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Hepcidin has a crucial role in iron homeostasis upon inflammatory conditions such as inflammatory bowel disease (IBD). Thus, we conducted a systematic review and meta-analysis to determine the overall association between serum hepcidin concentrations and IBD. Based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols, an electronic literature search was conducted on PubMed/MEDLINE, Scopus, and Web of Science until June 2020. Studies were deemed eligible for inclusion if they met the following criteria: (1) diagnosis of IBD, (2) observational design, and (3) measured serum hepcidin and prohepcidin concentrations in IBD patients and control group. Overall, 10 studies including 1184 participants were evaluated. Random-effects meta-analysis revealed that subjects with IBD had 7.22 ng/mL (95% CI: 2.10, 12.34; p  = .006) higher serum hepcidin concentrations compared to control groups. A nonsignificantly lower serum prohepcidin concentration (0.522 ng/mL, 95% CI: -1.983 to 0.939; p  = .484) was found for IBD patients compared to healthy subjects. However, there was significant heterogeneity among the studies regarding both hepcidin ( I 2  = 98%, p  < .001) and prohepcidin levels ( I 2  = 96%, p  < .001), respectively. In an age-based subgroup analysis, patients aged ≥18 years with IBD displayed higher serum hepcidin levels when compared to healthy individuals (22.36 ng/mL, 95% CI, 2.12-42.61; p =  .030). Hepcidin concentrations are elevated in subjects with IBD; however, the clinical relevance of this finding requires further evaluation in future investigations as the increase is relatively small compared to the wide range of normal hepcidin values., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Measures of insulin resistance (IR)/sensitivity (IS) are emerging tools to identify metabolic-associated fatty liver disease (MAFLD). However, the comprehensive assessment of the performance of various indicators is limited. Moreover, the utility of measures of IR/IS in detecting liver fibrosis remains unclear., Aims: To evaluate the predictive ability of seventeen IR/IS and two beta cell function indices to identify MAFLD and liver fibrosis., Methods: A cross-sectional study was conducted on individuals aged 25-75 years. Transient elastography was used to estimate liver stiffness and controlled attenuation parameter. The following measures were computed: homeostatic model assessment (HOMA/HOMA2) for IR, IS, and beta cell function; QUICKI; Bennett index; glucose/insulin; FIRI; McAuley index; Reynaud index; SPISE index; TyG; TyG-BMI; TyG-WC; TyG-WHtR; TG/HDL; and METS-IR. Subgroup analyses were performed according to age, gender, diabetes status, and body weight., Results: A total of 644 individuals were included in our analysis. MAFLD and significant liver fibrosis were detected in 320 (49.7%) and 80 (12.4%) of the participants, respectively. All measures of IR/IS identified MAFLD and liver fibrosis. However, TyG-WC, TyG-BMI, and TyG-WHtR were the top three indicators that identified MAFLD. Measures that include insulin level in their mathematical calculation, namely, Raynaud index, HOMA-IR, HOMA 2-IR, FIRI, and QUICKI had the best performance in identifying liver fibrosis in the entire population, as well as among the study subgroups., Conclusions: TyG-WC, TyG-BMI, and TyG-WHtR were the best predictors of MAFLD. Insulin-based measures had better performances in the detection of advanced fibrosis. This was independent of age, gender, obesity, or diabetes status., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This paper presents a systematic investigation into the effectiveness of Self-Supervised Learning (SSL) methods for Electrocardiogram (ECG) arrhythmia detection. We begin by conducting a novel analysis of the data distributions on three popular ECG-based arrhythmia datasets: PTB-XL, Chapman, and Ribeiro. To the best of our knowledge, our study is the first to quantitatively explore and characterize these distributions in the area. We then perform a comprehensive set of experiments using different augmentations and parameters to evaluate the effectiveness of various SSL methods, namely SimCRL, BYOL, and SwAV, for ECG representation learning, where we observe the best performance achieved by SwAV. Furthermore, our analysis shows that SSL methods achieve highly competitive results to those achieved by supervised state-of-the-art methods. To further assess the performance of these methods on both In-Distribution (ID) and Out-of-Distribution (OOD) ECG data, we conduct cross-dataset training and testing experiments. Our comprehensive experiments show almost identical results when comparing ID and OOD schemes, indicating that SSL techniques can learn highly effective representations that generalize well across different OOD datasets. This finding can have major implications for ECG-based arrhythmia detection. Lastly, to further analyze our results, we perform detailed per-disease studies on the performance of the SSL methods on the three datasets.

Objective: Low skeletal muscle mass index (SMI) is frequently identified in gastric cancer patients but its association with patient survival rate is not clear. This systematic review and meta-analysis aimed to clarify the association between SMI and overall survival in gastric cancer patients after gastrectomy., Methods: PubMed, Scopus, and Web of Science were searched from database inception until July 2021. Studies were eligible if they included gastric cancer patients, measured the SMI level, reported SMI before gastrectomy, defined sarcopenia according to SMI, and had a cohort or case-control design. Primary outcome was cancer survival rate. The risk of bias of individual studies was assessed using the Newcastle - Ottawa Scale., Results: Overall, 22 cohort studies including 7,203 participants were included. The quality of the included studies was moderate to high. A higher overall survival rate was associated with a higher SMI (RR = 1.62, 95% CI: 1.42-1.85). Subgroup analysis suggested a stronger association in overweight or obese patients (RR = 2.39, 95% CI: 1.13-5.09; I 2  = 77%; heterogeneity P < 0.01). But no significant differences in the association based on the surgery type (curative surgery vs radical surgery) or the type of gastrectomy (total gastrectomy vs sub-total gastrectomy) were observed., Conclusions: It is suggested that SMI can be a prognostic indicator for overall survival in gastric cancer patients, especially in overweight and obese patients., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

The aim of this study was to investigate whether dairy intake was associated with the severity of coronavirus disease 2019 (COVID-19) disease and the probability of hospitalization of patients. This cross-sectional study was conducted on 141 patients with COVID-19 with an average age of 46.23 ± 15.88 years. The number of men (52.5%) participating in this study was higher than that of women. The association between dairy intake and COVID-19 was evaluated by multivariable logistic regression analysis. The risk of hospitalization in the highest tertile of dairy intake was 31% lower than in the lowest tertile (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.37-1.25, p trend = 0.023). Higher milk and yogurt intake was associated with a reduced risk of hospitalization due to COVID-19. Patients in the third tertiles were about 65% (p for trend = 0.014) and 12% (p for trend = 0.050) less likely to be hospitalized than those in the first tertile, respectively. Dairy consumption, especially low-fat ones, was associated with a lower risk of hospitalization due to COVID-19 and lower severity of COVID-19., Competing Interests: Conflict of Interest: The authors declare that they have no competing interests., (Copyright © 2023. The Korean Society of Clinical Nutrition.)

Although previous findings have shown the beneficial role of healthy eating pattern on the human immune system, the association between plant-based diet and COVID-19 severity has not yet been elucidated. This study aimed to determine the possible role of plant-based diet index (PDI) in COVID-19 severity. This cross-sectional, multicentral study was conducted on 141 patients with confirmed COVID-19. Dietary intakes of the patients were evaluated using a validated food frequency questionnaire. Then, PDI was compared between patients who needed to be hospitalised (considered severe cases), and those who got treatment at home (considered non-severe cases). After adjustment for confounders including age, sex, energy intake and body mass index, lower odds of hospitalisation were found for participants having a greater score of overall PDI (OR per 10 units increase: 0.42; 95% CI 0.22 to 0.80) and healthy PDI (OR per 10 unit increase: 0.45; 95% CI 0.26 to 0.78). In conclusion, our data presented that there is a relation between PDI and lower risk of hospitalisation in COVID-19 patients, possibly through boosting the immune function., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: Managing dietary glycemic index (GI) deserves further attention in the interplay between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). This study aimed to evaluate the relationship between dietary GI and the odds of NAFLD in patients with T2DM., Methods: A cross-sectional study was carried out between April 2021 and February 2022, including 200 participants with T2DM aged 18-70 years, of which 133 had NAFLD and 67 were in the non-NAFLD group. Cardiometabolic parameters were analyzed using standard biochemical kits and dietary intake was assessed using a validated food frequency questionnaire. Binary logistic regression was applied to explore odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD according to tertiles of dietary GI., Results: Highest vs. lowest tertile (< 57 vs. > 60.89) of energy-adjusted GI was not associated with the odds of having NAFLD (OR 1.25, 95% CI = 0.6-2.57; P-trend = 0.54) in the crude model. However, there was an OR of 3.24 (95% CI = 1.03-10.15) accompanied by a significant trend (P-trend = 0.04) after full control for potential confounders (age, gender, smoking status, duration of diabetes, physical activity, waist circumference, HbA1c, triglycerides, total cholesterol, dietary intake of total carbohydrates, simple carbohydrates, fat, and protein)., Conclusion: High dietary GI is associated with increased odds of NAFLD in subjects with T2DM. However, interventional and longitudinal cohort studies are required to confirm these findings., 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 Salavatizadeh, Soltanieh, Ataei Kachouei, Abdollahi Fallahi, Kord-Varkaneh, Poustchi, Mansour, Khamseh, Alaei-Shahmiri, Santos and Hekmatdoost.)

Background and Aim: Given the importance of dietary habits in the immune system, the current study aimed at investigating the association between Dietary Approach to Stop Hypertension (DASH) diet and risk of hospitalization due to COVID-19., Methods: Dietary data of 141 patients with COVID-19 were collected using 147-item food frequency questionnaire. DASH score in this cross-sectional study was calculated based on eight components, including fruits, vegetables, legumes and nuts and seeds, whole grains, low-fat dairy, red or processed meats, sweetened beverages, and sodium. Multivariable logistic regression models were applied to estimate the OR and 95% CI for hospitalization due to COVID-19 in each tertile of DASH score., Results: Mean ± SD of DASH score in inpatients (n=74) and outpatients (n= 87) was 22.5 ± 4.57 and 25.34 ± 4.23, respectively. The risk of hospitalization in the highest tertile of DASH score was 81% lower than the lowest tertile (OR=0.19, 95%CI: 0.07-0.55, P trend = 0.001 after adjustment for age, sex, BMI, energy intake). Also, more intake of fruits, vegetables and low-fat dairy products and less intake of sodium, red and processed meat were each significantly associated with reduced risk of hospitalization due to COVID-19., Conclusions: Our data provide evidence that adherence to DASH-style diet was associated with lower risk of hospitalization due to COVID-19., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Background & Objective: High prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus results in deleterious complications and morbidities related to both diseases. Thus, we aimed to investigate dietary and anthropometric risk factors for progression of Non-alcoholic Fatty Liver Disease (NAFLD) in diabetic people., Methods: Anthropometric, and dietary intakes, and hepatic steatosis and fibrosis were assessed in two hundred participants with type two diabetes (T2DM). Subjects with CAP score of more than 270 dB/m were considered to have NAFLD. Multivariable-adjusted ORs and 95% CIs were used to investigate the association between NAFLD and dietary inflammatory index (DII) score and anthropometric indices., Results: Participants in the highest tertile of DII had 2.41 (95% CI:1.16-4.97), 2,53 (95% CI: 1.04-6.16), 2.78 (95% CI: 1.09-7.13) times higher odds of developing NAFLD in comparison to the lowest tertile in crude, adjusted model 1 and 2, respectively. Among those with the highest relative to the lowest tertile of trunk-to-leg fat ratio (TLR), ORs and 95% CI were OR = 1.88, 95% CI = 0.9-3.91, and OR = 7.99, 95% CI = 2.43-26.26 in crude and full-adjusted models. Odds of NAFLD in the third tertile of metabolic score for visceral fat (METS-VF) was higher than the first tertile in crude (OR = 9.5, 95% CI = 4.01-22.46) and full-adjusted models (OR = 4.55, 95% CI = 1.46-14.2)., Conclusions: In conclusion, this study highlighted an association between greater DII (pro-inflammatory diet) and higher NAFLD risk. Moreover, TLR and METS-VF are known as novel estimators of central obesity as a risk factor for NAFLD in diabetes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: The clinical application of normothermic ex vivo lung perfusion (EVLP) has increased donor lung utilization for transplantation through functional assessment. To develop it as a platform for donor lung repair, reconditioning and regeneration, the perfusate should be modified to support the lung during extended EVLP., Methods: Human lung epithelial cells and pulmonary microvascular endothelial cells were cultured, and the effects of Steen solution (commonly used EVLP perfusate) on basic cellular function were tested. Steen solution was modified based on screening tests in cell culture, and further tested with an EVLP cell culture model, on apoptosis, GSH, HSP70, and IL-8 expression. Finally, a modified formula was tested on porcine EVLP. Physiological parameters of lung function, histology of lung tissue, and amino acid concentrations in EVLP perfusate were measured., Results: Steen solution reduced cell confluence, induced apoptosis, and inhibited cell migration, compared to regular cell culture media. Adding L-alanyl-L-glutamine to Steen solution improved cell migration and decreased apoptosis. It also reduced cold preservation and warm perfusion-induced apoptosis, enhanced GSH and HSP70 production, and inhibited IL-8 expression on an EVLP cell culture model. L-alanyl-L-glutamine modified Steen solution supported porcine lungs on EVLP with significantly improved lung function, well-preserved histological structure, and significantly higher levels of multiple amino acids in EVLP perfusate., Conclusions: Adding L-alanyl-L-glutamine to perfusate may provide additional energy support, antioxidant, and cytoprotective effects to lung tissue. The pipeline developed herein, with cell culture, cell EVLP, and porcine EVLP models, can be used to further optimize perfusates to improve EVLP outcomes., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: This study was conducted to evaluate possible associations between Dietary Total Antioxidant Capacity (DTAC) and odds of non-alcoholic fatty liver disease (NAFLD) in people with type-2 diabetes mellitus (T2DM)., Materials and Methods: We recruited two hundred people with T2DM, and evaluated their liver steatosis using Fibroscan. Dietary intakes of participants were assessed using a validated food frequency questionnaire. DTAC was computed via ferric reducing antioxidant power (FRAP)., Results: In the crude model, no statistically significant association was found between DTAC and the odds of NAFLD in people with diabetes. However, after adjustment for potential confounders including age, gender, diabetes duration, smoking status, physical activity, BMI, waist circumference, and energy, the most reduced adjusted OR was indicated for the third tertile vs. the first one (OR: 0.28, 95% CI: 0.09-0.81, P = 0.02), meaning that diabetic patients in the third tertile of DTAC had 72% decreased risk of NAFLD in comparison to those in the first one. The relationship was remained significant after additional adjustment for HOMA-IR, HbA1c, serum Triglyceride (TG), and low-density lipoprotein-cholesterol (LDL) levels (OR: 0.29, 95% CI: 0.09-0.93, P = 0.03). Importantly, a dose-response pattern was demonstrated for DTAC and risk of NAFLD ( P = 0.04)., Conclusion: Higher DTAC was related with a decreased risk of NAFLD in individuals with diabetes., 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 © 2022 Salavatizadeh, Soltanieh, Poustchi, Yari, Shabanpur, Mansour, Khamseh, Alaei-Shahmiri and Hekmatdoost.)

Background & Aims: Ulcerative colitis (UC) poses a challenge to patients' health status and lifestyle. Micronutrient intake has been associated with the risk of UC, but the association has been inconsistent. Therefore, we performed a meta-analysis to clarify the overall association between micronutrient intake, as potentially modifiable risk factors, and the risk of UC., Methods: Based on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocols, systematic searches were conducted in PubMed, Scopus, and Web of Science up to September 2021. Studies were considered eligible for inclusion if they met the following criteria: (1) observational studies that compared dietary intake of zinc, calcium, or magnesium between the UC group and the control group and (2) had means and standard deviations or medians and interquartile ranges of outcome variables., Results: A total of 7 studies with 1197 participants were included in the meta-analysis. The random-effects meta-analysis showed that there was no significant association between the intake of calcium (WMD: -66.25 mg/day, 95% CI: -276.7 to 144.21, P = 0.54), magnesium (WMD: -21.47 mg/day, 95% CI: -95.54 to 52.6, P = 0.57), and zinc (WMD: 0.3 mg/day, 95% CI: -1.5 to 2, P = 0.74) and the risk of UC. However, there was high significant heterogeneity between studies in dietary intake of calcium (I 2  = 95.1%, P < 0.001), magnesium (I 2  = 96%, P < 0.001), and zinc (I 2  = 95.8%, P = <0.001). In a location-based subgroup analysis, calcium intake in non-Asian countries was significantly lower in patients with UC compared to healthy controls. In addition, magnesium intake was negatively associated with the risk of UC in studies with a sample size of less than 190 subjects. However, for the association between zinc intake and UC risk, subgroup analysis failed to find a source of heterogeneity., Conclusion: No significant association was found between dietary calcium, magnesium, and zinc intake and risk of UC., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The objective of this study is to accomplish a systematic review and meta-analysis of all randomized controlled trials that dissected the influence of tocotrienol supplementation on various anthropometric and cardiometabolic indices in all individuals, irrespective of health condition. This research was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. 17 eligible articles were included in the final quantitative analysis. Current study revealed that tocotrienol consumption was not associated with CRP, WC, MDA, BMI, IL-6, HbA1C, ALT, AST, creatinine TNF-α, FPG, BW, DBP, and SBP. We did observe an overall increase in BW (SMD: 0.063 kg, 95% CI: -0.200, 0.327, p  = 0.637) and DBP (SMD: 0.249 mmHg, 95% CI: 0.053, 0.446, p  = 0.013). In addition, a significant reduction in SBP was observed (SMD: -0.616 mmHg, 95% CI: -1.123, -0.110, p  = 0.017). In summary, our meta-analysis revealed that tocotrienol consumption was associated with increase in BW and DBP and decrease in SBP. Significant associations were not observed for other outcomes.

Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.

Background and Aims: Sleep, as well as diet and physical activity, plays a significant role in growth, maturation, health, and regulation of energy homeostasis. Recently, there is increasing evidence indicating a possible causal association between sleep duration and energy balance. We aimed to examine the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics, and appetite-regulating hormones by randomized controlled trials (RCTs)., Methods: Electronic literature searches were conducted on Medline, Web of Science, and Google Scholar until July 2020. The search was conducted with the following words: "Sleep Duration", "Circadian Rhythm", "Sleep Disorders" in combination with "Obesity", "Overweight", "Abdominal Obesity", "Physical Activity", "Energy Intake", "Body Mass Index", "Lipid Metabolism", "Caloric Restriction", Leptin, "Weight Gain", and "Appetite Regulation" using human studies.methods RESULTS: After screening 708 abstracts, 50 RCTs (7 on children or adolescents and 43 on adults) were identified and met the inclusion criteria. In general, the findings suggested that sleep restriction may leads to a significant increment in energy intake, fat intake, body weight, appetite, hunger, eating occasions, and portion size, while protein and carbohydrate consumption, total energy expenditure, and respiratory quotient remained unaffected as a result of sleep restriction. Serum leptin, ghrelin, and cortisol concentrations were not influenced by sleep duration as well., Conclusion: Insufficient sleep can be considered as a contributing factor for energy imbalance, weight gain, and metabolic disorders and it is suggested that to tackle disordered eating it may be necessary to pay more attention to sleep duration., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Fasting and energy-restricted diets have been evaluated in several studies as a means of improving cardiometabolic biomarkers related to body fat loss. However, further investigation is required to understand potential alterations of leptin and adiponectin concentrations. Thus, we performed a systematic review and meta-analysis to derive a more precise estimate of the influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans, as well as to detect potential sources of heterogeneity in the available literature., Methods: A comprehensive systematic search was performed in Web of Science, PubMed/MEDLINE, Cochrane, SCOPUS and Embase from inception until June 2019. All clinical trials investigating the effects of fasting and energy-restricted diets on leptin and adiponectin in adults were included., Results: Twelve studies containing 17 arms and a total of 495 individuals (intervention = 249, control = 246) reported changes in serum leptin concentrations, and 10 studies containing 12 arms with a total of 438 individuals (intervention = 222, control = 216) reported changes in serum adiponectin concentrations. The combined effect sizes suggested a significant effect of fasting and energy-restricted diets on leptin concentrations (WMD: -3.690 ng/ml, 95% CI: -5.190, -2.190, p ≤ 0.001; I 2  = 84.9%). However, no significant effect of fasting and energy-restricted diets on adiponectin concentrations was found (WMD: -159.520 ng/ml, 95% CI: -689.491, 370.451, p = 0.555; I 2  = 74.2%). Stratified analyses showed that energy-restricted regimens significantly increased adiponectin (WMD: 554.129 ng/ml, 95% CI: 150.295, 957.964; I 2  = 0.0%). In addition, subsequent subgroup analyses revealed that energy restriction, to ≤50% normal required daily energy intake, resulted in significantly reduced concentrations of leptin (WMD: -4.199 ng/ml, 95% CI: -7.279, -1.118; I 2  = 83.9%) and significantly increased concentrations of adiponectin (WMD: 524.04 ng/ml, 95% CI: 115.618, 932.469: I 2  = 0.0%)., Conclusion: Fasting and energy-restricted diets elicit significant reductions in serum leptin concentrations. Increases in adiponectin may also be observed when energy intake is ≤50% of normal requirements, although limited data preclude definitive conclusions on this point., Competing Interests: Conflict of interest GMT serves as a consultant for a phone app that aids users in tracking adherence to intermittent fasting regimens. This consulting consists of providing research-based information about intermittent fasting. The remaining authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, we used ascorbate peroxidase (APEX) proximity labeling, mass spectrometry, and immunofluorescence to identify ∼150 previously unknown human SG components. A highly integrated, pre-existing SG protein interaction network in unstressed cells facilitates rapid coalescence into larger SGs. Approximately 20% of SG diversity is stress or cell-type dependent, with neuronal SGs displaying a particularly complex repertoire of proteins enriched in chaperones and autophagy factors. Strengthening the link between SGs and neurodegeneration, we demonstrate aberrant dynamics, composition, and subcellular distribution of SGs in cells from amyotrophic lateral sclerosis (ALS) patients. Using three Drosophila ALS/FTD models, we identify SG-associated modifiers of neurotoxicity in vivo. Altogether, our results highlight SG proteins as central to understanding and ultimately targeting neurodegeneration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

DEAD-box RNA helicase Dbp4 is required for 18S rRNA synthesis: cellular depletion of Dbp4 impairs the early cleavage reactions of the pre-rRNA and causes U14 small nucleolar RNA (snoRNA) to remain associated with pre-rRNA. Immunoprecipitation experiments (IPs) carried out with whole-cell extracts (WCEs) revealed that hemagglutinin (HA)-tagged Dbp4 is associated with U3 snoRNA but not with U14 snoRNA. IPs with WCEs also showed association with the U3-specific protein Mpp10, which suggests that Dbp4 interacts with the functionally active U3 RNP; this particle, called the small-subunit (SSU) processome, can be observed at the 5' end of nascent pre-rRNA. Electron microscopy analyses indicated that depletion of Dbp4 compromised SSU processome formation and cotranscriptional cleavage of the pre-rRNA. Sucrose density gradient analyses revealed that depletion of U3 snoRNA or the Mpp10 protein inhibited the release of U14 snoRNA from pre-rRNA, just as was seen with Dbp4-depleted cells, indicating that alteration of SSU processome components has significant consequences for U14 snoRNA dynamics. We also found that the C-terminal extension flanking the catalytic core of Dbp4 plays an important role in the release of U14 snoRNA from pre-rRNA., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Different pre-ribosomal complexes are formed during ribosome biogenesis, and the composition of these complexes is highly dynamic. Dbp4, a conserved DEAD-box RNA helicase implicated in ribosome biogenesis, interacts with nucleolar proteins Bfr2 and Enp2. We show that, like Dbp4, Bfr2 and Enp2 are required for the early processing steps leading to the production of 18S ribosomal RNA. We also found that Bfr2 and Enp2 associate with the U3 small nucleolar RNA (snoRNA), the U3-specific protein Mpp10 and various pre-18S ribosomal RNA species. Thus, we propose that Bfr2, Dbp4 and Enp2 are components of the small subunit (SSU) processome, a large complex of ∼80S. Sucrose gradient sedimentation analyses indicated that Dbp4, Bfr2 and Enp2 sediment in a peak of ∼50S and in a peak of ∼80S. Bfr2, Dbp4 and Enp2 associate together in the 50S complex, which does not include the U3 snoRNA; however, they associate with U3 snoRNA in the 80S complex (SSU processome). Immunoprecipitation experiments revealed that U14 snoRNA associates with Dbp4 in the 50S complex, but not with Bfr2 or Enp2. The assembly factor Tsr1 is not part of the '50S' complex, indicating this complex is not a pre-40S ribosome. A combination of experiments leads us to propose that Bfr2, Enp2 and Dbp4 are recruited at late steps during assembly of the SSU processome.

Long-standing evidence gained from Pax6 mutant embryos pointed to an involvement of Pax6-dependent cell adhesion molecules in patterning the central nervous system and, in particular, the retina. However, direct evidence for such pathways remained elusive. We here present direct evidence that knockdown of Pax6 expression by morpholino antisense molecules in Xenopus embryos and knockdown of maternal N-cadherin (mNcad), N-cadherin (Ncad) and neural cell adhesion molecule (NCAM) produce similar phenotypes. Eye formation is reduced and retinal lamination is heavily disorganized. In Pax6 knockdown embryos, the levels of mRNAs coding for these cell adhesion molecules are markedly reduced. Overexpression of Pax6 efficiently rescues the phenotype of Pax6 knockdown embryos and restores expression of these putative target genes. Rescue of Pax6-deficiency by the putative target gene mNcad moderately rescues eye formation. The promoters of the genes coding for cell adhesion molecules contain several putative Pax6 binding sites, as determined by computer analysis. Chromatin immunoprecipitation shows that, in embryonic heads, Pax6 binds to promoter regions containing such predicted binding sites. Thus, several cell adhesion molecules are direct target genes of Pax6 and cooperate in retinal patterning.