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Ferroptosis is a unique modality of regulated cell death that is driven by iron-dependent phospholipid peroxidation. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. However, it remains elusive whether m6A reader Fragile X Mental Retardation Protein (FMRP) are involved in the modulation of ferroptosis in breast cancer (BC). In this study, we found that FMRP expression was elevated and associated with poor prognosis and pathological stage in BC patients. Overexpression of FMRP induced ferroptosis resistance and exerted oncogenic roles by positively regulating a critical ferroptosis defense gene SLC7A11. Mechanistically, upregulated FMRP catalyzes m6A modification of SLC7A11 mRNA and further influences the SLC7A11 translation through METTL3-dependent manner. Further studies revealed that FMRP interacts with splicing factor hnRNPM to recognize the splice site and then modulated the exon skip splicing event of SLC7A11 transcript. Interestingly, SLC7A11-S splicing variant can effectively promote FMRP overexpression-induced ferroptosis resistance in BC cells. Moreover, our clinical data suggested that FMRP/hnRNPM/SLC7A11 expression were significantly increased in the tumor tissues, and this signal axis was important evaluation factors closely related to the worse survival and prognosis of BC patients. Overall, our results uncovered a novel regulatory mechanism by which high FMRP expression protects BC cells from undergoing ferroptosis. Targeting the FMRP–SLC7A11 axis has a dual effect of inhibiting ferroptosis resistance and tumor growth, which could be a promising therapeutic target for treating BC.

Background: Disorders of glutamate metabolism and excessive release participat in multiple neuronal pathologies including ischemic stroke (IS), Alzheimer's disease (AD), or Parkinson's disease (PD). Recently, herbal medicines have been widely used and have shown satisfactory results in the treatment of neurological disorders. Gastrodin is a traditional Chinese medicine (TCM) used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. This research examines the neuroprotective effects of Gastrodin against glutamate-induced neurotoxicity in neuronal cells. Methods: The HERB database was used to explore the active ingredients and target genes of Gastrodia Elata. The STRING database and Cytoscape software were used to screen and construct the Protein-Protein Interaction (PPI). Furthermore, we used molecular docking to predict the potential targets of Gastrodin. The effects of Gastrodin were revealed by western blot, calcium imaging, membrane clamp, CCK8 and flow cytometry. Neuronal oxidative stress and damage were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Neuronal morphology was examined using Golgi-Cox staining. Finally, animal behavior was examined using novel object recognition and fear conditioning tests. Results: We have obtained 22 components such as TM10, TM17, TM25 (Gastrodin), and 281 targets such as AKT, EGFR, and CDK1 through network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed these genes were significantly enriched in protein phosphorylation, protein serine/threonine/tyrosine kinase activity, apoptosis and HIF-1 signaling pathways, etc. A higher affinity between Gastrodin and AKT was revealed by PPI analysis and molecular docking. Further, Gastrodin significantly inhibited Ca2+ influxes and excitatory synaptic transmission in cortical neurons. In addition, Gastrodin effectively alleviated neuron apoptosis, oxidative stress and damage. Conclusion: Gastrodin has neuroprotective effects against glutamate-induced neurotoxicity.

This is a case report of a 6-year-old girl with relapsed B cell acute lymphoblastic leukemia in which adoptive cell therapy was applied successfully to treat refractory human parvovirus (HPV) B19 infection. Allogenic chimeric antigen receptor (CAR) T-cell therapy (bispecific CD19/CD22) was bridged to hematopoietic stem cell transplantation (HSCT) using a haploidentical paternal donor. However, HPV B19 DNAemia progressed and transfusion-related graft versus host disease occurred. After finding a third-party related donor with a better HLA match, haploidentical HPV B19-seropositive CD45RA+ depleted cells (16.5 × 106/kg) were administered and paternal TCRαβ+ depleted stem cell were retransplanted. The HPV B19 DNAemia became negative within 1 week and the reticulocyte, neutrophil, hemoglobin, and platelet counts gradually normalized. The patient remained stable during the 1-year outpatient follow-up period. Thus, our case report highlights that persistent B19 infection can lead to pancytopenia, aplastic crisis, and graft rejection and TCRαβ+ depleted haplo-HSCT is an effective means of hematopoiesis recovery. CD45RO memory T-cell therapy is the key to treating and preventing the development of refractory severe HPV B19 infection.

Mixed fiber reinforced technique has been widely used in reinforcing the concrete due to its excellent performance in enhancing the strength, durability and stiffness. The improvement of fiber-reinforced soil (FRS) on the mechanical behaviour (e.g., stiffness and ductility) is limited due to the properties of single fibers. However, much studies focus on the single fiber based reinforced soil, two fibers or more mixing with soil do not be covered. Mixed fiber-reinforced soil (MFRS) is defined as the improvement of FRS, in which two different types of fibers are mixed into the soil to improve the shear strength and stiffness simultaneously. The tests were conducted using clay soil and Yongjiang sand, which were collected from the practical construction site of metro and Yongjiang River, respectively. The test results show that under the same test conditions (e.g., void ratio, confining pressure and fiber content), the MFRS always show higher deviator stress than the FRS. As carbon fibers and polypropylene fibers give higher stiffness and tensile strength respectively. Besides, the friction angle and cohesion of MFRS are also affected by fiber content. It is concluded that half of the carbon fiber content of MFRS has the same performance in the stress-strain relationship as the FRS with 100% carbon fiber content. However, the effectiveness of the reinforcement to clay soil is insignificant. As the reinforcements is relatively dependent on the characteristics of clay soil (e.g., mean diameter, coefficient uniformity). For the use of MFRS, it could decrease the cost of purchasing special fiber such as pure carbon fiber and aramid fiber, which are expensive, and it could be used in the long-terms constructions, which are required to last at least 100 years.

Waste tires pose significant environmental, health, and fire risks. Creative waste management solutions, including reuse, recycle and repurpose, are necessary to mitigate those impacts while enriching their valorisation. An innovative solution is the upcycling of recycled steel fibre (RSF) from waste tires to enhance strength and durability of concrete. This study thus experimentally examines dynamic and mechanical behaviours of high-strength concrete with varying proportions of RSF, from 0% to 1.2% by volume. The results reveal that high-strength concrete with 1.2% RSF exhibits the best improvement in strengths. In addition, the damping ratio, dynamic modulus of RSF concrete and SEM images confirm valorisation potentials of waste fibres. Via a robust critical lifecycle analysis, the new insights form a new sustainable design and carbon credited application framework for RSF. Our results portray that innovative recycling practices for end-of-life tires yield substantial environmental benefits, including a significant carbon emission reduction.

Driven by the development of innovative electrode materials, the brain-machine interface (BMI) has witnessed significant advancements in recent years. However, traditional implantable electrodes, such as metal-based and polymer-based electrodes, often face limitations in terms of flexibility, chronic stability, and long-term biocompatibility. Liquid metal-based electrodes have emerged as a promising alternative to traditional electrode materials, offering unique properties and numerous advantages for BMI applications. In this Review, we provided an in-depth overview of liquid metal-based electrodes. Liquid metal-based electrodes demonstrate several desirable features, including high electrical conductivity, flexibility, biocompatibility, and the ability to conform to the irregular and delicate structures of the brain. We also systematically and thematically discussed their material properties, biocompatibility considerations, performance characteristics, and assorted applications in neural recording, stimulation, brain-machine interfaces, closed-loop feedback systems, and neuroprosthetics. Meanwhile, long-term stability, biocompatibility, electrode-tissue interface, miniaturization, signal processing, and ethical considerations are areas that require further research and innovation. Addressing these challenges will contribute to the successful integration and widespread use of liquid metal-based electrodes in BMI systems.

Air handling units (AHUs) are essential for the regulation and circulation of indoor air in modern buildings and for providing a comfortable environment. However, the performance of AHUs can be easily affected by various sensor faults during long-term operation. To precisely detect and diagnose AHU faults, many researchers have applied model-based and data-driven approaches based on existing centralized architectures. However, such methods require comprehensive knowledge of physical constraints or sufficient labeled data and thus are impractical in real scenarios. Inspired by the merits of emerging decentralized systems, we implement insect intelligent building (I2B), a fully decentralized architecture, for intelligent buildings to improve building operation performance. In addition, to ensure the AHU efficiency, we optimize the process of AHU fault detection and diagnosis and propose a fully distributed voting strategy using only adjacent computing process nodes (CPNs) in a decentralized architecture. Extensive experiments were conducted to analyze the performance of the proposed method in different real scenarios. Based on a comparison with related state-of-the-art methods, the experimental results highlight the superiority of our method, which provides high accuracy, plug-in capability and strong adaptability.

Background: Essential oils (EOs) are a plant-derived volatile mixture. Due to their extensive biological activity, EOs have been utilized as ancient remedies to treat a variety of illnesses. Objectives: Our review aims to expand our understanding of EOs’ biological activity on the central nervous system (CNS) and to highlight the importance of utilizing EOs in CNS disorders. Method: A systematic literature search was conducted using PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), Springer Link, Wan-fang database, and Chinese Biomedicine Database (CBM). The search was conducted to collect relevant journals and contents using the following terms: ''essential oils'', ''aromatherapy'', ''essential oils'' and ''CNS''. Language of publications was unlimited. Results: EOs are concentrated volatile aromatic liquids extracted from natural plants with different chemical compositions, obtained by physical and chemical methods such as distillation and pressing. This paper explores the effects of EOs products on CNS including promoting intelligence, improving sleep, promoting cognition and memory, anti-anxiety and depression, sedation and anti-epilepsy. EOs exert their neuropharmacological effects through blood circulation or the olfactory system. This paper summarizes clinical studies showing that aromatherapy could improve sleep, relieve preoperative anxiety and postoperative PONV, relieve gynecological disease pain, and play a role in hospice care. Conclusion: The present findings suggest that EOs have neuropharmacological effects such as nootropic, sleep improvement, anti-dementia, anti-anxiety and depression, analgesic effect, and antiepileptic, emphasizing the importance of EOs in CNS disorders and indicating the potential clinical application.

The corneal endothelium is critical for maintaining corneal clarity by mediating hydration through barrier and pump functions. Progressive loss of corneal endothelial cells during aging has been associated with the development of Fuchs endothelial corneal dystrophy (FECD), one of the main causes of cornea-related vision loss. The mechanisms underlying FECD development remain elusive. Single-cell RNA sequencing of isolated healthy human corneas discovered 4 subpopulations of corneal endothelial cells with distinctive signatures. Unsupervised clustering analysis uncovered nuclear enriched abundant transcript 1 (NEAT1), a long non-coding RNA (lncRNA), as the top expressed gene in the C0-endothelial subpopulation, but markedly downregulated in FECD. Consistent with human corneas, a UVA-induced mouse FECD model validated the loss of NEAT1 expression. Loss of NEAT1 function by an in vivo genetic approach reproduced the exacerbated phenotype of FECD by ablating corneal endothelial cells. Conversely, gain of function by a CRISPR-activated adenoviral delivery system protected corneas from UVA-induced FECD. Our findings provide novel mechanistic insights into the development of FECD, and targeting NEAT1 offers an attractive approach for treating FECD.

Arsenite is a well-documented neurotoxic metalloid that widely distributes in the natural environment. However, it remains largely unclear how arsenite affects neurological function. Therefore, in this study, the healthy adult male mice were exposed to 0.5 mg/L and 5 mg/L arsenite through drinking water for 30 and 90 days, respectively. Our results showed that there was no significant alteration in the intestine and brain for 30 days exposure, but exposure to arsenite for 90 days significantly induced a reduction of locomotor activity and anxiety-like behavior, caused pathological damage and inflammatory responses in the brain and intestine. We also found that arsenite remarkably disrupted intestinal barrier integrity, decreased the levels of lysozyme and digestive enzymes. Intriguingly, chronic exposure to arsenite significantly changed the levels of gut-brain peptides. Taken together, this study provides meaningful insights that gut-brain communication may involve in the neurobehavioral impairments of arsenite.

The development of highly efficient magnetic resonance imaging (MRI) contrast agent contributes to the early and accurate diagnosis of cancer. Herein, we developed a novel iron oxide and gadolinium oxide (IO/GdO) nanocomposite as T1-T2 dual modal MRI contrast agent through hydrothermal synthesis method. Subsequently, tumor-targeting ligand (PDGFB-PEG) was further conjugated to the surface of IO/GdO nanocomposite (PDGFB-pIO/GdO) to fabricate tumor-targeting MRI probe for accurate diagnosis of orthotopic prostatic cancer. IO/GdO nanocomposite exhibited obvious mesoporous structure, which would promote the contact between water molecules and Gd or Fe centers and enhance the T1 relaxation rate (r1) and T2 relaxation rate (r2) of IO/GdO composite. In addition, the r1 and r2 values of IO/GdO composite were up to be 11.6 mM−1s−1 and 102.7 mM−1s−1, respectively, and the r2/r1 ratio of IO/GdO nanocomposite was calculated to be 8.85, demonstrating a great potential as dual-mode MRI contrast agent. Further study indicated that PDGFB-pIO/GdO exhibited an excellent biocompatibility. Besides, PDGFB-pIO/GdO presented a higher accumulation in tumor than untargeted pIO/GdO, confirming its excellent in vivo tumor-targeting ability. Lastly, in orthotopic prostatic cancer model, the systemic delivery of PDGFB-pIO/GdO significantly enhanced T1- and T2-weighted signal of orthotopic prostatic cancer, achieving high quality of MR images and realizing accurate diagnosis of orthotopic prostatic cancer. Collectively, we proposed a rational designed nanoplatform, PDGF-B conjugating mesoporous IO/GdO nanocomposites, suggesting potential for diagnostic identification of prostate cancer via T1-T2 dual-modal MRI contrast enhancement.

This study was aimed to explore the effects of fucoidan on iron overload and ferroptosis-induced liver injury, and the underlying mechanisms in rats exposed to alcohol. Sprague-Dawley rats were used to establish alcoholic liver injury model by intragastric administration with alcohol for 16 weeks. The results showed that fucoidan treatment reversed alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and increased glutathione peroxidase and glutathione levels, thus protecting against liver damage. Long-term alcohol feeding resulted in abnormal increase of serum ferritin, liver total iron and the ''free'' iron levels. Fucoidan treatment reduced serum ferritin level and alleviated liver iron deposition. Fucoidan reversed the reduction of hepcidin induced by alcohol exposure and decreased divalent metal transporter 1 (DMT1) and ferroportin1 (FPN1) expressions in the duodenum. Electron microscope observation of liver tissues showed that alcohol exposure induced ferroptosis changes in the liver. However, fucoidan treatment could alleviate alcohol-induced ferroptosis via upregulating the expressions of p62, Nrf2, SLC7A11 and GPX4. The liver endogenous metabolites analysis by liquid chromatography and mass spectrometry showed that after fucoidan intervention, mineral absorption, biosynthesis of amino acids pathways and lipid metabolism were changed. Fucoidan intervention reduced the levels of oxidized glutathione and regulated the levels of phosphatidylethanolamines in liver tissues. Our data showed that fucoidan supplementation could inhibit iron load via regulating hepcidin-intestinal DMT1/FPN1 axis, alleviate the liver oxidative damage and protect hepatocytes from ferroptosis induced by long-term alcohol exposure through upregulating p62/Nrf2/SLC7A11 pathway in rats.

As a new widespread contaminant, nanoplastics (NPs) pose a potential risk to human health. Nevertheless, the adverse effects of NPs on the male reproductive system are poorly understood. In this study, we aimed to determine the effects of polystyrene nanoplastics (PS-NPs) (50 nm) on sperm quality, with a focus on the acrosome defects. After 35 days of intragastric administration, sperm quality was decreased and testicular structures were impaired in mice exposed to PS-NPs in both the medium (1.0 mg/kg) and high dose (10 mg/kg) groups. No significant changes were observed in the low dose (0.2 mg/kg) group. Meanwhile, acrosome parameters including acrosome integrity and acrosome reaction were decreased after the administration of PS-NPs. These findings were consistent with the disruption of acrosome biogenesis, as identified by the changed testicular ultrastructure. Additionally, the findings were further validated using seven marker genes (Gba2, Pick1, Gopc, Hrb, Zpbp1, Spaca1 and Dpy19l2) essential for acrosome formation, which showed that two of these genes (Gopc and Dpy19l2) were significantly down-regulated. Moreover, repressed autophagy was observed in the testes of PS-NPs-exposed mice based on autophagy-related protein expression. This phenomenon was further verified in GC-2spd cells treated with PS-NPs (50 μg/mL, 100 μg/mL, 200 μg/mL for 24 h). The potential role of autophagy in such acrosome defects was explored by using the autophagy inhibitor 3-methyladenine (3-MA), autophagy activator rapamycin or beclin-1 siRNA. The results showed that Golgi-associated vesicle disorganization was exacerbated with the 3-MA and beclin-1 siRNA pretreatments, but decreased with the rapamycin pretreatment, and the expression of GOPC and DPY19L2 was also altered. These results indicated that autophagy might be involved in the PS-NPs-induced acrosome lesions based on the regulation of two key acrosome-formation proteins, GOPC and DPY19L2. Altogether, our results will provide new insights into the PS-NPs-induced male reproductive impairment.

Context: Analysis of diagnostic information in pathology reports for the purposes of clinical or translational research and quality assessment/control often requires manual data extraction, which can be laborious, time-consuming, and subject to mistakes. Objective: We sought to develop, employ, and evaluate a simple, dictionary- and rule-based natural language processing (NLP) algorithm for generating searchable information on various types of parameters from diverse surgical pathology reports. Design: Data were exported from the pathology laboratory information system (LIS) into extensible markup language (XML) documents, which were parsed by NLP-based Python code into desired data points and delivered to Excel spreadsheets. Accuracy and efficiency were compared to a manual data extraction method with concordance measured by Cohen’s κ coefficient and corresponding P values. Results: The automated method was highly concordant (90%–100%, P

Arsenite is a toxic metalloid that causes various adverse effects in brain. However, the underlying mechanisms of arsenite-induced neurotoxicity remain poorly understood. In this study, both adult beclin 1+/+ and beclin 1+/- mice were employed to establish a model of chronic arsenite exposure by treating with arsenite via drinking water for 6 months. The results clearly demonstrated that exposure of arsenite profoundly caused damage to the cerebral cortex, induced autophagy and impaired autophagic flux in the cerebral cortex. Heterozygous disruption of beclin 1 in animals remarkably alleviated the neurotoxic effects of arsenite. To verify the results obtained in the animals, a permanent U251 cell line was used. After treating of cells with arsenite, similar phenomenon was also observed, showing the significant elevation in the expression levels of autophagy-related genes. Importantly, lysosomal dysfunction caused by arsenite was observed in vitro and in vivo. Either knockdown of beclin in cells or heterozygous disruption of beclin 1 in animals remarkably alleviated the lysosomal dysfunction induced by arsenite. These findings indicate that downregulation of beclin 1 could restore arsenite-induced impaired autophagic flux possibly through improving lysosomal function, and suggesting that regulation of autophagy via beclin 1 would be an alternative approach for the treatment of arsenite neurotoxicity.

The aim of the study was to detect the neuroprotective activity of fucoidan in alcohol exposure and withdrawal mice and the underlying mechanisms. C57BL/6J mice were used to establish the murine model of chronic alcoholism and withdrawal over 10 weeks of alcohol exposure. After fucoidan treatment, the depression-like behaviors in mice with alcoholism were improved, and 5-hydroxytryptamine and brain derived neurotrophic factor levels were increased both in serum and brain tissues. Fucoidan treatment attenuated the increase of lipopolysaccharide induced by alcohol, and decreased tumor necrosis factor-α and interleukin-1β levels. In hippocampus fucoidan inhibited microglia cell activation, and down-regulated the levels of Toll-like receptor 4 and its downstream protein factors. In addition, fucoidan regulated the structure of gut flora and made the composition of microbiota more similar to that of the normal control mice with increased abundances of Prevotella and Alloprevotella. Oral administration of fucoidan could alleviate the depression-like behaviors of mice with alcoholism through the gut-microbiota-brain axis.

Long-chain PUFAs (LCPUFAs) occur in foods primarily in the natural lipid classes, triacylglycerols (TAGs) or phospholipids (PLs). We studied the relative efficacy of the neural omega-3 DHA provided in formula to growing piglets as a dose of 13C-DHA bound to either TAG or phosphatidylcholine (PC). Piglets were assigned to identical formula-based diets from early life and provided with TAG-13C-DHA or PC-13C-DHA orally at 16 days. Days later, piglet organs were analyzed for 13C-DHA and other FA metabolites. PC-13C-DHA was 1.9-fold more efficacious for brain gray matter DHA accretion than TAG-13C-DHA, and was similarly more efficacious in gray matter synaptosomes, retina, liver, and red blood cells (RBCs). Liver labeling was greatest, implying initial processing in that organ followed by export to other organs, and suggesting that transfer from gut to bloodstream to liver in part drove the difference in relative efficacy for tissue accretion. Apparent retroconversion to 22:5n-3 was more than double for PC-13C-DHA and was more prominent in neural tissue than in liver or RBCs. These data directly support greater efficacy for PC as a carrier for LCPUFAs compared with TAG, consistent with previous studies of arachidonic acid and DHA measured in other species.

Background: Acupuncture has been increasingly used in obese people, yet no bibliometric analysis of acupuncture studies for obesity exists. This bibliometric study analyzed research trends, cooperation, and knowledge dissemination on acupuncture for obesity over the past 20 years to inform future directions., Objectives: To investigate the characteristics, hotspots, and frontiers of global scientific output in acupuncture research for obesity over the past two decades., Methods: We retrieved publications on acupuncture for obesity published from 2004 to 2023 from the Web of Science Core Collection. Using Citespace, VOSviewer, and Bibliometrix, we analyzed and visualized the publications, countries, institutions, authors, journals, and keywords from various angles., Results: A total of 357 articles were retrieved. The results showed that the number of annual publications on acupuncture for obesity has increased over time. China had the most publications (217 articles, 60.87 %), with Chengdu University of Traditional Chinese Medicine (24 articles, 6.72 %) as the most prolific institution. Ergene Neyhan, Huang Wei, and Zhou Zhongyu were the most productive authors (9 articles), and the article published by Cho SH in 2009 was the most cited article (60 citations). The most published journal was Evidence-based Complementary and Alternative Medicine, while the Journal of American Journal of Chinese Medicine was the most frequently cited. Recently, "electroacupuncture" "insulin resistance" and "systematic review" appeared frequently. The research hotspots and trends of acupuncture for obesity mainly focus on interventions, hotspot diseases, and mechanism exploration. According to keyword analysis, randomized controlled trials of catgut embedding and mechanistic studies of gut flora are the trends for future research., Conclusion: Although China is the leading producer, multinational co-operation still needs to be strengthened. Currently, the main interventions for obesity were acupuncture and electroacupuncture, and the hot diseases were obesity combined with polycystic ovary syndrome and metabolic syndrome. In addition, randomised controlled trials of catgut embedding and mechanistic studies of gut flora may be potential directions for future research in the field of acupuncture for obesity., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)

Silk-producing animals use spigots to generate natural silk fibers for various purposes. These natural looms must be able to withstand prolonged silk extrusion. To gain insight into the functional basis of spigots, we report on the structural design of the spigot of the silkworm Bombyx mori. The B. mori spigot exhibits a unique triple-ridged strip surface structure, consisting of cuticle proteins, resilin, chitin, and metal ions (such as K and Ca). This multi-microstructure endows the spigot with superior hierarchical mechanical properties, enabling it to function as a spinning tool for silk formation, thereby influencing the structure and performance of the silk. These findings demonstrate new pathways for achieving specialized functions in confined spaces, providing theoretical support for understanding the natural spinning mechanism and inspiring new directions for developing innovative biomimetic materials., 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. Published by Elsevier B.V.)

Herein, the identification and analysis of a newly discovered hypolipidemic polysaccharide extracted from Suaeda salsa L., SS3-N1, is reported. The weight-average molecular weight (Mw), number-average molecular weight (Mn), and dispersity (Ð) of SS3-N1 were determined to be 45.50 kDa, 34.21 kDa, and 1.33, respectively. This polysaccharide primarily consists of galactose (50.80 %) and arabinose (30.70 %), with lower proportions of xylose, mannose, guluronic acid, rhamnose, glucuronic acid, ribose, and fucose. Methylation and NMR analyses indicated that its backbone was primarily composed of R → 3,6)-β-D-Galp-(1 → R and R → 5)-α-L-Araf-(1→ residues. The sugar units at the reducing and nonreducing ends were identified as R → 4)-β-D-Xylp-(1 → R and R → 3)-β-D-Galp-(1 → R, respectively. In addition, α-L-Araf (1 → R side branches were incorporated at the C-3 position of R → 3,6)-β-D-Galp-(1 → R. At 100 μg/mL, SS3-N1 surpassed the lipid-lowering efficacy of the positive control, atorvastatin (0.4 μM), in an egg yolk powder (EYP)-induced hyperlipidemic zebrafish model. This effect may be attributed to the modulation of cholesterol metabolism due to the upregulation of nrf2, ho-1, ampk, ppara, and cyp7a1 gene expression and the downregulation of acaca and hmgcr gene expression. Such dual gene regulation inhibits fatty acid and cholesterol synthesis, suggesting potential applications for the natural hypolipidemic polysaccharide derived from S. salsa L., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kuo Xu reports financial support was provided by Shandong Provincial Natural Science Foundation (No. ZR2022YQ71). Congmin Liu reports financial support was provided by Shandong Provincial Natural Science Foundation (No. ZR2020QC198). Qing Xia reports financial support was provided by Shandong Provincial Central Guidance Local Science and Technology Development Fund Project (No. YDZX2022164). Zongchang Xu reports was provided by National key research and development young scientist project (No. 2023YFD1901900). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate the role of polysaccharides from Ostrea rivularis Gloud (ORPs) in the progression of diabetic retinopathy (DR) and its anti-angiogenic effect on endothelial cell. Transgenic db/db mice with DR model were used to evaluate the protective effect of ORPs on retinal damage. It was found that ORPs could down-regulated levels of random blood glucose and fasting insulin, and further ameliorate retinal structure abnormalities as well as vascular network structure. Moreover, ORPs could reduce the expression of VEGF in retinal tissue and lessen pathological angiogenesis, thus slowing the progression of DR. In vitro, the proliferation, migration and tube formation of VGEF 165 -induced EA.hy926 cells were inhibited with ORPs administration. Furthermore, the expression of related proteins in the PI3K/AKT pathway and angiogenesis related factors were improved after ORPs intervention. Overall, these findings suggested that ORPs could effectively control the development of DR, and inhibit VGEF 165 -induced EA.hy926 cells proliferation, migration and tube formation, which effects might work through blocking the activation of PI3K/AKT signaling pathway., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Escherichia coli and Staphylococcus aureus are the most prevalent pathogenic bacteria, often resulting in the foodborne disease outbreaks through food spoilage and foodborne infections. To prevent and control food spoilage and foodborne infections induced by Escherichia coli and Staphylococcus aureus, the antibacterial hydrogels were fabricated using fibrinogen hydrolysate-carrageenan (AHs-C) and flavonoids (apigenin and quercetin), and the antibacterial effect of the composite hydrogels against Escherichia coli and Staphylococcus aureus was further investigated. The results of mechanical property exhibited that the composite hydrogels with 0.2 % of apigenin and quercetin (AHs-C-Ap/Que) showed the highest hardness and swelling property compared with the separate addition of apigenin or quercetin. Scanning electron microscopy and atomic force microscopy showed that the dense networks were formed in the hydrogels of AHs-C-Ap/Que., and the average roughness of AHs-C-Ap/Que. significantly increased to 30.70 nm compared with AHs-C. 1 H NMR and FTIR spectra demonstrated that apigenin and quercetin were bound to AHs-C by hydrogen bond, hydrophobic interaction and Schiff base, where the interactions between Ap/Que. and AHs-C was stronger compared with the separate addition of apigenin or quercetin. The hydrogels of AHs-C-Ap/Que. showed the highest antibacterial capacity and antibacterial adhesion against Escherichia coli and Staphylococcus aureus. The antibacterial adhesion assay showed that 99 % removal ratios for E. coli and S. aureus were observed in AHs-C-Ap/Que. hydrogels, which showed a great potential to prevent food spoilage and foodborne infections., 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.)

Proteinase inhibitors constitute a significant component of Lepidoptera cocoon. BmSPI51 is the most abundant protease inhibitors in silkworm cocoons. In this study, we aimed to elucidate the biological function of BmSPI51 in both the silkworm silk gland and cocoon formation. To achieve this, we utilized CRISPR/Cas9 gene editing to target the BmSPI51 gene, resulting in premature termination of translation at the 33rd amino acid residue. The mutation of BmSPI51 did not affect the growth and development. Nevertheless, it led to a substantial decrease in the economic traits of silkworm cocoons. Proteomic analysis indicated the abundance of fibroin heavy chain (Fib-H), fibroin light chain (Fib-L), and fibrohexamerin (P25) decreased significantly in the homozygous mutants. Further analysis of cocoon proteins found that the mutants significantly increased the secretion of other protease inhibitors in order to deal with the increased environmental stress resulting from the absence of BmSPI51. Surprisingly, homozygous mutant cocoons exhibited an enhanced inhibitory ability against Saccharomyces cerevisiae compared to the WT cocoons. In conclusion, our study provides a valuable insight into the biological function of protease inhibitors and revealed their roles in cocoon formation and potential applications in biotechnology., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Multidrug-resistant (MDR) Pseudomonas aeruginosa is a serious life-threatening pathogen. The rise in P. aeruginosa resistance rates has renewed interest in phages as an alternative therapeutic approach for treating bacterial infections. In this study, we investigated the characteristics of the first Pseudomonas phage, vB_PaP_HN01, isolated from Hainan, the only tropical island in China. The lytic rate of this phage against P. aeruginosa reached 64.3 % (27/42). Under the optimal multiplicity of infection (MOI) of 0.1, more than 90 % of phage particles absorb onto the host cell within 10 min, with an eclipse period of around 15 min, and a high titer phage production (10 11  PFU/ml) within 90 min was demonstrated. vB_PaP_HN01 maintains a robust titer after 1 h exposure to pH values and temperatures (up to 50 °C). Genome annotation revealed that vB_PaP_HN01 did not contain drug-resistance or lysogeny-associated genes. It can effectively inhibit the formation of biofilms of MDR P. aeruginosa and eliminated aggressive biofilms (removal rate about 70 %). In the in vivo infection models, it was demonstrated that the survival rate and lifespan of Galleria mellonella larvae were increased alongside the injection of vB_PaP_HN01. These data revealed the potential of vB_PaP_HN01 against P. aeruginosa in clinic., (Copyright © 2024. Published by Elsevier Masson SAS.)

Endometrial decidualization is critical for successful embryo implantation. Dysregulation of the immune microenvironment can disrupt normal decidualization processes, potentially resulting in early pregnancy loss. Ferroptosis, a form of cell death dependent on iron and lipid hydroperoxides, is closely associated with inflammation. In this study, we developed an inflammatory early pregnancy loss model to elucidate the mechanisms of decidual damage induced by lipopolysaccharide (LPS) and to assess whether ferroptosis contributes to LPS-induced early pregnancy loss. Through in vivo experiments, we observed that embryo implantation was significantly inhibited and endometrial decidualization was impaired during LPS-induced early pregnancy loss. LPS exposure resulted in abnormal mitochondrial morphology, reduced antioxidant capacity, accumulation of reactive oxygen species (ROS) and disruptions in iron metabolism during decidualization in mouse endometrial stromal cells (mESCs). The administration of ferroptosis inhibitors, specifically ferrostatin-1 (Fer-1) and deferoxamine (DFO), effectively reversed embryo loss and mitigated the decidual damage associated with LPS-induced early pregnancy loss. Fer-1 and DFO exhibited resistance to ferroptosis during decidualization by modulating the antioxidant system and iron metabolism in mESCs, respectively. Our findings indicate that the inhibition of ferroptosis can confer protective effects against decidual damage during LPS-induced early pregnancy loss in mice., Competing Interests: Declaration of competing interest 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 © 2024 Elsevier Inc. All rights reserved.)

Establishing natural background levels (NBLs) of nitrate‑nitrogen (NO 3 -N) is crucial for groundwater resource management and pollution prevention. Traditional statistical methods for evaluating NO 3 -N NBLs generally overlook the hydrogeochemical processes associated with NO 3 -N pollution. We propose using a method that combines principal component factor analysis and K-means clustering (PCFA-KM) to identify NO 3 -N anomalies in three typical areas of the Huaihe River Basin and evaluate the effectiveness of this method in comparison with the hydrochemical graphic method (Hydro) and the Gaussian mixture model (GMM). The results showed that PCFA-KM was the most robust and effective for identifying NO 3 -N anomalies caused by human activities. This method not only considers the data's discreteness but also combines the influencing factors of NO 3 -N pollution to identify anomalies, thus avoiding the influence of non-homogeneous hydrogeological conditions. Moreover, 70 % of the identified anomalies were explained by sampling survey data, geochemical ratios, and pollution percentage indices, confirming the method's effectiveness and reliability. The upper limits of NO 3 -N NBLs obtained by PCFA-KM were 12.97 mg/L (CUs-I), 4.42 mg/L (CUs-V), and 5.57 mg/L (CUs-VI). This study provides a new approach for NO 3 -N anomaly identification, which can guide future NO 3 -N NBLs assessments and pollution prevention and control efforts., (Copyright © 2024. Published by Elsevier B.V.)

Allograft fibrosis is increasingly detected in graft biopsies as the postoperative period extends, potentially emerging as a pivotal determinant of long-term graft function and graft survival among pediatric recipients. Currently, there is a paucity of non-invasive diagnostic tools capable of identifying allograft fibrosis in pediatric recipients of liver transplants. This study involved 507 pediatric liver transplant patients and developed a novel blood-based diagnostic assay, PT-LIFE, to noninvasively distinguish allograft fibrosis using blood samples, clinical data, and biopsy outcomes. The PT-LIFE assay was derived from a matrix of 23 variables and validated in two independent cohorts. It integrates three biomarkers (LECT2, YKL-40, FBLN3) with an AUROC of 0.91. In the pooled analysis, a PT-LIFE score lower than 0.12 identified LAFSc 0-2 with a sensitivity of 91.9%, whereas scores above 0.29 indicated LAFSc 3-6, with a specificity of 88.4%. The PT-LIFE assay presents as a promising non-invasive diagnostic tool for the detection of allograft fibrosis in pediatric liver transplant recipients. The study is registered with ClinicalTrials.gov, identifier NCT05308628., (Copyright © 2024. Published by Elsevier Inc.)

Nitrites in meat products are important food additives with coloring, antibacterial and antioxidant effects, but excessive intake of nitrites can pose health risks, including an increased risk of cancer due to the formation of carcinogenic nitrosamines. In the present study, Limosilactobacillus fermentum CGMCC 1.7434 was screened and the effects of it and Debaryomyces hansenii GDMCC 2.149 and their combination on nitrite degradation were investigated. It was found that the co-culture of L. fermentum CGMCC 1.7434 and D. hansenii GDMCC 2.149 significantly enhanced nitrite degradation (99.58%). The findings on salt and ethanol tolerance suggest suitability for application in meat fermentation processes. Scanning electron microscopy and additional data indicate that D. hansenii GDMCC 2.149 facilitates the growth, acid production, adhesion, secretion of AI-2 signaling molecules, and biofilm formation of L. fermentum CGMCC 1.7434. Metabolomics analysis suggests that these microorganisms reduce nitrite levels by converting NH 3 derived from nitrite into L-glutamine, which is further transformed into N-nitroso compounds and their downstream derivatives through the ABC transporter pathway, the TCA cycle, and the amino acid metabolism pathway. Microbial community analyses showed that L. fermentum CGMCC 1.7434 and D. hansenii GDMCC 2.149 were successfully inoculated into air-dried ducks, becoming dominant strains and effectively inhibiting the growth of pathogenic bacteria. Furthermore, during the processing of air-dried duck, the combination of ultrasonic cavitation (250 W, 4 min, 30°C, 40 kHz) with the co-fermentation of L. fermentum CGMCC 1.7434 and D. hansenii GDMCC 2.149 effectively reduced nitrite content (84.55%) and TVB-N levels in the meat, without compromising color or TBARS values. This is crucial for understanding the mechanism of nitrite degradation by LAB in synergy with yeast and for the advancement of low-nitrite air-dried duck products., Competing Interests: DISCLOSURES 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 Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Microwave ablation (MWA) has gained attention as a minimally invasive and safe alternative to surgical intervention for patients with small renal masses; however, its cost-effectiveness in Australia remains unclear. This study conducted a cost-effectiveness analysis to evaluate the relative clinical and economic merits of MWA compared to robotic-assisted partial nephrectomy (RA-PN) in the treatment of small renal masses., Methods: A Markov state-transition model was constructed to simulate the progression of Australian patients with small renal masses treated with MWA versus RA-PN over a 10-year horizon. Transition probabilities and utility data were sourced from comprehensive literature reviews, and cost data were estimated from the Australian health system perspective. Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated. Modelled uncertainty was assessed using both deterministic and probabilistic sensitivity analyses. A willingness-to-pay (WTP) threshold of $50,000 per QALY was adopted. All costs are expressed in 2022 Australian dollars and discounted at 3% annually. To assess the broader applicability of our findings, a validated cost-adaptation method was employed to extend the analysis to 8 other high-income countries., Results: Both the base case and cost-adaptation analyses revealed that MWA dominated RA-PN, producing both lower costs and greater effectiveness over 10 years. The cost-effectiveness outcome was robust across all model parameters. Probabilistic sensitivity analyses confirmed that MWA was dominant in 98.3% of simulations at the designated WTP threshold, underscoring the reliability of the model under varying assumptions., Conclusion: For patients with small renal masses in Australia and comparable healthcare settings, MWA is the preferred strategy to maximize health benefits per dollar, making it a highly cost-effective alternative to RA-PN., 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.)

Background: Cholesterol crystals (CCs) are recognized as a risk factor for vulnerable atherosclerotic plaque rupture (PR) and major adverse cardiovascular events. However, their predictive factors and association with plaque vulnerability in patients with acute myocardial infarction (AMI) remain insufficiently explored. Therefore, This study aims to investigate the association between CCs and plaque vulnerability in culprit lesions of AMI patients, identify the factors influencing CCs formation, and develop a predictive model for CCs., Methods: A total of 431 culprit lesions from AMI patients who underwent pre-intervention optical coherence tomography (OCT) imaging were analyzed. Patients were divided into groups based on the presence or absence of CCs and PR. The relationship between CCs and plaque vulnerability was evaluated. A risk nomogram for predicting CCs was developed using the least absolute shrinkage and selection operator and logistic regression analysis., Results: CCs were identified in 64.5 % of patients with AMI. The presence of CCs was associated with a higher prevalence of vulnerable plaque features, such as thin-cap fibroatheroma (TCFA), PR, macrophage infiltration, neovascularization, calcification, and thrombus, compared to patients without CCs. The CCs model demonstrated an area under the curve (AUC) of 0.676 for predicting PR. Incorporating CCs into the TCFA model (AUC = 0.656) significantly enhanced predictive accuracy, with a net reclassification improvement index of 0.462 (95 % confidence interval [CI]: 0.263-0.661, p < 0.001) and an integrated discrimination improvement index of 0.031 (95 % CI: 0.013-0.048, p = 0.001). Multivariate regression analysis identified the atherogenic index of plasma (odds ratio [OR] = 2.417), TCFA (OR = 1.759), macrophage infiltration (OR = 3.863), neovascularization (OR = 2.697), calcification (OR = 1.860), and thrombus (OR = 2.430) as independent risk factors for CCs formation. The comprehensive model incorporating these factors exhibited reasonable discriminatory ability, with an AUC of 0.766 (95 % CI: 0.717-0.815) in the training set and 0.753 (95 % CI: 0.704-0.802) in the internal validation set, reflecting good calibration. Decision curve analysis suggested that the model has potential clinical utility within a threshold probability range of approximately 18 % to 85 %., Conclusions: CCs were associated with plaque vulnerability in the culprit lesions of AMI patients. Additionally, this study identified key factors influencing CCs formation and developed a predictive model with potential clinical applicability., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Signal Transducer and Activator of Transcription (STAT) proteins represent a critical transcription factor family with multifaceted roles in diverse fundamental eukaryotic processes. In Drosophila, STAT exerts a pivotal regulatory influence on oogenesis, governing the early differentiation of follicular cells and ensuring proper encapsulation of germ-line cells. However, the role of STAT in egg development in silkworms remains unknown. In the present study, using CRISPR/Cas9 technology, we successfully generated a strain of silkworms with targeted deletion of the STAT-L gene, which resulted in significant reproductive abnormalities observed in female moths, including shortened fallopian tubes and reduced egg production. The ovaries dissected from STAT-L knockout silkworms during the pupal stage of silkworm exhibited varying degrees of fusion among egg chambers. Additionally, paraffin sections of prepupal ovaries also revealed evidence of egg chambers fusion. To elucidate the molecular mechanism underlying the role of the STAT-L gene regulation on egg development in silkworm, we performed ovarian transcriptomic analysis following STAT-L knockout. Our findings indicated that STAT-L gene can modulate Notch signaling pathway by down-regulating APH-1 gene expression. These results suggest that STAT-L gene plays a crucial role in normal egg chamber formation in silkworms, potentially through its influence on Notch signaling pathway expression., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The silkworm is an incredibly valuable insect that produces silk through its silk gland. Within this organ, Fibroinase has been identified and named due to its ability to fibroin degradation. The expression of Fibroinase in the silk gland significantly increases during the larval-pupal stage, which might be associated with the degeneration of the silk gland. In this study, Fibroinase was overexpressed and knocked down specifically both in the middle and posterior silk glands, respectively, using transgenic technology. The investigation of silk gland development in these transgenic silkworms showed that Fibroinase plays a direct role in accelerating silk gland degeneration. The staining analyses performed in the silk glands of transgenic silkworms suggest that Fibroinase is involved in the processes of autophagy and apoptosis during silk gland degeneration. Further experiments demonstrated that Fibroinase, acting as a lysosomal regulator, negatively regulates autophagy via the mTOR (mechanistic target of rapamycin) pathway. Moreover, during apoptosis, Fibroinase could activate Caspase3 by increasing the activity of BmCaspase1, ultimately accelerating the apoptosis process. These findings enhance our understanding of the physiological role of Fibroinase in promoting silk gland degeneration, which plays a role in breaking down proteins in the silk gland and coordinating the regulation of autophagy and apoptosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The long-term stability of Fe III -As V coprecipitates, a typically hydrometallurgical or naturally produced As-bearing wastes in tailings or in other environments, is critical to evaluating the As risk caused by them. A wide pH range, different Fe/As molar ratios, reaction media, and neutralization reagents were considered in order to find the mechanisms controlling the fate of As during the 1640 days of transformation at 25 °C. The results indicated that at pH 4 and 12, As continuously released from the solid phase. The components and their proportions determined the fate of As at pH 4. However, at pH 12, crystalline calcium carbonates (CCA) formed due to the CO 2 in the air and this combined with the adsorption capacity of As on the 2-line ferrihydrite controlling the fate of As. If pH changed to 8 and 10, yukonite formed after the release of As. The CCA also appeared in the presence of Ca. Therefore, these two processes controlled the fate of As at this pH range. These findings are important for understanding and predicting the transport of As under various environmental conditions. The technology chosen for As remediation in soils and As removal from waste waters will also be benefit from these results., Competing Interests: Declaration of Competing Interest No conflict of interest of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Homozygous familial hypercholesterolemia (HoFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset cardiovascular disease. To assess the therapeutic effects of liver transplantation (LT) on HoFH patients, we observed and analyzed the outcomes of HoFH children after LT., Study Design: This prospective cohort study included all LT candidates under 18 years old diagnosed with HoFH at Ren Ji Hospital between November 2017 and July 2021. The patients were followed until October 2023. They were treated according to the standard protocol at our center. We collected data on changes in lipid profiles, clinical manifestations, and cardiovascular complications at different time points, and recorded postoperative recipient and graft survival., Results: Fourteen HoFH patients with a median age of 7 (2-12) years were included. Preoperatively, xanthomas and arcus corneas occurred in 14 and 3 patients, respectively, with 10 patients showing mild cardiovascular disease. All patients underwent LT. Recipient and graft survival rates were 100 % over a median follow-up duration of 35 (27-71) months. Median LDL-C levels dropped from 11.83 (7.99-26.14) mmol/L preoperatively to 2.3 (1.49-3.39) mmol/L postoperative at the last measurement. Thirteen patients discontinued lipid-lowering treatment after LT, while only one patient resumed statins 6 months post-operation. Xanthomas and arcus corneas significantly improved. Cardiovascular complications regressed in five patients, with no progression observed in the others., Conclusions: LT is a safe and effective treatment for severe HoFH patients beyond lipid-lowering control. Early LT improves prognosis and quality of life while minimizing the risk of cardiovascular complications., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Thermosonication (UT) prestress treatments combining with varied fermentation patterns has been revealed as an effective method to regulate post-acidification as exerted by Lactobacillus delbrueckii subsp. bulgaricus (L. delbrueckii), but sono-biochemical controlling mechanisms remain elusive. This study employed physiological and transcriptomic analysis to explore the response mechanism of L. delbrueckii to UT-induced microstress (600 W, 33 kHz, 10 min). UT stress-induced inhibition of acidification of L. delbrueckii during (post)-fermentation was first confirmed, relying on the UT process parameters such as stress exposure duration and UT power. The significantly enhanced membrane permeability in cells treated by 600 W for 10 min than the microbes stressed by 420 W for 20 min suggested the higher dependence of UT-derived stresses on the treatment durations, relative to the ultrasonic powers. In addition, ultrasonication treatment-induced changes in cell membrane integrity enhanced and/or disrupted permeability of L. delbrueckii, resulting in an imbalance in intracellular conditions associated with corresponding alterations in metabolic behaviors and fermentation efficiencies. UT-prestressed inoculum exhibited a 21.46% decrease in the membrane potential during the lag phase compared to untreated samples, with an intracellular pH of 5.68 ± 0.12, attributed to the lower activities of H + -ATPase and lactate dehydrogenase due to UT stress pretreatments. Comparative transcriptomic analysis revealed that UT prestress influenced the genes related to glycolysis, pyruvate metabolism, fatty acid synthesis, and ABC transport. The genes encoding 3-oxoacyl-[acyl-carrier-protein] reductases I, II, and III, CoA carboxylase, lactate dehydrogenase, pyruvate oxidase, glucose-6-phosphate isomerase, and glycerol-3-phosphate dehydrogenase were downregulated, thus identifying the relevance of the UT microstresses-downregulated absorption and utilization of carbohydrates with the attenuated fatty acid production and energy metabolisms. These findings could contribute to provide a better understanding of the inactivated effects on the post-acidification of L. delbrueckii by ultrasonic pretreatments, thus providing theoretical basis for the targeted optimization of acidification inhibition efficiencies for yogurt products during chilled preservation processes., 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.)

A new polysaccharide, named SP40015A01, was obtained from Saposhnikoviae Radix by water extraction, isolation and purification. SP40015A01 (9.7 × 10 5  Da) is composed of Rhamnose (Rha), Galacturonic acid (GalA), Galactose (Gal), and Arabinose (Ara) with the proportion of 1.6:85.6:5.8:7.6. The backbone of SP40015A01 is composed of 3-α-GalAp, 2-α-GalAp, 2,3-β-GalAp and 2,3-β-Galp, and branched at C3 of 2,3-β-GalAp, C3 of 2,3-β-Galp. Zebrafish experiments were used to explore the immunomodulatory activity of SP40015A01. Results showed that SP40015A01 could significantly improve the neutrophils density of immunocompromised zebrafish and reduce the content of nitric oxide (NO) and interleukin-1β (IL-1β). This study demonstrated that SP40015A01 has significant immunomodulatory activity, which can improve the neutrophils density and reduce inflammatory factor content, suggesting SP40015A01 may be a potential immunomodulator in Saposhnikoviae Radix (SR) for treatment of hypoimmunity related disease. This study supplemented the research on the polysaccharide components in traditional Chinese medicine and provided a scientific explanation for the development and clinical applications of SR., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LIU BIN reports financial support was provided by National Natural Science Foundation of China (82074283). If there are other authors, they 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.)

Hepatocellular carcinoma (HCC) is among the most fatal types of malignancy, with a high prevalence of relapse and limited treatment options. As a critical regulator of ferroptosis and redox homeostasis, glutathione peroxidase 4 (GPX4) is commonly upregulated in HCC and is hypothesized to facilitate cancer metastasis, but this has not been fully explored in HCC. Here, we report that up-regulated GPX4 expression in HCC is strongly associated with tumor metastasis. FACS-based in vivo and in vitro analysis revealed that a cell subpopulation featuring lower cellular reactive oxygen species levels and ferroptosis resistance were involved in GPX4-mediated HCC metastasis. Mechanistically, GPX4 overexpressed in HCC tumor cells was enriched in the nucleus and transcriptionally silenced GRHL3 expression, thereby activating PTEN/PI3K/AKT signaling and promoting HCC metastasis. Functional studies demonstrated that GPX4 amino acids 110-145 are a binding site that interacts with the GRHL3 promoter. As AKT is a downstream target of GPX4, we combined the AKT inhibitor, AKT-IN3, with lenvatinib to effectively inhibit HCC tumor cell metastasis. Overall, these results indicate that the GPX4/GRHL3/PTEN/PI3K/AKT axis controls HCC cell metastasis and lenvatinib combined with AKT-IN3 represents a potential therapeutic strategy for patients with metastatic HCC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Protein misfolding and aggregation can lead to various diseases. Recent studies have shed light on the aggregated protein in breast cancer pathology, which suggests that it is crucial to design chemical sensors that visualize protein aggregates in breast cancer, especially in clinical patient-derived samples. However, most reported sensors are constrained in cultured cell lines., Results: In this work, we present the development of two isophorone-based crystallization-induced-emission fluorophores for detecting proteome aggregation in breast cancer cell line and tissues biopsied from diseased patients, designated as A1 and A2. These probes exhibited viscosity sensitivity and recovered their fluorescence strongly at crystalline state. Moreover, A1 and A2 exhibit selective binding capacity and strong fluorescence for various aggregated proteins. Utilizing these probes, we detect protein aggregation in stressed breast cancer cells, xenograft mouse model of human breast cancer and clinical patient-derived samples. Notably, the fluorescence intensity of both probes light up in tumor tissues., Significance: The synthesized isophorone-based crystallization-induced-emission fluorophores, A1 and A2, enable sensitive detection of protein aggregation in breast cancer cells and tissues. In the future, aggregated proteins are expected to become indicators for early diagnosis and clinical disease monitoring of breast cancer., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To determine the frequency and clinical impact of loss-of-interruption (LOI) and duplication-of-interruption modifier variants of the HTT CAG and CCG repeat in a cohort of individuals with Huntington disease (HD)., Methods: We screened symptomatic HD participants from the UBC HD Biobank and 5 research sites for sequence variants. After variant identification, we examined the clinical impact and frequency in the reduced penetrance range., Results: Participants with CAG-CCG LOI and CCG LOI variants have a similar magnitude of earlier onset of HD, by 12.5 years. The sequence variants exhibit ancestry-specific differences. Participants with the CAG-CCG LOI variant also have a faster progression of Total Motor Score by 1.9 units per year. Symptomatic participants with the CAG-CCG LOI variant show enrichment in the reduced penetrance range. The CAG-CCG LOI variant explains the onset of 2 symptomatic HD participants with diagnostic repeats below the pathogenetic range., Conclusion: Our findings have significant clinical implications for participants with the CAG-CCG LOI variant who receive inaccurate diagnoses near diagnostic cutoff ranges. Improved diagnostic testing approaches and clinical management are needed for these individuals. We present the largest and most diverse HTT CAG and CCG sequence variant cohort and emphasize their importance in clinical presentation in HD., Competing Interests: Conflict of Interest Michael R. Hayden is the CEO of Prilenia Therapeutics, a private company, and serves on the public boards of Ionis Pharmaceuticals, AbCellera and 89bio. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The diagnosis of dengue virus (DENV) has been challenging particularly in areas far from clinical laboratories. Early diagnosis of pathogens is a prerequisite for the timely treatment and pathogen control. An ideal diagnostic for viral infections should possess high sensitivity, specificity, and flexibility. In this study, we implemented dual amplification involving Cas13a and Cas12a, enabling sensitive and visually aided diagnostics for the dengue virus. Cas13a recognized the target RNA by crRNA and formed the assembly of the Cas13a/crRNA/RNA ternary complex, engaged in collateral cleavage of nearby crRNA of Cas12a. The Cas12a/crRNA/dsDNA activator ternary complex could not be assembled due to the absence of crRNA of Cas12a. Moreover, the probe, with 5' and 3' termini labeled with FAM and biotin, could not be separated. The probes labeled with FAM and biotin, combined the Anti-FAM and the Anti-Biotin Ab-coated gold nanoparticle, and conformed sandwich structure on the T-line. The red line on the paper strip caused by clumping of AuNPs on the T-line indicated the detection of dengue virus. This technique, utilizing an activated Cas13a system cleaving the crRNA of Cas12a, triggered a cascade that amplifies the virus signal, achieving a low detection limit of 190 fM with fluorescence. Moreover, even at 1 pM, the red color on the T-line was easily visible by naked eyes. The developed strategy, incorporating cascade enzymatic amplification, exhibited good sensitivity and may serve as a field-deployable diagnostic tool for dengue virus., 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.)

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1 α )-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13 C 6 -glucose to 13 C 3 -lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1 α -mediated LDHA and NLRP3 signaling pathways., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)