Whether ultra‐processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population‐based cohort of 98 ...265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra‐processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow‐up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra‐processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1:1.49; 95% confidence interval CI: 1.07‐2.07; Ptrend = .021) in a linear dose‐response manner (Pnonlinearity = .075). Subgroup analysis further found that the positive association of ultra‐processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1:2.17; 95% CI: 1.14‐4.15) than in those aged ≥65 years (HRquartile 4 vs 1:1.32; 95% CI: 0.88‐1.94), though the interaction test failed to achieve the statistical significance (Pinteraction = .061). These findings suggest that reducing ultra‐processed food consumption may be beneficial in decreasing pancreatic cancer incidence.
What's new?
“Ultra‐processed” foods, industrially formulated products consisting of ingredients extracted from foods, but no intact foods, now make up as much as 58.5% of Americans' daily calorie intake. Think frozen meals, hot dogs and packaged snacks. Here, the authors investigate the relationship between ultra‐processed foods and pancreatic cancer in a cohort of 98 265 American adults. High consumption of ultra‐processed foods was associated with increased risk of pancreatic cancer, and the association was more pronounced for those under age 65.
Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. The present study aimed to clarify this issue. A systematic search of PubMed ...and Embase was conducted through October 2018. Studies providing risk estimates of NAFLD and mortality were included. A random-effects model was employed to calculate summary risk estimates. Subgroup analyses were performed to identify potential effect modifiers. Fourteen studies, involving 498501 subjects and 24234 deaths, were included. Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without hazard ratio (HR) = 1.34; 95% confidence interval (CI) 1.17-1.54). The significantly positive association between NAFLD and all-cause mortality could not be modified by age, sex, follow-up duration, and adjustment for body mass index, diabetes, smoking or hypertension (all P
> 0.05), and remained in sensitivity analyses. No significant associations of NAFLD with CVD (HR = 1.13; 95% CI 0.92-1.38) and cancer (HR = 1.05; 95% CI 0.89-1.25) mortality were found. In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. These findings have important implications for decision making in public health and clinical practice, and highlight the urgency of developing effective treatments for NAFLD.
Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. ...We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person‐years of follow‐up and 100 PLC deaths during 1,198,021.3 person‐years of follow‐up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratiotertile 3 vs. 1: 0.44; 95% confidence interval: 0.24, 0.80; ptrend = 0.0065) and mortality (subdistribution hazard ratiotertile 3 vs. 1: 0.37; 95% confidence interval: 0.19, 0.71; ptrend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose–response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all pnonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose–response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.
What's new?
Magnesium is believed to be involved in cancer pathogenesis, with magnesium intake reducing the risk for a variety of cancers. Epidemiological studies on magnesium intake and primary liver cancer (PLC) remain scarce, however. Using prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, here the authors found that total (diet + supplements) and dietary magnesium intakes were inversely associated with risks of PLC incidence and mortality in a non‐linear dose–response manner. These findings suggest that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality in the US population.
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•UPLC-MS/MS was used to analyze bile acids (BAs) in serum, liver, colon, bile, and feces of UC mice.•The modified 16S rDNA high-throughput sequencing was performed to examine the gut ...microbiota of feces.•Baitouweng Tang can improve the bile acids and gut microbiota disorder by DSS-induced UC.•The mechanism of Baitouweng Tang therapeutic effect could be related to the by increasing the expression of FXR and TGR5.
In China, Baitouweng Tang (BTWT) is a commonly prescribed remedy for the treatment of ulcerative colitis (UC). Herein, the present study aims to assess the anti-colitis activity of BTWT and its underlying mechanisms in UC BALB/c mice. Induction of UC in BALB/c mice was carried out by adding 3.5% DSS in the drinking water of underlined mice. After UC induction, the mice were administrated with BTWT for 7 days. Clinical symptoms were assessed, followed by analyzing the bile acids (BAs) in serum, liver, colon, bile, and feces of UC mice through UPLC-MS/MS. The modified 16S rDNA high-throughput sequencing was carried out to examine the gut microbiota of feces. BTWT significantly improved the clinical symptoms such as and histological injury and colon shortening in UC induced mice. Furthermore, BTWT remarkably ameliorated colonic inflammatory response. After BTWT treatment, the increased concentrations of UDCA, HDCA, αMCA, βMCA, CA, and GLCA in UC were decreased, and the levels of some BAs, especially CA, αMCA, and βMCA were normalized. Moreover, the relative species abundance and gut microbiota diversity in the BTWT-exposed groups were found to be considerably elevated than those in the DSS-treated group. BTWT increased the relative abundance of Firmicutes, Proteobacteria, Actinobacteria, Tenericutes, and TM7, which were statistically lower in the fecal microbiota of UC mice. The relative abundance of Bacteroidetes was found to be elevated in the DSS group and normalized after BTWT treatment. BTWT increased the expression of FXR and TGR5 in the liver. BTWT administration improved DSS-induced mice signs by increasing the TGR5 and FXR expression levels. This result was achieved by the regulation of the BAs and gut microbiota.
Species of Baylisascaris (Nematoda: Ascarididae) are of great veterinary and zoonotic significance, owing to cause Baylisascariosis or Baylisascariasis in wildlife, captive animals and humans. ...However, the phylogenetic relationships of the current 10 Baylisascaris species remain unclear. Moreover, our current knowledge of the detailed morphology and morphometrics of the important zoonotic species B. procyonis is still insufficient. The taxonomical status of B. procyonis and B. columnaris remains under debate. In the present study, the detailed morphology of B. procyonis was studied using light and scanning electron microscopy based on newly collected specimens from the raccoon Procyon lotor (Linnaeus) in China. The results of the ASAP analysis and Bayesian inference (BI) using the 28S, ITS, cox1 and cox2 genetic markers did not support that B. procyonis and B. columnaris represent two distinct species. Integrative morphological and molecular assessment challenged the validity of B. procyonis, and suggested that B. procyonis seems to represent a synonym of B. columnaris. Molecular phylogenetic results indicated that the species of Baylisascaris were grouped into 4 clades according to their host specificity. The present study provided new insights into the taxonomic status of B. procyonis and preliminarily clarified the phylogenetic relationships of Baylisascaris species.
•Both airborne PBDD/Fs and PCDD/Fs around the MSWI show medium levels and TEQs.•Airborne dioxins around the MSWI show spatially declining trend with the distance.•Airborne PBDD/Fs and PCDD/Fs around ...the MSWI show distinct profiles and sources.•Meteorological factors exert apparent influence over the dioxin levels and sources.•Bioassay-based TEQs of dioxins are much higher than their concentration-based TEQs.
Municipal solid waste incinerator (MSWI) not only is deemed one of the uppermost sources of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), but also produces substantial amount of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) owing to the existence of brominated flame retardants (BFRs) in the waste. So far, however, PBDD/Fs in the vicinal environments of MSWI and their associated risks remain rarely studied. Based on a one-year passive air sampling (PAS) scheme, we investigated airborne PBDD/Fs and PCDD/Fs around a large-scale MSWI that has been operated for multi-years. Both the concentrations of PBDD/Fs and PCDD/Fs showed spatially decreasing trends with the distance away from the MSWI, confirming the influence of the MSWI on the dioxin levels in its ambient air. But its influence on PBDD/Fs was less because PBDD/Fs exhibit lower volatility and therefore lower gaseous concentrations than PCDD/Fs. Compared to the existing global data of airborne PCDD/Fs and PBDD/Fs, our data of the MSWI vicinity were at medium levels, despite PAS samples only represent the concentrations of gaseous dioxins in theory. The seasonal data suggest that meteorological conditions exerted apparent influences over the concentrations and sources of airborne dioxins around the MSWI. As for PCDD/Fs, the MSWI was diagnosed as their uppermost source, followed by local traffic and volatilization/deposition. Whereas the top three PBDD/F sources were related to PBDEs, bromophenol/bromobenzene, and traffic vehicles, respectively. The bioassay-derived TEQs based on the aryl hydrocarbon receptor activation of airborne dioxins around the MSWI were one or two orders of magnitudes higher than their concentration-based TEQs, and the corresponding carcinogenic risks at some MSWI-vicinal sites exceeded the acceptable threshold proposed by the U. S. EPA (10−6 ∼ 10−4) and deserve continuous attention.
Reinforcement learning (RL) stands as one of the three fundamental paradigms within machine learning and has made a substantial leap to build general-purpose learning systems. However, using ...traditional electrical computers to simulate agent-environment interactions in RL models consumes tremendous computing resources, posing a significant challenge to the efficiency of RL. Here, we propose a universal framework that utilizes a photonic integrated circuit (PIC) to simulate the interactions in RL for improving the algorithm efficiency. High parallelism and precision on-chip optical interaction calculations are implemented with the assistance of link calibration in the hybrid architecture PIC. By introducing similarity information into the reward function of the RL model, PIC-RL successfully accomplishes perovskite materials synthesis task within a 3472-dimensional state space, resulting in a notable 56% improvement in efficiency. Our results validate the effectiveness of simulating RL algorithm interactions on the PIC platform, highlighting its potential to boost computing power in large-scale and sophisticated RL tasks.
Abstract
Context
Current dietary guidelines recommend eggs as a part of a healthy diet. However, whether egg consumption is associated with risk of mortality remains controversial. Moreover, the ...dose-response association of egg consumption with risk of mortality has not been determined.
Objective
To determine the potential dose-response association of egg consumption with risk of mortality in the general population.
Data Sources
The PubMed and Embase databases were searched for publications meeting eligibility criteria through November 2021.
Data Extraction
Required data were extracted by 1 reviewer and then checked for accuracy by another reviewer. A random-effects dose-response meta-regression model was used to calculate the pooled risk estimates. A restricted cubic spline model was used to test nonlinearity. The certainty of evidence was assessed using the GRADE system.
Data Analysis
Nineteen prospective cohort studies, involving 1 737 893 participants, were included. The pooled hazard ratios for an increase of 1 egg/d were 1.08 (95%CI, 1.01–1.15) for all-cause mortality, 1.07 (95%CI, 0.97–1.18) for cardiovascular disease–caused mortality, and 1.16 (95%CI, 1.04–1.30) for cancer-caused mortality. The certainty of evidence for these observations was rated as very low. Nonlinear dose-response associations were found for egg consumption and all-cause, cardiovascular disease–caused, and cancer-caused mortality. Moreover, the positive association between egg consumption and all-cause mortality was more pronounced in studies with adjustment for blood cholesterol-related covariates than those without (Pinteraction = 0.011).
Conclusions
Greater amount of egg consumption confers higher risks of death from all causes, cardiovascular disease, and canc er in a nonlinear dose-response pattern. These findings should be treated with caution and need to be confirmed by future studies.
Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated ...structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development.
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•The N-terminal tails of LGG-1 and LGG-2 adopt unique closed and open forms•lgg-2 exhibits temporal-specific and cargo-specific functions in autophagy•LGG-1 and LGG-2 differentially interact with autophagy substrates and ATG proteins•Lipidated LGG-1 and LGG-2 exhibit different membrane tethering and fusion activity
Wu et al. present high-resolution crystal structures of LGG-1 and LGG-2, two C. elegans homologs of the yeast autophagy protein ATG8. Structural differences between the two proteins reflect their differential functions in degradation of protein aggregates during development.
The role of signal transducer and activator of transcription 3 (Stat3) in liver fibrosis is still controversial. Since hepatic stellate cells (HSCs) and transforming growth factor-β1 (TGF-β1) are ...central to the fibrogenesis, our goal was to clarify the mechanism of Stat3 crosslinking of TGF-β1 signaling.
Stat3, TGF-β1 mRNA and protein expressions were examined in liver tissues of chronic hepatitis B (CHB) patients and diethylinitrosamine (DEN)-induced rat fibrosis model. The effect of Stat3 activation or suppression on TGF-β1 signaling in HSCs was tested in vitro and in vivo.
Stat3 expression as well as TGF-β1 was increased in CHB patients and DEN-induced fibrosis rat model. This was strongly correlated with increase in fibrosis staging. TGF-β1, a mediator of fibrosis, was enhanced by Stat3, but suppressed by siRNA-mediated RNA knockdown of Stat3 (siStat3) or Janus kinase 2 inhibitor (AG490) both in vivo and in vitro. Stat3 crosslinking TGF-β1 signaling plays an important role in HSC activation and increasing fibrosis related products. TGF-β1 could not achieve profibrogenic cytokine and anti-apoptosis characteristics without Stat3 activation in HSCs.
We provide a novel role of Stat3 cooperating TGF-β1 in activation and anti-apoptotic effect of HSCs. Stat3 worsens liver fibrosis through the up-regulation of TGF-β1 and fibrotic product expression.
•Stat3 and TGF-β1 expression is identified in fibrotic hepatic tissues.•TGF-β1 is activated by IL-6/Stat3 in vivo and in vitro.•Stat3 crosslinking TGF-β1 facilitates HSC activation and aggravates fibrogenesis.•TGF-β1 could not achieve anti-apoptosis function without Stat3 activation in HSC.•Suppression Stat3 can reverse liver fibrosis in rats treated with DEN.
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