Abstract The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural ...network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.
Being restrained by the limited peak capacity, one‐dimensional chromatography usually leads to an unsatisfactory separation with low purity of compounds in a complex mixture. To obtain more highly ...pure targets for standard reference and to discover new substances for structural elucidation, two‐dimensional chromatography is more and more prevalent in many fields. As few metrics on assessment of the preparative capability of two‐dimensional chromatographic separations are reported, a methodology of in silico screening of various two‐dimensional chromatographic separations with a minimal number of experiments was demonstrated in this work, which was based on three descriptors including the occupation rate of peaks and system homogeneity of a two‐dimensional separation space, and the minimal distance of all nearest‐neighbor distances of peaks. Combining the advantages of counter‐current chromatography and liquid chromatography, we elaborated the methodology by employing off‐line comprehensive two‐dimensional counter‐current chromatography with liquid chromatography to be in silico screened for separation of four saponins from Panax notoginseng at an analytical scale to simulate the case of preparative scale transfer. The predictive results were presented by two‐dimensional contour plots and verified by experiments. The result showed that the experimental results were in general accord with the predictive results.
The near-infrared (NIR) electrogenerated chemiluminescence (ECL) of water-dispersed Ag2Se quantum dots (QDs) with ultrasmall size was presented for the first time. The Ag2Se QDs have shown a strong ...and efficient cathodic ECL signal with K2S2O8 as coreactant on the glassy carbon electrode (GCE) in aqueous solution. The ECL spectrum exhibited a peak at 695 nm, consistent with the peak in photoluminescence (PL) spectrum of the Ag2Se QDs solution, indicating that the Ag2Se QDs had no deep surface traps. Dopamine was chosen as a model analyte to study the potential of Ag2Se QDs in the ECL analytical application. The ECL signal of Ag2Se QDs can also be used for the detection of the dopamine concentration in the practical drug (dopamine hydrochloride injection) containing several adjuvants such as edetate disodium, sodium bisulfite, sodium chloride and so on. The Ag2Se QDs could be a promising candidate emitter of ECL biosensors in the future due to their fantastic features, such as ultrasmall size, low toxicity, good water solubility, and near infrared (NIR) fluorescent emission.
How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3' flap nuclease ...that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3' nuclease, excises flaps at the immediate 3' end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.
Drought and salt stresses, the major environmental abiotic stresses in agriculture worldwide, affect plant growth, crop productivity, and quality. Therefore, developing crops with higher drought and ...salt tolerance is highly desirable. This study reported the isolation, biological function, and molecular characterization of a novel maspardin gene, OsMas1, from rice. The OsMas1 protein was localized to the cytoplasm. The expression levels of OsMas1 were up-regulated under mannitol, PEG6000, NaCl, and abscisic acid (ABA) treatments in rice. The OsMas1 gene was introduced into the rice cultivar Zhonghua 11 (wild type, WT). OsMas1-overexpression (OsMas1-OE) plants exhibited significantly enhanced salt and drought tolerance; in contrast, OsMas1-interference (OsMas1-RNAi) plants exhibited decreased tolerance to salt and drought stresses, compared with WT. OsMas1-OE plants exhibited enhanced hypersensitivity, while OsMas1-RNAi plants showed less sensitivity to exogenous ABA treatment at both germination and post-germination stages. ABA, proline and K+ contents and superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and photosynthesis activities were significantly increased. In contrast, malonaldehyde (MDA), hydrogen peroxide (H2O2), superoxide anion radical (O2-·), and Na+ contents were significantly decreased in OsMas1-OE plants compared with OsMas1-RNAi and WT plants. Overexpression of OsMas1 up-regulated the genes involved in ABA signaling, proline biosynthesis, reactive oxygen species (ROS)-scavenging system, photosynthesis, and ion transport under salt and drought stresses. Our results indicate that the OsMas1 gene improves salt and drought tolerance in rice, which may serve as a candidate gene for enhancing crop resistance to abiotic stresses.
Background
The aim of this study was to determine the effect of human urine‐derived stem cells (HUSCs) for the treatment of spinal cord injury (SCI) and investigate associated the molecular network ...mechanism by using bioinformatics combined with experimental validation.
Methods
After the contusive SCI model was established, the HUSC‐expressed specific antigen marker was implanted into the injury site immediately, and the Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) was utilized to evaluate motor function so as to determine the effect of HUSCs for the neural repair after SCI. Then, the geneCards database was used to collect related gene targets for both HUSCs and SCI, and cross genes were merged with the findings of PubMed screen. Subsequently, protein–protein interaction (PPI) network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, as well as core network construction, were performed using Cytoscape software. Lastly, real‐time quantitative polymerase chain reaction (PCR) and immunofluorescence were employed to validate the mRNA expression and localization of 10 hub genes, and two of the most important, designated as cadherin 1 (CDH1) and integrin subunit beta 1 (ITGB1), were identified successfully.
Results
The immunophenotypes of HUSCs were marked by CD90+ and CD44+ but not CD45, and flow cytometry confirmed their character. The expression rates of CD90, CD73, CD44 and CD105 in HUSCs were 99.49, 99.77, 99.82 and 99.51%, respectively, while the expression rates of CD43, CD45, CD11b and HLA‐DR were 0.08, 0.30, 1.34 and 0.02%, respectively. After SCI, all rats appeared to have severe motor dysfunction, but the BBB score was increased in HUSC‐transplanted rats compared with control rats at 28 days. By using bioinformatics, we obtained 6668 targets for SCI and 1095 targets for HUSCs and identified a total of 645 cross targets between HUSCs and SCI. Based on the PPI and Cytoscape analysis, CD44, ACTB, FN1, ITGB1, HSPA8, CDH1, ALB, HSP90AA1 and GAPDH were identified as possible therapeutic targets. Enrichment analysis revealed that the involved signal pathways included complement and coagulation cascades, lysosome, systemic lupus erythematosus, etc. Lastly, quantificational real‐time (qRT)‐PCR confirmed the mRNA differential expression of CDH1/ITGB1 after HUSC therapy, and glial fibrillary acidic protein (GFAP) immunofluorescence staining showed that the astrocyte proliferation at the injured site could be reduced significantly after HUSC treatment.
Conclusions
We validated that HUSC implantation is effective for the treatment of SCI, and the underlying mechanisms associated with the multiple molecular network. Of these, CDH1 and ITGB1 may be considered as important candidate targets. Those findings therefore provided the crucial evidence for the potential use of HUSCs in SCI treatment in future clinic trials.
Human urine stem cells (HUSCs) showed a positive spinal cord injury (SCI) repair effect through the complex gene network, and ITGB1, HSP90AA1, GAPDH, HSPA8, ACTB, FN1, MMP9, CD44, ALB and CDH1 were possible candidate genes. Among them, CDH1 and ITGB1 may be the key genes affecting the damage repair of HUSCs. These findings may contribute to the application of HUSCs in future clinical trials and reveal valuable potential mechanisms for treating SCI based on HUSCs strategies.
In this work, the microstructures and mechanical properties of nine different Mg–Y–Zn–Zr alloys have been investigated. The investigated Mg–Y–Zn alloys mainly contain four types: W-phase, W−+X-phase ...and X-phase+Mg24Y5 alloys, which should be determined by both the Y/Zn mole ratios and the total alloying content. The phase compositions and content play a fatal role on the mechanical properties of the as-extruded Mg–Y–Zn–Zr alloys. However, the Mg–Y–Zn–Zr alloys received almost no aging hardening response, except for the alloy containing X-phase and Mg24Y5. This is because a supersaturated matrix was not available to these alloys containing only the stable ternary X- or W-phase. Nevertheless, the as-extruded Mg–12Y–5Zn–0.6Zr alloy could still own extraordinary high strength, whose ultimate tensile strength and yielding tensile strength were 429MPa and 351MPa, respectively. It should be attributed to the X-phase strengthening effects. After peak-aging, the Mg–12Y–3Zn–0.6Zr alloy established an ultimate tensile strength and yielding tensile strength of 440MPa and 350MPa, respectively. The effects of phase compositions and content on mechanical properties have been discussed in detail.
•Nine high strength Mg–Y–Zn–Zr alloys with different Y/Zn ratios have been studied.•Phase composition and content are determined by Y/Zn ratio and alloy addition.•X-phase is more effective to toughen alloy than W phase do.•Mg–Y–Zn alloys containing X-phase and Mg24Y5 receive good aging hardening response.
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The big data acquired by AIS system contains abundant maritime traffic information. With the wide application of data mining in various fields in recent years, the mining on AIS data has draw ...attention of related researchers. Based on the ship AIS location data, this paper studies the relevant spot area detection algorithm. Firstly, the sample data are pre-processed from the original data, and the residence point of each ship is identified according to the ship speed and course change. Then a DBSCAN based clustering algorithm is used to cluster several latitude and longitude lattice, that is spot areas. The experiments on real AIS data sets shows that the algorithm is efficient and correct.
Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. Tumor suppressor long noncoding RNA on chromosome 8p12 (TSLNC8) is a newly identified long noncoding RNA (lncRNA) and play an ...important role in human cancers. However, the function and molecular mechanism of TSLNC8 in PC progression remain to be elucidated. Our results showed a significant increase of TSLNC8 expression in PC tissues and cell lines. Upregulation of TSLNC8 expression in PC tissues was closely correlated with TNM stage, distant and lymph node metastasis, and poor prognosis of PC patients. Functional experiments demonstrated that TSLNC8 promoted PC cells proliferation and invasion in vitro, and enhanced PC growth and metastasis in vivo. Mechanistically, TSLNC8 associated with HuR, promoted the binding of HuR with CTNNB1 mRNA and increased the stability of CTNNB1 mRNA, thus activating WNT/β-catenin signaling pathway. Taken together, our present study revealed that oncogenic lncRNA TSLNC8 positively regulate PC growth and metastasis via HuR-mediated mRNA stability of CTNNB1, extending the understanding of PC pathogenesis regulated by lncRNAs.
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