Immune defense in Drosophila melanogaster depends on diet, sex, and mating status.

Immune defense is a complex trait that affects and is affected by many other host factors, including sex, mating, and dietary environment. We used the agriculturally relevant fungal emtomopathogen, Beauveria bassiana, and the model host organism Drosophila melanogaster to examine how the impacts of sex, mating, and dietary environment on immunity are interrelated. We showed that the direction of sexual dimorphism in immune defense depends on mating status and mating frequency. We also showed that post-infection dimorphism in immune defense changes over time and is affected by dietary condition both before and after infection. Supplementing the diet with protein-rich yeast improved post-infection survival but more so when supplementation was done after infection instead of before. The multi-directional impacts among immune defense, sex, mating, and diet are clearly complex, and while our study shines light on some of these relationships, further study is warranted. Such studies have potential downstream applications in agriculture and medicine.

An Approach toward Artificial Intelligence Alzheimer's Disease Diagnosis Using Brain Signals.

BACKGROUND: Electroencephalography (EEG) signal analysis is a rapid, low-cost, and practical method for diagnosing the early stages of dementia, including mild cognitive impairment (MCI) and Alzheimer's disease (AD). The extraction of appropriate biomarkers to assess a subject's cognitive impairment has attracted a lot of attention in recent years. The aberrant progression of AD leads to cortical detachment. Due to the interaction of several brain areas, these disconnections may show up as abnormalities in functional connectivity and complicated behaviors. METHODS: This work suggests a novel method for differentiating between AD, MCI, and HC in two-class and three-class classifications based on EEG signals. To solve the class imbalance, we employ EEG data augmentation techniques, such as repeating minority classes using variational autoencoders (VAEs), as well as traditional noise-addition methods and hybrid approaches. The power spectrum density (PSD) and temporal data employed in this study's feature extraction from EEG signals were combined, and a support vector machine (SVM) classifier was used to distinguish between three categories of problems. RESULTS: Insufficient data and unbalanced datasets are two common problems in AD datasets. This study has shown that it is possible to generate comparable data using noise addition and VAE, train the model using these data, and, to some extent, overcome the aforementioned issues with an increase in classification accuracy of 2 to 7%. CONCLUSION: In this work, using EEG data, we were able to successfully detect three classes: AD, MCI, and HC. In comparison to the pre-augmentation stage, the accuracy gained in the classification of the three classes increased by 3% when the VAE model added additional data. As a result, it is clear how useful EEG data augmentation methods are for classes with smaller sample numbers.

Targeted delivery and controlled release of doxorubicin to cancer cells by smart ATP-responsive Y-shaped DNA structure-capped mesoporous silica nanoparticles.

In this study, a dual-receptor doxorubicin-targeted delivery system based on mesoporous silica nanoparticles (MSNs) modified with mucine-1 and ATP aptamers (DOX@MSNs-Apts) was developed. An amine-modified mucine-1 (MUC1) aptamer was covalently anchored on the surface of carboxyl-functionalized MSNs. Then, ATP aptamers (ATP1 and ATP2 aptamers) were immobilized on the surface of MSNs through partial hybridization with the MUC1 aptamer by forming a Y-shaped DNA structure on the MSNs surface (DOX@MSNs-Apts) as a gatekeeper. The developed DOX@MSNs-Apts exhibited high DOX loading capacity. In addition, it indicated an ATP-responsive feature, leading to the release of DOX in the environment with high ATP concentration (10 mM), similar to the intracellular environment of tumor cells. This property demonstrated that anticancer drug (DOX) could be entrapped inside the nanocarrier with nearly no leakage in blood and a very low concentration of ATP (1 µM). It was found that after the internalization of DOX@MSNs-MUC1 by cancer cells via the MUC1 receptor-mediated endocytosis, the ATP aptamers left the surface of the nanocarrier, allowing for rapid DOX release. DOX@MSNs-Apts indicated higher cellular uptake in MCF-7 and C26 cancer cells (MUC1+), rather than CHO cells (MUC1-). The in vitro cytotoxicity and the in vivo antitumor efficacy of DOX@MSNs-Apts showed greater cytotoxicity than the nanoparticles decorated with scrambled ATP aptamers (DOX@MSNs-Apts scrambled) in C26 and MCF-7 cell lines (MUC1+). The biodistribution and in vivo anticancer efficacy on the C26 tumor bearing mice indicated that the DOX@MSNs-Apts had a higher tumor accumulation and superior tumor growth inhibitory effect compared to free DOX and their scrambled aptamers, DOX@MSNs-Apts scrambled. Overall, the obtained results indicated that the prepared smart platform could reveal new insights into the treatment of cancer.

Aptamer-based ATP-responsive delivery systems for cancer diagnosis and treatment.

In recent years, many stimuli-triggered drug delivery platforms have been designed to deliver drugs accurately to specific sites and reduce their side effects, improving "on-demand" therapeutic efficacy. Adenosine-5'-triphosphate (ATP)-responsive drug delivery methods are examples of these systems that use ATP molecules as a trigger for delivery of therapeutic agents. Since intra- and extra-cellular ATP concentrations are significantly different from each other (1-10 mM and <0.4 mM, respectively), the use of ATP can be a practical method for regulating drug release. Aptamers possess unique properties including, ligand-specific response, short sequence (~ 20-80 bases) and easy functionalization. Thus, their combination with ATP-responsive systems results in more accurate drug delivery systems and greater control of drug release. A wide range of nanoparticles, such as polymeric nanogels, liposomes, metallic nanoparticles, protein, or DNA nano-assemblies, have been employed in the fabrication of nanocarriers. In this review, we describe several ATP-responsive drug delivery systems based on the various carriers and discuss the challenges and strengths of each method.

CRISPR-cas9 genome editing delivery systems for targeted cancer therapy.

The prokaryotic CRISPR-Cas systems could be applied as revolutionized genome editing tool in live cells of various species to modify, visualize and identify definite sequences of DNA and RNA. CRISPR-Cas could edit the genome by homology-directed repair and non-homologous end joining mechanisms. Furthermore, DNA-targeting modification by CRISPR-Cas methodology provides opportunity for diagnosis, therapy and the genetic disorders investigation. Here, we summarized delivery systems employed for CRISPR-Cas9 for genome editing. Then preclinical studies of the CRISPR-Cas9-based therapeutics will be discussed considering the associated challenges and developments in its translation to clinic for cancer therapy.

Silica-Quantum Dot Nanomaterials as a Versatile Sensing Platform.

Traditional analytical methods are bounded due to required high consumption of reagents, time, expensive equipment and complicated sample preparation. Thus, there is a demand for easy, fast and sensitive procedure to determine various analytes. In this regards, quantum dots (QDs) as fluorescent nanomaterials have attracted considerable attention due to their unique optical properties. Numerous studies have been reported regarding the application of QDs in sensor development for the detection of different analytes. Moreover, mesoporous silica nanoparticles which show ideal properties including biocompatibility, uniform pore size, stability in wide range of pH and an extremely high surface area could offer great opportunity in combination with QDs for the construction of sensing platforms. The fluorescent, chemiluminescent and electrochemical sensors based on silica-QDs materials could be used for the quantitative recognition of an extensive range of analytes like organic compounds, metal cations, toxic industrial compounds, drugs, and biogenic composites. In this review, we have summarized sensors based on combined QD-silica nanomaterials and their applications in the recognition of different analytes which are published over approximately the past five years.

Targeted doxorubicin-loaded mesenchymal stem cells-derived exosomes as a versatile platform for fighting against colorectal cancer.

Exosomes hold great potential for cancer treatment to deliver therapeutics due to its inherent low immunogenicity. Exosomes are biocompatible cell-exocytosed secreted vesicles by most cell types, which can be used to construct novel biomanufacturing platform for drug delivery and cancer therapy. In this study, we implemented nano-sized vesicles which were secreted by mesenchymal stem cell (MSC), to encapsulate doxorubicin (DOX) through electroporation method (DOX@exosome). DOX was loaded into exosomes, with an encapsulation efficiency of up to 35% and separated by ultracentrifugation. Subsequently, carboxylic acid-end MUC1 aptamer was used to covalently decorate the surface amine groups of the exosomes via amide bond formation to provide selective guided drug delivery (DOX@exosome-apt). The data showed that the DOX@exosome-apt provided highly efficient DOX transportation to MUC1-positive cancer cells in vitro as confirmed by MTT and flow cytometry experiments. Moreover, in vivo study on ectopic model of C26 (mouse colon adenocarcinoma) in BALB/c mice indicated that the single dose intravenous injection of DOX@exosome-apt significantly suppress tumor growth in comparison with free DOX. Ex vivo fluorescent imaging also verified the desirable biodistribution of DOX@exosome-apt by exhibiting higher tumor accumulation and faster liver clearance in comparison with DOX@exosome and free DOX. It could be concluded that MUC1 aptamer-decorated exosomes can be implemented therapeutically for the safe and versatile delivery of DOX to colon adenocarcinoma, thus offering valuable platform for clinical applications.

Sensors design based on hybrid gold-silica nanostructures.

Hybrid silica-gold based sensors show attractive performance in sensing technologies. Due to their interesting optical properties and biological compatibility, gold nanoparticles (AuNPs) have been extensively implemented in sensing technology. Hybridization of AuNPs with silica NPs as a material with unique characteristic comprising large surface area, narrow pore distribution, tunable pore size and excellent charge transport provides great opportunity to fabricate promising sensing materials. This review summarizes the current developments on sensing devices based on gold-silica hybrid materials and discussing their interest in designing biosensors for improved analytes detection.

Folate conjugation improved uptake and targeting of porous hydroxyapatite nanoparticles containing epirubicin to cancer cells.

As hydroxyapatite (HAp) with the hexagonal crystal structure is biocompatible and bioactive. In the present study, HAp nanoparticles were synthesized and functionalized with polyethylene glycol and folic acid. The anticancer drug, epirubicin, was loaded to the folic acid-conjugated polyethylene glycol-coated HAp (FA-PEG-HAp) nanoparticles. The prepared nanoparticles were used for in vitro and in vivo experiments. Particle size analyzer showed that the hydrodynamic size of PEG-HAp and FA-PEG-HAp nanoparticles was 150.3 ± 1.5 nm and 217.2 ± 14.9 nm, respectively. The release behavior of epirubicin from nanoparticles showed an increase in the rate of release in acidic pH. The released drug in acidic pH was 2.5 fold more than pH 7.4. The results of in vitro study indicated an increase in cellular uptake of nanoparticles due to folate ligand. In vivo treatment with both PEG-HAp and FA-PEG-HAp nanoparticles had notably higher inhibition efficacy towards tumor growth than free epirubicin. In conclusion, folate conjugation provided higher uptake and better targeting of hydroxyapatite nanoparticles to cancer cells.

DNA origami-based aptasensors.

Traditional analytical techniques face many limitations such as time-consuming process, complicated sample preparation, high consumption of reagents and need for expensive equipment. So, it is important that simple, rapid and sensitive detection methods are introduced. Nucleic acids-based assays, particularly aptamers, have a great impact on modern life sciences for biological analysis and target detection. Aptamer-based biosensors with unique recognition properties including high specificity and affinity, rapid response and simple fabrication have attracted much attention. It is believed that two- and three-dimensional structures, sometimes referred to as DNA origami, using DNA aptamers can show more selective binding affinity and better stability over other nucleic acids forms. In this review, we will focus on recent advances in the development and uses of electrochemical and optical DNA origami-based aptasensors to supply readers with a comprehensive understanding of their improvements. Also, the challenges and awards of these approaches are discussed.

Triple-helix molecular switch-based aptasensors and DNA sensors.

Utilization of traditional analytical techniques is limited because they are generally time-consuming and require high consumption of reagents, complicated sample preparation and expensive equipment. Therefore, it is of great interest to achieve sensitive, rapid and simple detection methods. It is believed that nucleic acids assays, especially aptamers, are very important in modern life sciences for target detection and biological analysis. Aptamers and DNA-based sensors have been widely used for the design of various sensors owing to their unique features. In recent years, triple-helix molecular switch (THMS)-based aptasensors and DNA sensors have been broadly utilized for the detection and analysis of different targets. The THMS relies on the formation of DNA triplex via Watson-Crick and Hoogsteen base pairings under optimal conditions. This review focuses on recent progresses in the development and applications of electrochemical, colorimetric, fluorescence and SERS aptasensors and DNA sensors, which are based on THMS. Also, the advantages and drawbacks of these methods are discussed.

Silica based hybrid materials for drug delivery and bioimaging.

Silica hybrid materials play an important role in improvement of novel progressive functional nanomaterials. Study in silica hybrid functional materials is supported by growing interest in providing intelligent materials that combine best of the inorganic silica structure along with organic or biological realms. Hybrid silica materials do not only provide fantastic opportunities for the design of novel materials for research but their represented unique properties open versatile applications specifically in nanomedicine since it was recognized by US FDA as a safe material for human trials. By combining various materials with different characteristics along with silica NPs as building blocks, silica-based hybrid vehicles were developed. In this regard, silica-based hybrid materials have shown great capabilities as unique carriers for bioimaging and/or drug delivery purposes. In the aforementioned hybrid systems, silica was preferred as a main building block of the hybrid structure, which is easily functionalized with different materials, bio-molecules and targeting ligands while providing biocompatibility for the system. This review will cover a full description of different hybrids of silica nanoparticles including silica-polymer, silica-protein, silica-peptide, silica-nucleic acid, silica-gold, silica-quantum dot, and silica-magnetic nanoparticles and their applications as therapeutic or imaging systems.