Layer-Dependent Electromechanical Response in Twisted Graphene Moiré Superlattices.

The coupling of mechanical deformation and electrical stimuli at the nanoscale has been the subject of intense investigation in the realm of materials science. Recently, twisted van der Waals (vdW) materials have emerged as a platform for exploring exotic quantum states. These states are intimately tied to the formation of moiré superlattices, which can be visualized by directly exploiting the electromechanical response. However, the origin of the response, even in twisted bilayer graphene (tBLG), remains unsettled. Here, employing lateral piezoresponse force microscopy (LPFM), we investigate the electromechanical responses of marginally twisted graphene moiré superlattices with different layer thicknesses. We observe distinct LPFM amplitudes and spatial profiles in tBLG and twisted monolayer-bilayer graphene (tMBG), exhibiting effective in-plane piezoelectric coefficients of 0.05 and 0.35 pm/V, respectively. Force tuning experiments further underscored a marked divergence in their responses. The contrasting behaviors suggest different electromechanical couplings in tBLG and tMBG. In tBLG, the response near the domain walls is attributed to the flexoelectric effect, while in tMBG, the behaviors can be comprehended within the context of the piezoelectric effect. Our results not only provide insights into electromechanical and corporative effects in twisted vdW materials with different stacking symmetries but may also offer a way to engineer them at the nanoscale.

COVID-19 and retinal layer thickness: A bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have reported that COVID-19 is associated with alterations in retinal layer thickness, including changes in the ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL). However, the causal relationships remain unknown. Therefore, we assessed the direction and strength of the causal relationship between COVID-19 and GCIPL and RNFL thicknesses using a bidirectional two-sample Mendelian randomization (MR) design. METHODS: Data were obtained from a large-scale COVID-19 Host Genetics Initiative (Nsample = 6,512,887), GCIPL dataset (Ncase = 31,434), and RNFL dataset (Ncase = 31,434). The inverse-variance weighted (IVW) method is the primary approach used to estimate causal effects. MR Egger, weighted median, weighted mode, MR Egger (bootstrap), and penalized weighted median methods were applied. Sensitivity analyses were implemented with RadialMR, MRPRESSO, MR-Egger regression, Cochran's Q statistic, leave-one-out analysis, and the funnel plot. RESULTS: Forward MR analysis revealed that genetically identified COVID-19 susceptibility significantly increased the risk of GCIPL thickness (OR = 2.428, 95 % confidence interval [CI]:1.493-3.947, PIVW = 3.579 × 10-4) and RNFL thickness (OR = 1.735, 95 % CI:1.198-2.513, PIVW = 3.580 × 10-3) after Bonferroni correction. Reverse MR analysis did not indicate a significant causal association between GCIPL and RNFL thicknesses and COVID-19 phenotypes. No significant horizontal pleiotropy was found in the sensitivity analysis. CONCLUSIONS: The host genetic liability to COVID-19 susceptibility was causally associated with increased GCIPL and RNFL thicknesses. Documenting this association increases our understanding of the pathophysiological mechanisms underlying COVID -19 susceptibility in retinopathy.

Genetically predicted processed meat, red meat intake, and risk of mental disorders: A multivariable Mendelian randomization analysis.

BACKGROUND: Previous observational studies have highlighted potential links between the consumption of processed meat and red meat (such as pork, mutton, and beef intake) and the occurrence of mental disorders. However, it is unclear whether a causal association exists. Therefore, we employed the Mendelian randomization (MR) study to investigate the causal effects of genetically predicted processed meat and red meat on mood disorders (MD), anxiety disorders (AD), and major depressive disorder (MDD). METHODS: Genetic instruments for processed and red meat were selected from the Genome-Wide Association Study (GWAS) of the UK Biobank Study. Their associations with MD (42,746 cases 254,976), AD (35,385 cases and 254,976 controls), and MDD (38,225 cases and 299,886 controls) were obtained from the FinnGen Consortium. The inverse variance weighted (IVW) method was the primary method for two-sample MR analysis. Additionally, we employed complementary analysis to assess the robustness of our MR findings (eg, MR Egger and weighted median). We also conducted multiple sensitivity analyses to investigate horizontal pleiotropy and heterogeneity. Moreover, we performed a univariate and multivariable MR (MVMR) study to evaluate these associations. RESULTS: In our univariate MR analysis, we observed that genetically predicted beef intake was associated with a reduced risk of MD [odds ratio (OR) = 0.403, 95 % confidence interval (CI) = 0.246-0.659; PIVW = 4.428 × 10-5], AD (OR = 0.443, 95 % CI = 0.267-0.734; PIVW = 1.563 × 10-3), and MDD (OR = 0.373, 95 % CI = 0.216-0.643; PIVW = 3.878 × 10-4). After adjusting for processed meat, pork, and mutton intake in the MVMR analysis, the protective association of beef intake against MD and MDD remained. However, there was no substantial evidence indicating a significant causal relationship between processed meat, pork, and mutton intake and the occurrence of mental disorders. Furthermore, our sensitivity analysis revealed no significant evidence of horizontal pleiotropy. CONCLUSION: These findings support a causal relationship between genetically predicted beef intake and reducing the risk of MD and MDD.

Genetic Insights into Glycine's Protective Role Against CAD - European and East Asia, 2015 and 2020.

Introduction: The purpose of this study is to examine the potential causal relationship between levels of circulating glycine and coronary artery disease (CAD) using a two-step Mendelian randomization (MR) analysis. Methods: We analyzed data from genome-wide association studies (GWAS) conducted on European and East Asian populations. To assess the causal effects of circulating glycine levels on the risk of CAD. We used the inverse-variance weighting (IVW), weighted median (WM), MR-Egger, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Furthermore, we conducted mediation analysis to investigate the contribution of blood pressure and other cardiovascular disease-related traits. Results: The two-step Mendelian randomization analysis revealed that higher levels of glycine in the blood were associated with a reduced risk of CAD in Europeans [odds ratio ( OR)=0.84, 95% confidence interval ( CI): 0.72, -0.98; P=0.029] and East Asians: ( OR=0.76, 95% CI: 0.66, -0.89; P=3.57×10 -4). Sensitivity analysis confirmed the robustness of these findings. Additionally, our results suggest that about 6.06% of the observed causal effect is mediated through genetically predicted systolic blood pressure (SBP) in the European population. Discussion: Our results contribute to the current knowledge regarding the involvement of glycine in the progression of CAD, and provide valuable methodological insights for the prevention and treatment of this condition.

Effects of Phlorotannins from Sargassum on In Vitro Rumen Fermentation, Microbiota and Fatty Acid Profile.

The fatty acid profiles of ruminant-derived products are closely associated with human health. Ruminal microbiota play a vital role in modulating rumen biohydrogenation (BH). The aim of this study was to assess the influence of dietary supplementation with phlorotannins (PTs) extracted from Sargassum on rumen fermentation, fatty acid composition and bacterial communities by an in vitro culture study. The inclusion of PTs in the diet increased dry matter digestibility and gas production, and reduced ammonia-N concentration and pH. PT extract inhibited rumen BH, increasing the content of trans-9 C18:1, cis-9 C18:1, trans-9 and trans-12 C18:2 and reducing C18:0 concentration. 16S rRNA sequencing revealed that PTs caused an obvious change in rumen bacterial communities. The presence of Prevotella decreased while carbohydrate-utilizing bacteria such as Prevotellaceae_UCG-001, Ruminococcus, Selenomonas, Ruminobacter and Fibrobacter increased. Correlation analysis between rumen FA composition and the bacterial microbiome revealed that Prevotellaceae_UCG-001, Anaerovorax, Ruminococcus, Ruminobacter, Fibrobacter, Lachnospiraceae_AC2044_group and Clostridia_UCG-014 might have been involved in the BH process. In conclusion, the results suggest that the inclusion of PTs in the diet improved rumen fermentation and FA composition through modulating the rumen bacterial community.

Carbon Nanocage with Maximum Utilization of Atomically Dispersed Iron as Efficient Oxygen Electroreduction Nanoreactor.

As key parameters of electrocatalysts, the density and utilization of active sites determine the electrocatalytic performance toward oxygen reduction reaction. Unfortunately, prevalent oxygen electrocatalysts fail to maximize the utilization of active sites due to inappropriate nanostructural design. Herein, a nano-emulsion induced polymerization self-assembly strategy is employed to prepare hierarchical meso-/microporous N/S co-doped carbon nanocage with atomically dispersed FeN4 (denoted as Meso/Micro-FeNSC). In situ scanning electrochemical microscopy technology reveals the density of available active sites for Meso/Micro-FeNSC reach to 3.57 × 1014 sites cm-2 , representing more than threefold improvement compared to micropore-dominant Micro-FeNSC counterpart (1.07 × 1014 sites cm-2 ). Additionally, the turnover frequency of Meso/Micro-FeNSC is also improved to 0.69 from 0.50 e- site-1 s-1 for Micro-FeNSC. These properties motivate Meso/Micro-FeNSC as efficient oxygen electroreduction electrocatalyst, in terms of outstanding half-wave potential (0.91 V), remarkable kinetic mass specific activity (68.65 A g-1 ), and excellent robustness. The assembled Zn-air batteries with Meso/Micro-FeNSC deliver high peak power density (264.34 mW cm-2 ), large specific capacity (814.09 mA h g-1 ), and long cycle life (>200 h). This work sheds lights on quantifying active site density and the significance of maximum utilization of active sites for rational design of advanced catalysts.

The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes.

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

Effects of Water Extract from Artemisia argyi Leaves on LPS-Induced Mastitis in Mice.

In the context of the unsatisfactory therapeutic effect of antibiotics, the natural products of plants have become a research hotspot. Artemisia argyi (A. argyi) is known as a traditional medicine in China, and its extracts have been reported to have a variety of active functions, including anti-inflammatory. Therefore, after establishing the mouse mastitis model by lipopolysaccharide (LPS), the effects of A. argyi leaves extract (ALE) were evaluated by pathological morphology of the mammary gland tissue, gene expression, and serum oxidation index. Studies have shown that ALE has a restorative effect on LPS-induced mammary gland lesions and significantly down-regulated the rise of myeloperoxidase (MPO) induced by LPS stimulation. In addition, ALE played a positive role in LPS-induced oxidative imbalance by restoring the activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) and preventing the increase in nitric oxide (NO) concentration caused by the over-activation of total nitric oxide synthase (T-NOS). Further analysis of gene expression in the mammary gland showed that ALE significantly down-regulated LPS-induced up-regulation of inflammatory factors IL6, TNFα, and IL1ß. ALE also regulated the expression of MyD88, a key gene for toll-like receptors (TLRs) signaling, which, in turn, regulated TLR2 and TLR4. The effect of ALE on iNOS expression was similar to the effect of T-NOS activity and NO content, which also played a positive role. The IκB gene is closely related to the NF-κB signaling pathway, and ALE was found to significantly alleviate the LPS-induced increase in IκB. All of these results indicated that ALE may be considered a potential active substance for mastitis.

Preparation of Highly Substituted Sulfated Alfalfa Polysaccharides and Evaluation of Their Biological Activity.

Alfalfa polysaccharides (AP) receive wide attention in the field of medicine, because of their anti-inflammatory property. However, AP has high molecular weight and poor water solubility, resulting in low biological activity. We wanted to obtain highly bioactive alfalfa polysaccharides for further research. Herein, we successfully synthesized highly substituted sulfated alfalfa polysaccharides (SAP) via the chlorosulfonic acid (CSA)-pyridine (Pyr) method, which was optimized using response surface methodology (RSM). Under the best reaction conditions, that is, the reaction temperature, time, and ratio of CSA to Pyr being 55 °C, 2.25 h, and 1.5:1, respectively, the maximum degree of substitution of SAP can reach up to 0.724. Fourier transform infrared spectroscopy also confirmed the existence of sulfonic acid groups on SAP. Despite the increased average molecular weight of SAP, its water solubility is improved, which is beneficial for its biological activity. Further in vitro results showed that SAP exhibited better antioxidant activity and antibacterial ability than AP. Besides, the former can efficiently enhance the viability of oxidatively stressed intestinal epithelial cells compared with the latter. Furthermore, SAP has the potential to inhibit obesity. It is concluded that sulfation modification could improve the antioxidant, antibacterial, bovine intestinal epithelial cells' proliferation-promoting, and the obesity inhibition abilities of AP. The improvement of AP biological activity may provide references for the utilization of plant extracts that have weaker biological activity.

Soyasaponins A1 and A2 exert anti-atherosclerotic functionalities by decreasing hypercholesterolemia and inflammation in high fat diet (HFD)-fed ApoE-/- mice.

Atherosclerosis is a chronic inflammatory disease causing coronary heart attacks and strokes. Soyasaponins (SS), the phytochemicals naturally existing in soybeans and their products, have been shown to reduce hypercholesterolemia and inflammation, which are intimately related to the genesis and development of atherosclerosis. However, the anti-atherosclerotic functionality of soyasaponins remains unknown. The aim of this study was to investigate the effects of the supplementation of two types of soyasaponin monomers (A1 and A2) on atherosclerotic plaque formation, serum lipid profiles, and inflammation in ApoE gene knockout (ApoE-/-) mice. Sixty 5-week-old ApoE-/- male mice were fed with a high-fat diet (HFD) and intervened by SSA1 and SSA2 (10 and 20 µmol per kg BW, respectively) or simvastatin (10 µmol per kg BW) for 24 weeks. The atherosclerotic lesions in the aorta, aortic root, and innominate artery, lipid profile and inflammatory markers in serum, and TLR4/MyD88/NF-κB signaling in arterial tissues were determined. SSA1 and SSA2 decreased the plaque ratio in the aortic root and innominate artery but not in the entire aorta. In serum, SSA1 reduced TG, TC, and LDL-C but increased HDL-C; SSA2 decreased TC, TG, and LDL-C but did not affect HDL-C. Meanwhile, SSA1 increased TG, SSA2 increased TC, and both of them increased bile acids in the feces. SSA1 and SSA2 lowered TNF-α, MCP-1, and hs-crp in serum. Furthermore, SSA1 and SSA2 reduced the TLR4 and MyD88 expressions in the aorta and innominate artery and inhibited NF-κB p65 and IκBα phosphorylation in the aorta. These results suggest that SSA1 and SSA2 exert anti-atherosclerotic functionalities by decreasing hypercholesterolemia and inflammation in HFD-fed ApoE-/- mice.