Polygonum multiflorum Thunb. (PMT), a commonly used Chinese herbal medicine for treating diseases such as poisoning and white hair, has attracted constant attention due to the frequent occurrence of ...liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential hepatotoxic mechanisms are still unclear. In order to clarify the HEMs of PMT and further explore the potential mechanisms of hepatotoxicity, firstly, the chemical constituents in PMT extract were globally characterized, and the fingerprints of PMT extracts were established along with the detection of their hepatotoxicity in vivo. Then, the correlations between hepatotoxic features and component contents were modeled by chemometrics to screen HEMs of PMT, which were then further evaluated. Finally, the hepatotoxic mechanisms of PMT were investigated using liver metabolomics and molecular docking. The results show that the chemical combination of 2,3,5,4-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) and emodin-8-O-glucoside (EG) was discovered as the HEMs of PMT through pre-screening and verifying process. Liver metabolomics revealed that PMT caused liver injury by interfering with purine metabolism, which might be related to mitochondrial function disorder and oxidative injury via the up-regulations of xanthosine and xanthine, and the down-regulation of 5′ nucleotidase (NT5E) and adenylate kinase 2 (AK2). This study not only found that the HEMs of PMT were TSG and EG, but also clarified that PMT might affect purine metabolism to induce liver injury, which contributed to our understanding of the underlying mechanisms of PMT hepatotoxicity.
The high-storage density, long-life cycle, and low-energy consumption of DNA molecules make it the future of next-generation storage technology. However, DNA storage has the disadvantages of ...high-synthesis cost and low-random access efficiency. A high-density DNA-coding scheme can effectively reduce the cost of DNA synthesis. This paper first proposes a DNA-mapping method based on codebook and a random access method for DNA information based on encoded content. The mapping method satisfies the two biological constraints of homopolymer length and GC content. The random access method can efficiently and selectively read specific files in the DNA pool. To increase storage density, convolutional neural networks are combined with mapping methods to generate base sequences. In the experiments, our method was compared with the results of existing DNA information storage methods, which showed that the proposed scheme has better information storage density.
Software evolution and update play a vital role in software engineering. It has many advantages, such as improving the efficiency of programming, reducing the cost of maintenance and promoting the ...development of software systems. This paper further analyzes the evolution and update processes of three typical kinds of real-world object-oriented software systems by using the tools of complex networks. It discovers some underlying dynamical evolution characteristics and rules of the object- oriented software systems. These results are very useful for the design and development of the object-oriented software systems.
Abstract Background: Pancreatic cancer is the third most prevalent cause of cancer death in the U.S. with a ~10% survival rate. Surgery represents one of the best opportunities for extending survival ...and potential cures. Fluorescence-guided surgery (FGS) employing near-infrared (NIR) fluorescence-based targeting agents improves resection margins, allowing removal of small lesions not visible under white light. We previously reported a targeted NIR tracer (V-1520) of translocator protein (TSPO) expression that demonstrated proof-of-principle utility in high-grade pancreatic lesions arising in Ptf1a-Cre; LSL-KrasG12D/+; Smad4flox/flox (KCS) of pancreatic cancer. The purpose of the present study is to evaluate the utility of V-1520 to identify low-grade, premalignant yet high risk lesions in KCS mice; in this scenario we attempted to model use of V-1520 to remove lesions likely to manifest as future recurrence. We compared the uptake of the tracer in these mice from weaning to adulthood to systematically evaluate the efficacy of FGS as a function of lesion grade. Experimental: The tracer, V-1520, was synthesized and KCS mice were generated as reported.1 Mice were injected with 30μg of V-1520 intravenously 24 hours before imaging. Images were acquired using the 800nm channel. KCS and WT mice were imaged as a function of from 4 to 11 weeks age. After imaging, tumor tissues and major organs were harvested for ex-vivo imaging, histopathology and Cryo-Fluorescent Tomography (CFT). Summary: We found, V-1520 prominently localized in low-grade, premalignant PanIN cystic lesions with malignancy potential, as well as pancreatic tumors with and without local invasion. In contrast, V-1520 did not accumulate in healthy pancreata of KCS or WT mice. Mice as young as 4 weeks exhibited localized accumulation of the tracer with low grade PanIN and early dysplasia. The fluorescence intensity was further enhanced in mice with higher grade disease, whereby the pathology was characterized by high-grade cyst formation, increased nuclear/cytoplasm ratio, acinar to ductal metaplasia and invasion. Low and high-grade neoplasia was characterized by high TSPO immunoreactivity, consistent with in-vivo imaging. Confocal microscopy was used to colocalize V-1520 accumulation and TSPO immunoreactivity; V-1520 was found to prominently localized to premalignant epithelia pancreatic cancer cells. CFT illustrated that the primary localization of V-1520 included the liver, kidneys, and pancreatic diseases. Conclusion: These studies suggest the utility of V-1520 to identify high-risk pancreatic lesions that could be removed with surgery. Encouragingly, the V-1520 was capable of differentiating tumors from surrounding non-tumor tissue at an early stage, which could lead to better resections and delay and/or prevent recurrence in the future. 1. Clinical Cancer Research 26(22), 15 Nov. 2020 5914-5925 Citation Format: Shilpa Sharma, Denise Hernandez, Xiaoxia Wen, Jianbo Wang, Cong-Dat Pham, Beibei Huang, Henry Charles Manning. TSPO-targeted near-infrared optical probe for early identification and localization of high-risk premalignant pancreatic lesions abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4166.
With the rapid growth of sequencing technology, a number of genomes and transcriptomes of various species have been sequenced, contributing to the study of lineage-specific genes (LSGs). We ...identified two sets of LSGs using BLAST: one included Caenorhabditis elegans species-specific genes (1423, SSGs), and the other consisted of Caenorhabditis genus-specific genes (4539, GSGs). The subsequent characterization and analysis of the SSGs and GSGs showed that they have significant differences in evolution and that most LSGs were generated by gene duplication and integration of transposable elements (TEs). We then performed temporal expression profiling and protein function prediction and observed that many SSGs and GSGs are expressed and that genes involved with sex determination, specific stress, immune response, and morphogenesis are over-represented, suggesting that these specific genes may be related to the Caenorhabditis nematodes' special ability to survive in severe and extreme environments.
•We characterized the genetic features of LSGs and analyzed their expression profiles at different developmental stages.•The origin analysis of LSGs showed that gene duplication and exaptation from TEs mainly are the generating mechanisms.•Predicted functions of LSGs may indicate how Caenorhabditis nematodes exhibit strong adaptation to environments..
AOC (allene oxide cyclase; EC 5.3.99.6), an essential enzyme in jasmonic acid and its methyl ester biosynthesis, was cloned from Camptotheca acuminata (named as CaAOC), a native medicinal plant ...species in China. CaAOC had significant similarity at the amino-acid level with AOCs from other plant species. Comparison between the sequences of the full-length cDNA and genomic DNA of CaAOC revealed that the genomic DNA of CaAOC contained an 89-bp intron and a 240-bp intron. Southern-blot analysis indicated that CaAOC was a multiple-copy gene, and real-time quantitative PCR analysis showed that CaAOC was expressed constitutively in all organs tested, with the highest expression level in leaves. The results from treatment experiments using different signalling components, including methyl jasmonate, abscisic acid, salicylic acid and H(2)O(2), revealed that expression of CaAOC had a prominent diversity. Heavy metal (copper) significantly enhanced CaAOC expression, whereas wounding (induced by UV-B) was not so effective.
Various experiments were conducted to study the combustion characteristics of partially premixed methane enrichment of syngas by using the OH-PLIF technique. Experiments were conducted on a co-flow ...burner, and the methane concentration (XCH4 = CH4/(H2+CO+CH4)) was varied from 0 to 20%, the overall equivalence ratio was varied from 0.4 to 1.2 and the inner equivalence ratio was varied from 1.5 to 3.5. Kinetic simulation was conducted by using OPPDIF module of CHEMKIN-Pro software. Results show that an increase in XCH4 and πoverall weakens the OH signal intensity. Adding methane into the fuel greatly increases the height of the inner flame front, and the increase of methane concentration has a negative effect on flame propagation speed. Meanwhile, simulation results remain consistent with the experiments. The main OH radical production reaction changes from R46: H+HO2 = 2OH to R38: H+O2 = O+OH when methane concentration contained in the fuel mixture increases. Sensitivity analysis also indicates that reaction which plays a dominant effect on temperature changes with the increase of methane concentration.
Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that ...venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.
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•Venetoclax enhances NK cell cytotoxicity, likely independent of BCL-2 inhibition•Venetoclax increases NK cell avidity for AML cells and improves IS formation•Venetoclax boosts mitochondrial metabolism via NF-κB, enhancing IS formation•The CD161lowCD218b+ NK cell subpopulation exhibits high sensitivity to venetoclax
Wang et al. reveal that venetoclax activates NK cells, enhancing their cytotoxicity against leukemia through NF-κB-mediated metabolic and cytoskeletal changes. This improves NK cell avidity and IS formation in leukemic cells, with CD161lowCD218b+ NK cells showing heightened sensitivity, indicating potential targets for NK cell-based immunotherapy.
DNA has been recognized as a promising natural medium for information storage. The expensive DNA synthesis process makes it an important challenge to utilize DNA nucleotides optimally and increase ...the storage density. Thus, a novel scheme is proposed for the storage of digital information in synthetic DNA with high storage density and perfect error correction capability. The proposed strategy introduces quaternary Huffman coding to compress the binary stream of an original file before it is converted into a DNA sequence. The proposed quaternary Huffman coding is based on the statistical properties of the source and can gain a very high compression ratio for files with a non-uniform probability distribution of the source. Consequently, the amount of information that each base can store increases, and the storage density is also improved. In addition, quaternary Hamming code with low redundancy is proposed to correct errors occurring in the synthesis and sequencing. We have successfully converted a total of 5.2 KB of files into 3934 bits in DNA bases. The results of biological experiment indicate that the storage density of the proposed scheme is higher than that of state-of-the-art schemes.
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