Recent Advances in Nanodrug Delivery Systems Production, Efficacy, Safety, and Toxicity.

In the last three decades, the development of nanoparticles or nano-formulations as drug delivery systems has emerged as a promising tool to overcome the limitations of conventional delivery, potentially to improve the stability and solubility of active molecules, promote their transport across the biological membranes, and prolong circulation times to increase efficacy of a therapy. Despite several nano-formulations having applications in drug delivery, some issues concerning their safety and toxicity are still debated. This chapter describes the recent available information regarding safety, toxicity, and efficacy of nano-formulations for drug delivery. Several key factors can influence the behavior of nanoparticles in a biological environment, and their evaluation is crucial to design non-toxic and effective nano-formulations. Among them, we have focused our attention on materials and methods for their preparation (including the innovative microfluidic technique), mechanisms of interactions with biological systems, purification of nanoparticles, manufacture impurities, and nano-stability. This chapter places emphasis on the utilization of in silico, in vitro, and in vivo models for the assessment and prediction of toxicity associated with these nano-formulations. Furthermore, the chapter includes specific examples of in vitro and in vivo studies conducted on nanoparticles, illustrating their application in this field.

Organic-Inorganic Hybrid Materials from Vegetable Oils.

The production of materials based on fossil resources is yielding more sustainable and ecologically beneficial methods. Vegetable oils (VO) are one example of base materials whose derivatives rival the properties of their petro-based counterparts. Gaps exist however and one way to fill them is by employing sol-gel processes to synthesize organic-inorganic hybrid materials, often derived from silane/siloxane compounds. Creating Si─O─Si inorganic networks in the organic VO matrix permits the attainment of necessary strength, among other property enhancements. Consequently, many efforts have been directed to optimally achieve organic-inorganic hybrid materials with VOs. However, compatibilization is challenging, and desirable conditions for matching the inorganic filler in the organic matrix remain a key stumbling block toward wider application. Therefore, this review aims to detail recent progress on these new hybrids, focusing on the main strategies to polymerize and functionalize the raw VO, followed by routes highlighting the addition of the inorganic fillers to obtain desirable composites.

Controlled Fabrication of Wafer-Scale, Flexible Ag-TiO2 Nanoparticle-Film Hybrid Surface-Enhanced Raman Scattering Substrates for Sub-Micrometer Plastics Detection.

As an important trace molecular detection technique, surface-enhanced Raman scattering (SERS) has been extensively investigated, while the realization of simple, low-cost, and controllable fabrication of wafer-scale, flexible SERS-active substrates remains challenging. Here, we report a facile, low-cost strategy for fabricating wafer-scale SERS substrates based on Ag-TiO2 nanoparticle-film hybrids by combining dip-coating and UV light array photo-deposition. The results show that a centimeter-scale Ag nanoparticle (AgNP) film (~20 cm × 20 cm) could be uniformly photo-deposited on both non-flexible and flexible TiO2 substrates, with a relative standard deviation in particle size of only 5.63%. The large-scale AgNP/TiO2 hybrids working as SERS substrates show high sensitivity and good uniformity at both the micron and wafer levels, as evidenced by scanning electron microscopy and Raman measurements. In situ bending and tensile experiments demonstrate that the as-prepared flexible AgNP/TiO2 SERS substrate is mechanically robust, exhibiting stable SERS activity even in a large bending state as well as after more than 200 tensile cycles. Moreover, the flexible AgNP/TiO2 SERS substrates show excellent performance in detecting sub-micrometer-sized plastics (≤1 µm) and low-concentration organic pollutants on complex surfaces. Overall, this study provides a simple path toward wafer-scale, flexible SERS substrate fabrication, which is a big step for practical applications of the SERS technique.

Epitranscriptome in action: RNA modifications in the DNA damage response.

Complex pathways involving the DNA damage response (DDR) contend with cell-intrinsic and -extrinsic sources of DNA damage. DDR mis-regulation results in genome instability that can contribute to aging and diseases including cancer and neurodegeneration. Recent studies have highlighted key roles for several RNA species in the DDR, including short RNAs and RNA/DNA hybrids (R-loops) at DNA break sites, all contributing to efficient DNA repair. RNAs can undergo more than 170 distinct chemical modifications. These RNA modifications have emerged as key orchestrators of the DDR. Here, we highlight the function of enzyme- and non-enzyme-induced RNA modifications in the DDR, with particular emphasis on m6A, m5C, and RNA editing. We also discuss stress-induced RNA damage, including RNA alkylation/oxidation, RNA-protein crosslinks, and UV-induced RNA damage. Uncovering molecular mechanisms that underpin the contribution of RNA modifications to DDR and genome stability will have direct application to disease and approaches for therapeutic intervention.

Exploiting the potential of rivastigmine-melatonin derivatives as multitarget metal-modulating drugs for neurodegenerative diseases.

The multifaceted nature of the neurodegenerative diseases, as Alzheimer's disease (AD) and Parkinson's disease (PD) with several interconnected etiologies, and the absence of effective drugs, led herein to the development and study of a series of multi-target directed ligands (MTDLs). The developed RIV-IND hybrids, derived from the conjugation of an approved anti-AD drug, rivastigmine (RIV), with melatonin analogues, namely indole (IND) derivatives, revealed multifunctional properties, by associating the cholinesterase inhibition of the RIV drug with antioxidant activity, biometal (Cu(II), Zn(II), Fe(III)) chelation properties, inhibition of amyloid-ß (Aß) aggregation (self- and Cu-induced) and of monoamine oxidases (MAOs), as well as neuroprotection capacity in cell models of AD and PD. In particular, two hybrids with hydroxyl-substituted indoles (5a2 and 5a3) could be promising multifunctional compounds that inspire further development of novel anti-neurodegenerative drugs.

Natural AIEgens as Ultraviolet Sunscreens and Photosynergists for Solar Fuel Production.

Bio-nano hybrids (BNH), combining semiconductors and microorganisms, have shown great promise for effective solar-to-fuel energy conversion. However, the high-energy ultraviolet (UV) photons in the solar spectrum can cause severe photocorrosion of semiconductors and irreversible photodamage to microorganisms within BNH. Here, we developed an encapsulation strategy using natural luminogens with aggregation-induced emission characteristics (AIEgens) to construct a protective layer for BNH, effectively shielding them against high-energy UV photons. We incorporated natural berberine (BBR) into the BNH composed of Methanosarcina barkeri and polymeric carbon nitrides (CNx). The self-assembled BNH-BBR system displayed a 2.75-fold higher CH4 yield than BNH under simulated solar irradiation. Mechanism analysis revealed that BBR acted as a UV sunscreen for BNH by converting high-energy short wavelengths into low-energy long wavelengths, thereby reducing the accumulation of reactive oxygen species and alleviating the photocorrosion of CNx. Furthermore, BBR functioned as a photosynergist for BNH by regulating photoelectron production and utilization, enhancing the intracellular energy formation in M. barkeri for growth and metabolism. This work provides important insights into the effective and scalable conversion of CO2 into valuable biofuels with BNH under light illumination containing high-energy photons.

Performance evaluation of hybrid maize (Zea mays L.) in Burkina Faso, sub-Saharan region of Africa.

Maize (Zea mays L.) is a staple food for many people in Burkina Faso. The cultivation of maize hybrid genotypes plays a crucial role in increasing maize production and productivity. Feeding the growing population of the country, expected to reach thirty million by 2035, using hybrid genotypes of maize is a challenge. The objective of this study was to identify the hybrid maize genotypes having a best adaptability in the agro-ecological context of Burkina Faso. Nine (09) hybrid maize genotypes were evaluated during the 2018/2019 cropping season, in nine locations of the country characterized by a rainfall varying between 800 and 1200 mm. The experimental design was a Randomized Complete Block Design (RCBD) with three replications. The results showed that grain yield of the hybrids varied depending on the genotype nature and the cropping environment. The use of hybrid maize significantly increased the grain yield per hectare in maize production. Among the tested hybrid maize genotypes, SD1 (9.054 tons ha-1), SD3 (7.683 tons ha-1), and SD6 (9.385 tons ha-1) significantly presented higher yields. Based on the grain yield, the best growing environments of hybrid maize are NEBOUM1, BAMA and SOUNGALODAGO. The best genotypes for most of the environments are the hybrids of pure line varieties. The heritability was more than 80 % for all the studied yield traits.

Uncovering the Potential of Chalcone-Sulfonamide Hybrids: A Systematic Review on Their Anticancer Activity and Mechanisms of Action.

Cancer is the second leading cause of death worldwide and is considered a major public health problem. Despite the significant advances in cancer research, the conventional cancer treatment approaches often lead to serious side effects that affect the quality of life of cancer patients. Thus, searching for new alternatives for cancer treatment is crucial to minimize these problems. Chalcone-sulfonamide hybrids display a range of biological activities and have been widely investigated for their anticancer potential, being considered promising molecules for cancer treatment. This systematic review aimed to summarize the information available in the literature about the anticancer potential of chalcones-sulfonamides in vitro and in vivo and their mechanisms of action. Our analysis demonstrated that chalcones-sulfonamides have relevant cytotoxic potential against different cancer cell lines in vitro, especially against the human colorectal carcinoma cell line HCT-116. These molecules have also reduced tumor growth in vivo. Some chalcones-sulfonamides had improved cytotoxicity after chemical modification and could become more selective or even more potent than reference chemotherapeutics. The mechanisms underlying these effects demonstrated that chalcones-sulfonamides may lead to cell death by different pathways, predominantly via apoptosis or necroptosis. This review may encourage researchers to advance studies with chalcones-sulfonamides, especially to elucidate their mechanisms of action, contributing to the development of new alternatives to cancer treatment.

Atomically dispersed iron sites from eco-friendly microbial mycelium as highly efficient hydrogenation catalyst.

Iron, one of the most abundant elements on earth and an essential element for living organisms, plays a crucial role in our daily metabolism. In the field of catalysis, the development of high-performance catalysts based on less toxic iron element is also of significant importance for green chemistry and a sustainable future. To construct Fe-based heterogeneous catalysts with excellent hydrogenation performance, precise modulation of the atomic coordination structure is a key strategy for enhancing catalytic activity. In this study, we present an in-situ coating method for applying a zeolitic imidazolate framework (ZIF) onto the surface of fungal hyphae. The asymmetric coordination structure of Fe1-N3P1 was precisely tailored by utilizing the phosphorus source from the fungus and the nitrogen source in the ZIFs. Detailed characterizations and density functional theory calculations revealed that the incorporation of ZIFs not only increased the specific surface area of catalysts, but also facilitated the dispersion of Fe2P nanoparticles into the Fe1-N3P1 center, making the lowest reaction energy barrier and resulting in the best performance for nitrobenzene hydrogenation when compared to the Fe2P nanoparticles and clusters. This research introduces a novel design concept for constructing asymmetric monoatomic configuration based on the inherent characteristics of natural microorganisms and the exogenous porous coordination polymers.

Thiazepine-based Hybrids as Promising Anti-colon Cancer Agents: Design, Synthesis, Computational and In Vitro Screening.

Novel thiazepine-based hybrids (9a-d) were designed and synthesized to create lead molecules with exceptional anti-colon cancer efficacy. Analytical methods, including IR, NMR, and HR-MS, characterized the synthesized compounds. The in vitro colorectal study was carried out to compare the biological activity of newly developed compounds with the computational data. The tested compounds induced cytotoxicity in HT-29 cells for both 24h and 48h in a dose-dependent manner. However, compound 9a induced cytotoxicity at much higher concentrations compared to the rest of the compounds. 9b and 9c caused 50% cell death (compared to the untreated cells) at a dose of ~ 50µM and 40 µM in case of 24-hour exposure, respectively. On the contrary, for 48h exposure, both 9b and 9c induced 50% cell death concerning untreated cells at a dose of around ~20 µM, whereas 9d exhibited 50% cell death at 5 µM in the case of 48 h exposure. In silico ADMET was also carried out to understand the pharmacokinetics and safety profiles of the drug candidates. We found some of the critical targets of these compounds, which eventually will be integral to exploring the mechanistic actions of these compounds in colon cancer.

The Sol-Gel Process, a Green Method Used to Obtain Hybrid Materials Containing Phosphorus and Zirconium.

The sol-gel process is a green method used in the last few decades to synthesize new organic-inorganic phosphorus-containing hybrid materials. The sol-gel synthesis is a green method because it takes place in mild conditions, mostly by using water or alcohol as solvents, at room temperature. Therefore, the sol-gel method is, among others, a promising route for obtaining metal-phosphonate networks. In addition to phosphorus, the obtained hybrid materials could also contain titanium, zirconium, boron, and other elements, which influence their properties. The sol-gel process has two steps: first, the sol formation, and second, the transition to the gel phase. In other words, the sol-gel process converts the precursors into a colloidal solution (sol), followed by obtaining a network (gel). By using the sol-gel method, different organic moieties could be introduced into an inorganic matrix, resulting in organic-inorganic hybrid structures (sometimes they are also referred as organic-inorganic copolymers).

Isatin Bis-Imidathiazole Hybrids Identified as FtsZ Inhibitors with On-Target Activity Against Staphylococcus aureus.

In the present study, a series of isatin bis-imidathiazole hybrids was designed and synthesized to develop a new class of heterocyclic compounds with improved antimicrobial activity against pathogens responsible for hospital- and community-acquired infections. A remarkable inhibitory activity against Staphylococcus aureus was demonstrated for a subset of compounds (range: 13.8-90.1 µM) in the absence of toxicity towards epithelial cells and human red blood cells. The best performing derivative was further investigated to measure its anti-biofilm potential and its effectiveness against methicillin-resistant Staphylococcus aureus strains. A structure-activity relationship study of the synthesized molecules led to the recognition of some important structural requirements for the observed antibacterial activity. Molecular docking followed by molecular dynamics (MD) simulations identified the binding site of the active compound FtsZ, a key protein in bacterial cell division, and the mechanism of action, i.e., the inhibition of its polymerization. The overall results may pave the way for a further rational development of isatin hybrids as FtsZ inhibitors, with a broader spectrum of activity against human pathogens and higher potency.

Ultrasound protein-copolymer microbubble library engineering through poly(vinylpyrrolidone-co-acrylic acid) structure.

HYPOTHESIS: While albumin-coated microbubbles are routine contrast agents for ultrasound imaging, their short duration of contrast enhancement limits their use, yet can be improved by incorporating protein-copolymer hybrids into microbubble shells. The incorporation of N-vinyl-2-pyrrolidone and acrylic acid copolymer (P(VP-AA)) has been shown to enhance the performance of bovine serum albumin (BSA)-coated microbubbles. However, the impact of the copolymer structural properties on key microbubble characteristics (i.e., concentration, mean diameter and acoustic response) remains poorly understood. Therefore, we hypothesize that the copolymer structure affects its capacity to form micelle-like nanoaggregates, protein-copolymer hybrids, and microbubble shells, ultimately influencing the physicochemical and acoustic properties of the microbubbles. EXPERIMENTS: Here we evaluate the production and performance of BSA@P(VP-AA) microbubbles synthesized using a series of P(VP-AA) copolymers with -C8H17 and -C18H37 end groups and molecular weight cutoffs between 3.5 and 15 kDa. Both simulation and experimental data demonstrate that interactions between BSA and the copolymers significantly influence the performance of the resulting microbubbles across the library of 60 formulations. FINDINGS: The introduction of -C8H17 terminated copolymers into microbubble shells resulted in up to 200-fold higher concentration, 7-fold greater acoustic response, and 5-fold longer ultrasound contrast enhancement compared to plain BSA microbubbles. The enhanced acoustic performance was sustained during in vivo cardiac ultrasound imaging, without altering liver accumulation after copolymer introduction. These findings underscore how optimizing copolymer structure (specifically the terminal end group and molecular weight) can tailor the formation and performance of protein-copolymer-coated microbubbles, offering valuable insights for designing ultrasound contrast agents.

Engineering Protein-Nanoparticle Hybrids as Targeted Contrast Agents.

Iron oxide nanoparticles (IONPs) have shown great promise in biomedical applications, particularly as MRI contrast agents due to their magnetic properties and biocompatibility. Although several IONPs have been approved by regulatory agencies as MRI contrast agents, their primary application as negative contrast agents limits their usage. Additionally, there is an emerging need for the development of molecular contrast agents that can specifically target biomarkers, enabling more accurate and sensitive diagnostics. To address these challenges, we exploited the engineerability of proteins to stabilize IONPs with tailored magnetic properties, creating protein-stabilized iron oxide nanoparticles (Prot-IONPs) and leveraged the chemical diversity of proteins to functionalize Prot-IONPs with targeting moieties. As a proof-of-concept, we used alendronate (Ald) to target atherosclerotic plaques in the aorta. Simple protein functionalization allowed targeting while maintaining the stability and relaxation properties of the Prot-IONPs. Prot-IONPs-Ald successfully enabled positive contrast imaging of atherosclerotic plaques in vivo in an atherosclerotic mouse model (ApoE-/- mice on a high-fat diet). This study demonstrates the potential of engineering protein-nanoparticle hybrids as versatile platforms for developing targeted in vivo MRI contrast agents.

Eradicating the Photogenerated Holes in a Photocatalyst-Microbe Hybrid System: A Review.

Finding advanced technologies to store solar energy in chemical bonds efficiently is of great significance for the sustainable development of our society. The recently reported photocatalyst-microbe hybrid (PMH) system couples photocatalysts intimately with microbes and endows heterotrophic microbes with light-harvesting capacity. Generally, when PMH systems are exposed to light, photocatalytic reactions occur on the surface of photocatalysts and the photogenerated electrons enter microbial cells to promote the generation of energy carriers (such as nicotinamide adenine dinucleotide phosphate hydrogen and adenosine triphosphate) and the following chemical synthesis. PMH system applications have expanded from synthesizing value-added products (chemicals, fuels, and polymers) to treating pollutants. However, the successful operation of the PMH system relies on the timely eradication of the photogenerated holes as they recombine with the photogenerated electrons and cause the photocorrosion of the photocatalyst. This review summarizes the strategies for scavenging the photogenerated holes in PMH systems and provides insight into the current gaps and outlooks for future opportunities in this field.

Exploitation of heterosis and combining ability potential for improvement in okra (Abelmoschus esculentus L.).

Okra (Abelmoschus esculentus L. Moench) is a vital vegetable crop known for its nutritional and economic significance, especially in tropical and subtropical regions. Studying heterosis and combining ability in okra is crucial for enhancing its yield, quality, and resistance to pests and diseases. Heterosis can lead to superior offspring with enhanced traits while understanding combining ability helps in identifying the best parent combinations for breeding programs. Okra is an often cross-pollinated crop; therefore, exploiting heterosis is advantageous. The study was conducted from 2021 to 2022 at the Experimental Farm and Quality Analysis Laboratory, Department of Vegetable Science, College of Horticulture, Dr Yashwant Singh Parmar University of Horticulture and Forestry, Nauni, Solan, Himachal Pradesh, India to evaluate the heterosis and combining ability in okra to facilitate the development of high-yielding, resilient cultivars. The experimental material consisted of an F1 population of 30 crosses obtained from 10 parental lines crossed with three testers in a Line × Tester mating design, plus a standard check (Punjab-8). Estimates of heterosis (heterobeltiosis and standard heterosis) of the cross combinations UHFO-6 × Pusa Bhindi-5, UHFO-6 × Arka Anamika and UHFO-9 × Arka Anamika were high for inter-nodal distance, number of pods per plant, average pod weight, pod yield per plant, harvest duration, hundred seed weight, mucilage content, etc. Higher estimates of general combining ability (GCA) effects for pod yield per plant were observed in the parental lines UHFO-6 (123.47) and UHFO-9 (7.49). Among the cross combinations, UHFO-10 × Hisar Unnat (38.81), UHFO-2 × Pusa Bhindi-5 (38.29), UHFO-2 × Arka Anamika (17.42), and UHFO-5 × Arka Anamika (15.06) demonstrated higher estimates of specific combining ability (SCA) effects for pod yield per plant. The cross UHFO-2 × Hisar Unnat (160.00) exhibited the highest heterobeltiosis for mucilage content, while UHFO-10 × Arka Anamika (562.03) showed the highest standard heterosis for total polyphenol content. These cross combinations could produce okra with enhanced nutritional and medicinal properties. The highest GCA and SCA effects for pod yield per plant were observed in UHFO-6 (123.47) and UHFO-10 × Hisar Unnat (38.81), respectively. Identifying these parental lines and cross combinations based on their combining ability can result in the development of okra hybrids with substantially higher yields. In future, after multi-location trials, these parents and crosses can be released to replace existing okra cultivars (hybrids/varieties). Higher yielding and better quality okra cultivars can enhance the profitability for farmers, contribute to food security, and meet market demands more efficiently.

A model for transcription-dependent R-loop formation at double-stranded DNA breaks: Implications for their detection and biological effects.

R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. During R-loop formation an RNA strand invades the DNA duplex, displacing the homologous DNA strand and binding the complementary DNA strand. Here we analyze a model for transcription-dependent R-loop formation at double-stranded DNA breaks (DSBs). In this model, R-loop formation is preceded by detachment of the non-template DNA strand from the RNA polymerase (RNAP). Then, strand exchange is initiated between the nascent RNA and the non-template DNA strand. During that strand exchange the length of the R-loop could either increase, or decrease in a biased random-walk fashion, in which the bias would depend upon the DNA sequence. Eventually, the restoration of the DNA duplex would completely displace the RNA. However, as long as the RNAP remains bound to the template DNA strand it prevents that displacement. Thus, according to the model, RNAPs stalled at DSBs can increase the lifespan of R-loops, increasing their detectability in experiments, and perhaps enhancing their biological effects.

In vitro antiplasmodium and antitrypanosomal activities, ß-haematin formation inhibition, molecular docking and DFT computational studies of quinoline-urea-benzothiazole hybrids.

Quinoline-urea-benzothiazole hybrids exhibited low to sub-micromolar in vitro activities against the Plasmodium falciparum (P. falciparum) 3D7 chloroquine (CQ)-sensitive strain, with compounds 5a, 5b and 5f showing activities ranging from 0.33 to 0.97 µM. Against the formation of ß-haematin, the majority of the tested compounds were comparable to the reference drug, chloroquine (CQ), with compounds 5c (IC50 = 9.55 ± 0.62 µM) and 5h (IC50 = 9.73 ± 1.38 µM), exhibiting slightly better in vitro efficacy than CQ. The hybrids also exhibited low micromolar to submicromolar activities against Trypanosoma brucei brucei, with 5j-5k being comparable to the reference drug, pentamidine. Compound 5b displayed higher in silico binding energy than CQ when docked against P. falciparum dihydroorotate dehydrogenase enzyme. Compounds 5j and 5k showed higher binding energies than pentamidine within the trypanothione reductase enzyme binding pocket. The root means square deviations of the hit compounds 5b, 5j and 5k were stable throughout the 100 ns simulation period. Post-molecular dynamics MMGBSA binding free energies showed that the selected hybrids bind spontaneously to the respective enzymes. The DFT investigation revealed that the compounds have regions that can bind to the electropositive and electronegative sites of the proteins.

A dataset on multi-trait selection approach for the evaluation of F1 tomato hybrids along with their parents under hot and humid conditions in Bangladesh.

This dataset aims to evaluate the use of multiple trait-based selection methods with multi-trait genotype-ideotype distance index (MGIDI) models to identify superior summer F1 tomato hybrids suitable for the climatic conditions of countries like Bangladesh. The dataset was generated using 14 cross combinations from a Line × Tester mating design, along with seven parental lines and two tester parents of tomatoes with diverse genetic bases and heat tolerance qualities in a randomized complete block (RCB) design. The likelihood ratio (LR) test indicated highly significant genotype effects for most of the analyzed traits. A heatmap of correlation analyses between 16 traits identified a highly significant positive correlation (r > 0.8) between NFrPC and NFPC and between AFW and FW, preliminarily indicating a clear trace of multicollinearity among these traits. The traits NFPP, YPP, and Yield showed the highest predicted genetic gains, indicating their potential for substantial improvement through selection. Additionally, the heritability estimates ranged from 0.54 to 0.99, highlighting high heritability across the traits, which suggests favourable conditions for effective selection strategies. The strengths and weaknesses of hybrids AVTOV1002×C41 and AVTOV1010×C41 were evaluated based on their contributions to MGIDI across four major factors. These hybrids demonstrated strong performance, particularly excelling in traits associated with FA1, FA2, and FA4. The dataset of MGIDI can be universally applied to rank treatments based on desired values of multiple traits, with its potential for rapid expansion in evaluating various types of plant experiments.