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The escalating issue of water pollution, especially the accumulation of organic off-flavor pollutants, poses significant challenges. Geosmin, a typical off-flavor compound in aquatic environments, not only compromises the quality of aquatic products but also deters consumers. Its impact extends to aquatic organisms, with current research focusing on dose-response and ecotoxicity, while neglecting the molecular-level study of geosmin-binding proteins. This study employs an integrated approach combing affinity-responsive target stability in vitro, tandem mass tag proteomics in vivo, and molecular docking to identify geosmin-binding proteins in the gill tissue of grass carp (Ctenopharyngodon idella). ARTS analysis identified 56 proteins, predominantly membrane-associated proteins, such as catenin beta-1, annexin, and integrin beta. Proteomic analysis revealed 256 differentially expressed proteins in geosmin-exposure group, with 18 common proteins screened by in vivo and in vitro methods. Among these, annexin, cathepsin D, and interleukin-1 receptors were highlighted as potential geosmin targets, with annexin demonstrating the highest binding affinity in silico. This study provides a robust protocol integrating in vivo, in vitro, and in silico approaches to elucidate geosmin's target proteins in grass carp gill tissue, advancing our understanding of pollutant-biological interactions and enhancing environmental risk assessment accuracy., 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.)

Employing an optical microcavity interacting with a nitrogen-vacancy (NV) center with excellent optical performance and scalability, two logic-qubit controlled-not (CNOT) gates in decoherence-free subspaces (DFSs) are successfully constructed against collective-rotating noise and collective-dephasing noise, respectively. The circuit has a heralded function that can filter out incorrect components. Furthermore, a waveform corrector (WFC) is adopted to balance the amplitude of two components in different spatial modes, thereby achieving high fidelity.

A new aggregation-induced emission (AIE) luminogen is obtained by dimerizing acridin-9(10H)-one (Ac), an aggregation-caused quenching (ACQ) effect monomer via an N─N bond and forming 9H,9'H-[10,10'-biacridine]-9,9'-dione (DiAc) with D 2d symmetry. The quenching of DiAc in solution is ascribed to the enhanced basicity promoting hydrogen bonding and then a hydrogen abstraction (HA) reaction and/or an unallowed transition in frontier orbitals with the same symmetry facilitating intersystem crossing. It is found that emissive Ac is one product of the non-emissive DiAc solution in the HA reaction activated by UV irradiation. By exploiting the AIE properties and the HA reaction of DiAc, photolithographic patterning is demonstrated with a paper wetted with DiAc solution., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Although evidence suggests that perfluoroalkyl and polyfluoroalkyl substances (PFASs) are positively correlated to several disease risks, no studies have proven if plasma PFASs are related to ovarian cancer survival., Objective: To explore the association between plasma PFASs and high-grade serous ovarian cancer (HGSOC) overall survival (OS) in the population who did not smoke., Methods: We conducted a nested case-control study within the Ovarian Cancer Follow-Up Study, matching 159 dead patients and 159 survival ones based on body mass index, sample date, and age at diagnosis. Nine plasma PFASs were extracted by solid phase extraction and measured using a liquid chromatography system coupled with tandem mass spectrometry. Baseline plasma concentrations of perfluorinated carboxylic acids (PFCAs) [perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroheptanoic acid (PFHpA)] and perfluorinated sulfonic acids (PFSAs) [perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)] were calculated. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated via conditional logistic regression models. To elucidate the combined effects, Bayesian kernel machine (BKMR), and regression quantile g-computation (QGC) models were utilized., Result: In full-adjusted model, significant differences were observed between HGSOC survival and perfluorobutane sulfonic acid, PFHpA, PFHxS, PFOS, PFCA, and PFSA. ORs and 95 %CIs were 2.74 (1.41-5.31), 1.97 (1.03-3.76), 2.13 (1.15-3.95), 2.28 (1.16-4.47), 3.74 (1.78-7.85), and 2.56 (1.31-5.01), respectively for the highest tertile compared with the lowest tertile. The QGC and BKMR models indicated that elevated concentrations of PFAS mixtures were associated with poor OS in HGSOC., Conclusions: Both individual and mixed plasma PFASs may relate to poor OS of HGSOC. Further research is necessary to establish causality, and it is recommended to reinforce environmental risk mitigation strategies to minimize PFAS exposure., 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.)

Amyloid β peptide (Aβ) induces neurodegeneration in the early stage of Alzheimer's disease (AD), resulting in neuroinflammation, oxidative damage, and mitochondrial impaired function. These reactions were closely associated with the pathological changes of brain microglia. Therefore, it was crucial to investigate the precise process of neuroinflammation induced by Aβ in microglia and discover therapies to alleviate its harmful consequences. This study evaluated the toxicity detection of primary microglia generated by Aβ42 ADDL. identification of inflammatory markers, measurement of ROS, and assessment of mitochondrial energy metabolism, mitochondrial membrane potential damage and mitochondrial ROS to evaluate the reparative properties of natural small molecule compounds Gallic acid and Loganic acid on primary mouse microglia. The findings indicated that Gallic acid and Loganic acid exhibited diverse reparative effects on impaired microglia. Thus, it can be provisionally predicted that Aβ42 ADDL affects microglia and promotes modifications in the NF-кB signaling pathway. Gallic acid and Loganic acid were expected to initially restore the NF-кB signaling pathway, leading to a reduction in M1-microglia and an elevation in M2-microglia, thereby decreasing various inflammatory factors and increasing anti-inflammatory factors. The mitochondrial metabolism, mitochondrial membrane potential, and mitochondrial ROS of primary microglia were restored, leading to a reduction in neuroinflammation., Competing Interests: Declaration of competing interest The authors declare no competing interests in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mycobacterium tuberculosis enters the body through the respiratory tract, produces and releases virulence proteins through a variety of mechanisms, regulates the host immune mechanism through a variety of ways, and then survives in the body for a long time. These depend on virulence genes encoded by Mycobacterium tuberculosis. Previous studies found that the Rv3435c gene of Mycobacterium tuberculosis is highly conserved in pathogenic mycobacterium, but not conserved in non-pathogenic mycobacterium, which may be a potential virulence gene, and inhibit the secretion of inflammatory factors in RAW264.7 cells and inhibit cell apoptosis. Based on previous studies, the function of Rv3435c gene in mice was studied by infecting mice with recombinant strains. In vivo infection experiments showed that overexpression of Rv3435c significantly promoted the survival of Ms in the lung. Ms-pMV361-Rv3435c specifically inhibits the secretion of inflammatory cytokines, including TNF-α, IL-6, IL-1β, IL-12, and IFN-γ. Rv3435c can inhibit lung cell apoptosis and cause pathological damage to lung. Therefore, Rv3435c enhances the survival of mycobacterium in mice and promotes the pathogenicity and spread of Mycobacterium tuberculosis by inhibiting the production of cytokines., 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 Ltd.. All rights reserved.)

Assessing blending of instruments is important in music performance and perception research, but remains underexplored due to its complex multi-dimensional nature. Despite extensive research on source-level blending, the influence of room acoustics on this process is rarely examined. This study proposes a computational modelling approach to evaluate the perceived overall blending between instruments examining the blending at the source-level and its alteration brought by room acoustics. Three audio stimuli, each showcasing different degrees of source-level blending between two violins, were auralized in 25 simulated room acoustic environments, with expert listeners assessing their overall perceived blending. The correlation analysis of room acoustic parameters revealed that their influence on overall blending is contingent upon source-level blending. A random forest regression model is proposed to predict perceived overall blending ratings using source-level blending ratings and room acoustic parameters. Its viability was confirmed through twofold evaluation, including Leave-one-out-cross-validation and separate training and test data, with a mean absolute error of 6% in each case. Feature importance analysis revealed that source-level blending contributes 60%, while room acoustics contribute 40% of the overall perceived blending ratings, with perceived reverberance being the primary contributor. Overall, this investigation contributes to a more holistic understanding of blending perception., (© 2025 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Aim: Physician visual assessment (PVA) in invasive coronary angiography (ICA) is clinically used to determine stenosis severity and guide coronary intervention. However, PVA provides limited information regarding the haemodynamic significance of stenosis. This prospective study aimed to develop a model combining visual diameter stenosis (DS PVA ) and quantitative coronary angiography (QCA)-derived parameters to diagnose ischaemic lesions using invasive fractional flow reserve (FFR) with pharmacologically induced maximal hyperaemia as the gold standard., Methods: A total of 103 patients (148 lesions) who underwent ICA and FFR measurement were included in the study. Quantitative coronary angiography was used to evaluate various parameters, including anatomical parameters such as lesion length (LL), minimal lumen diameter (MLD), and minimal lumen area, along with haemodynamic parameters like LL/MLD 4 and stenotic flow reserve (SFR). Plaque area, a characteristic parameter of plaque, was also assessed. Lesion-specific ischaemia was defined as invasive FFR ≤0.8., Results: The LL/MLD 4 (r= -0.66, p<0.001) and SFR (r=0.66, p<0.001) exhibited inverse and positive correlations, respectively, with invasive FFR. In the multivariable logistic regression analysis, LL/MLD 4 (≥10.6 mm -3 vs <10.6 mm -3 ; Odds ratio [OR] 10.59, 95% confidence interval [CI] 3.94-28.50; p<0.001) and SFR (≤2.85 vs >2.85; OR 4.38, 95% CI 1.63-11.79; p=0.004) were identified as the optimal dichotomised predictors for discriminating ischaemia. The area under the curve (AUC) was 0.77 using DS PVA ≥70% as a single predictor. Adding LL/MLD 4 ≥10.6 mm -3 and SFR ≤2.85 into the model significantly increased the AUC to 0.87 (p<0.001)., Conclusion: Incorporating QCA-derived haemodynamic parameters provided significant incremental value in the model's discriminatory capability for ischaemic lesions compared with visual diameter assessment alone., Competing Interests: Declaration of Competing Interests K.K.Y. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, Novartis (via institution); Consulting fees from Abbott Vascular, Medtronic, Novartis, Peijia Medical; Speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Shockwave Medical, Amgen, Novartis, Astra Zeneca, Microport, Terumo, Omnicare. K.K.Y. is also co-founder and owns equity in Trisail for which Orbus Neich is an investor., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Inactivation of p53 by mutations commonly occurs in human cancer. The mutated p53 proteins may escape proteolytic degradation and exhibit high expression in tumors and acquire gain-of-function activity that promotes tumor progression and chemo-resistance. Therefore, selectively targeting of the gain-of-function p53 mutants may serve as a promising therapeutic strategy for cancer prevention and treatment. In this study, we identified cabozantinib, a multikinase inhibitor currently used in the clinical treatment of several types of cancer, as a selective inducer of proteasomal degradation of the p53-Y220C mutant. We demonstrate that cabozantinib disrupts the interaction between p53Y220C and USP7, a deubiquitylating enzyme, resulting in the dissociation of p53Y220C protein from its binding with USP7 and subsequent ubiquitination and degradation mediated by CHIP (the carboxyl terminal of Hsp70-interacting protein). We also show that cabozantinib displays preferential cytotoxicity to p53Y220C-harboring cancer cells both in vitro and in vivo. This study demonstrates a novel, p53-Y220C mutant-targeted anticancer action and mechanism for cabozantinib and provides the rationale for use of this drug in the treatment of cancers that carry the p53-Y220C mutation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives:  This study aimed to establish the cephalometric norms of H angle soft tissue and H angle hard tissue of Malaysian Malay adult females, and to evaluate the correlation between H angles and visual perception in skeletal Class I Malay adult females., Materials and Methods:  Eighty-five lateral cephalograms of skeletal Class I (mean ANB value = 3.15 ± 0.77) Malaysian Malay female patients aged 20 to 40 years (mean age = 28.6 ± 5.86 degrees) taken from October 2017 to December 2021 were measured for H angle soft tissue and H angle hard tissue. Twenty silhouettes were then converted from cephalometric films and were rated according to facial convexity/concavity by 20 laypersons, with re-evaluation after 2 weeks for intra- and interexaminer reliabilities., Results:  The means of the H angle soft tissue and H angle hard tissue were 15.75 ± 4.16 degrees and 11.64 ± 4.71 degrees, respectively. The intraexaminer reliability test for visual perception ranged from -0.89 to 0.99 indicating poor to excellent reliability, whereas the interexaminer reliability test was 0.82 indicating good reliability. A highly statistically significant association between the H angle soft tissue and H angle hard tissue ( r  = 0.938; p  < 0.01) was found. There was no correlation between H angles and visual perception., Conclusion:  The cephalometric norms of H angle hard tissue and H angle soft tissue in the Malaysian Malay female population were established: 11.64 degrees (±4.71 degrees) and 15.75 degrees (±4.16 degrees), respectively. There was a strong correlation between H angle soft tissue and H angle hard tissue among skeletal Class I Malay adult females. There was no correlation between H angles and the visual perception of laypersons., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

The evolution of insect metamorphosis has profoundly influenced their successful adaptation and diversification. Two key physiological processes during insect metamorphosis are notable: wing maturation and prothoracic gland (PG) histolysis. The ecdysone-induced protein 93 (E93) is a transcription factor indispensable for metamorphosis. While it has been established that both wing maturation and PG histolysis are dependent on E93, the molecular mechanisms through which E93 regulates these seemingly 'opposing' events remain poorly understood. In this study, time-course transcriptome profiles were generated for wing pads and PGs during metamorphosis in Blattella germanica, a hemimetabolous model insect. Comparative transcriptomic analyses demonstrated that E93 exerts predominant control over extensive gene transcription during wing morphogenesis and PG histolysis. During wing morphogenesis, E93 selectively enhances the expression of genes associated with cell proliferation, energy supply, signal transduction, actin cytoskeleton organization, and cell adhesion, etc. Additionally, E93 activates the transcription of the majority of genes within the wing gene network that are crucial for wing development in B. germanica. During PG histolysis, E93 preferentially promotes the expression of genes related to endocytosis, focal adhesion, the AMPK signaling pathway, adipocytokine signaling pathway, Toll and Imd signaling pathways, and autophagy, etc. The key genes involved in the aforementioned pathways were subsequently confirmed to contribute to the E93-dependent degeneration of the PG in B. germanica. In summary, our results reveal that E93 functions as a master transcriptional regulator orchestrating both tissue morphogenesis and histolysis during insect metamorphosis. These findings contribute to a deeper understanding of the genetic underpinnings of insect metamorphosis., Competing Interests: Conflicts of interests The authors declare no competing or financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China., Methods: The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China. Data on demographics, comorbidities, and aetiological testing results were collected from adult patients with bronchiectasis at baseline and annual follow-up. Patients who met the inclusion criteria (age ≥18 years; received chest high-resolution CT in the past year showing bronchiectasis affecting one or more lung lobes; and clinical history consistent with bronchiectasis, including chronic cough, daily sputum production, and history of exacerbations) were included. Patients with known cystic fibrosis were excluded. To investigate variations according to different economic regions, two groups were compared based on whether per capita disposable income of residents was greater than US$5553. Clinical characteristics were compared with the European (EMBARC) registry and other national registries., Findings: Between Jan 10, 2020, and March 31, 2024, 10 324 patients from 97 centres were included in the study. Among 9501 participants with available data, the most common cause of bronchiectasis was post-infective disease (4101 [43·2%] patients), followed by idiopathic (2809 [29·6%] patients). 6676 (70·0%) of 9541 patients with available data had at least one exacerbation in the year before enrolment and 5427 (57·2%) of 9489 patients with available data were hospitalised at least once due to exacerbations. Treatments commonly used in high-income countries, such as inhaled antibiotics and macrolides, were infrequently used in China. Implementation of airway clearance in China was scarce, with only 1177 (12·2%) of 9647 patients having used at least one method of airway clearance. Compared with upper-middle-income regions, patients from lower-middle-income regions were younger (61·0 years [SD 14·0] vs 63·9 years [14·2]) with a higher proportion of pulmonary comorbidities (521 [17·8%] of 2922 patients vs 639 [8·6%] of 7402 with chronic obstructive pulmonary disease and 194 [6·6%] of 2922 patients vs 364 [4·9%] of 7402 patients with asthma), a higher tuberculosis burden (442 [16·0%] of 2768 patients vs 715 [10·6%] of 6733 patients), more severe radiological involvement (1160 [42·4%] of 2736 patients vs 2415 [35·4%] of 6816 patients with cystic bronchiectasis), more exacerbations (median 1·4 [IQR 0-2] in both groups; mean 1·4 [SD 1·6] vs 1·2 [1·4] in the previous year) and hospitalisations (1662 [60·6%] of 2743 patients vs 3765 [55·8%] of 6746 patients hospitalised at least once in the previous year), and poorer quality of life (median 57·4 [IQR 53·5-63·1] vs 58·7 [54·8-64·8] assessed by the Bronchiectasis Health Questionnaire)., Interpretation: The clinical characteristics of patients with bronchiectasis in China show differences compared with cohorts in Europe and India. Bronchiectasis is more severe with a higher burden of exacerbations in lower-income regions. The management of patients with bronchiectasis in China urgently needs standardisation and improvement., Funding: National Natural Science Foundation of China, Innovation Program of the Shanghai Municipal Education Commission, Program of the Shanghai Municipal Science and Technology Commission, and Program of the Shanghai Shenkang Development Center., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JDC declares grants or contracts from Astrazeneca, Genentech, Gilead Sciences, GlaxoSmithKline, Insmed, Grifols, Novartis, and Boehringer Ingelheim; and consulting fees from Astrazeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio, and Zambon. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The aim of this work is to investigate the assembly of foxtail millet prolamin (FP) with chitosan hydrochloride (CHC) and carboxymethyl-beta-cyclodextrin (CMCD) in acetic acid aqueous solutions. The proportion of acetic acid has a positive impact on the disintegration of FP. With the use of 91.0 % (v/v) acetic acid, FP forms smaller particles of approximately 45 nm (naked FP particles) and 220 nm (FP - CHC - CMCD hybrid particles). In the case of using 61.5 % (v/v) acetic acid, the microstructures of bare FP particles and 570 nm composite FP nanoparticles (NPs) are looser, about 485 nm. Acetic acid inhibits the noncovalent bonds, including the hydrophobic interactions, hydrogen bonding and electrostatic attractions between FP and polysaccharides. Therefore, 3.8 % (v/v) acetic acid can nucleate FP to form more compact FP hybrid particles for delivering curcumin (Cur) with higher encapsulation efficiency, storage stability and release performance, and improve the antibacterial and anticancer activity of Cur., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Atherosclerosis is a lipid-driven, systemic immune-inflammatory disease characterized by the accumulation of plaque within the arterial walls. Plaque regression can occur following appropriate treatment interventions. Optical coherence tomography (OCT), a high-resolution imaging modality, is frequently employed to assess plaque morphology. This study aims to explore the correlation between plaque characteristics identified using OCT, particularly macrophage infiltration, and subsequent plaque regression., Methods: In this retrospective study, data from 112 individuals with coronary artery plaques, who underwent OCT imaging at our hospital, between June 2019 and June 2024, were evaluated. Plaques were classified as lipid-rich, fibrous, or calcified based on the initial OCT findings. Macrophage infiltration levels within each plaque type were quantified. After one year of follow-up, repeat OCT imaging was performed to evaluate plaque regression. Statistical analyses were conducted to assess the relationship between initial plaque characteristics and regression outcomes., Results: Plaques that underwent regression were more commonly lipid-rich and exhibited higher levels of macrophage infiltration compared to those without regression. Multivariate analysis identified the histological inflammation score (HIS) as an independent factor influencing plaque regression., Conclusion: Macrophage-rich plaques, as detected by OCT, are significant predictors of plaque regression. The identification of vulnerable plaque features through OCT can enhance the early diagnosis and treatment strategies for atherosclerotic cardiovascular disease., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest regarding this work., (Copyright © 2025. Published by Elsevier B.V.)

Gel electrolytes have emerged as a promising solution for enhancing the performance of zinc-ion batteries (ZIBs), particularly in flexible devices. However, they face challenges such as low-temperature inefficiency, constrained ionic conductivity, and poor mechanical strength. To address these issues, this study presents a novel PAMCD gel electrolyte with tunable freezing point and mechanical properties for ZIBs, blending the high ionic conductivity of polyacrylamide with the anion interaction capability of β-cyclodextrin. Leveraging the Hofmeister effect, the chaotropic anions of ClO 4 - are integrated to weaken hydrogen bonds, enhancing the mechanical and anti-freezing properties. The chaotropic salt disrupts the hydrogen bond network within water molecules, increasing weaker bonds and forming contact ion pairs, while polyacrylamide chains bind water molecules, further destabilizing hydrogen bonds. These changes improve Zn 2+ ion mobility, mechanical resilience, and reduce the freezing point, significantly boosting ZIB performance. Consequently, the Zn-Zn symmetric cells achieve remarkable lifespans over 5290 hours at 0.5 mA cm -2 and 1960 hours at 5 mA cm -2 , and the Zn-polyaniline full batteries maintain a high capacity of 100.8 mAh g -1 at 2 A g -1 , even at -40 °C, over 7600 cycles, showcasing superior cyclability and rate performance., (© 2024 Wiley‐VCH GmbH.)

Lung cancer is the most common cause of cancer mortality globally, and the prevalence of lung adenocarcinoma, the most common lung cancer subtype, has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in nonsmokers. In this study, we performed whole-exome sequencing and RNA sequencing of samples from 94 East Asian patients with precancerous lesions [25 with atypical adenomatous hyperplasia (AAH); 69 with adenocarcinoma in situ (AIS)] and 73 patients with early invasive lesions [minimally invasive adenocarcinoma (MIA)]. Cellular analysis revealed that the activities of endothelial and stromal cells could be used to categorize tumors into molecular subtypes within pathologically defined types of lesions. The subtypes were linked with the radiologically defined type of lesions and corresponded to immune cell infiltration throughout the early progression of lung adenocarcinoma. Spatial transcriptomic analysis revealed the distribution of epithelial cells, endothelial cells, fibroblasts, and plasma cells within MIA samples. Characterization of the molecular lesion subtypes identified positively selected mutational patterns and suggested that angiogenesis in the late-stage AIS type potentially contributes to tissue invasion of the MIA type. This study offers a resource that may help improve early diagnosis and patient prognosis, and the findings suggest possible approaches for early disease interception. Significance: Integrative analysis of multiomics data revealed coordination between immune and nonimmune cells during early progression of precancerous lesions to lung adenocarcinomas and shed light on the molecular characteristics of clinically defined subtypes., (©2024 The Authors; Published by the American Association for Cancer Research.)

The translocation of an aryl group from selenium into carbon enabled by the cleavage of the C-Se bond is reported by using nitrogen atom-linked 1,7-diynes and diaryl diselenides as starting materials, leading to various selenophene derivatives in a regioselective manner. This method enables the construction of two C-Se bonds and two C-C bonds through sequential radical bicyclization and 1,2-aryl migration under metal-free conditions. Control experiments and mechanistic studies suggest that this reaction proceeds through the cleavage of the inert C(Ph)-Se bond, facilitating the aryl translocation process. This transformation enables the one-step conversion of simple diselenides into diverse selenopheno[3,4- c ]quinolines via a radical-promoted process, holding significant potential for new seleniferous heterocycles.

Three seco-norabietane diterpenoids, salvicsites A-C ( 1 - 3 ), along with two known compounds, were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Salvicsite A ( 1 ) represents an unprecedented structural combination, featuring an eight-membered α-methyl-α,β-unsaturated lactone ring and a five-membered α,β-unsaturated lactone ring, based on a 6/6/5/8 ring system. Their structures were elucidated through comprehensive spectroscopic analyses, X-ray crystallography, and quantum chemical calculations. Putative biosynthetic pathways of 1 - 3 were proposed, with compound 5 being the plausible biogenetic precursor. The AChE inhibition assay demonstrated that salvicsite A ( 1 ) exhibited a notable inhibitory effect against AChE, with an IC 50 value of 9.56 ± 1.05 μM. Enzymatic kinetic studies indicated that salvicsite A ( 1 ) acted as a mixed-type inhibitor, and its binding mode was explored through molecular docking. The results of the cytotoxic activity demonstrated that only compound 5 exhibited inhibitory activity.

Background and Aim: The APAGE Position Statements aimed to provide guidance to healthcare practitioners on clinical practices aligned with climate sustainability., Methods: A taskforce convened by APAGE proposed provisional statements. Twenty-two gastroenterologists from the Asian Pacific region participated in online voting and consensus was assessed through an anonymized and iterative Delphi process., Results: There were five sections that addressed the rationale for climate action, the importance of adopting principles of waste management, clinical practice, gastrointestinal endoscopy, and issues related to advocacy and research. Sixteen statements achieved consensus and included the following: 1. APAGE recommends adopting prompt measures to reduce the carbon footprint of clinical practice due to the importance of climate action and its health cobenefits. 5. APAGE recommends adherence to professional clinical guidelines to optimize clinical care delivery in gastroenterology and hepatology to avoid the environmental impact of unnecessary procedures and tests. 8. APAGE recommends an emphasis on health promotion, disease prevention, and appropriate screening and surveillance, when resources are available, to reduce the environmental impact of managing more advanced diseases that require more intensive resources. 12. APAGE recommends that technological advances in endoscopic imaging and artificial intelligence, when available, be used to improve the precision of endoscopic diagnosis to reduce the risk of missed lesions and need for unnecessary biopsies. 13. APAGE recommends against the routine use of single-use endoscopes., Conclusion: The position statements provide guidance to healthcare practitioners on clinical practices in gastroenterology, hepatology, and endoscopy that promote climate sustainability., (© 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

This study proposed a miniaturized multi-sensor device prepared using a flexible printed circuit board (FPCB) and applied to detect glucose (Glu) and pH value, where both the readout circuit board and the sensors possess flexible characteristics. Additionally, this work implemented the potentiometric readout circuit. It integrated the die onto the readout circuit board using wire bonding techniques, while the area of the readout circuit board is 5.5 cm × 4.0 cm. The readout circuit board is equipped with a power supply, a readout circuit chip, and a multi-sensor. It is worth mentioning that this study designs the multi-sensor in a double-sided manner. The advantage of this design lies in the fact that both sides of the sensor can be utilized as a working electrode or reference electrode, providing convenience to users during measurement analysis. In addition, the magnesium oxide (MgO) multi-sensor is interconnected with the readout circuit board using slot type. This means the MgO multi-sensor can also be used as a disposable sensor. In this study, the multi-sensor system can measure hydrogen ions and Glu at the same time. The sensitivity of the two is 25.27 mV/pH and 16.78 mV/mM, respectively, and the linearity can reach 99.9 %.

Radiative cooling, a passive cooling technology, functions by reflecting the majority of solar radiation (within the solar spectrum of 0.3-2.5 μm) and emitting thermal radiation (within the atmospheric windows of 8-13 μm and 16-20 μm). Predominantly, synthetic polymers are effectively utilized for radiative cooling while posing potential environmental hazards due to their complex components, toxicity, or nonbiodegradation. Bacterial cellulose, a natural and renewable biopolymer, stands out due to its environmentally friendly, scalability, high purity, and significant infrared emissivity. In this work, we developed a bacterial cellulose-based composite film (BCF) with a cross-linked network structure by a facile agitation spraying method to achieve enhanced and sustainable radiative cooling performance. The BCF exhibited superior optical properties and environmental tolerance, with a notable infrared emissivity of 94.6%. As a result, the thermal emitter demonstrates a substantial subambient cooling capacity (11:00 to 13:00, maximum drop of 7.15 °C, average drop of 4.85 °C; 22:00 to 2:00, maximum drop of 2.7 °C, average drop of 2.32 °C). Additionally, the BCF maintained stable emissivity after 240 h of continuous UV irradiation. Furthermore, BCF can effectively preserve the freshness of fruits under intense solar irradiation. Hence, BCF with high radiative cooling performance presents a broad application prospect in building energy conservation, solar cells efficiency enhancement, and food transportation packaging.

Objectives: To assess the therapeutic effects and safety of Tongxie Yaofang (TXYF) granules vs placebo as an alternative treatment for diarrhoea-predominant irritable bowel syndrome (IBS-D). We hypothesised that TXYF would improve clinical responses among patients with IBS-D., Design: A randomised, double-blind, placebo-controlled, phase II, superiority trial., Setting: Outpatients attending the Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China., Participants: 96 eligible participants included men and women ranging from late adolescence to middle adulthood (18-65 years), diagnosed with IBS-D according to the Rome IV criteria. In addition, they were required to have an irritable bowel syndrome symptom severity score (IBS-SSS) of at least 75., Interventions: TXYF granules (3.7 g) twice daily (taken orally before meals) or placebo for 8 weeks., Primary and Secondary Outcomes: The primary outcome was the response rate measured by the change in IBS-SSS compared with baseline at week 8. Secondary outcomes included stool frequency; stool consistency at weeks 4, 8 and 20; and quality of life, anxiety and depression at week 8; and safety was monitored throughout the trial., Results: The TXYF and placebo groups each comprised 48 participants. The response rate was not significantly different at week 8 between the two groups (the unadjusted treatment effect estimate (intention-to-treat analysis) was 1.12 (95% CI (0.89, 1.41)), p=0.348). Both groups had a high and similar rate of symptom reduction (79.2% (38/48) vs 70.8% (34/48)). There were no statistically significant differences between the two groups on secondary outcomes, although both groups showed substantial improvements. Adverse events in the TXYF and placebo groups were one (sinus arrhythmia) and two (elevated transaminases, weakly positive faecal occult blood), respectively. No serious adverse events occurred., Conclusions: Despite showing clinically meaningful improvements in IBS-D symptoms and a reasonable safety profile after 8 weeks, no significant differences were observed between the TXYF and placebo groups. This suggests that the severity of IBS-D symptoms in both treatment arms might have decreased over time, regardless of the treatment, and highlights the need to investigate the relationship between IBS-D and patient psychology. Future large-scale, rigorously designed trials with longer treatment and follow-up periods are essential to evaluate the therapeutic effects and safety of TXYF, and to explore the psychological factors., Trial Registration Number: ISRCTN12453166., Competing Interests: Competing interests: NR is the guest professor of Beijing University of Chinese Medicine, Centre of Evidence-Based Chinese Medicine (certification number 20210017)., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objective: Investigating the clinical efficacy of treating dorsally displaced distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires., Methods: Retrospectively analyzed the clinical data of 15 patients with distal radial double-column Die-punch fractures treated with an external fixator combined with Kirschner wire between July 2020 and January 2023. There were 10 males and 5 females;6 cases on the left side and 9 on the right;age ranged from 22 to 76 years old. Recorded the preoperative and the final follow-up Cooney wrist function scores for the patients. The fracture healing time, and occurrence of complications were recorded., Results: All 15 patients were followed up ranged from 12 to 16 months post-operation. All fractures achieved bony union, healing time ranging form 8 to 16 weeks. Not a single patient exhibited complications such as surgical site infection, fracture redislocation, or tendon injury. All individuals had their Kirschner wires and external fixation devices removed six weeks post-operatively and commenced rehabilitative therapy for wrist articulation. The Cooney wrist function scores at preoperative and ranged from 5 to 45 scores, at the latest follow-up ranged from 65 to 100 scores. At the final follow-up, the results were assessed as excellent in 10 patients, good in 4 patients, and fair in 1 patient., Conclusion: The clinical efficacy of treating distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires is satisfactory.

A Cu-catalyzed relay process for the preparation of diazidated quinazolinone and polycyclic imidazole derivatives in which readily available alkene-tethered substrates undergo an addition/cyclization/C(sp 3 )-H functionalization of alkene sequences with high efficiency is described. Various functionalized N-heteropolycyclic compounds were readily prepared in good yields with a broad substrate scope. Moreover, the direct azidation of the α-C(sp 3 )-H bond of the corresponding N-heterocycles has been demonstrated on the basis of mechanistic studies, which provide an alternative late-stage functionalization approach for the derivatization of N-heterocyclic scaffolds.

Background: Hypospadias is a prevalent pediatric urological condition. Perididymis covering is often used as a surgical procedure for the treatment of hypospadias. This study aims to investigate the risk factors associated with postoperative complications following perididymis covering in the treatment of hypospadias., Methods: This study involved 204 patients with hypospadias who underwent perididymis cove ring at Tangshan Maternal and Child Health Hospital from May 2018 to May 2024. Patients were followed up for 1 year, with 63 experiencing complications (30.88%) and 141 not experiencing complications (69.12%). Baseline data from both groups were collected and compared. Binary logistic regression analysis was used to analyze the relationship between various factors and postoperative complications. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to evaluate the predictive value of the nomogram model for postoperative complications., Results: The complication group had a higher mean age and longer formed urethra lengths compared to the non-complication group. The types of hypospadias were categorized as intermediate, proximal, and those associated with preoperative penile curvature. The AUC for the nomogram model in the prediction of the postoperative complications was 0.909 [95% confidence interval (CI): 0.866-0.952], with a sensitivity of 0.746, a specificity of 0.929, and a Youden's index of 0.675., Conclusions: Age, length of the formed urethra, types of hypospadias, preoperative penile curvature, and surgical methods are significantly associated with postoperative complications following perididymis covering in patients with hypospadias. These indicators can guide the formulation of clinical treatment plans to reduce the incidence of postoperative complications., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-368/coif). The authors have no conflicts of interest to declare., (Copyright © 2025 AME Publishing Company. All rights reserved.)

TXA9, a cardiac glycoside isolated from the root of Streptocaulon juventas (Lour.) Merr., with better therapeutic effect in vitro on non-small cell lung cancer (NSCLC) than cisplatin and has no toxic side effects on the body. However, poor water solubility and rapid metabolism limited its clinical application. Multi-arm star PEG have many advantages over linear PEG, such as high drug loading due to more terminals and better anti-hemodilution ability, which have become popular carriers for drug delivery. In this study, to improve the efficacy of TXA9, 6/8armPEG n -Glycine Carbamate (Gly) (n = 10, 20, and 40 kDa) were used as carriers to prepare star PEG-TXA9 conjugates. The particle size and zeta potential of six prodrug NPs for effective tumor targeting, with suitable drug loading, and good water solubility. Compared with free TXA9, 6/8APG n -T NPs had more significant anti-tumor effects in vitro. Since the multi-arm star PEG formed an "umbrella" structure on the surface of NPs, the 8APG 40k -T NPs with the best pharmacokinetic properties increased half-life of TXA9 about 60 times in vivo. In addition, the arm numbers and molecular weight of multi-arm star PEGs significantly influenced the in vivo destiny of prodrugs. In vivo experiments showed that the same dose of 8APG 40k -T NPs increased the tumor inhibition rate about 3.56 or 1.22 times compared with TXA9 or cisplatin, and had good biocompatibility. This study provides a simple but effective strategy to solve the challenges caused by the poor water solubility and short half-life of TXA9 for developing the TXA9 as a safe and effective drug against NSCLC., Competing Interests: Declarations. Ethics approval: All animal procedures were approved by the Animal Ethics Committee of Shenyang Pharmaceutical University (approval number: SYPU-IACUC-S2023-0710-101). All animal procedures conformed to the NIH Guide for Care and Use of Laboratory Animals. Consent for participate: Not applicable. No human studies have been performed in this research. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. Controlled Release Society.)

Grain size and weight of main-crop are larger than those of ratoon rice, indicating that increasing grain size and weight of ratoon rice is an effective way to increase rice yield. Thus, grain length (GL), grain width (GW), and thousand-grain weight (TGW) of main-crop and ratoon rice in 159 indica rice accessions were used to associate with 2 017 495 SNP markers to detect quantitative trait nucleotides (QTNs) and their interactions with meteorological factors (QMIs), such as temperature and sunlight hours. Around 59 QMIs identified for temperature and 80 QMIs identified for sunlight hours, first, candidate gene LOC&#95;Os02g40840 for GW and LOC&#95;Os04g45480 for TGW were found to interact with temperature, while LOC&#95;Os01g19970 for GL, LOC&#95;Os02g39360 and LOC&#95;Os07g05720 for GW, and LOC&#95;Os07g49460 for TGW were found to interact with sunlight hours. Based on the results of previous studies, LOC&#95;Os04g45480 exhibits high expression levels in the main-crop under higher temperature, thereby enhancing the accumulation of the auxin receptor TIR1. TIR1, in turn, promotes starch accumulation in the endosperm, explaining why TGW is heavier in main-crop than in ratoon rice. Finally, the analysis of best linear unbiased prediction values revealed 1 (LOC&#95;Os08g10350) and 3 (LOC&#95;Os02g50860, LOC&#95;Os08g28680, and LOC&#95;Os08g29160) candidate genes responsible for GW and TGW, respectively. In addition, we discussed the four available and six unavailable candidate genes in ratoon rice breeding. This study provides new method and genes for studying differences in grain size-related traits between main-crop and ratoon rice., (© 2025 John Wiley & Sons Ltd.)

Branched-chain amino acids (BCAAs) are important for normal growth, development, and function. In urea cycle disorders (UCDs), plasma BCAA levels can be relatively low; this has been attributed variously to low protein intake, hyperammonaemia, and nitrogen scavenger treatment. We undertook a retrospective review of plasma BCAA levels in individuals with UCDs comprising ornithine carbamoyltransferase deficiency (OTCD n  = 22), arginosuccinate lyase deficiency (ASLD n  = 12), and argininosuccinate synthase deficiency (ASSD n  = 6). Scavenger treatment groups comprised sodium benzoate (NaBz, n  = 20), sodium phenylbutyrate (NaPBA, n  = 5), NaBz+NaPBA ( n  = 14), and a control group receiving neither NaBz nor NaPBA (n = 14). In these treatment groups, respectively, median (IQR) plasma levels of leucine were 54 (32), 55 (25), 58 (19), and 91 (70) μmol/L (leucine was lower in the NaBz group than the control, p  = 0.0282) and numbers of individuals (%) with leucine below normal were 10/20 (50 %), 1/4 (25 %), 10/14 (71 %), and 2/9 (20 %). The pattern was similar for isoleucine and valine. In the NaBz group, plasma BCAA levels were inversely correlated with protein intake ( p  ≤ 0.01 to p  ≤ 0.001), plasma ammonia level (p ≤ 0.01 to p  ≤ 0.0001), and scavenger dose (p ≤ 0.0001). We speculate that individuals with greater disease severity may be prone to BCAA deficiency, caused by BCAA consumption when alternative urea disposal pathways are used. Practical reflections on our audit were that to increase the proportion of plasma BCAA levels in the normal range, we needed to alter the biological value of protein intake, prescribe higher doses of scavenger to facilitate safe levels of protein intake, and give EAA supplements if indicated., Competing Interests: Mildrid Yeo and Marjorie Dixon have received speaker honoraria from Immedica. The remaining authors declare no conflicts of interest., (© 2025 The Authors. Published by Elsevier Inc.)

Considerable efforts have been made to develop microscale multiplexing strategies. However, challenges remain due to the difficulty in deploying functional objects and decoding high-density signals on anisotropic microcarriers. Here, we report a microfluidic method to fabricate architecture-marked anisotropic particles for performing designable multiplexed assays in a label-free manner. By controlling fluid assembly and rapid in-air cross-linking, the particles are endowed with multiple functional regions and a unique architecture identifier. The marked architecture enables an addressing mechanism that allows the profiling of embedded label-free objects by mapping a well-defined reference architecture onto the target particle. By loading analytes of interest, such as molecular probes or cells, we showed the potential of these structurally flexible particles for detecting microRNAs and studying cell interactions. The architecture-marked particles represent a new approach for single-entity assays and can be the basis for exploring more advanced microscale multiplexed applications., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)

Background: Quality of life (QOL) is important for evaluating medical care outcomes. In chronic kidney disease (CKD) population, generic instruments, such as WHOQOL-BREF and EQ-5D, are commonly used for comparing various medical conditions for policy-making purposes. However, their psychometric properties have not yet been validated in non-dialysis CKD population., Methods: Patients who were in CKD care programs at a medical center in Taiwan were recruited and self-filled WHOQOL-BREF Taiwan version (TW) and EQ-5D questionnaires. Rasch model, confirmatory factor analysis (CFA), and Pearson correlations were used to validate psychometric properties of these two QOL instruments., Results: 634 participants, aged 66 ± 14 years old, were enrolled. Rasch model revealed almost all items (23 of 26) in WHOQOL-BREF (TW) and all items in EQ-5D were well-fit in their domains. Both instruments demonstrated relatively robust psychometric properties in CFA and Rasch analysis, with WHOQOL-BREF (TW) performing slightly better. Fewer items in WHOQOL-BREF (TW) displayed substantial differential item functioning compared to EQ-5D, particularly across different CKD stages (1 or 2 of 26 versus 4 of 5), diabetes mellitus (DM) and non-DM status (1 of 26 versus 4 of 5), and different age groups. The original domain scores/utility scores were highly correlated with Rasch scores (all absolute correlation coefficients >0.90)., Conclusions: Both WHOQOL-BREF (TW) and EQ-5D have relatively good psychometric properties in non-dialysis CKD population. The direct use of original WHOQOL-BREF (TW) domain scores/EQ-5D utility score for parametric analyses is acceptable non-dialysis in CKD population. However, when using the EQ-5D for cost-effective comparison in CKD patients with different stages or characteristics potential bias should be concerned., Competing Interests: Conflicts of interest All authors declare no conflicts of interest related to this research., (Copyright © 2025 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Diatomic catalysts (DACs) present unique opportunities for harnessing ensemble effects between adjacent metal atoms, thus, expanding the properties of single-atom catalysts (SACs). However, the precise preparation and characterization of this type of catalyst remains challenging. Following a precursor-preselected strategy, here, we report the synthesis of a carbon nitride-supported Pd-DAC, which achieves an excellent yield of 92% for photocatalytic water-donating transfer hydrogenation of 4-vinylphenol to 4-ethylphenol, far exceeding that of other metal species, including Pd single atoms (47%) and nanoparticles (1%). Combining transmission electron microscopy with standardized machine learning atom-detection methods confirms the stabilization of a substantial fraction of dimeric Pd species over carbon nitride. Density functional theory (DFT) simulations associate the outstanding performance of Pd-DAC to enhanced substrate activation in the hydrogenation path compared to Pd-SAC. The work provides criteria for DACs characterization and demonstrates a transfer hydrogenation application that is sustainable and eco-friendly over conventional hydrogenation technologies.

This study was undertaken to develop a high-throughput screening strategy using a whole-cell biosensor to enhance methyl-group transfer, a rate-limiting step influenced by intracellular methyl donor availability and methyltransferase efficiency. An l-homocysteine biosensor was designed based on regulatory protein MetR from Escherichia coli, which rapidly reported intracellular l-homocysteine accumulation resulted from S-adenosyl-l-homocysteine (SAH) formation after methyl-group transfer. Using S-adenosyl-l-methionine (SAM) as a methyl donor, this biosensor was applied to caffeic acid 3-O-methyltransferase derived from Arabidopsis thaliana (AtComT). After several rounds of directed evolution, the modified enzyme achieved a 13.8-fold improvement when converting caffeic acid to ferulic acid. The best mutant exhibited a 5.4-fold improvement in catalytic efficiency. Characterization of beneficial mutants showed that improved O-methyltransferase dimerization greatly contributed to enzyme activity. This finding was verified when we switched and compared the N-termini involved in dimerization across different sources. Finally, with tyrosine as a substrate, the evolved AtComT mutant greatly improved ferulic acid biosynthesis, yielding 3448 mg L -1 with a conversion rate of 88.8%. These results have important implications for high-efficiency O-methyltransferase design, which will greatly benefit the biosynthesis of a wide range of natural products. In addition, the l-homocysteine biosensor has the potential for widespread applications in evaluating the efficiency of SAM-based methyl transfer., 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.)

Background: The aim of this study is to identify factors associated with the development of long-term severe tricuspid regurgitation (TR) following mitral valve replacement (MVR)., Methods: A retrospective analysis was conducted involving 308 patients who underwent single-valve MVR at Xuzhou Central Hospital between April 2017 and December 2022. Preoperative color Doppler ultrasound indicated that all patients had either no or mild to moderate tricuspid regurgitation. Postoperative follow-up was carried out over several years, and patients were categorized into two groups based on the severity of TR: 258 patients with non-severe TR (observation group) and 50 patients with severe TR (control group). Clinical data, medical history, the performance of tricuspid valvuloplasty during surgery, and echocardiographic parameters before and after the procedure were recorded. Comparative analysis between the two groups was performed, and logistic regression analysis was used to identify factors associated with the long-term development of severe TR post-MVR., Results: Logistic regression analysis indicated that serum creatinine levels (OR = 1.023, P = 0.026), atrial fibrillation (OR = 2.780, P = 0.040), and a history of permanent pacemaker implantation (OR = 3.029, P = 0.039) were significantly associated with the development of severe TR over time. In contrast, concurrent intraoperative tricuspid valvuloplasty was associated with a reduced risk of TR (OR = 0.315, P = 0.002)., Conclusions: Elevated serum creatinine, atrial fibrillation, and a history of permanent pacemaker implantation were positively associated with the long-term occurrence of severe TR following MVR. In contrast, concurrent intraoperative tricuspid valvuloplasty was found to reduce the likelihood of severe TR development., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki. The study was approved by Ethics Committee of the Xuzhou Central Hospital (No.XZXY-LK-20240807-0115). Written informed consent was obtained from all participants. Consent to publish: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hyperoxaluria can easily induce calcium oxalate (CaOx) crystals and cause cell damage, thereby increasing the risk of kidney stone formation. In this study, three sulfated Pelvetia siliquosa polysaccharides (PSPs) were obtained by the sulfur trioxide-pyridine method. The antioxidant activity of PSPs and the inhibitory effects of PSPs on CaOx crystallization, cellular oxidative damage, and cellular inflammation were explored in vitro, and PSPs were used to treat hyperoxaluria-induced crystallization model mice in order to validate the stone-preventive effect of PSPs in vivo. PSPs can inhibit CaOx crystal formation, as well as reduce reactive oxygen species (ROS) levels through their own antioxidant properties and up-regulation of antioxidant enzyme (SOD and CAT) expression, which in turn reduces the release of lactate dehydrogenase (LDH) and malondialdehyde (MDA), improves lysosomal integrity, cellular morphology, and cytoskeleton, inhibits the decrease of mitochondrial membrane potential, reduces adhesion protein (CD44 and OPN) expression, alleviates cellular inflammatory factor (IL-6, TNF-α, and IL-1β) levels, and inhibits apoptosis. PSP3, which has the highest degree of sulfation, had the best protection capacity. PSP3 also showed good antistone ability in mice, and it may be a potential drug for kidney stone prevention.

Machine learning methods for fitting potential energy surfaces and molecular dynamics simulations are becoming increasingly popular due to their potentially high accuracy and savings in computational resources. However, existing application models often rely on basic architectures like artificial neural networks (ANNs) and multilayer perceptron (MLP), lagging behind cutting-edge technologies in the machine learning domain. Furthermore, the complexity of current machine learning frameworks leads to reduced interpretability and challenges for improvement. Herein, we developed a model analysis method based on the feature-representation-transfer approach to directly perform causal analysis on the model. The internal action characteristics of the SchNet framework were successfully analyzed by constructing different source tasks and we proposed interatomic interactions attention for the characterization of doped clusters. The accuracy was enhanced by 0.015 eV/atom compared to the original model. The ability to capture atomic environment characteristics was significantly improved. The activation function was smoothed resulting in a 23.47% increase in the convergence speed. Our SchNet&#95;IIA model demonstrates superior performance in capturing interatomic interactions. Our present work is of distinctive value as it presents a novel transfer learning analysis method with the potential to evolve into a generalized model analysis approach, providing new perspectives and solutions for the field.

Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity. Notably, a DNA vaccine encoding the spike protein, delivered via LNP-M, induced stronger antigen-specific antibody and T cell immune responses compared to electroporation. Single-cell RNA sequencing (scRNA-seq) analysis revealed that the LNP-M/pSpike vaccine enhanced CD80 activation signaling in CD8 + T cells, NK cells, macrophages, and DCs, while reducing the immunosuppressive signals. The enrichment of TCR and BCR by LNP-M/pSpike suggested an increase in immune response specificity and diversity. Additionally, LNP-M effectively delivered DNA-encoded antigens, such as mouse PD-L1 and p53 R172H , or monoclonal antibodies targeting mouse PD1 and human p53 R282W . This approach inhibited tumor growth or metastasis in several mouse models. The long-term anti-tumor effects of LNP-M-delivered anti-p53 R282W antibody relied on memory CD8 + T cell responses and enhanced MHC-I signaling from APCs to CD8 + T cells. These results highlight LNP-M as a promising and effective platform for delivering DNA-based vaccines and cancer immunotherapies., Competing Interests: Declarations. Ethics approval and consent to participate: Animal experimentation was approved by the Institutional Animal Care and Use Committee (IACUC) of Baylor College of Medicine. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Embryonic development and tumor genesis share numerous similarities, with OCT4 standing out as a pivotal transcription factor in embryonic development. Expression of OCT4 is associated with poor prognosis of lung adenocarcinoma. VEGF-correlated chemokine-1 (VCC-1), also known as C-X-C motif chemokine ligand 17 (CXCL17), has been suggested to play a role in promoting tumor angiogenesis and metastasis. In the present study, we show a positive correlation between OCT4 expression levels and tumor metastatic potential, where an increase in OCT4 expression parallels an upregulation of VCC-1 in lung cancer. This relationship was substantiated through DNA microarray analysis and further confirmed by tissue staining of clinical lung cancer samples, demonstrating a positive correlation between OCT4 and VCC-1 expression. In A549 and H1299 human lung cancer cells, modulations in OCT4 expression directly influenced VCC-1 levels, as evidenced by the reporter assay of the VCC-1 promoter, indicating the regulatory role of OCT4 in transactivating VCC-1 expression. Furthermore, enhanced VCC-1 expression in H1299 cells promoted transforming growth factor-β (TGF-β) secretion, contributing to lung cancer cell aggressiveness. Additionally, VCC-1 secretion by H1299 cells could attract THP-1 macrophages, further implicating its role in tumor progression. NOD/SCID mice inoculated with VCC-1-knockdown A549 lung cancer cells exhibited significantly smaller tumors than those inoculated with control cells. On the basis of these findings, we highlight the importance of the OCT4-VCC-1 axis in lung cancer progression. Our findings also provide therapeutic targets for lung cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Topological magnetoelectricity was recently revealed as an emergent topic, which opens a unique route to precisely control magnetoelectric functionality. Here we report the synchronous magnetic-electric-cycle operation of topological magnetoelectric switching in GdMn&#95;{2}O&#95;{5}. Compared with pure magnetic-cycle operation, this topological winding can be accessed in a much broader parameter space, i.e., orientation of the magnetic field is not limited to the magic angle and the effect can persist up to the Curie temperature. The fine-tuning of the free energy landscape is responsible for this topological behavior.

Background: Chronic coronary syndromes (CCS) is a common clinical condition that increases the risk of cardiovascular events at any time. Tongxinluo capsules (TXL) are widely used in China for treating CCS., Objectives: To systematically evaluate the therapeutic effects and safety of adding TXL to Western medical treatment (WM) for CCS., Methods: We searched PubMed, Cochrane Library, CNKI, VIP, and Wanfang databases up to August 2024 for randomized controlled trials (RCTs) investigating the therapeutic effects and safety of combining TXL with WM compared to WM alone for CCS. Data analyses were conducted using RevMan 5.4 software., Results: Twenty studies involving 2091 participants were identified. Evidence supports the use of TXL plus WM for reducing angina frequency [SMD -2.50, 95% CI (-3.53, -1.48)], improving seattle angina questionnaire scores ( P  < 0.05), decreasing nitroglycerin dose [SMD -1.63, 95% CI (-2.26, -1.00)], and shortening angina duration [MD -1.50 min/once, 95% CI (-1.98, -1.02)]. Adding TXL to WM showed a non-significant trend toward reducing myocardial infarction [RR 0.34, 95% CI (0.05, 2.12); NNT = 41] and sudden cardiac death [RR 0.34, 95% CI (0.01, 8.28); NNT = 65]. No increase in adverse events was observed when TXL was added to WM [RR 1.02, 95% CI (0.70, 1.49); NNT = 149]., Conclusions: Our review suggests that TXL may offer additional therapeutic benefits for CCS patients and appears to be safe when combined with WM. Further investigations are warranted to confirm the potential impact of adding TXL to WM for CCS., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42024499031, PROSPERO (CRD42024499031)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025 Liang, Wang, Niu, Li, Zheng, Huan, Yuan, Robinson, Liu and Li.)

The nucleus accumbens-associated protein 1 (NAC1) has recently emerged as a pivotal factor in oncogenesis by promoting glycolysis. Deletion of NAC1 in regulatory T cells (Tregs) has been shown to enhance FoxP3 stability, a suppressor of glycolysis. This study delves into the intriguing dual role of NAC1, uncovering that Treg-specific deletion of NAC1 fosters metabolic fitness in Tregs, thereby promoting tumorigenesis. Our results unveil that NAC1-deficient Tregs exhibited prolonged survival and heightened function, particularly in acidic environments. Mechanistically, we find that NAC1-deficient Tregs adapted to adverse conditions by upregulating FoxP3 expression, engaging in CD36-mediated lipid metabolism, and enhancing peroxisome proliferator-activated receptor gamma coactivator 1-alpha-regulated mitochondrial function. In mouse tumor xenograft models, NAC1-deficient mice demonstrated increased susceptibility to tumor growth. Notably, Tregs lacking NAC1 not only displayed elevated lipid metabolism and mitochondrial fitness but also exhibited enhanced tumoral infiltration. Adoptive Treg transfer experiments further underscored the supportive role of NAC1-deficient Tregs in tumor growth. These findings suggest that modulating NAC1 expression in FoxP3+ Tregs could serve as a promising approach to augment antitumor immunity. Understanding the intricate interplay between NAC1 and Tregs opens avenues for potential therapeutic strategies targeting the tumor microenvironment.

In-sensor computing has emerged as an ultrafast and low-power technique for next-generation machine vision. However, in situ training of in-sensor computing systems remains challenging due to the demands for both high-performance devices and efficient programming schemes. Here, we experimentally demonstrate the in situ training of an in-sensor artificial neural network (ANN) based on ferroelectric photosensors (FE-PSs). Our FE-PS exhibits self-powered, fast (<30 μs), and multilevel (>4 bits) photoresponses, as well as long retention (50 days), high endurance (10 9 ), high write speed (100 ns), and small cycle-to-cycle and device-to-device variations (~0.66% and ~2.72%, respectively), all of which are desirable for the in situ training. Additionally, a bi-directional closed-loop programming scheme is developed, achieving a precise and efficient weight update for the FE-PS. Using this programming scheme, an in-sensor ANN based on the FE-PSs is trained in situ to recognize traffic signs for commanding a prototype autonomous vehicle. Moreover, this in-sensor ANN operates 50 times faster than a von Neumann machine vision system. This study paves the way for the development of in-sensor computing systems with in situ training capability, which may find applications in new data-streaming machine vision tasks., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Severe disruption of lipid metabolism in vivo is one of the central mechanisms in the development of atherosclerotic vascular injury (AVI). Reverse cholesterol transport (RCT) plays a pivotal role in eliminating excess cholesterol, preventing lipid deposition in the aorta, and reducing plaque formation associated with AVI. Floralozone (FL) reduces endothelial cell injury in AVI rats by regulating sphingosine-1-phosphate (S1P) expression. However, FL's potential to prevent AVI by modulating cholesterol metabolism remains unknown., Methods: In this study, network pharmacology and molecular docking predicted FL's potential targets in AVI protection. AVI rats were induced with a high-sugar, high-fat diet and vitamin D3 injection. FL intervention's effects on aortic pathology and lipid levels were assessed. The expression levels of SREBP-1c, PPARγ, ABCA1, and ABCG1 were evaluated. Raw264.7 macrophages were induced to form foam cells with ox-LDL, and FL's effects on the AMPKα/SREBP-1c pathway and miR-33-5p were investigated., Results: FL reduced lipid levels and SREBP-1c expression, increased HDL-C, promoted ABCA1- and ABCG1-mediated cholesterol efflux, and reduced aortic cholesterol accumulation. The AMPKα inhibitor dorsomorphin blocked FL's inhibition of intracellular cholesterol accumulation and SREBP1 down-regulation in foam cells. FL decreased miR-33-5p expression but up-regulated PPARγ, promoting ABCA1- and ABCG1-mediated cholesterol efflux. However, miR-33-5p mimic reduced FL-induced cholesterol efflux, while miR-33-5p inhibitor increased it., Conclusion: FL may promote foam cell cholesterol efflux by modifying the AMPKα/SREBP-1c pathway and down-regulating miR-33-5p, which targets cholesterol metabolism genes (PPARγ, ABCA1, and ABCG1). These findings provide a new insight into the protective effect of FL on AVI., Competing Interests: Declarations. Ethics approval and consent to participate: The animal protocol was approved by the Animal Care and Use Committee of Xinxiang Medical University. This article does not contain any studies with human participants performed by any of the authors. Consent for publication: All authors approved its publication. Competing interests: The authors declare that they have no conflict of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Chronic kidney disease (CKD) is a significant global health problem associated with high morbidity and mortality rates. Traditional Chinese Medicine (TCM) utilizes tongue diagnosis to differentiate symptoms and predict prognosis. This study examines the relationship between tongue characteristics and CKD severity using an automatic tongue diagnosis system (ATDS), which captures tongue images non-invasively to provide objective diagnostic information., Methods: This cross-sectional, case-control study was conducted from July 1, 2019, to December 31, 2021. Participants were divided into three groups based on estimated glomerular filtration rate (eGFR): control (eGFR > 60 ml/min/1.732), CKD stage 3 (30 ≤ eGFR < 60 ml/min/1.732), and CKD stage 4-5 (eGFR < 30 ml/min/1.732). Tongue images were analyzed using ATDS to extract nine primary features: tongue shape, color, fur, saliva, fissures, ecchymosis, tooth marks, and red dots. Statistical analyses included non-parametric methods and ordinal logistic regression., Results: This study revealed that significant differences in the fur thickness, tongue color, amount of ecchymosis, and saliva among three groups. Ordinal logistic regression indicated that pale tongue color (OR: 2.107, P < 0.001), bluish tongue color (OR: 2.743, P = 0.001), yellow fur (OR: 3.195, P < 0.001), wet saliva (OR: 2.536, P < 0.001), and ecchymoses (OR: 1.031, P = 0.012) were significantly associated with increased CKD severity. Additionally, each red dot and tooth mark decreased the odds of severe CKD., Conclusion: Tongue features such as paleness, wet saliva, yellow fur, and ecchymosis are prevalent in CKD patients and can serve as early clinical indicators of the disease. This study demonstrates that TCM tongue diagnosis, facilitated by ATDS, is a valuable, non-invasive method for identifying CKD and distinguishing its stages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Hsu, Chen, Chang, Chang, Chiu, Chiang and Lo.)

In this paper, we demonstrated a novel bidirectional high-speed transmission system integrating a free-space optical (FSO) communication with a 5G wireless link, utilizing a high-power erbium-doped fibre amplifier (EDFA) for enhanced loss compensation. The system supports downlink rates of 1-Gb/s/4.5-GHz and 10-Gb/s at 24-GHz and 39-GHz, and an uplink rate of 10-Gb/s/28-GHz. The high-power EDFA boosts signal strength, facilitating reliable long-distance transmission through the FSO transmission link while compensating for losses and reducing bit error rates (BER) and error vector magnitude (EVM). Fibre Bragg grating sensors are employed as wavelength selectors for both downlink and uplink, offering a simpler, cost-effective solution compared to previously utilized reflective semiconductor optical amplifiers and multiple laser sources. The system successfully transmits 16-quadrature amplitude modulation orthogonal frequency division multiplexing signals across various carrier frequencies, achieving total data rates of 21-Gb/s for downlink and 30-Gb/s for uplink across a 1.6-km FSO transmission link integrated with 10/15-m 5G links. Performance metrics, including low EVM and BER, and well-defined constellation patterns, indicate the reliability and effectiveness of the system. This bidirectional FSO-5G wireless communication system offers a high-speed and cost-effective solution for extending 5G coverage in both densely and sparsely populated areas., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/purpose: We aimed to assess the effects of Helicobacter pylori (H. pylori) eradication on the rebound of reflux-related symptoms among gastroesophageal reflux disease (GERD) patients., Methods: This prospective randomized study recruited patients with typical reflux symptoms and reflux esophagitis on esophagogastroduodenoscopy (NCT02934152). Patients positive for H. pylori via a urea breath test (UBT) were randomly assigned to receive bacterial eradication with triple therapy for 2 weeks either before or after proton-pump inhibitor (PPI) treatment for 4 weeks. Follow-up was implemented with serial GerdQ evaluation and a subsequent UBT. The primary outcome was the incidence rates of symptom rebound between patients with and without H. pylori infection. The secondary outcomes included the severity of symptom rebound, incidence rates of symptom rebound, and successful eradication rates between the early and late eradication groups., Results: A total of 248 patients were enrolled, of whom 107 (43.1%) tested positive for H. pylori infection. All patients with and without concurrent H. pylori infection had significant symptom improvement over the entire treatment. Patients with H. pylori infection had significantly lower rates of symptom rebound (19.8% vs. 34.2%, p = 0.034) and rebound severity (1.8 ± 0.7 vs. 2.8 ± 1.6, p = 0.031) 4 weeks after eradication and PPI treatment than those without. The incidence rates of symptom rebound and successful eradication rates were not significantly different between the early and late eradication groups., Conclusions: GERD patients with concurrent H. pylori infection were less susceptible to symptom rebound after H. pylori eradication compared to those without., Trial Registration: ClinicalTrial.gov (NCT02934152)., (© 2025 John Wiley & Sons Ltd.)

Tetrabromobisphenol A (TBBPA), a brominated flame retardant (BFR), has been implicated as the neurotoxic effects in mammalian. However, the exact mechanisms underlying TBBPA-induced neurotoxicity remain unclear. In the present study, Neuro-2a cells, a mouse neural crest-derived cell line, were used to examine the mechanism of TBBPA-induced neuronal cytotoxicity. TBBPA exposure caused alterations in cell viability and mitochondrial membrane potential (MMP) and induction of apoptotic events, such as increased apoptotic cell population and cleaved caspase-3, -7, -9, and poly (ADP-ribose) polymerase (PARP) protein expression). TBBPA exposure triggered CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) activation. Transfection with CHOP-specific small interfering RNA (siRNA) obviously prevented the expression of CHOP protein and markedly attenuated MMP loss, and caspase-3 and -7 activation in TBBPA-exposed Neuro-2a cells. In addition, TBBPA exposure significantly evoked the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular-signal regulated kinase1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38-MAPK), and AMP-activated protein kinase (AMPK)α proteins. Pretreatment of cells with pharmacological inhibitors of p38-MAPK (SB203580) and AMPK (compound C), but not inhibitors of JNK (SP600125) or ERK1/2 (PD98059), effectively prevented the increase in caspase-3 activity, MMP loss, and activated CHOP and cleaved caspase-3 and -7 protein expression in TBBPA-treated cells. Notably, transfection with either p38α-MAPK- or AMPKα1/2-specific siRNAs markedly attenuated the expression of CHOP, and cleaved caspase-3 and -7. Interestingly, transfection with each siRNA significantly reduced the TBBPA-induced phosphorylation of p38-MAPK and AMPKα proteins. Collectively, these findings suggest that CHOP activation-mediated mitochondria-dependent apoptosis contributes to TBBPA-induced neurotoxicity. An interdependent p38-MAPK and AMPKα signaling-regulated apoptotic pathway may provide new insights into the mechanism understanding TBBPA-elicited neurotoxicity., 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.)

Objective: This study aimed to examine decisional conflict and identify its predictors in Chinese pregnant women who were making decisions about further prenatal testing after receiving a screening result of high-risk for Down syndrome., Method: A cross-sectional study was conducted from September 2020 to July 2021 in Guangzhou, China. Two-hundred and sixty pregnant women receiving a screening result of high-risk for Down syndrome completed a questionnaire comprising the Decisional Conflict Scale, Self-rating Anxiety Scale, and Social Support Rating Scale., Results: The mean decisional conflict score was 28.8 ± 13.6, representing a moderate level. Advanced age (≥35 years), having a religious belief, not knowing about non-invasive or invasive prenatal testing, choosing NIPT for further prenatal testing, high levels of anxiety, and low levels of social support were significant predictors of decisional conflict, explaining 28.4% of its variance (F = 18.115, p  < 0.001)., Conclusions: The results highlighted the necessity of assessing patients' decisional conflict and providing adequate interventions along the prenatal care trajectory. The results also showed that providing good support has an essential value for women by relieving their decisional conflict.

Background: Reconstruction of significant soft tissue defects in the head and neck region after resection of extensive plexiform neurofibromas, as well as preservation and restoration of cosmetic and functional aspects, presents a considerable challenge., Aims: The purpose is to evaluate the feasibility of eTMF in repairing substantial defects after the complete resection of NF1 PN., Patients and Methods: Patients diagnosed with substantial neurofibromatosis (NP) type 1 (NF1), according to the revised criteria, underwent complete resection and remodeling of the facial aesthetic unit. An extended vertical lower trapezius island myocutaneous flap (eTIMF) was used for the defect reconstruction. Perioperative complications were evaluated using the Clavien-Dindo classification. ECOG PS was assessed. Postoperative follow-up at 6 months and completion of UW-QOL. The questionnaire included swallowing, chewing, speech, and quality of life scores. Two patients had pathogenic missense variants: c.5609G>A (p.Arg1870Gln) in exon 38 of NF1 in the first case, and c.4600C>T (p.Arg1534*) in exon 35 in the second case., Results: Two eTMFs were harvested successfully. Five facial esthetic units were remodeled, and 4 units were remodeled. Two extensive tumors were nearly entirely removed. No severe complications were noted. The ECOG PS improved from grade 3 in the first week postsurgery to grade 0 by the eighth week. The UW-QOL results indicated that swallowing, chewing, and speaking functions returned to their preoperative levels, with a 40% improvement in quality of life, reaching 60% and 80%, respectively., Conclusions: eTMF to repair substantial defects following total resection of NF1 PN and facial esthetic unit remodeling enhances appearance, function, and psychosocial outcomes. This technique is safe, efficient, resource-conserving, and simple to implement., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Obtaining the high-resolution distribution characteristics of urban air pollutants is crucial for effective pollution control and public health. In order to fulfill it, mobile monitoring offers a novel and practical approach compared to traditional fixed monitoring methods. However, the sparsity of mobile monitoring data still makes it a challenge to recover the high-resolution pollutant concentration across an entire area. To tackle the sparsity issue and fulfill a prediction of the spatiotemporal distribution of PM 2.5 , a high-resolution urban PM 2.5 prediction method was proposed based on mobile monitoring data in this study. This method enables prediction with a spatial resolution of 500m × 500m and a temporal resolution of 1 h. First, a Light Gradient Boosting Machine (LightGBM) was trained using mobile monitoring of PM 2.5 concentration and exogenous features to obtain complete spatiotemporal PM 2.5 concentration. Second, a model consisting of Convolutional Neural Network and Transformer (CNN-Transformer) with a customised loss function was established to predict high-resolution PM 2.5 concentration based on complete spatiotemporal data. The method was validated using real-world data collected from Cangzhou, China. The numerical results from cross-validation showed an R 2 of 0.925 for imputation and 0.887 for prediction, demonstrating this method is suitable for high-resolution spatiotemporal prediction of PM 2.5 concentration based on mobile monitoring data., 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.)