Glucose oxidase and MnO2 functionalized liposome for catalytic radiosensitization enhanced synergistic breast cancer therapy.

In recent years, the integration of radiotherapy and nanocatalytic medicine has gained widespread attention in the treatment of breast cancer. Herein, the glucose oxidase (GOx) and MnO2 nanoparticles co-modified multifunctional liposome of GOx-MnO2@Lip was constructed for enhanced radiotherapy. Introduction of GOx would not only elevate the glucose consumption to starve the cancer cells, but also increased the endogenous H2O2 level. Meanwhile, high intracellular GSH concentration facilitated the release of Mn2+ to amplify the cytotoxic ·OH through cascade catalytic reactions within the tumor microenvironment, resulting in a favorable tumor suppression rate of 74.45 %. Furthermore, the blood biochemical and blood routine demonstrated that GOx-MnO2@Lip had no obvious toxic side effects. Therefore, this work provided a potential vehicle for synergistic cancer starving therapy, chemodynamic therapy and radiotherapy for improving therapeutic efficacy of breast cancer.

Unraveling the cross-talk between N6-methyladenosine modification and non-coding RNAs in breast cancer: Mechanisms and clinical implications.

In recent years, breast cancer (BC) has surpassed lung cancer as the most common malignant tumor worldwide and remains the leading cause of cancer death in women. The etiology of BC usually involves dysregulation of epigenetic mechanisms and aberrant expression of certain non-coding RNAs (ncRNAs). N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, widely exists in ncRNAs to affect its biosynthesis and function, and is an important regulator of tumor-related signaling pathways. Interestingly, ncRNAs can also regulate or target m6A modification, playing a key role in cancer progression. However, the m6A-ncRNAs regulatory network in BC has not been fully elucidated, especially the regulation of m6A modification by ncRNAs. Therefore, in this review, we comprehensively summarize the interaction mechanisms and biological significance of m6A modifications and ncRNAs in BC. Meanwhile, we also focused on the clinical application value of m6A modification in BC diagnosis and prognosis, intending to explore new biomarkers and potential therapeutic targets.

Single-cell transcriptomics provide insight into metastasis-related subsets of breast cancer.

Breast cancer metastasis is a complex, multi-step process, with high cellular heterogeneity between primary and metastatic breast cancer, and more complex interactions between metastatic cancer cells and other cells in the tumor microenvironment. High-resolution single-cell transcriptome sequencing technology can visualize the heterogeneity of malignant and non-malignant cells in the tumor microenvironment in real time, especially combined with spatial transcriptome analysis, which can directly compare changes between different stages of metastatic samples. Therefore, this study takes single-cell analysis as the first perspective to deeply explore special or rare cell subpopulations related to breast cancer metastasis, systematically summarizes their functions, molecular features, and corresponding treatment strategies, which will contribute to accurately identify, understand, and target tumor metastasis-related driving events, provide a research basis for the mechanistic study of breast cancer metastasis, and provide new clues for its personalized precision treatment.

Machine learning: a powerful tool for identifying key microbial agents associated with specific cancer types.

Machine learning (ML) includes a broad class of computer programs that improve with experience and shows unique strengths in performing tasks such as clustering, classification and regression. Over the past decade, microbial communities have been implicated in influencing the onset, progression, metastasis, and therapeutic response of multiple cancers. Host-microbe interaction may be a physiological pathway contributing to cancer development. With the accumulation of a large number of high-throughput data, ML has been successfully applied to the study of human cancer microbiomics in an attempt to reveal the complex mechanism behind cancer. In this review, we begin with a brief overview of the data sources included in cancer microbiomics studies. Then, the characteristics of the ML algorithm are briefly introduced. Secondly, the application progress of ML in cancer microbiomics is also reviewed. Finally, we highlight the challenges and future prospects facing ML in cancer microbiomics. On this basis, we conclude that the development of cancer microbiomics can not be achieved without ML, and that ML can be used to develop tumor-targeting microbial therapies, ultimately contributing to personalized and precision medicine.

A study on the pesticides-loading capacity of dendritic fibrous nano silica synthesized from 1-pentanol-water microemulsion with a low oil-water ratio.

Dendritic fibrous nano silica (DFNS) represents an optimal carrier material for pesticide constituents, due to its radial accessibility channels and high specific surface area. A low-energy methodology for synthesizing DFNS at a low volume ratio of oil to water is provided by employing 1-pentanol as the oil solvent in the microemulsion synthesis system, renowned for its remarkable stability and exceptional solubility. The DFNS@KM nano-pesticide was fabricated using a diffusion supported loading (DiSupLo) method and kresoxim-methyl (KM) as the template drug. Findings from Fourier-transform infrared spectroscopy, XRD, thermogravimetric, differential thermal analysis, and Brunauer-Emmet-Teller analyzes revealed the physical adsorption of KM onto the synthesized DFNS without any chemical bonding, with KM mainly existing in an amorphous state within the channels. High-performance liquid chromatography measurements demonstrated that only the loading amount of DFNS@KM was primarily dependent on the KM to DFNS ratio, with minimal effects observed from loading temperature and time. The loading amount and encapsulation efficiency of DFNS@KM were found to be 63.09% and 84.12%, respectively. Furthermore, DFNS effectively prolonged the release of KM, with a cumulative release rate of 85.43% over 180 h. The successful loading of pesticide components into DFNS synthesized with a low oil-to-water ratio provides theoretical support for the industrialization of nano-pesticides, with significant implications for enhancing pesticide utilization, reducing pesticide dosage, augmenting agricultural efficiency, and promoting sustainable agricultural development.

Iron oxide nanoparticles served as the primary carrier to increase drug loading in macrophages.

The specific chemotaxis of macrophages to inflammatory site makes them good candidate for inflammation drug delivery. However, the loading capacity of free drug is low. The goal of the manuscript is to enhance the loading capacity by encapsulating drug onto iron oxide nanoparticles (IONPs) and investigate the size effect on the cellular uptake. IONPs with different sizes (10 nm, 70 nm, and 200 nm) were synthesized. The loading capacities of model drug protoporphyrin IX (PPIX) on different sized IONPs were studied, showing similar loading capacity. However, the cellular internalization of PPIX loaded IONPs (Fe3O4-PPIX) was quite different. 70 nm IONPs indicated maximum uptake by the macrophages. The results also demonstrate that the IONPs could significantly improve the loading capacity when compared with free drug. All the three sized nanoparticles demonstrated minimal effects on cellular viability and would not induce the polarization of macrophages. This study not only provides an efficient method to increase the drug loading capacity in macrophages, but also indicates the optimal size of nanoparticles for cellular uptake.

Tunable synthesis of dendritic fibrous nano silica using 1-pentanol-water microemulsion at low oil to water ratio.

Dendritic fibrous nanosilica (DFNS) is a suitable nano-carrier for loading pesticides with radially oriented pores and a large surface area. The microemulsion method is standard method to prepare DFNS, and 1-pentanol is taken to replace cyclohexane as an oil solvent due to its high stability and nontoxic property. The results showed that the volume ratio of 1-pentanol (oil) to water (O/W) and the molar ratio of hexadecyltrimethylammonium bromide (CTAB) to tetraethylorthosilicate (TEOS) had effected on morphology and adsorption properties of DFNS in the water-CTAB-1-pentanol-ethanol-trimethylbenzene (TMB) microemulsion system. DFNS with bicontinuous concentric lamellar morphologies can be synthesized in this microemulsion at the meager O/W volume ratio (0.025-0.045). It features a tight mesoporous structure with a thin dendritic fibrous in 0.03 to 0.04 O/W volume ratio. The particle sizes, surface areas, and porosity of DFNS were positively correlated with the addition of the silica precursor TEOS. The size of DFNS increased from 123 to about 220 nm with the CTAB/TEOS molar ratio decreasing from 0.119 to 0.050. When the molar ratio of CTAB to TEOS  = 0.119, DFNS has a smaller particle size (123 nm) with a larger surface area and abundant honeycomb mesopores; the low O/W volume ratio strategy provides theoretical support for the industrialization development of DFNS and nano-pesticides, which plays a profound role in promoting the sustainable development of pesticide reduction, efficiency and green agriculture.

Ultrasound responsive self-assembled micelles loaded with hypocrellin for cancer sonodynamic therapy.

Nanoparticles have been demonstrated to be effective in targeted drug delivery to tumor due to the enhanced permeability and retention (EPR) effect. However, the inhomogeneous distribution of the nanoparticles in the tumor and the slow release of the drug make the therapeutic effect unsatisfied. Here, we present reactive oxygen species (ROS)-responsive micelles comprising poly (ethylene glycol)-poly(propylene sulfide) (PEG-PPS) for targeted delivery and in situ release of drug. Upon the irradiation of ultrasound, the loaded sonosensitizer hypocrellin (HC) will generate ROS to trigger the disassembly of the micelles and meanwhile realize sonodynamic therapy (SDT) effect of cancer. The in vivo experiment indicates that the HC loaded PEG-PPS are biocompatible and much more efficacious than an equivalent amount of free HC in inhibiting the growth of cancer.

Genome-wide association analysis reveals the genetic locus for high reproduction trait in Chinese Arbas Cashmere goat.

BACKGROUND: Litter size is the most important reproductive trait which plays a crucial role in goat production. Therefore, improvement of litter size trait has been of increasing interest in goat industry as small improvement in litter size may lead to large profit. The recent Cashmere goat breeding program produced a high-reproductive genetic line of Arbas Cashmere goat. But the genetic mechanism of high reproduction rate remains largely unknown in this Chinese native goat breed. To address this question, we performed a genome-wide association studies (GWAS) using two groups of goats varying in fecundity. OBJECTIVES: Our study was aimed to investigate the significant SNPs and genes associated with high reproduction trait in Inner Mongolia Arbas Cashmere Goat. METHODS: We used logistic model association to perform GWAS using 47 goats from high fecundity group (~ 190%) and 314 goats from low fecundity group (~ 130%) of the Arbas Cashmere goat breed. RESULTS: We identified 66 genomic regions associated with genome wide significant level wherein six loci were found to be associated with reproduction traits. Further analysis showed that five key candidate genes including KISS1, KHDRBS2, WNT10B, SETDB2 and PPP3CA genes are involved in goat fecundity trait. Gene ontology enrichment analysis revealed that several biological pathways could be involved in the variation of fecundity in female goats. CONCLUSIONS: The identified significant SNPs or genes provide useful information about the underlying genetic control of fecundity trait which will be helpful to use them in goat breeding programs for improving the reproductive efficiency of goats.

Magnetic thermosensitive micelles with upper critical solution temperature for NIR triggered drug release.

Smart micelles which undergo dramatic property changes in response to temperature have aroused extensive interest in specific cancer therapy. To date, studies on thermosensitive polymers have mainly focused on lower critical solution temperature (LCST) polymers. Materials with upper critical solution temperature (UCST) which can swell and disassemble at elevated temperatures have much less been documented, although they have been reported to be ideal carriers for quick and complete drug release upon applying a stimulus. Here, magnetic micelles with UCST are developed for doxorubicin (DOX) delivery. Hydrophobic Fe3O4 magnetic nanoparticles with a particle size of 8 nm are fabricated and enveloped in an amphiphilic polymer, poly(AAm-co-AN)-g-PEG (PAAP), to form UCST micelles (Fe3O4@PAAP). The resulting micelles exhibit excellent photothermal effects and burst drug release in response to near infrared (NIR) laser irradiation. The in vitro and in vivo antitumor experiments indicate that DOX-Fe3O4@PAAP micelles can significantly enhance the therapeutic effect upon NIR light irradiation. A novel thermosensitive platform is thus offered for in situ drug release and combined photothermal-chemotherapy, holding a favorable prospect for cancer therapy.