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Objectives: Limited normative reference data are available for validated outcomes of flexible endoscopic evaluation of swallowing (FEES). We aimed to examine healthy swallowing via FEES in community-dwelling healthy adults to derive a preliminary reference dataset of normative validated FEES outcomes to guide clinical interpretation and diagnostic decision-making., Methods: Adults with no history of dysphagia-related disease underwent simultaneous videofluoroscopy and FEES imaging using a standardized 11-item bolus protocol. Trained raters performed duplicate, independent, blinded ratings of the New Zealand Secretion Scale (NZSS), Penetration-Aspiration Scale (PAS), and Dynamic Imaging Grade of Swallowing Toxicity-FEES (DIGEST-FEES) validated scales. Descriptive statistics were performed at the bolus (PAS) and participant level (NZSS, DIGEST-FEES)., Results: 361 swallows from 33 community-dwelling adults (36.6 ± 14.7 years old) were analyzed. In rank order, distribution profiles were: (1) NZSS: 95% normal (NZSS = 0), 5% abnormal (NZSS = 4); (2) Worst PAS: 73% safe (PAS 1-2, n = 24), 21% penetration above the true vocal folds (PAS 3, n = 7), 6% deep penetration to the true vocal folds (PAS = 5, n = 2); (3) DIGEST-FEES Safety Grades: 91% Grade 0 (normal, n = 30), 9% Grade 1 (mild impairment, n = 3); (4) DIGEST-FEES Efficiency Grades: 73% Grade 0 (normal, n = 24), 24% Grade 1 (mild impairment, n = 8), 3% Grade 2 (moderate impairment, n = 1)., Conclusion: This preliminary healthy FEES dataset highlights variation in swallowing safety and efficiency and suggests careful interpretation of FEES outcomes to avoid over-pathologizing impairment. Future studies are warranted to obtain additional normative data in diverse populations to further understand normal variation in FEES outcomes to guide clinically meaningful diagnostic cut-points., Level of Evidence: Level 3 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background. Nitric oxide (NO) is an important vascular signaling molecule that plays a role in vascular homeostasis. A reduction in NO bioavailability is thought to contribute to endothelial dysfunction, an early risk factor for both cardiovascular disease and type 2 diabetes. Dietary nitrate, through the nitrate-nitrite-NO pathway, may provide an alternate source of NO when the endogenous eNOS system is compromised. In addition to a role in the vascular system, NO may also play a role in the metabolic syndrome including obesity and glucose tolerance. Aim. To investigate the effect of long-term dietary nitrate supplementation on development of the metabolic syndrome in mice fed a high-fat diet. Methods. Following 1 week of acclimatisation, male (6–8 weeks) C57BL6 mice were randomly assigned to the following groups (10/group) for 12 weeks: (i) normal chow + NaCl (1 mmol/kg/day), (ii) normal chow + NaNO3 (1 mmol/kg/day), (iii) high-fat diet + NaCl (1 mmol/kg/day), and (iv) high-fat diet + NaNO3 (1 mmol/kg/day). Body weight and food consumption were monitored weekly. A subset of mice (5/group) underwent running wheel assessment. At the end of the treatment period, all mice underwent fasting glucose tolerance testing. Caecum contents, serum, and tissues (liver, skeletal muscle, white and brown adipose, and kidney) were collected, frozen, and stored at −80°C until analysis. Results. Consumption of the high-fat diet resulted in significantly greater weight gain that was not affected by dietary nitrate. Mice on the high-fat diet also had impaired glucose tolerance that was not affected by dietary nitrate. There was no difference in adipose tissue expression of thermogenic proteins or energy expenditure as assessed by the running wheel activity. Mice on the high-fat diet and those receiving dietary nitrate had reduced caecum concentrations of both butyrate and propionate. Conclusions. Dietary nitrate does not prevent development of the metabolic syndrome in mice fed a high-fat diet. This may be due, in part due, to reductions in the concentration of important short-chain fatty acids. [ABSTRACT FROM AUTHOR]

Aims To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. Methods Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. Results PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0–9.6) µg/ml, vs. complication-free patients [5.3 (4.7–6.0) µg/ml, P < 0.001] and control subjects [5.3 (4.6–6.1) µg/ml, P < 0.001;anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients ( P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure ( r = 0.317), pulse pressure ( r = 0.337), small artery elasticity ( r = –0.269), glycated haemoglobin ( r = 0.245), body mass index ( r = 0.362), renal dysfunction [including serum creatinine ( r = 0.491), cystatin C ( r = 0.500)], triglycerides ( r = 0.367), and inflammation [including logeC-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 ( r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and logeCRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age ( r2 = 0.427). Conclusions In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation. [ABSTRACT FROM AUTHOR]

Aim Oxidative stress may play an important role in the pathogenesis of hypertension. The aim of our study is to examine whether increased expression of the predominant endothelial l-arginine transporter, cationic amino acid transporter-1 ( CAT1), can prevent oxidative stress-induced hypertension. Methods Wild-type mice ( WT; n = 9) and endothelial CAT1 overexpressing ( CAT+) mice ( n = 6) had telemetry probes implanted for the measurement of mean arterial pressure ( MAP), heart rate ( HR) and locomotor activity. Minipumps were implanted for infusion of the superoxide dismutase inhibitor diethyldithiocarbamic acid ( DETCA; 30 mg kg−1 day−1; 14 days) or its saline vehicle. Baseline levels of MAP, HR and locomotor activity were determined before and during chronic DETCA administration. Mice were then killed, and their plasma and kidneys collected for analysis of F2-isoprostane levels. Results Basal MAP was less in CAT+ (92 ± 2 mmHg; n = 6) than in WT (98 ± 2 mmHg; n = 9; P < 0.001). During DETCA infusion, MAP was increased in WT (by 4.2 ± 0.5%; P < 0.001) but not in CAT+, when compared to appropriate controls ( PDETCA*genotype = 0.006). DETCA infusion increased total plasma F2-isoprostane levels (by 67 ± 11%; P = 0.05) in WT but not in CAT+. Total renal F2-isoprostane levels were greater during DETCA infusion in WT (by 72%; P < 0.001), but not in CAT+, compared to appropriate controls. Conclusion Augmented endothelial l-arginine transport attenuated the prohypertensive effects of systemic and renal oxidative stress, suggesting that manipulation of endothelial CAT1 may provide a new therapeutic approach for the treatment of cardiovascular disease associated with oxidative stress. [ABSTRACT FROM AUTHOR]

Oxidized cholesterols in the diet have been shown to exacerbate arterial cholesterol deposition and the development of atherosclerosis in animal models. Dietary oxidized cholesterols are absorbed through the intestine and incorporated into lymph chylomicrons. The aim of this study was to investigate the effect of oxidized cholesterols on the metabolism of nascent chylomicrons in vivo. It was shown that oxidized cholesterols markedly delay the clearance of chylomicrons from plasma compared to rats given TG alone. However, there was no difference in the clearance of chylomicrons containing oxidized cholesterols vs. purified cholesterol, although the presence of oxysterols did appear to exacerbate the removal of these particles from circulation. The impaired clearance of chylomicrons containing oxidized cholesterols was not due to impaired lipolysis and slower conversion to the remnant form. Moreover, the incorporation of oxidized cholesterols did not alter the hepatic or splenic uptake of chylomicrons compared to chylomicrons isolated from rats given purified cholesterol or TG alone. Collectively, the results of this study suggest that the exacerbated delay in clearance of chylomicron remnants enriched with oxysterols may be due to impaired uptake by tissues other than the liver and spleen. Apolipoprotein (apo) analysis showed that oxysterol incorporation reduced the apoE content and altered the apoC phenotype of chylomicrons, which may have an impact on the removal of chylomicron remnants from plasma. In conclusion, dietary oxysterols appear to have the potential to adversely affect chylomicron metabolism. Therefore, further investigations in humans are required to determine whether dietary oxidized cholesterols found in cholesterol-rich processed foods delay the clearance of postprandial remnants, which may contribute to and exacerbate the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

Purpose: One major consequence of lung transplantation is the development of oropharyngeal dysphagia. This systematic review aims to appraise and synthesize the available evidence of the use of instrumental assessments to outline the characteristics of post‐lung transplant dysphagia. Methods: Following the identification of appropriate search terms for the question, a literature search was conducted in PubMed, Scopus, and the Health and Medical Collection of Proquest Research Library and included records between inception and September 14, 2023. Search strategies included the use of text words and subject headings (e.g., MeSH and Index terms) related to (1) dysphagia or swallowing (swallow*, deglutition disorder*), (2) lung transplant (lung transplant*, post‐operative, post‐lung), and (3) complications (adverse effects, *complications, treatment outcome). Results: The literature search strategy yielded a total of 883 studies from the electronic database search, with no additional records identified through other sources. After the removal of duplicates (n = 96), a total of 787 studies were screened through title and abstracts which eliminated 775 studies. Six studies were ultimately included in the systematic review. The selected articles included patients who underwent lung transplantation and all but one study utilized a retrospective design. A lack of transparency regarding instrumental evaluation protocols (videofluoroscopic [VFSS] and Flexible Endoscopic Evaluation of Swallowing [FEES]) including the number and bolus types used during the instrumental evaluations appeared as a theme in the studies included. The Penetration‐Aspiration Scale (PAS) was systematically utilized to measure dysphagia safety outcome. Handling of the PAS scale was not consistent across studies, however penetration or aspiration ranged from 52.4% up to 100%. Additionally, silent aspiration rates ranged from 14.2% to 61.9%. Conclusions: This review sought to describe the post‐operative swallowing function and its physiological parameters following lung transplantation. We examined the results reported and the methods utilized in obtaining these results in the existing literature. Limited reporting practices for physiological parameters were found, however the airway invasion was reported in all studies with variation in degrees of swallowing safety related deficits, with PAS being the most widely used scale to describe airway invasion depth and response. Future studies exploring dysphagia outcomes post‐lung transplant should comment on the altered physiological mechanisms of the swallow to further expand on the physiological deficits observed following transplantation in this group and allow for treatment planning. Level of evidence: Level 1. [ABSTRACT FROM AUTHOR]

Artemisia abyssinica and Artemisia arborescens are unique plants that show significant bioactive properties and are used for the treatment of a variety of diseases. This study assessed the nutritional values, functional properties, chemical composition, and bioactive attributes of these plants as functional nutritional supplements. Compared to A. arborescens, A. abyssinica had higher fat (4.76%), fiber (16.07%), total carbohydrates (55.87%), and energy (302.15 kcal/100 g DW), along with superior functional properties, including higher water and oil absorption capacities (638.81% and 425.85%, respectively) and foaming capacity and stability (25.67% and 58.48%). The investigation of volatile compounds found that A. abyssinica had higher amounts of hotrienol (4.53%), yomogi alcohol (3.92%), caryophyllene (3.67%), and carvotanacetone (3.64%), which possess anti‐inflammatory, antimicrobial, and antioxidant properties. Artemisia abyssinica contributed over 30% of the recommended dietary intake (RDI) of amino acids. It displayed superior levels of sodium (31.46 mg/100 g DW) and calcium (238.07 mg/100 g DW). It also exhibited higher levels of organic acids, particularly malic acid, butyric acid, and succinic acid, compared to A. arborescens. Fatty acid analysis revealed palmitic and linoleic acids as primary components in both plants, with A. abyssinica having a higher palmitic acid content. Artemisia abyssinica also had higher vitamin C and thiamine levels. Although A. arborescens showed the highest total phenolic content (TPC), antioxidant activity, and capacity, A. abyssinica demonstrated acceptable efficiency in TPC and antioxidant content. These findings highlight the potential of both Artemisia species, particularly A. abyssinica, as valuable sources of nutrients and bioactive compounds for various applications. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS), which is a major consequence of obesity, increases mortality risks. Evidence shows favorable effects of nutritional approaches in the management of MetS. Accordingly, the use of functional foods has increased to enhance weight loss and reduce the risk factors associated with MetS. So, we aimed to investigate the effects of daily consumption of a functional acorn‐based cake in conjunction with energy‐restricted diet on some complications of patients with MetS. The study included 66 participants who were randomly assigned to either (A) a calorie‐restricted diet + functional cake (FC) (n = 33) or (B) a calorie‐restricted diet + a placebo cake (PC) (n = 33). Sociodemographic information, anthropometric measurements, dietary intakes, and serum biochemical parameters (inflammatory and oxidative stress markers, leptin, and endothelin) were measured before and after 8 weeks of intervention. Sixty‐three participants completed this trial. After adjustment for baseline levels, consumption of FC compared to the PC resulted in a significant decrease in IL‐6 (p =.03) and high‐sensitivity C‐reactive protein (p =.04) levels. No differences were observed between groups with regard to serum malondialdehyde, total antioxidant capacity, endothelin, and leptin levels (p >.05). Acorn‐based cake could improve inflammation as an adjunct to an energy‐restricted diet in overweight and obese patients with MetS. However, it is not clear whether acorn‐based cake can be used to prevent or treat MetS because of indecisive findings regarding its ability to manage oxidative stress and serum hormones. [ABSTRACT FROM AUTHOR]

Bisphenol A, a traditional endocrine disruptor, has been implicated in male infertility. This study investigated the effect of Cucumeropsis mannii seed oil (CMSO) on bisphenol A (BPA)‐induced biochemical toxicity in the testicular mitochondria of male albino rats. The rats were assigned randomly to six experimental groups (n = 6), A, B, C, D, E, and F. Group A received 1 mL of olive oil. Groups B and C received 100 mL/kg body weight (BW) of BPA and 7.5 mL/kg BW CMSO, respectively. Rats in groups D, E, and F received preadministered doses of 100 mL/kg BW of BPA, 5 mL/kg BW of BPA, and 2.5 mL/kg BW of CMSO, respectively, followed by 6 weeks of exposure to those doses. Some mitochondrial enzymes, mitochondrial membrane potential (MMP), mitochondria testicular protein, and body weight of rats were determined using standard methods. BPA significantly reduced succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, NADH dehydrogenase, and monoamine oxidase activity. Also, BPA prominently decreased the MMP, mitochondrial testicular protein, and body weight of rats. Interestingly, coadministration of BPA and CMSO restored the dysregulated activities of the enzymes and levels of other biomarkers. We postulated that CMSO may be a promising drug for treating systemic toxicity caused by environmental toxicants such as BPA. [ABSTRACT FROM AUTHOR]

Cholesterol oxidation products (oxysterols) induce macrophage lipid loading and accumulate in early arterial fatty streaks. The origin of lesion oxysterols has not been elucidated. The absorption of oxysterols from the diet and transport to the arterial wall by postprandial lipoprotein remnants may be a significant source. This study aimed to investigated the extent of oxysterol absorption and the effect on chylomicron composition. Cholesterol was heat-treated, causing 30% oxidation; the major oxidation products were 7β-hydroxycholesterol, 7-ketocholesterol, 5α,6α-epoxycholesterol, and 5β,6β-epoxycholesterol. Conscious lymph-cannulated rats were given a bolus gastric infusion of 50 mg oxidized cholesterol or 50 mg purified cholesterol in a vehicle of triglyceride. In the rats given the oxidized cholesterol, 6% of the oxysterol load was absorbed and incorporated into lymph chylomicrons. Rats given pure cholesterol had no increase in oxysterols above baseline levels. The incorporation of oxysterols into lymph chylomicrons differed over time with 7β-hydroxycholesterol, having peak absorption at 3 h, followed by 7-ketocholesterol at 4 h and 5α,6α-epoxycholesterol at 5 h. The absorption of oxysterols in animals given the oxidized cholesterol gastric infusate was associated with lymph chylomicron compositional changes at 2–4 h. The oxidized cholesterol-treated group has a twofold increase in the cholesterol (890±84 μg vs. 440±83 μg at 3 h) and triglyceride content (19.76±3.4 μg vs. 8.49±3.8 μg at 3 h). This led to a doubling of chylomicron size over this postprandial period, with particles having a mean diameter of 294 nm in the oxidized cholesterol-treated animals, compared to 179 nm in the purified cholesterol group. In conclusion, dietary oxysterols appear to influence postprandial lipoprotein particle size and composition. These changes may have effects on the clearance of chylomicrons from plasma, arterial delivery of oxysterols, and possible deposition in arterial lesions. [ABSTRACT FROM AUTHOR]

Overall there is good evidence that alcohol consumption induces oxidative stress, and leads to lipid peroxidation, effects which have been linked to alcohol-related toxicity and disease and may be relevant to alcoholatherosclerosis interrelationships. On the other hand, a protective effect of light to moderate alcohol consumption against cardiovascular disease is well recognized, with the further hypothesis that red wine offers extra cardiovascular protection due to its rich content of antioxidant phenolic compounds. Although this hypothesis is given some credence from in vitro data, controlled studies in humans have produced conflicting results. Clearly, the equally well described pro-oxidant effects of alcohol and its metabolism have been insufficiently considered in the pursuit of what to many is an intuitively attractive hypothesis. Further studies are required to determine if red wine phenolics are actually absorbed from the gut and whether they offer any overall antioxidant protection in vivo. The hypothesis that red wine offers extra cardiovascular protection compared to other alcoholic beverages is not proven and must await the outcome of studies in which the full spectrum of the pro-oxidant and antioxidant effects of alcoholic beverages are duly considered. In the absence of such studies, there are no grounds at present for the promotion of the consumption of alcoholic beverages on the basis of their putative "antioxidant" properties. [ABSTRACT FROM AUTHOR]

The current study pioneers a comprehensive exploration into the influence of ripening stages on the nutritional composition and antioxidant attributes of the New Zealand damson plums (Prunus domestica ssp. Insititia). Sampled at early‐, mid‐, and late‐ripening stages from randomly selected plum trees, the investigation unveiled notable significant (p <.05) declines in multiple parameters as ripening progressed. Noteworthy reductions in dry matter (from 21% to 19.33%), stone weight (from 30.23% to 24.30%), total dietary fiber (from 3.15% to 2.5%), energy content (from 280 to 263 kJ/100 g), vitamin D3 (from 1.67 to 1.53 μg/100 g), vitamin A (from 4.2 to 3.87 μg/100 g), and specific minerals (e.g., Ca, Mg, and P) emerged as a hallmark of this progression. Additionally, plums harvested at the advanced ripening stage exhibited heightened moisture content in contrast to their early‐stage counterparts. Conversely, ash, protein, carbohydrates, total sugar, and minerals (including K, Na, Zn, and Se) demonstrated no significant alteration (p >.05) across ripening stages. Remarkably, damson plums that were harvested at the end of the ripening stage displayed reduced phenolic content and total antioxidant activity compared to those acquired at the early–mid ripening phase. This research collectively highlights the substantive impact of harvesting time and ripening stage on the nutritional and antioxidant profiles of damson plums cultivated in New Zealand. [ABSTRACT FROM AUTHOR]

Absorption​ of free radicals in the body cannot be done by antioxidant compounds originating from the human body, so exogenous antioxidants are required to help in their natural antioxidant action. Oxidative stress can be caused by an imbalance of free radical inhibitors and the accumulation of free radicals that enter cellular structures. Synthetic antioxidants found in external antioxidants are not the primary choice because they are harmful and carcinogenic. Therefore, using natural ingredients provides a necessary alternative to constructing novel natural antioxidants. Recent studies have highlighted critical analysis and evaluation that flavonoids are a unique class of secondary metabolites found in plants and used in communities as traditional therapeutics with proven bioactivity. This could support new discoveries based on various herbal medicines and in addition, the functional effectiveness of flavonoids as antioxidants against free radicals. In this review, there are several strengths in the discussion. First, the study takes a comprehensive approach by covering various aspects, including the properties and sources of free radicals, oxidative stress in relation to different diseases, antioxidant defense mechanisms, and the specific antioxidant mechanisms of flavonoids. Second, the focus on natural antioxidants, especially flavonoids, and also discussion about clinical applications and human studies, limitations, global perspectives, and future research directions of flavonoids compounds become references in the selection of natural medicines. But, several constraints should be considered when interpreting the findings of this review. First, the discussion about the mechanism of antioxidant compounds is only discussed in general and only takes one example of a compound (flavonoid) that has the potential as an antioxidant. Second, the lack of findings regarding the relationship between several diseases discussed with free radicals. Third, a limited number of studies investigated regarding clinical applications and human studies of some of the diseases discussed. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is characterized by an elevated risk for cerebrovascular disease including stroke. One mechanism that may contribute to this heightened risk is an impairment in cerebrovascular carbon dioxide reactivity (CVR). We compared CVR between CKD patients stages III–IV and controls (CON) without CKD but matched for hypertension and diabetes status. CVR was measured via 5% CO2 inhalation followed by voluntary hyperventilation in 14 CKD and 11 CON participants while mean arterial pressure, end‐tidal carbon dioxide, and middle cerebral artery blood velocity (MCAv) were measured continuously. CVR was quantified as the linear relationship between etCO2 and MCAv. We observed no difference in CVR between groups. Hypercapnic CVR: CKD = 1.2 ± 0.9 cm/s/mm Hg, CON = 1.3 ± 0.8 cm/s/mm Hg, hypocapnic CVR: CKD = 1.3 ± 0.9 cm/s/mm Hg, CON = 1.5 ± 0.7 cm/s/mm Hg, integrated CVR: CKD = 1.5 ± 1.1 cm/s/mm Hg, CON = 1.7 ± 0.8 cm/s/mm Hg, p ≥ 0.48. Unexpectedly, CVR was inversely related to estimated glomerular filtration rate in CKD (R2 = 0.37, p = 0.02). We report that CVR remains intact in CKD and is inversely related to eGFR. These findings suggest that other mechanisms beyond CVR contribute to the elevated stroke risk observed in CKD. [ABSTRACT FROM AUTHOR]

Following eye gaze is fundamental for many social-cognitive abilities, for example, when judging what another agent can or cannot know. While the emergence of gaze following has been thoroughly studied on a group level, we know little about (a) the developmental trajectory beyond infancy and (b) the sources of individual differences. In Study 1, we examined gaze following across the lifespan (N = 478 3- to 19-year-olds from Leipzig, Germany; and N = 240 20- to 80-year-old international, remotely tested adults). We found a steep performance improvement during preschool years, in which children became more precise in locating the attentional focus of an agent. Precision levels then stayed comparably stable throughout adulthood with a minor decline toward old age. In Study 2, we formalized the process of gaze following in a computational cognitive model that allowed us to conceptualize individual differences in a psychologically meaningful way (N = 60 3- to 5-year-olds, 50 adults). According to our model, participants estimate pupil angles with varying levels of precision based on observing the pupil location within the agent's eyes. In Study 3, we empirically tested how gaze following relates to vector following in non-social settings and perspective-taking abilities (N = 102 4- to 5-year-olds). We found that gaze following is associated with both of these abilities but less so with other Theory of Mind tasks. This work illustrates how the combination of reliable measurement instruments and formal theoretical models allows us to explore the in(ter)dependence of core social-cognitive processes in greater detail. RESEARCH HIGHLIGHTS: Gaze following develops beyond infancy. The highest precision levels in localizing attentional foci are reached in young adulthood with a slight decrease towards old age. We present a computational model that describes gaze following as a process of estimating pupil angles and the corresponding gaze vectors. The model explains individual differences and recovers signature patterns in the data. To estimate the relation between gaze- and vector following, we designed a non-social vector following task. We found substantial correlations between gaze following and vector following, as well as Level 2 perspective-taking. Other Theory of Mind tasks did not correlate., (© 2024 The Author(s). Developmental Science published by John Wiley & Sons Ltd.)

Background. Diabetes mellitus (DM) presents a significant global health challenge with considerable cardiovascular implications. Coenzyme Q10 (CoQ10) has gained recognition for its potential as a natural antioxidant supplement in the management of diabetes and its associated cardiovascular complications. Aim. This comprehensive review systematically examines the scientific rationale underlying the therapeutic properties of CoQ10 in mitigating the impact of diabetes and its cardiovascular consequences. The analysis encompasses preclinical trials (in vitro and in vivo) and clinical studies evaluating the efficacy and mechanisms of action of CoQ10. Result & Discussion. Findings reveal that CoQ10, through its potent antioxidant and anti-inflammatory attributes, demonstrates significant potential in reducing oxidative stress, ameliorating lipid profiles, and regulating blood pressure, which are crucial aspects in managing diabetes-induced cardiovascular complications. CoQ10, chemically represented as C59H90O4, was administered in capsule form for human studies at doses of 50, 100, 150, 200, and 300 mg per day and at concentrations of 10 and 20 μM in sterile powder for experimental investigations and 10 mg/kg in powder for mouse studies, according to the published research. Clinical trials corroborate these preclinical findings, demonstrating improved glycemic control, lipid profiles, and blood pressure in patients supplemented with CoQ10. Conclusion. In conclusion, CoQ10 emerges as a promising natural therapeutic intervention for the comprehensive management of diabetes and its associated cardiovascular complications. Its multifaceted impacts on the Nrf2/Keap1/ARE pathway, oxidative stress, and metabolic regulation highlight its potential as an adjunct in the treatment of diabetes and related cardiovascular disorders. However, further extensive clinical investigations are necessary to fully establish its therapeutic potential and assess potential synergistic effects with other compounds. [ABSTRACT FROM AUTHOR]

Cellular senescence and the senescence‐associated secretory phenotype (SASP) contribute to age‐related arterial dysfunction, in part, by promoting oxidative stress and inflammation, which reduce the bioavailability of the vasodilatory molecule nitric oxide (NO). In the present study, we assessed the efficacy of fisetin, a natural compound, as a senolytic to reduce vascular cell senescence and SASP factors and improve arterial function in old mice. We found that fisetin decreased cellular senescence in human endothelial cell culture. In old mice, vascular cell senescence and SASP‐related inflammation were lower 1 week after the final dose of oral intermittent (1 week on—2 weeks off—1 weeks on dosing) fisetin supplementation. Old fisetin‐supplemented mice had higher endothelial function. Leveraging old p16‐3MR mice, a transgenic model allowing genetic clearance of p16INK4A‐positive senescent cells, we found that ex vivo removal of senescent cells from arteries isolated from vehicle‐ but not fisetin‐treated mice increased endothelium‐dependent dilation, demonstrating that fisetin improved endothelial function through senolysis. Enhanced endothelial function with fisetin was mediated by increased NO bioavailability and reduced cellular‐ and mitochondrial‐related oxidative stress. Arterial stiffness was lower in fisetin‐treated mice. Ex vivo genetic senolysis in aorta rings from p16‐3MR mice did not further reduce mechanical wall stiffness in fisetin‐treated mice, demonstrating lower arterial stiffness after fisetin was due to senolysis. Lower arterial stiffness with fisetin was accompanied by favorable arterial wall remodeling. The findings from this study identify fisetin as promising therapy for clinical translation to target excess cell senescence to treat age‐related arterial dysfunction. [ABSTRACT FROM AUTHOR]

The dairy–cereal‐based food, known as Doowina, is one of the traditional fermented foods in Iran. We aimed to improve the health‐promoting properties of Doowina by using turnips, butternut squash, and sourdough as a new functional food with high nutritional value and antioxidant activity. Therefore, the physicochemical, microbial, and sensory properties of samples with nutritional supplements (8% turnip and 8% butternut squash) and different concentrations of sourdough (0, 0.5, and 1%) were studied during 0, 3, 6, and 9 days of fermentation time. The results showed that there was no significant difference (p <.05) in the moisture and ash content between the different formulations of Doowina. There was also no significant difference (p <.05) in the phenolic compound content and antioxidant activity of the Doowina samples during the fermentation period. However, the number of lactic acid bacteria (LAB) increased significantly (p <.05) until the 6th day of fermentation, and the protein content decreased significantly (p <.05) in all samples during the fermentation period. According to the results, the samples with butternut squash and sourdough had the highest total phenolic content, the highest antioxidant activity, the highest linoleic acid content, and the highest sensory rating of all samples. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis‐3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid‐chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro‐inflammatory signaling lipids from ω‐6 poly‐unsaturated fatty acids (PUFAs), including 15‐hydroxyeicosatetraenoic (HETE), 12‐HETE, and 11‐HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro‐resolving lipid mediator from ω‐3 PUFAs, 14(S)‐hydroxy docosahexaenoic acid (14S‐HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor‐outcome patients with sepsis and may serve as targets for future therapies. [ABSTRACT FROM AUTHOR]

Enhancing electronic transport properties of thermoelectric oxides is of great technological importance. Oxides are promising candidates for waste heat harvesting at elevated temperatures as well as for electricity generation in low‐power applications. To this purpose, fundamental understanding of their electrical and thermal conduction mechanisms is essential. Herein, the conduction mechanism of CaMnO3 materials is focused on and how dopant identity and amount alter the kinetic properties of charge transport is investigated. Ca1−xRxMnO3 compounds with R = Y and La are synthesized, where 0 ≤ x ≤ 0.13, and the electrical conductivity and Seebeck coefficient for temperatures ranging from 300 to 1050 K, indicating that Y‐doped compounds are usually more conductive than their La‐doped counterparts, are measured. Analysis of both in terms of the small polaron hopping model reveals that Y doping reduces conduction activation energies, resulting in higher electrical conductivity and charge carrier mobility. Remarkably high values of thermoelectric power factor for the Ca0.97La0.03MnO3 compound, for example, 300 μWm−1 K−2 at 1050 K are observed; furthermore, these values are preserved for a wide temperature range, rendering this compound a good candidate for heat‐to‐electrical power generation at elevated temperatures. [ABSTRACT FROM AUTHOR]

Background. Diabetes is a rising disorder that affects millions of people annually. It also creates more complications, such as neuropathy, oxidative stress, and hepatic and kidney impairment. Aphanamixis polystachya plant, which possesses multiple medicinal values, is used in this study to explore its potential in treating diabetes. Methods. A single dose (65 mg/kg) of intraperitoneal streptozotocin injection was utilized to mediate diabetes in Sprague-Dawley rats. Diabetic animals were treated orally with 250 or 500 mg/kg of standardized leaves' extract of A. polystachya (AP) for 28 days to evaluate the antidiabetic and organ-protective effects of the plant. Different biochemical and histological markers are measured according to the established protocol. Results. Our results demonstrated a significant decrease in blood glucose (p < 0.001) and HbA1c (p < 0.05) levels in the diabetic animal after administering AP (250 and 500 mg/kg doses) compared to the control groups. AP can also regularize lipids, glycogen, alanine aminotransferase, and aspartate aminotransferase. Furthermore, serum urea nitrogen and creatinine decreased after treatment with AP in diabetic rats. AP also reduced oxidative stress markers and showed a substantial elevation in antioxidant enzymes in diabetic animals. Overall, AP at 500 mg/kg revealed comparable results against the standard antidiabetic drug glyburide. Besides, the histological investigation showed the AP's efficacy in attenuating kidney tissue inflammation and damage. HPLC data elucidated that the AP leaf extract contains polyphenols with potential antioxidant, antidiabetic, and organ protective agents: gallic acid, rutin hydrate, and quercetin hydrate. Conclusion. Taken together, AP may be one of the potential sources of antidiabetic agents. [ABSTRACT FROM AUTHOR]

The geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field. [ABSTRACT FROM AUTHOR]

We investigated the effects of processing (roasting and extrusion puffing) on the antihypertensive activity of blended grains both in vitro and in vivo. The blended grains were composed of sorghum (Sorghum bicolor), adzuki bean (Vigna angularis), and finger millet (Eleusine coracana). In the in vitro studies, total phenolic content (TPC), total flavonoid content (TFC), and angiotensin-converting enzyme (ACE) inhibitory activity of blended grains were evaluated. The results showed a significant decreasing trend in TPC, TFC, and ACE inhibitory activity in the following order: nonprocessed blended grains (NPBG) > roasted blended grains (RBG) > extrusion puffed blended grains (EPBG). Spontaneously hypertensive rats (SHRs) were fed a diet containing 40% blended grains (replacing the standard diet) for 8 weeks. None of the blended grains had any effects on feed intake, liver function, and serum lipid profile. Notably, NPBG showed the greatest reduction in systolic blood pressure compared to the model control (MC), followed by RBG, and EPBG, whereas diastolic blood pressure was significantly decreased in NPBG and RBG. Serum ACE activity and angiotensin II levels significantly decreased in all blended grains, with NPBG and RBG showing the most significant decrease in angiotensin II levels. Moreover, the mRNA expression of renin, a hormone involved in hypertension, was significantly decreased in NPBG and RBG. Only NPBG ameliorated aortic vascular remodeling compared to the MC. These results suggest that NPBG exhibited the most potent antihypertensive activity; however, roasting could be an effective processing method for maintaining antihypertensive effects compared to extrusion puffing. [ABSTRACT FROM AUTHOR]

Background: Foot orthoses and footwear interventions are advocated for the management of lower limb musculoskeletal conditions including the hip, but much of the research is focused on knee disorders. The aim of this systematic review was to synthesise the literature that investigates the use of foot orthoses or footwear in people with hip‐related pain. Methods: MEDLINE, EMBASE, CINAHL, AMED and SPORTDiscus were searched from inception to March 2023. Randomised controlled trials (RCT), cohort and pre‐post studies reporting on footwear and foot orthoses interventions, in participants with hip‐related pain, were eligible for inclusion. Outcomes included pain, physical function, and quality of life (QoL). Effect sizes were calculated where sufficient data were available. Reporting quality was assessed using the Cochrane Risk of Bias Tool (Rob‐2) and the Joanna Briggs Institute Checklist. The overall quality of evidence was rated according to the Grading of Recommendations, Assessment, Development, and Evaluations framework. Results: Of the seven included studies (n = 266 participants), there was one RCT, one cohort and five single‐group pre‐post designs. Interventions included customised and non‐customised arch supports, heel lifts, and footwear modifications, used in the following hip conditions: trochanteric pain, non‐specific hip pain, hip osteoarthritis, and leg length dysfunction following total hip arthroplasty. Meta‐analysis was possible for outcomes in two studies, demonstrating moderate improvement in pain following foot orthoses use. Overall certainty of evidence ranged from very low to low. Conclusion: Single‐group pre‐post study designs describe positive relationships between foot orthoses and footwear use and improvements in hip pain, function, and QoL. However, these results were not supported by the only available RCT. Given this is a relatively inexpensive and non‐invasive treatment approach, further rigorous studies are warranted. [ABSTRACT FROM AUTHOR]

In this paper, a well‐motivated parameterization of the Hubble parameter (H) is revisited that renders two models of dark energy showing some intriguing features of the late‐time accelerating Universe. A general quintessence field is considered as a source of dark energy. Tighter constraints using recently updated cosmic observational datasets for the considered models have been obtained. The two models described here show a nice fit to the considered uncorrelated Hubble datasets, Standard candles, Gamma Ray Bursts, Quasars, and uncorrelated Baryonic Acoustic Oscillations datasets. Using the constrained values of the model parameters, some features of the late‐time accelerating models and obtained the present value of the deceleration parameter (q0), the present value of the Hubble parameter (H0) and the transition redshift (zt$z_{t}$) from deceleration to acceleration have been discussed. The current value of the deceleration parameter for both models is consistent with the Planck 2018 results. The evolution of the geometrical and physical parameters is discussed through graphical representations for both models with some diagnostic analysis. The statistical analysis performed here shows greater results and overall, the outcomes of this investigation are superior to those previously found. [ABSTRACT FROM AUTHOR]

Senolytics are a category of drugs that reduce the impact of cellular senescence, an effect associated with a range of chronic and age‐related diseases. Since the discovery of the first senolytics in 2015, the number of known senolytic agents has grown dramatically. This review discusses the broad categories of known senolytics—kinase inhibitors, Bcl‐2 family protein inhibitors, naturally occurring polyphenols, heat shock protein inhibitors, BET family protein inhibitors, P53 stabilizers, repurposed anti‐cancer drugs, cardiac steroids, PPAR‐alpha agonists, and antibiotics. The approaches used to screen for new senolytics are articulated including a range of methods to induce senescence, different target cell types, various senolytic assays, and markers. The choice of methods can greatly influence the outcomes of a screen, with high‐quality screens featuring robust systems, adequate controls, and extensive validation in alternate assays. Recent advances in single‐cell analysis and computational methods for senolytic identification are also discussed. There is significant potential for further drug discovery, but this will require additional research into drug targets and mechanisms of actions and their subsequent rigorous evaluation in pre‐clinical models and human trials. [ABSTRACT FROM AUTHOR]

Phenothiazine derivatives can unselectively inhibit the trypanothione‐dependent antioxidant system enzyme trypanothione reductase (TR). A virtual screening of 2163 phenothiazine derivatives from the ZINC15 and PubChem databases docked on the active site of T. cruzi TR showed that 285 compounds have higher affinity than the natural ligand trypanothione disulfide. 244 compounds showed higher affinity toward the parasite's enzyme than to its human homolog glutathione reductase. Protein‐ligand interaction profiling predicted that the main interactions for the top scored compounds were with residues important for trypanothione disulfide binding: Phe396, Pro398, Leu399, His461, Glu466, and Glu467, particularly His461, which participates in catalysis. Two compounds with the desired profiles, ZINC1033681 (Zn_C687) and ZINC10213096 (Zn_C216), decreased parasite growth by 20 % and 50 %, respectively. They behaved as mixed‐type inhibitors of recombinant TR, with Ki values of 59 and 47 μM, respectively. This study provides a further understanding of the potential of phenothiazine derivatives as TR inhibitors. [ABSTRACT FROM AUTHOR]

Background: The exposed pulp has been the topic of numerous studies, but well‐designed and well‐executed comparative trials on the outcome and treatment of these teeth have been limited. Objectives: This study was conducted to answer the following questions: in patients with nontraumatic pulpitis associated with no or nonspontaneous pain in permanent teeth, (i) is direct pulp capping or pulpotomy (partial/full) as effective as selective or stepwise caries removal [Population/participants, Intervention(s), Comparator(s)/control, Outcome(s) (PICO) 1], (ii) is pulpotomy (partial/full) as effective as direct pulp capping (PICO 2) and (iii) is pulpotomy (partial/full) as effective as a pulpectomy (PICO 3), in terms of a combination of patient and clinical reported outcomes, with 'tooth survival' as the most critical outcome? Methods: A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Central Register of Controlled Trials from inception to November 3rd 2021. Grey literature and contents of the major subject journals were examined. Eligibility criteria followed the PICO questions. Two independent reviewers performed study selection, data extraction and appraisal; disagreements were resolved by a third reviewer. The risk of bias was assessed by the revised Cochrane risk‐of‐bias tool for randomized trials. Results: Three randomized clinical trials (RCTs) were included in the review. No study fulfilled the criteria to answer PICO 1. There were no significant differences in the reported outcomes between investigated treatments in all included RCTs. None of the included studies reported the most critical outcome 'tooth survival'. A high loss of patients during the follow‐up period was observed. Discussion: Although a few studies fulfilled strict eligible criteria, the results of this systematic review clearly highlight a paucity of available evidence. At the present time, clinical decisions cannot be substantiated by direct comparative trials. Conclusions: Based on limited evidence, this systematic review discovered no significant differences in effectiveness between compared vital pulp treatments in managing nontraumatic pulpitis associated with no or nonspontaneous pain. Further high‐quality RCTs are necessary to investigate the effectiveness of direct pulp capping or pulpotomy (partial/full) compared to selective or stepwise caries removal. Registration: PROSPERO database (CRD42021259742). [ABSTRACT FROM AUTHOR]

Perspective‐taking, which is important for communication and social activities, can be cultivated through joint actions, including musical activities in children. We examined how rhythmic activities requiring coordination affect perspective‐taking in a referential communication task with 100 Chinese 4‐ to 6‐year‐old children. In Study 1, 5‐ to 6‐year‐old children played an instrument with a virtual partner in one of three coordination conditions: synchrony, asynchrony, and antiphase synchrony. Eye movements were then monitored with the partner giving instructions to identify a shape referent which included a pre‐nominal scalar adjective (e.g., big cubic block). When the target contrast (a small cubic block) was in the shared ground and a competitor contrast was occluded for the partner, participants who used perspective differences could, in principle, identify the intended referent before the shape was named. We hypothesized that asynchronous and antiphase synchronous musical activities, which require self‐other distinction, might have stronger effects on perspective‐taking than synchronous activity. Children in the asynchrony and antiphase synchrony conditions, but not the synchrony condition, showed anticipatory looks at the target, demonstrating real‐time use of the partner's perspective. Study 2 was conducted to determine if asynchrony and antiphase asynchrony resulted in perspective‐taking that otherwise would not have been observed, or if synchronous coordination inhibited perspective‐taking that would otherwise have occurred. We found no evidence for online perspective‐taking in 4‐ to 6‐year‐old children without music manipulation. Therefore, playing instruments asynchronously or in alternation, but not synchronously, increases perspective‐taking in children of this age, likely by training self‐other distinction and control. A video abstract of this article can be viewed at https://youtu.be/TM9h%5fGpFlsA. Research Highlights: This study is the first to show that rhythmic coordination, a form of non‐linguistic interaction, can affect children's performance in a subsequent linguistic task.Eye‐movement data revealed that children's perspective‐taking in language processing was facilitated by prior asynchronous and antiphase synchronous musical interactions, but not by synchronous coordination.The results challenge the common "similar is better" view, suggesting that maintaining self‐other distinction may benefit social interactions that involve representing individual differences. [ABSTRACT FROM AUTHOR]

In cognitive science, altered Theory of Mind is a central pillar of etiological models of autism. Yet, recent evidence, showing comparable Theory of Mind abilities in autistic and non‐autistic people, draws a more complex picture and renders previous descriptions of Theory of Mind abilities in autism and their role in autistic symptomatology insufficient. Here, we addressed self‐other control as a potential candidate cognitive mechanism to explain subtle Theory of Mind reasoning differences between autistic and non‐autistic adults. We investigated flexible shifting between another's and one's own congruent or incongruent points of view, an ability that is important for reciprocal social interaction. Measuring response accuracy and reaction time in a multiple‐trial unexpected location false belief task, we found evidence for altered self‐other control in Theory of Mind reasoning in autistic adults, with a relative difficulty in flexibly considering the other's perspective and less interference of the other's incongruent viewpoint when their own perspective is considered. Our results add to previous findings that social cognitive differences are there but subtle and constitute one step further in characterizing Theory of Mind reasoning in autism and explaining communication and interaction difficulties with non‐autistic people in everyday life. Lay Summary: Researchers found that autistic people have problems solving Theory of Mind tasks and concluded that this problem explains communication and interaction difficulties in autism. However, in recent years, many studies found only little differences between autistic and non‐autistic participants in Theory of Mind tasks. This challenges the idea that Theory of Mind difficulties cause autistic symptoms. To explain the subtle differences between autistic and non‐autistic adults, we tested in this study how flexibly and efficiently they use their Theory of Mind to attribute beliefs to others and themselves. This is an important ability for smoothly interacting with others. In our task, we compared the response accuracy and reaction time of autistic and non‐autistic adults to determine how well they handle another person's and their own perspective. Autistic adults had more difficulties in flexibly switching toward the other's perspective. This can be a problem in real life social interactions, in which the perspective of the interaction partner must be continuously monitored to have a smooth and balanced conversation. Autistic participants were also less distracted by the other's perspective when it did not match one's own viewpoint. This can be an advantage in situations where such an influence might be distracting. With other earlier findings, our study shows that social cognitive differences between autistic and non‐autistic people are there but subtle. This finding helps to better understand Theory of Mind in autism and explain communication and interaction difficulties with non‐autistic people in everyday life. [ABSTRACT FROM AUTHOR]

Apples and their products exemplify the recently reemphasized link between dietary fruit intake and the alleviation of human disease. Their consumption does indeed improve human health due to their high phytochemical content. To identify potentially relevant articles from clinical trials, some epidemiological studies and meta‐analyses, and in vitro and in vivo studies (cell cultures and animal models), PubMed was searched from January 1, 2012, to May 15, 2022. This review summarized the potential effects of apple and apple products (juices, puree, pomace, dried apples, extracts rich in apple bioactives and single apple bioactives) on health. Apples and apple products have protective effects against cardiovascular diseases, cancer, as well as mild cognitive impairment and promote hair growth, healing of burn wounds, improve the oral environment, prevent niacin‐induced skin flushing, promote the relief of UV‐induced skin pigmentation, and improve the symptoms of atopic dermatitis as well as cedar hay fever among others. These effects are associated with various mechanisms, such as vascular endothelial protection, blood lipids lowering, anti‐inflammatory, antioxidant, antiapoptotic, anti‐invasion, and antimetastatic effects. Meanwhile, it has provided an important reference for the application and development of medicine, nutrition, and other fields. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p‐GSK‐3β, and β‐catenin, whereas it up‐regulated the expressions of GSK‐3β and p‐β‐catenin. Baicalin also reduced the expressions of Bcl‐2, C‐myc, Cyclin D1, MMP‐9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of −9 kcal/mol between the two. In addition, lentivirus‐mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK‐3β/β‐catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti‐HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK‐3β/β‐catenin signaling. [ABSTRACT FROM AUTHOR]

Many neuromuscular disorders can have a differential impact on a specific myofibre type, forming the central premise of this review. The many different skeletal muscles in mammals contain a spectrum of slow‐ to fast‐twitch myofibres with varying levels of protein isoforms that determine their distinctive contractile, metabolic, and other properties. The variations in functional properties across the range of classic 'slow' to 'fast' myofibres are outlined, combined with exemplars of the predominantly slow‐twitch soleus and fast‐twitch extensor digitorum longus muscles, species comparisons, and techniques used to study these properties. Other intrinsic and extrinsic differences are discussed in the context of slow and fast myofibres. These include inherent susceptibility to damage, myonecrosis, and regeneration, plus extrinsic nerves, extracellular matrix, and vasculature, examined in the context of growth, ageing, metabolic syndrome, and sexual dimorphism. These many differences emphasise the importance of carefully considering the influence of myofibre‐type composition on manifestation of various neuromuscular disorders across the lifespan for both sexes. Equally, understanding the different responses of slow and fast myofibres due to intrinsic and extrinsic factors can provide deep insight into the precise molecular mechanisms that initiate and exacerbate various neuromuscular disorders. This focus on the influence of different myofibre types is of fundamental importance to enhance translation for clinical management and therapies for many skeletal muscle disorders. [ABSTRACT FROM AUTHOR]

Azaserine is a bacterial metabolite containing a biologically unusual and synthetically enabling α‐diazoester functional group. Herein, we report the discovery of the azaserine (aza) biosynthetic gene cluster from Glycomyces harbinensis. Discovery of related gene clusters reveals previously unappreciated azaserine producers, and heterologous expression of the aza gene cluster confirms its role in azaserine assembly. Notably, this gene cluster encodes homologues of hydrazonoacetic acid (HYAA)‐producing enzymes, implicating HYAA in α‐diazoester biosynthesis. Isotope feeding and biochemical experiments support this hypothesis. These discoveries indicate that a 2‐electron oxidation of a hydrazonoacetyl intermediate is required for α‐diazoester formation, constituting a distinct logic for diazo biosynthesis. Uncovering this biological route for α‐diazoester synthesis now enables the production of a highly versatile carbene precursor in cells, facilitating approaches for engineering complete carbene‐mediated biosynthetic transformations in vivo. [ABSTRACT FROM AUTHOR]

Inspired by early proposals in philosophy, dominant accounts of language posit a central role for mutual knowledge, either encoded directly in common ground, or approximated through other cognitive mechanisms. Using existing empirical evidence from language and memory, we challenge this tradition, arguing that mutual knowledge captures only a subset of the mental states needed to support communication. In a novel theoretical proposal, we argue for a cognitive architecture that includes separate, distinct representations of the self and other, and a cognitive process that compares these representations continuously during conversation, outputting both similarities and differences in perspective. Our theory accounts for existing data, interfaces with findings from other cognitive domains, and makes novel predictions about the role of perspective in language use. We term this new account the Multiple Perspectives Theory of mental states in communication. [ABSTRACT FROM AUTHOR]

Recent metacognitive research using a partial knowledge task indicates that a firm understanding of 'knowing about knowing' develops surprisingly late, at around 6 years of age. To reveal the mechanisms subserving this development, the partial knowledge task was used in a longitudinal study with 67 children (33 girls) as an outcome measure at 5;9 (years;months). In addition, first- and second-order false belief was assessed at 4;2, 5;0, and 5;9. At 2;6, perspective taking and executive abilities were evaluated. Metacognition at 5;9 was correlated with earlier theory of mind and perspective taking - even when verbal intelligence and executive abilities were partialled out. This highlights the importance of perspective taking for the development of an understanding of one's own mind., (© 2020 The Authors. British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Dried fruit slices are important, healthy, and popular snacks and gain importance day by day due to their high nutritional content. In this context, this study mainly focused on the production of healthy apple chips snacks and the determination of degradation kinetics of antioxidant activity, total phenolic compounds, and color values of apple chip snacks during convective hot air drying at three different temperatures (45, 55, and 65°C) and sample thicknesses (1.5 and 5 ± 0.5 mm). The drying kinetics, desorption isotherms, activation energy, and half-life of the apple chip snack were also calculated. The Page and GAB models are the best models for the determination of the drying (>0.992) and desorption (>0.9979) behavior of apple snacks with the highest R2 values. The drying of all samples took place in the falling rate period. The Deff values increased depending on the increasing air temperature and slice thickness. The antioxidant activity, total phenolic compounds, and total color change of the 5 mm thick samples were degraded following the first-order reaction kinetics. The higher antioxidant activity, phenolic compounds, L∗ values, and lower half-life values were observed in conditions where the thickness (1.5 mm) and temperature (45°C) are low. The activation energy values calculated for the total phenolic compounds are higher than those calculated for the antioxidant activity. As a result, it can be concluded that apple chip snacks with high nutritional value can be produced by choosing low temperatures and slice thickness. [ABSTRACT FROM AUTHOR]

Objective: G‐protein coupled receptor 75 (GPR75) has been identified as the high‐affinity receptor of 20‐hydroxyeicosatetraenoic acid (20‐HETE), a vasoactive and proinflammatory lipid, and mice overproducing 20‐HETE have been shown to develop insulin resistance when fed a high‐fat diet (HFD), which was prevented by a 20‐HETE receptor blocker. Simultaneously, a large‐scale exome sequencing of 640,000 subjects identified an association between loss‐of‐function GPR75 variants and protection against obesity. Methods: Wild‐type (WT) and Gpr75‐deficient mice were placed on HFD for 14 weeks, and their obesity phenotype was examined. Results: Male and female Gpr75 null (knockout [KO]) and heterozygous mice gained less weight than WT mice when placed on HFD. KO mice maintained the same level of energy expenditure during HFD feeding, whereas WT mice showed a significant reduction in energy expenditure. Diet‐driven adiposity and adipocyte hypertrophy were greatly lessened in Gpr75‐deficient mice. HFD‐fed KO mice did not develop insulin resistance. Adipose tissue from Gpr75‐deficient mice had increased expression of thermogenic genes and decreased levels of inflammatory markers. Moreover, insulin signaling, which was impaired in HFD‐fed WT mice, was unchanged in KO mice. Conclusions: These findings suggest that GPR75 is an important player in the control of metabolism and glucose homeostasis and a likely novel therapeutic target to combat obesity‐driven metabolic disorders. [ABSTRACT FROM AUTHOR]

Starch is the most important energy‐providing component of food. It is useful for maintaining the structural and rheological consistency of food, ad thus, in turn, is responsible for maintaining the freshness of food. Polyphenols are present in plant products in huge amounts as secondary metabolites. Gallic acid, one of the potent plant polyphenols, has been reported to have excellent anti‐inflammatory, antioxidative, anticarcinogenic, microbicidal, and antidiabetic properties. Till date, very few articles on the starch–polyphenol inclusion complex are present. Quite a few hypotheses have been proposed as to how the formation of an inclusion complex of starch with polyphenol can slower the digestion or the hydrolysis of starch. The efficient qualities of starch–polyphenol systems, such as reduced starch digestion, lower blood glucose and preserving food freshness, have formed a necessity for investigation in this area. The focus of this review centers on the recent research on starch–polyphenol interactions and starch–gallic acid inclusion complexes in native and extruded food systems, as well as how the production of these complexes can aid in the treatment of diseases, particularly diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objectives: Swallow and cough dysfunction are possible surgical complications of lung transplantation (LT). We examined voluntary cough strength, sensorimotor reflexive cough integrity, and swallow‐related respiratory rate (RR) across swallowing safety and aspiration response groups in recovering LT recipients. Methods: Forty‐five LT recipients underwent flexible endoscopic evaluation of swallowing indexed by the validated Penetration Aspiration Scale. RR before and after a 3‐ounce water drinking task was measured. Voluntary and reflexive cough screening were performed to index motor and sensory outcomes. T‐tests, one‐way ANOVAs, and chi‐square (odds ratios) were used. Results: 60% of patients exhibited laryngeal penetration (n = 27) and 40% demonstrated tracheal aspiration (n = 18); 72% (n = 13) demonstrated silent aspiration. Baseline RR was higher in aspirators versus non‐aspirators (26.5 vs. 22.6, p = 0.04) and in silent aspirators compared to non‐silent aspirators (27.9 vs. 20.7, p = 0.01). RR change post‐swallowing did not differ between aspiration response groups; however, it was significantly higher in aspirators compared to non‐aspirators (3 vs. −2, p = 0.02). Compared to non‐silent aspirators, silent aspirators demonstrated reduced voluntary cough peak expiratory flow (PEF; 166 vs. 324 L/min, p = 0.01). PEF, motor and urge to cough reflex cough ratings did not differ between aspirators and non‐aspirators. Silent aspirators demonstrated a 7.5 times higher odds of failing reflex cough screening compared to non‐silent aspirators (p = 0.07). Conclusions: During the acute recovery period, all LT participants demonstrated some degree of unsafe swallowing and reduced voluntary cough strength. Silent aspirators exhibited elevated RR, reduced voluntary cough physiologic capacity to defend the airway, and a clinically distinguishable blunted motor response to reflex cough screening. [ABSTRACT FROM AUTHOR]