Maternal fish oil (FO) supplementation during pregnancy has been shown to improve pregnancy outcomes. FO is recognized as dietary source for n-3 polyunsaturated fatty acids (n-3 PUFAs). While early research has focused on the benefits of n-3 polyunsaturated fatty acids n-3 PUFAs for fetal neurodevelopment, retinal maturation and neonatal behavior, their roles in the placenta during late pregnancy and in the mammary gland during lactation still remain unknow.
Objectives
Here, we aim to clarify the mechanisms by which maternal supplementation with FO during pregnancy and lactation affects placental and mammary gland function.
Methods
We evaluated the effects of FO on maternal placental nutrient transport, mammary gland milk synthesis and offspring growth. We then explored the molecular mechanisms by which docosahexaenoic acid (DHA) affects the function of placental trophoblast cells and nutrient secretion of mammary epithelial cells through in vitro experiments. Finally, a lipopolysaccharide-challenged experiment was performed to access the potential of maternal FO supplementation in alleviating offspring intestinal inflammation.
Results
Maternal supplementation with FO during late pregnancy increased offspring birth weight, associated with enhanced maternal placental vascularization and nutrient transporter abundance. Additionally, maternal FO supplementation during lactation improved mammary gland secretion, increasing the fat, protein, and non-fat solids content in both colostrum and mature milk, thereby promoting offspring growth. The stimulatory effects of DHA on placental trophoblast cell function and nutrient secretion in mammary gland epithelial cells were mediated by GPR120 signaling pathways. Furthermore, maternal FO supplementation strengthened the placental barrier, reduced placental inflammation, oxidative stress and alleviated lipopolysaccharide-induced intestinal inflammation in offspring.
Conclusion
Maternal FO supplementation during late pregnancy and lactation enhances offspring growth by increasing placental nutrient transport and mammary gland secretion function, mediated by GPR120. Additionally, maternal FO supplementation reduces the susceptibility of offspring to intestinal inflammation.
{"title":"Maternal fish oil supplementation enhances placental nutrient transport and mammary gland secretion via the GPR120 signaling pathway","authors":"Qihui Li, Qianzi Zhang, Senlin Su, Siwang Yang, Jiayuan Shao, Wutai Guan, Shihai Zhang","doi":"10.1016/j.jare.2024.12.029","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.029","url":null,"abstract":"<h3>Introduction</h3>Maternal fish oil (FO) supplementation during pregnancy has been shown to improve pregnancy outcomes. FO is recognized as dietary source for n-3 polyunsaturated fatty acids (n-3 PUFAs). While early research has focused on the benefits of n-3 polyunsaturated fatty acids n-3 PUFAs for fetal neurodevelopment, retinal maturation and neonatal behavior, their roles in the placenta during late pregnancy and in the mammary gland during lactation still remain unknow.<h3>Objectives</h3>Here, we aim to clarify the mechanisms by which maternal supplementation with FO during pregnancy and lactation affects placental and mammary gland function.<h3>Methods</h3>We evaluated the effects of FO on maternal placental nutrient transport, mammary gland milk synthesis and offspring growth. We then explored the molecular mechanisms by which docosahexaenoic acid (DHA) affects the function of placental trophoblast cells and nutrient secretion of mammary epithelial cells through <em>in vitro</em> experiments. Finally, a lipopolysaccharide-challenged experiment was performed to access the potential of maternal FO supplementation in alleviating offspring intestinal inflammation.<h3>Results</h3>Maternal supplementation with FO during late pregnancy increased offspring birth weight, associated with enhanced maternal placental vascularization and nutrient transporter abundance. Additionally, maternal FO supplementation during lactation improved mammary gland secretion, increasing the fat, protein, and non-fat solids content in both colostrum and mature milk, thereby promoting offspring growth. The stimulatory effects of DHA on placental trophoblast cell function and nutrient secretion in mammary gland epithelial cells were mediated by GPR120 signaling pathways. Furthermore, maternal FO supplementation strengthened the placental barrier, reduced placental inflammation, oxidative stress and alleviated lipopolysaccharide-induced intestinal inflammation in offspring.<h3>Conclusion</h3>Maternal FO supplementation during late pregnancy and lactation enhances offspring growth by increasing placental nutrient transport and mammary gland secretion function, mediated by GPR120. Additionally, maternal FO supplementation reduces the susceptibility of offspring to intestinal inflammation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"62 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-17DOI: 10.1016/j.jare.2024.12.021
Yan Zhu, Haojie Yin, Xianli Zhong, Qin Zhang, Li Wang, Rong Lu, Ping Jia
Background
Despite earlier research indicating a potential link between the development of sarcopenia and an elevated risk of frailty, the lack of comprehensive prospective data on the correlation between sarcopenia and frailty incidence leaves open the question of whether depression and cognitive function mediate this association.
Objective
The principal aim of the current investigation was to evaluate the intricate interplay among sarcopenia, depression, and cognitive function collectively influence the risk of developing frailty.
Methods
The participants included in this study were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS), which collectively encompassed a total of 3,108 participants. To examine the interrelationships among sarcopenia, depression, cognitive function, and the incidence of frailty, we employed Cox regression models along with structural equation modelling, while making necessary adjustments for baseline demographic characteristics and various lifestyle factors.
Results
During a 4-year follow-up, we documented 753 frailty events. Compared to those with nonsarcopenia, those with possible sarcopenia and sarcopenia presented risk ratios for frailty events of 1.354 (95 % CI: 1.156, 1.586) and 1.514 (95 % CI: 1.203, 1.907), respectively. Stratified analyses by different statuses of sarcopenia further revealed that the significant effect of depression on frailty was present across all groups (nonsarcopenia, possible sarcopenia and sarcopenia), whereas the effect of cognitive function on frailty was limited to the non-sarcopenia and possible sarcopenia groups. Mediation analysis showed that sarcopenia was correlated not only with frailty through depression and cognitive function separately but also through a chain-mediated effect of depression and cognitive function together.
Conclusions
Sarcopenia is associated with frailty, depression and cognitive function playing partial, mediating roles. Frailty’s susceptibility to depression and cognitive function differs based on sarcopenia status. Therefore, comprehensive interventions that include sarcopenia screening, interventions, improvements in depression, the promotion of mental health, and delays in cognitive decline will be more effective in preventing and delaying frailty. This effectiveness is particularly relevant for middle-aged and older adults who reside in China.
{"title":"Exploring the mediating roles of depression and cognitive function in the association between sarcopenia and frailty: A Cox survival analysis approach","authors":"Yan Zhu, Haojie Yin, Xianli Zhong, Qin Zhang, Li Wang, Rong Lu, Ping Jia","doi":"10.1016/j.jare.2024.12.021","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.021","url":null,"abstract":"<h3>Background</h3>Despite earlier research indicating a potential link between the development of sarcopenia and an elevated risk of frailty, the lack of comprehensive prospective data on the correlation between sarcopenia and frailty incidence leaves open the question of whether depression and cognitive function mediate this association.<h3>Objective</h3>The principal aim of the current investigation was to evaluate the intricate interplay among sarcopenia, depression, and cognitive function collectively influence the risk of developing frailty.<h3>Methods</h3>The participants included in this study were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS), which collectively encompassed a total of 3,108 participants. To examine the interrelationships among sarcopenia, depression, cognitive function, and the incidence of frailty, we employed Cox regression models along with structural equation modelling, while making necessary adjustments for baseline demographic characteristics and various lifestyle factors.<h3>Results</h3>During a 4-year follow-up, we documented 753 frailty events. Compared to those with nonsarcopenia, those with possible sarcopenia and sarcopenia presented risk ratios for frailty events of 1.354 (95 % CI: 1.156, 1.586) and 1.514 (95 % CI: 1.203, 1.907), respectively. Stratified analyses by different statuses of sarcopenia further revealed that the significant effect of depression on frailty was present across all groups (nonsarcopenia, possible sarcopenia and sarcopenia), whereas the effect of cognitive function on frailty was limited to the non-sarcopenia and possible sarcopenia groups. Mediation analysis showed that sarcopenia was correlated not only with frailty through depression and cognitive function separately but also through a chain-mediated effect of depression and cognitive function together.<h3>Conclusions</h3>Sarcopenia is associated with frailty, depression and cognitive function playing partial, mediating roles. Frailty’s susceptibility to depression and cognitive function differs based on sarcopenia status. Therefore, comprehensive interventions that include sarcopenia screening, interventions, improvements in depression, the promotion of mental health, and delays in cognitive decline will be more effective in preventing and delaying frailty. This effectiveness is particularly relevant for middle-aged and older adults who reside in China.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-17DOI: 10.1016/j.jare.2024.12.013
Kaichong Teng, Neng Zhao, Yonghong Xie, Rongbai Li, Jianxiong Li
Introduction
The floret of rice is a main component of the spikelet, and the ovule of pistil is a critical organ for successful reproduction and determines the number of seeds. However, the molecular mechanisms underlying the ovule development remain elusive.
Objective
Twin-seedling rice has great potential for application in rice production. The study was to isolate the gene that controls twin-seedling in rice and explore the molecular function of the gene in floret development.
Methods
We discovered a twin-seedling rice (tsr) mutant and constructed different segregating populations to clone TSR gene using map-based cloning method. To explore the molecular functions of TSR in determination of the ovary number and development, we applied molecular technologies such as yeast two-hybrid assay, electrophoretic mobility shift assay (EMSA), and dual-LUC transient expression assay to search for the TSR-interacting proteins and the target genes regulated by TSR.
Results
We report here the map-based cloning of TSR which encodes an AP2/ERF transcription factor. Mutations in TSR lead to occurrence of the twin-seedling rice. The tsr mutant showed open hulls of the spikelets and displayed changes in the number of stamens and ovules of the florets. The ovary of tsr mutant contained two conjugated ovules which developed into a mature seed with two viable embryos. Mechanistic studies revealed that TSR regulates the expression levels of genes related to spikelet determination and ovule identity by binding to their promoters. Furthermore, TSR interacted with OsMADS1 and this interaction allowed OsMADS1 to modulate the transcriptional activities of TSR on gene expression. The molecular study of TSR provides new insights into the formation and development of rice floret and helps breeders generate twin-seedling rice in production.
引言水稻的小花是小穗的主要组成部分，而雌蕊的胚珠是成功繁殖的关键器官，决定着种子的数量。目的双苗水稻在水稻生产中具有巨大的应用潜力。方法 我们发现了双苗水稻（tsr）突变体，并利用基于图谱的克隆方法构建了不同的分离群体来克隆 TSR 基因。为了探索TSR在决定子房数量和发育中的分子功能，我们应用酵母双杂交实验、电泳迁移实验（EMSA）和双LUC瞬时表达实验等分子技术寻找TSR的相互作用蛋白和受TSR调控的靶基因。TSR 基因突变导致双苗水稻的出现。tsr突变体的小穗呈开壳状，小花的雄蕊和胚珠数量也发生了变化。tsr突变体的子房中有两个结合胚珠，这些胚珠发育成带有两个可存活胚的成熟种子。机理研究发现，TSR 通过与小穗确定和胚珠特征相关基因的启动子结合来调节这些基因的表达水平。此外，TSR 与 OsMADS1 相互作用，这种作用使 OsMADS1 能够调节 TSR 对基因表达的转录活动。对TSR的分子研究为水稻小花的形成和发育提供了新的见解，有助于育种者在生产中培育双苗水稻。
{"title":"An AP2/ERF transcription factor controls generation of the twin-seedling rice","authors":"Kaichong Teng, Neng Zhao, Yonghong Xie, Rongbai Li, Jianxiong Li","doi":"10.1016/j.jare.2024.12.013","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.013","url":null,"abstract":"<h3>Introduction</h3>The floret of rice is a main component of the spikelet, and the ovule of pistil is a critical organ for successful reproduction and determines the number of seeds. However, the molecular mechanisms underlying the ovule development remain elusive.<h3>Objective</h3>Twin-seedling rice has great potential for application in rice production. The study was to isolate the gene that controls twin-seedling in rice and explore the molecular function of the gene in floret development.<h3>Methods</h3>We discovered a twin-seedling rice (<em>tsr</em>) mutant and constructed different segregating populations to clone <em>TSR</em> gene using map-based cloning method. To explore the molecular functions of <em>TSR</em> in determination of the ovary number and development, we applied molecular technologies such as yeast two-hybrid assay, electrophoretic mobility shift assay (EMSA), and dual-LUC transient expression assay to search for the TSR-interacting proteins and the target genes regulated by <em>TSR</em>.<h3>Results</h3>We report here the map-based cloning of <em>TSR</em> which encodes an AP2/ERF transcription factor. Mutations in <em>TSR</em> lead to occurrence of the twin-seedling rice. The <em>tsr</em> mutant showed open hulls of the spikelets and displayed changes in the number of stamens and ovules of the florets. The ovary of <em>tsr</em> mutant contained two conjugated ovules which developed into a mature seed with two viable embryos. Mechanistic studies revealed that <em>TSR</em> regulates the expression levels of genes related to spikelet determination and ovule identity by binding to their promoters. Furthermore, TSR interacted with OsMADS1 and this interaction allowed OsMADS1 to modulate the transcriptional activities of TSR on gene expression. The molecular study of <em>TSR</em> provides new insights into the formation and development of rice floret and helps breeders generate twin-seedling rice in production.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"77 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Altered epigenetic reprogramming enables breast cancer cells to adapt to hypoxic stress. Hypoxic microenvironment can alter immune cell infiltration and function, limiting the effectiveness of immunotherapy.
Objectives
The study aimed to identify how fat mass and obesity-associated protein (FTO) helps breast cancer cells cope with the hypoxic microenvironment and the mechanisms behind breast cancer cell resistance to tumor immunity.
Methods
Clinical samples were utilized to analyze the impact of FTO on breast cancer progression and the effect of programmed cell death protein 1/ programmed cell death 1 ligand 1(PD-1/PD-L1) immune checkpoint inhibitor treatment. Utilized MeRIP-seq and mRNA-seq to analyze the downstream genes regulated by FTO under hypoxia. Methylation modification regulation of PDK1 by FTO was clarified using RIP. Then mouse models were utilized to analyze the efficacy of inhibiting FTO and 3-Phosphoinositide-dependent protein kinase 1(PDK1) in combination with PD-1/PD-L1 immune checkpoint inhibitor treatment.
Result
N6-Methyladenosine(m6A) demethylase FTO was transcriptionally activated by hypoxia inducible factor 1α(HIF-1α). PDK1 was identified as a potential target of FTO under hypoxic conditions through high-throughput sequencing. Mechanistically, overexpression of FTO decreases m6A modification sites on PDK1 mRNA, preventing YTH domain family 3(YTHDF3) from recognizing and binding to these sites, thereby inhibiting the degradation of PDK1 mRNA. Overexpression of PDK1 activates the AKT/STAT3 pathway, leading to enhanced PD-L1 expression. Targeting the FTO and PDK1-AKT pathways with FB23 and BX-912 inhibit breast cancer growth, enhance cytotoxic T lymphocyte (CTL) activity, and enhance the effectiveness of the PD-1/PD-L1 checkpoint inhibitor Atezolizumab.
Conclusion
This study reveals that HIF-1α promotes FTO transcription under hypoxic conditions, thereby increasing PD-L1 expression through the PDK1/AKT/STAT3 axis. Inhibition of FTO and PDK1 under hypoxic conditions could serve as a promising immunotherapeutic strategy for breast cancer.
{"title":"FTO activates PD-L1 promotes immunosuppression in breast cancer via the m6A/YTHDF3/PDK1 axis under hypoxic conditions","authors":"Siyu Wang, Xingda Zhang, Quanrun Chen, Hao Wu, Shihan Cao, Shilu Zhao, Guozheng Li, Jianyu Wang, Yajie Gong, Xinheng Wang, Da Pang, Song Gao","doi":"10.1016/j.jare.2024.12.026","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.026","url":null,"abstract":"<h3>Introduction</h3>Altered epigenetic reprogramming enables breast cancer cells to adapt to hypoxic stress. Hypoxic microenvironment can alter immune cell infiltration and function, limiting the effectiveness of immunotherapy.<h3>Objectives</h3>The study aimed to identify how fat mass and obesity-associated protein (FTO) helps breast cancer cells cope with the hypoxic microenvironment and the mechanisms behind breast cancer cell resistance to tumor immunity.<h3>Methods</h3>Clinical samples were utilized to analyze the impact of FTO on breast cancer progression and the effect of programmed cell death protein 1/ programmed cell death 1 ligand 1(PD-1/PD-L1) immune checkpoint inhibitor treatment. Utilized MeRIP-seq and mRNA-seq to analyze the downstream genes regulated by FTO under hypoxia. Methylation modification regulation of PDK1 by FTO was clarified using RIP. Then mouse models were utilized to analyze the efficacy of inhibiting FTO and 3-Phosphoinositide-dependent protein kinase 1(PDK1) in combination with PD-1/PD-L1 immune checkpoint inhibitor treatment.<h3>Result</h3>N6-Methyladenosine(m<sup>6</sup>A) demethylase FTO was transcriptionally activated by hypoxia inducible factor 1α(HIF-1α). PDK1 was identified as a potential target of FTO under hypoxic conditions through high-throughput sequencing. Mechanistically, overexpression of FTO decreases m<sup>6</sup>A modification sites on PDK1 mRNA, preventing YTH domain family 3(YTHDF3) from recognizing and binding to these sites, thereby inhibiting the degradation of PDK1 mRNA. Overexpression of PDK1 activates the AKT/STAT3 pathway, leading to enhanced PD-L1 expression. Targeting the FTO and PDK1-AKT pathways with FB23 and BX-912 inhibit breast cancer growth, enhance cytotoxic T lymphocyte (CTL) activity, and enhance the effectiveness of the PD-1/PD-L1 checkpoint inhibitor Atezolizumab.<h3>Conclusion</h3>This study reveals that HIF-1α promotes FTO transcription under hypoxic conditions, thereby increasing PD-L1 expression through the PDK1/AKT/STAT3 axis. Inhibition of FTO and PDK1 under hypoxic conditions could serve as a promising immunotherapeutic strategy for breast cancer.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"48 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-17DOI: 10.1016/j.jare.2024.12.024
Shiqiang Yan, Yan Lu, Changming An, Wanglai Hu, Yaofeng Chen, Ziwen Li, Wenbo Wei, Zongzheng Chen, Xianhai Zeng, Wei Xu, Zhenghua Lv, Fan Pan, Wei Gao, Yongyan Wu
Background
Cells in the body reside in a dynamic microenvironment subjected to various physical stimuli, where mechanical stimulation plays a crucial role in regulating cellular physiological behaviors and functions.
Aim of Review
Investigating the mechanisms and interactions of mechanical transmission is essential for understanding the physiological and functional interplay between cells and physical stimuli. Therefore, establishing an in vitro biomechanical stimulation cell culture system holds significant importance for research related to cellular biomechanics.
Key Scientific Concepts of Review
In this review, we primarily focused on various biomechanically relevant cell culture systems and highlighted the advancements and prospects in their preparation processes. Firstly, we discussed the types and characteristics of biomechanics present in the microenvironment within the human body. Subsequently, we introduced the research progress, working principles, preparation processes, potential advantages, applications, and challenges of various biomechanically relevant in vitro cell culture systems. Additionally, we summarized and categorized currently commercialized biomechanically relevant cell culture systems, offering a comprehensive reference for researchers in related fields.
{"title":"Biomechanical research using advanced micro-nano devices: In-Vitro cell Characterization focus","authors":"Shiqiang Yan, Yan Lu, Changming An, Wanglai Hu, Yaofeng Chen, Ziwen Li, Wenbo Wei, Zongzheng Chen, Xianhai Zeng, Wei Xu, Zhenghua Lv, Fan Pan, Wei Gao, Yongyan Wu","doi":"10.1016/j.jare.2024.12.024","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.024","url":null,"abstract":"<h3>Background</h3>Cells in the body reside in a dynamic microenvironment subjected to various physical stimuli, where mechanical stimulation plays a crucial role in regulating cellular physiological behaviors and functions.<h3>Aim of Review</h3>Investigating the mechanisms and interactions of mechanical transmission is essential for understanding the physiological and functional interplay between cells and physical stimuli. Therefore, establishing an in vitro biomechanical stimulation cell culture system holds significant importance for research related to cellular biomechanics.<h3>Key Scientific Concepts of Review</h3>In this review, we primarily focused on various biomechanically relevant cell culture systems and highlighted the advancements and prospects in their preparation processes. Firstly, we discussed the types and characteristics of biomechanics present in the microenvironment within the human body. Subsequently, we introduced the research progress, working principles, preparation processes, potential advantages, applications, and challenges of various biomechanically relevant in vitro cell culture systems. Additionally, we summarized and categorized currently commercialized biomechanically relevant cell culture systems, offering a comprehensive reference for researchers in related fields.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"30 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-15DOI: 10.1016/j.jare.2024.12.012
Xia Yu, Xinyi Zhou, Tong Wu, Bohua Ren, Tao Fang, Chaonan Cong, Guofang Wu, Lihong Yao, Xiaoding Wei, Bo Liu, Yun Lu
Introduction
Materials exhibiting a Poisson’s ratio of zero have attracted considerable interest due to their unique properties and potential applications in various fields, including aerospace, athletic footwear, and sporting equipment. However, the high costs associated with their structural fabrication and the dependence on synthetic chemical materials for most zero Poisson’s ratio materials complicate the preparation processes of current elastic materials, resulting in negative environmental impacts.
Objectives
This study presents a sustainable treatment strategy that utilizes the inherent cellular structure of wood to achieve a zero Poisson’s ratio, thereby enhancing its elasticity.
Methods
By strategically selecting tree species with varying tissue compositions and employing simple chemical and heat treatments, we developed a commercially viable elastic wood material with a zero Poisson’s ratio that meets diverse stress rebound requirements.
Results
The unique internal structure of the wood not only provides high fatigue resistance—capable of withstanding 5000 cycles of compression at a strain of 40 %—but also ensures excellent resilience and processability. At a deformation level of 60 %, the elastic modulus reaches 90.9 MPa. Additionally, the material retains its elasticity even at extremely low temperatures of −196 °C and demonstrates the ability to endure elevated temperatures following carbonization at 1200 °C.
Conclusion
This study demonstrates that wood-based materials with a zero Poisson’s ratio exhibit remarkable stability after cyclic compression, presenting a viable pathway for developing superelastic materials suitable for both high- and low-temperature applications.
{"title":"Selective Regulation of ray tissue for achieving ultrastable Zero-Poisson’s-ratio material out of wood","authors":"Xia Yu, Xinyi Zhou, Tong Wu, Bohua Ren, Tao Fang, Chaonan Cong, Guofang Wu, Lihong Yao, Xiaoding Wei, Bo Liu, Yun Lu","doi":"10.1016/j.jare.2024.12.012","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.012","url":null,"abstract":"<h3>Introduction</h3>Materials exhibiting a Poisson’s ratio of zero have attracted considerable interest due to their unique properties and potential applications in various fields, including aerospace, athletic footwear, and sporting equipment. However, the high costs associated with their structural fabrication and the dependence on synthetic chemical materials for most zero Poisson’s ratio materials complicate the preparation processes of current elastic materials, resulting in negative environmental impacts.<h3>Objectives</h3>This study presents a sustainable treatment strategy that utilizes the inherent cellular structure of wood to achieve a zero Poisson’s ratio, thereby enhancing its elasticity.<h3>Methods</h3>By strategically selecting tree species with varying tissue compositions and employing simple chemical and heat treatments, we developed a commercially viable elastic wood material with a zero Poisson’s ratio that meets diverse stress rebound requirements.<h3>Results</h3>The unique internal structure of the wood not only provides high fatigue resistance—capable of withstanding 5000 cycles of compression at a strain of 40 %—but also ensures excellent resilience and processability. At a deformation level of 60 %, the elastic modulus reaches 90.9 MPa. Additionally, the material retains its elasticity even at extremely low temperatures of −196 °C and demonstrates the ability to endure elevated temperatures following carbonization at 1200 °C.<h3>Conclusion</h3>This study demonstrates that wood-based materials with a zero Poisson’s ratio exhibit remarkable stability after cyclic compression, presenting a viable pathway for developing superelastic materials suitable for both high- and low-temperature applications.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"244 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-14DOI: 10.1016/j.jare.2024.12.020
Weiwei Zeng, Huan Deng, Yuning Luo, Shilong Zhong, Min Huang, Brian Tomlinson
Background: Elevated low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Statins are the cornerstone of preventing and treating cardiovascular disease and can reduce LDL cholesterol by more than 60%. Although statins have high tolerability and safety, as the number of users increases, their adverse reactions in the liver, kidneys, skeletal muscles, and their potential to induce diabetes have also received widespread attention.Aim of review: How to maximize the lipid-lowering effect of statins, reduce the incidence of adverse reactions, promote the rational application of statins in the clinic, and improve the risk–benefit level, in order to benefit more cardiovascular patients and provide reference for the related basic research of statins.Key scientific concepts of review: This article provides a comprehensive review of the clinical manifestations of statin-related adverse reactions (associated myopathy, hepatotoxicity, nephrotoxicity, glycemic effects, central nervous system, hemorrhagic stroke, etc.), risk factors for triggering adverse reactions, statin interactions with other drugs (food), potential etiopathological mechanisms and common interventions in the clinic. Genetic diversity is strongly associated with statin adverse effects, and thus, in the future genetic testing may also be key to mitigating statin adverse effects.
{"title":"Advances in statin adverse reactions and the potential mechanisms: A review","authors":"Weiwei Zeng, Huan Deng, Yuning Luo, Shilong Zhong, Min Huang, Brian Tomlinson","doi":"10.1016/j.jare.2024.12.020","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.020","url":null,"abstract":"<strong>Background:</strong> Elevated low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Statins are the cornerstone of preventing and treating cardiovascular disease and can reduce LDL cholesterol by more than 60%. Although statins have high tolerability and safety, as the number of users increases, their adverse reactions in the liver, kidneys, skeletal muscles, and their potential to induce diabetes have also received widespread attention.Aim <strong>of review:</strong> How to maximize the lipid-lowering effect of statins, reduce the incidence of adverse reactions, promote the rational application of statins in the clinic, and improve the risk–benefit level, in order to benefit more cardiovascular patients and provide reference for the related basic research of statins.<strong>Key scientific concepts of review:</strong> This article provides a comprehensive review of the clinical manifestations of statin-related adverse reactions (associated myopathy, hepatotoxicity, nephrotoxicity, glycemic effects, central nervous system, hemorrhagic stroke, etc.), risk factors for triggering adverse reactions, statin interactions with other drugs (food), potential etiopathological mechanisms and common interventions in the clinic. Genetic diversity is strongly associated with statin adverse effects, and thus, in the future genetic testing may also be key to mitigating statin adverse effects.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"20 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liver fibrosis is the common fate of NASH and poses a major health threat with very limited pharmacological treatments.
Objectives
This study aims to investigate the preventive effect of hinokitone (HO), an isolated compound from Agathis dammara, on NASH fibrosis and its underlying mechanism.
Methods
To investigate the effect of HO on NASH fibrosis, C57BL/6 mice were either fed a high-fat diet (HFD) in conjunction with intraperitoneal injection of CCl4 for 8 weeks or single CCl4 for 14 days to establish mouse liver fibrosis model, and HO was administered by gavage simultaneously. To elucidate the underlying mechanisms, HepG2 cells were stimulated by palmitic acid (PA) or tumor necrosis factor α plus actinomycin-D (Act-D + TNFα) to induce hepatocyte apoptosis model. Furthermore, hepatocyte Farnesoid-X-receptor (FXR) specifically knocked out mice were established by the albumin-Cre-loxP recombination enzyme system to ascertain the role of FXR in the anti-NASH fibrosis effects of HO.
Results
The results showed that HO presented dose-dependent anti-liver fibrosis efficacy in NASH mice induced by HFD + CCl4 and CCl4-induced mouse liver fibrosis. Cellularly, HO significantly inhibited PA-induced lipotoxic apoptosis and Act-D + TNFα-induced exogenous apoptosis in hepatocytes, which in turn prevented HSC activation. Mechanistically, bioinformatics analysis and surface plasmon resonance assay had identified hepatocyte FXR as a target of HO. Specifically, HO directly bound to FXR and upregulated its protein level by inhibiting proteasomal degradation. In turn, HO attenuated hepatocyte lipid deposition through upregulating the FXR’s downstream target genes SHP and CES1, and reduced cleaved-CASP8 level, thereby inhibiting hepatocyte apoptosis. Furthermore, HO lost its function in the inhibition of hepatocyte apoptosis and liver fibrosis when knockout hepatocyte FXR.
Conclusion
In conclusion, HO has an inhibitory effect on NASH fibrosis. This effect is mediated by targeting upregulation of hepatocyte FXR, which in turn attenuates hepatocyte apoptosis and thus indirectly inhibits the activation of HSCs.
{"title":"Natural small molecule hinokitone mitigates NASH fibrosis by targeting regulation of FXR-mediated hepatocyte apoptosis","authors":"Ze-Jiang Ma, Ying-Kun Qiu, Zhe-Wei Yu, Tian-Tian Song, Yi-Tong Hu, An-Kang Peng, Rong Qi","doi":"10.1016/j.jare.2024.12.016","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.016","url":null,"abstract":"<h3>Introduction</h3>Liver fibrosis is the common fate of NASH and poses a major health threat with very limited pharmacological treatments.<h3>Objectives</h3>This study aims to investigate the preventive effect of hinokitone (HO), an isolated compound from <em>Agathis dammara</em>, on NASH fibrosis and its underlying mechanism.<h3>Methods</h3>To investigate the effect of HO on NASH fibrosis, C57BL/6 mice were either fed a high-fat diet (HFD) in conjunction with intraperitoneal injection of CCl<sub>4</sub> for 8 weeks or single CCl<sub>4</sub> for 14 days to establish mouse liver fibrosis model, and HO was administered by gavage simultaneously. To elucidate the underlying mechanisms, HepG2 cells were stimulated by palmitic acid (PA) or tumor necrosis factor α plus actinomycin-D (Act-D + TNFα) to induce hepatocyte apoptosis model. Furthermore, hepatocyte Farnesoid-X-receptor (FXR) specifically knocked out mice were established by the albumin-Cre-loxP recombination enzyme system to ascertain the role of FXR in the anti-NASH fibrosis effects of HO.<h3>Results</h3>The results showed that HO presented dose-dependent anti-liver fibrosis efficacy in NASH mice induced by HFD + CCl<sub>4</sub> and CCl<sub>4</sub>-induced mouse liver fibrosis. Cellularly, HO significantly inhibited PA-induced lipotoxic apoptosis and Act-D + TNFα-induced exogenous apoptosis in hepatocytes, which in turn prevented HSC activation. Mechanistically, bioinformatics analysis and surface plasmon resonance assay had identified hepatocyte FXR as a target of HO. Specifically, HO directly bound to FXR and upregulated its protein level by inhibiting proteasomal degradation. In turn, HO attenuated hepatocyte lipid deposition through upregulating the FXR’s downstream target genes <em>SHP</em> and <em>CES1</em>, and reduced cleaved-CASP8 level, thereby inhibiting hepatocyte apoptosis. Furthermore, HO lost its function in the inhibition of hepatocyte apoptosis and liver fibrosis when knockout hepatocyte FXR.<h3>Conclusion</h3>In conclusion, HO has an inhibitory effect on NASH fibrosis. This effect is mediated by targeting upregulation of hepatocyte FXR, which in turn attenuates hepatocyte apoptosis and thus indirectly inhibits the activation of HSCs.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"146 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aging influences the regenerative and reparative functions of dental pulp, and an in-depth and complete understanding of aged dental pulp is highly important.
Objective
This study aimed to explore the heterogeneity of young and aged dental pulp tissue via single-cell RNA sequencing (scRNA-seq), search novel markers of aged dental pulp, and further explore their mechanism.
Methods
ScRNA-seq was employed to analyze the heterogeneity of young and aged dental pulp tissue, and immunohistochemical staining was used to detect new marker Insulin-like Growth Factor Binding Protein 7 (IGFBP7) in aged dental pulp. Differentially expressed genes (DEGs) between young and aged dental pulp tissue related with senescence-associated secretory phenotype (SASP) were validated in aging model of H2O2-induced dental pulp fibroblast (DPF). The effect of IGFBP7 on cellular senescence were validated by SA-β-Gal, γ-H2AX, and F-actin cytoskeletal staining. RNA-seq was used to analyze the mechanism of IGFBP7 alleviating senescence of H2O2-induced DPFs.
Results
A total of 32,012 cells were sequenced from 8 dental pulp samples and categorized into 8 main clusters, including fibroblasts (FB), endothelial cells, monocytes, T cells, B cells, mesenchymal stem cells, Schwann cells, and nonmyelinating ScCs. The ratio of fibroblasts was the highest, and FB1 was the largest subcluster of fibroblasts in the young group. In aged dental pulp, the ratio of fibroblasts was relatively low, and fibroblasts had more cellular communication with other cell types in fibroblast growth factor (FGF) and insulin-like growth factor (IGF) signal pathways. IGFBP7 was significantly upregulated in the aged group. Recombinant IGFBP7 reduced the senescence of H2O2-induced DPFs.
Conclusions
These findings offer insights into the mechanisms of dental pulp aging and enhance our understanding of dental pulp at the single-cell level. Further comprehensive studies are required to clarify the exact mechanisms through which IGFBP7 influences dental pulp aging.
{"title":"Insulin-like growth factor binding protein 7 identified in aged dental pulp by single-cell RNA sequencing","authors":"Zhongchun Tong, Jie Wu, Qimei Gong, Yifang Yuan, Shengchao Wang, Wenkai Jiang","doi":"10.1016/j.jare.2024.12.018","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.018","url":null,"abstract":"<h3>Introduction</h3>Aging influences the regenerative and reparative functions of dental pulp, and an in-depth and complete understanding of aged dental pulp is highly important.<h3>Objective</h3>This study aimed to explore the heterogeneity of young and aged dental pulp tissue via single-cell RNA sequencing (scRNA-seq), search novel markers of aged dental pulp, and further explore their mechanism.<h3>Methods</h3>ScRNA-seq was employed to analyze the heterogeneity of young and aged dental pulp tissue, and immunohistochemical staining was used to detect new marker Insulin-like Growth Factor Binding Protein 7 (IGFBP7) in aged dental pulp. Differentially expressed genes (DEGs) between young and aged dental pulp tissue related with senescence-associated secretory phenotype (SASP) were validated in aging model of H<sub>2</sub>O<sub>2</sub>-induced dental pulp fibroblast (DPF). The effect of IGFBP7 on cellular senescence were validated by SA-β-Gal, γ-H2AX, and F-actin cytoskeletal staining. RNA-seq was used to analyze the mechanism of IGFBP7 alleviating senescence of H<sub>2</sub>O<sub>2</sub>-induced DPFs.<h3>Results</h3>A total of 32,012 cells were sequenced from 8 dental pulp samples and categorized into 8 main clusters, including fibroblasts (FB), endothelial cells, monocytes, T cells, B cells, mesenchymal stem cells, Schwann cells, and nonmyelinating ScCs. The ratio of fibroblasts was the highest, and FB1 was the largest subcluster of fibroblasts in the young group. In aged dental pulp, the ratio of fibroblasts was relatively low, and fibroblasts had more cellular communication with other cell types in fibroblast growth factor (FGF) and insulin-like growth factor (IGF) signal pathways. IGFBP7 was significantly upregulated in the aged group. Recombinant IGFBP7 reduced the senescence of H<sub>2</sub>O<sub>2</sub>-induced DPFs.<h3>Conclusions</h3>These findings offer insights into the mechanisms of dental pulp aging and enhance our understanding of dental pulp at the single-cell level. Further comprehensive studies are required to clarify the exact mechanisms through which IGFBP7 influences dental pulp aging.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1016/j.jare.2024.11.034
Yu Liu, Qin Han, Jiaming Zhang, Xuehai Zhang, Yuqin Chen, Mingbo Li, Yongfang Hao, Yujie Hong, Ruizhen Tang, Brett J. Ferguson, Peter M. Gresshoff, Jie Kuai, Guangsheng Zhou, Xia Li, Hongtao Ji
Introduction
Crop rotation, a crucial agricultural practice that enhances soil health and crop productivity, is widely used in agriculture worldwide. Soybeans play a crucial role in crop rotation owing to their nitrogen-fixing ability, which is facilitated by symbiotic bacteria in their root systems. The soybean-rapeseed rotation is an effective agricultural practice in the Yangtze River Basin of China. However, the mechanism underlying the effectiveness of this system remains unknown.
Objectives
The aim of this study was to decipher the mechanisms by which previous soybean cultivation enhances the growth of subsequent rapeseed.
Methods
Soybeans with three distinct nodulation genotypes were rotated with rapeseed, and the impact of previous soybean cultivation on subsequent rapeseed growth was evaluated by examining the soybean root secretome and soil rhizosphere microbiome.
Results
Soybean-rapeseed rotation significantly enhanced subsequent rapeseed growth and yield, especially when supernodulating soybean plants were used, which released the most nitrogen into the soil rhizosphere. The differences in soybean nodulation capability led to variations in root exudation, which in turn influenced the bacterial communities in the rhizosphere. Notably, the supernodulating soybean plants promoted Sphingomonadaceae family of bacteria growth by secreting oleic acid and cis-4-hydroxy-D-proline, and further attracted them through cis-4-hydroxy-D-proline. Furthermore, the exogenous application of Sphingomonadaceae bacteria, either alone or in combination with rhizobia, significantly enhanced the growth of rapeseed.
Conclusion
Our data definitively demonstrated the crucial role of previous soybean cultivation in enhancing the yield of rapeseed, with the assistance of Sphingomonadaceae bacteria and rhizobia. This study elucidates the role of soybean nodulation in rhizosphere bacterial dynamics, highlighting its importance in sustainable agricultural practices.
{"title":"Soybean nodulation shapes the rhizosphere microbiome to increase rapeseed yield","authors":"Yu Liu, Qin Han, Jiaming Zhang, Xuehai Zhang, Yuqin Chen, Mingbo Li, Yongfang Hao, Yujie Hong, Ruizhen Tang, Brett J. Ferguson, Peter M. Gresshoff, Jie Kuai, Guangsheng Zhou, Xia Li, Hongtao Ji","doi":"10.1016/j.jare.2024.11.034","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.034","url":null,"abstract":"<h3>Introduction</h3>Crop rotation, a crucial agricultural practice that enhances soil health and crop productivity, is widely used in agriculture worldwide. Soybeans play a crucial role in crop rotation owing to their nitrogen-fixing ability, which is facilitated by symbiotic bacteria in their root systems. The soybean-rapeseed rotation is an effective agricultural practice in the Yangtze River Basin of China. However, the mechanism underlying the effectiveness of this system remains unknown.<h3>Objectives</h3>The aim of this study was to decipher the mechanisms by which previous soybean cultivation enhances the growth of subsequent rapeseed.<h3>Methods</h3>Soybeans with three distinct nodulation genotypes were rotated with rapeseed, and the impact of previous soybean cultivation on subsequent rapeseed growth was evaluated by examining the soybean root secretome and soil rhizosphere microbiome.<h3>Results</h3>Soybean-rapeseed rotation significantly enhanced subsequent rapeseed growth and yield, especially when supernodulating soybean plants were used, which released the most nitrogen into the soil rhizosphere. The differences in soybean nodulation capability led to variations in root exudation, which in turn influenced the bacterial communities in the rhizosphere. Notably, the supernodulating soybean plants promoted <em>Sphingomonadaceae</em> family of bacteria growth by secreting oleic acid and <em>cis</em>-4-hydroxy-D-proline, and further attracted them through <em>cis</em>-4-hydroxy-D-proline. Furthermore, the exogenous application of <em>Sphingomonadaceae</em> bacteria, either alone or in combination with rhizobia, significantly enhanced the growth of rapeseed.<h3>Conclusion</h3>Our data definitively demonstrated the crucial role of previous soybean cultivation in enhancing the yield of rapeseed, with the assistance of <em>Sphingomonadaceae</em> bacteria and rhizobia. This study elucidates the role of soybean nodulation in rhizosphere bacterial dynamics, highlighting its importance in sustainable agricultural practices.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"46 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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