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Ethnopharmacological Relevance: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, largely due to the limitations of available therapeutic strategies. The traditional Chinese medicine Qizhu Anticancer Prescription (QZACP) can improve the quality of life and prolong the survival time of patients with HCC. However, the precise mechanisms underlying the anti-cancer properties of QZACP remain unclear., Purpose: This study examined the anti-hepatocarcinogenic properties of QZACP, with a specific focus on its influence on the p21-activated secretory phenotype (PASP)-mediated immune surveillance, to elucidate the underlying molecular pathways involved in HCC., Materials and Methods: Cell proliferation was measured using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and clonogenic assays. The cell cycle was evaluated using flow cytometry, and senescence was identified by staining with senescence-associated beta-galactosidase (SA-β-gal). A primary liver cancer model produced by diethylnitrosamine was established in C57 BL/6 mice to assess the tumor-inhibitory effect of QZACP. The liver's pathological characteristics were examined using hematoxylin and eosin staining. PASP screening was performed using GeneCards, DisGeNet, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas databases. Western blot analysis, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and Transwell migration assays were performed., Results: Serum containing QZACP enhanced p21 expression, triggered cell cycle arrest, accelerated cell senescence, and suppressed cell proliferation in Huh7 and MHCC-97H liver cancer cells. QZACP reduced the quantity and dimensions of liver tumor nodules and enhanced p21 protein expression, SA-β-Gal staining in tumor lesions, and cytotoxic CD8 + T cell infiltration. Bioinformatic analyses indicated that PASP factors, including hepatocyte growth factor, decorin (DCN), dermatopontin, C-X-C motif chemokine ligand 14 (CXCL14), and Wnt family member 2 (WNT2), play an important role in the development of HCC. In addition, these factors are associated with the presence of natural killer cells and CD8 + T cells within tumors. Western blotting and ELISA confirmed that QZACP increased DCN, CXCL14, and WNT2 levels in tumor tissues and peripheral blood., Conclusions: QZACP's suppression of HCC progression may involve cell senescence mediated via p21 upregulation, DCN, CXCL14, and WNT2 secretion, and reversal of the immunosuppressive microenvironment. This study provides insights that can be used in the development of new treatment strategies for HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Treatment of hemorrhagic shock (HS) induced multi-organ injury remains a challenge. Bergapten (BeG) is a bioactive coumarin-derived compound, and previous articles have suggested that BeG may serve as a prospective therapeutic modality for HS. This study was designed to investigate the efficacy of BeG in the treatment of HS and its underlying mechanisms., Methods: In this research, we established a rat model of HS, following which we assessed the protective effects of BeG on HS induced multi-organ injury. Subsequently, we scrutinized the activation of NLRP3 inflammasomes and pyroptosis in damaged organs. Additionally, we conducted examinations of AMPK and the downstream mitophagy pathway in damaged organs. Finally, we established a hypoxia/reoxygenation (H/R) model in HK-2 cells to simulate the in vitro HS process. Following AMPK inhibition with compound C, we evaluated the levels of mitophagy and cellular pyroptosis in BeG-treated HK-2 cells subjected to H/R., Results: BeG treatment alleviated HS induced multi-organ injury. Subsequent analyses indicated that the therapeutic effects of BeG were related to the attenuation of NLRP3 inflammasome activation and pyroptosis. Additionally, we found BeG treatment stimulated the phosphorylation of AMPK, thereby enhancing mitophagy. Lastly, we found that the inhibition of AMPK in vitro attenuates BeG's enhancement of mitophagy and its suppression of pyroptosis., Conclusion: Our research indicates that BeG has the potential to alleviate multi-organ injury induced by HS. The protective effect of BeG is likely associated with its promotion of mitophagy through AMPK activation, thereby inhibiting NLRP3 inflammasome-mediated pyroptosis., 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.)

The inadequate water resistance and mechanical properties of waterborne anticorrosive coatings is a serious problem that leads to coating failure. When the bark of acacia trees sustains damage, the liquid Gum Arabic (GA) that oozes from the trunk coagulates at the site of injury to safeguard it, which is called "gummosis" self-protection. Inspired by this, biomimetic GA microgel-based waterborne anticorrosive coatings are designed. Microgel exhibits a crosslinked polymer network structure with a combination of advantageous characteristics derived from both solids and liquids. By encapsulating the liquid corrosion inhibitors (MeBT) within the solid microgel matrix, the coating system is endowed with self-protective capabilities. The as-prepared GAMG-MeBT microgels are introduced into waterborne epoxy (WE) matrix and sprayed onto the surface of Q235 steel. Corrosion studies reveal the 3.0-wt% GAMG-MeBT/WE coating exhibits an impedance modulus value in the low-frequency region (Z 0.01Hz ) of 1.37 × 10 9  Ω cm 2 after immersing in 3.5-wt% NaCl solution for 60 days, which is nearly two orders of magnitude higher than that of the pure WE coatings. Moreover, the coatings display improved water resistance, enhanced abrasive resistance, and active corrosion protection. This work provides a new approach to solving the failure of WE anticorrosive coatings., 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.)

To investigate the mechanisms of flavor formation in dry-fermented tilapia sausages, the volatiles, bacterial community, and lipid composition during fermentation were analyzed using gas chromatography-ion mobility spectrometry, 16S high throughput sequencing, and ultra-performance liquid chromatography-mass spectrometer. Pediococcus pentosaceus, Staphylococcus xylosus, and Staphylococcus carnosus became dominant bacteria during the fermentation. A total of 66 volatiles and 293 lipids (48 differential lipids) were identified. PC and PE content decreased. Aldehyde and 1-octen-3-ol content decreased. Most esters and ketones content increased during fermentation. Six metabolic pathways associated with differential lipids were identified by enrichment analysis. Glycerophospholipid metabolism was the main metabolic pathway. Correlation analysis revealed that PC and PE were precursors for volatiles, including PC 16:0/18:2 and PE 18:0/22:6. The dominant bacteria facilitate the hydrolysis of PC and PE, leading to the formation of esters and ketones. This study provides a theoretical basis for the targeted regulation of fermented sausage flavors., 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.)

Outdoor jogging is one of the most popular practised exercises worldwide, providing various benefits for health and wellbeing. However, PM 2.5 exposure risks of jogging behaviors were rarely explored. This study aims to investigate the association between jogging behavior and PM 2.5 exposure with big data. PM 2.5 exposure concentration and dose inhalation of individuals were calculated by integrating hourly PM 2.5 concentration data and jogging GPS trajectory recorded by a sports app during 2015 in Beijing, after which relationships between jogging behaviors and PM 2.5 exposure were unpacked using statistics analysis and structural equation modelling. Experimental results on massive jogging trajectories show that: (1) the average jogging PM 2.5 exposure concentration is 60.43 μg/m 3 , and female joggers inhaled significantly less air pollution dose (19.70 μg) than men (24.91 μg). (2) There exist significant spatiotemporal disparities in jogging exposure to PM 2.5 . Joggings in the city center, in the morning, on weekdays and in autumn and winter seasons were exposed to higher pollution concentrations. (3) Jogging behavior characteristics, especially distance, activity space size, duration and rotation, were systematically associated with PM 2.5 exposure across space and time. (4) The role of gender directly shaped joggers' dose inhalation of PM 2.5 pollution and indirectly via duration, timing choice and distance. (5) The effects of weather conditions on joggers' exposure to PM 2.5 are mainly via direct effects, whereas the direct impacts of precipitation and wind speed are mitigated by indirect effects stemming from jogging behavior patterns. Our findings provide insights for personal guidance and policy intervention for the sake of promoting physical activity and reducing PM 2.5 exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The focus on phytoremediation in soil cadmium (Cd) remediation is driven by its cost-effectiveness and eco-friendliness. Selecting suitable hyperaccumulators and optimizing their growth conditions are key to enhance the efficiency of heavy metal absorption and accumulation. Our research has concentrated on the role of salicylic acid (SA) and jasmonic acid (JA) in facilitating Cd phytoextraction by "Sedum alfredii (S. alfredii)" through improved soil-microbe interactions. Results showed that SA or JA significantly boosted the growth, stress resistance, and Cd extraction efficiency in S. alfredii. Moreover, these phytohormones enhanced the chemical and biochemical attributes of the rhizosphere soil, such as pH and enzyme activity, affecting soil-root interactions. High-throughput sequencing analysis has shown that Patescibacteria and Umbelopsis enhanced S. alfredii's growth and Cd extraction by modifying the bioavailability and the chemical conditions of Cd in soil. Structural Equation Model analysis further verified that phytohormones significantly enhanced the interaction between S. alfredii, soil, and microbes, leading to a marked increase in Cd accumulation in the plant. These discoveries emphasized the pivotal role of phytohormones in modulating the hyperaccumulators' response to environmental stress and offered significant scientific support for further enhancing the potential of hyperaccumulators in ecological restoration technologies using phytohormones., 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.)

The alkaline solid-state electrolytes have received widespread attention for their good safety and electrochemical stability. However, they still suffer from low conductivity and poor mechanical properties. Herein, we report the synthesis of double-network featured hydroxide-conductive membranes fabricated by polyvinyl alcohol (PVA) and chitosan (CS) as the double-skeletons. Then, we implanted quaternary ammonium salt guar hydroxypropyltrimonium chloride (GG) as the OH - conductor for high-performance electrochemical devices. By virtue of the unique stripe-like structure shared from the double skeleton with a high degree of compatibility and stronger hydrogen bond interactions, the polyvinyl alcohol/chitosan-guar hydroxypropyltrimonium chloride (PCG) solid-state electrolytes achieved optimal thermal stability (> 300 °C), mechanical property (∼ 34.15 MPa), dimensional stability (at any bending angle), and high ionic conductivity (13 mS cm -1 ) and ion mobility number (t ion  ∼ 0.90) compared with chitosan-guar hydroxypropyltrimonium chloride (CG) and polyvinyl alcohol-guar hydroxypropyltrimonium chloride (PG) electrolyte membrane. As a proof-of-concept application, the "sandwich"-type zinc-air battery (ZAB) assembled using PCG membrane as the electrolyte realized a high open-circuit voltage (1.39 V) and an excellent power density (128 mW cm -2 ). Notably, in addition to its long-term cycle life (30 h, 2 mA cm -2 ) and stable discharge plateau (12 h, 5 mA cm -2 ), it could even enable a flexible ZAB (F-ZAB) to readily power light-emitting diodes (LED) at any bending angle. These merits afford the PCG membrane a promising electrolyte for improving the performance of solid-state batteries., 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 Inc. All rights reserved.)

Artificial reefs (ARs) are widespread globally and play a positive role in enhancing fish communities and restoring habitat. However, the effect of ARs on phytoplankton, which are fundamental to the marine food chain, remains inconclusive. Conducting a literature review and meta-analysis, this study investigates how ARs influence phytoplankton community dynamics by comparing the biomass, density, and diversity of phytoplankton between ARs and natural water bodies across varying deployment durations, constituent materials, and climatic zones. The study findings suggest that, overall, ARs enhance the biomass, density, and diversity of phytoplankton communities, with no significant differences observed compared to natural water bodies. The enhancement effect of ARs on phytoplankton communities becomes progressively more pronounced with increasing deployment time, with the overall status of phytoplankton communities being optimal when artificial reefs are deployed for 5 years or longer. Concrete and stone ARs can significantly enhance the biomass and diversity of phytoplankton, respectively. The effect of ARs on phytoplankton diversity is unrelated to climatic zones. However, deploying ARs in temperate waters significantly enhances phytoplankton biomass, while in tropical waters, it significantly reduces phytoplankton density. The research findings provide practical implications for the formulation of artificial reef construction strategies tailored to the characteristics of different aquatic ecosystems, emphasizing the need for long-term deployment and appropriate material selection. This study offers a theoretical basis for optimizing AR design and deployment to achieve maximum ecological benefits., 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.)

The presence of Total Polar Materials (TPM) in edible oils is a crucial indicator for assessing oil quality. It is of paramount importance to develop a rapid and dependable technique for monitoring polarity in frying oil. Sensitive polarity responsive fluorescence carbon dots (F-CDs) were synthesized by using p-phenylenediamine as precursors and 2-formylphenylboronic acid pinacol ester (2-FAPE) as a post-modifier. The construction of the fluorescent probe F-CDs involved a strong intramolecular charge-transfer (ICT) mechanism, with 2-FAPE serving as the electron-withdrawing fluorophore and the π-conjugated structure acting as a potent electron-donating group. A strong linear relationship was observed between the emission wavelength and the TPM value of frying oil within a range of 11% to 30%. Notably, the fluorescence color of the probe transitioned from blue to yellow under UV light at 365 nm as the TMP value increased. This study expands the range of sensing applications for CDs in food safety., 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.)

Atmospheric hydrogen peroxide (H 2 O 2 ), as an important oxidant, plays a key role in atmospheric chemistry. To reveal its characteristics in polluted areas, comprehensive observations were conducted in Zhengzhou, China from February 22 to March 4, 2019, including heavy pollution days (HP) and light pollution days (LP). High NO concentrations (18 ± 26 ppbv) were recorded in HP, preventing the recombination reaction of two HO 2 • radicals. Surprisingly, higher concentrations of H 2 O 2 were observed in HP (1.5 ± 0.6 ppbv) than those in LP (1.2 ± 0.6 ppbv). In addition to low wind speed and relative humidity, the elevated H 2 O 2 in HP could be mainly attributed to intensified particle-phase photoreactions and biomass burning. In terms of sulfate formation, transition-metal ions (TMI)-catalyzed oxidation emerged as the predominant oxidant pathway in both HP and LP. Note that the average H 2 O 2 oxidation rate increased from 3.6 × 10 -2 in LP to 1.1 × 10 -1  μg m -3  h -1 in HP. Moreover, the oxidation by H 2 O 2 might exceed that of TMI catalysis under specific conditions, emerging as the primary driver of sulfate formation., 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.)

Antibiotic resistance genes (ARGs) are a growing problem that is widespread in river-lake ecosystems, where they pose a threat to the aquatic environment's health and public safety. These systems serve as critical nodes in water management, as they facilitate the equitable allocation of water resources through long-term and frequent water diversions. However, hydrological disturbances associated with water-regulation practices can influence the dynamics of their potential host microorganisms and associated resistance genes. Consequently, identifying the key ARGs and their resistance mechanisms in heavily regulated waters is vital for safeguarding human health and that of river-lake ecosystems. In this study, we examined the impact of water-regulation factors on ARGs and their hosts within a river-lake continuum using 16S rRNA and metagenomic sequencing. We found that a significant increase in ARG abundance during regulation periods (p < 0.05), especially in the aquatic environment. Key resistance genes were macB, tetA, evgS, novA, and msbA, with increased efflux pinpointed as their principal resistance mechanism. Network analysis identified Flavobacteriales, Acinetobacter, Pseudomonas, Burkholderiaceae, and Erythrobacter as key potential host microorganisms, which showed increased abundance within the water column during regulation periods (p < 0.05). Flow velocity and water depth both drove the host microorganisms and critical ARGs. Our findings underscore the importance of monitoring and mitigating the antibiotic resistance risk during water transfers in river-lake systems, thereby supporting informed management and conservation strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Inorganic nitrates were considered to be a potential source of atmospheric NO 2 - /HONO during the daytime. To better evaluate the contribution of nitrate photochemistry on NO 2 - /HONO formation, the photolysis of nitrates in the real atmospheric environment needs to be further explored. Here, the NO 2 - generation by the photolysis of inorganic nitrates in the presence of total water-soluble organic carbon (WSOC) was quantified. The physicochemical properties of WSOC were measured to understand the underlying mechanism for the photolysis of inorganic nitrates with WSOC. WSOC enhanced or suppressed the photochemical conversion of nitrates to NO 2 - , with the quantum yield of NO 2 - (Φ NO2 - ) varying from (0.07 ± 0.02)% to (3.11 ± 0.04)% that depended on the light absorption properties of WSOC. Reactive oxygen species (ROS) generated from WSOC, including O 2 - /HO 2 and OH, played a dual role in the NO 2 - formation. Light-absorbing substances in WSOC, such as N-containing and carbonyl aromatics, produced O 2 - /HO 2 that enhanced the secondary conversion of NO 2 to NO 2 - . On the other hand, OH deriving from the WSOC photochemistry inhibited the nitrate photodegradation and the NO 2 - formation. HONO source strength by the aqueous photolysis of nitrates with WSOC was estimated to be lower than 100 ppt h -1 , which may partly contribute to the atmospheric HONO source in some cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microplastics (MPs) pollution in freshwater poses a risk to various ecosystems and health security. In 2018, the Chinese government banned fishing since 2018 in the Three Gorges Reservoir (TGR), but the fate and risk of MPs in wild fish remain unclear. Therefore, a detailed investigation was conducted into the occurrence of MPs in 18 wild fish species in the TGR using a Micro Fourier Transform Infrared Spectrometer, and the trophic transfer and risks were assessed. MPs in fish were aged, with abundances ranging from 0.68 ± 0.98 to 4.00 ± 2.12 items/individual. Most particles were less than 1 mm in size (73.4 %), with fibers being the dominant shape (48.9 %) and transparent as the dominant color (35 %). Polyethylene (PE) was the most prevalent type. The bioconcentration factor (BCF), bioaccumulation factor (BAF), trophic magnification factor (TMF) and polymer hazard index (PHI) were low, suggesting no trophic transfer and a low risk of MPs. The BAF may provide a more reasonable description of the degree of enrichment of MPs, and 'items/individual' or 'g/individual' can be used to describe MPs concentrations in fish. This study proposes new insights and prospectives that can help researchers better understand MPs enrichment in fish across various trophic levels., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Helicobacter pylori infection (HPI) is extremely common in the world, particularly in less developed areas, but the primary causes of childhood HPI are unspecified., Objectives: To determine the influences of exposure to home environmental factors (HEFs), outdoor air pollutants (OAPs), and parental stress (PS), as well as their interactions on children's HPI., Methods: We implemented a retrospective cohort study with 8689 preschoolers from nine districts at Changsha, China, was conducted using questionnaires to collect data of health and HEFs. Temperature and OAPs data were collected from ten and eight monitoring stations, individually. Temperature and OAPs exposures were calculated for all home addresses using the inversed distance weighted (IDW) model. Multiple logistic regression analysis was carried out to determine the separate and combined impacts of HEFs, OAPs, and PS on HPI., Results: Children's HPI was significantly associated with exposure to moisture-specific indoor allergens in one-year preceding conception, gestation, and first year, smoke-specific air pollution throughout life, and plant-specific allergens in previous year. Outdoor exposures to CO in the 7th-9th month before conception, as well as PM 2.5 in the second trimester and previous year, were associated with HPI, with ORs (95 % CIs) of 1.22 (1.05-1.41), 1.23 (1.03-1.46), and 1.33 (1.14-1.55). Parents' socioeconomic and psychological stress indicators were positively related to HPI. High socioeconomic indicators and psychological stresses increased the roles of indoor renovation and moisture indicators as well as outdoor SO 2 , PM 2.5 and O 3 on children's HPI over their entire lives. Parental psychological stress interacts with indoor renovation-specific air pollution, moisture- and plant-specific allergens, as well as outdoor traffic-related air pollution on HPI, during a critical time window in early life., Conclusions: Indoor and outdoor air pollutants, as well as allergens, separately and interactively exert important effects on childhood HPI, lending support to the "(pre-) fetal origin of HPI" hypothesis., 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.)

Clinical trials have demonstrated conclusively the non-inferiority of breast-conserving surgery followed by breast radiation therapy (BCT) compared with mastectomy for the treatment of early-stage invasive breast cancer (BC). The definition of the required surgical margin to ensure adequate removal of the cancer by BCT to obtain an acceptable low local recurrence (LR) rate remains controversial. Meta-analyses published by Houssami et al. in 2010 and 2014 demonstrated significantly lower LR rates for patients with a negative margin compared with those with positive (ink on tumour) or close (defined as ≤1 mm or ≤2 mm) margins. Neither meta-analysis addressed whether 'no ink on tumour' was adequate to define a negative margin because of a lack of data. Nevertheless, in 2014, the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) with advice from pathologists reviewed these data together and published guidelines recommending that a margin of 'no ink on tumour' was sufficient to define a clear margin in BCT. Subsequently, clinical practice has varied with some national and international bodies endorsing 'no ink on tumour', whilst others have recommended a ≥1 mm margin as acceptable margins for BCT. A more recent meta-analysis conducted by Bundred and colleagues in 2022 did have sufficient data to compare 'no ink on tumour' and 1 mm and concluded that 1 mm rather than 'no ink on tumour', should be used as a minimum negative margin, and recommended that international guidelines be revised. The current review presents a balanced assessment of the evidence relating margin width and local recurrence after BCT. This review concludes that guidelines should consider re-defining a negative margin as ≥1 mm rather than 'no ink on tumour' in the context of BCT, recognising there will be variation to tailor therapy for any individual patient situation to ensure optimal patient care., Competing Interests: Declaration of competing interest None All authors declare that no financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the correlation between programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) and evaluate the prognostic value of PD-L1 and TILs in Chinese triple-negative breast cancer (TNBC) patients with different molecular subtype METHODS: This retrospective study was conducted at 2020. Specifically, the pre-chemotherapy clinical data and non-stained tissue blocks of 465 TNBC patients visited the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014 were collected, with their blocks sliced and stained using PD-L1(SP142), and the outcome of subsequent chemotherapy obtained in 2020. The relapse-free survival (RFS) of the study population was calculated. The baseline PD-L1 expression status correlations with TILs and molecular subtypes were assessed using Spearman's rank correlation analysis and the Kruskal-Wallis test. Kaplan-Meier survival analyses were undertaken to evaluate the prognosis value of TILs and PD-L1 expression., Results: PD-L1 expression status on IC was moderately and positively correlated with stromal tumor-infiltrating lymphocytes (sTILs) (r s = 0.502, P <0.001) and iTILs (r s = 0.410, P < 0.001), respectively. PD-L1 expression status and TILs showed significant differences among molecular subtypes (P < 0.001), with the highest proportion of PD-L1+ and high TILs patients observed in the immunomodulatory (IM) subtype. TILs were significantly associated with RFS. Moreover, sTILs could act as an independent predictor of RFS (RR 0.953, 95 % CI 0.920 ∼ 0.987, P = 0.007), while PD-L1 expression status did not show the same prognostic significance., Conclusions: The incorporation of pre-treatment TILs and PD-L1 expression status as valuable tools for optimizing patient selection for immunotherapy and managing the risks associated with chemotherapy in Chinese TNBC patients., Data Availability: The data sets generated and analyzed during the current study are available from the corresponding author., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Intertidal wetlands undergo dynamic water and salinity variations, creating both promising and challenging habitats for diverse organisms. Crabs respond strongly to these variations by means such as altering their movements, thereby restructuring their spatial distribution and influencing coastal ecosystem resilience. However, the movements of crabs under varying environmental conditions require further elucidation. We conducted a systematic mesocosm experiment using the ubiquitous intertidal crab species Helice tientsinensis with four amount levels and six salinity levels of sprayed water applied through a custom apparatus, with a primary focus on crab movement. Crab movement from the experimental side of the apparatus (with altered conditions) to the control side (resembling field conditions of the intertidal wetlands of China's Yellow River Delta) and vice versa was recorded. The results revealed significant differences in moving out of the experimental side and moving in among the different water and salinity conditions, both separately for the two factors and simultaneously. Decreases in water content had a more pronounced effect on crab movement, leading to an increased number of crabs moving out of the experimental side of the apparatus. Conversely, as the experimental side became wetter, crabs tended to move towards it, and this movement was intensified by increases or decreases in water salinity. A structural equation model revealed that the moving-out and moving-in played fundamental roles in determining the number of resident crabs at the end of each experiment. While crabs preferred moist sediment with lower salinity, changes in salinity alone had minimal direct effect compared to sediment water contents. Our results clarify crab movements under varying water and salinity conditions, offering valuable insights to support adaptive interventions for crab populations and inform adaptive conservation and management strategies in intertidal wetlands., 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.)

Cyclic di-GMP (c-di-GMP), a ubiquitous secondary messenger in bacteria, affects multiple bacterial behaviors including motility and biofilm formation. c-di-GMP is synthesized by diguanylate cyclase harboring a GGDEF domain and degraded by phosphodiesterase harboring an either EAL or HD-GYP domain. Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis, harbors more than 60 genes involved in c-di-GMP metabolism. However, roles of most of these genes including vpa0198, which encodes a GGDEF-domain containing protein, are still completely unknown. AphA and OpaR are the master quorum sensing (QS) regulators operating at low (LCD) and high cell density (HCD), respectively. QsvR integrates into QS to control gene expression via direct regulation of AphA and OpaR. In this study, we showed that deletion of vpa0198 remarkably reduced c-di-GMP production and biofilm formation, whereas promoted the swimming motility of V. parahaemolyticus. Overexpression of VPA0198 in the vpa0198 mutant strain significantly reduced the swimming and swarming motility and enhanced the biofilm formation ability of V. parahaemolyticus. In addition, transcription of vpa0198 was under the collective regulation of AphA, OpaR and QsvR. AphA activated the transcription of vpa0198 at LCD, whereas QsvR and OpaR coordinately and directly repressed vpa0198 transcription at HCD, thereby leading to a cell density-dependent expression of vpa0198. Therefore, this work expanded the knowledge of synthetic regulatory mechanism of c-di-GMP in V. parahaemolyticus., 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.)

Oil crops have the potential to remediate cadmium (Cd)-contaminated farmland while producing safe vegetable oil. However, it is currently unknown whether different oil crops can remediate varying levels of Cd contamination in farmland. This study assessed agricultural fields in southern China contaminated with Cd levels ranging from 0.42 to 10.3 mg/kg. Three representative oilseed crops winter rape, oil sunflower, and peanut were selected for field experiments under two rotation systems. The effects of different rotation systems on remediating various Cd contamination levels were compared to evaluate the feasibility and potential of a two oil crop rotation system. All three crops showed good tolerance to Cd without signs of biomass deficiency. The biomass produced by the rape-oil sunflower and rape-peanut rotation systems was 33.44-459.00 g/ha and 30.64-281.40 g/ha, respectively. The Cd concentration in the oil products obtained complied with existing national and international standards (0.05 mg/kg). The remediation efficiency of the rape-oil sunflower and rape-peanut rotation systems was 1.98-7.37 % and 1.21-4.94 %, respectively. However, the remediation efficiencies and enrichment capacities of both rotation systems were somewhat inhibited by heavy Cd contamination (10.3 mg/kg). Therefore, the agricultural model of rotating two oilseed crops can be implemented in Cd-contaminated farmland at all levels but is more suitable for light to moderate Cd contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Gastric structure recognition systems have become increasingly necessary for the accurate diagnosis of gastric lesions in capsule endoscopy. Deep learning, especially using transformer models, has shown great potential in the recognition of gastrointestinal (GI) images according to self-attention. This study aims to establish an identification model of capsule endoscopy gastric structures to improve the clinical applicability of deep learning to endoscopic image recognition., Methods: A total of 3343 wireless capsule endoscopy videos collected at Nanfang Hospital between 2011 and 2021 were used for unsupervised pretraining, while 2433 were for training and 118 were for validation. Fifteen upper GI structures were selected for quantifying the examination quality. We also conducted a comparison of the classification performance between the artificial intelligence model and endoscopists by the accuracy, sensitivity, specificity, and positive and negative predictive values., Results: The transformer-based AI model reached a relatively high level of diagnostic accuracy in gastric structure recognition. Regarding the performance of identifying 15 upper GI structures, the AI model achieved a macroaverage accuracy of 99.6% (95% CI: 99.5-99.7), a macroaverage sensitivity of 96.4% (95% CI: 95.3-97.5), and a macroaverage specificity of 99.8% (95% CI: 99.7-99.9) and achieved a high level of interobserver agreement with endoscopists., Conclusions: The transformer-based AI model can accurately evaluate the gastric structure information of capsule endoscopy with the same performance as that of endoscopists, which will provide tremendous help for doctors in making a diagnosis from a large number of images and improve the efficiency of examination., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A type of colorectal cancer (CRC)，Colitis-associated colorectal cancer (CAC)， is closely associated with chronic inflammation and gut microbiota dysbiosis. Berberine (BBR) has a long history in the treatment of intestinal diseases, which has been reported to inhibit colitis and CRC. However, the mechanism of its action is still unclear. Here, this study aimed to explore the potential protective effects of BBR on azoxymethane (AOM)/dextransulfate sodium (DSS)-induced colitis and tumor mice, and to elucidate its potential molecular mechanisms by microbiota, genes and metabolic alterations. The results showed that BBR inhibited the gut inflammation and improved the function of mucosal barrier to ameliorate AOM/DSS-induced colitis. And BBR treatment significantly reduced intestinal tumor development and ki-67 expression of intestinal tissue along with promoted apoptosis. Through microbiota analysis based on the 16 S rRNA gene, we found that BBR treatment improved intestinal microbiota imbalance in AOM/DSS-induced colitis and tumor mice, which were characterized by an increase of beneficial bacteria, for instance Akkermanisa, Lactobacillus, Bacteroides uniformis and Bacteroides acidifaciens. In addition, transcriptome analysis showed that BBR regulated colonic epithelial signaling pathway in CAC mice particularly by tryptophan metabolism and Wnt signaling pathway. Notably, BBR treatment resulted in the enrichment of amino acids metabolism and microbiota-derived SCFA metabolites. In summary, our research findings suggest that the gut microbiota-amino acid metabolism-Wnt signaling pathway axis plays critical role in maintaining intestinal homeostasis, which may provide new insights into the inhibitory effects of BBR on colitis and colon cancer., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Brain-computer interfaces (BCIs), representing a transformative form of human-computer interaction, empower users to interact directly with external environments through brain signals. In response to the demands for high accuracy, robustness, and end-to-end capabilities within BCIs based on motor imagery (MI), this paper introduces STaRNet, a novel model that integrates multi-scale spatio-temporal convolutional neural networks (CNNs) with Riemannian geometry. Initially, STaRNet integrates a multi-scale spatio-temporal feature extraction module that captures both global and local features, facilitating the construction of Riemannian manifolds from these comprehensive spatio-temporal features. Subsequently, a matrix logarithm operation transforms the manifold-based features into the tangent space, followed by a dense layer for classification. Without preprocessing, STaRNet surpasses state-of-the-art (SOTA) models by achieving an average decoding accuracy of 83.29% and a kappa value of 0.777 on the BCI Competition IV 2a dataset, and 95.45% accuracy with a kappa value of 0.939 on the High Gamma Dataset. Additionally, a comparative analysis between STaRNet and several SOTA models, focusing on the most challenging subjects from both datasets, highlights exceptional robustness of STaRNet. Finally, the visualizations of learned frequency bands demonstrate that temporal convolutions have learned MI-related frequency bands, and the t-SNE analyses of features across multiple layers of STaRNet exhibit strong feature extraction capabilities. We believe that the accurate, robust, and end-to-end capabilities of the STaRNet will facilitate the advancement of BCIs., 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.)

Ferroptosis is a new programmed cell death characterized by iron-dependent lipid peroxidation. Targeting ferroptosis is considered a promising strategy for anti-cancer therapy. Recently, natural compound has gained increased attention for their advantage in cancer treatment, and the exploration of natural compounds as ferroptosis inducers offers a hopeful avenue for advancing cancer treatment modalities. Emodin is a natural anthraquinone derivative in many widely used Chinese medicinal herbs. In our previous study, we predicted that the anti-cancer effect of Emodin might related to ferroptosis by using RNA-seq in colorectal cancer (CRC). Thus, in this study, we aim to investigate the molecular mechanism underlying Emodin-mediated ferroptosis in CRC. Cell-based assays including CCK-8, colony formation, EdU, and Annexin V/PI staining were employed to assess Emodin's impact on cell proliferation and apoptosis. Furthermore, various techniques such as FerroOrange staining, C11-BODIPY 581/591 staining, iron, MDA, GSH detection assay and transmission electron microscopy were performed to examine the role of Emodin in ferroptosis. Additionally, specific NCOA4 knockdown cell lines were generated to elucidate the involvement of NCOA4 in Emodin-induced ferroptosis. Moreover, the effects of Emodin on ferroptosis were further confirmed through the application of inhibitors, including Ferrostatin-1, 3-MA, DFO, and PMA. As a results, Emodin inhibited proliferation and induced apoptosis in CRC cells. Emodin could decrease GSH content, xCT and GPX4 expression, meanwhile increasing ROS generation, MDA, and lipid peroxidation, and these effects could reverse by ferroptosis inhibitor, Ferostatin-1, iron chelator DFO, autophagy inhibitor 3-MA and NCOA4 silencing. Moreover, Emodin could inactivate NF-κb pathway, and PMA, an activator of NF-κb pathway could alleviate Emodin-induced ferroptosis in CRC cells. Xenograft mouse model also showed that Emodin suppressed tumor growth and induced ferroptosis in vivo. In conclusion, these results suggested that Emodin induced ferroptosis through NCOA4-mediated ferritinophagy by inactivating NF-κb pathway in CRC cells. These findings not only identified a novel role for Emodin in ferroptosis but also indicated that Emodin may be a valuable candidate for the development of an anti-cancer agent., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The postharvest quality of winter jujubes is prone to deterioration, including inevitable pericarp reddening and rapid nutrient loss from the flesh, significantly impacting its edible quality and commercial value. As a crucial metabolic pathway in plants, phenylpropane metabolism not only regulates plant stress resistance but also closely relates to various coloration effects. In this study, we investigated the effects of luteolin solutions on postharvest color changes and phenylpropanoid metabolism in winter jujube. The results indicated that compared to the control group, winter jujube fruit treated with 200 mg L -1 luteolin exhibited improved quality indexes, increased antioxidant capacity (capability of eliminating ABTS and DPPH radicals), and higher activities of antioxidant enzymes(superoxide dismutase (SOD), and catalase (CAT)). This led to a reduction in the oxidation of phenolic substances in winter jujube. Furthermore, luteolin treatment inhibited phenylpropanoid metabolism by suppressing the activities of 4-Coumarate: coenzyme A ligase (4CL), phenylalanine ammonilyase (PAL), and cinnamate 4 hydroxylase (C4H), as well as the expression of ZjUFGT, ZjDFT, and ZjPAL genes. Consequently, anthocyanin and quercetin synthesis were limited while the degradation rate of chlorophyll and carotenoid synthesis were slowed down after luteolin treatment. This resulted in delayed reddening of winter jujube following luteolin treatment. In conclusion, luteolin exhibits potential application prospects as a preservative for inhibiting reddening and browning in winter jujubes., 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 Masson SAS. All rights reserved.)

Pesticide residues may enter the human body through the food chain when livestock and poultry consume pesticide-contaminated feed. Therefore, monitoring and limiting pesticide residues in animal feed and animal-origin foods is necessary. Carbendazim is one of the most frequently detected pesticides in food and feed and has various toxic effects on non-target animals. This study investigated the effects of varying concentrations of carbendazim contamination in feed on broiler chicken growth performance, serum biochemical indicators, histopathology, and carbendazim residues in broiler muscles and livers. The results demonstrated that contamination of 5-100 mg/kg carbendazim in feed did not affect broiler growth performance or health. Carbendazim contamination in feed at 200-800 mg/kg slightly reduced growth performance. Broiler kidneys showed minor histopathological alterations after 400 mg/kg carbendazim exposure. Furthermore, when the carbendazim content in feed was less than 25 mg/kg, the residual carbendazim in the muscles and livers of broilers did not exceed the maximum residue level set by the European Union and China. Based on the above findings, carbendazim residues in the feed of less than 25 mg/kg can be considered safe for chicken products., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Mitochondria-derived peptides (MDPs) represent a recently discovered family of peptides encoded by short open reading frames (ORFs) found within mitochondrial genes. This group includes notable members including humanin (HN), mitochondrial ORF of the 12S rDNA type-c (MOTS-c), and small humanin-like peptides 1-6 (SHLP1-6). MDPs assume pivotal roles in the regulation of diverse cellular processes, encompassing apoptosis, inflammation, and oxidative stress, which are all essential for sustaining cellular viability and normal physiological functions. Their emerging significance extends beyond this, prompting a deeper exploration into their multifaceted roles and potential applications., Aim of Review: This review aims to comprehensively explore the biogenesis, various types, and diverse functions of MDPs. It seeks to elucidate the central roles and underlying mechanisms by which MDPs participate in the onset and development of cardiovascular diseases (CVDs), bridging the connections between cell apoptosis, inflammation, and oxidative stress. Furthermore, the review highlights recent advancements in clinical research related to the utilization of MDPs in CVD diagnosis and treatment., Key Scientific Concepts of Review: MDPs levels are diminished with aging and in the presence of CVDs, rendering them potential new indicators for the diagnosis of CVDs. Also, MDPs may represent a novel and promising strategy for CVD therapy. In this review, we delve into the biogenesis, various types, and diverse functions of MDPs. We aim to shed light on the pivotal roles and the underlying mechanisms through which MDPs contribute to the onset and advancement of CVDs connecting cell apoptosis, inflammation, and oxidative stress. We also provide insights into the current advancements in clinical research related to the utilization of MDPs in the treatment of CVDs. This review may provide valuable information with MDPs for CVD diagnosis and treatment., 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. Production and hosting by Elsevier B.V.)

PURPOSETo assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC).PATIENTS AND METHODSWe conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT.RESULTSOf the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis ( P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment.CONCLUSIONThe iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

Objective: To investigate the associations between apparent diffusion coefficient (ADC) values extracted from three different region of interest (ROI) position approaches and programmed cell death ligand-1 (PD-L1) expression, and evaluate the performance of the nomogram established based on ADC values and clinicopathological parameters in predicting PD-L1 expression in cervical cancer (CC) patients., Methods: Through retrospective recruitment, a training cohort of 683 CC patients was created, and a validation cohort of 332 CC patients was prospectively recruited. ROIs were delineated using three different methods to measure the mean ADC (ADC mean ), single-section ADC (ADC ss ), and the minimum ADC of tumors (ADC min ). Logistic regression was employed to identify independent factors related to PD-L1 expression. A nomogram was drawn based on ADC values combined with clinicopathological features, its discrimination and calibration performances were estimated using the area under the curve (AUC) of receiver operating characteristic and calibration curve. The clinical benefits were evaluated by decision curve analysis., Results: The ADC min independently correlated with PD-L1 expression. The nomogram constructed with ADC min and other independent clinicopathological-related factors: FIGO staging, pathological grade, parametrial invasion, and lymph node status demonstrated excellent diagnostic performance (AUC = 0.912 and 0.903, respectively), good calibration capacities, and greater net benefits compared to the clinicopathological model in both the training and validation cohorts., Conclusion: ADC min independently correlated PD-L1 expression, and the nomogram established with ADC min and clinicopathological independent prognostic factors had a strong predictive performance for PD-L1 expression, thereby serving as a promising tool for selecting cases eligible for immunotherapy., Clinical Relevance Statement: The minimum ADC can serve as a reliable imaging biomarker related to PD-L1 expression; the established nomogram combines the minimum ADC and clinicopathological factors that can assist clinical immunotherapy decisions., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Invertebrate lectins exhibit structural diversity and play crucial roles in the innate immune responses by recognizing and eliminating pathogens. In the present study, a novel lectin containing a Gal&#95;Lectin, a CUB and a transmembrane domain was identified from the Pacific oyster Crassostrea gigas (defined as CgGal-CUB). CgGal-CUB mRNA was detectable in all the examined tissues with the highest expression in adductor muscle (11.00-fold of that in haemocytes, p < 0.05). The expression level of CgGal-CUB mRNA in haemocytes was significantly up-regulated at 3, 24, 48 and 72 h (8.37-fold, 12.13-fold, 4.28-fold and 10.14-fold of that in the control group, respectively) after Vibrio splendidus stimulation. The recombinant CgGal-CUB (rCgGal-CUB) displayed binding capability to Mannan (MAN), peptidoglycan (PGN), D-(+)-Galactose and L-Rhamnose monohydrate, as well as Gram-negative bacteria (Escherichia coli, V. splendidus and Vibrio anguillarum), Gram-positive bacteria (Micrococcus luteus, Staphylococcus aureus, and Bacillus sybtilis) and fungus (Pichia pastoris). rCgGal-CUB was also able to agglutinate V. splendidus, and inhibit V. splendidus growth. Furthermore, rCgGal-CUB exhibited the activities of enhancing the haemocyte phagocytosis towards V. splendidus, and the phagocytosis rate of haemocytes was descended in blockage assay with CgGal-CUB antibody. These results suggested that CgGal-CUB served as a pattern recognition receptor to bind various PAMPs and bacteria, and enhanced the haemocyte phagocytosis towards V. splendidus., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The enzyme-like properties of nanozymes may be considerably affected by the structure and surface groups, which thus need to be optimized. Here, through a simple NaOH chemical corrosion method, the chemical structure similar to N-Methylpyrrolidone (NMP), which possessed intrinsic oxidase-like activity, was introduced into polypyrrole (PPy), and then this nanomaterial became oxygen-functionalized PPy (o-PPy) with excellent oxidase-like activity from PPy without this property. Furthermore, after compounding magnetic Fe 3 O 4 , the obtained nanocomposites Fe 3 O 4 @o-PPy nanoparticles (Fe 3 O 4 @o-PPy NPs) showed superiorities in separation during synthesis and real-time control of enzyme catalysis. Studies have found that the enzymatic activity of Fe 3 O 4 @o-PPy NPs depended on the amount of functionalized oxygen and the conjugation extent of o-PPy. Fe 3 O 4 @o-PPy NPs had efficient oxidase-like activity under a wide range of pH and temperature. Based on the oxidase-like activity of Fe 3 O 4 @o-PPy NPs, a colorimetric sensor for glutathione (GSH), which presented rich color changes and satisfactory colorimetric resolution by adding the amaranth, was realized. We believe that the functional modification and structural regulation of PPy can not only realize its wider application but also promote the discovery of novel and efficient nanozymes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Contaminated foods are a major source of bisphenol A (BPA) and are widely used in food packaging. Prolonged exposure to BPA can cause reproductive dysfunction in humans. Procyanidine (PC) is a potent natural antioxidant; however, the exact mechanism by which PC mitigates Leydig cell damage caused by BPA is unknown. In this study, the protective effect of PC against BPA-induced TM3 cell damage was investigated, and the underlying mechanism was assessed. PC treatment attenuates BPA-induced TM3 cell damage by suppressing oxidative stress and inhibiting TM3 apoptosis. In addition, PC upregulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant target genes. Treatment with the NRF2 inhibitor ML385 reversed the PC-induced upregulation of the mRNA expression of these genes. Overall, PC may mitigate BPA-induced cell damage by activating the Nrf2 signaling pathway, suggesting that PC supplementation may alleviate BPA toxicity in TM3 cells., 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.)

Objective: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy., Study Design: We conducted an institutional review board-approved, retrospective cohort study of children with newly diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models., Results: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17%, respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR], 1.7; P = .0072), clinically documented infection (aHR, 1.73; P = .025), and likely bacterial infection (aHR, 1.86; P = .008). Conversely, vitamin A deficiency was associated solely with a lower risk of sepsis (aHR, 0.19; P = .027)., Conclusions: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Exploring more efficient pancreatic cancer drug screening platforms is of significant importance for accelerating the drug development process. In this study, we developed a high-sensitivity bioluminescence system based on smartphones and smart tablets, and constructed a pancreatic cancer drug screening platform (PCDSP) by combining the pancreatic cancer cell sensing model (PCCSM) on the multiwell plates (MTP). A smart tablet was used as the light source and a smartphone as the colorimetric sensing device. The smartphone dynamically controls the color and brightness displayed on the smart tablet to achieve lower LOD and wider detection ranges. We constructed PCCSM for 24 h, 48 h, and 72 h , and performed colorimetric experiments using both PCDSP and a commercial plate reader (CPR). The results showed that the PCDSP had a lower LOD than that of CPR. Moreover, PCDSP even exhibited a lower LOD for 24 h PCCSM testing compared to CPR for 48 h PCCSM testing, effectively shortening the drug evaluation process. Additionally, the PCDSP offers higher portability and efficiency compared with CPR, making it a promising platform for efficient pancreatic cancer drug screening., 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 introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To investigate air-sea CO 2 flux at the Qingdao nearshore site and its temporal variations, a high-resolution continuous observation of surface carbon dioxide partial pressure (pCO 2 ) was carried out at Zhongyuan Pier near Tuandao from May 25 to July 8, 2019. It was observed that during this period, surface pCO 2 varied between ∼490 and ∼690 μatm, mainly associated with sea surface temperature. Surface pCO 2 also displayed substantial diurnal variations, with an average amplitude of 64 ± 21 μatm, largely dominated by biological activities. During the observational period, this site acted as a source of atmospheric CO 2 , releasing 361 mmol CO 2 m -2 . The notable diurnal variations in air-sea CO 2 flux, such as the observed average amplitude of 10.9 mmol m -2 d -1 in this study, pose a challenge for accurately estimating the air-sea CO 2 flux in coastal regions without high-resolution observations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the safety and efficacy of high-intensity focused ultrasound (HIFU) ablation combined with pharmacogenomic-guided chemotherapy in treating patients with advanced pancreatic cancer (PC)., Methods: Thirty-one patients with unresectable PC (stage III 17, stage IV 14) were enrolled in this study. The patients were divided into group A (pharmacogenomic-guided chemotherapy following HIFU treatment, n = 13) and group B (traditional chemotherapy following HIFU treatment, n = 18). Contrast-enhanced computed tomography and magnetic resonance imaging were used to evaluate tumor response. Pain intensity was assessed using the numerical rating scale. The Kaplan-Meier method and log-rank test were used to analyze survival., Results: The mean pain intensity score in 18 patients decreased from 6.6 ± 2.2 before HIFU to 3.3 ± 1.0 after HIFU (p = 0.000). The mean duration of pain relief was 5.2 ± 3.2 mo in group A and 2.4 ± 1.3 mo in group B (p = 0.026). There was no significant difference of the non-perfused volume ratio (83.5% ± 22.3% in group A and 85.3% ± 16.8% in group B) between the two groups. The median survival time was 14 mo in group A and 5 mo in group B. The 6 and 12-mo survival rates were 74.1% and 59.3% in group A, and 32.4% and 19.4% in group B, respectively. The difference in survival between the two groups was significant (p = 0.04). No severe complications (≥grade 3) related to HIFU were observed. Bone marrow depression was the main adverse reaction related to chemotherapy, with grade 3 bone marrow depression observed 2 (15.4%) patients in group A and 7 (38.9%) patients in group B., Conclusion: HIFU combined with pharmacogenomic-guided chemotherapy is safe and effective in treating patients with advanced PC. It provides better clinical outcomes in pain relief, quality of life and survival benefits for patients with advanced PC compared to HIFU combined with traditional chemotherapy. This combined approach may have the potential to become an important supplement to the treatment of advanced PC., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With the increasing emphasis on sustainability and eco-friendliness, a novel biodegradable packaging materials has received unprecedented attention. Nanocellulose, owing to its high crystallinity, degradability, minimal toxicity, and outstanding biocompatibility, has gained considerable interest in the field of sustainable packaging. This review provided a comprehensive perspective about the recent advances and future development of cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs). We first introduced the utilization of agricultural waste for nanocellulose production, such as straw, bagasse, fruit byproducts, and shells. Next, we discussed the preparation process of nanocellulose from various agricultural wastes and expounded the advantages and shortcomings of different methods. Subsequently, this review offered an in-depth investigation on the application of nanocellulose in food packaging, especially the function and packaged form of nanocellulose on food preservation. Finally, the safety evaluation of nanocellulose in food packaging is conducted to enlighten and promote the perfection of relevant regulatory documents. In short, this review provided valuable insights for potential research on the biobased materials utilized in future food packaging., 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.)

Gliomas are one of the most aggressive types of brain tumors and are associated with high morbidity and mortality rates. Currently, conventional treatments for gliomas such as surgical resection, radiotherapy, and chemotherapy have limited effectiveness, and new approaches are needed to improve patient outcomes. mRNA-based vaccines represent a promising therapeutic strategy for cancer treatment, including gliomas. Recent advances in immunotherapy using mRNA-based dendritic cell vaccines have shown great potential in preclinical and clinical trials. Dendritic cells are professional antigen-presenting cells that play a crucial role in initiating and regulating immune responses. In this review, we summarize the current progress of mRNA-based vaccines for gliomas, with a focus on recent advances in dendritic cell-based mRNA vaccines. We also discuss the feasibility and safety of mRNA-based clinical applications for gliomas., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC., Methods: In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM., Results: The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM., Conclusions: Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care., (© 2024. Society of Surgical Oncology.)

Objectives: China introduced an innovative Supplementary High-Cost Illness Insurance (SHCII) program to enhance existing social health insurance by providing extra financial support for individuals facing catastrophic illnesses in 2015. The SHCII has notably increased access to healthcare and alleviated financial strain for economically disadvantaged individuals. However, there is a lack of information regarding the program's impact on the mental health of its beneficiaries. This study aims to assess the impact of SHCII on the mental well-being of middle-aged and older individuals., Methods: Using data from the China Health and Retirement Longitudinal Study (2011, 2013, 2015, and 2018), this study examined how SHCII affects mental health among middle-aged and older individuals in China using propensity score matching with the time-varying difference-in-differences method., Results: We found that SHCII implementation can significantly reduce the Center for Epidemiologic Studies-Depression Scale scores of middle-aged and older individuals. This reduction was more pronounced among older individuals with poor self-rated health, chronic disease, and low household wealth when compared to their counterparts., Discussion: The implementation of SHCII has had a significant and positive impact on mental health outcomes. We recommend that governments consider expanding the program to other areas within China, focusing especially on the most economically disadvantaged segments of the population., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. 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.)

A near-infrared fluorescent "turn on" probe DTMI featuring simple skeleton was constructed easily. It undergoes a structure transformation from an A-π-A to a D-π-A framework towards SO 3 2- . Besides, DTMI is capable of distinctive sensing sulfite with a fast response and a significant Stokes shift as well as with high sensitivity, excellent selectivity, long-term stability of fluorescence signals, and good anti-interference ability. The detection limit (LOD) of DTMI for sulfite within the linear concentration range of 0.5-10 μM is 27.39 nM. More importantly, DTMI has been favorably utilized for detecting sulfite in food samples such as red wine and vermicelli. Based on its low biotoxicity, DTMI has been successfully applied in imaging experiments involving HeLa cells, onion inner epidermal cells, and zebrafish. Therefore, the results show that the presented probe possesses potential sensing activity towards sulfite in complex biological system and food samples., 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.)

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and accumulated in the liver of mammals. PFOS exposure is closely associated with the development of pyroptosis. Nevertheless, the underlying mechanism is unclear. We found here that PFOS induced pyroptosis in the mice liver and L-02 cells as demonstrated by activation of the NOD-like receptor protein 3 inflammasome, gasdermin D cleavage and increased release of interleukin-1β and interleukin-18. The level of cytoplasmic calcium was accelerated in hepatocytes upon exposure to PFOS. The phosphorylated/activated form of calcium/calmodulin-dependent protein kinase II (CaMKII) was augmented by PFOS in vivo and in vitro. PFOS-induced pyroptosis was relieved by CaMKII inhibitor. Among various CaMKII subtypes, we identified that CaMKIIγ was activated specifically by PFOS. CaMKIIγ interacted with Smad family member 3 (Smad3) under PFOS exposure. PFOS increased the phosphorylation of Smad3, and CaMKII inhibitor or CaMKIIγ siRNA alleviated PFOS-caused phosphorylation of Smad3. Inhibiting Smad3 activity was found to alleviate PFOS-induced hepatocyte pyroptosis. This study puts forward that CaMKIIγ-Smad3 is the linkage between calcium homeostasis disturbance and pyroptosis, providing a mechanistic explanation for PFOS-induced pyroptosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Laccase, a prominent enzyme biomacromolecule, exhibits promising catalytic efficiency in degrading phenolic compounds like bisphenol A (BPA). The laccase immobilized on conventional materials frequently demonstrates restricted loading and suboptimal catalytic performance. Hence, there is a pressing need to optimized external surface utilization to enhance catalytic performance. Herein, we synthesized amino-functionalized modified silica particles with a hierarchical hollow silica spherical (HHSS) structure for laccase immobilization via crosslinking, resulting in HHSS-LE biocatalysts. Through Box-Behnken design (BBD) and response surface methodology (RSM), we achieved a remarkably high enzyme loading of up to 213.102 mg/g. The synergistic effect of adsorption by HHSS and degradation by laccase facilitated efficient removal of BPA. The HHSS-LE demonstrated superior BPA removal capabilities, with efficiencies exceeding 100 % in the 50-200 mg/L BPA concentration range. Compared to MCM-41 and solid silica spheres (SSS), HHSS showed the highest enzyme loading capacity and catalytic activity, underscoring its superior external surface utilization rate per unit mass. Remarkably, the HHSS-LE biocatalyst exhibited remarkable recyclability even after 11 successive cycles of reuse. By preparing high immobilization rate with efficient external surface utilization, this study lays the foundation for the design of universally applicable and efficient enzyme immobilization catalysts., 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.)

The aim of this study is to optimize the extraction process of oat saponins (Os) and to evaluate their antioxidant potential. Single factor experiment, response surface optimization design, and orthogonal test were employed to optimize the process of ultrasonic-assisted extraction of Os, and the optimal extraction conditions were as followed: ethanol volume fraction of 80 %, material-solvent ratio of 1:14, ultrasonic power of 400 W, ultrasonic time of 25 min, extraction temperature of 60℃, extraction time of 180 min, and the extraction rate of Os was 0.317 %±0.105 %. Using the method, the crude extract of Os was prepared and its abilities of scavenging radicals in vitro and inhibiting protein oxidation in pork were determined, with ascorbic acid (Vc) as the control. Results revealed that the scavenging ability of Os against DPPH radical, hydroxyl radical (·OH) and superoxide anion (O 2 - ) increased with the concentration of Os. Interestingly, the scavenging abilities of Os against DPPH and O 2 - were far lower than that of Vc, but its scavenging ability against ·OH was very close to that of Vc, reaching 84.59 % and 96.33 %, respectively. Furthermore, the experiments of pork storage and Fenton oxidation system showed that Os with 0.09-0.72 mg/mL could reduce the production of carbonyl (8.49 %-50.05 %) and the oxidation of total sulfhydryl (1.29 %-25.86 %), and effectively inhibit the oxidation of protein in pork by 7.82 %-22.53 %. The results of this study will provide a theoretical basis for the application of oat saponins as a natural anti-protein oxidant in meat processing and storage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to analyze the independent risk factors of malignant subpleural pulmonary lesions (SPLs) on B-mode ultrasound (US) images, to construct the combined predictive indicators, and to prospectively verify their predictive efficacy., Methods: A total of 336 patients with SPLs were included in the prospective study, of whom the single-center included patients between September 2019 and December 2019 were the development cohort (DC) (n = 219); Patients who were concurrently enrolled in three centers between January and February 2020 were the validation cohort (VC) (n = 117). The clinical features and B-mode US parameters were collected. Based on the DC, a combined predictive indicators model was developed using binary logistic regression. Then the discrimination was verified externally in the VC. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians., Results: The combined predictive indicators model was finally constructed by five parameters: age, borderline, angle between the lesion border and thoracic wall, posterior echo of the lesion and invasion of the pleura. The fitting degree of the model was good (χ 2 = 9.198, p = 0.326). The area under ROC curve of the model was 0.872 (DC) and 0.808 (VC), yielding a higher net benefit than individual risk factors., Conclusion: The combined predictive indicators are useful in the assessment of malignant SPLs and are a useful adjunct diagnostic tool, especially in primary healthcare settings in developing countries., Competing Interests: Conflict of 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 article., (Copyright © 2024. Published by Elsevier Inc.)

A significant reduction in plasma concentration of cholesterol during early lactation is a common occurrence in high-yielding dairy cows. An insufficient synthesis of cholesterol in the liver has been linked to lipid accumulation caused by high concentrations of fatty acids during negative energy balance (NEB). As ruminant diets do not provide quantitative amounts of cholesterol for absorption, phytosterols such as β-sitosterol may serve to mitigate the shortfall in cholesterol within the liver during NEB. To gain mechanistic insights, primary hepatocytes were isolated from healthy female 1-day old calves for in vitro studies with or without 1.2 mM fatty acids (FA) to induce metabolic stress. Furthermore, hepatocytes were treated with 50 μM β-sitosterol with or without FA. Data were analyzed by one-way ANOVA with subsequent Bonferroni correction. Results revealed that calf hepatocytes treated with FA had greater content of non-esterified fatty acids (NEFA) and triacylglycerol (TAG), and greater mRNA and protein abundance of the lipid synthesis-related SREBF1 and FASN. In contrast, mRNA and protein of CPT1A (fatty acid oxidation) and the cholesterol metabolism-related targets SREBF2, HMGCR, ACAT2, APOA1, ABCA1 and ABCG5 was lower. Content of the antioxidant-related glutathione (GSH) and activities of superoxide dismutase (SOD) also was lower. Compared with FA challenge alone, 50 μM β-sitosterol led to greater mRNA and protein abundance of SREBF2, HMGCR, ACAT2 and ABCG5, and greater content of GSH and activity of SOD. In contrast, compared with the FA group, the mRNA and protein abundance of SREBF1 and ACC1 and the content of TAG and NEFA in the β-sitosterol + FA group were lower. Overall, β-sitosterol can promote cholesterol metabolism and reduce oxidative stress while reducing lipid accumulation in hepatocytes challenged with high concentrations of fatty acids., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Patients with hypertrophic scarring tend to experience recurrence after treatment, which often occurs in areas of the body with high skin tension., Aims: To evaluate better treatments aimed at reducing the risk of scar recurrence in areas of high skin tension., Methods: Patients were randomly divided into the following three treatment groups: botulinum toxin type A (BTA) via dual-plane micro-drop injections, triamcinolone acetonide (TAC) suspension, and CO 2 via fractional CO 2 laser. Interventions were implemented in all three groups once a month for three consecutive sessions. After the final treatment, scarring was evaluated at 1, 3, 6, 12, and 24 months using the Patient and Observer Scar Assessment Scale (POSAS)., Results: The 3-month POSAS score for each scar indicator in the treatment groups was significantly lower than that in the preoperative groups (p < 0.001). The scar score in the TAC group decreased at 3 months and increased thereafter. For other groups, the scar score continually decreased at all time points according to the Patient Scar Assessment Scale. Based on the Observer Scar Assessment Scale, the scar score continuously decreased at all time points in the BTA group; in the TAC group, it decreased at 1 month and increased thereafter; and in the CO 2 group, the scar score decreased at 3 months and subsequently stabilized., Conclusions: All three treatment methods were effective. However, the BTA group experienced a reduced risk of scar recurrence and maintained long-term treatment effects., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Myocardial ischemia-reperfusion (MI/R) can lead to structural and functional abnormalities in the hippocampal neurons of the brain. High-mobility group box-l (HMGB1) is implicated in the activation of immune cells and the stimulation of inflammatory responses. However, the specific role of HMGB1 in cognitive impairment induced by MI/R in elderly rats has yet to be elucidated., Methods: Elderly rats underwent surgical procedures to induce MI/R. To evaluate the learning and memory abilities of these rats, a water maze test and a new-object recognition test were administered. Nissl staining was utilised to examine hippocampal neuron damage. Enzyme-linked immunosorbent assay, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were conducted to measure the expression levels of HMGB1, inflammatory cytokines, and molecular pathways., Results: The study found that MI/R induced cognitive impairment in elderly rats. There was an observed increase in serum HMGB1 levels, along with elevated concentrations of pro-inflammatory cytokines in the plasma and hippocampus, accompanied by a decrease in anti-inflammatory cytokines. Moreover, substantial damage was evident in the hippocampal neurons of rats exposed to MI/R. In the brains of these rats, there was an increased expression of HMGB1, the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), phosphorylated p65, interleukin-1β (IL-1β), IL-6, IL-23, tumour necrosis factor-α (TNF-α), caspase-3, and Bax. In contrast, the expression of B-cell lymphoma 2 was decreased. The RT-qPCR analyses indicated elevated levels of HMGB1, RAGE, TLR4, IL-1β, IL-6, IL-23, TNF-α, caspase-3, and Bax mRNA., Conclusion: The increased concentration of serum and hippocampal inflammatory factors in the brains of elderly rats subjected to MI/R suggests that cognitive impairment may be induced through the activation of the HMGB1/TLR4/NF-κB signalling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)