Autophagy
·
2021
·
IF 16.016
Di Peng,Chen Ruan,Shanshan Fu,Chengwen He,Jingzhen Song,Hui Li,Yiran Tu,Dachao Tang,Lan Yao,Shaofeng Lin,Ying Shi,Weizhi Zhang,Hao Zhou,Le Zhu,Cong Ma,Cheng Chang,Jie Ma,Zhiping Xie,Chenwei Wang,Yu Xue
In Saccharomyces cerevisiae, Atg9 is an important autophagy-related (Atg) protein, and interacts with hundreds of other proteins. How many Atg9-interacting proteins are involved in macroautophagy/autophagy is unclear. Here, we conducted a multi-omic profiling of Atg9-dependent molecular landscapes during nitrogen starvation-induced autophagy, and identified 290 and 256 genes to be markedly regulated by ATG9 in transcriptional and translational levels, respectively. Unexpectedly, we found most of known Atg proteins and autophagy regulators that interact with Atg9 were not significantly changed in the mRNA or protein level during autophagy. Based on a hypothesis that proteins with similar molecular characteristics might have similar functions, we developed a new method named inference of functional interacting partners (iFIP) to integrate the transcriptomic, proteomic and interactomic data, and predicted 42 Atg9-interacting proteins to be potentially involved in autophagy, including 15 known Atg proteins or autophagy regulators. We validated 2 Atg9-interacting partners, Glo3 and Scs7, to be functional in both bulk and selective autophagy. The mRNA and protein expressions but not subcellular localizations of Glo3 and Scs7 were affected with or without ATG9 during autophagy, whereas the colocalizations of the 2 proteins and Atg9 were markedly enhanced at early stages of the autophagic process. Further analyses demonstrated that Glo3 but not Scs7 regulates the retrograde transport of Atg9 during autophagy. A working model was illustrated to highlight the importance of the Atg9 interactome. Taken together, our study not only provided a powerful method for analyzing the multi-omics data, but also revealed 2 new players that regulate autophagy.Abbreviations: ALP: alkaline phosphatase; Arf1: ADP-ribosylation factor 1; Atg: autophagy-related; Co-IP: co-immunoprecipitation; Cvt: cytoplasm-to-vacuole targeting; DEM: differentially expressed mRNA; DEP: differentially expressed protein; DIC: differential interference contrast; E-ratio: enrichment ratio; ER: endoplasmic reticulum; ES: enrichment score; FC: fold change; FPKM: fragments per kilobase of exon per million fragments mapped; GAP: GTPase-activating protein; GFP: green fluorescent protein; GO: gene ontology; GSEA: gene set enrichment analysis; GST: glutathione S-transferase; HA: hemagglutinin; iFIP: inference of functional interacting partners; KO: knockout; LR: logistic regression; OE: over-expression; PAS: phagophore assembly site; PPI: protein-protein interaction; RFP: red fluorescence protein; RNA-seq: RNA sequencing; RT-PCR: real-time polymerase chain reaction; SCC: Spearman’s correlation coefficient; SD-N: synthetic minimal medium lacking nitrogen; THANATOS: The Autophagy, Necrosis, ApopTosis OrchestratorS; Vsn: variance stabilization normalization; WT: wild-type.
研究领域:
分子生物学
·
基因组学
·
系统生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2025
·
IF 4.3
Cheng Han,Shanshan Fu,Dachao Tang,Yuting Chen,Dan Liu,Zihao Feng,Yujie Gou,Chi Zhang,Weizhi Zhang,Leming Xiao,Jiayi Zhang,Cong Yi,Yu Xue,Di Peng
In Saccharomyces cerevisiae , Atg1 is a core autophagy-related (Atg) protein kinase (PK) in regulating macroautophagy/autophagy, by physically interacting with numerous other proteins, or by phosphorylating various substrates. It is unclear how many Atg1-interacting partners and substrates are also involved in regulating autophagy. Here, we conducted transcriptomic, proteomic and phosphoproteomic profiling of Atg1-dependent molecular landscapes during nitrogen starvation-triggered autophagy, and detected 244, 245 and 217 genes to be affected by ATG1 in the autophagic process at mRNA, protein, and phosphorylation levels, respectively. Based on the Atg1 interactome, we developed a novel artificial intelligence (AI) framework, inference of autophagy regulators from multi-omic data (iAMD), and predicted 12 Atg1-interacting partners and 17 substrates to be potentially functional in autophagy. Further experiments validated that Rgd1 and Whi5 are required for bulk autophagy, as well as physical interactions and co-localizations with Atg1 during autophagy. In particular, we demonstrated that 2 phosphorylation sites (p-sites), pS78 and pS149 of Whi5, are phosphorylated by Atg1 to regulate the formation of Atg1 puncta during autophagy initiation. A working model was illustrated to emphasize the importance of the Atg1-centered network in yeast autophagy. In addition, iAMD was extended to accurately predict Atg proteins and autophagy regulators from other PK interactomes, indicating a high transferability of the method. Taken together, we not only revealed new autophagy regulators from the Atg1 interactome, but also provided a useful resource for further analysis of yeast autophagy.
研究领域:
分子生物学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Qiuxiang Tang,Yi Zhang,Jun Huang,Rongqing Zhou
Tri-colored Jiangqu , including white (WQ), yellow (YQ), and black (BQ)-color Daqu , significantly influence fresh Baijiu yield and quality. The differences in attributes of these Jiangqu types, sourced from two renowned Baijiu enterprises, were investigated using multi-omics approaches. Color intensity negatively correlated with ammonia nitrogen content, but positively with pyroglutamic acid content. 182 volatiles and 291 non-volatiles were identified, with each types exhibiting unique metabolites. Esters, pyrazines, ketones and phenols were predominant in WQ, YQ, and BQ, respectively. The content of peptides, amines, and amino acids with derivatives also showcased the differences of microbiota and metabolic pathways among tri-colored Jiangqu . BQ's characteristic components of L-Tyrosine and acetyl tributyl citrate were closely associated with melanin formation. In YQ, Scopulibacillus and Rhizopus correlated positively with tetramethylpyrazine. Moreover, the bacterial community significantly influenced the metabolic profiles, and synergistic interactions between fungal and bacterial communities were crucial in determining metabolite abundance.
研究领域:
微生物学
·
食品科学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Zheng Zhou,Guoan Jing,Liang Wang,Shuang Cui,Lei Qin,Xuhui Huang
The nutrition and flavor of egg yolks can be affected by poultry species. However, chicken, duck, and goose eggs, as the most common poultry egg products, have not been fully explored. This study explored the lipid composition and flavor differences among three egg yolks via multi-omics, unraveling the flavor-formation mechanisms during thermal treatment. 194, 202, and 227 lipids were detected in goose, chicken, and duck yolks, respectively, with nearly 100 differential lipids between each pair. Duck yolks had higher concentrations of unsaturated fatty acids. Chicken yolks had higher concentrations of lysophosphatidylcholines and lower concentrations sterol lipids. Chicken yolks produced more volatile alcohols and pyrazines. Duck and goose yolks produced more aromatic hydrocarbons and alkanes, respectively. Fourteen aroma-active compounds were identified, and some can be formed from phosphatidylethanolamines and ether phosphatidylethanolamines through free radical chain reactions. This study provides theoretical basis for the regulation of flavor and nutrition of egg products.
研究领域:
食品科学
·
营养学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRIEFINGS IN BIOINFORMATICS
·
2020
·Vol. 22
·期 4
·
IF 8.99
Zheng Shuangjia,Rao Jiahua,Song Ying,Zhang Jixian,Xiao Xianglu,Fang Evandro Fei,Yang Yuedong,Niu Zhangming
Biomedical knowledge graphs (KGs), which can help with the understanding of complex biological systems and pathologies, have begun to play a critical role in medical practice and research. However, challenges remain in their embedding and use due to their complex nature and the specific demands of their construction. Existing studies often suffer from problems such as sparse and noisy datasets, insufficient modeling methods and non-uniform evaluation metrics. In this work, we established a comprehensive KG system for the biomedical field in an attempt to bridge the gap. Here, we introduced PharmKG, a multi-relational, attributed biomedical KG, composed of more than 500 000 individual interconnections between genes, drugs and diseases, with 29 relation types over a vocabulary of ~8000 disambiguated entities. Each entity in PharmKG is attached with heterogeneous, domain-specific information obtained from multi-omics data, i.e. gene expression, chemical structure and disease word embedding, while preserving the semantic and biomedical features. For baselines, we offered nine state-of-the-art KG embedding (KGE) approaches and a new biological, intuitive, graph neural network-based KGE method that uses a combination of both global network structure and heterogeneous domain features. Based on the proposed benchmark, we conducted extensive experiments to assess these KGE models using multiple evaluation metrics. Finally, we discussed our observations across various downstream biological tasks and provide insights and guidelines for how to use a KG in biomedicine. We hope that the unprecedented quality and diversity of PharmKG will lead to advances in biomedical KG construction, embedding and application.
研究领域:
生物信息学
·
医学信息学
·
系统生物学
✓ 已验证
DOI
高影响因子
Genome Medicine
·
2025
·Vol. 17
·期 1
·1-25
·
IF 11.2
Zhou Ren,Chen Jibao,Tang Yunhan,Wei Chuijin,Yu Ping,Ding Xinmei,Zhu Li’ao,Yao Jiajia,Ouyang Zengqiang,Qiao Jing,Xiong Shumin,Dong Liaoliao,Yin Tong,Li Haiqing,Feng Ye,Cheng Lin
Background Exercise rehabilitation therapy has garnered widespread recognition for its beneficial effects on the restoration of locomotor function in individuals with spinal cord injury (SCI). Notably, resistance exercise has demonstrated significant improvements in muscle strength, coordination, and overall functional recovery. However, to optimize clinical management and mimic exercise-like effects, it is imperative to obtain a comprehensive understanding of the molecular alterations that underlie these positive effects. Methods We conducted a randomized controlled clinical trial investigating the effects of resistance exercise therapy for incomplete SCI. We integrated the analysis of plasma proteomics and peripheral blood mononuclear cells (PBMC) transcriptomics to explore the molecular and cellular changes induced by resistance exercise. Subsequently, we established a weight-loaded ladder-climbing mouse model to mimic the physiological effects of resistance exercise, and we analyzed the plasma proteome and metabolome, as well as the transcriptomes of PBMC and muscle tissue. Lastly, to confirm the transmissibility of the neuroprotective effects induced by resistance exercise, we intravenously injected plasma obtained from exercised male mice into SCI female mice during the non-acute phase. Results Plasma proteomic and PBMC transcriptomic profiling underscored the notable involvement of the complement pathways and humoral immune response in the process of restoring locomotor function following SCI in the human trial. Moreover, it was emphasized that resistance exercise interventions could effectively modulate these pathways. Through employing plasma proteomic profiling and transcriptomic profiling of PBMC and muscle tissues in mice, our study revealed immunomodulatory responses that parallel those observed in human trials. In addition, our analysis of plasma metabolomics revealed an enhancement in lipid metabolism following resistance exercise. We observed that resistance exercise plasma exhibited significant effects in ameliorating locomotor disability after SCI via reducing demyelination and inhibiting neuronal apoptosis. Conclusions Our investigation elucidates the molecular alterations associated with resistance exercise therapy promoting recovery of locomotor function following incomplete SCI. Moreover, we demonstrate the direct neuroprotective effects delivered via exercise plasma injection, which facilitates spinal cord repair. Mechanistically, the comprehensive multi-omics analysis involving both human and mice reveals that the principal constituents responsible for the observed neuroprotective effects within the plasma are predominantly immunoregulatory factors, warranting further experimental validation. Trial registration The study was retrospectively registered on 17 July, 2024, in Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at https://www.chictr.org.cn/ .
研究领域:
医学
·
神经科学
·
运动康复
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Gege Hu,Hangyu Hu,Zengjia Zhou,Tariq Aziz,Zhennai Yang,Zhang Yang,Nada K. Alharbi,Ashwag Shami,Fahad Al-Asmari,Hajar AlQadeeb,Maher S. Alwethaynani,Fakhria A. Al-Joufi
One of the vital functional biopolymers produced by lactic acid bacteria (LAB) is exopolysaccharide (EPS) that has been extensively studied, but less research has been done on the EPS production by pediococci . In this study, the EPS synthesis in Pediococcus acidilactici BCB1H regulated by Fe 2+ was investigated by a multi-omics method. Adding Fe 2+ (0.6 g/L) in a semi-defined medium was shown to significantly increase the EPS production from 225.5 to 271.5 mg/L by BCB1H. Joint transcriptomics and proteomics analyses on BCB1H under Fe 2+ interference revealed upregulation of phosphotransferase systems (PTS), the key pathway to synthesizing EPSs. Further joint transcriptomics and metabolomics analyses showed a total of 22 differential metabolic pathways, including overall metabolic pathways, biosynthesis of secondary metabolites, metabolism of microorganisms in different environments. Integrated multi-omics analysis for the key differentially expressed genes, proteins and metabolites with synergistic effects revealed decarboxylating 6-phosphogluconate dehydrogenase (Gnd), acetyl-CoA carboxylase biotin carboxylase subunit (AccD) and EII sugar-specific permease (EIIs) genes that were upregulated, while glycerol kinase (GlpK) and alcohol dehydrogenase (AdhP) downregulated. Therefore, Fe 2+ enhanced the EPS synthesis in BCB1H by promoting accumulation of fructose-6-phosphate, glycerate and malate, and reducing production of d -fructose-1,6-diphosphate and glycerone-phosphate, mainly by regulation of the pentose phosphate pathway, tricarboxylic acid cycle, glycolysis and gluconeogenesis pathways, and glycerolipid metabolism pathways. The present study was significant for further understanding the regulatory mechanism of EPS biosynthesis in LAB.
研究领域:
微生物学
·
分子生物学
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jiying Zhu,Wei Jia,Jian Peng
Crocus sativus L. is a both medicinal and food bulbous flower whose qualities are geographically characterized. However, identification involving different places of origin of such substances is currently limited to single-omics mediated content analysis. Integrated metabolomics and proteomics, 840 saffron samples from six countries (Spain, Greece, Iran, China, Japan, and India) were analyzed using the QuEChERS extraction method. A total of 77 differential metabolites and 14 differential proteins were identified. The limits of detection of the method were 1.33 to 8.33 μg kg −1 , and the recoveries were 85.56% to 105.18%. Using homology modeling and molecular docking, the Gln84, Lys195, Val182 and Pro184 sites of Crocetin glucosyltransferase 2 were found to be the targets of crocetin binding. By multivariate statistical analysis (PCA and PLS-DA), different saffron samples were clearly distinguished. The results provided the basis for the selection and identification of high quality saffron from different producing areas.
研究领域:
植物化学
·
分子生物学
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxics
·
2023
·Vol. 11
·期 2
·184
·
IF 4.6
Huazhong Zhang,Jinsong Zhang,Jinquan Li,Zhengsheng Mao,Jian Qian,Cheng Zong,Hao Sun,Beilei Yuan
Diquat (DQ), a widely used bipyridyl herbicide, is associated with significantly higher rates of kidney injuries compared to other pesticides. However, the underlying molecular mechanisms are largely unknown. In this study, we identified the molecular changes in the early stage of DQ-induced kidney damage in a mouse model through transcriptomic, proteomic and metabolomic analyses. We identified 869 genes, 351 proteins and 96 metabolites that were differentially expressed in the DQ-treated mice relative to the control mice (p< 0.05), and showed significant enrichment in the PPAR signaling pathway and fatty acid metabolism. Hmgcs2, Cyp4a10, Cyp4a14 and Lpl were identified as the major proteins/genes associated with DQ-induced kidney damage. In addition, eicosapentaenoic acid, linoleic acid, palmitic acid and (R)-3-hydroxybutyric acid were the major metabolites related to DQ-induced kidney injury. Overall, the multi-omics analysis showed that DQ-induced kidney damage is associated with dysregulation of the PPAR signaling pathway, and an aberrant increase in Hmgcs2 expression and 3-hydroxybutyric acid levels. Our findings provide new insights into the molecular basis of DQ-induced early kidney damage.Keywords:diquat;kidney injury;multi-omics;fatty acid metabolism;PPAR signaling pathway
研究领域:
毒理学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-19
·
IF 9.429
Peng Xin,Xie Zhuomi,Wang Xiuhua,Zhao Yuxiang,Yang Chuyun,Zhang Zhongyi,Li Mingjie,Zheng Jianping,Wang Yuhui
Background Luminescent nanomaterials (LNMs), especially newly-exploited fluorescent carbon-dots (CDs), have demonstrated promising candidates for sunlight harvesting and enhanced photosynthesis efficiency of crops. However, most of the studies focus on the design and synthesis of LNMs and primary metabolism in biomass acceleration, secondary metabolism that closely associated with the quality ingredients of plants is rarely mentioned. Results UV-absorptive and water-soluble NIR-CDs were harvested via a facile microwave-assisted carbonization method. The effect and regulatory mechanism of NIR-CDs on the secondary metabolism and bioactive ingredients accumulation in Tetrastigma hemsleyanum were explored. A total of 191 differential secondary metabolites and 6874 differentially expressed genes were identified when the NIR-CDs were adopted for enhancing growth of T. hemsleyanum . The phenolic acids were generally improved, but the flavonoids were more likely to decrease. The pivotal differentially expressed genes were involved in biosynthesis of secondary metabolites, flavonoid biosynthesis, porphyrin and chlorophyll metabolism, etc. The gene-metabolite association was constructed and 44 hub genes highly related to quality ingredients accumulation and growth were identified, among which and the top 5 genes of the PPI network might be the key regulators. Conclusion This research provided key regulatory genes and differentially accumulating quality ingredients under NIR-CDs-treatment, which could provide a theoretical basis for expanding the applications of nanomaterial in industrial crop agriculture. Graphical Abstract
研究领域:
植物学
·
分子生物学
·
农业科学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Food Chemistry-X
·
2025
·
IF 8.2
Qishan Dong,Lizhi Lu,Tiantian Gu,Yong Tian,Yibo Zong,Jing Sun,Yu Huang,Qiuling Fu,Jun He,Tao Zeng
This study employed a multi-omics approach to examine the impact of feed fermentation on the lipid profile and volatile flavor of duck eggs. Sensory evaluation and GC × GC-TOFMS analyses demonstrated that microbial fermentation in feed significantly reduced the off-odor of duck eggs. Among the thirty-nine differential volatile compounds identified, six—namely 3-methylbutanal, 1-octen-3-ol, hexanal, acetophenone, 2-heptanone, and 2-pentylfuran—were likely responsible for the alteration in yolk aroma. Lipidomics and metabolomics identified twenty-five key differential lipids ( p < 0.05, VIP > 1.85) and a modified metabolic pathway associated with linoleic acid (LA), involving four metabolites. Correlation analysis revealed significant associations between LA-containing lipids (e.g., DG (18: 2/18:2)), LA metabolites, and differential volatiles (e.g., 3-methylbutanal) ( p < 0.05). These results provide insights into the mechanisms underlying off-odor reduction and offer a potential strategy for enhancing the flavor profile of duck eggs.
研究领域:
食品科学
·
代谢组学
·
动物营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2024
·Vol. 14
·期 19
·7534
·
IF 12.4
Wenfang He,Chenguang Ding,Ting Lin,Binqi Wang,Wenjing Wang,Zhichao Deng,Taian Jin,Yiwei Shang,Danna Zheng,Ting Bai,Mingzhen Zhang,Runqing Li,Juan Jin,Qiang He
Rationale : Ischemia-reperfusion-induced acute kidney injury (IR-AKI), characterized by the abrupt decline in renal function, is distinguished by the intricate interplay between oxidative stress and inflammation. In this study, a reactive oxygen species (ROS) scavenger-CF@PDA was developed to effectively target antioxidant and anti-inflammatory pathways to disrupt the oxidative stress-inflammation cycle in IR-AKI. Methods : UV-vis absorption spectra, FTIR spectra, and TEM were employed to determine the successful construction of CF@P. ABTS, TMB, and NBT analyses were performed to detect the antioxidant ability and enzyme-mimicking ability of CF@P. In vitro and in vitro , the antioxidant/anti-inflammatory effect of CF@P was detected by MTT, qPCR, fluorescence, and flow cytometry. Multi-omics revealed the mechanism of CF@P in IR-AKI therapy, and molecular docking was further used to determine the mechanism. MRI and photoacoustic imaging were employed to explore the dual-mode imaging capacity of CF@P in IR-AKI management. Results : CF@P could disrupt the oxidative stress-inflammatory cascade by scavenging ROS, reducing pro-inflammatory cytokines, and modulation of macrophage polarization. Subsequent multi-omics indicated that the renal protective effects may be attributed to the inhibition of pyruvate dehydrogenase kinase 4 (PDK4). Metabolomics demonstrated that CF@P could improve the production of antioxidant compounds and reduce nephrotoxicity. Additionally, CF@P exhibited promising capabilities in T1-MRI and photoacoustic imaging for AKI management. Conclusions : Collectively, CF@P, possessing antioxidant/anti-inflammatory properties by inhibiting PDK4, as well as imaging capabilities and superior biocompatibility, holds promise as a therapeutic strategy for IR-AKI.
研究领域:
医学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）