Chlorogenic Acid/Linoleic Acid-Fortified Wheat-Resistant Starch Ameliorates High-Fat Diet-Induced Gut Barrier Damage by Modulating Gut Metabolism.

This study aimed to investigate alterations in gut microbiota and metabolites mediated by wheat-resistant starch and its repair of gut barrier dysfunction induced by a high-fat diet (HFD). Structural data revealed that chlorogenic acid (CA)/linoleic acid (LA) functioned through noncovalent interactions to form a more ordered structure and fortify antidigestibility in wheat starch (WS)-CA/LA complexes; the resistant starch (RS) contents of WS-CA, WS-LA, and WS-CA-LA complexes were 23.40 ± 1.56%, 21.25 ± 1.87%, and 35.47 ± 2.16%, respectively. Dietary intervention with WS-CA/LA complexes effectively suppressed detrimental alterations in colon tissue morphology induced by HFD and repaired the gut barrier in ZO-1 and MUC-2 levels. WS-CA/LA complexes could augment gut barrier-promoting microbes including Parabacteroides, Bacteroides, and Muribaculum, accompanied by an increase in short-chain fatty acids (SCFAs) and elevated expression of SCFA receptors. Moreover, WS-CA/LA complexes modulated secondary bile acid metabolism by decreasing taurochenodeoxycholic, cholic, and deoxycholic acids, leading to the activation of bile acid receptors. Collectively, this study offered guiding significance in the manufacture of functional diets for a weak gut barrier.

Transport and risk of airborne pathogenic microorganisms in the process of decentralized sewage discharge and treatment.

Sewage treatment processes are a critical anthropogenic source of bioaerosols and may present significant health risks to plant workers. Compared with the specialization and scale of urban sewage treatment, many decentralized treatment models are flexible and extensive. These treatment facilities are usually close to residential areas owing to the pipe network layout and other restrictions. Bioaerosols generated by these facilities may present a serious and widespread occupational and non-occupational exposure risk to nearby residents, particularly the elderly and children. An understanding of the characteristics and exposure risks of bioaerosols produced during decentralized sewage treatment is lacking. We compared bioaerosol emission characteristics and potential exposure risks under four decentralized sewage discharge methods and treatment models: small container collection (SCC), open-channel discharge (OCD), single household/combined treatment (SHCT), and centralized treatment (CT) in northwest China. The OCD mode had the highest bioaerosol production, whereas the CT mode had the lowest. The OCD model contained the most pathogenic bacterial species, up to 43 species, including Sphingomonas, Pseudomonas, Cladosporium, and Alternaria. Risk assessments indicated bioaerosol exposure was lower in the models with sewage treatment (SHCT and CT) than in those without (SCC and OCD). Different populations exhibited large variations in potential risks owing to differences in time spent indoors and outdoors. The highest risk was observed in males exposed to the SCC model. This study provides a theoretical basis and theories for the future joint prevention and control of the bioaerosol exposure risk from decentralized sewage treatment.

Mendelian randomization: causal inference leveraging genetic data.

Mendelian randomization (MR) leverages genetic information to examine the causal relationship between phenotypes allowing for the presence of unmeasured confounders. MR has been widely applied to unresolved questions in epidemiology, making use of summary statistics from genome-wide association studies on an increasing number of human traits. However, an understanding of essential concepts is necessary for the appropriate application and interpretation of MR. This review aims to provide a non-technical overview of MR and demonstrate its relevance to psychiatric research. We begin with the origins of MR and the reasons for its recent expansion, followed by an overview of its statistical methodology. We then describe the limitations of MR, and how these are being addressed by recent methodological advances. We showcase the practical use of MR in psychiatry through three illustrative examples - the connection between cannabis use and psychosis, the link between intelligence and schizophrenia, and the search for modifiable risk factors for depression. The review concludes with a discussion of the prospects of MR, focusing on the integration of multi-omics data and its extension to delineating complex causal networks.

Pre-dry heat treatment alters the structure and ultimate in vitro digestibility of wheat starch-lipids complex in hot-extrusion 3D printing.

Herein, we proposed dry heat treatment (DHT) as a pre-treatment method for modifying printed materials, with a particular focus on its application in the control of starch-lipid interactions during hot-extrusion 3D printing (HE-3DP). The results showed that pre-DHT could promote the complexation of wheat starch (WS) and oleic acid (OA)/corn oil (CO) during HE-3DP and thus increase the resistant starch (RS) content. From the structural perspectives, pre-DHT could break starch molecular chains into lower relative molecular weight which enhanced the starch-lipids hydrophobic interactions to form the V-type crystalline structure during HE-3DP. Notably, pre-DHT could also induce the formation of complexed structure which was maintained during HE-3DP. Compared with CO, OA with linear hydrophobic chains was easier to enter the spiral cavity of starch to form more ordered structures, resulting in higher RS content of 27.48 %. Overall, the results could provide basic data for designing nutritional starchy food systems by HE-3DP.

Bidirectional two-sample Mendelian randomization study of differential white blood cell counts and schizophrenia.

BACKGROUND: Schizophrenia and white blood cell counts (WBC) are both complex and polygenic traits. Previous evidence suggests that increased WBC are associated with higher all-cause mortality, and other studies have found elevated WBC in first-episode psychosis and chronic schizophrenia. However, these observational findings may be confounded by antipsychotic exposures and their effects on WBC. Mendelian randomization (MR) is a useful method for examining the directions of genetically-predicted relationships between schizophrenia and WBC. METHODS: We performed a two-sample MR using summary statistics from genome-wide association studies (GWAS) conducted by the Psychiatric Genomics Consortium Schizophrenia Workgroup (N = 130,644) and the Blood Cell Consortium (N = 563,946). The MR methods included inverse variance weighted (IVW), MR Egger, weighted median, MR-PRESSO, contamination mixture, and a novel approach called mixture model reciprocal causal inference (MRCI). False discovery rate was employed to correct for multiple testing. RESULTS: Multiple MR methods supported bidirectional genetically-predicted relationships between lymphocyte count and schizophrenia: IVW (b = 0.026; FDR p-value = 0.008), MR Egger (b = 0.026; FDR p-value = 0.008), weighted median (b = 0.013; FDR p-value = 0.049), and MR-PRESSO (b = 0.014; FDR p-value = 0.010) in the forward direction, and IVW (OR = 1.100; FDR p-value = 0.021), MR Egger (OR = 1.231; FDR p-value < 0.001), weighted median (OR = 1.136; FDR p-value = 0.006) and MRCI (OR = 1.260; FDR p-value = 0.026) in the reverse direction. MR Egger (OR = 1.171; FDR p-value < 0.001) and MRCI (OR = 1.154; FDR p-value = 0.026) both suggested genetically-predicted eosinophil count is associated with schizophrenia, but MR Egger (b = 0.060; FDR p-value = 0.010) and contamination mixture (b = -0.013; FDR p-value = 0.045) gave ambiguous results on whether genetically predicted liability to schizophrenia would be associated with eosinophil count. MR Egger (b = 0.044; FDR p-value = 0.010) and MR-PRESSO (b = 0.009; FDR p-value = 0.045) supported genetically predicted liability to schizophrenia is associated with elevated monocyte count, and the opposite direction was also indicated by MR Egger (OR = 1.231; FDR p-value = 0.045). Lastly, unidirectional genetic liability from schizophrenia to neutrophil count were proposed by MR-PRESSO (b = 0.011; FDR p-value = 0.028) and contamination mixture (b = 0.011; FDR p-value = 0.045) method. CONCLUSION: This MR study utilised multiple MR methods to obtain results suggesting bidirectional genetic genetically-predicted relationships for elevated lymphocyte counts and schizophrenia risk. In addition, moderate evidence also showed bidirectional genetically-predicted relationships between schizophrenia and monocyte counts, and unidirectional effect from genetic liability for eosinophil count to schizophrenia and from genetic liability for schizophrenia to neutrophil count. The influence of schizophrenia to eosinophil count is less certain. Our findings support the role of WBC in schizophrenia and concur with the hypothesis of neuroinflammation in schizophrenia.

Introduction of chlorogenic acid into thermal processed starch- oleic acid system controls the ordered structure and inhibits oleic acid oxidation through molecular interactions.

In this study, the effects of starch- oleic acid (OA)- chlorogenic acid (CA) molecular interaction on OA oxidation during thermal processing were investigated based on structural analysis, oxidation characteristics and quantum calculations. The results showed that in the ternary system, on the one hand, OA could enter the spiral cavity of starch through hydrophobic forces and form V-type crystalline structure, which delayed its oxidation. On the other hand, CA could further inhibit the oxidation of OA through free radical reaction and did not affect the molecular interactions between OA and starch due to the steric hindrance and hydrophily. Notably, starch-OA-CA interactions could effectively decrease total oxidation value (19.07), prolong the induction time of oxidation (114.6 min) and reduce the abundance of oxidation products through hydrogen atom transfer reactions with active phenolic hydroxyl to protect the α-methylene groups at C=C. Overall, these results provided insights into functional property regulation by the interaction of starch-based multi-component systems.

Reciprocal causation mixture model for robust Mendelian randomization analysis using genome-scale summary data.

Mendelian randomization using GWAS summary statistics has become a popular method to infer causal relationships across complex diseases. However, the widespread pleiotropy observed in GWAS has made the selection of valid instrumental variables problematic, leading to possible violations of Mendelian randomization assumptions and thus potentially invalid inferences concerning causation. Furthermore, current MR methods can examine causation in only one direction, so that two separate analyses are required for bi-directional analysis. In this study, we propose a ststistical framework, MRCI (Mixture model Reciprocal Causation Inference), to estimate reciprocal causation between two phenotypes simultaneously using the genome-scale summary statistics of the two phenotypes and reference linkage disequilibrium information. Simulation studies, including strong correlated pleiotropy, showed that MRCI obtained nearly unbiased estimates of causation in both directions, and correct Type I error rates under the null hypothesis. In applications to real GWAS data, MRCI detected significant bi-directional and uni-directional causal influences between common diseases and putative risk factors.

Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits.

Power calculation is a necessary step when planning genome-wide association studies (GWAS) to ensure meaningful findings. Statistical power of GWAS depends on the genetic architecture of phenotype, sample size, and study design. While several computer programs have been developed to perform power calculation for single SNP association testing, it might be more appropriate for GWAS power calculation to address the probability of detecting any number of associated SNPs. In this paper, we derive the statistical power distribution across causal SNPs under the assumption of a point-normal effect size distribution. We demonstrate how key outcome indices of GWAS are related to the genetic architecture (heritability and polygenicity) of the phenotype through the power distribution. We also provide a fast, flexible and interactive power calculation tool which generates predictions for key GWAS outcomes including the number of independent significant SNPs, the phenotypic variance explained by these SNPs, and the predictive accuracy of resulting polygenic scores. These results could also be used to explore the future behaviour of GWAS as sample sizes increase further. Moreover, we present results from simulation studies to validate our derivation and evaluate the agreement between our predictions and reported GWAS results.

Effect of starch-catechin interaction on regulation of starch digestibility during hot-extrusion 3D printing: Structural analysis and simulation study.

Recent developments of hot-extrusion 3D printing (HE-3DP) have made it possible to manipulate starch digestibility. This work investigated the regulating mechanism of starch-catechin (EC) interactions on rice starch digestibility during HE-3DP by using modern analytical techniques and computational models. The results showed that the HE-3DP processing with starch-EC interactions could significantly decrease the starch digestibility (p < 0.05) due to the formation of ordered structures including short-range ordered structure, nano-aggregates and V-type crystalline structure. Meanwhile, molecular dynamics simulations were performed to reveal the mechanism of EC as an enzyme inhibitor to enhance the resistant starch contents of rice starch to 46.1%. Results showed that EC could loosely attach to starch chains, thereby facilitating binding to Trp59 of pancreatic α-amylase and preventing starch from binding to its active pocket. These findings provide useful structural information for EC to reduce starch digestibility in the HE-3DP environment.

Metal Hydrides with In Situ Built Electron/Ion Dual-Conductive Framework for Stable All-Solid-State Li-Ion Batteries.

Due to their high theoretical specific capacity, metal hydrides are considered to be one of the most promising anode material for all-solid-state Li-ion batteries. Their practical application suffers, however, from the poor cycling stability and sluggish kinetics. Herein, we report the in situ fabrication of MgH2 and Mg2NiH4 that are uniformly space-confined by inactive Nd2H5 frameworks with high Li-ion and electron conductivity through facile hydrogenation of single-phase Nd4Mg80Ni8 alloys. The formation of MgH2 and Mg2NiH4 nanocrystals could not only shorten Li-ion and electron diffusion pathways of the whole electrode but also relieve the induced stress upon volume changes. Additionally, the robust frameworks constructed by homogeneous distribution of inactive Nd2H5 based on a molecular level could effectively alleviate the volume expansion and phase separation of thus-confined MgH2 and Mg2NiH4. More importantly, it is theoretically and experimentally verified that the uniform distribution of Nd2H5, which is an electronic conductor with a Li-ion diffusion barrier that is much lower than that of MgH2 and Mg2NiH4, could further facilitate the electron and Li-ion transfer of MgH2 and Mg2NiH4. Consequently, the space-confined MgH2 and Mg2NiH4 deliver a reversible capacity of 997 mAh g-1 at 2038 mA g-1 after 100 cycles.

Control of starch-lipid interactions on starch digestibility during hot-extrusion 3D printing for starchy foods.

The nutritional design of personalized starchy foods has become a research hotspot in the field of food science. Driven by the immense functional and nutritional implications of starch-lipid binary interactions, this study is aimed at designing starch digestibility by controlling the interaction between starch and glycerol monostearate (GMS)/stearic acid (SA) using a hot-extrusion 3D printing (HE-3DP) environment. The results indicated that the thermal shear force in the HE-3DP environment promoted hydrophobic interactions between starch and lipids, forming a V-type starch-lipid complex with a compact and ordered structure, thus enhancing enzymatic resistance. Compared with GMS, SA with linear hydrophobic chains was inclined to compound with starch to form a more ordered structure. Interestingly, the slowly digestible starch (SDS) and resistant starch (RS) content reached 25.06% when the added SA content was 10%. Besides, correlations between the structural parameters and digestibility were established, which provided crucial information for designing nutritional starchy food systems using HE-3DP.

Bioleaching Performance of Titanium from Bauxite Residue Under a Continuous Mode Using Penicillium Tricolor.

The present study performed a continuous mode of bioleaching to investigate the leaching efficiency of Titanium (Ti) from bauxite residue using Penicillium Tricolor at between 4% and 12% pulp densities during a 120-day running. Obtained results of the current study showed that increased pulp density led to a decrease in biomass, dissolved oxygen, and amount of leaching Ti as well as an increase in pH value. Further, it was found that efficiency of bioleaching can be enhanced by increasing the rate of aeration, retention time, and concentration of carbon source. However, it was also evident that, at high pulp density, excessive agitation did not give an expected leaching efficiency but a collapse of biomass. In addition, results of the present study showed that the maximum leaching amount of Ti was 3202 mg/L with a corresponding leaching ratio of 50.35% during the whole bioleaching process. Moreover, it was noted that the biomass showed a significant negative correlation with the pH value and dissolved oxygen. However, the biomass showed a significant positive correlation with leaching amount of Ti and thus indicate that microbial metabolic activities are the uppermost factor affecting the continuous leaching performance.

Visualizing Graph Neural Networks With CorGIE: Corresponding a Graph to Its Embedding.

Graph neural networks (GNNs) are a class of powerful machine learning tools that model node relations for making predictions of nodes or links. GNN developers rely on quantitative metrics of the predictions to evaluate a GNN, but similar to many other neural networks, it is difficult for them to understand if the GNN truly learns characteristics of a graph as expected. We propose an approach to corresponding an input graph to its node embedding (aka latent space), a common component of GNNs that is later used for prediction. We abstract the data and tasks, and develop an interactive multi-view interface called CorGIE to instantiate the abstraction. As the key function in CorGIE, we propose the K-hop graph layout to show topological neighbors in hops and their clustering structure. To evaluate the functionality and usability of CorGIE, we present how to use CorGIE in two usage scenarios, and conduct a case study with five GNN experts. Availability: Open-source code at https://github.com/zipengliu/corgie-ui/, supplemental materials & video at https://osf.io/tr3sb/.

Susceptibility of ECE1 polymorphisms to Hirschsprung's disease in southern Chinese children.

Background: Hirschsprung's disease (HSCR) is currently considered to be a congenital gastrointestinal malformation caused mainly by genetic factors. Endothelin Converting Enzyme-1 (ECE1) has been reported to be associated with HSCR. However, the relationship between ECE1 single nucleotide polymorphism (SNP) rs169884 and HSCR in the southern Chinese population remains unknown. Methods: 1,470 HSCR patients and 1,473 controls from a southern Chinese population were recruited. The intronic SNP rs169884 in ECE1 was genotyped in all samples. We tested the association between rs169884 and HSCR under various genetic models. We also evaluated the effect of rs169884 on HSCR subtypes, including short-segment HSCR (S-HSCR), long-segment HSCR (L-HSCR) and total colonic aganglionosis (TCA). External epigenetic data were integrated to investigate the potential biological function of rs169884. Results: Chromatin states data from derived neuron cells or fetal colon tissue revealed that rs169884 might control ECE1 expression through regulating its enhancer function. We did not find a significant association between rs169884 and HSCR. For HSCR subtypes, although no significant associations were detected between rs169884 and S-HSCR (OR = 1.00, 95% CI: 0.89∼1.12, Padj = 0.77) or TCA (OR = 1.00, 95% CI: 0.72∼1.38, Padj = 0.94), we found that rs169884 could increase the risk of L-HSCR (OR = 1.23, 95% CI 1.02∼1.45, Padj = 0.024). Conclusion: These results suggested that rs169884 might play a regulatory role for ECE1 expression and increase susceptibility of L-HSCR in southern Chinese children.

Numerical study of transverse position monitor and compensation for x-ray polarization diagnosis.

Diagnosing free electron laser (FEL) polarization is critical for polarization-modulated research such as x-ray FEL diffraction imaging and probing material magnetism. In an electron time-of-flight (eTOF) polarimeter, the flight time and angular distribution of photoelectrons were designed based on x-ray polarimetry for on-site diagnosis. However, the transverse position of x-ray FEL pulses introduces error into the measured photoelectron angular distribution. This work, thus, proposes a method of compensating transverse position jitters for the polarization by the eTOF polarimeter itself without an external x-ray beam-position monitor. A comprehensive numerical model is developed to demonstrate the feasibility of the compensation method, and the results reveal that a spatial resolution of 20 µm and a polarity improved by 0.02 are possible with fully polarized FEL pulses. The impact of FEL pulses and a method to calibrate their linearity are also discussed.

Effect of stearic acid on the microstructural, rheological and 3D printing characteristics of rice starch.

The aim of this study was to investigate the changes of the microstructural, rheological and printing properties of rice starch-stearic acid (SA) paste during the hot-extrusion 3D printing (HE-3DP). The results showed that starch chains could complex with SA to form V-type crystalline structure and its molecular kinematic behaviors were changed under shear force, and crystalline structure were then embedded and rearranged to constitute an ordered sea-island structure, thus improving the rigidity and dynamic storage modulus of network structure, leading to the increased layer number. Interestingly, with the increase of SA addition, the network structure became weakened and the viscosity decreased which might due to the destroyed continuity and the breaking of entanglement and hydrogen bonding between starch chains, and finally impairing the printing accuracy of objects. Overall, this study provided important information for the application of lipid in the preparation of starch-based food by HE-3DP.

Up-regulation of circRNA_0068481 promotes right ventricular hypertrophy in PAH patients via regulating miR-646/miR-570/miR-885.

CircRNA-0068481 and several miRNAs are important in the pathogenesis of right ventricular hypertrophy (VH), while the inhibition of eye absent transcriptional coactivator and phosphatase 3 (EYA3) was proved to reverse vascular remodelling in rats. In this study, we tried to study the diagnostic value and mechanistic role of circRNA_0068481 in the diagnosis of RVH in PAH patients. qPCR was done to measure circRNA-0068481, miR-646, miR-750, miR-885 and EYA3 mRNA expression. Luciferase assay was done to explore the regulatory relationship between circRNA-0068481/EYA3 and the miRNAs. Western blot was done to measure EYA3 expression in AC16 cells. The expression of circRNA-0068481, miR-646 and miR-570 showed a considerable capability to diagnose RVH in PAH patients. The luciferase activity of circRNA-0068481 was remarkably suppressed by miR-646, miR-570 or miR-885. The luciferase signal of EYA3 was also inhibited by miR-646, miR-570 and miR-885. Up-regulation of circRNA-0068481 expression in AC16 significantly decreased miR-646, miR-570 and miR-885 expression, and up-regulated EYA3 expression, whereas circRNA-0068481 down-regulation significantly increased miR-646, miR-570 and miR-885 expression, and repressed EYA3 expression. CircRNA_0068481 sponged several miRNAs including miR-646, miR-570 and miR-885. These miRNAs were all found to target the expression of EYA3 mRNA, which is involved in the onset of right ventricular hypertrophy. Therefore, it can be concluded that the up-regulation of circRNA_0068481 can predict the diagnosis of right ventricular hypertrophy in pulmonary arterial hypertension patients.

The support of genetic evidence for cardiovascular risk induced by antineoplastic drugs.

Cardiovascular dysfunction is one of the most common complications of long-term cancer treatment. Growing evidence has shown that antineoplastic drugs can increase cardiovascular risk during cancer therapy, seriously affecting patient survival. However, little is known about the genetic factors associated with the cardiovascular risk of antineoplastic drugs. We established a compendium of genetic evidence that supports cardiovascular risk induced by antineoplastic drugs. Most of this genetic evidence is attributed to causal alleles altering the expression of cardiovascular disease genes. We found that antineoplastic drugs predicted to induce cardiovascular risk are significantly enriched in drugs associated with cardiovascular adverse reactions, including many first-line cancer treatments. Functional experiments validated that retinoid X receptor agonists can reduce triglyceride lipolysis, thus modulating cardiovascular risk. Our results establish a link between the causal allele of cardiovascular disease genes and the direction of pharmacological modulation, which could facilitate cancer drug discovery and clinical trial design.

Coronary heart disease is associated with nonalcoholic fatty liver disease in patients without hypertension and diabetes.

This study was performed to explore the relationship between coronary heart disease (CHD) and nonalcoholic fatty liver disease (NAFLD) in patients without hypertension and diabetes with a focus on predicting CHD.In total, 78 consecutive patients without hypertension and diabetes who were suspected of CHD underwent coronary angiography (CAG) or computed tomography CAG. They were segregated into the CHD and non-CHD group according to the CAG or computed tomography angiography results. The Gensini score was calculated based on CAG results in the CHD group. All patients underwent ultrasonographic measurement of the liver, subcutaneous fat, and visceral fat thickness.The CHD and the Gensini score were significantly correlated with V1, V2, and NAFLD. As the grade of NAFLD increases, the Gensini score was increased. After correcting for confounding factors, NAFLD (B = 2.474, P < .001, 95% confidence interval: 3.32-42.406) and cholesterol (B = 1.176, P = 0.025, 95% confidence interval: 1.155-9.101) were predictor for CHD.The CHD is associated with NAFLD in the patients without hypertension and diabetes. The high-grade NAFLD may be predicted the risk of CHD in patients without hypertension and diabetes.