Metabolic Profiling Study of Yang Deficiency Syndrome in Hepatocellular Carcinoma by H

This study proposes a 1H NMR-based metabonomic approach to explore the biochemical characteristics of Yang deficiency syndrome in hepatocellular carcinoma (HCC) based on serum metabolic profiling. Serum samples from 21 cases of Yang deficiency syndrome HCC patients (YDS-HCC) and 21 cases of non-Yang deficiency syndrome HCC patients (NYDS-HCC) were analyzed using 1H NMR spectroscopy and partial least squares discriminant analysis (PLS-DA) was applied to visualize the variation patterns in metabolic profiling of sera from different groups. The differential metabolites were identified and the biochemical characteristics were analyzed. We found that the intensities of six metabolites (LDL/VLDL, isoleucine, lactate, lipids, choline, and glucose/sugars) in serum of Yang deficiency syndrome patients were lower than those of non-Yang deficiency syndrome patients. It implies that multiple metabolisms, mainly including lipid, amino acid, and energy metabolisms, are unbalanced or weakened in Yang deficiency syndrome patients with HCC. The decreased intensities of metabolites including LDL/VLDL, isoleucine, lactate, lipids, choline, and glucose/sugars in serum may be the distinctive metabolic variations of Yang deficiency syndrome patients with HCC. And these metabolites may be potential biomarkers for diagnosis of Yang deficiency syndrome in HCC

Fused Deposition Modeling PEEK Implants for Personalized Surgical Application: From Clinical Need to Biofabrication

Three-dimensional printing (3DP) technology is suitable for manufacturing personalized orthopedic implants for reconstruction surgery. Compared with traditional titanium, polyether-ether-ketone (PEEK) is the ideal material for 3DP orthopedic implants due to its various advantages, including thermoplasticity, thermal stability, high chemical stability, and radiolucency suitable elastic modulus. However, it is challenging to develop a well-designed method and manufacturing technique to meet the clinical needs because it requires elaborate details and interplays with clinical work. Furthermore, establishing surgical standards for new implants requires many clinical cases and an accumulation of surgical experience. Thus, there are few case reports on using 3DP PEEK implants in clinical practice. Herein, we formed a team with a lot of engineers, scientists, and doctors and conducted a series of studies on the 3DP PEEK implants for chest wall reconstruction. First, the thoracic surgeons sort out the specific types of chest wall defects. Then, the engineers designed the shape of the implant and performed finite element analysis for every implant. To meet the clinical needs and mechanical requirements of implants, we developed a new fused deposition modeling technology to make personalized PEEK implants. Overall, the thoracic surgeons have used 114 personalized 3DP PEEK implants to reconstruct the chest wall defect and further established the surgical standards of the implants as part of the Chinese clinical guidelines. The surface modification technique and composite process are developed to overcome the new clinical problems of implant-related complications after surgery. Finally, the major challenges and possible solutions to translating 3DP PEEK implants into a mature and prevalent clinical product are discussed in the paper

Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation

厦门大学医学院、神经科学研究所张杰教授团队发现了抑郁症新的致病基因MEN1，并阐明了MEN1调控星形胶质细胞炎症导致抑郁发生发展的新机制，为抑郁症的诊治提供了新靶点和方向。抑郁症是严重威胁人类健康的重大神经系统疾病，危及全球30%的人口。但对其发病机制并不清楚。张杰教授团队发现，在慢性不可预测以及LPS处理的模拟抑郁小鼠模型中，多发性内分泌肿瘤蛋白(menin)在大脑中的表达显著降低，并且在星形胶质细胞中降低最明显。为了研究menin是否参与了小鼠抑郁表型的产生，研究团队制作了多种神经系统menin条件性敲除小鼠。通过对这些小鼠行为学的检测，锁定了只有在星形胶质细胞中敲除menin后，小鼠才会表现出抑郁样表型。证实了menin可能是通过调控星形胶质细胞的功能促进了抑郁的发生。 MEN1基因的突变会导致多发性内分泌肿瘤，而内分泌的紊乱和抑郁等精神疾病有着密切的联系。下丘脑-垂体-肾上腺轴（HPA轴）的功能紊乱直接参与了抑郁的产生。基于此研究团队推测MEN1的基因突变是否也会导致抑郁的发生。通过和中国医学科学院基础所的许琪教授合作，研究团队对1000多例重度抑郁患者和800多例对照人群进行了MEN1基因的外显子测序。通过测序发现MEN1的一个SNP s375804228和抑郁的发生有着显著关联。该SNP导致menin第503位的氨基酸由G突变成D。通过功能研究进一步证实该突变可以阻断menin和p65的结合，从而过度激活NF-κB-IL-1β通路，导致神经炎症的发生。 张杰，厦门大学特聘教授、博士生导师。国家优秀青年科学基金；教育部新世纪优秀人才；福建省杰出青年科学基金；厦门市五四青年奖章等获得者。2011年8月加入厦门大学医学院神经科学研究所担任教授至今。张杰博士主要从事重大神经系统疾病（老年痴呆、帕金森、抑郁症、自闭症、术后认知障碍、胶质瘤）等的发病机制和药物开发研究。至今以第一作者或者通讯作者在国际知名期刊发表研究论文21篇。其中回国独立开展研究工作以后，作为通讯作者在 Neuron，Cell Reports, PNAS, The Journal of Neuroscience, Clinical Cancer Research，Cell Death and Disease, JBC, Chemistry，Chem. Biol. Drug Des.等杂志上发表多篇研究论文。【Abstract】Astrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte-specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We observed enhanced NF-κB activation and IL-1β production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-κB inhibitor or IL-1β receptor antagonist. Importantly, we identified a SNP, rs375804228, in human MEN1, where G503D substitution is associated with a higher risk of MDD onset. G503D substitution abolished menin-p65 interactions, thereby enhancing NF-κB activation and IL-1β production. Our results reveal a distinct astroglial role for menin in regulating neuroinflammation in depression, indicating that menin may be an attractive therapeutic target in MDD.We thank Prof. Guanghui Jin (Xiamen University) and Prof. Xianxin Hua (University of Pennsylvania) for providing the Men1-floxp mice. This work was supported by the National Natural Science Foundation of China (grants 81522016, 81271421, and 31571055 to J.Z.; 81625008 and 31430048 to Q.X.; 81630026 to Z.Y.; 81771163 and U1405222 to H.X.; U1505227 to G.B.; 81472725 to W.M.), the Natural Science Foundation of Fujian Province of China (grant 2013J01147 and 2014J06019 to J.Z.), the Fundamental Research Funds for the Central Universities (grants 20720150062 and 20720180049 to J.Z.), the National Key Research and Development Program of China (2016YFC1305903), and CAMS Innovation Fund for Medical Sciences (grant 2016I2M1004 to Q.X.).研究工作得到国家自然科学基金项目（81522016、81271421、31571055）以及厦门大学校长基金等资助

Genome-Wide Association Study Reveals Novel Genomic Regions Associated With High Grain Protein Content in Wheat Lines Derived From Wild Emmer Wheat

Grain protein content (GPC) and yield are of two important traits in wheat, but their negative correlation has hampered their simultaneous improvement in conventional breeding. Wild emmer wheat (Triticum turgidum ssp. dicoccoides) is an important genetic resource for wheat quality improvement. In this study, we report a genome-wide association study (GWAS) using 13116 DArT-seq markers to characterize GPC in 161 wheat lines derived from wild emmer. Using a general linear model, we identified 141 markers that were significantly associated with GPC, and grouped into 48 QTL regions. Using both general linear model and mixed linear model, we identified four significant markers that were grouped into two novel QTL regions on chromosomes 2BS (QGpc.cd1-2B.1) and 7BL (QGpc.cd1-7B.2). The two QTLs have no negative effects on thousand kernel weight (TKW) and should be useful for simultaneous improvement of GPC and TKW in wheat breeding. Searches of public databases revealed 61 putative candidate/flanking genes related to GPC. The putative proteins of interest were grouped in four main categories: enzymes, kinase proteins, metal transport-related proteins, and disease resistance proteins. The linked markers and associated candidate genes provide essential information for cloning genes related to high GPC and performing marker-assisted breeding in wheat

Metabolic dysfunction-associated fatty liver disease increased the risk of subclinical carotid atherosclerosis in China

Background and aimsMetabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to substitute NAFLD in 2020. This new term highlights the systematic metabolic disturbances that accompany fatty liver. We evaluated the correlations between MAFLD and subclinical carotid atherosclerosis (SCA) based on a nationwide health examination population in China.MethodsWe performed a nationwide cross-sectional population and a Beijing retrospective cohort from 2009 to 2017. SCA was defined as elevated carotid intima-media thickness. The multivariable logistic and Cox models were used to analyze the association between MAFLD and SCA.Results153,482 participants were included in the cross-sectional study. MAFLD was significantly associated with SCA in fully adjusted models, with an odds ratio of 1.66; 95% confidence interval (CI): 1.62-1.70. This association was consistent in the cohort, with a hazard ratio (HR) of 1.31. The association between baseline MAFLD and incident SCA increased with hepatic steatosis severity. Subgroup analysis showed an interaction between age and MAFLD, with a higher risk in younger groups (HR:1.67, 95% CI: 1.17-2.40).ConclusionIn this large cross-section and cohort study, MAFLD was significantly associated with the presence and development of SCA. Further, the risk was higher among MAFLD individuals with high hepatic steatosis index and young adults

A machine learning method for the quantitative detection of adulterated meat using a MOS-based e-nose

Meat adulteration is a global problem which undermines market fairness and harms people with allergies or certain religious beliefs. In this study, a novel framework in which a one-dimensional convolutional neural network (1DCNN) serves as a backbone and a random forest regressor (RFR) serves as a regressor, named 1DCNN-RFR, is proposed for the quantitative detection of beef adulterated with pork using electronic nose (E-nose) data. The 1DCNN backbone extracted a sufficient number of features from a multichannel input matrix converted from the raw E-nose data. The RFR improved the regression performance due to its strong prediction ability. The effectiveness of the 1DCNN-RFR framework was verified by comparing it with four other models (support vector regression model (SVR), RFR, backpropagation neural network (BPNN), and 1DCNN). The proposed 1DCNN-RFR framework performed best in the quantitative detection of beef adulterated with pork. This study indicated that the proposed 1DCNN-RFR framework could be used as an effective tool for the quantitative detection of meat adulteration

Identification of Traditional Chinese Medicine Constitutions and Physiological Indexes Risk Factors in Metabolic Syndrome: A Data Mining Approach

Objective. In order to find the predictive indexes for metabolic syndrome (MS), a data mining method was used to identify significant physiological indexes and traditional Chinese medicine (TCM) constitutions. Methods. The annual health check-up data including physical examination data; biochemical tests and Constitution in Chinese Medicine Questionnaire (CCMQ) measurement data from 2014 to 2016 were screened according to the inclusion and exclusion criteria. A predictive matrix was established by the longitudinal data of three consecutive years. TreeNet machine learning algorithm was applied to build prediction model to uncover the dependence relationship between physiological indexes, TCM constitutions, and MS. Results. By model testing, the overall accuracy rate for prediction model by TreeNet was 73.23%. Top 12.31% individuals in test group (n=325) that have higher probability of having MS covered 23.68% MS patients, showing 0.92 times more risk of having MS than the general population. Importance of ranked top 15 was listed in descending order . The top 5 variables of great importance in MS prediction were TBIL difference between 2014 and 2015 (D_TBIL), TBIL in 2014 (TBIL 2014), LDL-C difference between 2014 and 2015 (D_LDL-C), CCMQ scores for balanced constitution in 2015 (balanced constitution 2015), and TCH in 2015 (TCH 2015). When D_TBIL was between 0 and 2, TBIL 2014 was between 10 and 15, D_LDL-C was above 19, balanced constitution 2015 was below 60, or TCH 2015 was above 5.7, the incidence of MS was higher. Furthermore, there were interactions between balanced constitution 2015 score and TBIL 2014 or D_LDL-C in MS prediction. Conclusion. Balanced constitution, TBIL, LDL-C, and TCH level can act as predictors for MS. The combination of TCM constitution and physiological indexes can give early warning to MS

The Physicochemical Properties of Starch Are Affected by Wxlv in Indica Rice

Amylose largely determines rice grain quality profiles. The process of rice amylose biosynthesis is mainly driven by the waxy (Wx) gene, which also affects the diversity of amylose content. The present study assessed the grain quality profiles, starch fine structure, and crystallinity characteristics of the near-isogenic lines Q11(Wxlv), NIL(Wxa), and NIL(Wxb) in the indica rice Q11 background containing different Wx alleles. Q11(Wxlv) rice contained a relatively higher amylose level but very soft gel consistency and low starch viscosity, compared with rice lines carrying Wxa and Wxb. In addition, starch fine structure analysis revealed a remarkable decrease in the relative area ratio of the short amylopectin fraction but an increased amylose fraction in Q11(Wxlv) rice. Chain length distribution analysis showed that Q11(Wxlv) rice contained less amylopectin short chains but more intermediate chains, which decreased the crystallinity and lamellar peak intensity, compared with those of NIL(Wxa) and NIL(Wxb) rice. Additionally, the starches in developing grains showed different accumulation profiles among the three rice lines. Moreover, significant differences in starch gelatinization and retrogradation characteristics were observed between near-isogenic lines, which were caused by variation in starch fine structure. These findings revealed the effects of Wxlv on rice grain quality and the fine structure of starch in indica rice

The Underlying Physicochemical Properties and Starch Structures of <i>indica</i> Rice Grains with Translucent Endosperms under Low-Moisture Conditions

Rice grain quality is a complex trait that includes processing, appearance, eating, cooking, and nutrition components. The amylose content (AC) in the rice endosperm affects the eating and cooking quality along with the appearance of milled rice. In this study, four indica rice varieties with different ACs were used to study the factors affecting endosperm transparency along with the physical and chemical characteristics and eating quality of translucent endosperm varieties. Endosperm transparency was positively correlated with water content and negatively correlated with the cumulative area of cavities within starch granules. The indica landrace 28Zhan had a translucent endosperm and exhibited good taste. Based on starch fine structure analysis, long-chain amylopectin and the B2 chain of amylopectin might be major contributors to the good taste and relatively slow digestion of this landrace