C1 to T3. Patient 2, an 18-year-old female, reported acute-onset numbness and weakness in both lower limbs, with MRI showing lesions from T1 to T4, along with multiple intracranial leptomeningeal enhancements. Both patients had elevated cerebrospinal fluid (CSF) cell counts and protein levels, and positive blood T-cell spot test (T-SPOT.TB), but no microbiological evidence of Mycobacterium tuberculosis was found. Diagnosis was based on clinical presentation, medical history, chest computed tomography (CT) findings, and CSF analysis. Over the past decade, 14 cases of TB-LETM have been reported. Common symptoms include fever, acute paralysis, sensory deficits in the lower limbs, and dysuria. Elevated CSF protein, lymphocytosis, and decreased glucose levels are essential for differentiating TB-LETM from autoimmune disorders., Conclusion: Longitudinally extensive transverse myelitis (LETM), especially when involving the cervical and thoracic cords, should be considered a potential manifestation of tuberculosis infection. Analysis of cerebrospinal fluid, MRI findings, and T-SPOT testing can provide crucial diagnostic insights. A combination of anti-tuberculosis therapy and corticosteroids has proven clinically effective in managing this condition.

Mitochondrial quality control is paramount for cellular development, with mitochondrial electron flow (Mito-EF) playing a central role in maintaining mitochondrial homeostasis. However, unlike visible protein entities, which can be monitored through chemical biotechnology, regulating mitochondrial quality control by invisible entities such as Mito-EF has remained elusive. Here, a Mito-EF tracker (Mito-EFT) with a four-pronged probe design is presented to elucidate the dynamic mechanisms of Mito-EF's involvement in mitochondrial quality control. Heightened aggregation of Mito-EF in fiber-like healthy mitochondria compared to round-like damaged mitochondria is demonstrated, revealed Mito-EF aggregation correlated with mitochondrial morphological remodeling, particularly in regions undergoing mitochondrial fission and fusion, and show the Mito-EF signal associated with mitochondrial cristae maintained by Dynamin-Related Protein 1 (DRP1). This underscores the importance of considering Mito-EF in assessing mitochondrial quality control parameters. A novel drug screening evaluation parameter, Mito-EF is also introduced to screen and discover mitochondrial-targeted therapeutic modulators. This tracker provides new avenues for investigating the role of Mito-EF in maintaining mitochondrial homeostasis and quality control, offering a potent tool for assessing mitochondrial quality and drug screening., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Transcranial ultrasound stimulation (TUS) has shown promising prospects as a non-invasive neuromodulation technique for both animals and humans. However, ultrasonic propagation characteristics within the brain differ significantly from those in free space. There is currently a lack of comprehensive studies on the effects of skull thickness on focal point position, full width at half maximum (FWHM), and acoustic intensity., Objective: This study investigates the transcranial acoustic field characteristics of 500 kHz focused ultrasound, with a focus on the impact of skull thickness., Methods: The study combined finite element simulations to evaluate the effects of skull thickness on 500 kHz focused ultrasound with experimental investigations across multiple species (mouse, rat, pig, and human)., Results: The simulation and experimental results indicate that the skull changes focal length (-4.4-4.7 mm) and axial focal region (-7.93-7.59 mm), and the skull causes significant attenuation of acoustic intensity, which increases with skull thickness. The attenuation rate of human skulls is greater than 80 %. We found that the skull thickness has little effect on focal point position (<0.9 mm) and focal region (<1.44 mm) in lateral and vertical directions., Conclusion: Skull thickness has great influence on focal length, axial focal region and acoustic intensity, but has little effect on focal point position and focal region in lateral and vertical directions. And improving axial spatial resolution is a potential method to reduce changes of axial focal region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Corydalisdecumbens (Thunb.) (CD) is a traditional Chinese medicine and as a single herb or formula has been used to treat RA for decades. Rheumatoid arthritis (RA) is a persistent, systemic autoimmune inflammatory disease. However, the anti-inflammatory target, effective constituents and mechanism was unclear., Aim of the Study: The purpose of this study was to identify anti-RA and anti-inflammatory targets of CD, elucidate effective constituents and molecular pharmacological mechanism., Materials and Methods: Anti-RA and anti-inflammatory effect of CD were evaluated on CIA-rats and in LPS-induced RAW264.7 cells respectively. The anti-inflammatory target of CD was identified using thermal proteome profiling (TPP). The recombinant Fosl2 protein was expressed and purified and the target-based effective constituents was screened with bio-layer interferometry (BLI) analysis. Combining photoaffinity probe, LC-MS/MS analysis, docking and point mutation, the binding site was confirmed between Fosl2 and THP. Furtherly, immunofluorescence (IF), co-immunoprecipitation (co-IP) were used to research the pharmacological mechanism of THP and the THP-influenced downstream pathways were elucidated by transcriptomics analysis., Results: CD had therapeutic effect on CIA-rats and a significant anti-inflammation on macrophages. Fosl2 was identified as a target of CD and we elucidated the target-based effective constituents was protoberberine-type alkaloids. THP can inhibit inflammation and transcription of AP-1 via targeting Fosl2 on LPS-induced RAW264.7 cells. For mechanism, THP promoted Fosl2 nuclear translocating and interacting with c-Jun., Conclusions: These findings firstly elucidated the target and effective constituents of CD treating RA, and found that "undruggable target" Fosl2 can be used as therapeutic targets for RA. Meanwhile, our research suggested that THP has a significant potential for the treatment of RA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

A simple and fast LC-MS/MS method was developed and validated for simultaneous quantification of 20 L-amino acids (AAs) in human plasma. Chromatographic separation was achieved on an Agilent AdvanceBio Hilic column within 15 min via gradient elution with an aqueous solution containing 5 mM ammonium formate, 5 mM ammonium acetate and 0.1 % formic acid and an organic mobile phase containing 0.1 % formic acid, 5 mM ammonium formate and 5 mM ammonium acetate acetonitrile-water (90:10, v/v) at the flow rate of 0.25 mL/min. Individual AAs and internal standard were analyzed by multiple reaction monitoring (MRM) in positive ion mode under optimized conditions. Method validation consisted of linearity, sensitivity, accuracy and precision, recovery, matrix effect, and stability, and the results demonstrated this LC-MS/MS method as a specific, accurate, and reliable assay. The method was thus utilized to compare the dynamics of individual plasma AAs between healthy females and patients with ovarian tumors. Our results revealed that, in cancer group, plasma 3-Methyl-L-Histidine, L-Proline, L-Phenylalanine and L-Lysine concentrations were significantly increased in patients with malignant ovarian tumors while L-Leucine and L-Isoleucine levels were sharply decreased. These findings support the utilities of this LC-MS/MS method and the promise of specific AAs as possible biomarkers for ovarian cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

In shallow water, reverberation complicates the detection of low-intensity, variable-echo moving targets, such as divers. Traditional methods often fail to distinguish these targets from reverberation, and data-driven methods are constrained by the limited data on intruding targets. This paper introduces the online robust principal component analysis and multimodal anomaly detection (ORMAD) method to address these challenges. ORMAD efficiently performs online low-rank and sparse decomposition while utilizing unsupervised multimodal anomaly detection to enhance detection performance. The multimodal anomaly detection process involves two phases: modality extraction and anomaly detection. During modality extraction, echo data are separated into echo structure and spatial trajectory modalities, providing complementary information that improves the network representation of both reverberation and moving targets. The subsequent anomaly detection phase unsupervisedly learns the modalities of fluctuating reverberation, thereby achieving stable reconstruction while maintaining sensitivity to moving targets. This sensitivity allows effective identification of moving targets by detecting reconstruction loss. Experimental results demonstrate that ORMAD effectively improves detection performance in complex reverberation scenarios. In a real-world sonar dataset, ORMAD increased the average precision for detecting diver targets from 60% to 75% compared to the state-of-the-art method., (© 2025 Acoustical Society of America.)

Dietary fiber (DF) and polyphenols (DP) are typical blood sugar-lowering components, and both play distinct yet interconnected roles in exerting their blood sugar-lowering effects. We comprehensively summarized the single and combined effects of DF and DP on blood glucose homeostasis through regulating the relevant factors in the upper gastrointestinal tract (UGT) and lower gastrointestinal tract (LGT). In the UGT, DF slowed down glucose metabolism by enhancing digesta viscosity and hindering enzyme-substrate interaction. DP primarily targeted enzymes and substrates. When combined, DP enhanced the adsorption capacity of DF for glucose. DF weakened DP's inhibitory effect on enzymes. Both DF and DP disrupted glucose intestinal uptake via physical or genomic modulation, but the co-consumption of DF and DP demonstrated a lower inhibitory effect on glucose uptake than DP alone. In the LGT, DF and DP showed synergistic or antagonistic effects on gut microbiota. Remarkably, whole foods exhibited potent prebiotic effects due to their compound-rich matrix, potentially enhancing glucose homeostasis and expanding dietary options for glucose regulation research.

Type 3 resistant starches (RS3) were prepared from debranched starch (DBS) with different average degree of polymerization (DP) generated from high-amylose pea starch (HAPS) and high-amylose maize starch (HAMS). The results showed that RS3 with DP 35 and DP 39 had the highest RS content (74.5 % and 75.0 %, respectively) after cooking, which were remarkably higher than those of RS3 prepared from mixed fractions (60.6 % and 49.0 %, respectively) and other separated fractions (34.1-63.0 %). The multi-scale structures of RS3, including short-range molecular order, crystalline structure, micro-ordered aggregate structure, microscopic structure, and particle size distribution, were influenced by the average DP. Notably, RS content was positively correlated with the proportion of DP 51-80 and negatively correlated with the proportion of DP 21-30. DBS with DP 51-80 contributed to a more organized micro-ordered aggregate structure at nanometer scale and a larger aggregate structure at micrometer scale, which improved the resistance of RS3 to amylolytic enzymes. However, DBS with DP 21-30 tended to form random coil structure that were more easily to be digested. This research offered new insights into the structure-digestibility relationship of RS3, which is meaningful for the development of RS3 with high resistance to amylolytic enzymes after cooking., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose To evaluate the safety and efficacy of US-guided thermal ablation in the treatment of Bethesda III thyroid nodules with negative eight-gene panel testing results. Materials and Methods This retrospective single-center study included patients with thyroid nodules diagnosed as Bethesda category III (atypia of undetermined significance) at fine-needle aspiration biopsy and with negative eight-gene testing results who were treated with US-guided microwave ablation (MWA) between July 2020 and September 2023. Incidence of complications, technical success rate (TSR), volume reduction rate (VRR), nodule recurrence, and thyroid function were evaluated over a follow-up period of 2 years. Data before and after MWA were compared using variance analysis and the Cochran-Mantel-Haenszel χ 2 test. Results A total of 101 Bethesda III nodules were detected in 95 patients (mean ± SD age, 47.08 years ±14.63; 79 female patients, 16 male patients), all of which were completely ablated (100% TSR). Two patients experienced mild neck swelling and pressure sensation after the minimally invasive operation, and the incidence of postoperative complications was 2% (two of 95). None of the patients experienced tumor recurrence or progression. At 2-year follow-up, the mean VRR of the ablated area was 90.88% ± 13.59 in 15 patients; 87% (13 of 15) of these patients had a 100% VRR. There was no evidence of a difference in thyroid function before and after MWA from 1 to 24 months ( P = .15-.99). Conclusion US-guided MWA was safe and effective for the treatment of Bethesda III thyroid nodules with negative eight-gene panel testing results. Keywords: Ablation Techniques, Radiation Therapy/Oncology, Head/Neck, Thyroid, Safety, Observer Performance Published under a CC BY 4.0 license.

Abstract: Background : The interrelation between the plasma proteome and plasma metabolome with sepsis presents a multifaceted dynamic that necessitates further research to elucidate the underlying causal mechanisms. Methods : Our investigation used public genome-wide association study data to explore the relationships among the plasma proteome, metabolome, and sepsis, considering different sepsis subgroup. Initially, two-sample Mendelian randomization established causal connections between the plasma proteome and metabolome with sepsis. Subsequently, multivariate and iterative Mendelian randomization analyses were performed to understand the complex interactions in plasma during sepsis. The validity of these findings was supported by thorough sensitivity analyses. Result : The study identified 25 plasma proteins that enhance risk and 34 that act as protective agents in sepsis. After P value adjustment (0.05/1306), ICAM5 emerged with a positive correlation to sepsis susceptibility ( P value = 2.14E-05, OR = 1.10, 95% CI = 1.05-1.15), with this significance preserved across three sepsis subgroup examined. Additionally, 29 plasma metabolites were recognized as risk factors, and 15 as protective factors for sepsis outcomes. After P value adjustment (0.05/997), elevated levels of 1,2,3-benzenetriol sulfate (2) was significantly associated with increased sepsis risk ( P value = 3.37E-05, OR = 1.18, 95% CI = 1.09-1.28). Further scrutiny revealed that this plasma metabolite notably augments the abundance of ICAM5 protein ( P value = 3.52E-04, OR = 1.11, 95% CI = 1.04-1.17), devoid of any detected heterogeneity, pleiotropy, or reverse causality. Mediated Mendelian randomization revealed ICAM5 mediated 11.9% of 1,2,3-benzenetriol sulfate (2)'s total effect on sepsis progression. Conclusion : This study details the causal link between the plasma proteome and metabolome with sepsis, highlighting the roles of ICAM5 and 1,2,3-benzenetriol sulfate (2) in sepsis progression, both independently and through crosstalk., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)