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Network pharmacology can ascertain the therapeutic mechanism of drugs for treating diseases at the level of biological targets and pathways. The effective mechanism study of traditional Chinese medicine (TCM) characterized by multi-component, multi-targeted, and integrative efficacy, perfectly corresponds to the application of network pharmacology. Currently, network pharmacology has been widely utilized to clarify the mechanism of the physiological activity of TCM. In this review, we comprehensively summarize the application of network pharmacology in TCM to reveal its potential of verifying the phenotype and underlying causes of diseases, realizing the personalized and accurate application of TCM. We searched the literature using “TCM network pharmacology” and “network pharmacology” as keywords from Web of Science, PubMed, Google Scholar, as well as Chinese National Knowledge Infrastructure in the last decade. The origins, development, and application of network pharmacology are closely correlated with the study of TCM which has been applied in China for thousands of years. Network pharmacology and TCM have the same core idea and promote each other. A well-defined research strategy for network pharmacology has been utilized in several aspects of TCM research, including the elucidation of the biological basis of diseases and syndromes, the prediction of TCM targets, the screening of TCM active compounds, and the decipherment of mechanisms of TCM in treating diseases. However, several factors limit its application, such as the selection of databases and algorithms, the unstable quality of the research results, and the lack of standardization. This review aims to provide references and ideas for the research of TCM and to encourage the personalized and precise use of Chinese medicine.

The influence of the microstructural characteristics on the mechanical and hydrogen embrittlement properties of 1800 MPa grade hot-stamped 22MnB5 steel was experimentally investigated using samples processed under various hot-stamping conditions,i.e., different heating temperatures and strain levels. The tensile strength increased with increasing hot-stamping temperature up to approximately 920 °C and subsequently decreased owing to the increasing sizes of the lath martensite and prior austenite phases. Some degree of internal strain was introduced into the 22MnB5 steel specimen during hot stamping at 920 °C, which led to a slightly higher hardness although no clear microstructural change was observed. The severity of hydrogen embrittlement of the hot-stamped 22MnB5 steel samples was investigated after immersion in a NH4SCN solution, and the degree of hydrogen embrittlement was found to be directly associated with the amount of hydrogen that penetrated into the grain boundary and lath martensite boundary. The high-strength 22MnB5 steel with a very small lath martensite phase exhibited severe hydrogen embrittlement due to the large amount of hydrogen in the sample, and the high internal strain (or high dislocation density) could lead to accelerated hydrogen embrittlement. Severe hydrogen embrittlement occurred upon charging with more than approximately 0.8 ppm hydrogen. Based on the obtained results, models are proposed for the hydrogen embrittlement characteristics of hot-stamped 22MnB5 steel.

Microglia mediated neuronal inflammation has been widely reported to be responsible for neurodegenerative disease. Deacetyl ganoderic acid F (DeGA F) is a triterpenoid isolated from Ganoderma lucidum, which is a famous edible and medicinal mushroom used for treatment of dizziness and insomnia in traditional medicine for a long time. In this study the inhibitory effects and mechanisms of DeGA F against lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo were investigated. On murine microglial cell line BV-2 cells, DeGA F treatment inhibited LPS-triggered NO production and iNOS expression and affected the secretion and mRNA levels of relative inflammatory cytokines. DeGA F inhibited LPS-induced activation of the NF-κB pathway, as evidenced by decreased phosphorylation of IKK and IκB and the nuclear translocation of P65. In vivo, DeGA F treatment effectively inhibited NO production in zebrafish embryos. Moreover, DeGA F suppressed the serum levels of pro-inflammatory cytokines, including TNF-α and IL-6 in LPS-stimulated mice model. DeGA F reduced inflammatory response by suppressing microglia and astrocytes activation and also suppressed LPS-induced NF-κB activation in mice brains. Taken together, DeGA F exhibited remarkable anti-inflammatory effects and promising therapeutic potential for neural inflammation associated diseases.

CRISPR/Cas9 technology has been widely used for targeted genome modification both in vivo and in vitro . However, an effective method for evaluating genome editing efficiency and screening single-cell clones for desired modification is still lacking. Here, we developed this real time PCR method based on the sensitivity of Taq DNA polymerase to nucleotide mismatch at primer 3′ end during initiating DNA replication. Applications to CRISPR gRNAs targeting EMX1 , DYRK1A and HOXB13 genes in Lenti-X 293 T cells exhibited comprehensive advantages. Just in one-round qPCR analysis using genomic DNA from cells underwent CRISPR/Cas9 or BE4 treatments, the genome editing efficiency could be determined accurately and quickly, for indel, HDR as well as base editing. When applied to single-cell clone screening, the genotype of each cell colony could also be determined accurately. This method defined a rigorous and practical way in quantify genome editing events.

Age-related muscle atrophy (sarcopenia) is the leading cause for disability in aged population, but the underlying molecular mechanisms are poorly understood. Here we identify a novel role for the secreted glycoprotein Dickkopf 3 ( Dkk3 ) in sarcopenia. Forced expression of Dkk3 in muscles in young mice leads to muscle atrophy. Conversely, reducing its expression in old muscles restores both muscle size and function. Dkk3 induces nuclear import of β-catenin and enhances its interaction with FoxO3, which in turn activates the transcription of E3 ubiquitin ligase Fbxo32 and Trim63 , driving muscle atrophy. These findings suggest that Dkk3 may be used as diagnostic marker and as therapeutic target for age-related muscle atrophy, and reveal a distinct transcriptional control of Fbxo32 and Trim63. Ageing is associated with muscle atrophy. Here, the authors show that the secreted glycoprotein Dickkopf 3 promotes muscle atrophy by inducing nuclear import of beta-catenin, its association with FoxO3 and the consequent activation of the atrophy-related genes Atrogin1 and MuRF1 .

Deep-sea minerals are regarded as the most economically viable and promising mineral resource. Vertical hydraulic lifting represents one of the most promising methods for deep-sea mining lifting systems. To mitigate the potential for clogging due to the aggregation of particles in vertical pipe transport during deep-sea mining operations, this paper employs numerical simulations utilizing the computational fluid dynamics and discrete element method (CFD-DEM) model to investigate the swirling flow transportation of mineral particles. The characteristics of the swirling flow field and the motion law of double-size particles at different swirling ratios are investigated. The findings demonstrate that, in comparison to axial transport within the pipeline, the particle movement observed in swirling flow transport exhibits an upward spiral trajectory. This phenomenon facilitates the orderly movement of particles, thereby enhancing the fluidization of particles within the pipeline. An increase in the swirling ratio (SR) has a considerable impact on the velocity within the pipe. The tangential velocity distribution undergoes a gradual transition from centrosymmetric to non-centrosymmetric as the distance from the inlet increases. An increase in the SR results in an enhanced aggregation of particles at the wall, accompanied by a notable rise in the local particle concentration. The value of SR = 0.3 represents a critical threshold. When SR exceeds this value, the distribution of particles in the cross-section reaches a relatively stable state, rendering it challenging to further alter the distribution and concentration of particles, even if the SR is augmented. Furthermore, the maximum local particle concentration in the vicinity of the wall tends to be stable. These results provide valuable insights into vertical pipe swirling flow transport for deep-sea mining.

Recent research has demonstrated the efficacy of traditional Chinese medicine (TCM) and its active compounds in combating cancer, leading to an increasing utilization of TCM as adjunctive therapy in clinical oncology. However, the optimal dosage of TCM remains unclear, and excessive use may result in cardiotoxicity, which poses a significant health concern for patients undergoing systemic treatment. Therefore, elucidating the underlying mechanisms of cytotoxicity induced by TCM can provide valuable insights for clinical management. In this study, we employed a comprehensive bioinformatics analysis to present sequencing data obtained from AC16 myocardial cells treated with two bioactive derived from botanical drugs: Matrine and Evodiamine. We aim to investigate the dysregulated signaling pathways associated with cardiotoxicity induced by these compounds. Based on our sequencing results, we observed consistent patterns of gene expression and epitranscriptome regulation (m6A and A-to-I modifications) across various drugs-treated AC16 cells when analyzed using KEGG pathway enrichment and gene ontology analyses. Furthermore, m6A writers VIRMA and A-to-I writers ADARB1 is consistent target of Evodiamine and Matrine. In general, our findings suggest that different Chinese botanical drugs induced cardiotoxicity may share common therapeutic strategies.

Deepwater drilling involves the use of a drill string that is slender and relatively large, making it a critical weak link in offshore drilling systems. Dynamic coupling within the drill string becomes more complex under the combined effects of ocean currents and synchronized rotation. Therefore, this study uses a Fluid-Structure Interaction (FSI) model to explore the dynamic characteristics of the rotating drill string. The model is primarily based on solutions of Navier-Stokes equations and structural mechanics control equations, with the interaction force between the fluid and structure coupled through boundary conditions to ensure force balance between the two. The results show that the larger the wave period is, the greater the maximum displacement magnitude of the drill string is. At a wave height of 0.1 m and a drill string rotational speed of 200 r/min, the maximum average displacement magnitude of the drill string monitoring position occurs when the wave period is 3 s. Additionally, under different wave periods, the displacement trajectory of the drill string over time shows periodic variations, with larger displacements occurring closer to the lower end of the drill string. The findings provide support for the structural design of open-hole coring drill strings and drilling plans.

Spermatogonial stem cells (SSC), the foundation of spermatogenesis and male fertility, possess lifelong self-renewal activity. Aging leads to the decline in stem cell function and increased risk of paternal age-related genetic diseases. In the present study, we performed a comparative genomic analysis of mouse SSC-enriched undifferentiated spermatogonia (Oct4-GFP+/KIT-) and differentiating progenitors (Oct4-GFP+/KIT+) isolated from young and aged testes. Our transcriptome data revealed enormous complexity of expressed coding and non-coding RNAs and alternative splicing regulation during SSC differentiation. Further comparison between young and aged undifferentiated spermatogonia suggested these differentiation programs were affected by aging. We identified aberrant expression of genes associated with meiosis and TGF-β signaling, alteration in alternative splicing regulation and differential expression of specific lncRNAs such as Fendrr . Epigenetic profiling revealed reduced H3K27me3 deposition at numerous pro-differentiation genes during SSC differentiation as well as aberrant H3K27me3 distribution at genes in Wnt and TGF-β signaling upon aging. Finally, aged undifferentiated spermatogonia exhibited gene body hypomethylation, which is accompanied by an elevated 5hmC level. We believe this in-depth molecular analysis will serve as a reference for future analysis of SSC aging.

Black phosphorus gives several advantages and complementarities over other two-dimensional materials. It has drawn extensive interest owing to its relatively high carrier mobility, wide tunable bandgap, and in-plane anisotropy in recent years. This manuscript briefly reviews the structure and physical properties of black phosphorus and targets on black phosphorus for photonic integrated circuits. Some of the applications are discussed including photodetection, optical modulation, light emission, and polarization conversion. Corresponding recent progresses, associated challenges, and future potentials are covered.