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Photocatalysis has high potential in the cleavage of C β -O bond in lignin into high-value aromatic monomers; however, the inefficient C α -H bond activation in lignin and a low hydrogen transfer efficiency on the photocatalyst's surfaces have limited its application in photocatalytic lignin conversion. This study indicates that the cleavage of the C β -O bond can be improved by the generation of the C α radical intermediate through C α -H bond activation, and the formation of desirable aromatic products can be significantly improved by the enhanced hydrogen transfer efficiency from photocatalyst surfaces to aromatic monomeric radicals. We elaborately designed the half-unit-cell MoS 2 /ZnIn 2 S 4 monolayer with a thickness of ∼1.7 nm to promote the hydrogen transfer efficiency on the photocatalyst surfaces. The ultrathin structure can shorten the diffusion distance of charge carriers from the interior to the surfaces and tight interface between MoS 2 and ZnIn 2 S 4 to facilitate the migration of photogenerated electrons from ZnIn 2 S 4 to MoS 2 , therefore improving the selectivity of desirable products. The adsorbed hydroxyl radical (*OH) on the surfaces of MoS 2 /ZnIn 2 S 4 from water oxidation can significantly reduce the bond dissociation energy (BDE) of C α -H bond in PP-ol from 2.38 to 1.87 eV, therefore improving the C α -H bond activation. The isotopic experiments of H 2 O/D 2 O indicate that the efficiency of *OH generation is an important step in C α -H bond activation for PP-ol conversion to aromatic monomers. In summary, PP-ol can completely convert to 86.6% phenol and 82.3% acetophenone after 1 h of visible light irradiation by using 3% MoS 2 /ZnIn 2 S 4 and the assistance of *OH, which shows the highest conversion rate compared to previous works.

The vessel-wall-volume (VWV) measured based on three-dimensional (3D) carotid artery (CA) ultrasound (US) images can help to assess carotid atherosclerosis and manage patients at risk for stroke. Manual involvement for measurement work is subjective and requires well-trained operators, and fully automatic measurement tools are not yet available. Thereby, we proposed a fully automatic VWV measurement framework (Auto-VWV) using a CA prior-knowledge embedded U-Net (CAP-UNet) to measure the VWV from 3D CA US images without manual intervention. The Auto-VWV framework is designed to improve the repeated VWV measuring consistency, which resulted in the first fully automatic framework for VWV measurement. CAP-UNet is developed to improve segmentation accuracy on the whole CA, which composed of a U-Net type backbone and three additional prior-knowledge learning modules. Specifically, a continuity learning module is used to learn the spatial continuity of the arteries in a sequence of image slices. A voxel evolution learning module was designed to learn the evolution of the artery in adjacent slices, and a topology learning module was used to learn the unique topology of the carotid artery. In two 3D CA US datasets, CAP-UNet architecture achieved state-of-the-art performance compared to eight competing models. Furthermore, CAP-UNet-based Auto-VWV achieved better accuracy and consistency than Auto-VWV based on competing models in the simulated repeated measurement. Finally, using 10 pairs of real repeatedly scanned samples, Auto-VWV achieved better VWV measurement reproducibility than intra- and inter-operator manual measurements.

Most computational methods for predicting driver mutations have been trained using positive samples, while negative samples are typically derived from statistical methods or putative samples. The representativeness of these negative samples in capturing the diversity of passenger mutations remains to be determined. To tackle these issues, we curated a balanced dataset comprising driver mutations sourced from the COSMIC database and high-quality passenger mutations obtained from the Cancer Passenger Mutation database. Subsequently, we encoded the distinctive features of these mutations. Utilizing feature correlation analysis, we developed a cancer driver missense mutation predictor called CDMPred employing feature selection through the ensemble learning technique XGBoost. The proposed CDMPred method, utilizing the top 10 features and XGBoost, achieved an area under the receiver operating characteristic curve (AUC) value of 0.83 and 0.80 on the training and independent test sets, respectively. Furthermore, CDMPred demonstrated superior performance compared to existing state-of-the-art methods for cancer-specific and general diseases, as measured by AUC and area under the precision-recall curve. Including high-quality passenger mutations in the training data proves advantageous for CDMPred's prediction performance. We anticipate that CDMPred will be a valuable tool for predicting cancer driver mutations, furthering our understanding of personalized therapy., Competing Interests: The authors declare there are no competing interests., (©2024 Wang et al.)

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Plastic waste has caused a global environmental crisis. Biocatalytic depolymerization mediated by enzymes has emerged as an efficient and sustainable alternative for plastic treatment and recycling. However, it is challenging and time-consuming to discover novel plastic-degrading enzymes using conventional cultivation-based or omics methods. There is a growing interest in developing effective computational methods to identify new enzymes with desirable plastic degradation functionalities by exploring the ever-increasing databases of protein sequences. In this study, we designed an innovative machine learning-based framework, named PEZy-Miner, to mine for enzymes with high potential in degrading plastics of interest. Two datasets integrating information from experimentally verified enzymes and homologs with unknown plastic-degrading activity were created respectively, covering eleven types of plastic substrates. Protein language models and binary classification models were developed to predict enzymatic degradation of plastics along with confidence and uncertainty estimation. PEZy-Miner exhibited high prediction accuracy and stability when validated on experimentally verified enzymes. Furthermore, by masking the experimentally verified enzymes and blending them into homolog dataset, PEZy-Miner effectively concentrated the experimentally verified entries by 14∼30 times while shortlisting promising plastic-degrading enzyme candidates. We applied PEZy-Miner to 0.1 million putative sequences, out of which 27 new sequences were identified with high confidence. This study provided a new computational tool for mining and recommending promising new plastic-degrading enzymes., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V. on behalf of International Metabolic Engineering Society.)

LRRK2 contains a kinase domain where both the N2081D Crohn's disease (CD) risk and the G2019S Parkinson's disease (PD)-pathogenic variants are located. The mechanisms by which the N2081D variant increase CD risk, and how these adjacent mutations result in distinct diseases, remain unclear. To investigate the pathophysiology of the CD-linked LRRK2 N2081D variant, we generated a knock-in (KI) mouse model and compared its effects to those of the LRRK2-G2019S mutation. We find that Lrrk2 N 2081 D KI mice demonstrate heightened sensitivity to induced colitis, resulting in more severe inflammation and intestinal damage than Lrrk2 G2019S KI and wild-type mice. Analysis of Colon tissue revealed distinct mutation-dependent LRRK2 RAB substrate phosphorylation, with significantly elevated phosphorylated RAB10 levels in Lrrk2 N2081D mice. In cells, we demonstrate that the N2081D mutation activates LRRK2 through a mechanism distinct from that of LRRK2-G2019S. We further find that proinflammatory stimulation enhances LRRK2 kinase activity, leading to mutation-dependent differences in RAB phosphorylation and inflammatory responses in dendritic cells. Finally, we show that genetic knockout of Rab12 , but not pharmacological LRRK2 kinase inhibition, significantly reduced colitis severity in Lrrk2 N2081D mice. Our study characterizes the pathogenic mechanisms of LRRK2-linked CD, highlights important structural and functional differences between disease-associated LRRK2 variants, and suggests RAB proteins as promising therapeutic targets for modulating LRRK2 activity in CD treatment.

Purpose: To investigate the value of multi-parametric MRI-based radiomics for preoperative prediction of lung metastases from soft tissue sarcoma (STS)., Methods: In total, 122 patients with clinicopathologically confirmed STS who underwent pretreatment T1-weighted contrast-enhanced (T1-CE) and T2-weighted fat-suppressed (T2FS) MRI scans were enrolled between Jul. 2017 and Mar. 2021. Radiomics signatures were established by calculating and selecting radiomics features from the two sequences. Clinical independent predictors were evaluated by statistical analysis. The radiomics nomogram was constructed from margin and radiomics features by multivariable logistic regression. Finally, the study used receiver operating characteristic (ROC) and calibration curves to evaluate performance of radiomics models. Decision curve analyses (DCA) were performed to evaluate clinical usefulness of the models., Results: The margin was considered as an independent predictor (p < 0.05). A total of 4 MRI features were selected and used to develop the radiomics signature. By incorporating the margin and radiomics signature, the developed nomogram showed the best prediction performance in the training (AUCs, margin vs. radiomics signature vs. nomogram, 0.609 vs. 0.909 vs. 0.910) and validation (AUCs, margin vs. radiomics signature vs. nomogram, 0.666 vs. 0.841 vs. 0.894) cohorts. DCA indicated potential usefulness of the nomogram model., Conclusions: This feasibility study evaluated predictive values of multi-parametric MRI for the prediction of lung metastasis, and proposed a nomogram model to potentially facilitate the individualized treatment decision-making for STSs., (© 2024. The Author(s).)

The particle size distribution in tailings notably influences their physical properties and behavior. Despite this, our understanding of how the distribution of tailings particle sizes impacts in situ pollution and ecological remediation in in-situ environment remains limited. In this study, an iron tailings reservoir was sampled along a particle flow path to compare the pollution characteristic and microbial communities across regions with different particle sizes. The results revealed a gradual reduction in tailings particle size along the flow direction. The predominant mineral composition shifts from minerals such as albite and quartz to layered minerals. Total nitrogen, total organic carbon, and total metal concentrations increased, whereas the acid-generating potential decreased. The region with the finest tailings particle size exhibited the highest microbial diversity, featuring metal-resistant microorganisms such as KD4-96, Micrococcaceae, and Acidimicrobiia. Significant discrepancies were observed in tailings pollution and ecological risks across different particle sizes. Consequently, it is necessary to assess tailings reservoirs pollution in the early stages of remediation before determining appropriate remediation methods. These findings underscore that tailings particle distribution is a critical factor in shaping geochemical characteristics. The responsive nature of the microbial community further validated these outcomes and offered novel insights into the ecological remediation of tailings., 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.)

Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body., 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.)

Grain and flag leaf size are two important agronomic traits that influence grain yield in rice (Oryza sativa). Many quantitative trait loci (QTLs) and genes that regulate these traits individually have been identified, however, few QTLs and genes that simultaneously control these two traits have been identified. In this study, we conducted a genome-wide association analysis in rice and detected a major locus, WIDTH OF LEAF AND GRAIN (WLG), that was associated with both grain and flag leaf width. WLG encodes a RING-domain E3 ubiquitin ligase. WLGhap.B, which possesses five single nucleotide polymophysim (SNP) variations compared to WLGhap.A, encodes a protein with enhanced ubiquitination activity that confers increased rice leaf width and grain size, whereas mutation of WLG leads to narrower leaves and smaller grains. Both WLGhap.A and WLGhap.B interact with LARGE2, a HETC-type E3 ligase, however, WLGhap.B exhibits stronger interaction with LARGE2, thus higher ubiquitination activity toward LARGE2 compared with WLGhap.A. Lysine1021 is crucial for the ubiquitination of LARGE2 by WLG. Loss-of-function of LARGE2 in wlg-1 phenocopies large2-c in grain and leaf width, suggesting that WLG acts upstream of LARGE2. These findings reveal the genetic and molecular mechanism by which the WLG-LARGE2 module mediates grain and leaf size in rice and suggest the potential of WLGhap.B in improving rice yield., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems 1,2 . However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications 3,4 . Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine., (© 2024. The Author(s).)

Background: Atopic dermatitis (AD) is a prevalent chronic inflammatory and highly pruritic skin condition characterized by the infiltration of immune cells, notably eosinophils and mast cells. Mast cells (MCs) critically participate in the complex pathogenesis of AD through multiple pathways and have recently garnered growing attention in research. Despite the abundance of related studies published over the years, a comprehensive bibliometric analysis on this topic remains lacking., Objective: Our objective was to perform an up-to-date bibliometric analysis of the literature focusing on the relationship between MCs and AD. This analysis would provide valuable insights through a thorough bibliometric review, enabling a clearer understanding of the current research landscape, pinpointing key studies, and detecting emerging trends within this field., Methods: We searched the Web of Science Core Collection (WoSCC) database on 15 July 2024. The data retrieval strategy was structured as follows: #1: TS = ("mast cells") OR TS = ("mast cell") OR TS = ("mastocyte"); #2: TS = ("atopic dermatitis") OR TS = ("atopic eczema") Final data: (#1 AND #2). A total of 2272 items published between 2001 and 2024 were included. Several scientometric visualization tools, including VOSviewer, R-bibliometrix, CiteSpace and an online analytical platform, were utilized to conduct text mining and to visualize the bibliometric data, facilitating a comprehensive analysis of research trends and patterns., Results: Out of the initial 2272 articles retrieved, 2168 were selected for analysis after applying inclusion and exclusion criteria based on publication type. The findings indicate a steady and substantial exponential growth in the annual number of publications focused on the relationship between over the years. The South Korea (547/2168), USA (465/2168) and Japan (436/2168) were the major contributors within this field, collectively constituting more than half of the total publications. To clarify the underlying mechanisms and role of MCs in the pathogenesis of AD and to make MCs prime targets for therapeutic intervention have garnered the most attention in this field. According to references analysis, the research emphasis has shifted to developing MC-related therapeutics and intervention and regulating the immune system of AD patients through modulating the activity of various immune cells. On the basis of keywords analysis, we outlined the following research frontiers and hotpots in the future: the role of oxidative stress in the pathogenesis; imbalance in the different types of T helper (Th) cells during immune response; skin barrier and barrier dysfunction; improving quality of life; sensory neurons; biological agents and small-molecule drugs. Furthermore, IL-13, IL-4, NFKB1, BCGF-1 and CD4 ranked as the top five genes that have received the most investigative attention in the intersection of MCs and AD., Conclusion: In a word, this analysis would greatly benefit from a thorough bibliometric review to gain a deeper understanding of the current research landscape, identify pivotal studies and pinpoint emerging trends in the field of MCs and AD. Meanwhile, our findings offered researchers a holistic perspective of ongoing developments, serving as a valuable resource for guiding future research and informing decision-making for both researchers and policymakers in this area., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies has demonstrated efficacy in multiple tumor types. Nofazinlimab is a humanized rat antibody targeting PD-1. A first-in-human study of nofazinlimab conducted in Australia found no dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) was not reached in the range of 1-10 mg/kg., Objective: We evaluated nofazinlimab for multiple advanced malignancies in Chinese patients., Patients and Methods: This was a phase 1a/1b, open-label, multicenter, dose-escalation/expansion trial. In phase 1a, patients received an abbreviated dose escalation of nofazinlimab at 60 mg and 200 mg every 3 weeks (Q3W) to determine DLTs and the recommended phase 2 dose (RP2D). In phase 1b, patients received the RP2D (monotherapy/combination) in six arms by tumor type; DLTs were evaluated for nofazinlimab plus lenvatinib in the unresectable hepatocellular carcinoma (uHCC) arm. Safety (continuously monitored in patients who received nofazinlimab) and efficacy (patients with measurable baseline disease) were assessed., Results: Overall, 107 patients were eligible and received nofazinlimab. In phase 1a, no DLTs were observed; the RP2D was 200mg Q3W. In phase 1b, no DLTs were observed with nofazinlimab plus lenvatinib. The safety profile was consistent with that observed in the first-in-human study (NCT03475251). In phase 1b, 21/88 (23.9%) patients achieved confirmed objective responses, 26 (29.5%) had stable disease, and 9/20 (45.0%) patients with uHCC achieved confirmed objective responses to nofazinlimab plus lenvatinib., Conclusions: Nofazinlimab was well tolerated in Chinese patients. Preliminary efficacy was encouraging, particularly for nofazinlimab plus lenvatinib in uHCC, which is being studied in an ongoing phase 3 trial., Clinical Trial Registration: NCT03809767; registered 18 January 2019., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study investigated the causal enhancing effect of transcranial photobiomodulation (tPBM) over the left inferior frontal gyrus (LIFG) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention via LIFG, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM for linear processing of unstructured sequences and visual WM performances; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

High-magnetization materials play crucial roles in various applications. However, the past few decades have witnessed a stagnation in the discovery of new materials with high magnetization. In this work, Ni/NiO nanocomposites are fabricated by depositing Ni and NiO thin layers alternately, followed by annealing at specific temperatures. Both the as-deposited samples and those annealed at 373 K exhibit low magnetization. However, the samples annealed at 473 K exhibit a significantly enhanced saturation magnetization exceeding 607 emu cm -3 at room temperature, surpassing that of pure Ni (480 emu cm -3 ). Material characterizations indicate that the composite comprises NiO nanoclusters of size 1-2 nm embedded in the Ni matrix. This nanoclustered NiO is primarily responsible for the high magnetization, as confirmed by density functional theory calculations. The calculations also indicate that the NiO clusters are ferromagnetically coupled with Ni, resulting in enhanced magnetization. This work demonstrates a new route toward developing artificial high-magnetization materials using the high magnetic moments of nanoclustered antiferromagnetic materials., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

Negative emotional states, such as anxiety and depression, pose significant challenges in contemporary society, often stemming from the stress encountered in daily activities. Stress (state or level) recognition is a crucial prerequisite for effective stress management and intervention. Presently, wearable devices have been employed to capture physiological signals and analyze stress states. However, their constant skin contact can lead to discomfort and disturbance during prolonged monitoring. In this paper, a peak attention-based multitasking framework is presented for non-contact stress recognition. The framework extracts rPPG signals from RGB facial videos, utilizing them as inputs for a novel multi-task attentional convolutional neural network for stress recognition (MTASR). It incorporates peak detection and HR estimation as auxiliary tasks to facilitate stress recognition. By leveraging multi-task learning, MTASR can utilize information related to stress physiological responses, thereby enhancing feature extraction efficiency. For stress recognition, two binary classification tasks are applied: stress state recognition and stress level recognition. The model is validated on the UBFC-Phys public dataset and demonstrates an accuracy of 94.33% for stress state recognition and 83.83% for stress level recognition. The proposed method outperforms the dataset's baseline methods and other competing approaches.

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality and significantly impairs quality of life. Astragali Radix-Curcumae Rhizoma (AC) is widely employed in the treatment of CRC in Chinese medicine, but the precise mechanisms remain unclear., Purpose: This study aimed to elucidate the mechanisms by which AC inhibits CRC progression., Methods: The active components of AC were identified using UPLC-MS/MS analysis. An orthotopic transplantation colorectal tumor model was established in BALB/c mice using the CT26-Lucifer cell line to evaluate the effects of AC. Tumor volumes were monitored using IVIS imaging technology. Histological examination of tumor morphology was performed with hematoxylin and eosin (H&E) staining. Transcriptomic sequencing of mouse tumor samples was conducted to identify critical pathways and molecular targets. The impact of AC on cell viability and migration was assessed using CCK-8 and wound healing assays, respectively. To investigate the effects of AC on CRC cells, an in vitro hypoxic model was established using cobalt chloride (CoCl 2 ), a hypoxia inducer. HIF-2α overexpression was achieved by constructing stable lentiviral vectors. Key targets identified from RNA-seq, such as c-Myc, Ki-67, β-catenin, cleaved caspase 3, CD133, and CD44, were evaluated using western blotting, qRT-PCR, and immunofluorescence assays. Epithelial-Mesenchymal Transition (EMT) and spheroid cloning assays were employed to evaluate phenotypic changes in cancer stem cells., Results: Twelve components of AC were identified. AC effectively inhibited CRC progression in vivo. Transcriptomic analysis highlighted hypoxic signaling as a significantly enriched pathway, implicating its role in suppressing CRC progression by AC. In the hypoxic model, AC inhibited the proliferation and migration of CRC cells in vitro. Furthermore, AC reduced cancer stemness by downregulating stemness markers, inhibiting EMT, and decreasing tumor sphere formation. The downregulation of hypoxic responses and the shift in stemness by AC involved attenuation of HIF-2α and WNT/β-catenin signaling., Conclusion: This study provides the first evidence that AC reduces the stemness of CRC and the inhibition of the transition of CRC to stem-like cells by AC is closely related to the downregulation of the HIF-2α/β-catenin pathway, especially under hypoxic conditions., 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 GmbH. All rights reserved.)

Oil adulteration is a global challenge in the production of high value-added natural oils. Raman spectroscopy combined with mathematical modeling can be used for adulteration detection of camellia oil (CAO). In this study, the advantages of traditional chemometrics and deep learning methods in identifying and quantifying adulterated CAO were compared from a statistical perspective, and no significant difference were founded in the identification of CAO at different levels of adulteration. The recognition rate of pure and adulterated CAO was 100 %, but there were misclassifications among different adulterated CAOs. The deep learning models outperformed chemometrics methods in quantitative prediction of adulteration level, with R P 2 , RMSEP, and RPD of the optimal ConvLSTM model achieved 0.999, 0.9 % and 31.5, respectively. The classifiers and models developed in this study based on deep learning have wide applicability and reliability, and provide a fast and accurate method for adulteration detection in CAO., 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.)

Objective: Developing machine learning (ML) models to predict cognitive impairment among Medicare beneficiaries in the United States., Methods: This retrospective study used the 2016-2019 Medicare Current Beneficiary Survey Cost and Use and Survey Public Use Files. Medicare beneficiaries aged 65 and older (n=4,965) with at least two consecutive years' data were included. Cognitive impairment was categorized into three stages: severe, moderate, and none based on self-reported data. Baseline year's demographic, socioeconomic factors, self-reported functional limitations, health status and comorbidities, number of concurrent medications, level of social engagement, behavioral variables, and satisfaction of medical care's quality were features assessed in ML algorithms to predict next years' cognitive function. ML models in six major categories were developed, tested, and compared (accuracy, AUC, and F1 score) using Python version 3.11. The importance of features was evaluated using the total reduction of the Gini. A subgroup analysis was conducted among beneficiaries who were 80 years and older., Results: Approximately 11.1% of beneficiaries aged ≥ 65 had moderate or severe cognitive function impairment. Baseline cognitive function was the most significant predictor for next year's cognitive function impairment, followed by baseline IADL, level of social activities, ADL, general health status, income, age, education, region of residence, and body mass index. Beneficiaries 80 years and older had satisfaction of medical care's quality among the top 10 most significant predictors., Conclusions: Older adults' baseline cognitive function and IADL were top two predictors of cognitive function impairment. Clinicians should regularly screen and monitor older adults' cognitive and daily function., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phthalates, particularly butyl benzyl phthalate (BBP), are ubiquitous environmental contaminants with potential neurotoxic effects. However, their impact on soil organisms, especially earthworms (Eisenia fetida), remains poorly understood. The current study investigated the neurotoxic effects of BBP on Eisenia fetida in artificial and red soils using an integrated approach combining biochemical assays, metabolomics, and molecular docking. Earthworms were exposed to 0, 1, and 10 mg kg -1 BBP for 14 and 28 days. Biochemical assays revealed significant increases in oxidative stress markers and disruptions in neurotransmission-related enzyme activities. Metabolomic analysis of the cerebral ganglia identified alterations in energy metabolism, lipid metabolism, and neuroactive ligand-receptor interaction signaling pathways. Molecular docking studies corroborated these findings, showing strong interactions between BBP and essential neuronal proteins, particularly the sodium pump. The integration of these data suggests that BBP-induced neurotoxicity in Eisenia fetida is primarily mediated by calcium signaling pathway dysfunction and calcium homeostasis imbalance. Notably, neurotoxic effects were more pronounced in red soil than in artificial soil, highlighting the importance of considering soil type in ecotoxicological assessments. The current study provides novel insights into the mechanisms of BBP-induced neurotoxicity in soil invertebrates and underscores the potential ecological risks associated with phthalate contamination in agricultural environments., 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: Present regulations regarding the management and recycling of spent Lithium-ion batteries (LIBs) are inadequate, which may lead to the pollution of lithium (Li) and heavy metals in water and soil during the informal disposal of such batteries. To comprehend the distribution of toxic metals within spent LIBs and contaminated environmental media, precise analytical methods for toxic metals in these materials are crucial. However, due to the chemical complexity of LIBs materials (e.g., lithium iron phosphate, graphite, separators, and electrolytes), there is still a lack of research on developing and validating analytical techniques for toxic metals in LIB materials across various environmental media., Results: This study establishes a comprehensive and highly precise analytical method for assessing toxic metal constituents in LIBs across various complex media, including sewage, soil, and biological matrices. We assessed the selection of digestion solutions for different LIB materials and identified the most suitable internal standard elements in the mass spectrometric analysis workflow. The devised digestion schemes for all components of LIBs are as follows: aqua regia for all cathode materials (excluding LiMn 0.6 Fe 0.4 PO 4 (LMFP)), nitric acid for diaphragm materials, aqua regia with hydrofluoric acid for the anode material Li 4 Ti 5 O 12 (LTO), and NaOH fusion for graphite and LMFP. LiPF 6 electrolyte can be directly dissolved in ultrapure water. By employing this method, the analysis of cathode materials of LIBs within diverse environmental matrices (sewage, soil, plants, animals) yields recovery rates ranging from 83.6 % to 115.5 %. Furthermore, this research reveals the remarkable accumulation of Li and heavy metals in anode (graphite) of spent LIBs., Significance: This is the first to develop and validate analytical techniques for toxic metals in LIB materials across various environmental media, incorporating both acid digestion and alkaline fusion techniques. This methodology offers comprehensive support for conducting environmental risk assessments of spent LIBs. Using this method, the research elucidates the occurrence characteristics of toxic metals within different parts of commercial spent LIBs, providing valuable insights to enhance recycling efforts and facilitate risk management of spent LIBs., 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.)

Purpose: A growing body of evidence has elucidated that the gut microbiota has a crucial impact on the pathophysiological process of atopic diseases. Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is a local atopic disease of the systemic immune response. Alterations in the gut microbiome in eCRSwNP patients remain largely undefined., Methods: 16S rRNA gene sequencing was performed in a cross-sectional study of 17 eCRSwNP patients, 9 noneCRSwNP patients and 13 healthy controls, and gut microbiota DNA sequencing between each pair of groups was compared using bioinformatic methods., Results: Compared with that of healthy controls, the gut microbiomes of eCRSwNP patients were characterised by a distinct overall microbial composition. However, no significant differences were found in the alpha diversity of the gut microbiota between patients and healthy controls. The distinct differences in microbial composition were significantly correlated with the severity of disease. At the genus level, the abundance of Faecalibacterium positively correlated with Lund-Mackay CT scores. Similarly, the abundance of Turicibacter positively correlated with the percentage of tissue eosinophils., Conclusions: We found alterations in the gut microbiome in eCRSwNP patients, and the alterations in the gut microbiome were correlated with the severity of disease., Competing Interests: Declarations Conflict of interest The authors declare that they have no competing interests. Ethical approval and consent to participate This study was approved by the Institutional Review Board of the Tianjin First Central Hospital, Tianjin, China (Approval number. 2021N037KY). This study was performed in accordance with the relevant guidelines and regulations. Written informed consent was obtained from all participants. all participants agreed to publish their data. Consent for publication Not applicable., (© 2024. The Author(s).)

Introduction: The platelet fluorescent counting (PLT-F) method is utilized as a reflex test method following the initial test of the platelet impedance counting (PLT-I) method in clinical practice on the Sysmex XN-series automated hematology analyzer. Our aim is to establish reflex test rules for the PLT-F method by combining multiple parameters provided by the "CBC + DIFF" mode of the Sysmex XN-series automated hematology analyzer., Methods: We tested 120 samples to evaluate the baseline bias between the PLT-F and PLT-I methods. Then, we selected 1256 samples to establish and test reflex test rules using seven machine learning models (decision Tree, random forest, neural network, logistic regression, k-nearest neighbor, support vector machine, and Naive Bayes). The training set and test set were divided at a ratio of 7:3. We evaluated the performance of machine learning models on the test set using various metrics to select the most valuable model., Results: The PLT-F method exhibited a high degree of correlation with the PLT-I method (r = 0.998). The random forest model emerged as the most valuable, boasting an accuracy of 0.893, an area under the curve of 0.954, an F1 score of 0.771, a recall of 0.719, a precision of 0.831, and a specificity of 0.950. The most important variable in the random forest model was mean cell volume, weighted at 15.09%., Conclusion: The random forest model, which demonstrated high efficiency in our study, can be used to establish PLT reflex test rules based on the PLT-F method for the Sysmex XN-series automated hematology analyzer., (© 2024 John Wiley & Sons Ltd.)

While deep learning-based methods for blind face restoration have achieved unprecedented success, they still suffer from two major limitations. First, most of them deteriorate when facing complex degradations out of their training data. Second, these methods require multiple constraints, e.g., fidelity, perceptual, and adversarial losses, which require laborious hyper-parameter tuning to stabilize and balance their influences. In this work, we propose a novel method named DifFace that is capable of coping with unseen and complex degradations more gracefully without complicated loss designs. The key of our method is to establish a posterior distribution from the observed low-quality (LQ) image to its high-quality (HQ) counterpart. In particular, we design a transition distribution from the LQ image to the intermediate state of a pre-trained diffusion model and then gradually transmit from this intermediate state to the HQ target by recursively applying a pre-trained diffusion model. The transition distribution only relies on a restoration backbone that is trained with L 1 loss on some synthetic data, which favorably avoids the cumbersome training process in existing methods. Moreover, the transition distribution can contract the error of the restoration backbone and thus makes our method more robust to unknown degradations. Comprehensive experiments show that DifFace is superior to current state-of-the-art methods, especially in cases with severe degradations.

Competing Interests: Conflicts of interest None disclosed.

Background: Neuropathic pain (NP), which results from injury or lesion of the somatosensory nervous system, is intimately associated with glial cells. The roles of microglia and astrocytes in NP have been broadly described, while studies on oligodendrocytes have largely focused on axonal myelination. The mechanisms of oligodendrocytes and their interactions with other glial cells in NP development remain uncertain., Methods: To explore the function of the interaction of the three glial cells and their interactions on myelin development in NP, we evaluated changes in NP and myelin morphology after a chronic constriction injury (CCI) model in mice, and used single-cell sequencing to reveal the subpopulations characteristics of oligodendrocytes, microglia, and astrocytes in the spinal cord tissues, as well as their relationship with myelin lesions; the proliferation and differentiation trajectories of oligodendrocyte subpopulations were also revealed using pseudotime cell trajectory and RNA velocity analysis. In addition, we identified chemokine ligand-receptor pairs between glial cells by cellular communication and verified them using immunofluorescence., Results: Our study showed that NP peaked on day 7 after CCI in mice, a time at which myelin lesions were present in both the spinal cord and sciatic nerve. Oligodendrocytes, microglia, and astrocytes subpopulations in spinal cord tissue were heterogeneous after CCI and all were involved in suppressing the process of immune defense and myelin production. In addition, the differentiation trajectory of oligodendrocytes involved a unidirectional lattice process of OPC-1-Oligo-9, which was arrested at the Oligo-2 stage under the influence of microglia and astrocytes. And the CADM1-CADM1, NRP1-VEGFA interactions between glial cells are enhanced after CCI and they had a key role in myelin lesions and demyelination., Conclusions: Our study reveals the close relationship between the differentiation block of oligodendrocytes after CCI and their interaction with microglia and astrocytes-mediated myelin lesions and NP. CADM1/CADM1 and NRP-1/VEGFA may serve as potential therapeutic targets for use in the treatment of NP., (© 2024. The Author(s).)

Purpose: The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of liver cancer patients. However, drug eruption associated with ICI monotherapy or combination therapy not only impacts the quality of life and treatment progress of liver cancer patients but also poses a potential threat to their lives. The study aims to investigate the risk factors of drug eruption in liver cancer patients undergoing ICIs in real-world settings., Methods: We retrospectively collected data from liver cancer patients who underwent ICI therapies at the Third Affiliated Hospital of Sun Yat-sen University between 2021 and 2022. A propensity score matching (PSM) method was employed to match 31 liver cancer patients with ICI-related drug eruption (drug eruption group) to 228 liver cancer patients without immune-related adverse reactions (control group) in a 1:2 ratio, creating two groups of patients with comparable baseline characteristics. Subsequently, logistic regression analysis was then conducted to analyze the clinical risk factors associated with drug eruption caused by ICIs., Results: Before PSM, there were statistically significant differences between the drug eruption group (31 cases) and the control group (228 cases) in two variables: Child-Pugh liver function classification and presence of vascular invasion (both p  < 0.05). However, after PSM, no statistically significant differences were found in the clinical variables between the drug eruption group (28 cases) and the control group (52 cases). Univariate analysis revealed significantly higher levels of aspartate amino-transferase, alanine aminotransferase, glutamyl transpeptidase, and systemic immune-inflammation index (SII) and a significantly lower rate of liver cancer resection surgery before immunotherapy in liver cancer patients with drug eruption compared to the control group ( p  < 0.05). Multivariate analysis indicated that an elevated SII level before immunotherapy was significantly associated with the occurrence of drug eruption in liver cancer patients treated with ICIs ( p  < 0.05). The predictive performance of SII before immunotherapy in liver cancer patients for ICI-related drug eruption yielded an area under the receiver operator characteristic curve of 0.852, with a critical value of 749.189. Sensitivity and specificity were determined as 85.7% and 75%, respectively ( p  < 0.05)., Conclusions: Elevated systemic immune-inflammation index is identified as a risk factor for drug eruption occurrence in liver cancer patients treated with ICI therapies.

Background: Articular cartilage has limited self-repair capacity, and current clinical treatment options for cartilage defects are inadequate. However, deer antler cartilage possesses unique regenerative properties, with the ability to rapidly repair itself. This rapid self-repair process is closely linked to the paracrine factors released by deer antler stem cells. These findings present potential for the development of cell-free therapies for cartilage defects in clinical settings. The aim of this study was to investigate a novel method for repairing cartilage., Methods: A rat model with articular cartilage defects was established through surgery. Hydrogels loaded with exosomes (Exos) derived from antler stem cells (ASC-Exos) were implanted into the rat cartilage defects. The extent of cartilage damage repair was assessed using histological methods. The effects of ASC-Exos on chondrocytes and rat bone marrow mesenchymal stem cells (BMSCs) were evaluated using cell viability assays, proliferation assays, and scratch assays. Additionally, the maintenance of the chondrocyte phenotype by ASC-Exos was assessed using real-time fluorescence quantitative PCR (qPCR) and western blot analysis. The protein components contained of the Exos were identified using data-independent acquisition (DIA) mass spectrometry., Results: ASC-Exos significantly promoted the repair of cartilage tissue damage. The level of cartilage repair in the experimental group (ASC-Exos) was higher than that in the positive control (human adipose-derived stem cells, hADSC-Exos) and negative control (dulbecco's modified eagle medium) groups ( p < 0.05). In vitro experiments demonstrated that ASC-Exos significantly enhanced the proliferation abilities of chondrocytes and the proliferation abilities and the migration abilities of BMSCs ( p < 0.05). ASC-Exos up-regulated the expression levels of Aggrecan, Collagen II (COLII), and Sox9 mRNA and proteins in chondrocytes. Analysis of ASC-Exos protein components revealed the presence of active components such as Serotransferrin (TF), S100A4, and Insulin-like growth factor-binding protein 1 (IGF1)., Conclusions: ASC-Exos have a significant effect on cartilage damage repair, which may be attributed to their promotion of chondrocyte and BMSCs proliferation and migration, as well as the maintenance of chondrocyte phenotype. This effect may be mediated by the presence of TF, S100A4, and IGF1., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Propagation through cuttings is a well-established and effective technique for plant multiplication. This study explores the regeneration of poplar roots using spatial transcriptomics to map a detailed developmental trajectory. Mapping of the time-series transcriptome data revealed notable alterations in gene expression during root development, particularly in the activation of cytokinin-responsive genes. Our analysis identified six distinct clusters during the second and third stages, each corresponding to specific anatomical regions with unique gene expression profiles. Auxin response cis -elements (AuxREs) were prevalent in the promoters of these cytokinin-responsive genes, indicating a regulatory interplay between auxin and cytokinin. Pseudo-temporal trajectory analysis mapped the differentiation from cambium cells to root primordium cells, revealing a complex pattern of cell differentiation. SAC56 and LOS1 emerged as potential novel biomarkers for enhancing root regeneration, with distinct spatial expression patterns confirmed by in situ hybridization. This comprehensive spatial analysis enhances our understanding of the molecular interactions driving root regeneration and provides insights for improving plant propagation techniques., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Learning dynamical networks based on time series of nodal states is of significant interest in systems science, computer science, and control engineering. Despite recent progress in network identification, most research focuses on static structures rather than switching ones. Therefore, this article develops a method for identifying the structures of switching networks by exploring and leveraging both temporal and spatial structural information that characterizes the switching process. The proposed method employs a new sparse Bayesian learning algorithm based on coupled hyperblocks to estimate unknown switching instants. Experimental results on benchmark artificial and real networks are elaborated to demonstrate the effectiveness and superiority of the proposed method.

Electrosynthesis of hydrogen peroxide (H 2 O 2 ) based on proton exchange membrane (PEM) reactor represents a promising approach to industrial-level H 2 O 2 production, while it is hampered by the lack of high-efficiency electrocatalysts in acidic medium. Herein, we present a strategy for the specific oxygen functional group (OFG) regulation to promote the H 2 O 2 selectivity up to 92 % in acid on cobalt-porphyrin molecular assembled with reduced graphene oxide. In situ X-ray adsorption spectroscopy, in situ Raman spectroscopy and Kelvin probe force microscopy combined with theoretical calculation unravel that different OFGs exert distinctive regulation effects on the electronic structure of Co center through either remote (carboxyl and epoxy) or vicinal (hydroxyl) interaction manners, thus leading to the opposite influences on the promotion in 2e - ORR selectivity. As a consequence, the PEM electrolyzer integrated with the optimized catalyst can continuously and stably produce the high-concentration of ca. 7 wt % pure H 2 O 2 aqueous solution at 400 mA cm -2 over 200 h with a cell voltage as low as ca. 2.1 V, suggesting the application potential in industrial-scale H 2 O 2 electrosynthesis., (© 2024 Wiley-VCH GmbH.)

The rapid development of neuromorphic computing has led to widespread investigation of artificial synapses. These synapses can perform parallel in-memory computing functions while transmitting signals, enabling low-energy and fast artificial intelligence. Robots are the most ideal endpoint for the application of artificial intelligence. In the human nervous system, there are different types of synapses for sensory input, allowing for signal preprocessing at the receiving end. Therefore, the development of anthropomorphic intelligent robots requires not only an artificial intelligence system as the brain but also the combination of multimodal artificial synapses for multisensory sensing, including visual, tactile, olfactory, auditory, and taste. This article reviews the working mechanisms of artificial synapses with different stimulation and response modalities, and presents their use in various neuromorphic tasks. We aim to provide researchers in this frontier field with a comprehensive understanding of multimodal artificial synapses., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Runze Li et al.)

A transcription factor (TF) is a sequence-specific DNA-binding protein, which plays key roles in cell-fate decision by regulating gene expression. Predicting TFs is key for tea plant research community, as they regulate gene expression, influencing plant growth, development, and stress responses. It is a challenging task through wet lab experimental validation, due to their rarity, as well as the high cost and time requirements. As a result, computational methods are increasingly popular to be chosen. The pre-training strategy has been applied to many tasks in natural language processing (NLP) and has achieved impressive performance. In this paper, we present a novel recognition algorithm named TeaTFactor that utilizes pre-training for the model training of TFs prediction. The model is built upon the BERT architecture, initially pre-trained using protein data from UniProt. Subsequently, the model was fine-tuned using the collected TFs data of tea plants. We evaluated four different word segmentation methods and the existing state-of-the-art prediction tools. According to the comprehensive experimental results and a case study, our model is superior to existing models and achieves the goal of accurate identification. In addition, we have developed a web server at http://teatfactor.tlds.cc, which we believe will facilitate future studies on tea transcription factors and advance the field of crop synthetic biology.

Three-dimensional (3D) tissue models have gained recognition for their improved ability to mimic the native cell microenvironment compared to traditional two-dimensional models. This progress has been driven by advances in tissue-engineering technologies such as 3D bioprinting, a promising method for fabricating biomimetic living tissues. While bioprinting has succeeded in generating various tissues to date, creating neural tissue models remains challenging. In this context, we present an accelerated approach to fabricate 3D sensory neuron (SN) structures using a transgenic human pluripotent stem cell (hPSC)-line that contains an inducible Neurogenin-2 (NGN2) expression cassette. The NGN2 hPSC line was first differentiated to neural crest cell (NCC) progenitors, then incorporated into a cytocompatible gelatin methacryloyl-based bioink for 3D bioprinting. Upregulated NGN2 expression in the bioprinted NCCs resulted in induced SN (iSN) populations that exhibited specific cell markers, with 3D analysis revealing widespread neurite outgrowth through the scaffold volume. Calcium imaging demonstrated functional activity of iSNs, including membrane excitability properties and voltage-gated sodium channel (Na V ) activity. This efficient approach to generate 3D bioprinted iSN structures streamlines the development of neural tissue models, useful for the study of neurodevelopment and disease states and offering translational potential., (Creative Commons Attribution license.)

Sugar beet (Beta vulgaris) has emerged as one of the two primary crops, alongside sugarcane, for global sugar production. Comprehensively understanding sucrose synthesis, transport, and accumulation in sugar beet holds great significance for enhancing sugar production. In this study, we collected a diverse set of 269 sugar beet accessions worldwide and measured 12 phenotypes, comprising biomass, soluble sugar content, and 10 taproot-related traits. We re-sequenced 207 accessions to explore genetic diversity and population structure. Then we employed a genome-wide association study (GWAS) and RNA-seq to identify single-nucleotide polymorphisms and genes associated with natural phenotypic variations. Our findings revealed a panel of genes potentially regulating biomass and sugar accumulation, notably the dual-role gene UDP-glucose 4-epimerase , which genetically balances sugar accumulation and cell wall synthesis. In summary, this study provides a foundation for molecular breeding in sugar beet., Competing Interests: The authors declare no competing financial interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Naringenin (NRG) is widely found in citrus fruits and has anti-inflammatory, hypoglycemic, and immunomodulatory effects. Previous studies have shown that NRG promotes gastrointestinal motility in mice constipation models, but there are few systematic evaluations of its effects on normal animals. This study first clarified the promotive effects of NRG on gastric emptying and small intestine propulsion ( p < 0.01). NRG can also regulate the release of gastrointestinal hormones, including enhancing gastrin (GAS) and motilin (MTL) ( p < 0.01), while reducing vasoactive intestinal peptide (VIP) secretion ( p < 0.01). Using NRG to stimulate the isolated stomach, duodenum, and colon showed similar promotive effects to those observed in vivo ( p < 0.01). A Western blot analysis indicated that this effect may be mediated by increasing the expression of stem cell factor (SCF) and its receptor (c-Kit) in these three segments, thus regulating their downstream pathways. It is worth noting that NRG can also increase the proportion of beneficial bacteria (Planococcaceae, Bacteroides acidifaciens , Clostridia&#95;UCG-014 ) in the intestine and reduce the quantity of harmful bacteria ( Staphylococcus ). These findings provide a new basis for the application of NRG.

The coal gangue dump may introduce heavy metal(oid)s (HMs) into surrounding agricultural soils, posing potential health risks to nearby communities. This study evaluated heavy metal(oid) pollution in agricultural soils adjacent to a gangue dump at an abandoned coal mine in Chongqing, Southwest China. The concentrations of HMs (As, Cd, Cr, Cu, Ni, Pb, and Zn) were quantified using ICP-MS, and the contamination status was assessed using the Geoaccumulation Index (I geo ), Contamination Factor (CF), Pollution Load Index (PLI), and Potential Ecological Risk Index (RI). Heavy metal(oid) contamination was detected in soils across a depth of 0-30 cm, particularly pronounced in the topsoil layer (0-10 cm and 10-20 cm depths). Cu emerged as the predominant contaminant across all examined depths, with average I geo values of 1.20, 1.21, and 1.16 for the 0-10 cm, 10-20 cm, and 20-30 cm depths, respectively, indicating moderate contamination. The CF for Cu was 3.55, 3.55, and 3.50 for these respective depths, classifying it as considerable contamination. The PLI values ranged from 1.61 to 2.50, with a mean value of 2.12, indicating overall contamination. The ecological risk assessment indicated that the soil's ecological risk was low at all depths. Cd was the major contributor to the RI, accounting for 48%, 47%, and 42% at 0-10 cm, 10-20 cm, and 20-30 cm depths, respectively. Health risk assessments revealed significant non-carcinogenic risks to children (mean HI = 1.30) and unacceptable carcinogenic risks to both adults and children (mean TCR = 3.26 × 10 -4 and 1.53 × 10 -3 , respectively). This study underscores the critical need for comprehensive risk assessments using multiple indicators to prioritize remediation efforts for HMs, providing a scientific basis for effective environmental management and public health protection in the Three Gorges Reservoir Area., (© 2024. The Author(s).)

Hybrid organic-inorganic binders based on blast furnace slag were produced using sodium (NaAc) or potassium (KAc) acetate as the sole activator, and their properties were compared with those of sodium- or potassium hydroxide-activated slag pastes. The acetate-activated binders showed significantly lower cumulative heat release and extended setting time (∼230 h) than the hydroxide-activated binders. The main reaction products forming in all binders were calcium aluminosilicate hydrate-type gels and a hydrotalcite-like phase, independently of the activator type used. Compressive strengths of the acetate-activated pastes (∼40 MPa at 180 days) were lower than those of the hydroxide-activated binders (∼80 MPa at 180 days). However, the acetate-based binders exhibited superior impermeability and reduced wettability at 28 days, likely due to hydrophobic acetate groups. It is hypothesized that acetates dissociate in water, forming calcium acetate and alkali silicates via a reaction with species dissolving from the slag. This study demonstrates alkali acetates are effective activators for creating hybrid slag-based binders with reduced permeability., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Conducting a comprehensive molecular-level evaluation of a photoacid generator (PAG) and its subsequent impact on lithography performance can facilitate the rational design of a promising 193 nm photoresist tailored to specific requirements. In this study, we integrated spectroscopy and computational techniques to meticulously investigate the pivotal factors of three prototypical PAG anions, p-toluenesulfonate (pTS-), 2-(trifluoromethyl)benzene-1-sulfonate (TFMBS-), and triflate (TF-), in the lithography process. Our findings reveal a significant redshift in the absorption spectra caused by specific PAG anions, attributed to their involvement in electronic transition processes, thereby enhancing the transparency of the standard PAG cation, triphenylsulfonium (TPS+), particularly at ∼193 nm. Furthermore, the electronic stability of PAG anions can be enhanced by solvent effects with varying degrees of strength. We observed the lowest vertical detachment energy of 6.6 eV of pTS- in PGMEA solution based on the polarizable continuum model, which prevents anion loss at 193 nm lithography. In addition, our findings indicate gas-phase proton affinity values of 316.4 kcal/mol for pTS-, 308.1 kcal/mol for TFMBS-, and 303.2 kcal/mol for TF-, which suggest the increasing acidity strength, yet even the weakest acid pTS- is still stronger than strong acid HBr. The photolysis of TPS+-based PAG, TPS+·pTS-, generated an excited state leading to homolysis bond cleavage with the lowest reaction energy of 83 kcal/mol. Overall, the PAG anion pTS- displayed moderate acidity, possessed the lowest photolysis reaction energy, and demonstrated an appropriate redshift. These properties collectively render it a promising candidate for an effective acid producer., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Image 1., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Two-dimensional (2D) halide perovskites (HPs) are of significant interest to researchers because of their natural structural frameworks and intriguing optoelectronic properties. However, the direct fabrication of ordered mixed-spacer quasi-2D HPs remains challenging. Herein, a synthetic strategy inspired by the principle of supramolecular synthons is employed for the self-assembly of a series of ordered mixed-spacer bilayered HPs. The key innovation involves the introduction of intermolecular hydrogen bonds using a bifunctional 3-aminopropionitrile cation. Three homogeneous n = 2 structures are obtained, with a subtly ordered perovskite connected by two distinct types of organic cation layers, resulting in a recurrent ABAB' stacking sequence. These three compounds exhibit attractive semiconducting properties. Moderate bandgaps in the range of 2.70 to 2.76 eV with an absorption wavelength range of 448-459 nm exhibit excellent photoelectric response. Moreover, the ordered structures facilitate excellent polarization-sensitive photodetection, with an impressive on/off ratio of 10 3 . The response speed ranged from 298 to 381 µs, and the out-of-plane polarization-related dichroism ratio is determined to be 1.19. Such ordered mixed-spacer bilayered perovskites have not been reported. These results enrich the HPs system and play a significant role in the direct assembly of novel perovskites with ordered structures., (© 2024 Wiley‐VCH GmbH.)

Argonaute (AGO) proteins are the core components of the RNA-induced silencing complexes (RISC) in the cytoplasm and nucleus, and are necessary for the development of plant shoot meristem, which gives rise to the above-ground plant body. In this study, we identified 23 Phyllostachys edulis AGO genes (PhAGOs) that were distributed unequally on the 14 unmapped scaffolds. Gene collinearity and phylogeny analysis showed that the innovation of PhAGO genes was mainly due to dispersed duplication and whole-genome duplication, which resulted in the enlarged PhAGO family. PhAGO genes were expressed in a temporal-spatial expression pattern, and they encoded proteins differently localized in the cytoplasm and/or nucleus. Overexpression of the PhAGO2 and PhAGO4 genes increased the number of tillers or leaves in Oryza sativa and affected the shoot architecture of Arabidopsis thaliana. These results provided insight into the fact that PhAGO genes play important roles in plant development., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest None declared.

A facile biphasic system composed of choline chloride (ChCl)-based deep eutectic solvent (DES) and methyl isobutyl ketone (MIBK) was developed to realize the furfural production, lignin separation and preparation of fermentable glucose from Eucalyptus in one-pot. Results showed that the ChCl/1,2-propanediol/MIBK system owned the best property to convert hemicelluloses into furfural. Under the optimal conditions (MR ChCl:1,2-propanediol  = 1:2, raw materials:DES:MIBK ratio = 1:4:8 g/g/mL, 0.075 mol/L AlCl 3 ·6H 2 O, 140 °C, and 90 min), the furfural yield and glucose yield reached 65.0 and 92.2 %, respectively. Meanwhile, the lignin with low molecular weight (1250-1930 g/mol), low polydispersity (D M  = 1.25-1.53) and high purity (only 0.08-2.59 % carbohydrate content) was regenerated from the biphasic system. With the increase of pretreatment temperature, the β-O-4, β-β and β-5 linkages in the regenerated lignin were gradually broken, and the content of phenolic hydroxyl groups increased, but the content of aliphatic hydroxyl groups decreased. This research provides a new strategy for the comprehensive utilization of lignocellulose in biorefinery process., 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.)

IL-1R-associated kinases (IRAKs) are signal transducers of the TLR/IL-1R-MyD88-TRAF6 pathways. Vertebrates possess two IRAK lineages, IRAK1/2/3 and IRAK4. In mammals, IRAK4/IRAK1 and IRAK4/IRAK2 are pathway enhancers, whereas IRAK3 is a repressor. However, in bony fish, IRAK2 is absent, and it remains elusive how fish IRAK1/3/4 functionally differ from their mammalian counterparts. In this study, we explored this using the zebrafish model. First, we showed that in human 293T cells, zebrafish IRAK1 and IRAK4 were components of the Myddosome (MyD88-IRAK4-IRAK1) complex, with IRAK1 serving as a potent pathway enhancer. Then, we discovered two zebrafish IRAK3 variants: one (IRAK3a) contains an N-terminal Death domain, a middle pseudokinase domain, and a C-terminal TRAF6-binding domain, whereas the other (IRAK3b) lost both the kinase and TRAF6-binding domains. This truncation of IRAK3 variants could be a conserved phenomenon in fish, because it is also observed in trout and grass carp. We proceeded to show that zebrafish IRAK3a acts as a pathway enhancer by binding with MyD88 and TRAF6, but its activity is milder than IRAK1, possibly because it has no kinase activity. Zebrafish IRAK3b, however, plays a sheer negative role, apparently because of its lack of kinase and TRAF6-binding domains. Moreover, zebrafish IRAK3a/3b inhibit the activity of IRAK1/4, not by interacting with IRAK1/4 but possibly by competing for MyD88 and TRAF6. Finally, we have verified the essential activities of zebrafish IRAK1/3a/3b/4 in zebrafish cells and embryos. In summary, to our knowledge, our findings provide new insights into the molecular functions of fish IRAKs and the evolution of the IRAK functional modes in vertebrates., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Myocardial infarction (MI) is a serious cardiovascular disease with complex complications and high lethality. Currently, exosome (Exo) therapy has emerged as a promising treatment of ischemic MI due to its antioxidant, anti-inflammatory, and vascular abilities. However, traditional Exo delivery lacks spatiotemporal precision and targeting of microenvironment modulation, making it difficult to localize the lesion site for sustained effects. In this study, an injectable oxidized hyaluronic acid-polylysine (OHA-PL) hydrogel was developed to conveniently load adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) and improve their retention under physiological conditions. The OHA-PL@Exo hydrogel with high spatiotemporal precision is transplanted minimally invasively into the ischemic myocardium to scavenge intracellular and extracellular reactive oxygen species, regulate macrophage polarization, and attenuate inflammation in the early phase of MI. In addition, this synergistic microenvironment modulation can effectively reduce myocardial fibrosis and ventricular remodeling, promote angiogenesis, and restore electrophysiological function in the late stage of MI. Therefore, this hyaluronic acid-polylysine to deliver exosomes has become a promising therapeutic strategy for myocardial repair., 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: Bipolar depression (BPD) is often misdiagnosed as a major depressive disorder (MDD) in clinical practice, which may be attributed to a lack of robust biomarkers indicative of differentiated diagnosis. This study analysed the differences in various hormones and inflammatory markers to explore peripheral biomarkers that differentiate BPD from MDD patients., Methods: A total of 2,048 BPD and MDD patients were included. A panel of blood tests was performed to determine the levels of sex hormones, stress hormones, and immune-related indicators. Propensity score matching (PSM) was used to control for the effect of potential confounders between two groups and further a receiver operating characteristic (ROC) curve was used to analyse the potential biomarkers for differentiating BPD from MDD., Results: Compared to patients with MDD, patients with BPD expressed a longer duration of illness, more hospitalisations within five years, and an earlier age of onset, along with fewer comorbid psychotic symptoms. In terms of biochemical parameters, MDD patients presented higher IgA and IgM levels, while BPD patients featured more elevated neutrophil and monocyte counts. ROC analysis suggested that combined biological indicators and clinical features could moderately distinguish between BPD and MDD. In addition, different biological features exist in BPD and MDD patients of different ages and sexes., Conclusions: Differential peripheral biological parameters were observed between BPD and MDD, which may be age-sex specific, and a combined diagnostic model that integrates clinical characteristics and biochemical indicators has a moderate accuracy in distinguishing BPD from MDD., (© 2024. The Author(s).)