Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2023.04.016
Weilin Xu , Jun Yan , Anwen Shao , Cameron Lenahan , Liansheng Gao , Haijian Wu , Jingwei Zheng , Jianmin Zhang , John H. Zhang
Peroxisomes and pexophagy have gained increasing attention in their role within the central nervous system (CNS) in recent years. In this review, we comprehensively discussed the physiological and pathological mechanisms of peroxisomes and pexophagy in neurological diseases. Peroxisomes communicate with mitochondria, endoplasmic reticulum, and lipid bodies. Their types, sizes, and shapes vary in different regions of the brain. Moreover, peroxisomes play an important role in oxidative homeostasis, lipid synthesis, and degradation in the CNS, whereas its dysfunction causes various neurological diseases. Therefore, selective removal of dysfunctional or superfluous peroxisomes (pexophagy) provides neuroprotective effects, which indicate a promising therapeutic target. However, pexophagy largely remains unexplored in neurological disorders. More studies are needed to explore the pexophagy's crosstalk mechanisms in neurological pathology.
{"title":"Peroxisome and pexophagy in neurological diseases","authors":"Weilin Xu , Jun Yan , Anwen Shao , Cameron Lenahan , Liansheng Gao , Haijian Wu , Jingwei Zheng , Jianmin Zhang , John H. Zhang","doi":"10.1016/j.fmre.2023.04.016","DOIUrl":"10.1016/j.fmre.2023.04.016","url":null,"abstract":"<div><div>Peroxisomes and pexophagy have gained increasing attention in their role within the central nervous system (CNS) in recent years. In this review, we comprehensively discussed the physiological and pathological mechanisms of peroxisomes and pexophagy in neurological diseases. Peroxisomes communicate with mitochondria, endoplasmic reticulum, and lipid bodies. Their types, sizes, and shapes vary in different regions of the brain. Moreover, peroxisomes play an important role in oxidative homeostasis, lipid synthesis, and degradation in the CNS, whereas its dysfunction causes various neurological diseases. Therefore, selective removal of dysfunctional or superfluous peroxisomes (pexophagy) provides neuroprotective effects, which indicate a promising therapeutic target. However, pexophagy largely remains unexplored in neurological disorders. More studies are needed to explore the pexophagy's crosstalk mechanisms in neurological pathology.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1389-1397"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48928316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2024.02.001
Juie Nahushkumar Rana , Sohail Mumtaz , Ihn Han , Eun Ha Choi
Lung cancer continues to be the second most common cancer diagnosed and the main cause of cancer-related death globally, which requires novel and effective treatment strategies. When considering treatment options, non-small cell lung cancer (NSCLC) remained a challenge, seeking new therapeutic strategies. High-power microwave (HPM) progressions have facilitated the advancement of new technologies as well as improvements to those already in use. The impact of HPM on NSCLC has not been investigated before. In this work, we uncovered the effect of pulsed HPM on NSCLC (H460 and A549) for the first time and the most likely underlying mechanisms. Two NSCLC (H460 and A549) cells and lung normal MRC5 were exposed to HPM (15, 30, 45, and 60) pulses (2.1 mJ/pulse). After exposure, the effects were observed at 12, 24, 48, and 72 h. HPM primarily increases the level of intracellular reactive species by a strong electric field of ∼27 kV/cm, which altered NSCLC viability, mitochondrial activity, and death rates. A model for the production of intracellular reactive species by HPM was also presented. NSCLC is found to be affected by HPM through DNA damage (upregulation of ATR/ATM, Chk1/Chk2, and P53) and increased expression of apoptotic markers. NAC scavenger and CPTIO-inhibitor confirm that the reactive species are mainly accountable for cellular effects. In order to ensure suitability for real-world usage, the skin depth was calculated as 30 mm. ROS played a main role in inducing cellular effects, with NO species possibly playing a contributing role. These findings clarify the cellular mechanisms underlying HPM-induced cell death, potentially advancing therapeutic approaches for treating NSCLC, and a useful first step for future investigations in this area. Moreover, this technique has the potential to serve as an adjunct to non-surgical methods in cancer therapy.
{"title":"Formation of reactive species via high power microwave induced DNA damage and promoted intrinsic pathway-mediated apoptosis in lung cancer cells: An in vitro investigation","authors":"Juie Nahushkumar Rana , Sohail Mumtaz , Ihn Han , Eun Ha Choi","doi":"10.1016/j.fmre.2024.02.001","DOIUrl":"10.1016/j.fmre.2024.02.001","url":null,"abstract":"<div><div>Lung cancer continues to be the second most common cancer diagnosed and the main cause of cancer-related death globally, which requires novel and effective treatment strategies. When considering treatment options, non-small cell lung cancer (NSCLC) remained a challenge, seeking new therapeutic strategies<strong>.</strong> High-power microwave (HPM) progressions have facilitated the advancement of new technologies as well as improvements to those already in use. The impact of HPM on NSCLC has not been investigated before. In this work, we uncovered the effect of pulsed HPM on NSCLC (H460 and A549) for the first time and the most likely underlying mechanisms. Two NSCLC (H460 and A549) cells and lung normal MRC5 were exposed to HPM (15, 30, 45, and 60) pulses (2.1 mJ/pulse). After exposure, the effects were observed at 12, 24, 48, and 72 h. HPM primarily increases the level of intracellular reactive species by a strong electric field of ∼27 kV/cm, which altered NSCLC viability, mitochondrial activity, and death rates. A model for the production of intracellular reactive species by HPM was also presented. NSCLC is found to be affected by HPM through DNA damage (upregulation of ATR/ATM, Chk1/Chk2, and P53) and increased expression of apoptotic markers. NAC scavenger and CPTIO-inhibitor confirm that the reactive species are mainly accountable for cellular effects. In order to ensure suitability for real-world usage, the skin depth was calculated as 30 mm. ROS played a main role in inducing cellular effects, with NO species possibly playing a contributing role. These findings clarify the cellular mechanisms underlying HPM-induced cell death, potentially advancing therapeutic approaches for treating NSCLC, and a useful first step for future investigations in this area. Moreover, this technique has the potential to serve as an adjunct to non-surgical methods in cancer therapy.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1542-1556"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139873171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2022.09.020
J.Y. Xu , F. Guillou , H. Yibole , V. Hardy
Peltier cell calorimetry is a powerful technique to record both the heat capacity and the latent heat, yet its availability is limited as it often requires homemade dedicated cryostats. Here, we describe the development of a Peltier cell differential scanning calorimeter facilitating the accessibility to the technique, since it is designed “as an option” for commonplace commercial cryostats equipped with high magnetic fields. This yields an apparatus well suited to detailed studies of magnetic transitions in general and of first-order magnetic transitions in particular. For magnetocaloric materials, our system can also be used to measure directly the isothermal entropy change ΔS induced by a magnetic field change; it even allows separating the cyclic (reversible) effect due to successive magnetization/demagnetization, which is the one relevant for applications, from the total magnetocaloric effect. To illustrate the versatility of this system, a thorough study of the ferromagnetic first-order transition of MnFe0.95P0.585Si0.34B0.075 is carried out. An exceptionally large cyclic entropy change at an intermediate field is observed in this compound, ΔScyclic = 13.2 J kg−1 K−1 for µ0ΔH = 1 T. This confirms that MnFe(P,Si,B) shows one of the most promising giant magnetocaloric effects to be used in emergent green technologies such as magnetocaloric cooling, heating or thermomagnetic waste heat recovery.
{"title":"Peltier cell calorimetry “as an option” for commonplace cryostats: Application to the case of MnFe(P,Si,B) magnetocaloric materials","authors":"J.Y. Xu , F. Guillou , H. Yibole , V. Hardy","doi":"10.1016/j.fmre.2022.09.020","DOIUrl":"10.1016/j.fmre.2022.09.020","url":null,"abstract":"<div><div>Peltier cell calorimetry is a powerful technique to record both the heat capacity and the latent heat, yet its availability is limited as it often requires homemade dedicated cryostats. Here, we describe the development of a Peltier cell differential scanning calorimeter facilitating the accessibility to the technique, since it is designed “as an option” for commonplace commercial cryostats equipped with high magnetic fields. This yields an apparatus well suited to detailed studies of magnetic transitions in general and of first-order magnetic transitions in particular. For magnetocaloric materials, our system can also be used to measure <em>directly</em> the isothermal entropy change Δ<em>S</em> induced by a magnetic field change; it even allows separating the cyclic (reversible) effect due to successive magnetization/demagnetization, which is the one relevant for applications, from the total magnetocaloric effect. To illustrate the versatility of this system, a thorough study of the ferromagnetic first-order transition of MnFe<sub>0.95</sub>P<sub>0.585</sub>Si<sub>0.34</sub>B<sub>0.075</sub> is carried out. An exceptionally large cyclic entropy change at an intermediate field is observed in this compound, Δ<em>S</em><sub>cyclic</sub> = 13.2 J kg<sup>−1</sup> K<sup>−1</sup> for µ<sub>0</sub>Δ<em>H</em> = 1 T. This confirms that MnFe(P,Si,B) shows one of the most promising giant magnetocaloric effects to be used in emergent green technologies such as magnetocaloric cooling, heating or thermomagnetic waste heat recovery.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1465-1473"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41995708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2023.05.003
Lin Cheng , Zuohuan Chen , Daquan Yu , Dongfang Pan
A transformer-in-package (TiP) isolated direct current–direct current (DC-DC) converter using glass-based fan-out wafer-level packaging (FOWLP) is proposed. By using 3-layer redistribution layers (RDLs), both the transformer and interconnections are built without an additional transformer chip, and the converter only has 2 dies: a transmitter (TX) chip and a receiver (RX) chip. The proposed solution results in a significant reduction in the cost and makes major improvements in the form factor and power density. Moreover, the transformer built by the RDLs achieves a high quality factor (Q) and high coupling factor (k), and the efficiency of the converter is thus improved. The TX and RX chips were implemented in a 0.18 µm Biopolar CMOS DMOS (BCD) process and embedded in a compact package with a size of 5 mm × 5 mm. With an output capacitance of 10 µF, the converter achieves a peak efficiency of 46.5% at 0.3 W output power and a maximum delivery power of 1.25 W, achieving a maximum power density of 50 mW/mm2.
{"title":"A high-efficiency transformer-in-package isolated DC-DC converter using glass-based fan-out wafer-level packaging","authors":"Lin Cheng , Zuohuan Chen , Daquan Yu , Dongfang Pan","doi":"10.1016/j.fmre.2023.05.003","DOIUrl":"10.1016/j.fmre.2023.05.003","url":null,"abstract":"<div><div>A transformer-in-package (TiP) isolated direct current–direct current (DC-DC) converter using glass-based fan-out wafer-level packaging (FOWLP) is proposed. By using 3-layer redistribution layers (RDLs), both the transformer and interconnections are built without an additional transformer chip, and the converter only has 2 dies: a transmitter (TX) chip and a receiver (RX) chip. The proposed solution results in a significant reduction in the cost and makes major improvements in the form factor and power density. Moreover, the transformer built by the RDLs achieves a high quality factor (<em>Q</em>) and high coupling factor (<em>k</em>), and the efficiency of the converter is thus improved. The TX and RX chips were implemented in a 0.18 µm Biopolar CMOS DMOS (BCD) process and embedded in a compact package with a size of 5 mm × 5 mm. With an output capacitance of 10 µF, the converter achieves a peak efficiency of 46.5% at 0.3 W output power and a maximum delivery power of 1.25 W, achieving a maximum power density of 50 mW/mm<sup>2</sup>.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1407-1414"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42608848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2023.05.005
Tianyang Wang , Songlin He , Qinghai Zhang , Lin Ding , Alexander Farnsworth , Fulong Cai , Chao Wang , Jing Xie , Guobiao Li , Jiani Sheng , Yahui Yue
Globally elevated temperatures during the Cretaceous extreme greenhouse climate interval were punctuated by the Valanginian cooling event, which was characterized by a positive carbon isotope excursion, global cooling, and a glacial event approximately at 135 Ma. Disentangling ocean temperature and continental ice volume trends enables us to better understand climate fluctuations over deep time. We investigated the ocean temperature–ice sheet dynamics of glaciation events that occurred in the Cretaceous greenhouse world. New clumped isotope and δ18O data from sites in the Tethyan Ocean show that seawater temperatures decreased by 5–6 °C, consistent with the development of glacial periods, and maximum ice volumes about half the size of present-day Antarctica. This cooling event provides a counter-example to other Mesozoic climate transitions driven by changes in atmospheric greenhouse gas contents. Our results emphasize the importance of quantitatively reconstructing continental ice volume, providing further support for exploring deep-time Earth climate dynamics.
{"title":"Ice sheet expansion in the Cretaceous greenhouse world","authors":"Tianyang Wang , Songlin He , Qinghai Zhang , Lin Ding , Alexander Farnsworth , Fulong Cai , Chao Wang , Jing Xie , Guobiao Li , Jiani Sheng , Yahui Yue","doi":"10.1016/j.fmre.2023.05.005","DOIUrl":"10.1016/j.fmre.2023.05.005","url":null,"abstract":"<div><div>Globally elevated temperatures during the Cretaceous extreme greenhouse climate interval were punctuated by the Valanginian cooling event, which was characterized by a positive carbon isotope excursion, global cooling, and a glacial event approximately at 135 Ma. Disentangling ocean temperature and continental ice volume trends enables us to better understand climate fluctuations over deep time. We investigated the ocean temperature–ice sheet dynamics of glaciation events that occurred in the Cretaceous greenhouse world. New clumped isotope and <em>δ</em><sup>18</sup>O data from sites in the Tethyan Ocean show that seawater temperatures decreased by 5–6 °C, consistent with the development of glacial periods, and maximum ice volumes about half the size of present-day Antarctica. This cooling event provides a counter-example to other Mesozoic climate transitions driven by changes in atmospheric greenhouse gas contents. Our results emphasize the importance of quantitatively reconstructing continental ice volume, providing further support for exploring deep-time Earth climate dynamics.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1586-1593"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43045779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2022.10.006
Liying Wang , Ruidan Zhang , Bingbing Wu , Yang Yu , Wei Li , Shiguo Li , Chao Liu
Spermiation is the process that releases mature spermatids from Sertoli cells into the lumen of the seminiferous tubule. Tubulobulbar complexes (TBCs) are elaborate cytoskeleton-related structures that are indispensable for spermiation. Despite well-defined ultrastructural events, the molecular regulation of TBCs during spermiation remains largely unknown. Here, we show that autophagy is active in TBC regions, and impaired autophagy in Sertoli cells affects spermiation. Further studies demonstrated that many TBC components bound to LC3 and could be selectively degraded through the autophagy-lysosome pathway. Perturbed autophagy impaired the degradation of some TBC components in Sertoli cells, such as VCL and CTTN, and led to the accumulation of TBC components surrounding the spermatid head, which may be associated with the sperm-releasing defect. Together, our results reveal that autophagy is essential for the TBC components degradation in mouse Sertoli cells and define a functional role of autophagy during spermiation.
{"title":"Autophagy mediated tubulobulbar complex components degradation is required for spermiation","authors":"Liying Wang , Ruidan Zhang , Bingbing Wu , Yang Yu , Wei Li , Shiguo Li , Chao Liu","doi":"10.1016/j.fmre.2022.10.006","DOIUrl":"10.1016/j.fmre.2022.10.006","url":null,"abstract":"<div><div>Spermiation is the process that releases mature spermatids from Sertoli cells into the lumen of the seminiferous tubule. Tubulobulbar complexes (TBCs) are elaborate cytoskeleton-related structures that are indispensable for spermiation. Despite well-defined ultrastructural events, the molecular regulation of TBCs during spermiation remains largely unknown. Here, we show that autophagy is active in TBC regions, and impaired autophagy in Sertoli cells affects spermiation. Further studies demonstrated that many TBC components bound to LC3 and could be selectively degraded through the autophagy-lysosome pathway. Perturbed autophagy impaired the degradation of some TBC components in Sertoli cells, such as VCL and CTTN, and led to the accumulation of TBC components surrounding the spermatid head, which may be associated with the sperm-releasing defect. Together, our results reveal that autophagy is essential for the TBC components degradation in mouse Sertoli cells and define a functional role of autophagy during spermiation.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1557-1567"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43470153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2022.06.023
Xiuting Sun, Jian Xu, Zhifeng Qi
By the biological construction of a bird neck, a bionic bird-neck multilevel rigid-flexible structure is proposed and some biometric properties are explained. The proposed structure can flexibly deform in six directions, which inspires the study of its mechanical properties for flexible deformations. First, the structural configuration and composition are determined based on the study of the anatomical characteristics of the woodpeckers. Since the skeletons and muscles have very different values for the elasticity modulus and the deformation is mostly dependent on the muscle tension, the bionic structure consists of rigid units and bio-syncretic components. For combined deformations, the mechanical model is established by the connectivity matrix to describe the connection of each level. Second, based on the principle of minimum potential energy, an integral form-finding method is proposed for flexible combination deformations. All of the integral forms obtained with the theoretical analysis are compared with the results with Finite Element Analysis. The structural parameters of the bionic structure were then tightly fixed to the actual shape of the bird's neck and the corresponding overall form took on an "S" shape, which perfectly matched the construction of the bird's neck. In addition, for the pre-deformation form, by analyzing the potential energy of the bionic structure, due to the adjustable dynamic stiffness property, an explanation is provided for the significant dynamic stability of the bird neck in bending. This study not only proposes a bionic rigid-flexible structure with high spatial accessibility but also explains biological properties of a bird neck based on the study of its mechanics characteristics. Based on the modeling and the mechanical properties of the bionic structure in flexible spatial combination deformations, the multi-steady state, and the variable dynamic stiffness, the bird-neck bionic rigid-flexible structure has significant applications such as aeronautical deployable systems, manipulator positioning, and dynamic stability fields.
{"title":"Mechanism properties of a bird-neck bionic rigid-flexible structure","authors":"Xiuting Sun, Jian Xu, Zhifeng Qi","doi":"10.1016/j.fmre.2022.06.023","DOIUrl":"10.1016/j.fmre.2022.06.023","url":null,"abstract":"<div><div>By the biological construction of a bird neck, a bionic bird-neck multilevel rigid-flexible structure is proposed and some biometric properties are explained. The proposed structure can flexibly deform in six directions, which inspires the study of its mechanical properties for flexible deformations. First, the structural configuration and composition are determined based on the study of the anatomical characteristics of the woodpeckers. Since the skeletons and muscles have very different values for the elasticity modulus and the deformation is mostly dependent on the muscle tension, the bionic structure consists of rigid units and bio-syncretic components. For combined deformations, the mechanical model is established by the connectivity matrix to describe the connection of each level. Second, based on the principle of minimum potential energy, an integral form-finding method is proposed for flexible combination deformations. All of the integral forms obtained with the theoretical analysis are compared with the results with Finite Element Analysis. The structural parameters of the bionic structure were then tightly fixed to the actual shape of the bird's neck and the corresponding overall form took on an \"S\" shape, which perfectly matched the construction of the bird's neck. In addition, for the pre-deformation form, by analyzing the potential energy of the bionic structure, due to the adjustable dynamic stiffness property, an explanation is provided for the significant dynamic stability of the bird neck in bending. This study not only proposes a bionic rigid-flexible structure with high spatial accessibility but also explains biological properties of a bird neck based on the study of its mechanics characteristics. Based on the modeling and the mechanical properties of the bionic structure in flexible spatial combination deformations, the multi-steady state, and the variable dynamic stiffness, the bird-neck bionic rigid-flexible structure has significant applications such as aeronautical deployable systems, manipulator positioning, and dynamic stability fields.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1613-1624"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46135193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2023.09.013
Xuan Ye , Philip N. Baker , Chao Tong
The rising rates of pregnancies associated with advanced maternal age (AMA) have created unique challenges for healthcare systems worldwide. The elevated risk of poor maternal outcomes among AMA pregnancies is only partially understood and hotly debated. Specifically, AMA is associated with reduced fertility and an increased incidence of pregnancy complications. Finding a balance between global fertility policy, socioeconomic development and health care optimization ultimately depends on female fertility. Therefore, there is an urgent need to develop technologies and identify effective interventions. Support strategies should include prepregnancy screening, intervention and postpartum maintenance. Although some reviews have considered the relationship between AMA and adverse pregnancy outcomes, no previous work has comprehensively considered the long-term health effects of AMA on mothers. In this review, we will begin by presenting the current knowledge of global health issues associated with AMA and the effects of advanced age on the female reproductive system, endocrine metabolism, and placental function. We will then discuss physiological alterations, pregnancy complications, and long-term health problems caused by AMA.
{"title":"The updated understanding of advanced maternal age","authors":"Xuan Ye , Philip N. Baker , Chao Tong","doi":"10.1016/j.fmre.2023.09.013","DOIUrl":"10.1016/j.fmre.2023.09.013","url":null,"abstract":"<div><div>The rising rates of pregnancies associated with advanced maternal age (AMA) have created unique challenges for healthcare systems worldwide. The elevated risk of poor maternal outcomes among AMA pregnancies is only partially understood and hotly debated. Specifically, AMA is associated with reduced fertility and an increased incidence of pregnancy complications. Finding a balance between global fertility policy, socioeconomic development and health care optimization ultimately depends on female fertility. Therefore, there is an urgent need to develop technologies and identify effective interventions. Support strategies should include prepregnancy screening, intervention and postpartum maintenance. Although some reviews have considered the relationship between AMA and adverse pregnancy outcomes, no previous work has comprehensively considered the long-term health effects of AMA on mothers. In this review, we will begin by presenting the current knowledge of global health issues associated with AMA and the effects of advanced age on the female reproductive system, endocrine metabolism, and placental function. We will then discuss physiological alterations, pregnancy complications, and long-term health problems caused by AMA.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1719-1728"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139192627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.fmre.2023.02.004
Arkadeep Ghosh, Nitin Nadella, A Paula Monaghan-Nichols, Xiang-Ping Chu
Autism spectrum disorder (ASD) is a complex neurological and developmental disorder that affects how a person acts, communicates, learns, and interacts with others. It affects the structure and function of the brain and nervous system. How ASD is caused remains uncertain and there is no effective treatment for this disorder. Searching for new technologies for treatment of this disorder becomes a priority. Genetic alterations have been implicated in the generation of this disorder. One of the most promising genes for potential treatment of ASD is sodium voltage-gated channel alpha subunit 2 gene (SCN2A). SCN2A, encoding the neuronal voltage-gated Na+ channel NaV1.2, is one of the most commonly affected loci linked to ASD. Here, we discuss the implications of loss of function (LOF) mutations in SCN2A and the potential efficacy of gene therapy by highlighting the usage of CRISPR restoration of various Scn2a-insufficiencies. Various therapeutics exist that can be extrapolated to address the needs of Scn2a LOF induced ASD. The current treatment that exists for ASD can be seen as outdated in comparison to the advent of new technologies that build upon CRISPR. Due to complications in treatment of ASD, genetic therapies may induce alterations such as insertion–deletion mutations, which may lead to further complications along with a negative public outlook on CRISPR technologies. Gene therapy can be applied to ASD but much work is yet to be done in order to address both biochemical and ethical considerations.
{"title":"Gene therapy as an emerging treatment for Scn2a mutation-induced autism spectrum disorders","authors":"Arkadeep Ghosh, Nitin Nadella, A Paula Monaghan-Nichols, Xiang-Ping Chu","doi":"10.1016/j.fmre.2023.02.004","DOIUrl":"10.1016/j.fmre.2023.02.004","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurological and developmental disorder that affects how a person acts, communicates, learns, and interacts with others. It affects the structure and function of the brain and nervous system. How ASD is caused remains uncertain and there is no effective treatment for this disorder. Searching for new technologies for treatment of this disorder becomes a priority. Genetic alterations have been implicated in the generation of this disorder. One of the most promising genes for potential treatment of ASD is sodium voltage-gated channel alpha subunit 2 gene <em>(SCN2A). SCN2A</em>, encoding the neuronal voltage-gated Na<sup>+</sup> channel Na<sub>V</sub>1.2, is one of the most commonly affected loci linked to ASD. Here, we discuss the implications of loss of function (LOF) mutations in <em>SCN2A</em> and the potential efficacy of gene therapy by highlighting the usage of CRISPR restoration of various <em>Scn2a</em>-insufficiencies. Various therapeutics exist that can be extrapolated to address the needs of <em>Scn2a</em> LOF induced ASD. The current treatment that exists for ASD can be seen as outdated in comparison to the advent of new technologies that build upon CRISPR. Due to complications in treatment of ASD, genetic therapies may induce alterations such as insertion–deletion mutations, which may lead to further complications along with a negative public outlook on CRISPR technologies. Gene therapy can be applied to ASD but much work is yet to be done in order to address both biochemical and ethical considerations.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"4 6","pages":"Pages 1401-1404"},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41535148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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