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Background: Cereal grains are rich in carbohydrates and could trigger a hyperglycemic response which is closely linked to blood pressure status. We aim to examine the associations between the consumption of cereals with different cooking methods and hypertension risk., Methods: We conducted a prospective analysis utilizing the nationwide data of 11,080 adult participants who were free of hypertension at baseline. Cereal intake was assessed using 3-day 24 h dietary recalls with a weighing technique. Hypertension incidence was identified in adherence with the Seventh Joint National Commission guidelines during the follow-up. Cox proportional hazards regression models were used to extrapolate hazard ratios associated with hypertension risk., Results: Over an average follow-up span of 7 years (77,560 person-years), we identified 3643 new hypertension cases. The intake of total, fried, and baked cereals was associated with 15%, 20%, and 20% higher risk of hypertension, respectively. Whole grain consumers had an 8% lower risk of hypertension compared with non-consumers, while total refined grain consumers showed no significant association. Replacing one daily serving of fried or baked cereals with an equivalent serving of boiled cereals was related to a 28% or 14% lower risk, respectively., Conclusions: Total, fried, and baked cereal consumption was positively associated with hypertension risk, while consuming whole grains was related to a lower risk. Modifying cooking methods from frying or baking to boiling for cereals may be beneficial to lower risk. The current study underscores the significance of considering both the degree of processing and cooking methods applied to cereals in addressing hypertension prevention and management.

Tissue engineering of small-diameter vessels remains challenging due to the inadequate ability to promote endothelialization and infiltration of smooth muscle cells (SMCs). Ideal vascular graft is expected to provide the ability to support endothelial monolayer formation and SMCs infiltration. To achieve this, vascular scaffolds with both orientation and dimension hierarchies were prepared, including hierarchically random vascular scaffold (RVS) and aligned vascular scaffold (AVS), by utilizing degradable poly(ε-caprolactone)-co-poly(ethylene glycol) (PCE) and the blend of PCE/gelatin (PCEG) as raw materials. In addition to the orientation hierarchy, dimension hierarchy with small pores in the inner layer and large pores in the outer layer was also constructed in both RVS and AVS to further investigate the promotion of vascular reconstruction by hierarchical structures in vascular scaffolds. The results show that the AVS with an orientation hierarchy that consists with the natural vascular structure had better mechanical properties and promotion effect on the proliferation of vascular cells than RVS, and also exhibited excellent contact guidance effects on cells. While the dimension hierarchy in both RVS and AVS was favorable to the rapid infiltration of SMCs in a short culture time in vitro. Besides, the results of subcutaneous implantation further demonstrate that AVS achieved a fully infiltrated outer layer with wavy elastic fibers-mimic strips formation by day 14, ascribing to hierarchies of aligned orientation and porous dimension. The results further indicate that the scaffolds with both orientation and dimension hierarchical structures have great potential in the application of promoting the vascular reconstruction., 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.)

Aim: To investigate the association between fish oil supplementation and subsequent risk of chronic kidney disease (CKD) among patients with diabetes, and further evaluate the mediation effect of typical glycolipid and inflammatory biomarkers., Methods: In total, 24 497 patients with diabetes from the UK Biobank were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD risk, and the rate advancement period was calculated to quantify and communicate the impact of fish oil upon that risk. In addition, we also used mediation analysis to assess the mediating role of plasma biomarkers., Results: Overall, 7122 patients reported taking fish oil supplements. During a mean of 11.3 years of follow-up, 3533 CKD cases occurred. In the fully adjusted model, fish oil use was inversely associated with the incidence of CKD (HR 0.90; 95% CI: 0.83, 0.97), which was mediated by serum levels of HbA1c (4.7%), C-reactive protein (CRP) (3.4%) and high-density lipoprotein cholesterol (HDL-C) (2.3%). Participants who took fish oil supplements displayed the same risk of CKD events, but that risk was delayed by approximately 2.79 years compared with non-users of fish oil., Conclusions: Our findings advocate the beneficial role of fish oil use in preventing CKD among patients with diabetes, which may be mediated by serum levels of HbA1c, CRP and HDL-C, and support public health policies aiming to promote fish oil supplementation for the prevention of diabetes complications., (© 2024 John Wiley & Sons Ltd.)

Background: The early detection of individuals who require palliative care is essential for the timely initiation of palliative care services. This systematic review and meta-analysis aimed to (1) Identify the screening instruments used by health professionals to promote early identification of patients who may benefit from palliative care; and (2) Assess the psychometric properties and clinical performance of the instruments., Methods: A comprehensive literature search was conducted in PubMed, Embase, CINAHL, Scopus, CNKI and Wanfang from inception to May 2023. We used the COnsensus-based Standards for the Selection of Health Measurement INstruments to assess the methodological quality of the development process for the instruments. The clinical performance of the instruments was assessed by narrative summary or meta-analysis. Subgroup analyses were conducted where necessary. The quality of included studies was assessed using the Newcastle-Ottawa Scale and the Cochrane Collaboration's risk of bias assessment tool., Results: We included 31 studies that involved seven instruments. Thirteen studies reported the development and validation process of these instruments and 18 studies related to assessment of clinical performance of these instruments. The content validity of the instruments was doubtful or inadequate because of very low to moderate quality evidence. The pooled sensitivity (Se) ranged from 60.0% to 73.8%, with high heterogeneity (I2 of 88.15% to 99.36%). The pooled specificity (Sp) ranges from 70.4% to 90.2%, with high heterogeneity (I2 of 96.81% to 99.94%). The Supportive and Palliative Care Indicators Tool (SPICT) had better performance in hospitals than in general practice settings (Se=79.8% vs 45.3%, p=0.004; Sp=59.1% vs 97.0%, p=0.000)., Conclusion: The clinical performance of existing instruments in identifying patients with palliative care needs early ranged from poor to reasonable. The SPICT is used most commonly, has better clinical performance than other instruments but performs better in hospital settings than in general practice settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The available evidence regarding the role of fruit and vegetable consumption in the development of colorectal polyps remains inconclusive, and there is a lack of data on different histopathologic features of polyps. We aimed to evaluate the associations of fruit and vegetable consumption with the prevalence of colorectal polyps and its subtypes in a high-risk population in China., Methods: We included 6783 Chinese participants aged 40-80 years who were at high risk of colorectal cancer (CRC) in the Lanxi Pre-colorectal Cancer Cohort (LP3C). Dietary information was obtained through a validated food-frequency questionnaire (FFQ), and colonoscopy screening was used to detect colorectal polyps. Dose-response associations of fruit and vegetable intake with the prevalence of polyps were calculated using multivariate-adjusted regression models, which was reported as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: 2064 cases of colorectal polyps were ascertained in the LP3C during 2018-2019. Upon multivariable adjustments, including the diet quality, fruit consumption was inversely associated with the prevalence of polyps (P trend = 0.02). Participants in the highest tertile of fruit intake had a 25% lower risk (OR: 0.75; 95% CI 0.62‒0.92) compared to non-consumers, while vegetable consumption had no significant association with polyp prevalence (P trend = 0.86). In terms of colorectal histopathology and multiplicity, higher fruit intake was correlated with 24, 23, and 33% lower prevalence of small polyps (OR: 0.76; 95% CI 0.62‒0.94; P trend = 0.05), single polyp (OR: 0.77; 95% CI 0.62‒0.96; P trend = 0.04), and distal colon polyps (OR: 0.67; 95% CI 0.51‒0.87; P trend = 0.003), respectively., Conclusions: Fresh fruit is suggested as a protective factor to prevent colorectal polyps in individuals at high risk of CRC, and should be underscored in dietary recommendations, particularly for high-risk populations., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection., Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival., Design, Setting, and Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023., Interventions: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression., Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator., Results: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07)., Conclusions and Relevance: This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies., Trial Registration: ClinicalTrials.gov Identifier: NCT02047474.

Background & Aims: Obesity has been linked to various detrimental health consequences. While there is established evidence of a negative correlation between seafood consumption and obesity in adults, the current research on the association between seafood intake in childhood/adolescence and the risk of obesity is lacking. Our aim was to evaluate the association between seafood intake in childhood/adolescence and the risk of obesity in a Chinese nationwide cohort., Methods: We utilized data from the China Health and Nutrition Survey (CHNS) from the year of 1997 to 2015. Seafood consumption was evaluated through 3-day 24-hour recalls. In our study, overweight/obesity status was determined based on the Chinese Criteria of Overweight and Obesity in School-age Children and Adolescents (WS/T 586-2018), while abdominal obesity status was determined according to the Chinese Criteria of Waist Circumference Screening Threshold among Children and Adolescents (WS/T 611-2018)., Results: During an average follow-up of 7.9 years, 404 cases developed overweight/obesity among 2206 participants in the seafood-overweight/obesity analysis, while 381 cases developed abdominal obesity among 2256 participants in the seafood-abdominal-obesity analysis. The high-consumer group was associated with 35% lower risk of overweight/obesity risk and 26% lower risk of abdominal obesity after fully adjusting for sociodemographic and lifestyle factors, compared with the non-consumer group. Considering different cooking methods, boiled seafood consumption was associated with 43% lower risk of overweight/obesity and 23% lower risk of abdominal obesity in the fully adjusted model, while stir-fried seafood did not demonstrate a statistical significance., Conclusion: Higher intake of seafood in childhood/adolescents, particularly in a boiled way, was associated with lower obesity risk., (© 2024. The Author(s).)

Consumption of fried foods is highly prevalent in the Western dietary pattern. Western diet has been unfavorably linked with high risk of developing cardiovascular diseases. Heart failure (HF) as a cardiovascular disease subtype is a growing global pandemic with high morbidity and mortality. However, the causal relationship between long-term fried food consumption and incident HF remains unclear. Our population-based study revealed that frequent fried food consumption is strongly associated with 15% higher risk of HF. The causal relationship may be ascribed to the dietary acrylamide exposure in fried foods. Further cross-sectional study evidenced that acrylamide exposure is associated with an increased risk of HF. Furthermore, we discover and demonstrate that chronic acrylamide exposure may induce HF in zebrafish and mice. Mechanistically, we reveal that acrylamide induces energy metabolism disturbance in heart due to the mitochondria dysfunction and metabolic remodeling. Moreover, acrylamide exposure induces myocardial apoptosis via inhibiting NOTCH1-phosphatidylinositol 3-kinase/AKT signaling. In addition, acrylamide exposure could affect heart development during early life stage, and the adverse effect of acrylamide exposure is a threat for next generation via epigenetic change evoked by DNA methyltransferase 1 (DNMT1). In this study, we reveal the adverse effects and underlying mechanism of fried foods and acrylamide as a typical food processing contaminant on HF from population-based observations to experimental validation. Collectively, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered HF and highlight the significance of reducing fried food consumption for lower the risk of HF., (Copyright © 2024 Anli Wang et al.)

Acrylamide exposure has become an emerging environmental and food safety issue, and its toxicity poses a potential threat to public health worldwide. However, limited studies have paid attention to the detrimental effects of parental exposure to acrylamide on the neurodevelopment in zebrafish offspring. In this study, the embryos were life-cycle exposed to acrylamide (0.125 and 0.25 mM) for 180 days. Subsequently, these zebrafish (F0) were allowed to mate, and their offspring (F1) were collected to culture in clean water from embryos to adults. We employed developmental and morphological observations, behavioral profiles, metabolomics analyses, and transcriptional level examinations to investigate the transgenerational neurotoxicity with parental exposure to acrylamide. Our results showed that parental exposure to acrylamide harms the birth, development, and behavior characterization of the F1 zebrafish larvae, including poor egg quality, increased mortality rates, abnormal heart rates, slowed swimming activity, and heightened anxiety behavior, and continuously disturbs mental health in F1 adult zebrafish. The transcriptional analysis showed that parental chronic exposure to acrylamide deteriorates the neurodevelopment in F1 larvae. In addition, metabolomics analyses revealed that sphingolipid metabolism disruption may be associated with the observed abnormal development and behavioral response in unexposed F1 offspring. Overall, the present study provides pioneer evidence that acrylamide induces transgenerational neurotoxicity via targeting and disrupting sphingolipid metabolism, which reveals intergenerational transmission of acrylamide exposure and unravels its spatiotemporal toxicological effect on neurodevelopment., 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.)

Cooking process for food significantly impacts household air and increases exposure to endocrine disruptors such as acrylamide, consequently affecting human health. In the past 30 years, the transformation of cooking methods to high-temperature thermal processing has occurred widely in China. Yet the transition of cooking methods on the onset of type 2 diabetes (T2D) remains unclear, which may hinder health-based Sustainable Development Goals. We aimed to estimate the associations between dietary intake with different cooking methods and T2D risk. We included 14,745 participants (>20 y) from the China Health and Nutrition Survey (1991-2015). Food consumption was calculated using three consecutive 24-h dietary recalls combined with both individual participant level and household food inventory. Cooking methods, including boiling, steaming, baking, griddling, stir-frying, deep-frying, and raw eating, were also recorded. The consumption of baked/griddled and deep-fried foods was positively associated with 39% and 35% higher of T2D risk by comparing the highest with the lowest category of food consumption, respectively. The use of unhealthy cooking methods for processing foods including baked/griddled and deep-fried foods was attributable for 15 million T2D cases of the total T2D burden in 2011, resulting in a medical cost of $2.7 billion and was expected to be attributable for 39 million T2D cases in 2030, producing a medical cost of $223.8 billion. Replacing one serving of deep-fried foods and baked/griddle foods with boiled/steamed foods was related to 50% and 20% lower risk of T2D, respectively. Our findings recommend healthy driven cooking methods for daily diet for nourishing sustainable T2D prevention in China., 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.)

Background: Limited research has explored the association between dietary soy products and colorectal polyps and adenomas, with insufficient attention given to cooking methods and subtypes of polyps. This study aimed to comprehensively assess the relationship between soy intake, its cooking methods, and the risk of colorectal polyps and adenomas within a high-incidence population of colorectal cancer (CRC) in China., Methods: Data were derived from 14,903 participants aged 40-80 years, enrolled in the extended Lanxi Pre-colorectal Cancer Cohort (LP3C) between March 2018 and December 2022. This cross-sectional study is based on the participants' baseline information. Long-term dietary information was collected through a validated food frequency questionnaire (FFQ), and colorectal polyps and adenomas were identified through electronic colonoscopy. Employing multivariate logistic regression, results were expressed as odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs)., Results: 4,942 cases of colorectal polyps and 2,678 cases of adenomas were ascertained. A significant positive association was found between total soy intake and the occurrence of polyps/adenomas. Considering cooking methods, a notable increase in polyp risk was associated with the consumption of fried soys while no association was detected for boiled or marinated soys. Furthermore, total soy intake demonstrated associations with large and multiple polyps, polyps Yamade-typed less than II, and polyps across all anatomical subsites., Conclusion: Within the high-risk CRC population in China, increased soy product intake was linked to a higher risk of polyps, primarily attributed to the consumption of fried soys. This suggests that modifying cooking methods to avoid fried soys may serve as a preventive strategy for colorectal polyps., 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 Zheng, Lin, Zhu, Ye, Hu, Liu, Hu, Zheng, Hu, Zhuang, Jiao and Zhang.)

Objectives: Severe macrovesicular steatosis in donor livers is associated with primary graft dysfunction. The Banff Working Group on Liver Allograft Pathology has proposed recommendations for steatosis assessment of donor liver biopsy specimens with a consensus for defining "large droplet fat" (LDF) and a 3-step algorithmic approach., Methods: We retrieved slides and initial pathology reports from potential liver donor biopsy specimens from 2010 to 2021. Following the Banff approach, we reevaluated LDF steatosis and employed a computer-assisted manual quantification protocol and artificial intelligence (AI) model for analysis., Results: In a total of 113 slides from 88 donors, no to mild (<33%) macrovesicular steatosis was reported in 88.5% (100/113) of slides; 8.8% (10/113) was reported as at least moderate steatosis (≥33%) initially. Subsequent pathology evaluation, following the Banff recommendation, revealed that all slides had LDF below 33%, a finding confirmed through computer-assisted manual quantification and an AI model. Correlation coefficients between pathologist and computer-assisted manual quantification, between computer-assisted manual quantification and the AI model, and between the AI model and pathologist were 0.94, 0.88, and 0.81, respectively (P < .0001 for all)., Conclusions: The 3-step approach proposed by the Banff Working Group on Liver Allograft Pathology may be followed when evaluating steatosis in donor livers. The AI model can provide a rapid and objective assessment of liver steatosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. 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.)

Furan represents one of the dietary-sourced persistent organic pollutants and thermal processing contaminants. Given its widespread occurrence in food and various toxicological effects, accurately assessing furan exposure is essential for informing public health risks. Furan is metabolized to a reactive primary product, cis-2-butene-1,4-dial (BDA) upon absorption. Some of the resulting BDA-derived metabolites have been proposed as potential exposure biomarkers of furan. However, the lack of quantification for recognized and feasible furan biomarkers has hampered the development of internal exposure risk assessment of furan. In this study, we employed reliable non-targeted metabolomics techniques to uncover urinary furan metabolites and elucidate their chemical structures. We characterized 8 reported and 11 new furan metabolites derived from the binding of BDA with glutathione (GSH), biogenic amines, and/or amino acids in the urine of male rats subjected to varying doses of furan. Notably, a mono-GSH-BDA adduct named cyclic GSH-BDA emerged as a highly prospective specific biomarker of furan exposure, as determined by an ultrahigh-performance liquid chromatography-tandem mass spectrometry method. Cyclic GSH-BDA demonstrated a robust mass spectrometry ion response intensity and exhibited evident time- and dose response. Additionally, we conducted a comprehensive profiling of the kinetics of potential furan biomarkers over time to capture the metabolic dynamics of furan in vivo. Most urinary furan metabolites reached peak concentrations at either the first (3 h) or second (6 h) sampling time point and were largely eliminated within 36 h following furan treatment. The present study provides novel insights into furan metabolism and sheds light on the biomonitoring of furan 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.)

Background and aims : Genetic and dietary factors contribute to adiposity risk, but little evidence supports genetic personalization of fried food intake recommendations for the management of obesity. This study aimed to assess the associations between fried food consumption and adiposity incidence and whether the associations were modified by an individual's genotype. Methods : We included 27 427 participants who had dietary data assessed by a validated 24 h dietary recall and available anthropometric information from the UK Biobank study. The genetic risk score (GRS) was calculated using 940 BMI associated variants. Results : With an average of 8.1 years of follow-up, 1472 and 2893 participants were defined as having overall obesity and abdominal obesity, respectively. Individuals in the highest categories of fried food consumption were positively associated with the risk of obesity (HR = 1.31; 95% CI 1.10-1.56) and abdominal obesity (HR = 1.27; 95% CI 1.12-1.45) compared with the lowest categories. Moreover, fried food consumption had a significant interatction with obesity GRS for abdominal obesity risk ( P interaction = 0.016). Fried food intake was associated with a higher abdominal obesity risk (HR = 1.59, 95% CI: 1.25-2.00) among participants with a lower genetic risk. Conclusions : Our findings indicated that fried food consumption had a higher abdominal obesity risk among individuals with a lower genetic risk, suggesting the restriction of fried food intake for this group of people.

Background: Although n-3 Polyunsaturated fatty acids (PUFAs) may benefit cognitive performance, the association of n-3 PUFA intake with dementia risk under dysglycemia has not been examined. We aimed to evaluate the relationship between fish oil supplement use or fish consumption and dementia risk among older patients with diabetes., Method: A total of 16,061 diabetic patients aged over 60 years were followed up in the UK Biobank. Fish oil supplements use (yes or no) was collected by the touch screen questionnaire. The diagnosis of dementia was ascertained by the UK Biobank Outcome Adjudication Group. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models., Results: A total of 337 cases of dementia were confirmed after a mean duration of 7.7 years (123,486 person-years) of follow-up. Habitual use of fish oil supplements showed a 24% lower dementia risk among older diabetic patients [HRs (95% CIs): 0.76 (0.60-0.98) (P = 0.031)] compared with non-users. Such inverse association was not modified by the APOE ε4 genotype. However, the consumption of both oily fish (≥2 times/week) and non-oily fish (≥2 times/week) had no significant association with dementia risk (p-trend = 0.271 and p-trend = 0.065) compared with non-consumers., Conclusion: In summary, fish oil supplementation may play a protective role in cognitive function across all APOE genotypes, while non-oily fish and oily fish consumption have no protective association among older diabetic patients., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Liver transplantation is an effective treatment for end-stage liver disease, acute liver failure, and primary hepatic malignancy. However, the limited availability of donor organs remains a challenge. Severe large-droplet fat (LDF) macrovesicular steatosis, characterized by cytoplasmic replacement with large fat vacuoles, can lead to liver transplant complications. Artificial intelligence models, such as segmentation and detection models, are being developed to detect LDF hepatocytes. The Segment-Anything Model, utilizing the DEtection TRansformer architecture, has the ability to segment objects without prior knowledge of size or shape. We investigated the Segment-Anything Model's potential to detect LDF hepatocytes in liver biopsies. Pathologist-annotated specimens were used to evaluate model performance. The model showed high sensitivity but compromised specificity due to similarities with other structures. Filtering algorithms were developed to improve specificity. Integration of the Segment-Anything Model with rule-based algorithms accurately detected LDF hepatocytes. Improved diagnosis and treatment of liver diseases can be achieved through advancements in artificial intelligence algorithms for liver histology analysis., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Metabolic syndrome (MetS), a cluster of metabolic abnormalities composed of central obesity, elevated blood pressure, glucose disturbances, hypercholesterolemia and dyslipidaemia, has increasingly become a public health problem in the 21st century worldwide. The dysfunction of telomeres, the repetitive DNA with highly conserved sequences (5'-TTAGGG-3'), is remarkably correlated with organismal aging, even suggesting a causal relationship with metabolic disorders. The health benefits of n-3 polyunsaturated fatty acids (PUFAs) in multiple disorders are associated with telomere length in evidence, which have recently drawn wide attention. However, functional targets and pathways for the associations of n-3 PUFAs and telomere with MetS remain scare. Few studies have summarized the role of n-3 PUFAs in DNA damage repair pathways, anti-inflammatory pathways, and redox balance, linking with telomere biology, and other potential telomere-related signaling pathways. This review aims to (i) elucidate how n-3 PUFAs ameliorate telomere attrition in the context of anti-oxidation and anti-inflammation; (ii) unravel the role of n-3 PUFAs in modulating telomere-related neuron dysfunction and regulating the neuro-endocrine-immunological network in MetS; (iii) epidemiologically implicate the associations of metabolic disorders and n-3 PUFAs with telomere length; and (iv) suggest promising biochemical approaches and advancing methodologies to overcome the inter-variation problem helpful for future research.

Background & Aims: Clinical trials for reducing fibrosis in steatotic liver disease (SLD) have targeted macrophages with variable results. We evaluated intrahepatic macrophages in patients with SLD to determine if activity scores or fibrosis stages influenced phenotypes and expression of druggable targets, such as CCR2 and galectin-3., Methods: Liver biopsies from controls or patients with minimal or advanced fibrosis were subject to gene expression analysis using nCounter to determine differences in macrophage-related genes (n = 30). To investigate variability among individual patients, we compared additional biopsies by staining them with multiplex antibody panels (CD68/CD14/CD16/CD163/Mac387 or CD163/CCR2/galectin-3/Mac387) followed by spectral imaging and spatial analysis. Algorithms that utilize deep learning/artificial intelligence were applied to create cell cluster plots, phenotype profile maps, and to determine levels of protein expression (n = 34)., Results: Several genes known to be pro-fibrotic ( e.g. CD206, TREM2, CD163, and ARG1) showed either no significant differences or significantly decreased with advanced fibrosis. Although marked variability in gene expression was observed in individual patients with cirrhosis, several druggable targets and their ligands ( e.g. CCR2, CCR5, CCL2, CCL5, and LGALS3) were significantly increased when compared to patients with minimal fibrosis. Antibody panels identified populations that were significantly increased ( e.g. Mac387+), decreased ( e.g. CD14+), or enriched ( e.g. interactions of Mac387) in patients that had progression of disease or advanced fibrosis. Despite heterogeneity in patients with SLD, several macrophage phenotypes and druggable targets showed a positive correlation with increasing NAFLD activity scores and fibrosis stages., Conclusions: Patients with SLD have markedly varied macrophage- and druggable target-related gene and protein expression in their livers. Several patients had relatively high expression, while others were like controls. Overall, patients with more advanced disease had significantly higher expression of CCR2 and galectin-3 at both the gene and protein levels., Impact and Implications: Appreciating individual differences within the hepatic microenvironment of patients with SLD may be paramount to developing effective treatments. These results may explain why such a small percentage of patients have responded to macrophage-targeting therapies and provide additional support for precision medicine-guided treatment of chronic liver diseases., Competing Interests: HSL and OAS have a filed patent titled “Systems and methods for spectral imaging characterization of macrophages for use in personalization of targeted therapies to prevent fibrosis development in patients with chronic liver disease." (Board or Regents, The University of Texas System, United States, Galveston, Texas; Pub. No: US 20210293814.) AR serves as a member of Voxel Analytics LLC and consults for Tempus Labs Inc, and Tata Consultancy Services Ltd. The remaining authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Postinfantile giant cell hepatitis (PIGCH) is a rare hepatitis pattern in adults with variable etiologies and clinical outcomes. We conducted a multi-institutional retrospective study to define the clinicopathologic characteristics of patients with PIGCH. A total of 70 PIGCH cases were identified and reviewed for pathological features, including fibrosis, cholestasis, inflammation, steatosis, necrosis, and apoptosis, as well as the distribution of giant cells and the maximum number of giant cells per high-power field. Demographic and clinical data, including age, sex, laboratory results, etiologies, and follow-up results, were recorded. Among the 70 cases, 40% (28/70) were associated with autoimmune liver diseases, followed by 9 (13%) with unknown etiology, 8 (11%) with viral infection, 5 (7%) with medications, 5 with combined etiologies, and 4 (6%) with malignancies (mostly chronic lymphocytic leukemia). Notably, another 16% were de novo PIGCH in liver allografts, most of which occurred after a rejection event. During follow-up, 26 (37%) patients died of the disease and 44 (63%) were alive. Deceased patients were characterized by older age (mean age, 54.9 vs 45.5 years; P = .02), higher alkaline phosphatase level (mean value, 253.3U/L vs 166.3 U/L; P = .03), higher fibrosis stage (stage 3-4 vs stage 0-2, 57.7% vs 29.6%; P = .03), being more likely to have de novo PIGCH after transplantation (23.1% vs 11.4%; P = .04), and being less likely to have primary autoimmune liver disease etiology (26.9% vs 47.7%; P = .04). These results indicate that PIGCH is a rare pattern of liver injury associated with different etiologies and variable clinical outcomes. Autoimmune liver disease with PIGCH is associated with better survival, whereas de novo PIGCH in allografts is associated with poorer survival. Older age, higher alkaline phosphatase level, and advanced fibrosis are adverse prognostic factors., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The role of fatty acids (FAs) in primary prevention of coronary artery disease (CAD) is highly debated, and the modification effect by genetic risk profiles remains unclear. Here, we report the prospective associations of circulating FAs and genetic predisposition with CAD development in 101,367 U.K. Biobank participants. A total of 3719 CAD cases occurred during a mean follow-up of 11.5 years. Plasma monounsaturated FAs (MUFAs) were positively associated with risk of CAD, whereas the risk was significantly lower with higher n-3 polyunsaturated FAs (PUFAs) and more reductions in risk were detected among TT carriers of rs174547. Furthermore, increased plasma saturated FAs (SFAs) and linoleic acid were related to a significant increase in CAD risk among participants with high genetic risk (genetic risk score > 90%). These findings suggest that individuals with high genetic risk need to reduce plasma SFAs levels for CAD prevention. Supplementation of n-3 PUFAs for CAD prevention may consider individuals' genetic makeup.

Purpose : Evidence is limited regarding the associations of different dietary patterns with cardiovascular disease (CVD) risk among the population with diabetes. Thus, we aimed to explore the associations between three dietary patterns and CVD incidence among the population with diabetes. Materials and methods : We prospectively followed 22 473 diabetic patients from the UK Biobank at the baseline. The healthy dietary pattern was derived from a food frequency questionnaire; meanwhile, the Alternate Mediterranean Diet (AMED) and the Dietary Approaches to Stop Hypertension (DASH) diet were assessed based on the Oxford WebQ online 24 h dietary questionnaire. Results : During an average of 10.8 years of follow-up, 5209 incident CVD cases, including 3552 coronary heart disease (CHD) events and 881 strokes, were documented. After multivariate adjustment, a higher healthy diet score was negatively associated with CVD, CHD, and stroke incidence. The hazard ratios and 95% confidence intervals across increasing quintiles of healthy diet score were 0.86 (0.79-0.95), 0.83 (0.75-0.93), and 0.71 (0.57-0.88) for CVD, CHD, and stroke, respectively. A similar protective association with CVD incidence was found for the AMED but not the DASH diet. Conclusions : Adherence to healthy dietary patterns is related to a lower risk of developing CVD among diabetic patients. Our findings further provide vigorous evidence for formulating dietary adherence guidelines for diabetic patients to reduce the burden of CVD complications.

Whether the consumption of different processed potatoes is detrimental to type 2 diabetes (T2D) is highly debated. This study aimed to assess the relations between potato consumption and the risk of T2D and whether the relationship was modified by the genetic predisposition to T2D. We included 174,665 participants from the UK Biobank at baseline. Potato consumption was evaluated using the 24-hour dietary questionnaire. The genetic risk score (GRS) was calculated based on 424 variants associated with T2D. After adjustment for demographic, lifestyle, and dietary factors, the consumption of total potatoes was significantly and positively associated with T2D risk [hazard ratio (HR) comparing two or more servings/day with non-consumers was 1.28 (95% CI: 1.13-1.45)]. HRs (95% CIs) of T2D for each 1-SD increment in boiled/baked potatoes, mashed potatoes, and fried potatoes were 1.02 (0.99-1.05), 1.05 (1.02-1.08), and 1.05 (1.02-1.09), respectively. There were no significant interactions between the consumption of total or different processed potatoes and overall GRS on T2D risk. Theoretically, replacing one serving/day of total potatoes with the same amount of non-starchy vegetables was related to a 12% (95% CI: 0.84-0.91) lower T2D risk. These results showed the positive associations of the consumption of total potatoes, mashed potatoes or fried potatoes and genetic risk with higher incident T2D. An unhealthy potato-based diet is associated with higher diabetes risk regardless of genetic risk., 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.)

Objectives: (1) To compare palliative care needs of patients admitted primarily with stroke and (2) to determine how the care needs of these patients affect their use of different types of specialist palliative care services., Methods: Observational study based on point-of-care data from the Australian Palliative Care Outcomes Collaboration. Multivariate logistic regression models were used to explore the association between patients' palliative care needs and use of community versus inpatient specialist palliative care services., Results: The majority of patients who had a stroke in this study population had mild or no symptom distress, but experienced a high degree of functional impairment and needed substantial help with basic tasks of daily living. A lower Australia-modified Karnofsky Performance Status score (OR=1.82, 95% CI 1.06 to 3.13) and occurrence of an 'unstable' palliative care phase (OR=28.34, 95% CI 9.03 to 88.94) were associated with use of inpatient versus community palliative care, but otherwise, no clear association was observed between the majority of symptoms and use of different care services., Conclusions: Many people with stroke could potentially have been cared for and could have experienced the terminal phases of their condition in a community setting if more community support services were available for their families., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

Background: This study investigates the utility of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in the categorization of pericardial fluid and assesses the diagnostic performance and risk of malignancy (ROM) for each of the diagnostic categories., Methods: All pericardial fluid cases at the Yale School of Medicine between January 1, 2017, and December 31, 2020, were reviewed. The diagnoses were reclassified into five categories according to the ISRSFC: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). ROM and performance parameters of each category were calculated., Results: After reclassification, the distribution of 465 pericardial fluid cases in each category was as follows: ND, 19 (4.1%); NFM, 332 (71.4%); AUS, 21 (4.5%); SFM, 11 (2.4%); and MAL, 82 (17.6%). Confirmatory follow-ups were available for 16 ND (66.7%), 299 NFM (90%), 15 AUS (71%), 5 SFM (45.5%), and 30 MAL cases (36.6%). The ROM was 0% for ND, 1.3% for NFM (4 of 332), 20% for AUS (3 of 15), and 100% for both SFM (5 of 5) and MAL (27 of 27). The diagnostic performance was as follows: sensitivity, 87% (27 of 31); specificity, 100% (292 of 292); positive predictive value (PPV), 100% (27 of 27); negative predictive value (NPV), 98.6% (292 of 296); and diagnostic accuracy, 98.8% (319 of 323)., Conclusions: The ISRSFC is a highly useful system for the reporting of pericardial fluid and risk assessment, given that it offers high sensitivity, specificity, PPV, NPV, and diagnostic accuracy. The application of this system may help to better categorize pericardial fluid and facilitate the standardization of cytopathology reporting., (© 2023 American Cancer Society.)

The spatial cellular alignment and multi-layer structure are vitally important for the physiological functions of natural blood vessels. However, the two features are difficult to be constructed in one scaffold simultaneously, especially in the small-diameter vascular scaffold. Here we report a general strategy to construct a gelatin-based biomimetic three-layer vascular scaffold with spatial alignment features mimicking the natural structure of blood vessels. By using a sequential electrospinning strategy combined with folding and rolling manipulation, a three-layer vascular scaffold with inner and middle layers spatially perpendicular to each other was obtained. The special features of this scaffold could fully mimic the natural multi-layer structures of blood vessels and also possess great potential for spatial arrangement guidance of corresponding cells in blood vessels., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Long Li reports financial support was provided by the National Natural Science Foundation of China., (Copyright © 2023. Published by Elsevier B.V.)

Background: Hepatocellular adenoma (HCA) in the pediatric population is very rare and there are only limited studies, especially with molecular characterization of the tumors. Main HCA subtypes recognized in the current WHO classification include HNF1A -inactivated HCA (H-HCA), inflammatory HCA (IHCA), β-catenin-activated HCA (b-HCA), and β-catenin-activated IHCA (b-IHCA) and sonic hedgehog HCA (shHCA) is reported as an emerging subtype., Methods: Clinical history, pathological information, and molecular studies for a series of 2 cases of pediatric HCA were reviewed., Results: Case 1 was a b-HCA characterized by somatic CTNNB1 S45 mutation in a 11-year-old male with Abernethy malformation. Case 2 was a H-HCA characterized by germline HNF1A variant (c.526+1G>A) in a 15-year-old male associated with maturity-onset diabetes of the young type 3 (MODY3)., Conclusion: Our findings highlight the rarity of these 2 cases associated with adenomatosis, and the contribution of molecular/genetic analysis for proper sub-typing, prognosis and family surveillance., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The treatment of osteochondral defects remains challenging due to the limited healing capacity of cartilage and the poor results of traditional methods. Inspired by the structure of natural articular cartilage, we have fabricated a biphasic osteochondral hydrogel scaffold using a Schiff base reaction and a free radical polymerization reaction. Carboxymethyl chitosan (CMCS), oxidized sodium alginate (OSA), and polyacrylamide (PAM) formed a hydrogel (COP) as the cartilage layer, while hydroxyapatite (HAp) was incorporated into the COP hydrogel to obtain a hydrogel (COPH) as an subchondral bone layer. At the same time, hydroxyapatite (HAp) was incorporated into the COP hydrogel to obtain a hydrogel (COPH) as an osteochondral sublayer, combining the two to obtain an integrated scaffold for osteochondral tissue engineering. Interlayer interpenetration through the continuity of the hydrogel substrate and good self-healing properties due to the dynamic imine bonding of the hydrogel resulted in enhanced interlayer bond strength. In addition, in vitro experiments have shown that the hydrogel exhibits good biocompatibility. It shows great potential for osteochondral tissue engineering applications.

Background: The role of specific unsaturated fatty acids (FAs) in the development of overweight/obesity remains unclear in the general population. Here, we aimed to explore the associations of different types of unsaturated FAs with overweight/obesity risk among the Chinese population., Methods: Eight thousand seven hundred forty-two subjects free of overweight/obesity at entry in the China Health and Nutrition Survey (CHNS) were followed up until 2015. Dietary unsaturated FAs were assessed by 3-day 24-h recalls with a weighing method in each wave. Cox regression models were used to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs) for overweight/obesity risk associated with unsaturated FAs., Results: During a median follow-up of 7 years, 2,753 subjects (1,350 males and 1,403 females) developed overweight/obesity. Consuming more monounsaturated FAs (MUFAs) was associated with a lower risk of overweight/obesity (highest vs. lowest quartile: HR 0.80, 95% CI 0.67-0.96; P -trend = 0.010). Similar inverse associations were observed for plant-MUFAs (HR Q4vsQ1 0.83, 95% CI: 0.73-0.94; P -trend = 0.003) and animal-MUFAs (HR Q4vsQ1 0.77, 95% CI: 0.64-0.94; P -trend = 0.004), total dietary oleic acid (OA) (HR Q4vsQ1 0.66, 95% CI: 0.55-0.79; P -trend <0.001), plant-OA (HR Q4vsQ1 0.73, 95% CI: 0.64-0.83; P -trend <0.001) and animal-OA (HR Q4vsQ1 0.68, 95% CI: 0.55-0.84; P -trend <0.001). In addition, the intakes of n-3 polyunsaturated FAs (PUFAs) (HR Q4vsQ1 1.24, 95% CI: 1.09-1.42; P -trend = 0.017) and α-linolenic acid (ALA) (HR Q4vsQ1 1.22, 95% CI: 1.07-1.39; P -trend = 0.039) but not marine n-3 PUFAs were positively linked to overweight/obesity risk. Consumption of n-6 PUFAs (HR Q4vsQ1 1.13, 95% CI: 0.99-1.28; P -trend = 0.014) and linoleic acid (LA) (HR Q4vsQ1 1.11, 95% CI: 0.98-1.26; P -trend = 0.020) had marginal and positive relationships with the incidence of overweight/obesity. N-6/n-3 PUFA ratio ranging from 5.7 to 12.6 was related to higher risk of overweight/obesity., Conclusion: Higher dietary intake of MUFAs was associated with lower overweight/obesity risk, which was mainly driven by dietary OA from either plant or animal sources. Intakes of ALA, n-6 PUFAs and LA were related to higher risk of overweight/obesity. These results support consuming more MUFAs for maintaining a healthy body weight among the Chinese population., 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 © 2023 Chen, Ao, Lan, Tong, Liu, Zhang, Ye, Li, Liu, Ye, Zhuang, Zhang, Zheng and Jiao.)

Purpose: Previous evidence indicated anti-ageing potential of docosahexaenoic acid (DHA), but the underlying mechanism remains unclear. We investigated protective effect of DHA on telomere attrition and lipid disturbance in male mice with premature ageing caused by telomerase deficiency., Methods: Wild-type (WT) and fourth-generation telomerase-deficient (G4 Terc -/- , Terc knockout, KO) male mice (C57BL/6, 2 months old) were fed control diet (WT-C and KO-C groups) or DHA-enriched diet containing 0.80% DHA by weight (WT-DHA and KO-DHA groups) for 10 months. The ageing phenotypes and metabolic level [carbon dioxide emission, oxygen consumption, and respiratory exchange ratio (RER)] were assessed at the end of the experiment. Telomere length in various tissues and the hepatic gene and protein expression for regulating lipid synthesis and lipolysis were measured. Data were tested using one- or two-factor ANOVA., Results: In KO male mice, DHA prevented weight loss, corrected high RER, and reduced fat loss. Telomere shortening was reduced by 22.3%, 25.5%, and 13.5% in heart, liver, and testes of the KO-DHA group compared with those in the KO-C group. The KO-DHA group exhibited higher gene transcription involved in glycerol-3-phosphate pathway [glycerol-3-phosphate acyltransferase (Gpat)], lower gene expression of β-oxidation [carnitine palmitoyltransferase 1a (Cpt1a)], and upregulation of proteins in lipid synthesis [mammalian target of rapamycin complex 1 (mTORC1) and sterol responsive element binding protein 1 (SREBP1)] in liver than the KO-C group., Conclusion: Long-term DHA intervention attenuates telomere attrition and promotes lipid synthesis via the tuberous sclerosis complex 2 (TSC2)-mTORC1-SREBP1 pathway in KO male mice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance detecting the progressors among F1/F2 NAFLD patients. We also characterized immune cell changes using multiplex immunofluorescence platforms. Fibrotic areas were strongly enriched in CD3 + T cells compared to CD68 + macrophages. While the number of CD68 + macrophages increased with fibrosis severity, the increase in CD3 + T-cell density was more substantial and progressive from F1 to F4. The strongest correlation with fibrosis progression was observed for CD3 + CD45R0 + memory T cells, while the most significant increase in density between F1/F2 and F3/F4 was for CD3 + CD45RO + FOXP3 + CD8 - and CD3 + CD45RO - FOXP3 + CD8 - regulatory T cells. A specific increase in the density of CD68 + CD11b + Kupffer cells with liver fibrosis progression was also observed.

Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression and underlying mechanisms remain unclear. Our population-based study with 140,728 people revealed that frequent fried food consumption, especially fried potato consumption, is strongly associated with 12% and 7% higher risk of anxiety and depression, respectively. The associations were more pronounced among male and younger consumers. Consistently, long-term exposure to acrylamide, a representative food processing contaminant in fried products, exacerbates scototaxis and thigmotaxis, and further impairs exploration ability and sociality of adult zebrafish, showing anxiety- and depressive-like behaviors. Moreover, treatment with acrylamide significantly down-regulates the gene expression of tjp2a related to the permeability of blood-brain barrier. Multiomics analysis showed that chronic exposure to acrylamide induces cerebral lipid metabolism disturbance and neuroinflammation. PPAR signaling pathway mediates acrylamide-induced lipid metabolism disorder in the brain of zebrafish. Especially, chronic exposure to acrylamide dysregulates sphingolipid and phospholipid metabolism, which plays important roles in the development of anxiety and depression symptoms. In addition, acrylamide promotes lipid peroxidation and oxidation stress, which participate in cerebral neuroinflammation. Acrylamide dramatically increases the markers of lipid peroxidation, including (±)5-HETE, 11(S)-HETE, 5-oxoETE, and up-regulates the expression of proinflammatory lipid mediators such as (±)12-HETE and 14(S)-HDHA, indicating elevated cerebral inflammatory status after chronic exposure to acrylamide. Together, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered anxiety and depression, and highlight the significance of reducing fried food consumption for mental health.

Background & Aims: Gut-produced hydrogen sulfide (H 2 S) has been associated with increased gut permeability and inflammation, which may be related to higher obesity risk. We investigated the association of sulfur microbial diet, a dietary index associated with 43 sulfur-metabolizing bacteria, with the incident obesity and whether the relationship was modified by the genetic predisposition to obesity., Methods: We included 27,429 participants with available body mass index (BMI) data from the UK Biobank. The sulfur microbial diet score was assessed using the 24-h dietary assessment method. Obesity and abdominal obesity were defined according to the World Health Organization criteria. Body fat percentage was assessed using a body composition analyzer. The genetic risk score (GRS) was calculated by 940 BMI-related variants., Results: We documented 1472 and 2893 cases of obesity and abdominal obesity during a mean follow-up of 8.1 years. After multivariable adjustment, the sulfur microbial diet score was positively associated with obesity (HR Q4vsQ1  = 1.63; 95% CI = 1.40-1.89, P-trend = 0.001) and abdominal obesity risk (HR Q4vsQ1  = 1.17; 95% CI = 1.05-1.30, P-trend = 0.002). We also observed that increased sulfur microbial diet score was positively related to several adiposity indicators, including a 5% increase in BMI, WC, and body fat percentage. Moreover, the sulfur microbial diet had no significant interactions with genetic risk on obesity incidence., Conclusions: Our results emphasized the significance of avoiding the sulfur microbial diet for obesity prevention across all levels of genetic risk., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Fresh vegetable consumption has been associated with lower incidence of cardiovascular disease (CVD). However, whether preserved vegetable consumption is linked with CVD and mortality remains unclear. This study aimed to assess the associations of preserved vegetable consumption with all-cause and cause-specific mortality., Methods: A total of 440,415 participants free of major chronic diseases, aged 30-79 years, were enrolled from 10 diverse regions in China between 2004 and 2008 and were followed up for an average of 10 years. Preserved vegetable consumption was assessed using a validated food frequency questionnaire. Cause-specific hazard models with the consideration of competing risk from various deaths were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality., Results: During 4,415,784 person-years of follow-up, we documented 28,625 deaths. After adjustment for major risk factors, preserved vegetable consumption was marginally associated with higher CVD mortality (P = 0.041 for trend and P = 0.025 for non-linearity) but not associated with cancer mortality and total mortality. For specific causes of death, consuming preserved vegetables was associated with higher hemorrhagic stroke mortality. The multivariable-adjusted HRs (95% CIs) of hemorrhagic stroke mortality compared with non-consumers were 1.32 (1.17-1.50) for 1-3 days/week and 1.15 (1.00-1.31) for regular consumers (≥4 days/week) (P = 0.006 for trend and P < 0.001 for non-linearity). In addition, regular preserved vegetable consumption was associated with increased risk of digestive tract cancer mortality [HR (95% CI): 1.13 (1.00-1.28); P = 0.053 for trend] and esophageal cancer mortality [HR (95% CI): 1.45 (1.17-1.81); P = 0.002 for trend]., Conclusions: Frequent consumption of preserved vegetables was associated with higher risk of mortality from hemorrhagic stroke and esophageal cancer in China. Our findings suggest limiting preserved vegetable consumption might be protective for premature death from hemorrhagic stroke and digestive tract cancer., (© 2023. The Author(s).)

Eggs contain high-quality protein, lavish vitamins and other bioactive nutrients but are rich in cholesterol. Our study is designed to assess the association of egg intake with polyp prevalence. A total of 7068 participants at a high risk of CRC from the Lanxi Pre-Colorectal Cancer Cohort Study (LP3C) were recruited. A food frequency questionnaire (FFQ) was utilized to obtain dietary data through a face-to-face interview. Cases of colorectal polyps were identified by electronic colonoscopy. The logistic regression model was exploited to achieve odds ratios (ORs) and 95% confidence intervals (CIs). Overall 2064 cases of colorectal polyps were identified in the 2018-2019 survey of LP3C. A positive association of egg consumption with colorectal polyp prevalence was found after the multivariable adjustment [OR Q4 vs . Q1 (95% CI): 1.23 (1.05-1.44); P trend = 0.01]. However, a positive relationship disappeared after further adjustment for dietary cholesterol ( P trend = 0.37), which explained that the harmful role of eggs could be ascribed to the high content of dietary cholesterol. Besides, a positive trend was found between dietary cholesterol and polyp prevalence [OR (95% CI): 1.21 (0.99-1.47); P trend = 0.04]. Furthermore, replacing 1 egg (50 g d -1 ) with an equal amount of total dairy products was related to 11% lower colorectal polyp prevalence [OR (95% CI): 0.89 (0.80-0.99); P = 0.03]. In summary, higher egg consumption was correlated with a higher polyp prevalence among the Chinese population at a high risk of CRC, which was ascribed to the high content of dietary cholesterol in eggs. Besides, individuals with the highest dietary cholesterol tended to have a higher polyp prevalence. Reducing the consumption of eggs and replacing eggs with total dairy products as alternative protein sources may prevent the occurrence of polyps in China.

Heterocyclic aromatic amines (HAAs) were not only present in cooked foods and cigarette smoke, but also measured in airborne particles and diesel-exhaust particles. Typical HAAs have been reported to induce carcinogenicity and metabolic disturbances, but how these hazardous compounds interfere with metabolic networks by regulating metabolic pathways and fingerprinting signature metabolites as biomarkers remains ambiguous. We developed an advanced strategy that adopted chemical isotope labeling ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry for urinary nontargeted metabolomics analysis to gain new insight into in vivo physiological responses stimulated by exposure to typical HAAs. Rats were orally administered with a single dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (1 and 10 mg/kg bw) and their D 3 -isotopic compounds, respectively, and urine samples were then continuously collected within 36 h. Metabolomics data were acquired and processed by classical multivariate statistical analysis, while urinary metabolites were further identified and characterized according to mass spectrometric fragmentation rules, time- and dose-dependent profiles, and calibration of synthesized standards. We monitored 23 and 37 urinary metabolites as the biotransformation products of PhIP and MeIQx, respectively, and first identified demethylated metabolites of PhIP, tentatively named 2-amino-6-phenylimidazo[4,5-b]pyridine, and dihydroxylation products of classical HAAs as short-term biomarkers of exposure to further unravel the metabolic networks. In addition, our findings revealed that both HAAs significantly disturb histidine metabolism, arginine and proline metabolism, tryptophan metabolism, pyrimidine metabolism, tricarboxylic acid cycle, etc. Furthermore, we found that histamine, methionine, alanine, and 4-guanidinobutanoic acid could be considered potential characteristic biomarkers for the oncogenicity or carcinogenicity of both PhIP and MeIQx and screened their specific key pivotal metabolites. The current metabolomics approach is applicable in mapping updated urinary metabolic fingerprints and identifying potential specific biomarkers for HAAs-induced early tumorigenesis., 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 © 2022 Elsevier Ltd. All rights reserved.)

Studies have demonstrated the influence of the cultural values of individualism and collectivism on individuals' economic behavior (e.g., competition and trade). By using individualistic and collectivistic texts to prime participants' minds in a lab experiment, we investigated the impact of the cultural values of individualism and collectivism on allocation behavior in an ultimatum game (UG) and dictator game (DG). In the dictator game, we found that participants in the collectivism-priming condition reported a slightly higher mean offer than in the individualism-priming condition, and participants had an average higher acceptance rate of the proposers' offer in the collectivism-priming (vs. individualism-priming) condition in the ultimatum game. Our findings suggest that participants exhibit more altruistic allocation behavior and are more tolerant of unfair allocation behavior after being primed by the collectivistic (vs. individualistic) texts. In comparison with participants who did not undergo initiation, we also found that Chinese participants who had been influenced by collectivist values for a long time remained unaffected after the initiation of collectivism, but shifted their allocation behavior (i.e., showed decreased altruistic allocation behavior and reduced tolerance of unfair allocation behavior) when individualism was primed.

3-Monochloropropane-1,2-diol (3-MCPD), glycidol, together with their fatty acid esters are commonly presented in various food and have shown carcinogenicity in various laboratory animals. Public health risk assessment of 3-MPCD and glycidol exposure relies on quantitative tools that represent their in vivo toxicokinetics. In order to better understand the absorption, distribution, metabolism, and excretion profiles of 3-MCPD and glycidol in male rats, a physiologically based pharmacokinetic (PBTK) model was developed. The model's predictive power was evaluated by comparing in silico simulations to in vivo time course data obtained from experimental studies. Results indicate that our PBTK model successfully captured the toxicokinetics of both free chemicals in key organs, and their metabolites in accessible biological fluids. With the validated PBTK model, we then gave an animal-free example on how to extrapolate the toxicological knowledge acquired from a single gavage to a realistic dietary intake scenario. Three biomarkers, free compound in serum, urinary metabolite DHPMA, and glycidol-hemoglobin adduct (diHOPrVal) were selected for in silico simulation following constant dietary intakes, and their internal levels were correlated with proposed external daily exposure via reverse dosimetry approaches. Taken together, our model provides a computational approach for extrapolating animal toxicokinetic experiments to biomonitoring measurement and risk assessment., 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 © 2022 Elsevier Ltd. All rights reserved.)

The health benefits of n-3 polyunsaturated fatty acids (PUFAs) in multiple age-related diseases are associated with telomere length. Telomerase is intimately related to inflammation and oxidative stress, but whether the underlying function of n-3 PUFAs on telomere maintenance is based on telomerase activation or related mechanisms remains unclear. Herein, we utilized late-generation (G4) telomerase-deficient (Terc -/- ) mice to perform a lifelong docosahexaenoic acid (DHA) intervention to determine the potential of DHA in telomere maintenance and health promotion. Unfortunately, DHA failed to prolong mouse longevity in either intrinsic or premature aging. However, intriguingly, lifelong dietary DHA intervention slowed the aging phenotypes and profoundly attenuated telomere attrition in blood leukocytes and multiple tissues, consistent with decreased β-galactosidase activity and other senescence hallmarks with no observed sex differences. Notably, DHA intervention alleviated telomere attrition-induced γ-H2AX accumulation dependent on poly (ADP-ribose) polymerase 1 (PARP1) recruitment, and further regulated mitochondrial dysfunction critically involved in the DNA damage response. Together with the improvement of mitochondria function, the blocked reactive oxygen species (ROS) accumulation and suppression of the nuclear factor-κB (NF-κB)/nucleotide-binding domain-like receptor protein 3 (NLRP3)/caspase-1 pathways partially indicated anti-oxidative and anti-inflammatory effects of DHA. These data revealed a regulatory paradigm involving DHA in the telomere-DNA-mitochondria feedback loop mediated by DNA damage response and inflammation in alleviating senescence, which may hold potential as a translatable intervention in telomere-related diseases during aging., Competing Interests: Declaration of competing interest The authors do not have any conflict of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Perchlorate is a stable and readily transportable thyroid hormone disruptor, and prevalent exposure to perchlorate through food and drinking water has raised public concern about its health effects. The physiologically based toxicokinetic (PBTK) model as a dose prediction method is effective to predict the toxicant exposure dose of an organism and helps quantitatively assess the dose-dependent relationship with toxic effects. The current study aimed to establish a multi-compartment PBTK model based on updated time-course datasets of single oral exposure to perchlorate in rats. With adjustment of the kinetic parameters, the model fitted well the toxicokinetic characteristics of perchlorate in urine, blood, and thyroid from our experiments and the literature, and the coefficient of determination (R 2 ) between the fitting values and the experimental data in regression analysis was greater than 0.91, indicating the robustness of the current model. The results of sensitivity analysis and daily repeated exposure simulations together confirmed its effective renal clearance. According to the distribution characteristic of perchlorate, a correlation study of internal and external exposure was conducted using urinary perchlorate as a bioassay indicator. The developed multi-compartment model for perchlorate updates important toxicokinetic data and kinetic parameters, providing analytical and modeling tools for deriving total exposure levels in the short term., 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 © 2022 Elsevier Ltd. All rights reserved.)

Background: Urinary incontinence is an increasingly common problem, especially among older people in nursing homes. Nursing assistants are the leading workforce in nursing homes, and their knowledge and attitudes regarding urinary incontinence have garnered considerable attention in the context of aging in China. However, most previous studies on this issue have focused on registered nurses. This study aimed to explore nursing assistants' knowledge, attitudes and training needs with regard to urinary incontinence., Methods: We conducted a two-part mixed-methods study. After institutional manager approval, we surveyed the knowledge and attitudes of 509 nursing assistants regarding urinary incontinence. We carried out semi-structured interviews with 40 nursing assistants to elicit detailed information on training needs., Results: In general, knowledge about urinary incontinence was poor (14.00 ± 4.18), although attitudes were primarily positive (35.51 ± 3.19). Most nursing assistants were very willing to learn more about urinary incontinence (93.9%, 478/509), but time constraints and low educational background may be barriers to learning motivation. The three preferred training styles among nursing assistants were face-to-face guidance from a mentor, training combining theory with practice, and online video training., Conclusions: Chinese nursing assistants had poor knowledge but positive attitudes toward urinary incontinence. Facility managers should focus on developing training and learning mechanisms regarding urinary incontinence. It is important to adopt diverse training styles according to the actual situation of nursing homes., (© 2023. The Author(s).)

The ubiquitous occurrence of acrylamide in various thermal processing food products poses a potential health risk for the public. An accurate exposure assessment is crucial to the risk evaluation of acrylamide. Machine learning emerging as a powerful computational tool for prediction was employed to establish the association between internal exposure and dietary exposure to acrylamide among a Chinese cohort of middle-aged and elderly population (n = 1,272). Five machine learning regression models were constructed and compared to predict the daily dietary acrylamide exposure based on urinary biomarkers including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Other important covariates such as age, gender, physical activities, and total energy intake were also considered as predictors in the models. Average dietary intake of acrylamide among Chinese elderly participants was 8.9 μg/day, while average urinary contents of AAMA, AAMA-sul, GAMA, and iso-GAMA were 52.2, 19.1, 4.4, and 1.7 nmol/g Ucr (urine creatinine), respectively. Support vector regression (SVR) model showed the best prediction performance with a R of 0.415, followed by light gradient boosting machine (LightGBM) model (R = 0.396), adjusted multiple linear regression (MLR) model (R = 0.378), neural networks (NN) model (R = 0.365), MLR model (R = 0.363), and extreme gradient boosting (XGBoost) model (R = 0.337). The present study firstly correlated dietary exposure with internal exposure to acrylamide among Chinese elderly population, providing an innovative perspective for the exposure assessment of acrylamide., 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 © 2022 Elsevier Ltd. All rights reserved.)

Background & Aims: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice., Methods: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and transcriptomic changes in fibrotic NAFLD livers.Results: pSTAT3 scores in non-hepatocyte areas progressively increased with fibrosis severity (r = 0.53, p <0.001). Correlation analyses between pSTAT3 scores and expression of 1,540 immune- and cancer-associated genes revealed a large effect of STAT3 activation on gene expression changes in non-hepatocyte areas and confirmed a major role for STAT3 activation in fibrogenesis. Digital spatial transcriptomic profiling was also performed on 13 regions selected in hepatocyte and non-hepatocyte areas from four NAFLD liver biopsies with advanced fibrosis, using a customized panel of markers including pSTAT3, PanCK+CK8/18, and CD45. The regions were further segmented based on positive or negative pSTAT3 staining. Cell deconvolution analysis revealed that activated STAT3 was enriched in hepatic progenitor cells (HPCs) and sinusoidal endothelial cells. Regression of liver fibrosis upon STAT3 inhibition in mice with NASH resulted in a reduction of HPCs, demonstrating a direct role for STAT3 in HPC expansion., Conclusion: Increased understanding of the spatial dependence of STAT3 signaling in NASH and liver fibrosis progression could lead to novel targeted treatment approaches., Impact and Implications: Advanced liver fibrosis is the main determinant of mortality in patients with NASH. This study showed using liver biopsies from 133 patients with NAFLD, that STAT3 activation in non-hepatocyte areas is strongly associated with fibrosis severity, inflammation, and progression to NASH. STAT3 activation was enriched in hepatic progenitor cells (HPCs) and sinusoidal endothelial cells (SECs), as determined by innovative technologies interrogating the spatial distribution of pSTAT3. Finally, STAT3 inhibition in mice resulted in reduced liver fibrosis and depletion of HPCs, suggesting that STAT3 activation in HPCs contributes to their expansion and fibrogenesis in NAFLD., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

The pathologic characteristics of squamous cell/adenosquamous carcinomas (SC/ASC) have not been well clarified. As a rare subtype of gallbladder cancer (GBC), no biological markers for diagnosis and prognosis are available. This research evaluated the expression of FOXP1 and FOXO3a in 69 SC/ASC, and 146 adenocarcinoma (AC) samples were analyzed via immunohistochemistry. SC/ASCs were associated with higher rates of lymph node metastasis, invasion, and patients older than 45 years comparing to ACs. FOXP1 and FOXO3a positivity rates were significantly lower in SC/ASC and AC samples from patients with large tumor size, a high TNM stage, lymph node metastasis, invasion, and no history of tumor resection (biopsy only). Positive FOXP1 expression levels were significantly decreased in cases of poorly differentiated AC. The univariate Kaplan-Meier analysis revealed that negative FOXP1 and FOXO3a expression, poor differentiation, large tumor size, high TNM stage, lymph node metastasis, invasion, and an inability to undergo curative resection were all closely associated with decreased overall survival in SC/ASC and AC patients. The multivariate cox regression analysis showed that negative FOXP1 and FOXO3a expression levels were independent predictors of poor prognosis in SC/ASC and AC patients. Our results indicate that negative FOXP1 and FOXO3a expression are closely associated with the pathogenesis, clinicopathologic properties, and prognosis of GBC patients. FOXP1 and FOXO3a may thus be biomarkers of GBC carcinogenesis, progression, and prognosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Polyphenolic antioxidants have been suggested to control the generation of acrylamide during thermal reactions. However, their role in protecting against the toxicity of acrylamide and the mechanism of action regarding profile alteration of biomarkers and metabolome remains unclear. A total of 65 adults were randomized into tea polyphenols (TP) and control groups and served with potato chips, which corresponded to an intake level of 12.6 μg/kg·bw of acrylamide, followed by capsules containing 200 mg, 100 mg or 50 mg TP, or equivalent placebo. Moreover, nontargeted urinary metabolomics analysis in acrylamide exposed rats was conducted using ultra-high performance liquid chromatography linked with a quadrupole-orbitrap high-resolution mass spectrometry. Our results showed that supplementation with catechins promoted the excretion of N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine in both humans and rats. We also found that epigallocatechin gallate (EGCG) or epicatechin (EC) intervention attenuated the ratio of hemoglobin adduct of glycidamide to hemoglobin adduct of acrylamide in rat blood. Metabolomics analysis revealed that EGCG/EC intervention regulated the differential expressed metabolites, including l-glutamic acid, 2-oxoglutarate, citric acid, and cysteinylglycine. Kyoto Encyclopedia of Genes and Genomes pathway analysis further showed acrylamide-induced metabolic disorders were improved after EGCG/EC supplementation by glycolipid metabolism (alanine, aspartate and glutamate metabolism, and d-Glutamine and d-glutamate metabolism) and energy metabolism (tricarboxylic acid cycle). Notably, the supplement use of EGCG prevented the cardiometabolic risk after exposure to acrylamide by mediating the phenylalanine and hippuric acid in phenylalanine metabolism. Here we showed the beneficial effect of catechins as major polyphenolic antioxidant ingredients on the toxicity of acrylamide by the changes in biomarkers from metabolic profile analysis based on human and animal studies. These findings shed light into the catechins as natural polyphenolic antioxidants that could be a therapeutic ingredient for preventing acrylamide-induced cardiometabolic toxicity., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acrylamide (AA) occurs in both various environmental and dietary sources and has raised widespread concern as a probable carcinogen. Glycidamide (GA) is the main genotoxic metabolite through P450 2E1 (CYP2E1). In the present study, we investigated the protective effect of (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin (EC) against AA- and GA-induced hepatotoxicity in HepG2 cells. The results demonstrated that EC and EGCG inhibited AA- and GA-induced cytotoxicity and mitochondria-mediated cellular apoptosis. Moreover, exposure to AA (100 μg/mL) and GA (50 μg/mL) caused cell cycle arrest and DNA damage, while EC and EGCG ranging from 12.5 to 50 μg/mL rescued cell cycle arrest and inhibited DNA damage. Furthermore, EC and EGCG down-regulated pro-apoptotic protein Bax and Caspase 3 after a 24-h treatment in HepG2 cells exposed to AA (100 μg/mL) or GA (50 μg/mL). Also, the intervention with EC or EGCG up-regulated the expression of DNA repair related protein PARP and down-regulated the expression of Cleaved-PARP. Besides, EC exerted better protective effect than EGCG against AA- and GA-induced cytotoxicity in HepG2 cells. Altogether, EC and EGCG were effective in protecting AA- and GA-induced hepatotoxicity via rescuing cellular apoptosis and DNA damage, as well as promoting cell cycle progression in HepG2 cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)