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Large yellow croaker (Larimichthys crocea) is susceptible to oxidative denaturation during storage. This work is to investigate the quality alterations by analyzing its physicochemical changes and proteomics throughout preservation under refrigeration, frozen, and slurry ice (SI) conditions. Results revealed that the freshness of large yellow croaker, as evaluated by indicators such as total volatile basic nitrogen, total viable count, and thiobarbituric acid reactive substances, was well maintained while stored in the SI group. Meanwhile, the water distribution in the muscle tissue of group SI exhibited slower fluctuations, thereby preserving the integrity of fish muscle cells. Based on label-free proteomic analysis, a considerable downregulation was observed in the mitogen-activated protein kinase (MAPK) signaling pathway, indicating that SI decelerated this metabolic pathway and effectively delayed the deterioration of muscle. Therefore, the application of SI provides potential for maintaining the quality stability of large yellow croaker., Competing Interests: Declaration of competing interest The authors declare that they do not possess any recognized competing financial interests or personal relationships that could have potentially influenced the findings presented in this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Wooden breast (WB) myopathy has raised a worldwide concern among broiler industry during the past decade. Despite progress in understanding its etiology from transcriptional regulation, post-transcriptional mechanisms including the regulation of microRNAs (miRNAs) remain largely unknown. In the current study, we described an integrative analysis between mRNA and miRNA expression profiles of pectoralis major muscle from normal and WB myopathic broilers. A total of 1983 differentially expressed mRNAs (DEmRNAs) and 155 DEmiRNAs were identified in WB. We screened crucial biological processes and core DEmRNAs enriched in functional pathways, and established the protein-protein interaction network. DEmiRNAs and negatively correlated DEmRNAs regulatory networks were constructed, including 44 exist DEmiRNAs and 478 DEmRNAs, forming 772 miRNA-mRNA pairs. Upregulated DEmiRNAs including gga-miR-21-3p, gga-miR-460a-5p and gga-miR-6631-5p, as well as downregulated DEmiRNAs including gga-miR-182-5p, gga-miR-183 and gga-miR-96-5p were identified as hub miRNAs. Meanwhile, functional enrichment analysis indicated that upregulated DEmRNAs in the network were enriched in biological processes of response to stimulus, inflammatory response, extracellular matrix organization, whereas downregulated DEmRNAs were enriched in carbohydrate, amino acid and nucleotide metabolic processes. Collectively, our integrative miRNA and mRNA analysis highlighted candidate miRNAs and mRNAs, as well as potential miRNA-mRNA regulatory mechanisms involved in WB myopathy in broiler chicken., 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 the present study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although acute myeloid leukemia (AML) affects hematopoietic stem cell (HSC)-supportive microenvironment, it is largely unknown whether leukemia-modified bone marrow (BM) microenvironment can be remodeled to support normal hematopoiesis after complete remission (CR). As a key element of BM microenvironment, endothelial progenitor cells (EPCs) provide a feasible way to investigate BM microenvironment remodeling. Here, we find reduced and dysfunctional BM EPCs in AML patients, characterized by impaired angiogenesis and high ROS levels, could be partially remodeled after CR and improved by N-acetyl-L-cysteine (NAC). Importantly, HSC-supporting ability of BM EPCs is partially recovered, whereas leukemia-supporting ability is decreased in CR patients. Mechanistically, the transcriptome characteristics of leukemia-modified BM EPCs return to near-normal after CR. In a classic AML mouse and chemotherapy model, BM vasculature and normal hematopoiesis are reversed after CR. In summary, we provide further insights into how leukemia-modified BM microenvironment can be remodeled to support normal hematopoiesis after CR, which can be further improved by NAC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Heat stress (HS) largely impairs the quality of broiler breast meat through protein oxidative modification. This study aimed to investigate the carbonylation pattern of Ca 2+ channels and apoptotic proteins in the breast muscle of heat-stressed broilers. A total of 144 twenty-eight-day-old male Arbor Acres broilers were randomly divided into three treatment groups. The normal control (NC) group was kept at 22°C and provided with unlimited feed. The HS group was exposed to 32°C and provided with unlimited feed. The pair-fed (PF) group was kept at 22°C and given an amount of feed equivalent to that consumed by the HS group on the previous day. Results showed that broilers under HS conditions had a higher respiratory rate than those in NC and PF groups (P < 0.05). HS disrupted the morphology and structure of breast muscle fibers by decreasing the average diameters and average density of myofibers compared to the NC group (P < 0.05). HS increased the mean fluorescence intensity of the positive carbonyl signal in breast muscle compared with the NC group (P < 0.05). Besides, the pectoral Ca 2+ concentration in the sarcoplasmic reticulum, cytoplasm, and mitochondria was elevated by HS when compared with the NC group (P < 0.05). In comparison to the NC and PF groups, HS increased the apoptosis rate and caspase-3 activity in the breast muscle (P < 0.05). Furthermore, HS elevated the relative protein expressions of plasma membrane Ca 2+ -ATPase, Na + /Ca 2+ exchanger 1, and sarco/endoplasmic reticulum calcium transport ATPase 1 compared to the NC group (P < 0.05). Higher relative protein expression of μ-calpain and lower relative protein expression of cytosolic cytochrome complex were found in the HS group than the NC group (P < 0.05). HS decreased the carbonylation levels of transient receptor potential canonical 1 and inositol 1,4,5-trisphosphate receptor compared to the NC group (P < 0.05). Additionally, the carbonylation levels of cleaved caspase-3 and precursor caspase-9 were increased and decreased, respectively, by HS treatment compared to the NC group (P < 0.05). In conclusion, HS damages the myofiber based on Ca 2+ dyshomeostasis and apoptosis, which are potentially associated with protein carbonylation. These results shed new light on the possible mechanism behind the development of poor meat quality in broilers due to HS., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This experiment aimed to reveal the dynamic changes of protein post-translational lactylation modifications and their correlations with the glycolytic process in broiler breast muscle within 48 h of postmortem acidification. The experiment involved 12 male AA broilers, 42 days old, with similar body weights (2.8 ± 0.05 kg). The breast fillets (Pectoralis major) were collected after slaughter, and samples were taken at various time points: 0, 15 min, 30 min, 45 min, 60 min, 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h, 36 h, and 48 h postmortem. The results showed that the rate of glycogen decline in the muscle was highest at 45 min postmortem, and glycogen levels tended to stabilize at 8 h postmortem. The lactate content in the breast reached its highest level at 4 h postmortem and began to decrease, stabilizing at 24 h postmortem. Additionally, the glycolytic potential increased gradually in the first 4 h postmortem, decreased rapidly from 4 to 8 h. Similarly, lactylation modification levels were highest at 8 h postmortem, but stabilized at 12 h postmortem. During this process, the protein expression of the enzymatic lactylation modifier p300 showed no significant difference, while the content of the nonenzymatic lactylation substrate lactoylglutathione significantly decreased at 8 h and 24 h postmortem. Correlation analysis found that lactylation levels were negatively correlated with glycogen content, glucose content, glycolytic potential, and pH value, while positively correlated with lactate content. Besides, there was a positive correlation between lactylation levels and the protein expression of hexokinase, phosphoglycerate kinase 2, phosphoglucomutase 1, and triosephosphate isomerase. Additionally, lactylation levels were positively correlated with the activities of lactate dehydrogenase and phosphofructokinase. In summary, our experiment elucidated the dynamic changes in the entire glycolytic pathway in broiler pectoral muscle during acidification. During this process, lactylation modifications may participate in the glycolysis process by regulating the protein expression and activity of glycolytic enzymes., Competing Interests: DISCLOSURES The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to explore the effects of substituting soybean meal with a mixture of solid-state fermented rapeseed meal, apple pomace, and wheat bran on the growth performance, slaughter performance, meat quality, blood biochemical indices and intestinal barrier function of Langshan chickens. A total of 144 30-day-old Langshan chickens with similar body weights were randomly divided into three treatment groups, with six replicates per group and eight chickens per replicate: the control group (CON) was fed a corn-soybean meal basal diet, while the rapeseed meal mixture group (RSM) and the fermented rapeseed meal mixture group (FRSM) were fed diets substituting 5 % of soybean meal with rapeseed meal mixture and fermented rapeseed meal mixture, respectively. The trial lasted from 30 to 58 days of age. The results showed that compared to the CON group, the RSM group exhibited no significant changes in average daily feed intake (ADFI), average daily gain (ADG) and feed to gain ratio (F/G) (P > 0.05); the dressing percentage, half-eviscerated yield and eviscerated yield decreased (P < 0.05); the pH 24h and yellowness of breast muscle increased (P < 0.05); the crypt depth of the jejunum decreased, and the villus height/crypt depth ratio increased (P < 0.05); the serum D-lactic acid content decreased (P < 0.05). Compared to the CON group, the FRSM group exhibited no significant changes in ADFI, ADG and F/G (P > 0.05); the eviscerated yield increased (P < 0.05); the serum glucose and uric acid levels decreased (P < 0.05); the crypt depth of the jejunum decreased, and the villus height/crypt depth ratio increased (P < 0.05); the serum D-lactic acid content decreased (P < 0.05). Furthermore, compared to the RSM group, the FRSM group exhibited no significant changes in ADFI, ADG and F/G (P > 0.05); the dressing percentage, half-eviscerated yield and eviscerated yield increased (P < 0.05); the pH 24h of breast muscle decreased; the serum glucose and uric acid levels decreased (P < 0.05).In conclusion, RSM reduced the slaughter performance of Langshan chickens, while FRSM improved their slaughter performance. Both RSM and FRSM improved the jejunal morphology and intestinal permeability in Langshan chickens. In conclusion, fermentation improved the feed value of the rapeseed meal mixture; replacing part of the soybean meal diet with fermented rapeseed meal mixture helped improve the slaughter performance and intestinal barrier of Langshan chickens., 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 Inc.)

Background: Chinese giant salamander protein hydrolysates (CGSPH) are beneficial to human health as a result of their high content of amino acids and peptides. However, the formation of bitter peptides in protein hydrolysates (PHs) would hinder their application in food industry. The ultrasound assisted wet-heating Maillard reaction (MR) is an effective way to improve the flavor of PHs. Thus, the effect of ultrasonic assisted wet-heating MR on the structure and flavor of CGSPH was investigated in the present study., Results: The results indicated that the ultrasound assisted wet-heating MR products (MRPs) exhibited a higher degree of graft and more significant changes in the secondary and tertiary structures of CGSPH compared to traditional wet-heating MRPs. Moreover, ultrasound assisted wet-heating MR could significantly increase the content of small molecule peptides and reduce the content of free amino acids of CGSPH, which resulted in more significant changes in flavor characteristics. The changed in flavor properties after MR (especially ultrasound assisted wet-heating MRPs) were mainly manifested by a significant reduction in bitterness, as well as a significant increase in the content of aromatic aldehyde ester compounds such as furan-2-carbaldehyde, butanal, benzaldehyde, furfural, etc. CONCLUSIONS: Ultrasound assisted wet-heating MR between CGSPH and xylose could be a promising way to improve the sensory characteristics of CGSPH. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Although it is an effective treatment for acute myeloid leukemia (AML), chemotherapy leads to myelosuppression and poor hematopoietic reconstruction. Hematopoiesis is regulated by bone marrow (BM) endothelial cells (ECs), and BM ECs are dysfunctional in acute leukemia patients with poor hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation. Thus, it is crucial to explore the underlying mechanism of EC impairment and establish strategies for targeted therapy. TGF-β signaling was found to be upregulated in ECs from AML patients in complete remission (CR ECs) and led to CR EC damage. Administration of a TGF-β inhibitor rescued the dysfunction of ECs caused by TGF-β1 expression in vitro, especially their hematopoiesis-supporting ability. Moreover, inhibition of TGF-β expression repaired the BM EC damage triggered by chemotherapy in both AML patients in vitro and in an AML-CR murine model, and restored normal hematopoiesis without promoting AML progression. Mechanistically, our data reveal alterations in the transcriptomic pattern of damaged BM ECs, accompanied by the overexpression of downstream molecules TGF-βR1, pSmad2/3, and functional genes related to adhesion, angiogenesis suppression and pro-apoptosis. Collectively, our findings reveal for the first time that the activation of TGF-β signaling leads to BM EC dysfunction and poor hematopoietic reconstitution. Targeting TGF-β represents a potential therapeutic strategy to promote multilineage hematopoiesis, thereby benefiting more cancer patients who suffer from myelosuppression after chemotherapy., Competing Interests: Declaration of competing interest The authors wish to confirm that there are no known conflicts of interest associated with this publication. All co-authors have seen and approved this version of the manuscript and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to improve the mechanical properties and microstructure of recycled aggregate concrete (RAC) by incorporating carbon fibers (CFs) and nano-SiO 2 (NS) to promote the optimal utilization of RAC. The mechanical properties of the RAC were enhanced by both single and hybrid additions of CFs and NS, and the hybrid addition had a better strengthening effect. From the experimental results, it was found that the addition of CFs could increase the 28 d compressive strength and splitting strength of the RAC by 9.05% and 22.36%, respectively. The hybrid CFs and NS were more conducive to improving the mechanical properties of the RAC, and the enhancement effect increased first and then decreased with an increase in the NS content. The optimal content of NS was 0.8 wt%, which increased the 28 d compressive strength and splitting strength of the RAC by 20.51% and 14.53%, respectively. The microstructure results indicated that the addition of CFs had little effect on the optimized pore structure of the RAC, but the crack inhibition action of the CFs could improve the mechanical properties of the RAC. The addition of NS reduced the content of CH and facilitated the formation of more (C-S-H) gel. The hydrated calcium silicate (C-S-H) gel significantly decreased the porosity and transformed harmful capillary pores and harmful pores into harmless capillary pores and gel pores, thus improving the mechanical properties of the RAC. Therefore, the use of hybrid CFs and NS was more conducive to enhancing the performance of RAC for building materials.

Membrane filtration is one of the preferred choices for petroleum wastewater disposal due to its simplicity and low energy consumption. In this paper, a biodegradable superhydrophobic membrane based on loofah and rice straw (LF-RS) was prepared and modified with dodecyltriethoxysilane to improve its stability, morphology, and performance. The membrane showed an efficiency of 99.06% for oil/water separation with an average water flux of 2057.37 Lm -2 h -1 and a tensile strength of 11.19 MPa. The tensile strength of the LF-RS membrane was 322.47% higher than that of the PVDF membrane and 126.58% higher than that of the commercially available nitrocellulose membrane. Through molecular simulations, we showed a 96.3% reduction in interaction energy between water and membrane post-modification, which is beneficial for increasing the contact angle and separation performance. This study provides an option for the large-scale, cost-effective fabrication of eco-friendly membranes for pollutant removal.

Frequency-modulated continuous-wave (FMCW) narrow linewidth lasers have served as the cornerstone behind applications such as autonomous driving, wearable technology, virtual reality, and remote sensing mapping. Strongly coherent lasers are typically used for these studies, with a clear demand for linear fast response and wide frequency tuning range. In this paper, profiting from the ultrahigh-quality factor of the crystalline whispering-gallery-mode resonator, by using a self-injection locking mechanism to suppress spontaneous emission noise and improve coherence, sub-kHz linewidth at 450 nm is obtained. Furthermore, based on the dispersive response principle, fast electrical tuning is realized by using the strain-influenced resonator, and the experimental test result reaches 81 pm/V. More importantly, we demonstrate the comprehensive performance of this type of FMCW laser in underwater detection, with a sensitivity of 319 MHz/m at a chirp frequency of 1 kHz.

Background: Chronic heat stress (CHS) is a detrimental environmental stressor with a negative impact on the meat quality of broilers. However, the underlying mechanisms are not fully understood. This study investigates the effects of CHS on long non-coding RNA (lncRNA) expression and muscle injury in broilers, with a focus on its implications for meat quality., Results: The results showed that CHS diminished breast muscle yield, elevated abdominal fat deposition, induced cellular apoptosis (P < 0.05), and caused myofibrosis. Transcriptomic analysis revealed 151 differentially expressed (DE) lncRNAs when comparing the normal control (NC) and HS groups, 214 DE lncRNAs when comparing the HS and PF groups, and 79 DE lncRNAs when comparing the NC and pair-fed (PF) groups. After eliminating the confounding effect of feed intake, 68 lncRNAs were identified, primarily associated with cellular growth and death, signal transduction, and metabolic regulation. Notably, the apoptosis-related pathway P53, lysosomes, and the fibrosis-related gene TGF-β2 were significantly upregulated by lncRNAs., Conclusions: These findings indicate that chronic heat stress induces cellular apoptosis and muscle injury through lncRNA, leading to connective tissue accumulation, which likely contributes to reduced breast muscle yield and meat quality in broilers., (© 2024. The Author(s).)

Wooden breast (WB) myopathy is a common myopathy found in commercial broiler chickens worldwide. Although extensive research on WB has been conducted using transcriptomics, effectively screening and analyzing key target information remains a challenge. In this present study, 5 transcriptomic datasets obtained from the National Center for Biotechnology Information (NCBI) were used. A meta-analysis was conducted to identify meta-differentially expressed genes (meta-DEGs) involved in the response of broilers to WB myopathy. These meta-DEGs were further analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA), supplemented by protein-protein interaction (PPI) network construction to pinpoint hub genes. These analyses help to reveal key genes, pathways, and biological processes associated with WB myopathy. The results showed that 645 up-regulated and 99 down-regulated significant meta-DEGs (|log 2 FC| ≥0.6, P-Meta < 0.05, and present in at least 4 datasets) were identified. GO analysis showed that multiple fibrosis-related pathways/biological processes, such as cell adhesion, connective tissue development, and collagen-rich extracellular matrix, as well as calcium ion binding were significantly upregulated. PPI analysis identified TGFB3, COL1A1, COL1A2, and COL3A1 as central hub genes involved in the fibrotic processes. KEGG analysis revealed significant upregulation of apoptosis and lysosomal pathways, with an enrichment of Ca 2+ -related signals and lysosomal cathepsins within the apoptosis pathway. Additionally, GSEA indicated a suppression of the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain (ETC) in WB myopathy, with PPI analysis also identifying specific hub genes associated with these pathways. In conclusion, our comprehensive analysis of meta-DEGs elucidated key biological processes and pathways implicated in WB myopathy, including fibrosis, apoptosis, altered calcium signaling, and metabolic disruption. The identification of specific hub genes offers avenues for further investigation into the pathogenesis of this condition, potentially guiding targeted therapeutic strategies., 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.)

This study aims to develop an experimental model of high lactate levels in broilers to mimic the condition of birds under stress or diseases and evaluate its consequent effects on meat quality. The injection sites and dosage effects were compared separately in 2 experiments. Experiment 1 includes 3 injection sites: intraperitoneal injection, intramuscular injection, and subcutaneous injection. Experiment 2 was a dosage experiment based on the results of Experiment 1: sodium lactate intraperitoneal injection group with 1.5, 3, 6 mM concentration. The results showed that injecting sodium lactate intraperitoneally, intramuscularly, or subcutaneously all significantly decreased body weight and breast muscle weight while elevating lactic acid levels in both the blood and breast muscle of broilers. Moreover, all 3 injection methods caused a significant reduction in pH 24h and an increase in the shear force value of breast muscle. In addition, dose-response experiments of intraperitoneal injection showed that a concentration of 3 mM and 6 mM were significantly decreased body weight and breast muscle weight in broiler chickens, accompanied by a notable increase in breast muscle lactate content. Compared to the control group, intraperitoneal injections of 1.5 mM, 3 mM, and 6 mM sodium lactate treatments significantly reduced the yellowness values of the breast muscle. As the dose of sodium lactate increased, the shear force value of the breast meat exhibited linear and quadratic increments, while the drip loss decreased linearly. Intraperitoneal injection of 3 mM sodium lactate also significantly reduced the pH 24h of broiler breast muscle. In addition, an increased dose of lactate injections up-regulated the glycolytic pathway responsible for endogenous lactate production in the breast muscle by upregulating the expression of phosphofructokinase, pyruvate kinase and lactate dehydrogenase A. In conclusion, intraperitoneal injection of sodium lactate at 3 mM directly increased breast muscle lactate levels, providing a valuable method for establishing a high-level lactate model in poultry., Competing Interests: DISCLOSURES The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Trans-cinnamaldehyde (TC), a typical plant-derived compound, has been widely used in the control of foodborne pathogen contamination. Nevertheless, the risk associated with the occurrence of viable but nonculturable (VBNC) bacteria induced by TC remains unclear. The results of this study showed that Salmonella Enteritidis ( S. Enteritidis) entered the VBNC state after being induced by TC at a minimum inhibitory concentration of 312.5 μg/mL and survived for at least 22 days under TC treatment. Enhanced resistance was found against heat treatment (75°C, 30 s), antibiotics (i.e., ampicillin, ceftriaxone sodium, chloramphenicol), and hydrogen peroxide (3%) in VBNC S. Enteritidis. A synergistic effect against VBNC S. Enteritidis occurred when TC was combined with acid treatment, including lactic acid and acetic acid (pH = 3.5). VBNC and resuscitated S . Enteritidis by sodium pyruvate treatment (100 mM) were found to retain the infectious ability to Caco-2 cells. Relative expression levels of the stress-related genes relA , spoT , ppx , lon , katG , sodA , dnaK , and grpE were upregulated in VBNC S . Enteritidis. Accumulation of reactive oxygen species (ROS) and protein aggregates was observed in VBNC cells. Besides, the resuscitation of VBNC cells was accompanied with clearance of ROS and protein aggregates. In summary, this study presents a comprehensive characterization of stress tolerance and resuscitation of VBNC S . Enteritidis induced by cinnamaldehyde, and the results provide useful information for the development of effective control strategy against VBNC pathogenic bacteria in food production.

Objectives: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms., Methods: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/β-catenin pathway., Results: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/β-catenin signaling, and that a Wnt/β-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells., Conclusions: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/β-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer., (© 2024. Springer Nature Switzerland AG.)

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs) with high levels of reactive oxygen species (ROS) are responsible for defective hematopoiesis in poor graft function (PGF) patients with acute leukemia or myelodysplastic neoplasms post-allotransplant. However, the underlying mechanism by which BM EPCs regulate their intracellular ROS levels and the capacity to support hematopoiesis have not been well clarified. Herein, we demonstrated decreased levels of peroxisome proliferator-activated receptor delta (PPARδ), a lipid-activated nuclear receptor, in BM EPCs of PGF patients compared with those with good graft function (GGF). In vitro assays further identified that PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, characterized by the impaired ability to support hematopoiesis, which were restored by PPARδ overexpression. Moreover, GW501516, an agonist of PPARδ, repaired the damaged BM EPCs triggered by 5-fluorouracil (5FU) in vitro and in vivo. Clinically, activation of PPARδ by GW501516 benefited the damaged BM EPCs from PGF patients or acute leukemia patients in complete remission (CR) post-chemotherapy. Mechanistically, we found that increased expression of NADPH oxidases (NOXs), the main ROS-generating enzymes, may lead to elevated ROS level in BM EPCs, and insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway. Collectively, we found that defective PPARδ contributes to BM EPC dysfunction, whereas activation of PPARδ in BM EPCs improves their hematopoiesis-supporting ability after myelosuppressive therapy, which may provide a potential therapeutic target not only for patients with leukemia but also for those with other cancers., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. All co-author shave seen and approved this version of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Wooden breast (WB) myopathy is a common myopathy found in commercial broiler chickens worldwide. Histological examination has revealed that WB myopathy is accompanied by damage to the pectoralis major (PM) muscle. However, the underlying mechanisms responsible for the formation of WB in broilers have not been fully elucidated. This study aimed to investigate the potential role of hypoxia-mediated programmed cell death (PCD) in the formation of WB myopathy., Results: Histological examination and biochemical analysis were performed on the PM muscle of the control (CON) and WB groups. A significantly increased thickness of the breast muscle in the top, middle, and bottom portions (P<0.01) was found along with pathological structure damage of myofibers in the WB group. The number of capillaries per fiber in PM muscle, and the levels of pO 2 and sO 2 in the blood, were significantly decreased (P < 0.01), while the levels of pCO 2 and TCO 2 in the blood were significantly increased (P < 0.05), suggesting hypoxic conditions in the PM muscle of the WB group. We further evaluated the PCD-related pathways including autophagy, apoptosis, and necroptosis to understand the consequence response to enhanced hypoxic conditions in the PM muscle of birds with WB. The ratio of LC3 II to LC3 I, and the autophagy-related factors HIF-1α, BNIP3, Beclin1, AMPKα, and ULK1 at the mRNA and protein levels, were all significantly upregulated (P < 0.05), showing that autophagy occurred in the PM muscle of the WB group. The apoptotic index, as well as the expressions of Bax, Cytc, caspase 9, and caspase 3, were significantly increased (P < 0.05), whereas Bcl-2 was significantly decreased (P < 0.05) in the WB-affected PM muscle, indicating the occurrence of apoptosis mediated by the mitochondrial pathway. Additionally, the expressions of necroptosis-related factors RIP1, RIP3, and MLKL, as well as NF-κB and the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, were all significantly enhanced (P < 0.05) in the WB-affected PM muscle., Conclusions: The WB myopathy reduces blood supply and induces hypoxia in the PM muscle, which is closely related to the occurrence of PCD including apoptosis, autophagy, and necroptosis within myofibers, and finally leads to abnormal muscle damage and the development of WB in broilers., (© 2024. The Author(s).)

Mesenchymal stem cells (MSCs) are increasingly becoming a potential treatment approach for bone injuries due to the multi-lineage differentiation potential, ability to recognize damaged tissue sites and secrete bioactive factors that can enhance tissue repair. The aim of this work was to improve osteogenesis of carbon fibers reinforced polyetheretherketone (CF/PEEK) implants through bone marrow mesenchymal stem cells (BMSCs)-based therapy. Moreover, bioactive graphene oxide (GO) was introduced into CF/PEEK by grafting GO onto CF to boost the osteogenic efficiency of BMSCs. Subsequently, CF/PEEK was implanted into the symmetrical skull defect models of SD rats. Then in vivo biosafety and osteogenesis were evaluated. The results indicated that surface wettability of CF/PEEK was effectively improved by GO, which was beneficial for the adhesion of BMSCs. The pathological tissue sections stained with H&E showed no significant pathological change in the main organs including heart, liver, spleen, lung and kidney, which indicated no acute systemic toxicity. Furthermore, bone mineralization deposition rate of CF/PEEK containing GO was 2.2 times that of pure CF/PEEK. The X-ray test showed that the surface of CF/PEEK containing GO was obviously covered by more newly formed bone tissue than pure CF/PEEK after 8 weeks of implantation. This work demonstrated that GO effectively enhanced surface bioactivity of CF/PEEK and assisted BMSCs in accelerating differentiation into bone tissue, providing a feasible strategy for improving osteogenesis of PEEK and CF/PEEK.

The fatigue behavior of a high-strength bearing steel tempered under three different temperatures was investigated with ultrasonic frequency and conventional frequency loading. Three kinds of specimens with various yield strengths exhibited obvious higher fatigue strengths under ultrasonic frequency loading. Then, a 2D crystal plasticity finite element method was adopted to simulate the local stress distribution under different applied loads and loading frequencies. Simulations showed that the maximum residual local stress was much smaller under ultrasonic frequency loading in contrast to that under conventional frequency at the same applied load. It was also revealed that the maximum local stress increases with the applied load under both loading frequencies. The accumulated plastic strain was adopted as a fatigue indicator parameter to characterize the frequency effect, which was several orders smaller than that obtained under conventional loading frequencies when the applied load was fixed. The increment of accumulated plastic strain and the load stress amplitude exhibited a linear relationship in the double logarithmic coordinate system, and an improved fatigue life prediction model was established.

As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AβPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AβPP/PS1 mice. Phosphorylated tau (p-tau) mediates AβPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AβPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Enzymolysis clearance strategy, characterized by releasing the non-reabsorbable radioactive fragment under the specific cleavage of enzymes, is confirmed to be a safe and effective way to reduce the renal radioactivity accumulation in mice. However, the effectiveness of this strategy in humans remains unknown. Human epidermal growth factor receptor 2 (HER2) is overexpressed in various types of tumors, and radiolabeled HER2 Affibody is believed to be an attractive tool for HER2-targeted theranostics. However, its wide application is limited by the high and persistent renal uptake. In this study, we intend to validate the effectiveness of enzymolysis clearance strategy in reducing renal accumulation by using a modified HER2 Affibody., Materials and Methods: A new HER2 Affibody ligand, NOTA-MVK-Z HER2:2891 , containing a cleavable Met-Val-Lys (MVK) linker was synthesized and labeled with 68 Ga. The microPET imaging study was performed in SKOV-3 tumor mice to assess the uptakes of the control ligand and the MVK one in tumors and kidneys. Seven healthy volunteers were included for biodistribution and dosimetric studies with both the control and MVK ligands performed 1 week apart. Urine and blood samples from healthy volunteers were collected for in vivo metabolism study of the two ligands. Four HER2-positive and two HER2-negative patients were recruited for [ 68 Ga]Ga-NOTA-MVK-Z HER2:2891 PET/CT imaging at 2 and 4 h post-injection (p.i.)., Results: [ 68 Ga]Ga-NOTA-MVK-Z HER2:2891 was stable both in PBS and in mouse serum. MicroPET images showed that the tumor uptake of [ 68 Ga]Ga-NOTA-MVK-Z HER2:2891 was comparable to that of [ 68 Ga]Ga-NOTA-Z HER2:2891 at all the time points, while the kidney uptake was significantly reduced 40 min p.i. (P < 0.05). The biodistribution study in healthy volunteers showed that the kidney uptake of MVK ligand was significantly lower than that of the control ligand at 1 h p.i. (P < 0.05), with the SUV mean of 34.3 and 45.8, respectively, while the uptakes of the two ligands in the other organs showed negligible difference. The effective doses of the MVK ligand and the control one were 26.1 and 28.7 µSv/MBq, respectively. The enzymolysis fragment of [ 68 Ga]Ga-NOTA-Met-OH was observed in the urine samples of healthy volunteers injected with the MVK ligand, indicating that the enzymolysis clearance strategy worked in humans. The PET/CT study of patients showed that the range of SUV max of HER2-positive lesions was 9.4-21, while that of HER2-negative lesions was 2.7-6.2, which suggested that the MVK modification did not affect the ability of Z HER2:2891 structure to bind with HER2., Conclusion: We for the first time demonstrated that enzymolysis clearance strategy can effectively reduce renal radioactivity accumulation in humans. This strategy is expected to decrease renal radiation dose of peptide and small protein-based radiotracers, especially in the field of radionuclide therapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Salmonella enterica is a common foodborne pathogen that poses significant safety risks across the world. And benzalkonium bromide (BK) is widely used as a disinfectant to sterilize the food processing equipment. It has been reported that sub-lethal concentration of disinfectants induced not only the homologous resistance but also cross-resistances. This work analyzed the induced resistances of Salmonella Enteritidis by short-term adaptation (STA) and long-term adaptation (LTA) to BK. We have demonstrated that inefficient sterilization exposes Salmonella Enteritidis to sub-lethal concentrations of BK, and adapts bacteria to a higher minimum inhibitory concentration and minimum bactericidal concentration. In addition, STA, but not LTA, to BK induced heterogeneous resistance to sodium hypochlorite, and cross-resistance to freezing, desiccation, and heating, which may be caused by the membrane composition change of Salmonella Enteritidis. This work could be useful to the optimization of cleaning protocol.

Due to the unique lamellar structures, physicochemical and biological properties, electronegative two-dimensional (2D) materials have been explored for surface modification of carbon fibers reinforced polyetheretherketone (CFR-PEEK) composite. Deposition of electronegative 2D materials based on a porous surface created by concentrated H 2 SO 4 has been studied to promote osteogenesis of CFR-PEEK. Generally, a porous layer will be pre-built on CFR-PEEK through severe corrosion of concentrated sulfuric acid to help the loading of 2D materials. However, the severe corrosion will greatly reduce surface mechanical strength, especially wear resistance and hardness, which increases the risk of collapse or even peeling of the bioactive coating by external force. Herein, instead of the severe corrosion, a mild corrosion by concentrated HNO 3 was applied to modify the surface of CFR-PEEK to pre-create a dense transition layer for the further surface decoration of electronegative 2D materials (graphene oxide (GO) and black phosphorus (BP), representatively). The results indicated that hardness and wear resistance of the dense transition layer were markedly higher than those of the porous layer. Although GO and BP can be both loaded on these two transition layers, -SO 3 H on the porous transition layer showed moderate cytotoxicity, while -NO 2 on the dense transition layer showed good cytocompatibility. The dense transition layer displayed higher mineralized deposition in vitro and new bone formation rate in vivo than the porous transition layer, moreover, GO and BP coatings improved osteogenesis. This work offers inspirations for the construction of electronegative 2D material coating on CFR-PEEK based on chemical transition layers., 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 Ltd.)

As cities have grown, conductor rail power supplies have been widely used in the field of urban rail transit. In order to improve the running performance of trains and reduce the occurrence of accidents, it is necessary to understand the vibration of shoegear-rail system under different initial contact forces and explore the dynamic performance of shoegear-rail system. Therefore, according to the structure of shoegear-rail system, a coupling model of shoegear-rail system is established in this paper. On the basis of the model, the numerical simulation of the shoegear-rail system under different initial contact forces is carried out, and finally the vibration data of the shoegear-rail system under different initial contact forces are obtained. The results show that with the increase of initial contact force in the range of 70-160 N, the vibration amplitude of the electric shoegear and the fluctuation amplitude of the contact force increase, but the maximum absolute shear force value of the conductor rail decreases. It indicates that the lower initial contact force, the better the performance of shoegear-rail system., (© 2024. The Author(s).)

Studies have demonstrated that chronic heat stress can accelerate glycolysis, decrease glycogen content in muscle, and affect muscle quality. However, the consequences of chronic heat stress on glycogen synthesis, miRNA expression in pectoralis major (PM) muscle, and its regulatory functions remain unknown. In this study, high-throughput sequencing and cell experiments were used to explore the effects of chronic heat stress on miRNA expression profiles and the regulatory mechanisms of miRNAs in glycogen synthesis under chronic heat stress. In total, 144 cocks were allocated into 3 groups: the normal control (NC) group, the heat stress (HS) group, and the pair-fed (PF) group. In total, 30 differently expressed (DE) miRNAs were screened after excluding the effect of feed intake, which were mainly related to metabolism, signal transduction, cell growth and death. Furthermore, the gga-miR-212-5p/GYS1 axis was predicted to participate in glycogen synthesis through the miRNA-mRNA analysis, and a dual-luciferase reporter test assay confirmed the target relationship. Mechanistically, chronic heat stress up-regulated gga-miR-212-5p, which could inhibit the expression of GYS1 in the PM muscle. Knocking down gga-miR-212-5p alleviates the reduction of glycogen content caused by chronic heat stress; overexpression of gga-miR-212-5p can reduce glycogen content. This study provided another important mechanism for the decreased glycogen contents within the PM muscle of broilers under heat stress, which might contribute to impaired meat quality., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (EBV + DLBCL) predicts poor prognosis and CD30 expression aggravates the worse consequences. Here, we reported that CD30 positivity was an independent prognostic indicator in EBV + DLBCL patients in a retrospective cohort study. We harnessed CRISPR/Cas9 editing to engineer the first loss-of-function models of CD30 deficiency to identify that CD30 was critical for EBV + DLBCL growth and survival. We established a pathway that EBV infection mediated CD30 expression through EBV-encoded latent membrane protein 1 (LMP1), which involved NF-κB signaling. CRISPR CD30 knockout significantly repressed BCL2 interacting protein 3 (BNIP3) expression and co-IP assay indicated a binding between CD30 and BNIP3. Moreover, silencing of CD30 induced mitochondrial dysfunction and suppressed mitophagy, resulting in the accumulation of damaged mitochondria by depressing BNIP3 expression. Additionally, CRISPR BNIP3 knockout caused proliferation defects and increased sensitivity to apoptosis. All the findings reveal a strong relationship between mitophagy and adverse prognosis of EBV + DLBCL and discover a new regulatory mechanism of BNIP3-mediated mitophagy, which may help develop effective treatment regimens with anti-CD30 antibody brentuximab vedotin to improve the prognosis of CD30 + EBV + DLBCL patients., 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.)

This study aimed to investigate the effect of wooden breast (WB) myopathy on chemical composition, meat quality attributes and physiochemical characteristics of intramuscular connective tissue (IMCT) of broiler pectoralis major (PM) muscle. Thirty-six fillets were classified into varying degrees of WB condition, including normal, moderate and severe. Results show that WB myopathy altered the collagen profile in PM muscle by increasing total collagen content and decreasing collagen solubility. The composition of macromolecules in IMCT, including hydroxylysyl pyridoxine cross-linking, decorin and glycosaminoglycans, were increased with the severity of WB myopathy. Differential scanning calorimetry analysis indicated higher denaturation temperatures and lower denaturation enthalpy of IMCT for WB. Secondary structures of α-helix and β-sheet in the IMCT of WB were changed to β-turn and random coil. In addition, chemical composition and meat quality attributes showed a correlation with collagen profile and IMCT characteristics. Overall, this study emphasizes the effect of WB myopathy on IMCT and their contributions to meat quality variation.

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) MΦs in regulating normal and malignant hematopoiesis in different clinical stages of MDS are largely unknown. Age-paired patients with lower-risk MDS (N = 15), higher-risk MDS (N = 15), de novo acute myeloid leukemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. Flow cytometry analysis showed increased pro-inflammatory monocyte subsets and a decreased classically activated (M1) MΦs/alternatively activated (M2) MΦs ratio in the BM of patients with higher-risk MDS compared to lower-risk MDS. BM MФs from patients with higher-risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower-risk MDS group. AML BM MΦs showed markedly higher S100A8/A9 levels than lower-risk MDS BM MΦs. More importantly, coculture experiments suggested that the HSC supporting abilities of BM MΦs from patients with higher-risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower-risk MDS. Gene Ontology enrichment comparing BM MΦs from lower-risk MDS and higher-risk MDS for genes was involved in hematopoiesis- and immunity-related pathways. Our results suggest that BM MΦs are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM MΦs may represent a promising therapeutic approach for patients with MDS., (© 2024 Wiley Periodicals LLC.)

Involvement of the transcriptional regulator RpoS in the persistence of viable but non-culturable (VBNC) state has been demonstrated in several species of bacteria. This study investigated the role of the RpoS in the formation and resuscitation of VBNC state in Salmonella enterica serovar Enteritidis CICC 21482 by measuring bacterial survival, morphology, physiological characteristics, and gene expression in wild-type (WT) and rpoS-deletion (ΔrpoS) strains during long-term storage in powdered infant formula (PIF). The ΔrpoS strain was produced by allelic exchange using a suicide plasmid. Bacteria were inoculated into PIF for 635-day storage. Survival, morphology, intracellular reactive oxygen species (ROS) levels and intercellular quorum sensing autoinducer-2 (AI-2) contents were regularly measured. Resuscitation assays were conducted after obtaining VBNC cells. Gene expression was measured using real-time quantitative polymerase chain reaction (qPCR). The results showed that RpoS and low temperature conditions were associated with enhanced culturability and recoverability of Salmonella Enteritidis after desiccation storage in low water activity (a w ) PIF. In addition, the synthesis of intracellular ROS and intercellular quorum sensing AI-2 was regulated by RpoS, inducing the formation and resuscitation of VBNC cells. Gene expression of soxS, katG and relA was found strongly associated with RpoS. Due to the lack of RpoS factor, the ΔrpoS strain could not normally synthesize SoxS, catalase and (p)ppGpp, resulting in its early shift to the VBNC state. This study elucidates the role of rpoS in desiccation stress and the formation and resuscitation mechanism of VBNC cells under desiccation stress. It serves as the basis for preventing and controlling the recovery of pathogenic bacteria in VBNC state in low a w foods., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plant essential oils are unstable due to high volatility and easy oxidation, while microencapsulation provides a potentially effective strategy for increasing the stability of natural essential oils and preserving their function. This study examined the effects of feeding coated oregano essential oil and cinnamaldehyde (COEC) compounds on growth, immune organ development, intestinal morphology, mucosal immune function, and the cecal microbiota populations of broilers. Three hundred one-day-old male Arbor Acres broiler chicks were organized into 5 groups: 1) negative control fed basal diet alone (NC), 2) positive control receiving basal diet plus 50 mg/kg of chlortetracycline (CTC), 3) basal diet plus 150 mg/kg COEC (COEC150), 4) plus 300 mg/kg COEC (COEC300), and 5) plus 450 mg/kg COEC (COEC450). The supplement trial was continued for 42 d. The results showed that CTC, COEC300, and COEC450 treatments decreased the feed conversion ratio of broilers both in the starter and whole experiment phases, increased the height of jejunal villi at 21 d and the number of goblet cells and IgA-producing cells at 21 or 42 d compared with NC group (P < 0.05). Members of the COEC300 treatment group had a higher thymus weight index and jejunum length index than birds of NC or CTC groups at 21 d (P < 0.05). CTC and all COEC treatments decreased malondialdehyde content in jejunal mucosa at 42 d (P < 0.05). The population of Escherichia coli (E. coli) in the cecal digesta at 21 d was lower in the CTC, COEC300, and COEC450 treatment groups compared with the NC group (P < 0.05). In contrast to the CTC group, COEC supplementation dose-dependently accelerated body weight gain, improved jejunal morphology, decreased malondialdehyde content in jejunal mucosa, increased numbers of jejunal goblet cells and IgA-producing cells, and decreased the E. coli population in cecal digesta at 21 or 42 d (P < 0.05). Thus, we concluded that feeding broiler chickens with 300 or 450 mg/kg in antibiotic-free diets can improve growth performance, enhance immune responses, and inhibit the proliferation of cecal pathogenic bacteria., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. 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.)

In this work, 1 wt% of graphite oxide (GO) was used to strengthen the interface of carbon fibers (CF) reinforced polyetheretherketone (CFR-PEEK) composites, so as to obtain sufficiently high mechanical properties and bioactive surfaces which are two fundamental requirements for orthopedic/dental implants. Concretely, aminated GO was grafted onto oxidized CF in aqueous solution in a mild and non-toxic manner, subsequently, the CF grafted by GO was used for injection molding to prepare CFR-PEEK implant. The dispersibility of CF in the composites were remarkably boosted. Mechanical tests indicated that the flexural strength, compressive strength and hardness of CFR-PEEK were increased by 51%, 46%, and 30%, respectively. Furthermore, the flexural modulus increased to 11.67 ± 0.20 GPa and the compression modulus increased to 6.12 ± 0.11 GPa, which both meet the elastic modulus of human bone (6-30 GPa). The wear resistance was slightly improved. In the in vitro cell evaluation, CFR-PEEK with interface strengthening by GO showed no cytotoxicity and exhibited significantly enhanced adhesion and proliferation of Bone marrow mesenchymal stem cells (BMSCs) on the surface. More importantly, osteogenesis-related protein expression in vitro and osteogenetic evaluation in vivo all disclosed greatly accelerated osteo-differentiation of BMSCs on the composites due to the additive effect of GO at the interface. Based on this scheme, the CFR-PEEK composites with the dual functions of mechanical enhancement and osteointegration promotion holds great potential as implants in orthopedic/dental applications., 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 © 2023 Elsevier Ltd. All rights reserved.)

Elevated blood pressure is highly prevalent among dialysis patients and is associated with high mortality. Irisin is a newly found myokine that has been indicated to be related to blood pressure regulation in animal experiments. Data regarding the effect of serum irisin levels on blood pressure in dialysis patients are limited. To identify the association between serum irisin levels and blood pressure and examine determinant factors of systolic blood pressure in dialysis patients, we recruited 300 dialysis patients at Xuanwu Hospital Capital Medical University. Serum irisin levels were assessed by enzyme-linked immunosorbent assay kits. Blood pressure was self-measured on 7 consecutive days by an automated sphygmomanometer. The Pearson correlation test showed that the natural logarithm of irisin was negatively correlated with systolic blood pressure (r = -0.462, P < 0.001) and pulse pressure (r = -0.487, P < 0.001), but not correlated with diastolic blood pressure (r = -0.022, P = 0.709). Multivariate analysis revealed that the natural logarithm of irisin (β = -0.336, P < 0.001), lean tissue mass (β = 0.164, P = 0.005), diabetes mellitus (β = 0.165, P = 0.003) and serum calcium (β = -0.135, P = 0.019) were significant determinant factors for systolic blood pressure. This study is the first to demonstrate that serum irisin levels are significantly negatively associated with blood pressure in dialysis patients. Further studies are needed to provide possible mechanisms. We demonstrated that serum irisin levels were negatively associated with blood pressure in dialysis patients, which may provide a new target for antihypertensive treatment., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Chronic heat stress has detrimental effects on the growth performance of broilers, and the potential mechanism is under exploration. In this study, the protein carbonyl modification was introduced to glycolytic enzymes to evaluate its relationship with the growth performance of heat-stressed (HS) broilers. A total of 144 male 28-day-old broilers were assigned to 3 treatments: the normal control group (NC, raised at 22°C with free access to feed and water), the HS group (raised at 32°C with free access to feed and water), and the pair-fed group (PF, raised at 22°C with an amount of feed equal to that consumed by the HS group on a previous day). Results showed that heat stress decreased the average daily growth, increased the feed-to-gain ratio (F/G), decreased breast muscle rate, and increased abdominal fat rate compared with the NC and PF groups (P < 0.05). Higher cloacal temperature and serum creatine kinase activity were found in the HS group than those of the NC and PF groups (P < 0.05). Heat stress increased the contents of carbonyl, advanced glycation end-products, malonaldehyde, and the activities of catalase, glutathione peroxidase, and total antioxidant capacity compared with the NC and PF groups (P < 0.05). Heat stress increased the contents of glucose and lactate, declined the glycogen content, and lowered the relative protein expressions of pyruvate kinase muscle type, lactate dehydrogenase A type (LDHA), and citrate synthase compared to those of the NC group (P < 0.05). In contrast to the NC and PF groups, heat stress intensified the carbonylation levels of phosphoglucomutase 1, triosephosphate isomerase 1, β-enolase, and LDHA, which were positively correlated with the F/G (P < 0.05). These findings demonstrate that heat stress depresses growth performance on account of oxidative stress and glycolysis disorders. It further increases the carbonylation of glycolytic enzymes, which potentially correlates with the F/G by disturbing the mode of energy supply of broilers., (Copyright © 2023. Published by Elsevier Inc.)

This study was purposed to investigate the efficacy of dietary creatine nitrate (CrN) supplementation on redox status and mitochondrial function in pectoralis major (PM) muscle of broilers that experienced preslaughter transport. A total of 288 Arbor Acres broilers (28-day-old) were randomly assigned into five dietary treatments, including a basal diet or the basal diet supplemented with 600 mg/kg guanidinoacetic acid (GAA), 300, 600, or 900 mg/kg CrN for 14 days, respectively. On the transportation day, the basal diet group was divided into two groups on average, resulting in six groups. The control group was transported for 0.5 h and the other groups for 3 h (identified as Control, T 3h , GAA 600 , CrN 300 , CrN 600 , and CrN 900 group, respectively), and all crates were randomly placed on the truck travelling at an average speed of 80 km/h. Our results showed that GAA 600 and CrN treatments decreased the muscle ROS level and MDA content ( P  < 0.05) and increased the mitochondrial membrane potential ( P  < 0.001), as well as a higher mRNA expression of avUCP ( P  < 0.001) and lower mRNA expressions of Nrf2 ( P  < 0.001), Nrf2 and PGC-1α ( P  < 0.05) compared with T 3h group. Meanwhile, the mRNA and protein expressions of Nrf1, TFAM, and PGC-1α in CrN 600 and CrN 900 groups were lower than those in the T 3h group ( P  < 0.05). Conclusively, dietary supplementation with GAA and CrN decreased muscle oxidative products and enhanced mitochondrial uncoupling mechanism and mtDNA copy number, which relieved muscle oxidative damage and maintained mitochondrial function.

Heat stress can cause systemic immune dysregulation and threaten the health of broilers. Guanidinoacetic acid (GAA) has been shown to be effective against heat stress, but whether it is beneficial for immunity is unclear. Therefore, the effects of dietary GAA supplementation on the immunity of chronic heat-stressed broilers were evaluated. A total of 192 Arbor Acres male broilers (28-day old) were randomly allocated to 4 treatments: the normal control group (NC, 22°C, ad libitum feeding), the heat stress group (HS, 32°C, ad libitum feeding), the pair-fed group (PF, kept at 22°C and received food equivalent to that consumed by the HS group on the previous day), and the GAA group (HG, 32°C, ad libitum feeding; basal diet supplemented with 0.6 g/kg GAA). Samples were collected on d 7 and 14 after treatment. Results showed that broilers exposed to heat stress exhibited a decrease (P < 0.05) in ADG, ADFI, thymus and bursa of Fabricius indexes, and an increase (P < 0.05) in feed conversion ratio and panting frequency, compared to the NC group. Levels of corticotropin-releasing factor, corticosterone (CORT), heat shock protein 70 (HSP70), IL-6, and TNF-α were elevated (P < 0.05) while lysozyme and IgG concentration was decreased (P < 0.05) in the HS group compared with the NC group after 7 d of heat exposure. The concentrations of IgG and IL-2 were decreased (P < 0.05) and CORT was increased (P < 0.05) in the HS group compared with the NC group after 14 d of heat exposure. Noticeably, GAA supplementation decreased the levels of CORT (P < 0.05) and increased the IL-2, IgG, and IgM concentrations (P < 0.05) compared with the HS group. In conclusion, chronic heat stress increased CORT release, damaged immune organs, and impaired the immunity of broilers. Dietary supplementation of 0.6 g/kg GAA can reduce the CORT level and improve the immune function of broilers under heat stress conditions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Low back pain (LBP) is the leading cause of disability worldwide, with a strong correlation to intervertebral disc degeneration (IDD). Inflammation-induced extracellular matrix (ECM) degradation plays a major role in IDD's progression. Emodin, known for its anti-inflammatory effects and ability to inhibit ECM degradation in osteoarthritis, but its role in IDD is unclear. Our study aimed to explore emodin's role and mechanisms on IDD both in vivo and in vitro. We discovered that emodin positively regulated anabolic markers (COL2A1, aggrecan) and negatively impacted catabolic markers (MMP3, MMP13) in nucleus pulposus cells, while also inhibiting cell apoptosis under inflammation environment. We revealed that emodin inhibits inflammation-induced NF-ĸB activation by suppressing the degradation of LRP1 via the proteasome pathway. Additionally, LRP1 was validated as essential to emodin's regulation of ECM metabolism and apoptosis, both in vitro and in vivo. Ultimately, we demonstrated that emodin effectively alleviates IDD in a rat model. Our findings uncover the novel pathway of emodin inhibiting ECM degradation and apoptosis through the inhibition of NF-κB via LRP1, thus alleviating IDD. This study not only broadens our understanding of emodin's role and mechanism in IDD treatment but also guides future therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no potential competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aplastic anemia (AA) is a life-threatening disease characterized by bone marrow (BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells (ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA. N-acetyl-L-cysteine (NAC, a reactive oxygen species scavenger) or exogenous EC infusion was administered to AA mice. Furthermore, the frequency and functions of BM ECs from AA patients and healthy donors were evaluated. BM ECs from AA patients were treated with NAC in vitro, and then the functions of BM ECs were evaluated. We found that BM ECs were significantly decreased and damaged in AA mice. Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized, whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice. Consistently, BM ECs in AA patients were decreased and dysfunctional. Furthermore, dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes, which could be repaired by NAC in vitro. The reactive oxygen species pathway was activated, and hematopoiesis- and immune-related signaling pathways were enriched in BM ECs of AA patients. In conclusion, our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA, suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients., (© 2023. Science China Press.)

This study was conducted to explore the influences of carbonyl modification on proteins within the breast muscle of heat-stressed broilers and their correlations to decreased meat quality. The results showed that birds that suffered from heat stress had higher lightness, drip loss, shear force value, and hardness, and lower redness and springiness of breast meat than those under normal control and pair fed treatments. Proteomic analysis identified a total of 921 differentially carbonylated sites, which were allocated to 419 proteins. The modified sites included Lys, Pro, Arg, Trp, Cys, His, and Met. Seven motif sequences were detected, where five motifs neighbored Lys and two neighbored Pro. The differentially carbonylated proteins in heat-stressed birds mainly participated in the glycolytic process, collagen fibril organization, calcium homeostasis, and apoptosis. This study provided a unique landscape of the muscular carbonyl modification rule and unraveled the potential impact of carbonylated protein on meat quality., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis., Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD., Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro., Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD., 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., (© 2023 Published by Elsevier Ltd.)

EBV-positive diffuse large B-cell lymphoma, not otherwise specified (EBV + DLBCL-NOS), is an EBV-positive clonal B-cell lymphoid proliferation and circulating EBV-DNA is a great indicator for prognosis among EBV associated disease. In this retrospective study, we report 66 EBV + DLBCL cases among 2137 DLBCL-NOS cases diagnosed from 2013 to 2021 (prevalence of 6.0%). After a median follow-up of 27 months, progression-free survival (PFS) and overall survival (OS) at 2 years were 39.5% ± 6.2% and 53.6% ± 6.4%, respectively. Multivariate analysis showed that only the biomarker of the positivity of post treatment EBV-DNA had a borderline correlation with shorter PFS and OS (PFS: P = 0.053; OS: P = 0.065). Patients were divided into three subgroups according to dynamic changes of EBV-DNA status: EBV-DNA persistently negative group, EBV-DNA persistently positive group, and EBV-DNA transformed from positive to negative group; among the three groups, patients of the persistently positive group had worst PFS and OS (P = 0.0527 and P = 0.0139, respectively). Decline in EBV copies correlated significantly with treatment response as well. In conclusion, circulating EBV-DNA level played a vital role in prognostic and monitoring marker for EBV + DLBCL-NOS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The incidence of wooden breast (WB) meat of commercial broiler chicken has been increasing in recent years. Histological examination found that the occurrence of WB myopathy was accompanied by the pectoralis major (PM) muscle damage. So far, the potential mechanisms are not fully understood. This study aimed to explore the underlying mechanism of the damage of WB-affected PM muscle caused by changes in mitochondrial function, mitochondrial redox status and Ca 2+ homeostasis. A total of 80 market-age Arbor Acres male broiler chickens were sampled and categorized into control (CON) and WB groups based on the evaluation of myopathic lesions. PM muscle samples were collected (n = 8 in each group) for histopathological evaluation and biochemical analyses. Ultrastructural examination and histopathological changes suggested the occurrence of PM muscle damage in broiler chickens with WB myopathy. The WB group showed an increased level of reactive oxygen species and enhanced antioxidant capacities in mitochondria of PM muscle. These changes were related to impaired mitochondria morphology and mitochondrial dysfunction. In addition, abnormal expressions of Ca 2+ channels led to substantial Ca 2+ loss in SR and cytoplasmic Ca 2+ overload, as well as Ca 2+ accumulation in mitochondria, resulting in Ca 2+ dyshomeostasis in PM muscle of broiler chickens with WB myopathy. Combined, these findings indicate that WB myopathy is related to mitochondrial dysfunction, mitochondrial redox status imbalance and Ca 2+ dyshomeostasis, leading to WB-affected PM muscle damage., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rational design of self-assembled DNA nanostructures has become one of the fastest-growing research areas in molecular science. Particular attention is focused on the development of dynamic DNA nanodevices whose configuration and function are regulated by specific chemical inputs. Herein, we demonstrate the concept of metal-mediated base-pair switching to induce inter- and intramolecular DNA strand displacement in a metal-responsive manner. The 5-hydroxyuracil (U OH ) nucleobase is employed as a metal-responsive unit, forming both a hydrogen-bonded U OH -A base pair and a metal-mediated U OH -Gd III -U OH base pair. Metal-mediated strand displacement reactions are demonstrated under isothermal conditions based on the base-pair switching between U OH -A and U OH -Gd III -U OH . Furthermore, metal-responsive DNA tweezers and allosteric DNAzymes are developed as typical models for DNA nanodevices simply by incorporating U OH bases into the sequence. The metal-mediated base-pair switching will become a versatile strategy for constructing stimuli-responsive DNA nanostructures, expanding the scope of dynamic DNA nanotechnology., (© 2023. Springer Nature Limited.)

Lymphocyte proliferation and tumourigenesis are dependent on nucleotide synthesis to support DNA, RNA and phospholipid synthesis. Here, we identified that reprogramming of nucleotide metabolism as an important factor divides mantle cell lymphoma (MCL) into two groups with different transcriptional signalling pathways and varying prognoses. We establish a nucleotide metabolism-related prognostic model that includes six genes with different regression coefficients, which significantly predicts prognosis for MCL patients (p < 0.0001). Of these six genes, de novo CTP synthesis pathway enzyme CTPS1 whose inhibitor (STP938) is already in clinical trials for relapsed/refractory lymphomas (NCT05463263) has the highest regression coefficient. An increase in CTPS1 expression predicts adverse overall survival and progression-free survival with independent prognostic significance in 105 primary MCL samples and GEO database (GSE93291). CRISPR CTPS1 knockout causes DNA damage and proliferation defects in MCL. Additionally, MYC positively regulates CTPS1 expression, and TP53-aberrant and ibrutinib-resistant MCL cells also rely on cytidine metabolism. Furthermore, besides the obvious decreased CTP pool caused by CTPS1 deficiency, CTPS1 inhibition may also induce immune-related responses via activating dsDNA-cGAS-STING pathway, which plays a crucial role in impeding tumour growth in MCL patients., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Temporomandibular joint osteoarthritis (TMJ OA) is a progressive degenerative disease of the temporomandibular joint (TMJ). The unclear etiology and mechanisms of TMJ OA bring great difficulties to early diagnosis and effective treatment, causing enormous burdens to patients' life and social economics. In this narrative review, we summarized the main pathological changes of TMJ OA, including inflammatory responses, degeneration of extracellular matrix (ECM), abnormal cell biological behaviors (apoptosis, autophagy, and differentiation) in TMJ tissue, and aberrant angiogenesis. All pathological features are closely linked to each other, forming a vicious cycle in the process of TMJ OA, which results in prolonged disease duration and makes it difficult to cure. Various molecules and signaling pathways are involved in TMJ OA pathogenesis, including nuclear factor kappa-B (NF-κB), mitogen-activated protein kinases (MAPKs), extracellular regulated protein kinases (ERKs) and transforming growth factor (TGF)-β signaling pathways et al. One molecule or pathway can contribute to several pathological changes, and the crosstalk between different molecules and pathways can further lead to a complicated condition TMJ OA. TMJ OA has miscellaneous etiology, complex clinical status, depressed treatment results, and poor prognosis. Therefore, novel in-vivo and in-vitro models, novel medicine, materials, and approaches for therapeutic procedures might be helpful for further investigation of TMJ OA. Furthermore, the role of genetic factors in TMJ OA needs to be elucidated to establish more reasonable and effective clinical strategies for diagnosing and treating TMJ OA., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Approaches for the diagnosis of wooden breast (WB) myopathy in live birds are urgently required before applying intervention strategies to reduce occurrence and severity for the poultry industry. The objective of this study was to characterize the serum metabolic profiles in male broilers affected by WB and to identify biomarkers related to this myopathy. Broilers were categorized into normal (CON) and WB groups based on gross scoring and histological evaluation. Gas chromatography-mass spectrometry-based metabolomics, multivariate analysis, and orthogonal partial least squares discriminant analysis revealed a clear separation between CON and WB. A total of 73 significantly different (P < 0.05) metabolites with 17 upregulated and 56 downregulated were identified, which were mainly involved in pathways of alanine, aspartate, and glutamate metabolism, carbohydrate metabolism, and taurine and hypotaurine metabolism. By using the nested cross-validation function of random forest analysis, 9 significantly altered (P < 0.05) metabolites (cerotinic acid, arabitol, phosphoenolpyruvate, terephthalic acid, cis-gondoic acid, N-acetyl-d-glucosamine, 4-hydroxymandelic acid, caffeine, and xanthurenic acid) were identified as biomarkers with an excellent discriminant performance for WB myopathy. Collectively, this study provides new insights for a deeper understanding of the pathogenesis and provides metabolites as biomarkers for diagnostic utilization of WB myopathy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)