Preparation and cytotoxicity evaluation of folic acid-modified YF8-OA self-assembled lipid prodrug nanoparticles.

This study aimed to improve the use of YF8, a matrine derivative obtained through chemical transformation of matrine extracted from Sophora alopecuroides. YF8 has demonstrated improved cytotoxicity compared to matrine, but its hydrophobic nature hinders its application. To overcome this, the lipid prodrug YF8-OA was synthesized by linking oleic acid (OA) to YF8 through an ester bond. Although YF8-OA could self-assemble into unique nanostructures in water, it was not sufficiently stable. To enhance the stability of YF8-OA lipid prodrug nanoparticles (LPs), we employed the strategy of PEGylation using DSPE-mPEG2000 or DSPE-mPEG2000 conjugated with folic acid (FA). This resulted in the formation of uniform spherical nanoparticles with greatly improved stability and a maximum drug load capacity upto 58.63%. Cytotoxicity was evaluated in A549, HeLa, and HepG2 cell lines. The results showed that in HeLa cells, the IC50 value of YF8-OA/LPs with FA-modified PEGylation was significantly lower than that of YF8-OA/LPs modified by PEGylation alone. However, no significant enhancement was observed in A549 and HepG2 cells. In conclusion, the lipid prodrug YF8-OA can form nanoparticles in aqueous solution to address its poor water solubility. Modification with FA resulted in further enhanced cytotoxicity, providing a potential avenue for exerting the antitumor activity of matrine analogs.

Sex Detection of Chicks Based on Audio Technology and Deep Learning Methods.

The sex detection of chicks is an important work in poultry breeding. Separating chicks of different sexes early can effectively improve production efficiency and commercial benefits. In this paper, based on the difference in calls among one-day-old chicks of different sexes, a sex detection method based on chick calls is designed. Deep learning methods were used to classify the calls of chicks and detect their sex. This experiment studies three different varieties of chicks. The short-time zero-crossing rate was used to automatically detect the endpoints of chick calls in audio. Three kinds of audio features were compared: Spectrogram, Cepstrogram and MFCC+Logfbank. The features were used as the input in neural networks, and there were five kinds of neural networks: CNN, GRU, CRNN, TwoStream and ResNet-50. After the cross-comparison experiment of different varieties of chicks, audio features and neural networks, the ResNet-50 neural network trained with the MFCC+Logfbank audio features of three yellow chick calls had the highest test accuracy of 83% when testing Three-yellow chicks' calls. The GRU neural network trained with the Spectrogram audio features of native chick calls had the highest test accuracy of 76.8% when testing Native chicks' calls. The ResNet-50 neural network trained with Spectrogram audio features of flaxen-yellow chick calls had the highest test accuracy of 66.56%when testing flaxen-yellow chick calls. Multiple calls of each chick were detected, and the majority voting method was used to detect the sex of the chicks. The ResNet-50 neural network trained with the Spectrogram of three yellow chick calls had the highest sex detection accuracy of 95% when detecting the three yellow chicks' sex. The GRU neural network trained with the Spectrogram and cepstrogram of native chick calls and the CRNN network trained with the Spectrogram of native chick calls had the highest sex detection accuracy of 90% when detecting the native chicks' sex. The Twostream neural network trained with MFCC+Logfbank of flaxen-yellow chick calls and the ResNet-50 network trained with the Spectrogram of flaxen-yellow chick calls had the highest sex detection accuracy of 80% when detecting the flaxen-yellow chicks' sex. The results of the cross-comparison experiment show that there is a large diversity between the sex differences in chick calls of different breeds. The method is more applicable to chick sex detection in three yellow chicks and less so in native chicks and flaxen-yellow chicks. Additionally, when detecting the sex of chicks of a similar breed to the training chicks, the method obtained better results, while detecting the sex of chicks of other breeds, the detection accuracy was significantly reduced. This paper provides further perspectives on the sex detection method of chicks based on their calls and help and guidance for future research.

Protein Tyrosine Phosphatase Receptor-type Q: Structure, Activity, and Implications in Human Disease.

Protein tyrosine phosphatase receptor-type Q (PTPRQ), a member of the type III tyrosine phosphatase receptor (R3 PTPR) family, is composed of three domains, including 18 extracellular fibronectin type III (FN3) repeats, a transmembrane helix, and a cytoplasmic phosphotyrosine phosphatase (PTP) domain. PTPRQ was initially identified as a transcript upregulated in glomerular mesangial cells in a rat model of glomerulonephritis. Subsequently, studies found that PTPRQ has phosphotyrosine phosphatase and phosphatidylinositol phosphatase activities and can regulate cell proliferation, apoptosis, differentiation, and survival. Further in vivo studies showed that PTPRQ is necessary for the maturation of cochlear hair bundles and is considered a potential gene for deafness. In the recent two decades, 21 mutations in PTPRQ have been linked to autosomal recessive hearing loss (DFNB84) and autosomal dominant hearing loss (DFNA73). Recent mutations, deletions, and amplifications of PTPRQ have been observed in many types of cancers, which indicate that PTPRQ might play an essential role in the development of many cancers. In this review, we briefly describe PTPRQ structure and enzyme activity and focus on the correlation between PTPRQ and human disease. A profound understanding of PTPRQ could be helpful in the identification of new therapeutic targets to treat associated diseases.

The Chemosensitizing Role of Metformin in Anti-Cancer Therapy.

Chemoresistance, which leads to the failure of chemotherapy and further tumor recurrence, presents the largest hurdle for the success of anti-cancer therapy. In recent years, metformin, a widely used first-line antidiabetic drug, has attracted increasing attention for its anti-cancer effects. A growing body of evidence indicates that metformin can sensitize tumor responses to different chemotherapeutic drugs, such as hormone modulating drugs, anti-metabolite drugs, antibiotics, and DNA-damaging drugs via selective targeting of Cancer Stem Cells (CSCs), improving the hypoxic microenvironment, and by suppressing tumor metastasis and inflammation. In addition, metformin may regulate metabolic programming, induce apoptosis, reverse Epithelial to Mesenchymal Transition (EMT), and Multidrug Resistance (MDR). In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-κB/HIF-1 α, and Mitogen- Activated Protein Kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and Pyruvate Kinase isoenzyme M2 (PKM2). Through a comprehensive understanding of the molecular mechanisms of chemosensitization provided in this review, the rationale for the use of metformin in clinical combination medications can be more systematically and thoroughly explored for wider adoption against numerous cancer types.>.