28 research outputs found

    Driving behavior-guided battery health monitoring for electric vehicles using machine learning

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    An accurate estimation of the state of health (SOH) of batteries is critical to ensuring the safe and reliable operation of electric vehicles (EVs). Feature-based machine learning methods have exhibited enormous potential for rapidly and precisely monitoring battery health status. However, simultaneously using various health indicators (HIs) may weaken estimation performance due to feature redundancy. Furthermore, ignoring real-world driving behaviors can lead to inaccurate estimation results as some features are rarely accessible in practical scenarios. To address these issues, we proposed a feature-based machine learning pipeline for reliable battery health monitoring, enabled by evaluating the acquisition probability of features under real-world driving conditions. We first summarized and analyzed various individual HIs with mechanism-related interpretations, which provide insightful guidance on how these features relate to battery degradation modes. Moreover, all features were carefully evaluated and screened based on estimation accuracy and correlation analysis on three public battery degradation datasets. Finally, the scenario-based feature fusion and acquisition probability-based practicality evaluation method construct a useful tool for feature extraction with consideration of driving behaviors. This work highlights the importance of balancing the performance and practicality of HIs during the development of feature-based battery health monitoring algorithms

    Loss‐of‐Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia

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    Background and aims: Hypoxia is a common feature of the tumor microenvironment (TME), which promotes tumor progression, metastasis, and therapeutic drug resistance through a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclinical development of this approach is lacking in the study of HCC. Approach and results: From a genome-wide CRISPR/CRISPR-associated 9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia. Knockdown of ALDOA in HCC cells leads to lactate depletion and consequently inhibits tumor growth. Supplementation with lactate partly rescues the inhibitory effects mediated by ALDOA knockdown. Upon hypoxia, ALDOA is induced by hypoxia-inducible factor-1α and fat mass and obesity-associated protein-mediated N6 -methyladenosine modification through transcriptional and posttranscriptional regulation, respectively. Analysis of The Cancer Genome Atlas shows that elevated levels of ALDOA are significantly correlated with poor prognosis of patients with HCC. In a screen of Food and Drug Administration-approved drugs based on structured hierarchical virtual platforms, we identified the sulfamonomethoxine derivative compound 5 (cpd-5) as a potential inhibitor to target ALDOA, evidenced by the antitumor activity of cpd-5 in preclinical patient-derived xenograft models of HCC. Conclusions: Our work identifies ALDOA as an essential driver for HCC cell growth under hypoxia, and we demonstrate that inhibition of ALDOA in the hypoxic TME is a promising therapeutic strategy for treating HCC

    RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer

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    Objective: Dysregulated cellular metabolism is a distinct hallmark of human colorectal cancer (CRC). However, metabolic programme rewiring during tumour progression has yet to be fully understood. Design: We analysed altered gene signatures during colorectal tumour progression, and used a complex of molecular and metabolic assays to study the regulation of metabolism in CRC cell lines, human patient-derived xenograft mouse models and tumour organoid models. Results: We identified a novel RNA-binding protein, RALY (also known as hnRNPCL2), that is highly associated with colorectal tumour aggressiveness. RALY acts as a key regulatory component in the Drosha complex, and promotes the post-transcriptional processing of a specific subset of miRNAs (miR-483, miR-676 and miR-877). These miRNAs systematically downregulate the expression of the metabolism-associated genes (ATP5I, ATP5G1, ATP5G3 and CYC1) and thereby reprogramme mitochondrial metabolism in the cancer cell. Analysis of The Cancer Genome Atlas (TCGA) reveals that increased levels of RALY are associated with poor prognosis in the patients with CRC expressing low levels of mitochondrion-associated genes. Mechanistically, induced processing of these miRNAs is facilitated by their N6-methyladenosine switch under reactive oxygen species (ROS) stress. Inhibition of the m6A methylation abolishes the RALY recognition of the terminal loop of the pri-miRNAs. Knockdown of RALY inhibits colorectal tumour growth and progression in vivo and in organoid models. Conclusions: Collectively, our results reveal a critical metabolism-centric role of RALY in tumour progression, which may lead to cancer therapeutics targeting RALY for treating CRC

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∌99% of the euchromatic genome and is accurate to an error rate of ∌1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Research on Furnace Temperature Curve Based on Heat Convection and Heat Radiation

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    Insights into the mechanism of reflow soldering temperature curve, a mathematical model of the temperature change of the circuit board surface is established. The heat transfer methods, heat radiation and heat convection is analyzed in detail. The curve of air temperature inside the reflow furnace is solved by establishing an one-dimensional heat conduction model and fitting coefficients. The heat radiation received by the circuit board mainly comes from the small temperature zone. Depending on the area where the circuit board is located, heat radiation is itemized into 3 types: heat radiation in the gap, the temperature zone and the adjacent temperature zone of the area before and after the furnace. The impacts of heat radiation is weighted and analyzed by relative distance. For coefficients, analyzing and fitting is further discussed

    N6-Methyladenosine modification: a novel pharmacological target for anti-cancer drug development

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    N6-Methyladenosine (m6A) modification is the most pervasive modification of human mRNA molecules. It is reversible via regulation of m6A modification methyltransferase, demethylase and proteins that preferentially recognize m6A modification as “writers”, “erasers” and “readers”, respectively. Altered expression levels of the m6A modification key regulators substantially affect their function, leading to significant phenotype changes in the cell and organism. Recent studies have proved that the m6A modification plays significant roles in regulation of metabolism, stem cell self-renewal, and metastasis in a variety of human cancers. In this review, we describe the potential roles of m6A modification in human cancers and summarize their underlying molecular mechanisms. Moreover, we will highlight potential therapeutic approaches by targeting the key m6A modification regulators for cancer drug development. Key words: N6-Methyladenosine, Human cancer, Pharmacological target, m6A modification regulator, Drug developmen

    A Meta Analysis of Doublets Versus Single-agent Chemotherapy 
for Elderly Patients with Advanced Non-small Cell Lung Cancer

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    Background and objective It remains disputed whether doublets are more effective than single-agent chemotherapy for elderly patients with advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the efficacy and safety of doublets and single-agent chemotherapy for elderly patients with NSCLC. Methods Data from all published, randomized trials that compared doublets and single-agent chemotherapy in elderly patients were collected from electronic databases (PubMed, EMBASE, Cochrane Library, CNKI and the CBMdice). Meta-analysis was completed using software Stata 11.0. Results The results of the meta-analysis, including 12 eligible trials (2,306 patients), showed that the doublets significantly increased the overall response rate (OR=1.80, 95%CI:1.50-2.17, P<0.000,1) and one-year survival rate (OR=1.45, 95%CI: 1.22-1.72, P<0.000,1) compared with single-agent chemotherapy. The results of one-year survival rate in platinum-based doublet chemotherapy arms (OR=1.55, 95%CI: 1.18-2.03, P=0.001) and non platinum-based ones (OR=1.38, 95%CI: 1.10-1.73, P=0.006) were both significantly higher than that of single-agent chemotherapy. However, grade 3/4 anemia, neutropenia, thrombocytopenia and neurotoxicity (P<0.05) were significantly associated with doublet chemotherapy. The incidence of toxicity effect in non platinum-based chemotherapy was similar to that of single-agent chemotherapy. Conclusion Compared with single-agent chemotherapy, doublet chemotherapy could increase the overall response rate and one-year survival rate significantly. Therefore, doublet chemotherapy would be more appropriate for elderly patients with advanced NSCLC as the first-line chemotherapy regimen. However, further prospective randomized controlled trials in elderly NSCLC patients is needed to verify the findings in this study
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