Indole contributes to tetracycline resistance via the outer membrane protein OmpN in Vibrio splendidus

As an interspecies and interkingdom signaling molecule, indole has recently received attention for its diverse effects on the physiology of both bacteria and hosts. In this study, indole increased the tetracycline resistance of Vibrio splendidus. The minimal inhibitory concentration of tetracycline was 10 mu g/mL, and the OD600 of V. splendidus decreased by 94.5% in the presence of 20 mu g/mL tetracycline; however, the OD600 of V. splendidus with a mixture of 20 mu g/mL tetracycline and 125 mu M indole was 10- or 4.5-fold higher than that with only 20 mu g/mL tetracycline at different time points. The percentage of cells resistant to 10 mu g/mL tetracycline was 600-fold higher in the culture with an OD600 of approximately 2.0 (higher level of indole) than that in the culture with an OD600 of 0.5, which also meant that the level of indole was correlated to the tetracycline resistance of V. splendidus. Furthermore, one differentially expressed protein, which was identified as the outer membrane porin OmpN using SDS-PAGE combined with MALDI-TOF/TOF MS, was upregulated. Consequently, the expression of the ompN gene in the presence of either tetracycline or indole and simultaneously in the presence of indole and tetracycline was upregulated by 1.8-, 2.54-, and 6.01-fold, respectively, compared to the control samples. The combined results demonstrated that indole enhanced the tetracycline resistance of V. splendidus, and this resistance was probably due to upregulation of the outer membrane porin OmpN

NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.

N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this study, we investigated the regulation of NMI on CSCs traits in breast cancer and uncovered the underlying molecular mechanisms. We found that NMI was lowly expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of NMI promoted CSCs traits while its overexpression inhibited CSCs traits, including the expression of CSC-related markers, the number of CD44+CD24- cell populations and the ability of mammospheres formation. We also found that NMI-mediated regulation of BCSCs traits was at least partially realized through the modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while its overexpression downregulated hTERT in breast cancer cells, and the changes in CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The in vivo study also validated that NMI knockdown promoted breast cancer growth by upregulating hTERT signaling in a mouse model. Moreover, further analyses for the clinical samples demonstrated that NMI expression was negatively correlated with hTERT expression and the low NMI/high hTERT expression was associated with the worse status of clinical TNM stages in breast cancer patients. Furthermore, we demonstrated that the interaction of YY1 protein with NMI and its involvement in NMI-mediated transcriptional regulation of hTERT in breast cancer cells. Collectively, our results provide new insights into understanding the regulatory mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a potential therapeutic target for breast cancers

Optimization of Armv9 architecture general large language model inference performance based on Llama.cpp

This article optimizes the inference performance of the Qwen-1.8B model by performing Int8 quantization, vectorizing some operators in llama.cpp, and modifying the compilation script to improve the compiler optimization level. On the Yitian 710 experimental platform, the prefill performance is increased by 1.6 times, the decoding performance is increased by 24 times, the memory usage is reduced to 1/5 of the original, and the accuracy loss is almost negligible

High-Temperature sensor based on peanut flat-end reflection structure

A high-temperature sensor based on a peanut flat-end reflection structure is demonstrated. The sensor can be simply fabricated by splicing the spherical end-faces of two segments of single-mode fibers and then cleaving one other end as a flat reflect surface. The proposed structure works as a reflected interferometer. When the ambient temperature changes, the resonant dip wavelength of the interferometer will shift due to the linear expansion or contraction and the thermo-optic effect. As a result, the temperature measurement can be achieved by monitoring the resonant dip wavelength of the interferometer. Experimental results show that the proposed sensor probe based on the peanut flat-end reflection structure works well and it can measure the temperature range from 100 °C to 900 °C with the sensitivity of 0.098 nm/ °C with R²  =  0.988. When temperature ranges from 400 °C to 900 °C, the sensitivity of 0.11 nm/ °C can be achieved with R² = 0.9995. Due to its compact and simple configuration, the proposed sensor is a good high temperature sensor probe.This work is supported by the Natural Science Foundation of Zhejiang Province China under Grant No.LY17F050010

Streptococcus Mutans Membrane Vesicles Enhance Candida albicans Pathogenicity and Carbohydrate Metabolism

Streptococcus mutans and Candida albicans, as the most common bacterium and fungus in the oral cavity respectively, are considered microbiological risk markers of early childhood caries. S. mutans membrane vesicles (MVs) contain virulence proteins, which play roles in biofilm formation and disease progression. Our previous research found that S. mutans MVs harboring glucosyltransferases augment C. albicans biofilm formation by increasing exopolysaccharide production, but the specific impact of S. mutans MVs on C. albicans virulence and pathogenicity is still unknown. In the present study, we developed C. albicans biofilms on the surface of cover glass, hydroxyapatite discs and bovine dentin specimens. The results showed that C. albicans can better adhere to the tooth surface with the effect of S. mutans MVs. Meanwhile, we employed C. albicans biofilm-bovine dentin model to evaluate the influence of S. mutans MVs on C. albicans biofilm cariogenicity. In the S. mutans MV-treated group, the bovine dentin surface hardness loss was significantly increased and the surface morphology showed more dentin tubule exposure and broken dentin tubules. Subsequently, integrative proteomic and metabolomic approaches were used to identify the differentially expressed proteins and metabolites of C. albicans when cocultured with S. mutans MVs. The combination of proteomics and metabolomics analysis indicated that significantly regulated proteins and metabolites were involved in amino acid and carbohydrate metabolism. In summary, the results of the present study proved that S. mutans MVs increase bovine dentin demineralization provoked by C. albicans biofilms and enhance the protein and metabolite expression of C. albicans related to carbohydrate metabolism

Unveiling the role of hexon-associated host proteins in fowl adenovirus serotype 4 replication

Fowl adenovirus serotype 4 (FAdV-4), a member of the family Adenoviridae and the genus Aviadenovirus, is responsible for a significant number of emerging diseases that cause substantial economic losses in the poultry industry worldwide. The hexon protein plays a crucial role in inducing autophagy and apoptosis and promoting virus replication. Identifying host factors that interact with the hexon protein is essential for elucidating the pathogenesis of FAdV-4. In this study, tandem affinity purification followed by mass spectrometry (TAP/MS) was used to screen the interacting proteins of hexon in leghorn male hepatoma (LMH) cells for the first time. A total of 82 hexon-associated proteins were identified in LMH cells expressing hexon compared with cells expressing the empty vector (NC). Gene Ontology and Ingenuity Pathway Analysis provided functional annotations of the hexon-interacting proteins and revealed that these proteins were associated with multiple biological functions, including virus infection, the cell cycle, endocytosis and the phagosome. Western blot and coimmunoprecipitation validation tests revealed that randomly selected significant proteins (CCT5, CCT7, and HSP70) interact with hexon, and these results are consistent with those of TAP/MS. Among them, the overexpression of CCT5 inhibited virus replication, whereas blocking CCT5 increased virus replication. In conclusion, this study demonstrated the successful screening of host proteins interacting with the hexon protein. The findings of this study will lead to a better understanding of the molecular mechanisms of hexon, thus benefiting the development of effective antiviral strategies

Advanced synaptic transistor device towards AI application in hardware perspective

For the past decades, the synaptic devices for the inmemory computing have been widely investigated due to the high-efficiency computing potential and the ability to mimic biological neurobehavior. However, the conventional twoterminal synaptic memristors show drawbacks of resistance reduction caused by large-scale paralleling and asynchronous storage-reading process, which limit its development. Recently, researchers have paid attention to the transistor-like artificial synapse. Due to the existence of insulator layer and the separation of input and read terminals, the three-terminal synaptic transistors are believed to have greater potential towards artificial intelligence (AI) application fields. In this work, a summary of recent progresses and the future challenges of synaptic transistors are discussed