Huabo Wang, Taylor Stevens, Jie Lu, Alexander Roberts, Clinton Van't Land, Radhika Muzumdar, Zhenwei Gong, Jerry Vockley, Edward V Prochownik
The "Mlx" and "Myc" transcription factor networks cross-communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max-like factor Mlx associate with the Myc-like factors MondoA or ChREBP. The current work demonstrates that body-wide Mlx inactivation, like that of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging-related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability, and aging. Whereas "MycKO" mice have an extended lifespan because of a lower cancer incidence, "MlxKO" mice have normal lifespans and a higher cancer incidence. Like Myc, the expression of Mlx, MondoA, and ChREBP and their control over their target genes deteriorate with age in both mice and humans. Collectively, these findings underscore the importance of lifelong and balanced cross-talk between the two networks to maintain proper function and regulation of the many factors that can affect normal aging.
{"title":"Body-Wide Inactivation of the Myc-Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence.","authors":"Huabo Wang, Taylor Stevens, Jie Lu, Alexander Roberts, Clinton Van't Land, Radhika Muzumdar, Zhenwei Gong, Jerry Vockley, Edward V Prochownik","doi":"10.1002/advs.202401593","DOIUrl":"https://doi.org/10.1002/advs.202401593","url":null,"abstract":"<p><p>The \"Mlx\" and \"Myc\" transcription factor networks cross-communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max-like factor Mlx associate with the Myc-like factors MondoA or ChREBP. The current work demonstrates that body-wide Mlx inactivation, like that of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging-related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability, and aging. Whereas \"MycKO\" mice have an extended lifespan because of a lower cancer incidence, \"MlxKO\" mice have normal lifespans and a higher cancer incidence. Like Myc, the expression of Mlx, MondoA, and ChREBP and their control over their target genes deteriorate with age in both mice and humans. Collectively, these findings underscore the importance of lifelong and balanced cross-talk between the two networks to maintain proper function and regulation of the many factors that can affect normal aging.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peihua Ma, Yixin Wu, Ning Yu, Xiaoxue Jia, Yiyang He, Yang Zhang, Michael Backes, Qin Wang, Cheng-I Wei
Addressing the critical need for swift and precise nutritional profiling in healthcare and in food industry, this study pioneers the integration of vision-language models (VLMs) with chemical analysis techniques. A cutting-edge VLM is unveiled, utilizing the expansive UMDFood-90k database, to significantly improve the speed and accuracy of nutrient estimation processes. Demonstrating a macro-AUCROC of 0.921 for lipid quantification, the model exhibits less than 10% variance compared to traditional chemical analyses for over 82% of the analyzed food items. This innovative approach not only accelerates nutritional screening by 36.9% when tested amongst students but also sets a new benchmark in the precision of nutritional data compilation. This research marks a substantial leap forward in food science, employing a blend of advanced computational models and chemical validation to offer a rapid, high-throughput solution for nutritional analysis.
{"title":"Integrating Vision-Language Models for Accelerated High-Throughput Nutrition Screening.","authors":"Peihua Ma, Yixin Wu, Ning Yu, Xiaoxue Jia, Yiyang He, Yang Zhang, Michael Backes, Qin Wang, Cheng-I Wei","doi":"10.1002/advs.202403578","DOIUrl":"https://doi.org/10.1002/advs.202403578","url":null,"abstract":"<p><p>Addressing the critical need for swift and precise nutritional profiling in healthcare and in food industry, this study pioneers the integration of vision-language models (VLMs) with chemical analysis techniques. A cutting-edge VLM is unveiled, utilizing the expansive UMDFood-90k database, to significantly improve the speed and accuracy of nutrient estimation processes. Demonstrating a macro-AUCROC of 0.921 for lipid quantification, the model exhibits less than 10% variance compared to traditional chemical analyses for over 82% of the analyzed food items. This innovative approach not only accelerates nutritional screening by 36.9% when tested amongst students but also sets a new benchmark in the precision of nutritional data compilation. This research marks a substantial leap forward in food science, employing a blend of advanced computational models and chemical validation to offer a rapid, high-throughput solution for nutritional analysis.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A 3D bulk metamaterial (MM) containing amorphous multilayered split-ring resonators is proposed, fabricated, and evaluated. Experimentally, the effective refractive index is engineered via the 3D bulk MM, with a contrast of 0.118 across the frequency span from 0.315 to 0.366 THz and the index changing at a slope of 2.314 per THz within this frequency range. Additionally, the 3D bulk MM exhibits optical isotropy with respect to polarization. Moreover, the peak transmission and optical dispersion are tailored by adjusting the density of the split-ring resonators. Compared to reported conventional approaches for constructing bulk MMs, this approach offers advantages in terms of the potential for large-scale manufacturing, the ability to adopt any shape, optical isotropy, and rapid optical dispersion. These features hold promise for dispersive optical devices operating at THz frequencies, such as high-dispersive prisms for high-resolution spectroscopy.
我们提出、制造并评估了一种包含非晶多层分环谐振器的三维体状超材料 (MM)。实验表明,有效折射率是通过三维块状超材料设计的,在 0.315 至 0.366 太赫兹的频率范围内,对比度为 0.118,在此频率范围内,折射率以每太赫兹 2.314 的斜率变化。此外,三维块状 MM 在偏振方面表现出光学各向同性。此外,通过调整劈环谐振器的密度,还可以定制峰值传输和光色散。与已报道的用于构建块状 MM 的传统方法相比,这种方法在大规模制造的潜力、采用任何形状的能力、光学各向同性和快速光色散方面具有优势。这些特点为在太赫兹频率下工作的色散光学器件(如用于高分辨率光谱学的高色散棱镜)带来了希望。
{"title":"3D Bulk Metamaterials with Engineered Optical Dispersion at Terahertz Frequencies Utilizing Amorphous Multilayered Split-Ring Resonators.","authors":"Ying Huang, Takanori Kida, Shun Wakiuchi, Taiyu Okatani, Naoki Inomata, Yoshiaki Kanamori","doi":"10.1002/advs.202405378","DOIUrl":"https://doi.org/10.1002/advs.202405378","url":null,"abstract":"<p><p>A 3D bulk metamaterial (MM) containing amorphous multilayered split-ring resonators is proposed, fabricated, and evaluated. Experimentally, the effective refractive index is engineered via the 3D bulk MM, with a contrast of 0.118 across the frequency span from 0.315 to 0.366 THz and the index changing at a slope of 2.314 per THz within this frequency range. Additionally, the 3D bulk MM exhibits optical isotropy with respect to polarization. Moreover, the peak transmission and optical dispersion are tailored by adjusting the density of the split-ring resonators. Compared to reported conventional approaches for constructing bulk MMs, this approach offers advantages in terms of the potential for large-scale manufacturing, the ability to adopt any shape, optical isotropy, and rapid optical dispersion. These features hold promise for dispersive optical devices operating at THz frequencies, such as high-dispersive prisms for high-resolution spectroscopy.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lin Zeng, Pengcheng Ma, Zeyang Li, Shengxing Liang, Chengkai Wu, Chang Hong, Yan Li, Hao Cui, Ruining Li, Jiaren Wang, Jingzhe He, Wenyuan Li, Lushan Xiao, Li Liu
Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.
{"title":"Multimodal Machine Learning-Based Marker Enables Early Detection and Prognosis Prediction for Hyperuricemia.","authors":"Lin Zeng, Pengcheng Ma, Zeyang Li, Shengxing Liang, Chengkai Wu, Chang Hong, Yan Li, Hao Cui, Ruining Li, Jiaren Wang, Jingzhe He, Wenyuan Li, Lushan Xiao, Li Liu","doi":"10.1002/advs.202404047","DOIUrl":"https://doi.org/10.1002/advs.202404047","url":null,"abstract":"<p><p>Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Heo, Alekos Segalina, Doyeong Kim, Doo-Sik Ahn, Key Young Oang, Sungjun Park, Hyungjun Kim, Hyotcherl Ihee
Metal-semiconductor interfaces are crucial components of optoelectronic and electrical devices, the performance of which hinges on intricate dynamics involving charge transport and mechanical interaction at the interface. Nevertheless, structural changes upon photoexcitation and subsequent carrier transportation at the interface, which crucially impact hot carrier stability and lifetime, remain elusive. To address this long-standing problem, they investigated the electron dynamics and resulting structural changes at the Au/TiO2 interface using ultrafast electron diffraction (UED). The analysis of the UED data reveals that interlayer electron transfer from metal to semiconductor generates a strong coupling between the two layers, offering a new way for ultrafast heat transfer through the interface and leading to a coherent structural vibration that plays a critical role in propagating mechanical stress. These findings provide insights into the relationship between electron transfer and interfacial mechanical and thermal properties.
{"title":"Ultrafast Interfacial Charge Transfer Initiates Mechanical Stress and Heat Transport at the Au-TiO<sub>2</sub> Interface.","authors":"Jun Heo, Alekos Segalina, Doyeong Kim, Doo-Sik Ahn, Key Young Oang, Sungjun Park, Hyungjun Kim, Hyotcherl Ihee","doi":"10.1002/advs.202400919","DOIUrl":"https://doi.org/10.1002/advs.202400919","url":null,"abstract":"<p><p>Metal-semiconductor interfaces are crucial components of optoelectronic and electrical devices, the performance of which hinges on intricate dynamics involving charge transport and mechanical interaction at the interface. Nevertheless, structural changes upon photoexcitation and subsequent carrier transportation at the interface, which crucially impact hot carrier stability and lifetime, remain elusive. To address this long-standing problem, they investigated the electron dynamics and resulting structural changes at the Au/TiO<sub>2</sub> interface using ultrafast electron diffraction (UED). The analysis of the UED data reveals that interlayer electron transfer from metal to semiconductor generates a strong coupling between the two layers, offering a new way for ultrafast heat transfer through the interface and leading to a coherent structural vibration that plays a critical role in propagating mechanical stress. These findings provide insights into the relationship between electron transfer and interfacial mechanical and thermal properties.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanhui Deng, Zhonghong Shi, Yaqin Zheng, Houjiao Zhang, Haoyang Li, Siyang Li, Zhang-Kai Zhou
Nonlinear nanophotonic devices have shown great potential for on-chip information processing, quantum source, 3D microfabrication, greatly promoting the developments of integrated optics, quantum science, nanoscience and technologies, etc. To promote the applications of nonlinear nanodevices, improving the nonlinear efficiency, expanding the spectra region of nonlinear response and reducing device thickness are three key issues. Herein, this study focuses on the nonlinear effect of third-harmonic generation (THG), and present a thin Si meta-sructure to improve the THG efficiency in the ultraviolet (UV) region. The measured THG efficiency is up to 10-5 at an emission wavelength of 309 nm. Also, the THG nanosystem is only 100 nm in thickness, which is two-five times thinner than previous all-dielectric nanosystems applied in THG studies. These findings not only present a powerful thin meta-structure with highly efficient THG emission in UV region, but also provide a constructive avenue for further understanding the light-matter interactions at subwavelength scales, guiding the design and fabricating of advanced photonic devices in future.
{"title":"Highly Efficient Ultraviolet Third-Harmonic Generation in an Isolated Thin Si Meta-Structure.","authors":"Yanhui Deng, Zhonghong Shi, Yaqin Zheng, Houjiao Zhang, Haoyang Li, Siyang Li, Zhang-Kai Zhou","doi":"10.1002/advs.202404094","DOIUrl":"https://doi.org/10.1002/advs.202404094","url":null,"abstract":"<p><p>Nonlinear nanophotonic devices have shown great potential for on-chip information processing, quantum source, 3D microfabrication, greatly promoting the developments of integrated optics, quantum science, nanoscience and technologies, etc. To promote the applications of nonlinear nanodevices, improving the nonlinear efficiency, expanding the spectra region of nonlinear response and reducing device thickness are three key issues. Herein, this study focuses on the nonlinear effect of third-harmonic generation (THG), and present a thin Si meta-sructure to improve the THG efficiency in the ultraviolet (UV) region. The measured THG efficiency is up to 10<sup>-5</sup> at an emission wavelength of 309 nm. Also, the THG nanosystem is only 100 nm in thickness, which is two-five times thinner than previous all-dielectric nanosystems applied in THG studies. These findings not only present a powerful thin meta-structure with highly efficient THG emission in UV region, but also provide a constructive avenue for further understanding the light-matter interactions at subwavelength scales, guiding the design and fabricating of advanced photonic devices in future.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.
{"title":"DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma.","authors":"Qing-Jie Li, Xue-Liang Fang, Ying-Qin Li, Jia-Yi Lin, Cheng-Long Huang, Shi-Wei He, Sheng-Yan Huang, Jun-Yan Li, Sha Gong, Na Liu, Jun Ma, Yin Zhao, Ling-Long Tang","doi":"10.1002/advs.202403262","DOIUrl":"https://doi.org/10.1002/advs.202403262","url":null,"abstract":"<p><p>Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuxin Jin, Ouqiang Wu, Qizhu Chen, Linjie Chen, Zhiguang Zhang, Haijun Tian, Hao Zhou, Kai Zhang, Jianyuan Gao, Xinzhou Wang, Zhenyu Guo, Jing Sun, Kenny Yat Hong Kwan, Morgan Jones, Yan Michael Li, Ehsan Nazarzadeh Zare, Pooyan Makvandi, Xiangyang Wang, Shuying Shen, Aimin Wu
Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.
{"title":"Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration.","authors":"Yuxin Jin, Ouqiang Wu, Qizhu Chen, Linjie Chen, Zhiguang Zhang, Haijun Tian, Hao Zhou, Kai Zhang, Jianyuan Gao, Xinzhou Wang, Zhenyu Guo, Jing Sun, Kenny Yat Hong Kwan, Morgan Jones, Yan Michael Li, Ehsan Nazarzadeh Zare, Pooyan Makvandi, Xiangyang Wang, Shuying Shen, Aimin Wu","doi":"10.1002/advs.202404275","DOIUrl":"https://doi.org/10.1002/advs.202404275","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guanming Cai, Lin Ren, Jiali Yu, Siqi Jiang, Gen Liu, Shujie Wu, Bin Cheng, Weichang Li, Juan Xia
Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant-derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan-Oxidized Dextran (CMCS-OD) hydrogel formed via dynamic chemical bonds exhibited self-healing capabilities and pH-responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis-induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis-induced bone destruction.
{"title":"A Microenvironment-Responsive, Controlled Release Hydrogel Delivering Embelin to Promote Bone Repair of Periodontitis via Anti-Infection and Osteo-Immune Modulation.","authors":"Guanming Cai, Lin Ren, Jiali Yu, Siqi Jiang, Gen Liu, Shujie Wu, Bin Cheng, Weichang Li, Juan Xia","doi":"10.1002/advs.202403786","DOIUrl":"https://doi.org/10.1002/advs.202403786","url":null,"abstract":"<p><p>Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant-derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan-Oxidized Dextran (CMCS-OD) hydrogel formed via dynamic chemical bonds exhibited self-healing capabilities and pH-responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis-induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis-induced bone destruction.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid-inducible gene I (RIG-I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections.
{"title":"Multi-Omics Analysis by Machine Learning Identified Lysophosphatidic Acid as a Biomarker and Therapeutic Target for Porcine Reproductive and Respiratory Syndrome.","authors":"Hao Zhang, Fangyu Hu, Ouyang Peng, Yihui Huang, Guangli Hu, Usama Ashraf, Meifeng Cen, Xiaojuan Wang, Qiuping Xu, Chuangchao Zou, Yu Wu, Bibo Zhu, Wentao Li, Qunhui Li, Chujun Li, Chunyi Xue, Yongchang Cao","doi":"10.1002/advs.202402025","DOIUrl":"https://doi.org/10.1002/advs.202402025","url":null,"abstract":"<p><p>As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid-inducible gene I (RIG-I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}