Developing biomass platform compounds into high value-added chemicals is a key step in renewable resource utilization.Herein,we report porous carbon-supported Ni-ZnO nanoparticles catalyst(Ni-ZnO/AC)synthesized via lo...Developing biomass platform compounds into high value-added chemicals is a key step in renewable resource utilization.Herein,we report porous carbon-supported Ni-ZnO nanoparticles catalyst(Ni-ZnO/AC)synthesized via low-temperature coprecipitation,exhibiting excellent performance for the selective hydrogenation of 5-hydroxymethylfurfural(HMF).A linear correlation is first observed between solvent polarity(E_(T)(30))and product selectivity within both polar aprotic and protic solvent classes,suggesting that solvent properties play a vital role in directing reaction pathways.Among these,1,4-dioxane(aprotic)favors the formation of 2,5-bis(hydroxymethyl)furan(BHMF)with 97.5%selectivity,while isopropanol(iPrOH,protic)promotes 2,5-dimethylfuran production with up to 99.5%selectivity.Mechanistic investigations further reveal that beyond polarity,proton-donating ability is critical in facilitating hydrodeoxygenation.iPrOH enables a hydrogen shuttle mechanism where protons assist in hydroxyl group removal,lowering the activation barrier.In contrast,1,4-dioxane,lacking hydrogen bond donors,stabilizes BHMF and hinders further conversion.Density functional theory calculations confirm a lower activation energy in iPrOH(0.60 eV)compared to 1,4-dioxane(1.07 eV).This work offers mechanistic insights and a practical strategy for solvent-mediated control of product selectivity in biomass hydrogenation,highlighting the decisive role of solvent-catalyst-substrate interactions.展开更多
GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a ...GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.展开更多
背景:目前发现miR-196b-5p在细胞增殖、迁移及抑制瘢痕增生中发挥作用,但在创面愈合过程中是否发挥作用缺乏相关研究。目的:探讨脂肪干细胞源性外泌体中miR-196b-5p对烧伤创面愈合的影响。方法:构建SD大鼠皮肤深Ⅱ度烧伤模型,随机分为4...背景:目前发现miR-196b-5p在细胞增殖、迁移及抑制瘢痕增生中发挥作用,但在创面愈合过程中是否发挥作用缺乏相关研究。目的:探讨脂肪干细胞源性外泌体中miR-196b-5p对烧伤创面愈合的影响。方法:构建SD大鼠皮肤深Ⅱ度烧伤模型,随机分为4组:空白对照组、外泌体组、agomiR-196b-5p组和外泌体+antagomiR-196b-5p组,每组10只,根据不同分组于创周注射PBS、脂肪干细胞源性外泌体、miR-196b-5p激动剂和miR-196b-5p抑制剂,伤后即刻和伤后7,14,21 d观察创面愈合情况,伤后7 d苏木精-伊红染色观察创面炎症表达,伤后14 d Masson染色观察创面胶原表达及免疫组化染色观察创面CD31表达,伤后7 d Western blot检测创面中α-平滑肌肌动蛋白、Ⅰ型胶原蛋白表达。结果与结论:①agomiR-196b-5p组创面愈合较快,空白对照组和外泌体+antagomiR-196b-5p组愈合较慢;②与空白对照组和外泌体+antagomiR-196b-5p组相比,外泌体组和agomiR-196b-5p组创面炎性细胞浸润较少,CD31表达明显增加(P<0.01);③与空白对照组和外泌体+antagomiR-196b-5p组相比,外泌体组和agomiR-196b-5p组中α-平滑肌肌动蛋白、Ⅰ型胶原蛋白表达升高(P<0.05)。结果表明,脂肪干细胞源性外泌体中miR-196b-5p能促进大鼠烧伤创面愈合。展开更多
This study proposes a lightweight rice disease detection model optimized for edge computing environments.The goal is to enhance the You Only Look Once(YOLO)v5 architecture to achieve a balance between real-time diagno...This study proposes a lightweight rice disease detection model optimized for edge computing environments.The goal is to enhance the You Only Look Once(YOLO)v5 architecture to achieve a balance between real-time diagnostic performance and computational efficiency.To this end,a total of 3234 high-resolution images(2400×1080)were collected from three major rice diseases Rice Blast,Bacterial Blight,and Brown Spot—frequently found in actual rice cultivation fields.These images served as the training dataset.The proposed YOLOv5-V2 model removes the Focus layer from the original YOLOv5s and integrates ShuffleNet V2 into the backbone,thereby resulting in both model compression and improved inference speed.Additionally,YOLOv5-P,based on PP-PicoDet,was configured as a comparative model to quantitatively evaluate performance.Experimental results demonstrated that YOLOv5-V2 achieved excellent detection performance,with an mAP 0.5 of 89.6%,mAP 0.5–0.95 of 66.7%,precision of 91.3%,and recall of 85.6%,while maintaining a lightweight model size of 6.45 MB.In contrast,YOLOv5-P exhibited a smaller model size of 4.03 MB,but showed lower performance with an mAP 0.5 of 70.3%,mAP 0.5–0.95 of 35.2%,precision of 62.3%,and recall of 74.1%.This study lays a technical foundation for the implementation of smart agriculture and real-time disease diagnosis systems by proposing a model that satisfies both accuracy and lightweight requirements.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
基金the National Nature Science Foundation of China for Excellent Young Scientists Fund(32222058)Fundamental Research Foundation of CAF(CAFYBB2022QB001).
文摘Developing biomass platform compounds into high value-added chemicals is a key step in renewable resource utilization.Herein,we report porous carbon-supported Ni-ZnO nanoparticles catalyst(Ni-ZnO/AC)synthesized via low-temperature coprecipitation,exhibiting excellent performance for the selective hydrogenation of 5-hydroxymethylfurfural(HMF).A linear correlation is first observed between solvent polarity(E_(T)(30))and product selectivity within both polar aprotic and protic solvent classes,suggesting that solvent properties play a vital role in directing reaction pathways.Among these,1,4-dioxane(aprotic)favors the formation of 2,5-bis(hydroxymethyl)furan(BHMF)with 97.5%selectivity,while isopropanol(iPrOH,protic)promotes 2,5-dimethylfuran production with up to 99.5%selectivity.Mechanistic investigations further reveal that beyond polarity,proton-donating ability is critical in facilitating hydrodeoxygenation.iPrOH enables a hydrogen shuttle mechanism where protons assist in hydroxyl group removal,lowering the activation barrier.In contrast,1,4-dioxane,lacking hydrogen bond donors,stabilizes BHMF and hinders further conversion.Density functional theory calculations confirm a lower activation energy in iPrOH(0.60 eV)compared to 1,4-dioxane(1.07 eV).This work offers mechanistic insights and a practical strategy for solvent-mediated control of product selectivity in biomass hydrogenation,highlighting the decisive role of solvent-catalyst-substrate interactions.
基金partially supported by grants PID2020-115096RB-I00 and PID2023-148273NB-I00 from Ministerio de Ciencia y Universidad (MICIU/AEI)(to EMS)。
文摘GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.
文摘背景:目前发现miR-196b-5p在细胞增殖、迁移及抑制瘢痕增生中发挥作用,但在创面愈合过程中是否发挥作用缺乏相关研究。目的:探讨脂肪干细胞源性外泌体中miR-196b-5p对烧伤创面愈合的影响。方法:构建SD大鼠皮肤深Ⅱ度烧伤模型,随机分为4组:空白对照组、外泌体组、agomiR-196b-5p组和外泌体+antagomiR-196b-5p组,每组10只,根据不同分组于创周注射PBS、脂肪干细胞源性外泌体、miR-196b-5p激动剂和miR-196b-5p抑制剂,伤后即刻和伤后7,14,21 d观察创面愈合情况,伤后7 d苏木精-伊红染色观察创面炎症表达,伤后14 d Masson染色观察创面胶原表达及免疫组化染色观察创面CD31表达,伤后7 d Western blot检测创面中α-平滑肌肌动蛋白、Ⅰ型胶原蛋白表达。结果与结论:①agomiR-196b-5p组创面愈合较快,空白对照组和外泌体+antagomiR-196b-5p组愈合较慢;②与空白对照组和外泌体+antagomiR-196b-5p组相比,外泌体组和agomiR-196b-5p组创面炎性细胞浸润较少,CD31表达明显增加(P<0.01);③与空白对照组和外泌体+antagomiR-196b-5p组相比,外泌体组和agomiR-196b-5p组中α-平滑肌肌动蛋白、Ⅰ型胶原蛋白表达升高(P<0.05)。结果表明,脂肪干细胞源性外泌体中miR-196b-5p能促进大鼠烧伤创面愈合。
文摘This study proposes a lightweight rice disease detection model optimized for edge computing environments.The goal is to enhance the You Only Look Once(YOLO)v5 architecture to achieve a balance between real-time diagnostic performance and computational efficiency.To this end,a total of 3234 high-resolution images(2400×1080)were collected from three major rice diseases Rice Blast,Bacterial Blight,and Brown Spot—frequently found in actual rice cultivation fields.These images served as the training dataset.The proposed YOLOv5-V2 model removes the Focus layer from the original YOLOv5s and integrates ShuffleNet V2 into the backbone,thereby resulting in both model compression and improved inference speed.Additionally,YOLOv5-P,based on PP-PicoDet,was configured as a comparative model to quantitatively evaluate performance.Experimental results demonstrated that YOLOv5-V2 achieved excellent detection performance,with an mAP 0.5 of 89.6%,mAP 0.5–0.95 of 66.7%,precision of 91.3%,and recall of 85.6%,while maintaining a lightweight model size of 6.45 MB.In contrast,YOLOv5-P exhibited a smaller model size of 4.03 MB,but showed lower performance with an mAP 0.5 of 70.3%,mAP 0.5–0.95 of 35.2%,precision of 62.3%,and recall of 74.1%.This study lays a technical foundation for the implementation of smart agriculture and real-time disease diagnosis systems by proposing a model that satisfies both accuracy and lightweight requirements.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
