Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study

Wang Qi,Dai Huajie,Hou Tianzhichao,Hou Yanan,Wang Tiange,Lin Hong,Zhao Zhiyun,Li Mian,Zheng Ruizhi,Wang Shuangyuan,Lu Jieli,Xu Yu,Liu Ruixin,Ning Guang,Wang Weiqing,Bi Yufang,Zheng Jie,Xu Min 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family, <i>Desulfovibrio</i> genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all <i>P</i><0.044). The causal associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas <i>Desulfovibrio</i> genus was negatively associated with ApoB/ApoA1 (all <i>P</i><0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (<i>P</i>=0.028) and 4.6% (<i>P</i>=0.033); the association between <i>Desulfovibrio</i> genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (<i>P</i>=0.019), 4.2% (<i>P</i>=0.035), and 9.1% (<i>P</i>=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

A national survey on how to improve traditional Chinese medicine learning internationally: Perceptions from both teachers and students

Zhu Yu-Hang,Yan Wu,Hao Zhang,Yanfei Zhao,Yule Ren,Wei Hu,Pan Li,Huiyi Wang,Ying Wang,Boda Zhang,Yujie Wang,Hongwen Yuan,Jiping Zhang,Wenqiang Li,Yufang Zhao,Jie Zhao,Yedong Shi,Yanye Shu,Xiao Zhang,Ya 한국한의학연구원 2022 Integrative Medicine Research Vol.11 No.4

Background With the increasing popularity of traditional Chinese medicine (TCM) by the global community, how to teach basic knowledge of TCM to international students and improve the teaching quality are important issues for teachers of TCM. The present study was to analyze the perceptions from both students and teachers on how to improve TCM learning internationally. Methods A cross-sectional national survey was conducted at 23 universities/colleges across China. A structured, self-reported on-line questionnaire was administered to 34 Chinese teachers who taught TCM course in English and to 1016 international undergraduates who were enrolled in the TCM course in China between 2017 and 2021. Results Thirty-three (97.1%) teachers and 900 (88.6%) undergraduates agreed Chinese culture should be fully integrated into TCM courses. All teachers and 944 (92.9%) undergraduates thought that TCM had important significance in the clinical practice. All teachers and 995 (97.9%) undergraduates agreed that modern research of TCM is valuable. Thirty-three (97.1%) teachers and 959 (94.4%) undergraduates thought comparing traditional medicine in different countries with TCM can help the students better understand TCM. Thirty-two (94.1%) teachers and 962 (94.7%) undergraduates agreed on the use of practical teaching method with case reports. From the perceptions of the undergraduates, the top three beneficial learning styles were practice (34.3%), teacher's lectures (32.5%), case studies (10.4%). The first choice of learning mode was attending to face-to-face teaching (82.3%). The top three interesting contents were acupuncture (75.5%), Chinese herbal medicine (63.8%), and massage (55.0%). Conclusion To improve TCM learning among international undergraduates majoring in conventional medicine, integration of Chinese culture into TCM course, comparison of traditional medicine in different countries with TCM, application of the teaching method with case reports, and emphasization of clinical practice as well as modern research on TCM should be fully considered.

The Effects of Structure of Inclusion Complex between β-Cyclodextrin and Poly(L-lactic acid) on Its Performance

YuFang Zhou,Weijun Zhen,YaNan Song,WenTao Wang 한국고분자학회 2015 Macromolecular Research Vol.23 No.12

The partial inclusion complexes (ICs) between poly(L-lactic acid) (PLLA) with high molecular weight and β-cyclodextrin (CD) were prepared and characterized by 1H nuclear magnetic resonance spectra (1H NMR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and polarizing optical microscopy (POM), respectively. The thermal results demonstrated that the crystallization performance of ICs were significantly improved, and the decomposition temperature of ICs were increased compared with PLLA. The mechanical tests indicated that the mechanical performance of ICs was improved, and the β-CD-PLLA ICs exhibited a higher non-Newtonian effect than PLLA. The degradation rate for the partial ICs in phosphate buffer solution accelerated as the ratio of β-CD increased, meanwhile, the partial ICs had a good shape memory behavior. The wetting measurements suggested the hydrophilicity of ICs was also enhanced markedly in comparison with the bulk PLLA.

Efficient Elicitation of Ginsenoside Biosynthesis in Cell Cultures of Panax notoginseng by Using Self-chemically-synthesized Jasmonates

Wang Wei,Zhao Zhen-Jiang,Xu Yufang,Qian Xu hong,Zhong Jian-Jiang The Korean Society for Biotechnology and Bioengine 2005 Biotechnology and Bioprocess Engineering Vol.10 No.2

A series of fluorine and hydroxyl containing jasmonate derivatives, which were chemically synthesized in our institute, were investigated for their effects on the biosynthesis and heterogeneity of ginsenosides in suspension cultures of Panax notoginseng cells. Com-pared to the control (without addition of elicitors), $100{\mu}M$ of each of the jasmonate was added on day 4 to the suspension cultures of P. notoginseng cells. It was observed that, jasmonates greatly enhanced the ginsenoside content and the ratio of Rb group to Rg group (i.e. $(Rb_1\;+\;Rd)/(Rg_1\;+\;Re)$ in the P. notoginseng cells. Some of the synthetic jasmonates, such as pentafluoropropyl jasmonate (PFPJA), 2-hydroxyethyl jasmonate (HEJA) and 2-hydroxye-thoxyethyl jasmonate (HEEJA), could promote the ginsenoside content to $2.55\;\pm\;0.11,\;3.65\;\pm\;0.13\;and\;2.94\;\pm\;0.06$mg/100 mg DW, respectively, compared to that of $0.64\;\pm\;0.06$mg/100 mg DW for the control and $2.17\;\pm\;0.04$ mg/100 mg DW by the commercially available methyl jasmonate (MJA); and they could change the respective Rb:Rg ratio to $1.60\;\pm\;0.04,\;1.87\;\pm\;0.01\;and\;1.56\;\pm\;0.05$, compared to that of $0.47\;\pm\;0.01$ for the control and $1.42\;\pm\;0.06$ by MJA. The results suggest that suitable esterification of MJA with fluorine or hydroxyl group could in-crease the elicitation activity to induce plant secondary metabolism. The information obtained from this study is useful for hyper-production of heterogeneous products by plant cell cultures.

Transcriptome analysis reveals molecular strategies of Bactrocera dorsalis (Hendel) larvae in response to anoxia

Deng Yufang,Jiang Fan,Hu Fan,Liang Liang,Wang Yuejin 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.4

Bactrocera dorsalis and its larvae have evolved to cope with the hypoxic environment during their lifetime. In this study, we sequenced the transcriptomes of B. dorsalis under and post anoxia stress. Our data revealed the different biological mechanisms of B. dorsalis in response to anoxia and during recovery from anoxia. The in duction of heat shock proteins (HSPs) might be one of the important mechanisms for B. dorsalis to tolerate anoxia. Furthermore, our data showed B. dorsalis acquires energy through gluconeogenesis rather than glycolysis under anoxia and upregulated its lipid metabolism post anoxia. The up-regulation of the genes involved in the Hippo signaling pathway might also play a role in eliminating damaged cells as a result of anoxia. Furthermore, the HIF system of B. dorsalis did not change in response to anoxia stress in this study. We hypothesized that the HIF system in B. dorsalis might be activated by a specific duration of anoxia.

Comparative portrayal of ocular surface microbe with and without dry eye

ZhenHao Li,Yufang Gong,ShuZe Chen,SiQi Li,Yu Zhang,HuiMin Zhong,ZhouCheng Wang,YiFan Chen,QiXin Deng,YuTing Jiang,LiYing Li,Min Fu,GuoGuo Yi 한국미생물학회 2019 The journal of microbiology Vol.57 No.11

To compare the ocular surface (OS) microbial communities and diversity between dry eye (DE) and non-DE (NDE). Furthermore, we compared meibomian gland dysfunction (MGD) and non-MGD (NMGD) among DE subjects. The V3-V4 region of 16S rRNA gene high-throughput sequencing was performed in the conjunctival swab samples to investigate the composition of the OS bacterial community in DE (n=35) and NDE (n=54) and compared the composition of MGD (n=25) and NMGD (n=10) among DE subjects. Deep sequencing of OS 16S rDNA from DE (n=35) and NDE (n=54) demonstrated great a difference in alpha and beta diversity between the OS bacterial flora (P < 0.05). The similar OS microbial structures were shown at the phylum and genus levels by bioinformatics analysis between them, and in LEfSe (linear discriminant analysis effect size) analysis, Bacteroidia and Bacteroidetes were enriched in DE, while Pseudomonas was plentiful in NDE (linear discriminant analysis [LDA] > 4.0). Among the DE group, there was no significant difference in α and β diversity between MGD and NMGD (P > 0.05). Surprisingly, Bacilli was the dominant microbe in MGD, and Bacteroidetes was the superior bacteria in NMGD among DE subjects (LDA > 4.0). Different diversity of OS bacteria composition between DE and NDE and the altered diversity of OS bacteria may play an important role in DE. Moreover, the lower dominance of OS bacteria in DE may be associated with the occurrence and development of DE. Although there was no significant difference in alpha and beta analysis, the OS dominant microbe between MGD and NMGD among DE was different.

Effect of adhesive layer properties on the shear strength of single-lap structures of dissimilar materials based on the cohesive zone model

Jiwei Huang,Jie Zeng,Yufang Bai,Zhuming Cheng,Yong Wang,Qidi Zhao,Dakai Liang 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.1

An analysis method for improving the shear strength for the single-lap joints of dissimilar materials based on the cohesive zone model (CZM) is presented in this paper. The shear-lag model is established for the single-lap joint, and the stress distribution of joints is derived on the basis of this model, which is verified by simulation. The bilinear CZM is constructed to simulate the fracture process of joints, and the influence of lap length and adhesive layer thickness on the stress distribution of adhesive layers is comprehensively analyzed through simulation. Therefore, the effects of different properties of adhesive layers on the bonded structure strength are discussed with experiments. Results show that the reasonable lap length and thickness in this work are, respectively, 20-22 and 0.4-0.6 mm. The research results will serve as a guide for the parameter design, fracture prediction, and performance optimization of bonded joints.

Efficient Elicitation of Ginsenoside Biosynthesis in Cell Cultures of Panax notoginseng by Using Self-chemically-synthesized Jasmonates

Jian-Jiang Zhong,Wei Wang,Zhen-Jiang Zhao,Yufang Xu,Xuhong Qian 한국생물공학회 2005 Biotechnology and Bioprocess Engineering Vol.10 No.2

A series of fluorine and hydroxyl containing jasmonate derivatives, which were chemically synthesized in our institute, were investigated for their effects on the biosynthesis and heterogeneity of ginsenosides in suspension cultures of Panax notoginseng cells. Compared to the control (without addition of elicitors), 100 M of each of the jasmonate was added on day 4 to the suspension cultures of P. notoginseng cells. It was observed that, jasmonates greatly enhanced the ginsenoside content and the ratio of Rb group to Rg group (i.e. (Rb1 + Rd)/(Rg1 + Re)) in the P. notoginseng cells. Some of the synthetic jasmonates, such as pentafluoropropyl jasmonate (PFPJA), 2-hydroxyethyl jasmonate (HEJA) and 2-hydroxye-thoxyethyl jasmonate (HEEJA), could promote the ginsenoside content to 2.55 0.11, 3.65 0.13 and 2.94 0.06 mg/100 mg DW, respectively, compared to that of 0.64 0.06 mg/100 mg DW for the control and 2.17 0.04 mg/100 mg DW by the commercially available methyl jasmonate (MJA); and they could change the respective Rb:Rg ratio to 1.60 0.04, 1.87 0.01 and 1.56 0.05, compared to that of 0.47 0.01 for the control and 1.42 0.06 by MJA. The results suggest that suitable esterification of MJA with fluorine or hydroxyl group could increase the elicitation activity to induce plant secondary metabolism. The information obtained from this study is useful for hyper-production of heterogeneous products by plant cell cultures.

Comparative analysis of the Down syndrome hippocampal non-coding RNA transcriptomes using a mouse model

Zhaowei Cai,Zhilan Xiao,Yufang Wang,Huazhen Liu,Kangdi Zhang,Xiaoning Zhen,Xiaoling Jiang 한국유전학회 2020 Genes & Genomics Vol.42 No.11

Background Down syndrome (DS), caused by trisomy 21, is the most common human chromosomal disorder. Hippocampalabnormalities have been believed to be responsible for the DS developmental cognitive deficits. Cumulative evidences indicatedthat non-coding RNAs (ncRNAs) participated in brain development and function. Currently, few was known whetherdysregulated ncRNAs existed in DS whether the dysregulated ncRNAs played important pathology roles in DS. Objective The purpose of this study was generating an overview map of the dysregulated ncRNAs in DS, including themicroRNA (miRNA), long ncRNA (lncRNA) and circular RNA (circRNAs). DS mouse models are invaluable tools forfurther mechanism and therapy studies. Methods The well-studied DS mouse model Dp(16)1/Yey was used in this study as it contains the trisomy of the whole humanchromosome 21 syntenic region on mouse chromosomes 16. Hippocampi were isolated from pups of seven-days-old. Librariesfor miRNA, lncRNA and circRNAs were constructed separately, and the next generation sequencing method was utilized. Results Differentially expressed (DE) miRNAs, lncRNAs and circRNAs were reported. Relative few regulating relationshipwere found between the DE miRNAs and DE mRNAs. LncRNAs originated from the trisomic regions expressed in clusters,but not all of them were 1.5-fold increased expressed. Dramatic DE circular RNAs were found in the DS hippocampus. The host genes of the DE circRNAs were enriched on functions which were well-known impaired in DS, e.g. long-termpotentiation,glutamatergic synapse, and GABAergic synapse. Conclusions We generated the first DS developmental hippocampal ncRNA transcriptome map. This work laid foundationsfor further investigations on role of ncRNAs in hippocampal functions.

Effects of processing method on the pharmacokinetics and tissue distribution of orally administered ginseng

Chen, Jianbo,Li, Meijia,Chen, Lixue,Wang, Yufang,Li, Shanshan,Zhang, Yuwei,Zhang, Lei,Song, Mingjie,Liu, Chang,Hua, Mei,Sun, Yinshi The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.1

Background: The use of different methods for the processing of ginseng can result in alterations in its medicinal properties and efficacy. White ginseng (WG), frozen ginseng (FG), and red ginseng (RG) are produced using different methods. WG, FG, and RG possess different pharmacological properties. Methods: WG, FG, and RG extracts and pure ginsenosides were administered to rats to study the pharmacokinetics and tissue distribution characteristics of the following ginsenosides-DRg1, Re, Rb1, and Rd. The concentrations of the ginsenosides in the plasma and tissues were determined using UPLC-MS/MS. Results: The rate and extent of absorption of Rg1, Re, Rb1, and Rd appeared to be affected by the different methods used in processing the ginseng samples. The areas under the plasma drug concentration-time curves (AUCs) of Rg1, Re, Rb1, and Rd were significantly higher than those of the pure ginsenosides. In addition, the AUCs of Rg1, Re, Rb1, and Rd were different for WG, FG, and RG. The amounts of Rg1, Re, Rd, and Rb1 were significantly (p < 0.05) higher in the tissues than those of the pure ginsenosides. The amounts of Re, Rb1, and Rd from the RG extract were significantly higher than those from the WG and FG extracts in the heart, lungs, and kidneys of the rats. Conclusion: Our results show that the use of different methods to process ginseng might affect the pharmacokinetics and oral bioavailability of ginseng as well as the tissue concentrations of Rg1, Re, Rd, and Rb1.