Assessing the Association between Important Dietary Habits and Osteoporosis: A Genetic Correlation and Two-Sample Mendelian Randomization Study

Objective: Osteoporosis (OP) is the most common bone disease. The genetic and metabolic factors play important roles in OP development. However, the genetic basis of OP is still elusive. The study aimed to explore the relationships between OP and dietary habits. Methods: This study used large-scale genome-wide association study (GWAS) summary statistics from the UK Biobank to explore potential associations between OP and 143 dietary habits. The GWAS summary data of OP included 9434 self-reported OP cases and 444,941 controls, and the GWAS summary data of the dietary habits included 455,146 participants of European ancestry. Linkage disequilibrium score regression (LDSC) was used to detect the genetic correlations between OP and each of the 143 dietary habits, followed by Mendelian randomization (MR) analysis to further assess the causal relationship between OP and candidate dietary habits identified by LDSC. Results: The LDSC analysis identified seven candidate dietary habits that showed genetic associations with OP including cereal type such as biscuit cereal (coefficient = −0.1693, p value = 0.0183), servings of raw vegetables per day (coefficient = 0.0837, p value = 0.0379), and spirits measured per month (coefficient = 0.115, p value = 0.0353). MR analysis found that OP and PC17 (butter) (odds ratio [OR] = 0.974, 95% confidence interval [CI] = (0.973, 0.976), p value = 0.000970), PC35 (decaffeinated coffee) (OR = 0.985, 95% CI = (0.983, 0.987), p value = 0.00126), PC36 (overall processed meat intake) (OR = 1.035, 95% CI = (1.033, 1.037), p value = 0.000976), PC39 (spirits measured per month) (OR = 1.014, 95% CI = (1.011, 1.015), p value = 0.00153), and servings of raw vegetables per day (OR = 0.978, 95% CI = (0.977, 0.979), p value = 0.000563) were clearly causal. Conclusions: Our findings provide new clues for understanding the genetic mechanisms of OP, which focus on the possible role of dietary habits in OP pathogenesis.     

Growth and Gastrointestinal Tolerance in Healthy Term Infants Fed Milk-Based Infant Formula Supplemented with Five Human Milk Oligosaccharides (HMOs): A Randomized Multicenter Trial

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.     

Magnetoacoustic Wave Scattering and Dynamic Stress Concentration around the Elliptical Opening in Exponential-Gradient Piezomagnetic Materials

Based on the theory of magnetoacoustic coupled dynamics, the purpose of this paper is to evaluate the dynamic stress concentration near an elliptical opening in exponential-gradient piezomagnetic materials under the action of antiplane shear waves. By the wave function expansion, the solutions for the acoustic wave fields and magnetic fields can be obtained. Stress analysis is performed by the complex function method and the conformal mapping method, which are used to solve the boundary conditions problem, and is used to express the dynamic stress concentration coefficient (DSCC) theoretically. As cases, numerical results of DSCCs are plotted and discussed with different incident wave numbers and material parameters by numerical simulation. Compared with circular openings, elliptical openings are widely used in material processing techniques and are more difficult to solve. Numerical results show that the dynamic stress concentration coefficient at the elliptical opening is strongly dependent on various parameters, which indicates that the elliptical opening is more likely to cause crack and damage to exponential-gradient piezomagnetic materials.     

Characterizing the Phase-Structure and Rheological Response-Behavior of Multi-Walled Carbon Nanotubes Modified Asphalt-Binder

In this study, the phase-structure and rheological response-behavior of multi-walled carbon nanotube (MWCNTs) modified asphalt-binder (MWCNTs-MA) were measured and quantified in the laboratory. The changes in the molecular dynamics due to MWCNTs modification were simulated and quantified based on the intermolecular interaction energy computations, electrostatic potential surface analyses and phase-structure modeling of the asphalt-binder matrix. The rheological properties such as the asphalt-binder viscosity and complex modulus, of both the base and modified asphalt-binders, were determined using the standard Brookfield viscometer (BV) and dynamic shear rheology (DSR) test devices, respectively. In comparison to the base asphalt-binder, the corresponding BV-DSR test results exhibited higher viscosity and complex modulus for the MWCNTs modified asphalt-binder, with reduced sensitivity and susceptibility to temperature variations. From the study results, it was observed that MWCNTs significantly improved the rheological properties and high-temperature performance of the asphalt-binder. Overall, the study has demonstrated that MWCNT modified asphalt-binder has great promising potential for application and usage as a road-pavement material, particularly with respect to mitigating the high temperature related distresses such as rutting.     

Microstructure and Friction Properties of CoCrFeMnNiTix High-Entropy Alloy Coating by Laser Cladding

To enhance the friction and wear properties of 40Cr steel’s surface, CoCrFeMnNi high-entropy alloy (HEA) coatings with various Ti contents were prepared using laser cladding. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) were used to characterize the phase composition, microstructure, and chemical composition of the samples. The findings demonstrated that the CoCrFeMnNiTi_x HEA coatings formed a single FCC phase. Fe₂Ti, Ni₃Ti, and Co₂Ti intermetallic compounds were discovered in the coatings when the molar ratio of Ti content was greater than 0.5. The EDS findings indicated that Cr and Co/Ni/Ti were primarily enriched in the dendrite and interdendrite, respectively. Ti addition can effectively enhance the coating’s mechanical properties. The hardness test findings showed that when the molar ratio of Ti was 0.75, the coating’s microhardness was 511 HV0.5, which was 1.9 times the hardness of the 40Cr (256 HV0.5) substrate and 1.46 times the hardness of the CrCrFeMnNi HEA coating (348 HV0.5). The friction and wear findings demonstrated that the addition of Ti can substantially reduce the coating’s friction coefficient and wear rate. The coating’s wear resistance was the best when the molar ratio of Ti was 0.75, the friction coefficient was 0.296, and the wear amount was 0.001 g. SEM and 3D morphology test results demonstrated that the coating’s wear mechanism changed from adhesive wear and abrasive wear to fatigue wear and abrasive wear with the increase in Ti content.     

Research on Hyperparameter Optimization of Concrete Slump Prediction Model Based on Response Surface Method

In this paper, eight variables of cement, blast furnace slag, fly ash, water, superplasticizer, coarse aggregate, fine aggregate and flow are used as network input and slump is used as network output to construct a back-propagation (BP) neural network. On this basis, the learning rate, momentum factor, number of hidden nodes and number of iterations are used as hyperparameters to construct 2-layer and 3-layer neural networks respectively. Finally, the response surface method (RSM) is used to optimize the parameters of the network model obtained previously. The results show that the network model with parameters obtained by the response surface method (RSM) has a better coefficient of determination for the test set than the model before optimization, and the optimized model has higher prediction accuracy. At the same time, the model is used to evaluate the influencing factors of each variable on slump. The results show that flow, water, coarse aggregate and fine aggregate are the four main influencing factors, and the maximum influencing factor of flow is 0.875. This also provides a new idea for quickly and effectively adjusting the parameters of the neural network model to improve the prediction accuracy of concrete slump.     

The role of toll-like receptors (TLRs) in pan-cancer

BackgroundToll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study''s goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis.MethodsThe expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data.ResultsOur multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research.ConclusionTLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators.

Key Messages

• Toll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.
• In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.
• TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

     

胎儿端脑突触素表达和突触发育的研究

为了探讨突触素(SYN)在不同周龄阶段胎儿端脑额叶中的表达与胎儿额叶皮质突触发育的关系,本研究采用免疫组织化学方法观察突触素在不同周龄阶段胎儿额叶的表达水平,利用计算机图像分析技术测量不同周龄阶段胎儿额叶突触素表达的平均光密度;同时取材、常规电镜技术处理、透射电镜观察额叶突触发育的超微结构变化。结果显示:(1)光镜下各组均可见SYN免疫阳性产物主要表达于胎儿的额叶皮层,其表达量随周龄的增加而增强,各组间呈现显著性差异(P<0.05),其中16～24周胎儿额叶的阳性产物位于神经元的胞浆内,呈均匀的浅黄色,神经元突起内未见阳性产物;25～29周额叶的阳性产物呈黄色,在胞浆和突起内均可见,但阳性产物的量却下降;而30～39周额叶的SYN阳性产物呈棕黄色的点状或颗粒状,主要位于神经元的突起内,神经元胞浆内未见阳性产物,阳性产物的量显著增加;(2)透射电镜下19～36周胎儿大脑额叶均可见到突触样结构,随着周龄的增加,突触的数量逐渐增多,结构逐渐清晰和完整。上述结果提示SYN的表达可以反映胎儿神经系统发育的程度,SYN的表达与突触的发育是一致的;SYN在胎儿大脑额叶的表达部位经历由神经元胞浆内表达为主到神经元终末表达为主的这一过程,可能是由于SYN先是在神经元胞浆内合成,再随着神经元的发育而逐步转移到神经元突起的末梢部位。     

两种给药途径致痫大鼠海马神经元超微结构损伤及caspase-3的表达特征

为了观察两种给药途径致痫大鼠海马神经元超微结构的损伤及caspase-3的表达特征,本研究分别采用海人酸腹膜腔注射(A组)和尾静脉注射(B组)诱发大鼠癫痫持续状态(SE)。分别于SE终止后3、6、24、48和72h取海马,电镜观察神经元超微结构的变化,免疫组化方法检测caspase-3的表达。结果显示:两组大鼠均在SE后3h出现线粒体损伤,细胞核的改变出现于SE后24h。A组致痫的潜伏期为97min±11min,神经元以凋亡为主;B组为48min±13min,神经元以坏死为主。SE后6～24h,两组大鼠海马内caspase-3的表达由胞浆向胞核逐渐移位,且均在SE后6h明显增高,24h达顶峰;A组高表达持续至72h,B组在48h显著降低。上述结果提示,线粒体的损伤出现于SE的早期,且可能是神经元损伤的关键环节;致痫方法不同,神经元的死亡形式也不同;而caspase-3的激活是神经元凋亡和坏死的共同通路。