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Innovative 3D Microfluidic Intestinal Organoid Model for Assessing Cadmium Bioavailability in Food: Implications for Enhanced Exposure Risk Assessment

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Food Science and Human Wellness 2024年

作者： Yan Li Wen Sun Qiao Wang Wan Shi yu Chen Zhiyong Gong Xiao Guo Xin Liu Yongning Wu Key Laboratory of Animal Biological Products & Genetic Engineering， Ministry of Agriculture and Rural， Sinopharm Animal Health Corporation Ltd. State Key Laboratory of Novel Vaccines for Emerging Infectious Diseases， China National Biotec Group Company Limited Key Laboratory for Deep Processing of Major Grain and Oil (The Chinese Ministry of Education)， College of Food Science and Engineering， Wuhan Polytechnic University Department of Oncology， Xiangya Hospital， Central South University NHC Key Laboratory of Food Safety Risk Assessment， China National Center for Food Safety Risk Assessment

Given the severe toxicity and widespread presence of cadmium (Cd) in staple foods such as rice， accurate dietary exposure assessments are imperative for public health. In vitro bioavailability is commonly used to adjust dietary exposure levels of risk factors; however， traditional planar Transwell models have limitations， such as cell dedifferentiation and lack of key intestinal components， necessitating a more physiologically relevant in vitro platform. This study introduces an innovative three-dimensional (3D) intestinal organoid model using a microfluidic chip to evaluate Cd bioavailability in food. Caco-2 cells were cultured on the chip to mimic small intestinal villi's 3D structure， mucus production， and absorption functions. The model's physiological relevance was thoroughly characterized， demonstrating the formation of a confluent epithelial monolayer with well-developed tight junctions (ZO-1)， high microvilli density (F-actin)， and significant mucus secretion (Alcian blue staining)， closely resembling the physiological intestinal epithelium. Fluorescent particle tracking confirmed its ability to simulate intestinal transport and diffusion. The Cd bioavailability in rice measured by the 3D intestinal organoid model (9.07% ± 0.21%) was comparable to the mouse model (12.82% ± 3.42%) but significantly lower than the Caco-2 monolayer model (26.97% ± 1.11%). This 3D intestinal organoid model provides a novel and reliable strategy for in vitro assessment of heavy metal bioavailability in food， with important implications for food safety and risk assessment.

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Rational protein engineering of thermostable heparinase I from Bacteroides thetaiotaomicron for highly efficient heparin degradation

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Food Science and Human Wellness 2024年

作者： Chuan Zhang Ruohan Zhao Leilei yu Qixiao Zhai Jianxin Zhao Hao Zhang Xuegang Luo Fengwei Tian Wei Chen State Key Laboratory of Food Science and Technology， Jiangnan University School of Food Science and Technology， Jiangnan University Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education & Tianjin Key Lab of Industrial Microbiology， College of Biotechnology， Tianjin University of Science and Technology National Engineering Research Center for Functional Food， Jiangnan University

Heparin， a glycosaminoglycan， is a stable source of carbon that supports the growth of microorganisms in the human intestine. It is also a commonly used anticoagulant drug in clinical practice， with significant therapeutic effects. Low molecular weight heparin （LMWH） is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin. LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients. Simultaneously， as a potential prebiotic， because of its low molecular weight， LMWH can be well degraded by the gut microbiota to maintain intestinal balance. Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation; however， only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years. The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes. Herein， we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening. Several Bt-HepI mutants were obtained and screened for high thermal stability. We obtained the Bt-HepID204C/K208C/H189W/Q198Rvariant， which features a stabilized protein surface structure， with a 1.3-fold increase in kcat/Km， a 2.44-fold increase in thermal stability at 50℃， and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃ compared with that seen with Bt-HepIWT. Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.

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Rapid growth in a large Cambrian apex predator

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National Science Review 2024年第03期11卷 128-136页

作者：吴雨 Stephen Pates Daniel Pauly 张兴亮傅东静 State Key Laboratory of Continental Dynamics and Shaanxi Key Laboratory of Early Life and Environment Department of Geology Northwest University Department of Zoology University of Cambridge Institute for the Oceans and Fisheries University of British Columbia Nanjing Institute of Geology and Palaeontology Chinese Academy of Sciences

Despite the importance of ontogenetic data on early diverging euarthropods to our understanding of the ecology and evolution of past life, the data are distinctly lacking, as reconstructing life histories of fossil animals is often challenging. Here we report the growth trajectory of frontal appendages of the apex predator Amplectobelua symbrachiata, one of the most common radiodont arthropods from the early Cambrian Chengjiang biota(c. 520 Ma) of China. Analysis of 432 specimens(9.1–137.1 mm length; 1.3–25.6 mm height) reveals that appendages grew isometrically, with an estimated maximum size of the whole animal of c. 90 cm. Individuals grew rapidly compared to extant arthropods, as assessed using the electronic length-frequency analysis(ELEFAN) approach. Therefore, we show that the Cambrian apex predator A. symbrachiata was an extremely fast-growing arthropod, with an unusual life history strategy that formed as part of the escalatory ‘arms race’ that shaped the Cambrian explosion over 500 Ma.

关键词： stem-group Euarthropoda Radiodonta post-embryonic development growth dynamics Cambrian Explosion

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基于声黑洞设计理论的径向夹心式径-弯复合换能器

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物理学报 2024年第8期73卷 159-168页

作者：刘洋陈诚林书玉陕西师范大学物理学与信息技术学院陕西省超声重点实验室西安710119

基于弯曲波在声黑洞(acoustic black hole,ABH)结构中振幅不断增大的特性,提出了一种新型径向夹心式径-弯复合换能器,该换能器由径向夹心式圆环换能器与外围的环形ABH结构组成.ABH结构的存在实现了换能器径向振动与弯曲振动之间的转换,... 详细信息

基于弯曲波在声黑洞(acoustic black hole,ABH)结构中振幅不断增大的特性,提出了一种新型径向夹心式径-弯复合换能器,该换能器由径向夹心式圆环换能器与外围的环形ABH结构组成.ABH结构的存在实现了换能器径向振动与弯曲振动之间的转换,提高了换能器的声辐射性能.利用几何声学的方法建立了ABH结构弯曲振动的解析模型,给出了其弯曲振动的本征频率,并结合有限元方法讨论了换能器机电转换性能随尺寸变化的关系.通过有限元方法给出了该换能器在空气中的辐射声压场、辐射声强以及辐射指向性,仿真结果表明,ABH结构的存在能够改善换能器弯曲振动的机电转换性能,提高换能器的声辐射性能,使换能器呈现出一定的辐射指向性.最后通过实验对换能器样机的电阻抗特性以及振动模态进行测量,实验结果与仿真相符合.

关键词：声黑洞换能器径向振动弯曲振动

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Sinensetin protects against periodontitis through binding to Bach1 enhancing its ubiquitination degradation and improving oxidative stress

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International Journal of Oral Science 2024年第03期 553-562页

作者： Zhiyao yuan Junjie Li Fuyu Xiao yu Wu Zhiting Zhang Jiahong Shi Jun Qian Xudong Wu Fuhua Yan Department of Periodontology Nanjing Stomatological Hospital Affiliated Hospital of Medical School Institute of Stomatology State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin(Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence *** immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant ***, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

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并购双方资源配置战略差异与全要素生产率提升研究

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南开管理评论 2024年第2期27卷 161-170,256,I0030,I0031页

作者：余鹏翼徐咏仪余言广东外语外贸大学会计学院暨南大学经济学院新加坡国立大学能源研究所

生产要素的合理配置既需要在宏观层面进行调控,也需要企业自身在微观层面妥善安排资源,提高资源配置效率。本文以中国上市公司并购事件为样本,探讨并购双方资源配置战略差异对企业全要素生产率的影响。研究结果显示,并购双方资源配置战... 详细信息

生产要素的合理配置既需要在宏观层面进行调控,也需要企业自身在微观层面妥善安排资源,提高资源配置效率。本文以中国上市公司并购事件为样本,探讨并购双方资源配置战略差异对企业全要素生产率的影响。研究结果显示,并购双方资源配置战略差异越大,并购后并购方全要素生产率越低;进一步分析发现,并购双方资源配置战略差异改变了并购方的资源配置倾向,加大整合难度;同时,资源配置战略差异会降低并购方的公司价值,全要素生产率起到了降低财务绩效的中介作用;最后,为了减少双方资源配置战略差异对全要素生产率的负面影响,并购方需要着重考虑被并购方特征与组织环境的调节效应。

关键词：资源配置并购战略差异全要素生产率并购绩效

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Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis

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World Journal of Orthopedics 2024年第4期15卷 363-378页

作者： Xu-Chang Zhou Dong-Xue Wang Chun-yu Zhang Ya-Jing Yang Ruo-Bing Zhao Sheng-Yao Liu Guo-Xin Ni School of Sport Medicine and Rehabilitation Beijing Sport UniversityBeijing 100084China Department of Acupuncture and Moxibustion Hubei University of Chinese MedicineWuhan 430065Hubei ProvinceChina Department of Spinal Surgery The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510260Guangdong ProvinceChina Department of Rehabilitation Medicine The First Affiliated Hospital of Xiamen UniversityXiamen 361003Fujian ProvinceChina

BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone *** To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying *** 20 growing mice were randomly divided into two groups:Con group(control group,n=10)and Ex group(treadmill exercise group,n=10).Hematoxylin-eosin staining,immunohistochemistry,and micro-CT scanning were used to assess the bone formation-related indexes of the mouse *** analysis was used to find potential miRNAs targets of long non-coding RNA H19(lncRNA H19).RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic *** Compared with the Con group,the expression of bone morphogenetic protein 2 was also significantly *** micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density,bone volume fraction,and the number of trabeculae,and decreased trabecular segregation in the femur of *** of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic *** addition,knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers,which is consistent with the results of autophagy-related protein changes detected in mouse femurs by *** Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice,thus enhancing the peak bone mass of *** lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

关键词： Exercise Osteogenic differentiation Bone formation Bone mesenchymal stem cells Autophagy

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Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles:Sequential Embryo Transfer or Double-blastocyst Transfer?

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Current Medical Science 2024年第1期44卷 212-222页

作者： Qiao-hang ZHAO yu-wei SONG Jian CHEN Xiang ZHOU Ji-lai XIE Qiu-ping YAO Qi-yin DONG Chun FENG Li-ming ZHOU Wei-ping FU Min JIN The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou 310052China Jiaxing Maternity and Child Health Care Hospital Jiaxing 314051China Huzhou Maternity and Child Care Hospital Huzhou 313002China Ningbo Women and Children's Hospital Ningbo 315000China

Objective Both sequential embryo transfer(SeET)and double-blastocyst transfer(DBT)can serve as embryo transfer strategies for women with recurrent implantation failure(RIF).This study aims to compare the effects of SeET and DBT on pregnancy *** Totally,261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective *** to different embryo quality and transfer strategies,they were divided into four groups:group A,good-quality SeET(GQ-SeET,n=38 cycles);group B,poor-quality or mixed-quality SeET(PQ/MQ-SeET,n=31 cycles);group C,good-quality DBT(GQ-DBT,n=121 cycles);and group D,poor-quality or mixed-quality DBT(PQ/MQ-DBT,n=71 cycles).The main outcome,clinical pregnancy rate,was compared,and the generalized estimating equation(GEE)model was used to correct potential confounders that might impact pregnancy *** GQ-DBT achieved a significantly higher clinical pregnancy rate(aOR 2.588,95%CI 1.267–5.284,P=0.009)and live birth rate(aOR 3.082,95%CI 1.482–6.412,P=0.003)than PQ/***,the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET(aOR 4.047,95%CI 1.218–13.450,P=0.023).The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT,and the same results were found between PQ/MQ-SeET and PQ/*** SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two *** clinical pregnancy outcomes could be obtained by transferring good-quality embryos,no matter whether in SeET or *** quality plays a more important role in pregnancy outcomes for RIF patients.

关键词： recurrent implantation failure sequential embryo transfer frozen-thawed embryo transfer embryo transfer strategies

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单向陶瓷基复合材料循环迟滞模型研究

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南京航空航天大学学报 2024年第1期56卷 116-123页

作者：段誉周储伟南京航空航天大学航空学院南京210016

为了模拟单向陶瓷基复合材料(Ceramic matrix composites, CMCs)在受到疲劳加载时的应力-应变关系,建立不同循环次数、不同疲劳峰值载荷的单向陶瓷基复合材料疲劳迟滞回线理论模型。将加载过程分为4个阶段且脱粘区域由新正向滑移区域、... 详细信息

为了模拟单向陶瓷基复合材料(Ceramic matrix composites, CMCs)在受到疲劳加载时的应力-应变关系,建立不同循环次数、不同疲劳峰值载荷的单向陶瓷基复合材料疲劳迟滞回线理论模型。将加载过程分为4个阶段且脱粘区域由新正向滑移区域、旧正向滑移区域和反向滑移区域组成,卸载过程滑移区域分为新正向滑移区域和反向滑移区域。分析了加载和卸载各个区域纤维轴向应力分布,推导了4个加载阶段和卸载对应的疲劳应力应变关系。预测了单向陶瓷基复合材料在不同峰值应力和不同循环的疲劳迟滞曲线,发现预测结果与文献中实验结果吻合较好。

关键词：发动机陶瓷复合材料循环失效

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Enteromorpha prolifera polysaccharide-Fe(Ⅲ) complex promotes intestinal development as a new iron supplement

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Science China Life Sciences 2024年

作者： Yingying Feng yuying Wu Jialu Wang Zhenglin Dong Qian yu Shuangshuang Xia Chunxue Liu Haihua Wang Xin Wu Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences CAS Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical Agriculture Chinese Academy of Sciences ANYOU Biotechnology Group Co.Ltd Qingdao Seawin Biotech Group Co. Ltd

Iron is a crucial micronutrient, and its deficiency can have detrimental effects on the health of infants. Dietary polysaccharide-iron(Ⅲ) complexes(PICs) are promising for addressing iron deficiency due to their minimal adverse reactions and high iron absorption rate. This study aimed to investigate the effects of dietary Enteromorpha prolifera polysaccharide-Fe(Ⅲ) complex(EP-Fe) on newborns, using 3-day weaned piglets as the iron-deficiency model. Results showed that EP-Fe improved iron levels and promoted intestinal development in piglets. Transcriptome sequencing revealed that EP-Fe increased the survival of intestinal epithelial cells under hypoxia by upregulating the expression of genes that promote the development of the vascular system. Additionally, EP-Fe enhanced the mucosal barrier functions by inhibiting myosin light chain kinase(MLCK)/phosphorylated myosin light chain(p-MLC)signaling pathway to increase the expression of intestinal tight junction proteins. Furthermore, the 16S rRNA gene sequencing of gut microbiota showed that EP-Fe promoted the enrichment of Bacteroides＿fragilis and other gut microbes that can metabolize carbohydrates. In conclusion, EP-Fe is an effective iron supplement for newborns, and it can be developed as a comprehensive nutritional supplement.

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