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Although protein-polysaccharide complexes with different phase behaviors all show potential for stabilizing high internal phase Pickering emulsions (HIPPEs), it is not clarified which aggregation state is more stable and age-friendly. In this study, we investigated and compared the stability and age friendliness of HIPPEs stabilized with egg yolk and carboxymethyl cellulose (EYCMC) in different phase behaviors. The results revealed differences in particle size, aggregation state, charge potential, and stability of secondary and tertiary structures of EYCMC. The behavior of EYCMC at the oil-water interface was mainly divided into three phases: rapid diffusion, permeation, and reorganization. The electrostatic interaction, kinetic hindrance, and depletion attraction were the mechanisms primarily involved in stabilizing HIPPEs by EYCMC. Rheological analysis results indicated that HIPPEs had excellent viscoelasticity, structural recovery properties and yield stress. HIPPEs were used in 3D printing, electronic nose testing, IDDSI testing and in vitro digestive simulations for the elderly, demonstrating a fine appearance, safe consumption and bioaccessibility of β-carotene. Soluble complexes showed the best stability and age friendliness compared to other aggregated forms. This study serves as a foundational source of information for developing innovative foods utilizing HIPPEs., Competing Interests: Declaration of competing interest All co-authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Quantitative CT (QCT) is a method of measuring bone mineral density (BMD) of human based on a CT machine,calibrated by QCT body model and analyzed by professional software.Compared with dual-energy X-ray absorptiometry,QCT can not only assess the cortical and cancellous BMD but also exclude the influences of osteophytes and aortic/vascular calcification,thus being capable of accurately reflecting patients' bone mass.In recent years,increasing studies on QCT and osteoporosis (OP) have been carried out,and the application of QCT in the diagnosis of OP,evaluation of vertebral bone conditions,prediction of fracture risks,and assessment of anti-OP treatment is garnering increasing attention from researchers at home and abroad.This article reviews the research progress in this field,aiming to provide a reference for the research on QCT in the diagnosis and treatment of OP.

Human papillomavirus (HPV), known for its oncogenic properties, is the primary cause of cervical cancer and significantly contributes to mortality rates. It also plays a considerable role in the globally rising incidences of head and neck cancers. These cancers pose a substantial health burden worldwide. Current limitations in diagnostic and treatment strategies, along with inadequate coverage of preventive vaccines in low- and middle-income countries, hinder the progress toward the World Health Organization (WHO) HPV prevention and control targets set for 2030. In response to these challenges, extensive research in structural virology has explored the properties of HPV proteins, yielding crucial insights into the mechanisms of HPV infection that are important for the development of prevention and therapeutic strategies. This review highlights recent advances in understanding the structures of HPV proteins and discusses achievements and future opportunities for HPV vaccine development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Epidemiology links noise to increased risk of metabolic diseases like diabetes and obesity. Translational studies in humans and experimental animals showed that noise causes reactive oxygen species (ROS)-mediated cardiovascular damage. The interaction between noise and diabetes, specifically potential additive adverse effects, remains to be determined., Methods and Results: C57BL/6 mice were treated with streptozotocin (i.p. injections, 50 mg/kg/d for 5d) to induce type-1 diabetes, with S961 (subcutaneous osmotic minipumps, 0.57 mg/kg/d for 7d) or fed a high-fat diet (HFD, 20 weeks) to induce type-2 diabetes. Control and diabetic mice were exposed to aircraft noise to an average sound pressure level of 72 dB(A) for 4d. While body weight was unaffected, noise reduced insulin production in all diabetes models. The oral glucose tolerance test showed only an additive aggravation by noise in the HFD model. Noise increased blood pressure and aggravated diabetes-induced aortic, mesenteric, and cerebral arterioles endothelial dysfunction. ROS formation in cerebral arterioles, the aorta, the heart, and isolated mitochondria was consistently increased by noise in all models of diabetes. Mitochondrial respiration was impaired by diabetes and noise, however without additive effects. Noise increased ROS and caused inflammation in adipose tissue in the HFD model. RNA sequencing data and alteration of gene pathway clusters also supported additive damage by noise in the setting of diabetes., Conclusion: In all three models of diabetes, aircraft noise exacerbates oxidative stress, inflammation, and endothelial dysfunction in mice with pre-existing diabetes. Thus, noise may potentiate the already increased cardiovascular risk in diabetic patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Isobavachin (IBA) is a dihydroflavonoid compound with various pharmacological effects. However, further investigation into the hepatotoxicity of IBA is necessary. This study aims to identify the hepatotoxic effects of IBA and explore its potential mechanisms. The study assessed the impact of IBA on the viability of AML12, HepG2, LO2, rat, and mouse primary hepatocytes using MTT and LDH assays. Autophagy was detected in AML12 cells after IBA treatment using electron microscopy, MDC, and Ad-mCherry-GFP-LC3B fluorescence. The effect of IBA on autophagy-related proteins was examined using Western blot. The results showed that IBA had dose-dependent inhibitory effects on five cells, induced autophagy in AML12 cells, and promoted autophagic flux. The study found that IBA treatment inhibited phosphorylation of PI3K, Akt, and mTOR, while increasing phosphorylation levels of AMPK and ULK1. Treatment with both AMPK and PI3K inhibitors reversed the expression of AMPK and PI3K-Akt-mTOR signaling pathway proteins. These results suggest that IBA may have hepatocytotoxic effects but can also prevent IBA hepatotoxicity by inhibiting the AMPK and PI3K/Akt/mTOR signaling pathways. This provides a theoretical basis for preventing and treating IBA hepatotoxicity in clinical settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential 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. The author was not involved in the editorial review or the decision to publish this article. Financial interests/personal relationships without potential competing interests:, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Immunoassays have been widely used for the determination of various analytes in the fields of disease diagnosis, food safety, and environmental monitoring. Dual-signal immunoassays are now advanced and integrated detection technologies with excellent self-correction and self-validation capabilities. In this work, we summarize the recent advances in the development of optical and electrochemical dual-signal immunoassays, including colorimetric, fluorescence, surface-enhanced Raman spectroscopy (SERS), electrochemical, electrochemiluminescence, and photoelectrochemical methods. This review particularly emphasizes the working principle of diverse dual-signal immunoassays and the utilization of dual-functional molecules and nanomaterials. It also outlines the challenges and prospects of future research on dual-signal immunoassays.

Recent evidence suggests that adaptive immune cells are important contributors to metabolic dysfunction-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease, NAFLD). In liver biopsies from MASLD patients, the accumulation of intrahepatic B cells is positively correlated with the MASLD activity score. Hepatic B-cell infiltration is observed in experimental models of metabolic dysfunction-associated steatohepatitis (MASH, formerly non-alcoholic steatohepatitis, NASH). Intrahepatic B2 cells have been shown to contribute to MASLD/MASH by activating T cells, macrophages and hepatic stellate cells, and by producing pathogenic IgG antibodies. In mice fed a MASH diet, selective depletion of B2 cells reduces steatohepatitis and fibrosis. Intestinal B cells are metabolically activated in MASH and promote T-cell activation independently of TCR signaling. In addition, B cells have been shown to contribute to liver fibrosis by activating monocyte-derived macrophages through the secretion of IgA immunoglobulins. Furthermore, our recent study indicates that certain B cell subsets, very likely regulatory B cells, may play a protective role in MASLD. This review summarizes the molecular mechanisms of B cell functions and discusses future research directions on the different roles of B cells in MASLD and MASH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li and Xia.)

This study proposes a kill two birds with one stone strategy to improve the health and safety of pork with high internal phase Pickering emulsions (HIPPEs). HIPPEs improved the pseudoplasticity and viscosity (from 619.3 to 1712 Pa·s at 0.1 s -1 ) of the pork, favoring smooth extrusion and adhesion of the ink. Shear recovery of pork gel increased from 39.20 % to 77.78 % by addition of HIPPEs. HIPPEs enhanced the pork gel viscoelastic properties (K 4  = 341.29, K 5  = 453.11) and yield stress (268.55 Pa). HIPPEs-adjusted pork gel (HPG) has favorable 3D printing, pork aroma, safe swallowing (level 5 food), and high digestibility (80.40 %), demonstrating its potential as a dysphagia diet. HPG reduced the cooking loss of pork (from 30.8 % to 1.9 %), which is suitable for dysphagic patients with reduced salivation. HIPPEs adjusts the properties of pork gel by filling and winding gel networks. These results provide new ideas for the development of special formula foods., 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.)

Chemokine CXCL12 plays a crucial role in both direct bactericidal activity and phagocytosis in humans. However, the mechanisms and evolutionary functions of these processes in vertebrates remain largely unknown. In this study, we found that the direct bactericidal activity of CXCL12 is highly conserved across various vertebrate lineages, including Arctic lamprey (Lampetra japonica), Basking shark (Cetorhinus maximus), grass carp (Ctenopharyngodon idella), Western clawed frog (Xenopus tropicalis), Green anole (Anolis carolinensis), chicken (Gallus gallus), and human (Homo sapiens). CXCL12 also has been shown to promote phagocytosis in lower and higher vertebrates. We then employed C. idella CXCL12a (CiCXCL12a) as a model to further investigate its immune functions and underlying mechanisms. CiCXCL12a exerts direct broad-spectrum antibacterial activity by targeting bacterial acidic phospholipids, resulting in bacterial cell membrane perforation, and eventual lysis. Monocytes/macrophages are attracted to the infection sites for phagocytosis through the rapid production of CiCXCL12a during bacterial infection. CiCXCL12a induces CDC42 and CDC42 GTPase activation, which in turn mediates F-actin polymerization and cytoskeletal rearrangement. The interaction between F-actin and Aeromonas hydrophila facilitates bacterial internalization into monocytes/macrophages. Additionally, A. hydrophila is colocalized within early endosomes, late endosomes and lysosomes, ultimately degrading within phagolysosomes. CiCXCL12a also activates PI3K-AKT, JAK-STAT5 and MAPK-ERK signaling pathways. Notably, only the PI3K-AKT signaling pathway inhibits LPS-induced monocyte/macrophage apoptosis. Thus, CiCXCL12a plays key roles in reducing tissue bacterial loads, attenuating organ injury, and decreasing mortality rates. Altogether, our findings elucidate the conserved mechanisms underlying CXCL12-mediated bactericidal activity and phagocytosis, providing novel perspectives into the immune functions of CXCL12 in vertebrates., (© 2024. Science China Press.)

Background: Irreversible electroporation has been proved as a feasible and safe method against tumor in liver. However, few studies focused on tumors adjacent to perihepatic important structure like vessels, biliary system and gall bladder. These structures limit the effectiveness of conventional treatments. The aim of this article is to analyze the clinical outcomes of patients with hepatic tumors at the special sites who received IRE treatment and provide reliable evidence for broadening the scope of IRE's clinical application., Methods: The clinical information of patients who underwent IRE ablation for tumors adjacent to perihepatic important structure between February 2017 and December 2021 was collected and retrospectively analyzed. All patients underwent contrast-enhanced CT or MRI for further evaluation at the 1-month follow-up and every 3 months thereafter. Post-ablation complications, recurrence, progression-free survival and overall survival were evaluated to analyze the prognosis of IRE ablation adjacent to perihepatic important structure. Categorical variables are presented as numbers followed by percentages. Continuous data are presented as the mean ± deviation. The tumor size and IRE ablation size were evaluated by the maximum diameters., Results: Thirty-two patients who underwent IRE ablation for tumor adjacent to perihepatic important structure were studied in this research. There were 39 lesions in 32 patients treated with IRE ablation. Fourteen of them (35.9%) were located adjacent to the porta hepatis, and 8 of them (20.5%) were located adjacent to the hepatocaval confluence. Subcapsular lesions accounted for 15.4% (6 of 39 lesions). The other 11 lesions were in the para gallbladder (5 of 39 lesions, 12.8%), the caudate lobe (5 of 39 lesions, 12.8%) and the colonic hepatic flexure (1 of 39 lesions, 2.6%). According to the Clavien-Dindo classification system for complications, all relative patients with cancer experienced complications below class III except one patient who developed postoperative hemorrhagic shock and improved after timely treatment. Recurrence in situ was observed in 5 of 32 (15.6%) patients. The median PFS of the patients who received IRE ablation was 384 days, and the median OS was 571 days., Conclusion: IRE ablation is a feasible and safe treatment strategy for tumors adjacent to perihepatic important structure. With improved equipment, optimized therapeutic parameters and long-term clinical trials, IRE will play an increasingly important role in the treatment of tumors in liver., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gong, Wang, Wang, Li, Li, Chen, Xia, Wang and Wang.)

An aggregation-induced emission (AIE)-based strategy was proposed for fluorescence immunoassays of protein biomarkers using Cu-based metal-organic frameworks (Cu-MOFs) to load recombinant targets and enzymes for dual signal amplification. The immunosensing platform was built based on the sequestration and consumption of the substrates of pyrophosphate (PPi) ions by Cu-MOFs and enzymatic catalysis. The negatively charged PPi could trigger the aggregation of positively charged tetraphenylethene (TPE)-substituted pyridinium salt nanoparticles (TPE-Py NPs) by electrostatic interactions, lighting up the fluorescence due to the AIE phenomenon. The consumption of PPi by the captured Cu-MOFs through the Cu 2+ -PPi chelation interaction and ALP-enzymatic hydrolysis depressed the aggregation of TPE-Py NPs. Capture of the tested targets in samples by the antibodies on the plate surface could prevent the attachment of target/ALP-loaded Cu-MOFs due to the competitive immunoreactions. The "signal-on" competitive immunoassay was applied for the detection of procalcitonin (PCT) as the model analyte with a linear range of 0.01-10 pg/mL and a detection limit down to 8 pg/mL. The conceptual integration of AIE with enzymatic and MOFs-based dual signal amplification endowed fluorescence immunoassays with high sensitivity and selectivity. The surface modification of Cu-MOFs with hexahistine (His 6 )-tagged recombinant proteins through metal coordination interactions should be evaluable for the design of novel biosensors., 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.)

Recent studies showed that patients with iron overload had increased risk of insulin resistance or diabetes. Ferroptosis is a new type of cell death mainly caused by iron-dependent oxidative damage. In the present study, we investigated potential mechanisms of iron overload induced hepatic ferroptosis and insulin resistance through in vivo and in vitro experiments. In vivo, the mice models of iron overload were established by intraperitoneal injection of iron dextran. The changes of body weight, serum ferritin and blood glucose were measured. Hematoxylin-eosin (HE) and Perl's stainings were used to observe the pathological changes and iron deposition in the liver of mice. In vitro, HepG2 cells were treated with ferric ammonium citrate (FAC, 9 mmol/L, 24 h) to establish the cell models of iron overload. The labile iron pool, cell viability, glucose consumption and glycogen contents were measured. The ultrastructure of mitochondria was observed by transmission electron microscope (TEM). The malondialdehyde (MDA) and glutathione (GSH) kits were used to detect lipid peroxidation in liver tissues of mice and HepG2 cells. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of ferroptosis factors and JAK2/STAT3 signaling pathway. In this study, we used the iron chelator deferasirox in mice and HepG2 cells. Iron overload caused weight loss, elevated serum ferritin, fasting blood glucose, fasting insulin, HOMA-IR, impaired glucose tolerance, and decreased insulin sensitivity in mice. HE staining and Perls staining showed clumps of iron deposition in the liver of iron overload mice. Iron overload could reduce the glucose consumption, increase MDA contents of HepG2 cells, while reduce glycogen and GSH contents in liver tissues of mice and HepG2 cells. TEM showed deletion of mitochondrial ridge and rupture of outer membrane in HepG2 cells with iron overload. Iron chelator deferasirox could significantly improve the above indicators, which might be related to the activation of JAK2/STAT3/SLC7A11 signaling pathway and hepatic ferroptosis. Iron overload could induce hepatic ferroptosis and insulin resistance by inhibiting the JAK2/STAT3/SLC7A11 signaling pathway, and the iron chelator deferasirox might improve hepatic insulin resistance induced by iron overload., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The adhesion of probiotics to the intestine is crucial for their probiotic function. In previous studies, Tremella polysaccharides (TPS) (with sodium casein) have shown the potential to encapsulate probiotics and protect them in a simulated gastrointestinal tract. This study explored the effect of TPS (with sodium casein) on the adhesion of probiotics., Results: Lactobacillus plantarum was coated with TPS and sodium casein in different proportions, and was freeze-dried. The rheological properties of the mixture of probiotics powder and mucin solution were determined by static and dynamic rheological analysis. Aqueous solutions of probiotic powder and mucin mixture exhibited pseudoplastic fluid rheological properties. The higher the proportion of TPS content, the higher the apparent viscosity and yield stress. The mixed bacterial powder and mucin fluid displayed thixotropy and was in accordance with the Herschel-Bulkley model. The TPS increased the bio-adhesive force of the probiotic powder and mucin. When using TPS as the only carbon source, the adhesion of L. plantarum to Caco-2 cells increased by 228% in comparison with glucose in vitro. Twelve adhesive proteins were also detected in the whole-cell proteome of L. plantarum. Among them, ten adhesive proteins occurred abundantly when grown with TPS as a carbon source., Conclusion: Tremella polysaccharides therefore possess probiotic properties and can promote the intestinal adhesion of L. plantarum. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Organic frameworks face a trade-off between the framework stability and the bond dynamics, which necessitates the development of innovative linkages that can generate stable frameworks without hindering efficient synthesis. Although iodine(I)-based halogen-bonded organic frameworks (XOFs) have been developed, constructing XOFs based on bromine(I) is desirable yet challenging due to the high sensitivity of bromine(I) species. In this work, we present the inaugural construction of stable bromine(I)-bridged two-dimensional (2D) halogen-bonded organic frameworks, XOF(Br)-TPy-BF 4 /OTf, based on sensitive [N⋅⋅⋅Br⋅⋅⋅N] + halogen bonds. The formation of XOF(Br)-TPy-BF 4 /OTf was monitored by 1 H NMR, XPS, IR, SEM, TEM, HR-TEM, SEAD. Their framework structures were established by the results from PXRD, theoretical simulations and SAXS. More importantly, XOF(Br) displayed excellent chemical and thermal stabilities. They exhibited stable two-dimensional framework structures in various organic solvents and aqueous media, even over a wide pH range (pH 3-12), while the corresponding model compounds BrPy 2 BF 4 /OTf decomposed quickly even in the presence of minimal water. Furthermore, the influence of the counterions were investigated by replacing BF 4 with OTf, which improved the stability of XOF(Br). This characteristic enabled XOF(Br) to serve as an efficient oxidizing reagent in aqueous environments, in contrast with the sensitivity of BrPy 2 BF 4 /OTf, which performed well only in organic media. This study not only deepens our fundamental understanding of organic frameworks but also opens new avenues for the development and application of multifunctional XOFs., (© 2024 Wiley-VCH GmbH.)

In this work, we report on an electrochemical method for the signal-on detection of caspase-3 and the evaluation of apoptosis based on the biotinylation reaction and the signal amplification of methylene blue (MB)-loaded metal-organic frameworks (MOFs). Zr-based UiO-66-NH 2 MOFs were used as the nanocarriers to load electroactive MB molecules. Recombinant hexahistidine (His 6 )-tagged streptavidin (rSA) was attached to the MOFs through the coordination interaction between the His 6 tag in rSA and the metal ions on the surface of the MOFs. The acetylated peptide substrate Ac-GDEVDGGGPPPPC was immobilized on the gold electrode. In the presence of caspase-3, the peptide was specifically cleaved, leading to the release of the Ac-GDEVD sequence. A N-terminal amine group was generated and then biotinylated in the presence of biotin-NHS. Based on the strong interaction between rSA and biotin, rSA@MOF@MB was captured by the biotinylated peptide-modified electrode, producing a significantly amplified electrochemical signal. Caspase-3 was sensitively determined with a linear range from 0.1 to 25 pg/mL and a limit of detection down to 0.04 pg/mL. Further, the active caspase-3 in apoptosis inducer-treated HeLa cells was further quantified by this method. The proposed signal-on biosensor is compatible with the complex biological samples and shows great potential for apoptosis-related diagnosis and the screening of caspase-targeting drugs.

Background: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine)., Methods: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log 10 plaque forming units (PFU; low-dose v7D group), 3·9 log 10 PFU (medium-dose v7D group), and 4·2 log 10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434., Findings: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related., Interpretation: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future., Funding: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests J-ZJ, J-LH, and X-ZY are employees of and have stock options in Beijing Wantai. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Primary Sjögren's syndrome (pSS) is an inflammatory systemic autoimmune disease, while the role and mechanisms of pyroptosis in pSS remain largely undefined., Methods: Pyroptosis-related genes and gene expression data were obtained from the Molecular Signatures Database and NCBI GEO databases. Differentially expressed genes (DEGs) and pyroptosis-related hub genes were identified by R software. Functional enrichment analyses were conducted using the "ClusterProfiler" R package and WebGestalt7. CIBERSORTx was used to calculate the correlations between immune cells and pyroptosis. Subsequently, histological staining was performed on salivary gland samples from non-pSS and pSS patients to identify the expression of pyroptosis-related genes. Immunofluorescence double staining was conducted to validate the correlation between immune cells and pyroptosis., Results: A total of 1494 DEGs were identified between eight pSS samples and 10 healthy volunteer samples. Five pyroptosis-related hub genes (AIM2, CASP1, CASP3, IL6, TNF) were recognised. DEGs were mostly enriched in immunity-related terms and several immune cells were associated with the hub genes in pSS. Among them, delta gamma T cell was significantly positively correlated with CASP3. Finally, the protein levels of these hub genes were validated to be elevated in the labial minor salivary gland biopsies of pSS patients compared to those of healthy volunteers using immunohistochemical staining. Immunofluorescence double staining further showed that IL-6, AIM2, CASP1and CASP3 were related to delta gamma T cells, and TNF was related to dendritic cells., Conclusions: This study uncovered a significant interaction between pyroptosis and the immune microenvironment in pSS patients. Besides, we identified five pyroptosis-related hub genes that might play a role in the pathogenesis of pSS. These findings could offer valuable insights for the development of novel treatment strategies for pSS.

Objective: To investigate current status of quality of life and the association between depression and symptom burden in a sample of Chinese maintenance hemodialysis (MHD) patients., Methods: A self-designed patient general information questionnaire, disease-related information questionnaire, dialysis patient symptom burden scale, depression scale, and quality of survival scale were used to investigate 380 maintenance haemodialysis patients in haemodialysis centres. A regression model of the factors affecting the quality of survival was established using structural equation modelling., Results: The regression model data had a high goodness of fit: c 2 /df = 4.736, RMSEA = 0.099, GFI = 0.918, CFI = 0.972, TLI = 0.962, SRMR = 0.0469. Structural equation model analysis showed that depression had a positive predictive effect on symptom burden, β = 0.398, P < 0.001; Symptom burden had a negative predictive effect on the quality of life, β =-0.851, P < 0.001; and Depression had a negative predictive effect on the quality of life, β =-0.151, P < 0.001. Depression indirectly affects the quality of life through symptom burdens., Conclusion: Depression and symptom burden directly or indirectly affect the quality of life in patients with maintenance hemodialysis. Symptom burden moderates the relationship between depression and quality of life as a mediating variable., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Xia et al.)

Background: Central pancreatectomy is a surgical procedure for benign and low-grade malignant tumors which located in the neck and proximal body of the pancreas that facilitates the preservation of pancreatic endocrine and exocrine functions but has a high morbidity rate, especially postoperative pancreatic fistula (POPF). The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness between minimally invasive central pancreatectomy (MICP) and open central pancreatectomy (OCP) basing on perioperative outcomes., Methods: An extensive literature search to compare MICP and OCP was conducted from October 2003 to October 2023 on PubMed, Medline, Embase, Web of Science, and the Cochrane Library. Fixed-effect models or random effects were selected based on heterogeneity, and pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated., Results: A total of 10 studies with a total of 510 patients were included. There was no significant difference in POPF between MICP and OCP (OR = 0.95; 95% CI [0.64, 1.43]; P = 0.82), whereas intraoperative blood loss (MD = - 125.13; 95% CI [- 194.77, -55.49]; P < 0.001) and length of hospital stay (MD = - 2.86; 95% CI [- 5.00, - 0.72]; P = 0.009) were in favor of MICP compared to OCP, and there was a strong trend toward a lower intraoperative transfusion rate in MICP than in OCP (MD = 0.34; 95% CI [0.11, 1.00]; P = 0.05). There was no significant difference in other outcomes between the two groups., Conclusion: MICP was as safe and effective as OCP and had less intraoperative blood loss and a shorter length of hospital stay. However, further studies are needed to confirm the results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive., Aim of the Study: The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats., Materials and Methods: Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results., Results: REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT 2 A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects., Conclusions: This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil., 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.)

Enzyme-linked electrochemical immunosensors have attracted considerable attention for the sensitive and selective detection of various targets in clinical diagnosis, food quality control, and environmental analysis. In order to improve the performances of conventional immunoassays, significant efforts have been made to couple enzyme-linked or nanozyme-based catalysis and redox cycling for signal amplification. The current review summarizes the recent advances in the development of enzyme- or nanozyme-based electrochemical immunosensors with redox cycling for signal amplification. The special features of redox cycling reactions and their synergistic functions in signal amplification are discussed. Additionally, the current challenges and future directions of enzyme- or nanozyme-based electrochemical immunosensors with redox cycling are addressed.

Background & Aims: HBV expresses more than 10 spliced RNAs from the viral pregenomic RNA, but their functions remain elusive and controversial. To address the function of HBV spliced RNAs, we generated splicing-deficient HBV mutants and conducted experiments to assess the impact of these mutants on HBV infection., Methods: HepG2-NTCP cells, human hepatocyte chimeric FRG mice (hu-FRG mice), and serum from patients with chronic hepatitis B were used for experiments on HBV infection. Additionally, SHifter assays and cryo-electron microscopy were performed., Results: We found the infectivity of splicing-deficient HBV was decreased 100-1,000-fold compared with that of wild-type HBV in hu-FRG mice. Another mutant, A487C, which loses the most abundant spliced RNA (SP1), also exhibits severely impaired infectivity. SP1 hypothetically encodes a novel protein HBc SP1 (HBc -Cys ) that lacks the C-terminal cysteine from full-length HBc. In the SHifter assay, HBc SP1 was detected in wild-type viral particles at a ratio of about 20-100% vs. conventional HBc, as well as in the serum of patients with chronic hepatitis B, but not in A487C particles. When infection was conducted with a shorter incubation time of 4-8 h at lower PEG concentrations in HepG2-NTCP cells, the entry of the A487C mutant was significantly slower. SP1 cDNA complementation of the A487C mutant succeeded in rescuing its infectivity in hu-FRG mice and HepG2-NTCP cells. Moreover, cryo-electron microscopy revealed a disulfide bond between HBc cysteine 183 and 48 in the HBc intradimer of the A487C capsid, leading to a locked conformation that disfavored viral entry in contrast to the wild-type capsid., Conclusions: Prior studies unveiled the potential integration of the HBc -Cys protein into the HBV capsid. We confirmed the proposal and validated its identity and function during infection., Impact and Implications: HBV SP1 RNA encodes a novel HBc protein (HBc SP1 ) that lacks the C-terminal cysteine from conventional HBc (HBc -Cys ). HBc SP1 was detected in cell culture-derived HBV and confirmed in patients with chronic infection by both immunological and chemical modification assays at 10-50% of capsid. The splicing-deficient mutant HBV (A487C) impaired infectivity in human hepatocyte chimeric mice and viral entry in the HepG2-NTCP cell line. Furthermore, these deficiencies of the splicing-deficient mutant could be rescued by complementation with the SP1-encoded protein HBc SP1 . We confirmed and validated the identity and function of HBc SP1 during infection, building on the current model of HBV particles., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Manganese (Mn) is an essential heavy metal in the human body, while excess Mn leads to neurotoxicity, as observed in this study, where 100 µM of Mn was administered to the human neuroblastoma (SH-SY5Y) cell model of dopaminergic neurons in neurodegenerative diseases. We quantitated pathway and gene changes in homeostatic cell-based adaptations to Mn exposure. Utilizing the Gene Expression Omnibus, we accessed the GSE70845 dataset as a microarray of SH-SY5Y cells published by Gandhi et al. (2018) and applied statistical significance cutoffs at p < 0.05. We report 74 pathway and 10 gene changes with statistical significance. ReactomeGSA analyses demonstrated upregulation of histones (5 out of 10 induced genes) and histone deacetylases as a neuroprotective response to remodel/mitigate Mn -induced DNA/chromatin damage. Neurodegenerative-associated pathway changes occurred. NF-κB signaled protective responses via Sirtuin-1 to reduce neuroinflammation. Critically, Mn activated three pathways implicating deficits in purine metabolism. Therefore, we validated that urate, a purine and antioxidant, mitigated Mn -losses of viability in SH-SY5Y cells. We discuss Mn as a hypoxia mimetic and trans-activator of HIF-1α, the central trans-activator of vascular hypoxic mitochondrial dysfunction. Mn induced a 3-fold increase in mRNA levels for antioxidant metallothionein-III, which was induced 100-fold by hypoxia mimetics deferoxamine and zinc.

The low solubility and stability of fat-soluble curcumin in water limit its application in active packaging. This study explored the use of a pH-driven method to investigate the preparation and enhancement of the performance of films loaded with curcumin in a matrix of sodium alginate (Alg) and egg white protein (EWP). In this study, the EWP, Alg, and curcumin primarily bind through hydrogen bonding, electrostatic interactions, and hydrophobic interactions. Compared to EWP films, the films loaded with curcumin through the pH-driven method exhibited enhanced extensibility and water resistance, with an elongation at break (EB) of 103.56 ± 3.13% and a water vapor permeability (WVP) of 1.67 ± 0.03 × 10 -10 g·m/m 2 ·Pa·s. The addition of Alg improved the encapsulation efficiency and thermal stability of curcumin, thereby enhancing the antioxidant activity of the film through the addition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, which resulted in 106.95 ± 2.61 μg TE/g and 144.44 ± 8.89 μg TE/g, respectively. It is noteworthy that the detrimental effect of Alg on the color responsiveness of films containing curcumin has also been observed. This study provides a potential strategy and consideration for the loading of low water-soluble active substances and the preparation of active packaging., Competing Interests: The authors declare no conflicts of interest.

Background: NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat., Methods: Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2 -/- mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O 2 - ) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study., Results: We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst., Conclusions: Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management., (© 2024. The Author(s).)

In this study, double cross-linked egg yolk granules (EYGs)/sodium alginate (SA) emulsion gel was constructed and used as butter substitute. The water binding capacity, rheology properties and microstructure of EYGs/SA emulsion gel showed that the network structure tended to be complete when the concentration of SA reached 1% (m/v). SA stabilized the EYGs/SA droplets and enhanced the spatial network structure of emulsion gel. After substitution for butter, the network structure of EYGs/SA emulsion gel with more water bounded and the polyhydroxy structure of SA molecules endowed dough with more water retention capacity. Meanwhile, the destruction of the microstructure of the replaced dough with EYGs/SA emulsion gel was significantly inhibited compared with the un-substituted dough after freezing. The baking ability results showed a satisfactory baking effect after substitution. Overall, this study provides a new avenue in the field of fat replacement and the application of EYGs/SA emulsion gels., 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.)

The long-term application of plant essential oils in food preservation coatings is limited by their poor water solubility and high volatility, despite their recognized synergistic antimicrobial effects in postharvest fruit preservation. To overcome these limitations, a Pickering emulsion loaded with thyme essential oil (TEO) was developed by utilizing hydrogen bonding and electrostatic interactions to induce cross-linking of chitosan particles. This novel emulsion was subsequently applied in the postharvest storage of strawberries. The shear-thinning behavior (flow index <1) and elastic gel-like characteristics of the emulsion made it highly suitable for spray application. Regarding TEO release, the headspace concentration of TEO increased from 0.21 g/L for pure TEO to 1.86 g/L after two instances of gas release due to the stabilizing effect of the chitosan particles at the oil-water interface. Notably, no phase separation was observed during the 10-day storage of the emulsion. Consequently, the emulsion was successfully employed for the postharvest storage of strawberries, effectively preventing undesirable phenomena such as weight loss, a decrease in firmness, an increase in pH, and microbial growth. In conclusion, the developed Pickering emulsion coating exhibits significant potential for fruit preservation applications, particularly for extending the shelf life of strawberries., Competing Interests: Declaration of competing interest No authors have any conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Simultaneous detection of active and inactive proteases is clinically meaningful for improving diagnostic specificity. In this work, we reported an electrochemical method for simultaneous immunoassays of active and total proteases. Magnetic beads (MBs) were used as the solid supports for immobilization of capture antibodies and enrichment of targets. For the detection of active protease, the proteolytic-reaction-based analysis was carried out by the generation of Cu 2+ -binding peptide, in which a label-free peptide was used as the proteolytic substrate. The redox potential of the resulting peptide-Cu 2+ complex was intrinsically distinguished from that of free Cu 2+ , thus allowing the "signal-on" detection of active protease. For the immunoassay of total protease in a sandwich-like format, electroactive metal-organic frameworks (Cu-MOFs) were used as the signal tags. The captured Cu-MOFs could directly produce a well-defined electrochemical signal from the reduction of Cu 2+ ions. The analytical performances of the immunoplatform were evaluated by determining the model analytes of free and total prostate-specific antigen (fPSA and tPSA) in buffer and serum. The detection limits were found to be 0.3 pM for fPSA and 2 pM for tPSA. This work proposed a new strategy for simultaneous detection of active and total proteases, which should be evaluable for clinical diagnosis and treatment of protease-relative diseases., 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 B.V. All rights reserved.)

Background: Pile fermentation is one of the key steps in developing the Liupao tea (LBT) quality and unique characteristics. The complex biochemical profile of LBT results from microorganisms present during the pile-fermentation process. However, the critical underlying microorganisms and the marker compounds still need to be determined., Results: Staphylococcus, Brevibacterium, Kocuria, Aspergillus, and Blastobotrys were the common dominant microorganisms at the end of the pile fermentation of LBT. Staphylococcus, Aspergillus, Blastobotrys, and nine other genera carried by raw tea are the core microorganisms in the LBT during pile fermentation. A total of 29 critical compounds contributed to the metabolic changes caused by the processing of LBT. Of these, gallic acid, adenine, hypoxanthine, uridine, betaine, 3,4-dihydroxybenzaldehyde, and α-linolenic acid could be characterized as potential marker compounds. Correlation analysis showed that the core microorganisms, including Sphingomonas, Staphylococcus, Kocuria, Aureobasidium, Blastobotrys, Debaryomyce, and Trichomonascus, were closely related to major chemical components and differential compounds. Moreover, the mutually promoting Staphylococcus, Kocuria, Blastobotrys, and Trichomonascus were correlated with the enrichment of marker compounds. Integrated molecular networking and metabolic pathways revealed relevant compounds and enzymes that possibly affect the enrichment of marker compounds., Conclusion: This study analyzed the LBT fermentation samples by omics analysis to reveal the stable microbial community structure, critical microorganisms, and markers compounds affecting the quality of LBT, which contributes to a better understanding of pile fermentation of LBT and the fermentation theory of dark tea. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Grass carp reovirus (GCRV), particularly the highly prevalent type II GCRV (GCRV-II), causes huge losses in the aquaculture industry. However, little is known about the mechanisms by which GCRV-II invades grass carp and further disseminates among tissues. In the present study, monocytes/macrophages (Mo/Mφs) were isolated from the peripheral blood of grass carp and infected with GCRV-II. The results of indirect immunofluorescent microscopy, transmission electron microscopy, real-time quantitative RT-PCR (qRT-PCR), western blot (WB), and flow cytometry analysis collectively demonstrated that GCRV-II invaded Mo/Mφs and replicated in them. Additionally, we observed that GCRV-II induced different types (M1 and M2) of polarization of Mo/Mφs in multiple tissues, especially in the brain, head kidney, and intestine. To assess the impact of different types of polarization on GCRV-II replication, we recombinantly expressed and purified the intact cytokines CiIFN-γ2, CiIL-4/13A, and CiIL-4/13B and successfully induced M1 and M2 type polarization of macrophages using these cytokines through in vitro experiments. qRT-PCR, WB, and flow cytometry analyses showed that M2 macrophages had higher susceptibility to GCRV-II infection than other types of Mo/Mφs. In addition, we found GCRV-II induced apoptosis of Mo/Mφs to facilitate virus replication and dissemination and also detected the presence of GCRV-II virus in plasma. Collectively, our findings indicated that GCRV-II could invade immune cells Mo/Mφs and induce apoptosis and polarization of Mo/Mφs for efficient infection and dissemination, emphasizing the crucial role of Mo/Mφs as a vector for GCRV-II infection.IMPORTANCEType II grass carp reovirus (GCRV) is a prevalent viral strain and causes huge losses in aquaculture. However, the related dissemination pathway and mechanism remain largely unclear. Here, our study focused on phagocytic immune cells, monocytes/macrophages (Mo/Mφs) in blood and tissues, and explored whether GCRV-II can invade Mo/Mφs and replicate and disseminate via Mo/Mφs with their differentiated type M1 and M2 macrophages. Our findings demonstrated that GCRV-II infected Mo/Mφs and replicated in them. Furthermore, GCRV-II infection induces an increased number of M1 and M2 macrophages in grass carp tissues and a higher viral load in M2 macrophages. Furthermore, GCRV-II induced Mo/Mφs apoptosis to release viruses, eventually infecting more cells. Our study identified Mo/Mφs as crucial components in the pathway of GCRV-II dissemination and provides a solid foundation for the development of treatment strategies for GCRV-II infection., Competing Interests: The authors declare no conflict of interest.

The increase of polysaccharides in the dark tea pile process is thought to be connected to the cell wall polysaccharides' breakdown. However, the relationship between tea polysaccharides (TPSs) and tea cell wall polysaccharides has not been further explored. In this study, the structural changes in the cell wall polysaccharides [e.g., cellulose, hemicellulose (HC), and pectin] in Liupao tea were characterized before and after traditional fermentation and tank fermentation. Additionally, the degradation mechanism of tea cell wall polysaccharides during fermentation was assessed. The results showed that cellulose crystallinity decreased by 11.9-49.6% after fermentation. The molar ratio of monosaccharides, such as arabinose, rhamnose, and glucose in HC, was significantly reduced, and the molecular weight decreased. The esterification degree and linearity of water-soluble pectin (WSP) were reduced. TPS content increases during pile fermentation, which may be due to HC degradation and the increase in WSP caused by cell wall structure damage. Microorganisms were shown to be closely associated with the degradation of cell wall polysaccharides during fermentation according to correlation analyses. Traditional fermentation had a greater effect on the cellulose structure, while tank fermentation had a more noticeable impact on HC and WSP.

The work aimed to develop the multi-protein mixture of egg yolk as natural particles to stabilize high internal phase Pickering emulsions (HIPPEs) to improve the bioaccessibility of β-carotene in the elderly. The results showed that the depletion attraction drove the adsorption of egg yolk protein particles at the oil-water interface and the formation of osmotic droplet clusters due to the attachment of particle-coated droplets in the dispersed phase, leading to kinetic blocking and stable gelation of HIPPEs. Rheological measurements showed that HIPPEs had shear thinning, low shear stress, viscoelastic properties, and structural recovery properties, which facilitated easy consumption for the elderly. The stability of HIPPEs was verified by ionic and centrifugal stability tests, demonstrating their potential for application to complex gastric environments. HIPPEs have been applied to the International Dysphagia Dietary Standardization Initiative (IDDSI) test and simulated in vitro digestion in older adults, demonstrating their safe swallowability and high β-carotene bioaccessibility. Our findings suggest solutions for food practitioners facing the aging problem and provide new insights for preparing age-friendly foods., 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: Shen Qi Wu Wei Zi capsules (SQWWZ) are often used to treat insomnia; however, the potential therapeutic mechanism is still unclear., Objective: This study aimed to investigate the mechanism underlying the therapeutic effects of the Shen Qi Wu Wei Zi capsules on insomnia., Methods: The components of SQWWZ were identified using the UPLC-Q-TOF-MS/MS technique in conjunction with relevant literature. Insomnia-related targets were searched in the Gene- Cards and DisGeNET databases, and the intersection targets were obtained using a Venn diagram. A component-target-insomnia network diagram was constructed using Cytoscape 3.7.2 software. Core targets underwent GO and KEGG enrichment analyses. Molecular docking techniques were employed to verify the key proteins involved in the pathway and their corresponding compounds. Insomnia was induced in SD rats through the intraperitoneal injection of pchlorophenylalanine (DL-4-chlorophenylalanine, PCPA). The rats were treated orally with SQWWZ, and the serum levels of 5-HT and GABA in each group were determined using ELISA. Histological analysis of hippocampal tissue sections from the rats was performed using HE staining., Results: Using UPLC-Q-TOF-MS/MS and reviewing relevant literature, we identified 49 components of SQWWZ. Additionally, we obtained 1,043 drug targets and 367 insomnia-related targets. Among these, 82 targets were found to be common to both drug and insomnia targets. Following drug administration, rats in the treatment group exhibited a significant increase in the serum levels of 5-HT and GABA. Moreover, histological analysis using HE staining revealed neatly arranged hippocampal neuronal cells in the treated rats., Conclusion: The active components of SQWWZ had good inhibition of insomnia. This study provides a reference and guidance for the in-depth study of SQWWZ for the treatment of insomnia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A two-step method for preparing smart labels that can monitor food freshness through color change is presented. The conventional casting method for such labels is not cost-effective, as it uses organic solvents and requires additional cutting processes. Our method is more eco-friendly and customizable, as it uses water as the sole solvent and 3D printing as the fabrication technique. First, curcumin was encapsulated with soy protein isolate (SPI) by a pH-driven method involving hydrogen bonding and hydrophobic interactions. Subsequently, the SPI-curcumin complex was blended with gelatin to create a printable ink. The ink has suitable rheological properties for extrusion, with a yield stress of 400-600 Pa and a viscosity of 122.93-142.82 Pa·s at the optimal printing temperature. The complex modulus of the ink increases to above 2 × 10 3  Pa when cooled to 25 °C, indicating rapid gel formation. The application of these smart labels to minced meat demonstrated their ability to reflect its freshness by transitioning from yellow to red. Furthermore, the printability and mechanical properties of the labels can be adjusted by changing the glycerol/water ratio. This innovative approach is a promising solution for producing environmentally friendly and customizable smart labels for food freshness monitoring., Competing Interests: Declaration of competing interest All coauthors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obesity is a significant health concern that leads to impaired vascular function and subsequent abnormalities in various organs. The impact of obesity on ocular blood vessels, however, remains largely unclear. In this study, we examined the hypothesis that obesity induced by high-fat diet produces vascular endothelial dysfunction in the ophthalmic artery. Mice were subjected to a high-fat diet for 20 weeks, while age-matched controls were maintained on a standard diet. Reactivity of isolated ophthalmic artery segments was assessed in vitro. Reactive oxygen species (ROS) were quantified in cryosections by dihydroethidium (DHE) staining. Redox gene expression was determined in ophthalmic artery explants by real-time PCR. Furthermore, the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), the receptor for advanced glycation end products (RAGE), and of the lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) was determined in cryosections using immunofluorescence microscopy. Ophthalmic artery segments from mice on a high-fat diet exhibited impaired vasodilation responses to the endothelium-dependent vasodilator acetylcholine, while endothelium-independent responses to nitroprusside remained preserved. DHE staining intensity in the vascular wall was notably stronger in mice on a high-fat diet. Messenger RNA expression for NOX2 was elevated in the ophthalmic artery of mice subjected to high fat diet. Likewise, immunostainings revealed increased expression of NOX2 and of RAGE, but not of LOX-1. These findings suggest that a high-fat diet triggers endothelial dysfunction by inducing oxidative stress in the ophthalmic artery via involvement of RAGE and NOX2., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript or in the decision to publish the results., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: Obesity is an epidemic that is a critical contributor to hypertension and other cardiovascular diseases. Current paradigms suggest that endothelial nitric oxide synthase (eNOS/NOS3) in the vessel wall is the primary regulator of vascular function and blood pressure. However, recent studies have revealed the presence of eNOS/NOS3 in the adipocytes of white adipose tissues and perivascular adipose tissues (PVATs). The current understanding of the role of adipocyte NOS3 is based mainly on studies using global knockout models. The present study aimed to elucidate the functional significance of adipocyte NOS3 for vascular function and blood pressure control., Methods and Results: We generated an adipocyte-specific NOS3 knockout mouse line using adiponectin promoter-specific Cre-induced gene inactivation. Control and adipocyte-specific NOS3 knockout (A-NOS3 KO) mice were fed a high-fat diet (HFD). Despite less weight gain, A-NOS3 KO mice exhibited a significant increase in blood pressure after HFD feeding, associated with exacerbated vascular dysfunction and remodelling. A-NOS3 KO mice also showed increased expression of signature markers of inflammation and hypoxia in the PVATs. Among the differentially expressed adipokines, we have observed an upregulation of a novel adipokine, chemerin, in A-NOS3 KO mice. Chemerin was recently reported to link obesity and vascular dysfunction. Treatment with chemerin neutralizing antibody normalized the expression of remodelling markers in the aorta segments cultured in serum from HFD-fed A-NOS3 KO mice ex vivo., Conclusion: These data suggest that NOS3 in adipocytes is vital in maintaining vascular homeostasis; dysfunction of adipocyte NOS3 contributes to obesity-induced vascular remodelling and hypertension., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Reduced slow wave sleep (SWS) has been linked to hypertension in some studies. The aim of the study is to investigate the association between SWS and office blood pressure (BP) in non-hypertensive obstructive sleep apnea (OSA)., Methods: This is a retrospective study of 3350 patients who underwent polysomnography (PSG) in our hospital. Based on quartiles of percent SWS, participants were classified into four groups. BP was measured manually on the randomly chosen arm in a seated position with sphygmomanometer after PSG in the morning, and the average of the second and third measurements was used for this analysis. Elevated office BP was defined as a systolic BP≥140 mmHg or diastolic BP≥90 mmHg., Results: There were 1365 patients with OSA and 597 primary snorers included in our study. In OSA group, OSA patients with SWS <13.5% had a significant elevated risk with elevated office BP (OR,1.49[95%CI 1.05-2.10], P=0.025), compared to the highest quartile (percent SWS >39.2%). However, no significant relationship between decreased SWS and elevated office BP was found in primary snorers group., Conclusion: In non-hypertensive OSA patients, decreased SWS is associated with elevated office BP.

Postoperative pancreatic fistula (POPF) is a severe complication after distal pancreatectomy (DP); however, it is unclear how to effectively reduce the incidence. The purpose of this meta-analysis is to determine whether reinforced stapling reduces POPF after DP. From February 2007 to April 2023, a comprehensive search of electronic data and references was conducted in PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. In this study, the perioperative outcomes were evaluated for the reinforced stapler (RS) group and the standard stapler (SS) group in DP using Review Manager Software. Using fixed- or random-effects models, pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. In total, three randomized clinical trials (RCTs) with 425 patients and five observational clinical studies (OCS) with 318 patients were included. In pooled meta-analyses from RCTs, there was no difference between the two groups in the incidence of POPF (OR = 0.79; 95% CI [0.47,1.35]; P = 0.39), intraoperative blood loss (MD = 10.66; 95% CI [- 28.83,50.16]; P = 0.6), operative time (MD = 9.88; 95% CI [- 8.92,28.67]; P = 0.3), major morbidity (OR = 1.12; 95% CI [0.67,1.90]; P = 0.66), reoperation (OR = 0.97; 95% CI [0.41,2.32]; P = 0.95), readmission (OR = 0.99; 95% CI [0.57,1.72]; P = 0.97) or hospital stay (MD = - 0.95; 95% CI [- 5.22,3.31]; P = 0.66). However, the results of POPF and readmission were favorable for RS in the OCS group., (© 2023. Italian Society of Surgery (SIC).)

Hepatitis E virus (HEV) is a pathogen of global significance, but the value of HEV-related markers in the diagnosis of hepatitis E remains controversial. Previous studies on hepatitis E profiles have been mainly cross-sectional and conducted among inpatients in large hospitals, and hepatitis E cases have been primarily defined by limited partial markers. In this community-based study, 4,110 active hepatitis cases from a population of nearly 600,000 were followed over 48 months and serial serum samples were collected. Both HEV pathogen (HEV RNA and antigen) and anti-HEV antibody markers were used to determine HEV infection status and the relationship between hepatitis and HEV infection. In total, 98 hepatitis E patients were identified and all available isolates from 58 patients belonged to HEV genotype 4. The mean age of the patients was 58.14 years, with an overwhelming proportion of males (70.4%). Hepatitis E accounted for 22.86% of active hepatitis cases with alanine aminotransferase levels ≥15.0-fold the upper limit of normal, suggesting the need to include HEV in routine testing for these patients. Ninety-two hepatitis E patients were positive for at least 2 of HEV antigen, anti-HEV IgM, and HEV RNA markers at presentation, and 90.22% of them were positive for HEV antigen and anti-HEV IgM. HEV antigen, HEV RNA, and anti-HEV IgM positivity were observed in 89.80%, 82.65%, and 93.88% of hepatitis E patients at presentation, respectively. However, only 57.14% of anti-HEV IgM positivity occurred in hepatitis E patients. These findings will advance our understanding of hepatitis E and improve diagnosis.

Objective: The purpose of this study was to investigate the mechanism through which rosemary essential oil treats atopic dermatitis., Methods: A dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model was established and treated with low (1%), medium (2%), and high (4%) doses of Rosmarinus officinalis essential oil (EORO). Serum levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in each group were determined using enzyme-linked immunosorbent assay (ELISA). Skin tissues were stained with hematoxylin-eosin and toluidine blue. We used network pharmacology and molecular docking techniques to verify the biological activity of essential proteins and their corresponding compounds in the pathway. Gas chromatography-mass spectrometry (GC-MS) was used for metabolomics analysis and multivariate statistical analysis of mouse serum to screen differential metabolites and metabolic pathway analysis. Protein expression of p-JAK1, CD4+ cells, and IL-4 in the skin tissue was detected by immunohistochemistry analysis. Protein levels of STAT3, p-STAT3, P65, and p-P65 in damaged skin tissues were detected using western blotting., Result: The skin of mice in the model group showed different degrees of erythema, dryness, scratches, epidermal erosion and shedding, and crusting. After treatment, the serum levels of IL-6 and TNF-α in EORO group were significantly decreased, and the expression of p-JAK1,CD4 + cells, IL-4, p-P65 / P65 and p-STAT3 / STAT3 proteins in skin tissues were decreased., Conclusion: EORO can effectively improve DNCB-induced AD-like skin lesions in mice by regulating the JAK/STAT/NF-κB signaling pathway, thereby reducing the production of downstream arachidonic acid metabolites, inhibiting skin inflammation, and restoring epidermal barrier function., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: An Escherichia coli-produced human papillomavirus (HPV) 16 and 18 bivalent vaccine (Cecolin) was prequalified by WHO in 2021. This study aimed to compare the immunogenicity of the E coli-produced HPV 9-valent vaccine Cecolin 9 (against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) with Gardasil 9., Methods: This was a randomised, single-blind trial conducted in China. Healthy non-pregnant women aged 18-26 years, who were not breastfeeding and with no HPV vaccination history, were enrolled in the Ganyu Centre for Disease Control and Prevention (Lianyungang City, Jiangsu Province, China). Women were stratified by age (18-22 years and 23-26 years) and randomly assigned (1:1) using a permutated block size of eight to receive three doses of Cecolin 9 or Gardasil 9 at day 0, day 45, and month 6. All participants, as well as study personnel without access to the vaccines, were masked. Neutralising antibodies were measured by a triple-colour pseudovirion-based neutralisation assay. The primary outcomes, seroconversion rates and geometric mean concentrations (GMCs) at month 7, were analysed in the per-protocol set for immunogenicity (PPS-I). Non-inferiority was identified for the lower limit of the 95% CI of the GMC ratio (Cecolin 9 vs Gardasil 9) at a margin of 0·5 and a seroconversion rate difference (Cecolin 9-Gardasil 9) at a margin of -5%. This study was registered at ClinicalTrials.gov (NCT04782895) and is completed., Findings: From March 14 to 18, 2021, a total of 553 potential participants were screened, of which 244 received at least one dose of Cecolin 9 and 243 received at least one dose of Gardasil 9. The seroconversion rates for all HPV types in both groups were 100% in the PPS-I, with the values of the lower limits of 95% CIs for seroconversion rate differences ranging between -1·8% and -1·7%. The GMC ratios of five types were higher than 1·0, with the highest ratio, for HPV 58, at 1·65 (95% CI 1·38-1·97), and those of four types were lower than 1·0, with the lowest ratio, for HPV 11, at 0·79 (0·68-0·93). The incidence of adverse reactions in both groups was similar (43% [104/244] vs 47% [115/243])., Interpretation: Cecolin 9 induced non-inferior HPV type-specific immune responses compared with Gardasil 9 and is a potential candidate to accelerate the elimination of cervical cancer by allowing for global accessibility to 9-valent HPV vaccinations, especially in low-income and middle-income countries., Funding: National Natural Science Foundation, Fujian Provincial Natural Science Foundation, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax., Competing Interests: Declaration of interests F-ZZ, Q-FZ, and X-MY report being current employees of Xiamen Innovax. GS and H-RP report being current employees of and have stock options in Xiamen Innovax. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations., Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Feng-Zhu Zheng and Qiu-Fen Zhang report being either current employees of Xiamen Innovax; Guang Sun report being current employees of and have stock options in Xiamen Innovax. All other authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Tank fermentation is a novel approach to fermenting teas; however, the species of microorganisms present remain unclear. The microbial community composition of Liupao tea at various stages of tank fermentation was analyzed using high-throughput sequencing. Sphingomonas, Aquabacterium, Pelomonas, Acinetobacter, Blastobotrys, Aspergillus, Debaryomyces, and Aureobasidium were the predominant genera, which is different from pile fermentation. Fifteen genera (including Lactobacillus, Debaryomyces, Candida, Allobaculum, Flavobacterium, Caulobacter, Blastobotrys, Aspergillus, and Rasamsonia) were identified as biomarkers. PICRUSt analysis predicted that the most abundant functional genes were related to metabolism of carbohydrates, amino acids, cofactors, vitamins, and other secondary metabolites. Using the pure culture method, 283 strains were isolated at various stages of fermentation, representing 20 genera and 29 species of bacteria, and 11 genera and 18 species of fungi. Most of the dominant Sphingomonas, Staphylococcus, Aspergillus, and Blastobotrys identified by sequencing were also isolated. Of these, Sphingomonas olei, Aspergillus luchuensis, Aspergillus niger, Aspergillus aculeatus, Aspergillus amstelodami, Blastobotrys adeninivorans, Candida metapsilosis, and Candida blankii were beneficial strains that might be used to ferment Liupao tea. This study provides a basis for the development of processing technologies and utilization of microbial strains in the production of dark teas. PRACTICAL APPLICATION: Microbial diversity in tank-fermented Liupao tea was reported for the first time. 8 microorganisms were the predominant genera. The species, functions and potential risks of microorganisms was revealed. We clarified the differences between tank and pile fermentation., (© 2023 Institute of Food Technologists.)

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, the vascular mechanics, lipid content, levels of reactive oxygen species (ROS), and expression of pro-oxidant redox enzymes and the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, the levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via the involvement of LOX-1, NOX1, and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. A lack of LOX-1 expression/overexpression in response to increased oxidized low-density lipoprotein levels may be a possible mechanism of action.

Chronic neuroinflammation is implicated in the pathogenesis of Parkinson's disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune-responsive gene 1 activity, may mediate anti-inflammatory responses by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. This study investigates the neuroprotective potential of 4-octyl itaconate (OI), a cell-permeable derivative of itaconate, in cellular models of PD. OI not only suppressed lipopolysaccharide-induced proinflammatory cascades of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines release in mouse BV2 microglial cells but also activated the Nrf2 signaling pathway and its downstream targets in these cells. Conditioned medium derived from OI-treated BV2 cells protected against rotenone- and MPP + -induced neurotoxicity in Neuro 2A cells. Overall, our findings support the anti-inflammatory neuroprotective potential of OI in PD., (© 2023. Springer Nature Limited.)

Aim: To explore the association between social capital and health-related quality of life (HRQoL) and to determine whether depression mediates the association among Chinese older adults in the context of the COVID-19 pandemic., Design: A descriptive cross-sectional research design., Methods: The Geriatric Depression Scale-15, Social Capital Questionnaire and 12-item Short-Form Health Survey were used to investigate 1201 older adults selected from Jinan, Shandong Province, China, using a multistage stratified cluster random sampling method., Results: Pearson's correlation analysis revealed a significant positive correlation between social capital and HRQoL (r = 0.269, p < 0.01). Multivariate linear regression analyses demonstrated that social capital was significantly negatively associated with depression (β = -0.072, p < 0.001) and that depression was associated with HRQoL (β = -1.031, p < 0.001). The mediation analyses showed that depression mediated the association between social capital and HRQoL, and the indirect effect size was 0.073 (95% confidence interval: 0.050, 0.100)., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Objective: The superficial zone cells in articular cartilage (SFZCs) have been identified as stem/progenitor chondrocytes and promoted cell self-renewal in the osteoarthritis (OA). Several studies emphasized the involvement of senescence and autophagy in OA. Interleukin-1β (IL-1β) is one of the main inflammatory mediators of OA, and whether it induces senescence and autophagy in SFZCs remains unclear. The present study aimed to investigate autophagy flux, mitochondrial function, and intracellular reactive oxygen species (ROS) that resulted in senescence in SFZCs induced by IL-1β., Methods: Using western blotting, reverse transcription-quantitative PCR, immunofluorescence, intracellular ROS detection, mitochondrial staining, and determination of mitochondrial membrane potential, we tested senescence and autophagy markers in SFZCs induced by IL-1β in vitro . The consequences of mitochondrial function and ROS were also studied with IL-1β-induced senescence., Results: IL-1β treatment decreased SFZC proliferation, induced SFZC senescence, and reduced SFZCs' chondrogenic differentiation capacity. Moreover, IL-1β impaired autophagy flux, and the autophagy activator, rapamycin, attenuated the senescence of SFZCs. IL-1β-induced autophagy defect resulted in mitochondrial dysfunction and overproduction of ROS, and autophagy activation notably protected against mitochondrial dysfunction and reduced the levels of ROS. Moreover, antioxidant N-acetylcysteine reversed the senescence of IL-1β in SFZCs., Conclusion: IL-1β promotes autophagy impairment and subsequently results in dysfunctional mitochondria and overproduction of ROS, which finally causes SFZC senescence.

Electrochemical immunosensors have shown great potential in clinical diagnosis, food safety, environmental protection, and other fields. The feasible and innovative combination of enzyme catalysis and other signal-amplified elements has yielded exciting progress in the development of electrochemical immunosensors. Alkaline phosphatase (ALP) is one of the most popularly used enzyme reporters in bioassays. It has been widely utilized to design electrochemical immunosensors owing to its significant advantages (e.g., high catalytic activity, high turnover number, and excellent substrate specificity). In this work, we summarized the achievements of electrochemical immunosensors with ALP as the signal reporter. We mainly focused on detection principles and signal amplification strategies and briefly discussed the challenges regarding how to further improve the performance of ALP-based immunoassays.