Search Results (408)

The formation and evolution of haze layers in planetary atmospheres play a critical role in shaping their chemical composition, radiative balance, and optical properties. In the outer solar system, the atmospheres of Titan and the giant planets exhibit a wide range of compositional and seasonal variability, creating environments favorable for the production of complex organic molecules under low-temperature conditions. Among them, Uranus—the smallest of the ice giants—has, since Voyager 2, emerged as a compelling target for future exploration due to unanswered questions regarding the composition and structure of its atmosphere, as well as its ring system and diverse icy moon population (which includes four possible ocean worlds). Titan, as the only moon to harbor a dense atmosphere, presents some of the most complex and unique organics found in the solar system. Central to the production of these organics are chemical processes driven by low-energy photons and electrons (<50 eV), which initiate reaction pathways leading to the formation of organic species and gas phase precursors to high-molecular-weight compounds, including aerosols. These aerosols, in turn, remain susceptible to further processing by low-energy UV radiation as they are transported from the upper atmosphere to the lower stratosphere and troposphere where condensation occurs. In this review, I aim to summarize the current understanding of low-energy (<50 eV) photon- and electron-induced chemistry, drawing on decades of insights from studies of Titan, with the objective of evaluating the relevance and extent of these processes on Uranus in anticipation of future observational and in situ exploration. Full article

Surfactants can be utilized to improve oil recovery by changing the performance of reservoirs in rock pores. Kerogen is the primary organic matter in shale; however, high temperatures will affect the overall performance of this surfactant, resulting in a decrease in its activity or even failure. The effect of surfactants on kerogen pyrolysis has rarely been researched. Therefore, this study synthesized a polymeric surfactant (PS) with high temperature resistance and investigated its effect on kerogen pyrolysis under the friction of drill bits or pipes via molecular dynamics. The infrared spectra and thermogravimetric and molecular weight curves of the PS were researched, along with its surface tension, contact angle, and oil saturation measurements. The results showed that PS had a low molecular weight, with an MW value of 124,634, and good thermal stability, with a main degradation temperature of more than 300 °C. It could drop the surface tension of water to less than 25 mN·m⁻¹ at 25–150 °C, and the use of slats enhanced its surface activity. The PS also changed the contact angles from 127.96° to 57.59° on the surface of shale cores and reversed to a water-wet state. Additionally, PS reduced the saturated oil content of the shale core by half and promoted oil desorption, indicating a good cleaning effect on the shale oil reservoir. The kerogen molecules gradually broke down into smaller molecules and produced the final products, including methane and shale oil. The main reaction area in the system was the interface between kerogen and the surfactant, and the small molecules produced on the interface diffused to both ends. The kinetics of the reaction were controlled by two processes, namely, the step-by-step cleavage process of macromolecules and the side chain cleavage to produce smaller molecules in advance. PS could not only desorb oil in the core but also promote the pyrolysis of kerogen, suggesting that it has good potential for application in shale oil exploration and development. Full article

A significant issue in healthcare is the growing prevalence of antibiotic-resistant strains. Therefore, it is necessary to develop strategies for discovering new antibacterial compounds, either by identifying natural products or by designing semisynthetic or synthetic compounds with this property. In this context, a great deal of research has recently been carried out on antimicrobial peptides (AMPs), which are natural, amphipathic, low-molecular-weight molecules that act by altering the cell surface and/or interfering with cellular activities essential for life. Progress is also being made in developing strategies to enhance the activity of these compounds through their association with other molecules. In addition to identifying AMPs, it is essential to ensure that they maintain their integrity after passing through the digestive tract and exhibit adequate activity against their targets. Significant advances are being made in relation to analyzing various types of conjugates and carrier systems, such as nanoparticles, vesicles, hydrogels, and carbon nanotubes, among others. In this work, we review the current knowledge of different types of AMPs, their mechanisms of action, and strategies to improve performance. Full article

Background/Objectives: This research presents a novel analytical method for breast tumor characterization and tissue classification by leveraging intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) combined with hyperspectral imaging techniques and deep learning. Traditionally, dynamic contrast-enhanced MRI (DCE-MRI) is employed for breast tumor diagnosis, but it involves gadolinium-based contrast agents, which carry potential health risks. IVIM imaging extends conventional diffusion-weighted imaging (DWI) by explicitly separating the signal decay into components representing true molecular diffusion ($D$) and microcirculation of capillary blood (pseudo-diffusion or $D*$). This separation allows for a more comprehensive, non-invasive assessment of tissue characteristics without the need for contrast agents, thereby offering a safer alternative for breast cancer diagnosis. The primary purpose of this study was to evaluate different methods for breast tumor characterization using IVIM-DWI data treated as hyperspectral image stacks. Dice similarity coefficients and Jaccard indices were specifically used to evaluate the spatial segmentation accuracy of tumor boundaries, confirmed by experienced physicians on dynamic contrast-enhanced MRI (DCE-MRI), emphasizing detailed tumor characterization rather than binary diagnosis of cancer. Methods: The data source for this study consisted of breast MRI scans obtained from 22 patients diagnosed with mass-type breast cancer, resulting in 22 distinct mass tumor cases analyzed. MR images were acquired using a 3T MRI system (Discovery MR750 3.0 Tesla, GE Healthcare, Chicago, IL, USA) with axial IVIM sequences and a bipolar pulsed gradient spin echo sequence. Multiple b-values ranging from 0 to 2500 s/mm² were utilized, specifically thirteen original b-values (0, 15, 30, 45, 60, 100, 200, 400, 600, 1000, 1500, 2000, and 2500 s/mm²), with the last four b-value images replicated once for a total of 17 bands used in the analysis. The methodology involved several steps: acquisition of multi-b-value IVIM-DWI images, image pre-processing, including correction for motion and intensity inhomogeneity, treating the multi-b-value data as hyperspectral image stacks, applying hyperspectral techniques like band expansion, and evaluating three tumor detection methods: kernel-based constrained energy minimization (KCEM), iterative KCEM (I-KCEM), and deep neural networks (DNNs). The comparisons were assessed by evaluating the similarity of the detection results from each method to ground truth tumor areas, which were manually drawn on DCE-MRI images and confirmed by experienced physicians. Similarity was quantitatively measured using the Dice similarity coefficient and the Jaccard index. Additionally, the performance of the detectors was evaluated using 3D-ROC analysis and its derived criteria (AUC_OD, AUC_TD, AUC_BS, AUC_TD−BS, AUC_ODP, AUC_SNPR). Results: The findings objectively demonstrated that the DNN method achieved superior performance in breast tumor detection compared to KCEM and I-KCEM. Specifically, the DNN yielded a Dice similarity coefficient of 86.56% and a Jaccard index of 76.30%, whereas KCEM achieved 78.49% (Dice) and 64.60% (Jaccard), and I-KCEM achieved 78.55% (Dice) and 61.37% (Jaccard). Evaluation using 3D-ROC analysis also indicated that the DNN was the best detector based on metrics like target detection rate and overall effectiveness. The DNN model further exhibited the capability to identify tumor heterogeneity, differentiating high- and low-cellularity regions. Quantitative parameters, including apparent diffusion coefficient ($ADC$), pure diffusion coefficient ($D$), pseudo-diffusion coefficient ($D*$), and perfusion fraction ($PF$), were calculated and analyzed, providing insights into the diffusion characteristics of different breast tissues. Analysis of signal intensity decay curves generated from these parameters further illustrated distinct diffusion patterns and confirmed that high cellularity tumor regions showed greater water molecule confinement compared to low cellularity regions. Conclusions: This study highlights the potential of combining IVIM-DWI, hyperspectral imaging techniques, and deep learning as a robust, safe, and effective non-invasive diagnostic tool for breast cancer, offering a valuable alternative to contrast-enhanced methods by providing detailed information about tissue microstructure and heterogeneity without the need for contrast agents. Full article

Background: RNA interference (RNAi) is a powerful tool that can target many proteins without the expensive and time-consuming drug development studies. However, due to the challenges in delivering RNA molecules, the potential impact of RNAi approaches is yet to be fully realized in clinical settings. Lipid nanoparticles (LNPs) have been the most successful delivery system for nucleic acids, but targeted delivery to a solid tumor still eludes the developed LNPs. We hypothesized that specially designed low-molecular-weight PEIs can partially or completely replace the ionizable lipids for more accommodating vehicles due to the structural flexibility offered by polymers, which could lead to safer and more efficient nucleic acid delivery. Methods: To achieve this, we first optimized the LNP formulations as a point of reference for three outcomes: cellular uptake, cytotoxicity, and silencing efficiency. Using a response surface methodology (Design Expert), we optimized siRNA delivery by varying mole fractions of lipid components. Leveraging the optimal LNP formulation, we integrated specifically designed cationic polymers as partial or complete replacements for the ionizable lipid. This methodological approach, incorporating optimal combined designs and response surface methodologies, refined the LPNPs to an optimal efficiency. Results: Our data revealed that DOPE and Dlin-MC3-DMA contributed to higher efficiency in selected breast cancer cells over DSPC and ALC-0315 as neutral and ionizable lipids, respectively, based on the software analysis and direct comparative experiments. Incorporation of selected polymers enhanced the cellular internalization significantly, which in some formulations resulted in higher efficiency. Conclusions: These findings offer a framework for the rational design of LPNPs, that could enhance the passive targeting and silencing efficiency in cancer treatment and broader applications for RNAi-based strategies. Full article

Tomato is among the most widely traded and consumed vegetables throughout the world; however, it is highly vulnerable to infection by the fungus Alternaria alternata. Fungal elicitors such as chitin oligomers have been shown to trigger the plant’s immune response, protecting the plant against pathogen attacks. Signaling molecules such as ethylene (Et), jasmonic acid (JA), and salicylic acid (SA) are key players in this immune response; however, it is unknown whether fungal chitin oligomers induce the production of these molecules. This study aimed to assess the effect of chitin oligomers isolated from the biomass of the A. alternata on the production of Et, JA, and SA in tomato fruits, as well as the expression of genes encoding transcription factors related with the signaling of Et (SlERF1), JA (SlMYC2), and SA (SlWRKY31). Low-molecular weight chitin oligomers were obtained from A. alternata. The results showed that SlMYC2 involved in JA signaling and production was the first gene induced by chitin oligomers 0.5 h post treatment. Furthermore, after 6 h, a second increase in gene expression was observed. However, SlERF1 involved in Et signaling increased 1 h post treatment and was highly correlated with high expression levels of the SlMYC2 gene, suggesting a strong relationship between Et and JA signaling. The most significant increase in gene expression was observed in SlWRKY31 involved in SA signaling 6 h post treatment with chitin oligomers, which showed a high correlation with Et production. It is concluded that the chitin oligomers of A. alternata elicit an early response in the production of Et, JA, and SA in tomato fruit, which play an important role as signaling molecules in the activation of plant defense mechanisms. Full article

We modified native wheat starch using 15, 30, and 60 min of acid hydrolysis (AH). The non-modified and AH-modified starches were converted to highly homogeneous thermoplastic starches (TPSs) using our two-step preparation protocol consisting of solution casting and melt mixing. Our main objective was to verify if AH can decrease the processing temperature of TPS. All samples were characterized in detail by microscopic, spectroscopic, diffraction, thermomechanical, rheological, and micromechanical methods, including in situ measurements of torque and temperature during the final melt mixing step. The experimental results showed that (i) AH decreased the average molecular weight preferentially in the amorphous regions, (ii) the lower-viscosity matrix in the AH-treated starches resulted in slightly higher crystallinity, and (iii) all AH-modified TPSs with a less viscous amorphous phase and higher content of crystalline phase exhibited similar properties. The effect of the higher crystallinity predominated at a laboratory temperature and low deformations, resulting in slightly stiffer material. The effect of the lower viscosity dominated during the melt mixing, where the shorter molecules acted as a lubricant and decreased the in situ measured processing temperature. The AH-induced decrease in the processing temperature could be beneficial for energy savings and/or possible temperature-sensitive admixtures for TPS systems. Full article

Cosmetic formulations are complex mixtures of ingredients that must fulfill several requirements. One of the challenges of the cosmetic industry is to find natural alternatives to replace synthetic polymers, preserving desirable sensory characteristics. The aim of this work is to induce the formation of gels, by replacing synthetic polymers with a low-molecular-weight gelator (LMWG), a small molecule able to self-assemble and form supramolecular networks. The impact of low-molecular-weight gelators on the environment is reduced as they are highly biodegradable. Thus, the behavior of solutions containing Boc-L-Dopa(Bn)₂-OH, an LMWG, together with ten different anionic surfactants, was studied to understand if the LMWG may act as a rheological modifier by increasing the viscosity of the formulation or forming gels with these ingredients. An amphoteric surfactant, cocamidopropyl betaine (CAPB), often used to increase cleansing gentleness, was also added to the solutions to better mimic a cosmetic formulation. In most cases, the addition of the gelator at only a 1% w/v concentration induces the gelification or an increase in the viscosity of the solutions, thus showing that this molecule is also able to self-assemble in complex mixtures. Full article

Proteolysis targeting chimeras (PROTACs), heterobifunctional molecules that hijack the ubiquitin–proteasome system (UPS) to degrade specific proteins, hold great promise in treating diseases driven by traditionally “undruggable” targets. However, their large molecular weight, high hydrophobicity, and other physicochemical hurdles contribute to their limited bioavailability, suboptimal pharmacokinetics, and attenuated therapeutic efficacy. Consequently, diverse formulation innovations have been investigated to optimize PROTAC delivery. This review examines current challenges and advances in specialized drug delivery approaches designed to bolster PROTAC pharmacological performance. We first outline the fundamental limitations of PROTACs—their low aqueous solubility, poor cell permeability, rapid clearance, and concentration-dependent “hook effect”. We then discuss how various enabling formulations address these issues, including polymeric micelles, emulsions, amorphous solid dispersions, lipid-based nanoparticles, liposomes, and exosomes. Collectively, these delivery technologies substantially improve the therapeutic outcomes of PROTACs in preclinical cancer models. Future applications may extend beyond oncology to address other complex diseases using newly emerging heterobifunctional molecules. By integrating advanced formulation science with innovative degrader design, the field stands poised to unlock the clinical potential of PROTACs for protein degradation therapies. Full article

Background: The blood–brain barrier (BBB) plays an important role in regulating homeostasis of the central nervous system (CNS), and it is an obstacle for molecules with a molecular weight higher than 500 Da seeking to reach it, making many drugs ineffective simply because they cannot be delivered to where they are needed. As a result, crossing the BBB remains the rate-limiting factor in brain drug delivery during the treatment of brain diseases, specifically tumors such as diffuse intrinsic pontine glioma (DIPG), a highly aggressive pediatric tumor with onset in the pons Varolii, the middle portion of the three contiguous parts of the brainstem, located above the medulla and below the midbrain. Methods: Currently, radiotherapy (RT) relieves DIPG symptoms but chemotherapy drugs do not lead to significant results as they do not easily cross the BBB. Focused ultrasound (FUS) and microbubbles (MBs) can temporarily open the BBB, facilitating radiotherapy and the entry of drugs into the CNS. A patient-derived xenograft DIPG model exposed to high-intensity focalized ultrasound (HIFU) or low-intensity focalized ultrasound (LIFU) combined with MBs was treated with doxorubicin, panobinostat, olaparib, ONC201 (Dordaviprone^®) and anti-PD1. Panobinostat has also been used in children with diffuse midline glioma, a broad class of brain tumors to which DIPG belongs. Results: Preliminary studies were performed using FUS to temporarily open the BBB and allow a milder use of radiotherapy and facilitate the passage of drugs through the BBB. The data collected show that after opening the BBB with FUS and MBs, drug delivery to the CNS significantly improved. Conclusions: FUS associated with MBs appears safe and feasible and represents a new strategy to increase the uptake of drugs in the CNS and therefore enhance their effectiveness. This review reports pre-clinical and clinical studies performed to demonstrate the usefulness of FUS in patients with DIPG treated with some chemotherapy. The papers reviewed were published in PubMed until the end of 2024 and were found using a combination of the following keywords: diffuse intrinsic pontine glioma (DIPG), DIPG H3K27-altered, blood–brain barrier and BBB, focused ultrasound (FUS) and radiotherapy (RT). Full article

Background: Nutraceuticals represent a strategy for maintaining health and constitute a brilliant market in Italy and across Europe. However, the absence of strict regulations regarding formulation requirements highlights a critical issue: their poor bioavailability. An example is coenzyme Q10 (CoQ10), a quinone known for its potential as a mitochondrial protective agent but characterized by low intestinal absorption. CoQ10 is a hydrophobic molecule with high molecular weight and poor water solubility, factors that significantly limit its intestinal bioaccessibility and, consequently, its oral bioavailability. Objectives: In this context, the present study describes a novel formulation designed to enhance CoQ10 bioaccessibility through in situ emulsification upon contact with gastroenteric fluids. This technology, termed Lipid-Based Auto-Emulsifying Drug Delivery System (LiBADDS), is unique because it combines a medium-chain triglyceride (MCT), a long-chain fatty acid, conjugated linoleic acid (CLA) with a high HLB solubilizer, Polysorbate 80 (PS80), and a sodium octenyl succinate starch derivative (SOS), which can create a nanometric emulsion simply by aqueous dispersion and upon contact with gastrointestinal fluids. This phenomenon promotes the prompt dispersion of CoQ10 and its rapid translocation into the serosal compartment of the intestinal epithelium. Methods: Its efficacy was evaluated in vitro through the Caco-2 cellular model and in vivo through a crossover study on healthy volunteers, measuring pharmacokinetic parameters such as AUC, C_max, T_max, ΔAUC, and ΔC_max. Results: Overall, LiBADDS demonstrated a significant improvement in both the bioaccessibility and bioavailability of CoQ10 compared to the unformulated substance. Conclusions: LiBADDS showed to be a promising tool to improve CoQ10 bioavailability by enhancing its bioaccessibility. Full article

Background: Diet is a key modifiable factor that can either support renal health or accelerate the onset and progression of chronic kidney disease (CKD). Recent advances in multiomics, particularly proteomics and metabolomics, significantly enhanced our understanding of the molecular mechanisms linking diet to CKD risk. Proteomics offers a comprehensive analysis of protein expression, structure, and interactions, revealing how dietary components regulate cellular processes and signaling pathways. Meanwhile, metabolomics provides a detailed profile of low-molecular-weight compounds, including endogenous metabolites and diet-derived molecules, offering insights into the metabolic states that influence kidney function. Methods: We have conducted a narrative review of key papers from databases such as PubMed, Scopus, and Web of Science to explore the potential of proteomic and metabolomic analysis in identifying molecular signatures associated with diet in human and animal biological samples, such as blood plasma, urine, and in kidney tissues. These signatures help elucidate how specific foods, food groups, and overall dietary patterns may either contribute to or mitigate CKD risk. Results: Recent studies the impact of high-fat diets on protein expression involved in energy metabolism, inflammation, and fibrosis, identifying early biomarkers of kidney injury. Metabolic, including disruptions in in fatty acid metabolism, glucose regulation, and amino acid pathways, have been recognized as key indicators of CKD risk. Additionally, several studies explore specific metabolites found in biological fluids and renal tissue in response to protein-rich foods, assessing their potential roles in a progressive loss of kidney function. Emerging evidence also suggests that dietary interventions targeting the gut microbiota may help alleviate inflammation, oxidative stress, and toxin accumulation in chronic kidney disease. Notably, recent findings highlight metabolomic signatures linked to beneficial shifts in gut microbial metabolism, particularly in the context of prebiotic supplementation. Conclusions: By integrating proteomics and metabolomics, future research can refine precision nutrition strategies, helping mitigate CKD progression. Expanding large-scale studies and clinical trials will be essential in translating these molecular insights into actionable dietary guidelines. Full article

Selenium–polysaccharides possess antioxidant properties, making them promising materials for functional foods, pharmaceuticals, and clinical applications. This study examines the incorporation of selenium into polysaccharides via mycelial biosynthesis and its effects on structure and antioxidant activity. Polysaccharides obtained from Lentinula edodes-submerged cultures grown in Se-supplemented and non-supplemented media were analysed for Se content (RP-HPLC/FLD), structure (FT-IR, HPLC, and HPGPC-ELSD), and antioxidant activity (DPPH scavenging, reducing power, and Fe²⁺ chelation). Two low-molecular-weight Se–heteropolysaccharides (Se-FE-1.1 and Se-FE-1.2) containing ~80 and 125 µg/g Se were isolated, primarily composed of glucose, mannose, and galactose with β-glycosidic linkages. Se incorporation into polysaccharides selectively enhanced their antioxidant activity in the DPPH radical scavenging assay, with minimal effects observed in iron chelation and reducing power assays. Crude Se–polysaccharides displayed the highest antioxidant activity, suggesting an additional contribution from protein components. Our findings demonstrate that Se is effectively incorporated into polysaccharides, altering monosaccharide composition while preserving glycosidic linkages. The selective enhancement of radical scavenging suggests that selenium plays a specific role in antioxidant activity, primarily influencing radical scavenging mechanisms rather than interactions with metal ions. Further research is needed to clarify the mechanisms of selenium incorporation, the nature of its bonding within the polysaccharide molecule, and its impact on biological activity. Full article

This study aimed to investigate the mediating effect of vanin-1 (VNN1) and its DNA methylation on the reduction in liver fat synthesis due to the role of betaine and 5-Azacytidine (5-AZA) in geese. Twenty-eight 35-day-old male Jiangnan white geese with similar body weight (BW) and good health conditions were randomized into four groups (seven birds per group). All the birds were housed with the same type of basal diet. The control group was treated with normal saline intraperitoneally (I.P.); the AZA group was treated I.P. with AZA (2 mg/kg); the betaine group was fed with betaine through the diet and treated I.P. with normal saline (1.2 g/kg); the AZA+betaine group was fed with betaine through the diet and treated I.P. with AZA. The results showed that the administration of AZA significantly increased serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and VNN1 enzyme activity (p < 0.05); additionally, the expression levels of the molecules in various tissues were up-regulated to different extents, such as VNN1, fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA dehydrogenase (SCD), and sterol regulatory element binding protein (SREBP); in contrast, the treatment of betaine reduced serum TC levels and the S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio; furthermore, hepatic DNA methylation in the AZA group was decreased in terms of the VNN1 promoter region. The results demonstrated that the expression of the VNN1 gene was negatively correlated with DNA methylation. This finding verified the key role of VNN1 and its methylation in the inhibition of liver lipid synthesis by betaine and provided a novel molecular mechanism for the regulation of liver lipid metabolism. Full article

Chitosan is widely used in drug delivery applications, due to its biocompatibility, bio-degradability, and low toxicity. Nevertheless, its properties can be enhanced through the physical or chemical modification of its amino and hydroxyl groups. This work explores the electrostatic complexation of two chitosan samples of differing lengths with two poly(N-isopropylacrylamide) (PNIPAM) homopolymers of different molecular weight carrying a chargeable carboxyl end group. This interaction enables the electrostatic binding of PNIPAM side chains onto the chitosan backbone through the amino groups, and could be considered as an alternative grafting method. Dynamic and electrophoretic light scattering techniques were employed in order to study the solution/dispersion properties of the formed complexes as a function of the PNIPAM concentration, or, equivalently, the molar/charge ratio of the two components. The obtained results revealed that their mass, size, and charge mostly depend on the length of the two individual constituents, as well as their mixing ratio. Furthermore, their response to changes in their environment, namely temperature and ionic strength, was also examined, demonstrating the effect of either the thermoresponsiveness of PNIPAM or the electrostatic charge screening, respectively. Fluorescence spectroscopy, utilizing pyrene as a probe, provided information regarding the hydrophobicity of the formed complexes, while images from scanning transmission electron and atomic force microscopies further elucidated their morphology, which was found to be closely related to that of the corresponding chitosan molecule. Finally, their potential as drug delivery vehicles was also investigated, utilizing curcumin as a model drug at various loading concentrations. Full article