Triorchidism: genetic and imaging evaluation in an adult male

We report the results of imaging and cytogenetic studies in a case of tri- orchidism in a 54 years old male without any associated anomaly. A scrotal ultrasonography revealed the presence of two testes within the left hemiscrotum with complete septa- tion and echotexture and vascular flow pattern similar to the vascular flow of the normal right testis. There was no focal abnormal echogenicity suggesting malignancy. Scrotal MRI confirmed two soft-tissue structures in the left hemiscrotum with normal signal intensity at T1w and T2w images. Both testes had a tunica albuginea with low-signal intensity. Cytogenetic analysis resulted in normal male karyotype 46XY. Array-CGH analysis detected the presence of two interstitial rearrangements: a ~120 Kb deletion of chro- mosome 1 and a ~140 Kb deletion of chromosome 16. Currently there are little details on the functions of both genes

Use of partial least squares regression to impute SNP genotypes in Italian Cattle breeds

Background The objective of the present study was to test the ability of the partial least squares regression technique to impute genotypes from low density single nucleotide polymorphisms (SNP) panels i.e. 3K or 7K to a high density panel with 50K SNP. No pedigree information was used. Methods Data consisted of 2093 Holstein, 749 Brown Swiss and 479 Simmental bulls genotyped with the Illumina 50K Beadchip. First, a single-breed approach was applied by using only data from Holstein animals. Then, to enlarge the training population, data from the three breeds were combined and a multi-breed analysis was performed. Accuracies of genotypes imputed using the partial least squares regression method were compared with those obtained by using the Beagle software. The impact of genotype imputation on breeding value prediction was evaluated for milk yield, fat content and protein content. Results In the single-breed approach, the accuracy of imputation using partial least squares regression was around 90 and 94% for the 3K and 7K platforms, respectively; corresponding accuracies obtained with Beagle were around 85% and 90%. Moreover, computing time required by the partial least squares regression method was on average around 10 times lower than computing time required by Beagle. Using the partial least squares regression method in the multi-breed resulted in lower imputation accuracies than using single-breed data. The impact of the SNP-genotype imputation on the accuracy of direct genomic breeding values was small. The correlation between estimates of genetic merit obtained by using imputed versus actual genotypes was around 0.96 for the 7K chip. Conclusions Results of the present work suggested that the partial least squares regression imputation method could be useful to impute SNP genotypes when pedigree information is not available

Intracellular delivery of therapeutic proteins. New advancements and future directions

Achieving the full potential of therapeutic proteins to access and target intracellular receptors will have enormous benefits in advancing human health and fighting disease. Existing strategies for intracellular protein delivery, such as chemical modification and nanocarrier-based protein delivery approaches, have shown promise but with limited efficiency and safety concerns. The development of more effective and versatile delivery tools is crucial for the safe and effective use of protein drugs. Nanosystems that can trigger endocytosis and endosomal disruption, or directly deliver proteins into the cytosol, are essential for successful therapeutic effects. This article aims to provide a brief overview of the current methods for intracellular protein delivery to mammalian cells, highlighting current challenges, new developments, and future research opportunities

Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering

Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolyticallydegradable polyamidoamine-based diamine crosslinker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxyamine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant post-formation gel syneresis. The results suggest that this novel class of injectable hydrogels may be attractive substrates for tissue engineering applications due to the synthetic versatility of the component materials and beneficial hydrogel gelation kinetics and stability

Statistical tools for genome-wide studies

The aim of genomic selection (GS) in livestock is to detect linkage disequilibrium between SNP and quantitative trait loci (QTL) across the whole genome, to improve the accuracy of the estimated breeding value (GEBV) in genetic improvement programs. Two main issues affect GS: the imbalance between the number of SNP and the number of involved animals and the high genotyping costs. In this thesis the principal component analysis (PCA) is proposed as a method to reduce the dimensionality of the SNP data. In particular, the study evaluated the effect of the rank of the variance-covariance matrix on the accuracy of GEBV when PCA was applied. In addition, a new approach is proposed to reduce the dimensionality of the data. First, this new method was used in a genomic wide association study to detect associations among markers and traits under study. Then the obtained results were used to reduce the number of SNPs useful to estimate the GEBV. Results show that, the accuracy of GEBV, when only the SNPs selected with the new method were used, was on average nearly equal to or sometimes greater than the accuracies obtained when all SNPs were used. This thesis also proposes the partial least squared regression (PLSR) to impute markers not present in economic chips and avoid a reduction in the accuracy of GEBV estimation. The study demonstrated that the PLSR imputation method can efficiently impute missing genotypes from low-density panels to HDP.</br

Advancing nucleic acid delivery through cationic polymer design: non-cationic building blocks from the toolbox

Polymers used for the delivery of nucleic acids (NAs) typically possess ionizable, cationic moieties enabling their electrostatic interactions with negatively charged NAs and form stable polyplexes. However, non-cationic building blocks have been harnessed to design cationic polymers with enhanced delivery of DNA/RNA to tissues, cells, and subcellular compartments while remaining stable in biological fluids. By customizing the chemistry of these functional groups, we can improve cell targeting behavior, uptake, endosomal escape, non-toxicity, and transfection efficiency. Additionally, the physicochemical properties, such as the loading capacity, complexation ability, size and morphology, biodegradability, pH sensitivity, and amphiphilicity, can be adjusted based on the specific application. This review summarizes the role of non-cationic moieties in various biomedical contexts, from therapeutic interventions to gene editing. By unpacking and critically summarizing the existing literature, this review provides valuable insights into the rational integration of these building blocks for designing more effective nanovectors to deliver NAs.The rational integration of non-cationic building blocks into cationic polymers can be devised to enhance the performance of the resulting gene delivery vectors, improving cell targeting behavior, uptake, endosomal escape, toxicity, and transfection efficiency

Analytical Challenges in Diabetes Management: Towards Glycated Albumin Point-of-Care Detection

Diabetes mellitus is a worldwide-spread chronic metabolic disease that occurs when the pancreas fails to produce enough insulin levels or when the body fails to effectively use the secreted pancreatic insulin, eventually resulting in hyperglycemia. Systematic glycemic control is the only procedure at our disposal to prevent diabetes long-term complications such as cardiovascular disorders, kidney diseases, nephropathy, neuropathy, and retinopathy. Glycated albumin (GA) has recently gained more and more attention as a control biomarker thanks to its shorter lifespan and wider reliability compared to glycated hemoglobin (HbA1c), currently the &ldquo;gold standard&rdquo; for diabetes screening and monitoring in clinics. Various techniques such as ion exchange, liquid or affinity-based chromatography and immunoassay can be employed to accurately measure GA levels in serum samples; nevertheless, due to the cost of the lab equipment and complexity of the procedures, these methods are not commonly available at clinical sites and are not suitable to home monitoring. The present review describes the most up-to-date advances in the field of glycemic control biomarkers, exploring in particular the GA with a special focus on the recent experimental analysis techniques, using enzymatic and affinity methods. Finally, analysis steps and fundamental reading technologies are integrated into a processing pipeline, paving the way for future point-of-care testing (POCT). In this view, we highlight how this setup might be employed outside a laboratory environment to reduce the time from measurement to clinical decision, and to provide diabetic patients with a brand-new set of tools for glycemic self-monitoring

Oligo(ethylene glycol) Methacrylate Copolymer-Modified Liposomes for Temperature-Responsive Drug Delivery System

A thermoresponsive copolymer based on oligo(ethylene glycol) methacrylate, Chol-P(MEO2MA-co-OEGMA), was synthesized using Atom Transfer Radical Polymerization (ATRP) and incorporated into thermosensitive liposomes (TSLs) for controlled drug release. The copolymer exhibited a lower critical solution temperature (LCST) of 37 °C, making it suitable for biomedical applications requiring precise thermal triggers. The copolymer was incorporated into various TSL formulations alongside phospholipids such as DPPC, Lyso-PC, HSPC, and DSPC. Physicochemical characterization of the liposomes, including average size, polydispersity index, loading efficiency (LE), and encapsulation efficiency (EE), was performed using dynamic light scattering and fluorescence spectroscopy. The results showed that the incorporation of the copolymer slightly affected particle size and decreased LE and EE in most formulations. Lyso-PC-containing formulations exhibited lower LE and EE, likely due to instability during purification. Albumin encapsulation demonstrated lower LE compared to the smaller carboxyfluorescein drug model, highlighting the influence of molecular weight on loading. Although copolymer-modified liposomes showed reduced loading capacity, they enhanced thermoresponsiveness in HSPC-based formulations. These findings suggest that incorporating thermoresponsive polymers into TSLs can optimize drug delivery systems for targeted, thermally triggered release

Complex polymeric architectures self-assembling in unimolecular micelles: Preparation, characterization and drug nanoencapsulation

Unimolecular polymeric micelles are a class of single-molecule amphiphilic core-shell polymeric architectures, where the hydrophobic core is well stabilized by the hydrophilic shell, avoiding intermolecular core-core interactions. Multi-arm copolymers with a dendritic core, as well as hyperbranched and comb-like polymers, can form unimolecular micelles easily. In this review, examples of polymers able to form detectable unimolecular micelles will be presented, summarizing the analytical techniques used to characterize the unimolecular micelles and discriminate them from other supramolecular aggregates, such as multi-micelle aggregates. Unimolecular micelles are suitable for the nanoencapsulation of guest molecules. Compared to traditional supramolecular micelles, unimolecular micelles do not disassemble under dilution and are stable to environmental modifications. Recent examples of their application as drug delivery systems, endowed with increased stability and transport properties, will be discussed