Hierarchical Self-Assembly of Water-Soluble Fullerene Derivatives into Supramolecular Hydrogels.

Controlling the self-assembly of nanoparticle building blocks into macroscale soft matter structures is an open question and of fundamental importance to fields as diverse as nanomedicine and next-generation energy storage. Within the vast library of nanoparticles, the fullerenes-a family of quasi-spherical carbon allotropes-are not explored beyond the most common, C60. Herein, a facile one-pot method is demonstrated for functionalizing fullerenes of different sizes (C60, C70, C84, and C90-92), yielding derivatives that self-assemble in aqueous solution into supramolecular hydrogels with distinct hierarchical structures. It is shown that the mechanical properties of these resultant structures vary drastically depending on the starting material. This work opens new avenues in the search for control of macroscale soft matter structures through tuning of nanoscale building blocks.

From the Design of Innovative Ti-Pt Heterometallic Complexes to the Development of Highly Anti-Proliferative Water-Soluble Cationic Titanocenes.

Two innovative early/late Ti-Pt-heterobimetallic complexes were synthesized, characterized, and screened in cell-based assays using several human (SW480 and MDA-MB-231) and murine cancer cell lines (CT26 and EMT6) as well as a non-cancerous cell line (HMEC). The combination of the two metals - titanium(IV) and platinum (IV) - in a single molecule led to a synergistic biological activity (higher anti-proliferative properties than a mixture of each of the corresponding monometallic complexes). This study also investigated the benefits of associating a metal-free terpyridine moiety (with intrinsic biological activity) with a water-soluble titanocene fragment. The present work reveals that these combinations results in water-soluble titanocene compounds displaying an anti-proliferative activity down to the submicromolar level. One of these complexes induced an antitumor effect in vivo in CT26 tumor bearing BALB/C mice. The terpyridine moiety was also used to track the complex in vitro by multiphoton microscopy imaging.

Soluble humic acid suppresses plant immunity and ethylene to promote soybean nodulation.

Symbiotic nitrogen fixation (SNF) is a crucial process for nitrogen geochemical cycling and plant-microbe interactions. Water-soluble humic acid (WSHM), an active component of soil humus, has been shown to promote SNF in the legume-rhizobial symbiosis, but its molecular mechanism remains largely unknown. To reveal the SNF-promoting mechanism, we conducted transcriptomic analysis on soybean treated with WSHM. Our findings revealed that up- and downregulated differentially expressed genes (DEGs) were mainly involved in plant cell-wall/membrane formation and plant defence/immunity in the early stage, while the late stage was marked by the flavonoid synthesis and ethylene biosynthetic process. Further study on representative DEGs showed that WSHM could inhibit GmBAK1d-mediated immunity and BR signalling, thereby promoting rhizobial colonisation, infection, and nodulation, while not favoring pathogenic bacteria colonisation on the host plant. Additionally, we also found that the ethylene pathway is necessary for promoting the soybean nodulation by WSHM. This study not only provides a significant advance in our understanding of the molecular mechanism of WSHM in promoting SNF, but also provides evidence of the beneficial interactions among the biostimulator, host plant, and soil microbes, which have not been previously reported.

Insulin and circadian rhythm genes of the Nile rat (Arvicanthis niloticus) are conserved and orthologous to those in the rat, mouse and human.

The African grass or Nile rat (NR) (Arvicanthis niloticus) is a herbivorous diurnal rodent which is used as a biological model for research on type 2 diabetes mellitus (T2DM) and the circadian rhythm. Similar to humans, male NRs develop T2DM with high-carbohydrate diets. The NR thus provides a unique opportunity to identify the nutritional and underlying genetic factors that characterise human T2DM, as well as the effects of potential anti-diabetic phytochemicals such as Water-Soluble Palm Fruit Extract. Whole genome sequencing (WGS) could help identify possible genetic causes why NRs spontaneously develop T2DM in captivity. In this study, we performed WGS on a hepatic deoxyribonucleic acid (DNA) sample isolated from a male NR using PacBio high-fidelity long-read sequencing. The WGS data obtained were then de novo assembled and annotated using PacBio HiFi isoform sequencing (Iso-Seq) data as well as previous Illumina RNA sequencing (RNA-Seq) data. Genes related to insulin and circadian rhythm pathways were present in the NR genome, similar to orthologues in the rat, mouse and human genomes. T2DM development in the NR is thus most likely not attributable to structural differences in these genes when compared to other biological models. Further studies are warranted to gain additional insights on the genetic-environmental factors which underlie the genetic permissiveness of NRs to develop T2DM.

Rationalizing Counterion Selection for the Development of Lipophilic Salts: A Case Study with Venetoclax.

The use of lipid-based formulations (LBFs) can be hindered by low dose loading due to solubility limitations of candidate drugs in lipid vehicles. Formation of lipophilic salts through pairing these drugs with a lipophilic counterion has been demonstrated as a potential means to enhance dose loading in LBFs. This study investigated the screening of appropriate counterions to form lipophilic salts of the BCS class IV drug venetoclax. The physical properties, lipid solubility, and in vitro performance of the salts were analyzed. This study illustrated the versatility of alkyl sulfates and sulfonates as suitable counterions in lipophilic salt synthesis with up to ∼9-fold higher solubility in medium- and long-chain LBFs when compared to that of the free base form of venetoclax. All salts formulated as LBFs displayed superior in vitro performance when compared to the free base form of the drug due to the higher initial drug loadings in LBFs and increased affinity for colloidal species. Further, in vitro studies confirmed that venetoclax lipophilic salt forms using alkyl chain counterions demonstrated comparable in vitro performance to venetoclax docusate, thus reducing the potential for laxative effects related to docusate administration. High levels of the initial dose loading of venetoclax lipophilic salts were retained in a molecularly dispersed state during dispersion and digestion of the formulation, while also demonstrating increased levels of saturation in biorelevant media. The findings of this study suggest that alkyl chain sulfates and sulfonates can act as a suitable alternative counterion to docusate, facilitating the selection of counterions that can unlock the potential to formulate venetoclax as an LBF.

Synthesis and Biological Evaluation of Methoxypolyethylene-Glycol-Substituted Abiraterone Derivatives as Potential Antiprostate Cancer Agents.

Globally, prostate cancer is the most commonly diagnosed tumor and a cause of death in older men. Abiraterone, an orally administered irreversible CYP17 inhibitor, is employed to treat prostate cancer. However, abiraterone has several clinical limitations, such as poor water solubility, low dissolution rate, low bioavailability, and toxic side effects in the liver and kidney. Therefore, there is a need to identify high-efficiency and low-toxicity water-soluble abiraterone derivatives. In this work, we aimed to design and synthesize a series of abiraterone derivatives by methoxypoly(ethylene glycol) (mPEG) modification. Their antitumor activities and toxicology were analyzed in vitro and in vivo. The most potent compound, 2e, retained the principle of action on the CYP17 enzyme target and significantly improved the abiraterone water solubility, cell permeability, and blood safety. No significant abnormalities were observed in toxicology. mPEG-modification significantly improved abiraterone's antitumor activity and efficiency while reducing the associated toxic effects. The finding will provide a theoretical basis for future clinical application of mPEG-modified abiraterone.

Customizable Porphyrin Platform Enables Folate Receptor PET Imaging Using Copper-64.

Folate receptors including folate receptor α (FRα) are overexpressed in up to 90% of ovarian cancers. Ovarian cancers overexpressing FRα often exhibit high degrees of drug resistance and poor outcomes. A porphyrin chassis has been developed that is readily customizable according to the desired targeting properties. Thus, compound O5 includes a free base porphyrin, two water-solubilizing groups that project above and below the macrocycle plane, and a folate targeting moiety. Compound O5 was synthesized (>95% purity) and exhibited aqueous solubility of at least 0.48 mM (1 mg/mL). Radiolabeling of O5 with 64Cu in HEPES buffer at 37 °C gave a molar activity of 1000 µCi/µg (88 MBq/nmol). [64Cu]Cu-O5 was stable in human serum for 24 h. Cell uptake studies showed 535 ± 12% bound/mg [64Cu]Cu-O5 in FRα-positive IGROV1 cells when incubated at 0.04 nM. Subcellular fractionation showed that most radioactivity was associated with the cytoplasmic (39.4 ± 2.7%) and chromatin-bound nuclear (53.0 ± 4.2%) fractions. In mice bearing IGROV1 xenografts, PET imaging studies showed clear tumor uptake of [64Cu]Cu-O5 from 1 to 24 h post injection with a low degree of liver uptake. The tumor standardized uptake value at 24 h post injection was 0.34 ± 0.16 versus 0.06 ± 0.07 in the blocking group. In summary, [64Cu]Cu-O5 was synthesized at high molar activity, was stable in serum, exhibited high binding to FRα-overexpressing cells with high nuclear translocation, and gave uptake that was clearly visible in mouse tumor xenografts.

Ubiquitous Role of Phosphine-Based Water-Soluble Ligand in Promoting Catalytic Reactions in Water.

Catalysis has been at the forefront of the developments that has revolutionised synthesis and provided the impetus in the discovery of platform technologies for efficient C-C or C-X bond formation. Current environmental situation however, demands a change in strategy with catalysis being promoted more in solvents that are benign (Water) and for that the development of hydrophilic ligands (especially phosphines) is a necessity which could promote catalytic reactions in water, allow recyclability of the catalytic solutions and make it possible to isolate products using column-free techniques that involve lesser usage of hazardous organic solvents. In this review, we therefore critically analyse such catalytic processes providing examples that do follow the above-mentioned parameter.

Effects of atmospheric CO2 concentration on transpiration and leaf elongation responses to drought in Triticum aestivum, Lolium perenne and Festuca arundinacea.

BACKGROUND AND AIMS: Leaf elongation is vital for Poaceae species' productivity, influenced by atmospheric CO2 concentration ([CO2]) and climate-induced water availability changes. Although [CO2] mitigates the effects of drought on reducing transpiration per unit leaf area, it also increases total leaf area and water use. These complex interactions associated with leaf growth pose challenges in anticipating climate change effects. This study aims to assess [CO2] effects on leaf growth response to drought in perennial ryegrass (Lolium perenne), tall fescue (Festuca arundinacea) and wheat (Triticum aestivum). METHODS: Plants were cultivated in growth chambers with [CO2] at 200 or 800 ppm. At leaf six to seven unfolding, half of the plants were subjected to severe drought treatment. Leaf elongation rate (LER) was measured daily, whereas plant transpiration was continuously recorded gravimetrically. Additionally, water-soluble carbohydrate (WSC) content along with water and osmotic potentials in the leaf growing zone were measured at drought onset, mid-drought and leaf growth cessation. KEY RESULTS: Elevated [CO2] mitigated drought impacts on LER and delayed growth cessation across species. A positive correlation between LER and soil relative water content (SRWC) was observed. At the same SRWC, perennial grasses exhibited a higher LER with elevated [CO2], likely due to enhanced stomatal regulation. Despite stomatal closure and WSC accumulation, CO2 did not influence nighttime water potential or osmotic potential. The marked increase in leaf area across species resulted in similar (wheat and tall fescue) or higher (ryegrass) total water use by the experiment's end, under both watered and unwatered conditions. CONCLUSIONS: In conclusion, elevated [CO2] mitigates the adverse effects of drought on leaf elongation in three Poaceae species, due to its impact on plant transpiration. Overall, these findings provide valuable insights into CO2 and drought interactions that may help anticipate plant responses to climate change.

Molecular Dynamic Simulations Reveal that Water-Soluble QTY-Variants of Glutamate Transporters EAA1, EAA2 and EAA3 Retain the Conformational Characteristics of Native Transporters.

OBJECTIVE: Glutamate transporters play a crucial role in neurotransmitter homeostasis, but studying their structure and function is challenging due to their membrane-bound nature. This study aims to investigate whether water-soluble QTY-variants of glutamate transporters EAA1, EAA2 and EAA3 retain the conformational characteristics and dynamics of native membrane-bound transporters. METHODS: Molecular dynamics simulations and comparative genomics were used to analyze the structural dynamics of both native transporters and their QTY-variants. Native transporters were simulated in lipid bilayers, while QTY-variants were simulated in aqueous solution. Lipid distortions, relative solvent accessibilities, and conformational changes were examined. Evolutionary conservation profiles were correlated with structural dynamics. Statistical analyses included multivariate analysis to account for confounding variables. RESULTS: QTY-variants exhibited similar residue-wise conformational dynamics to their native counterparts, with correlation coefficients of 0.73 and 0.56 for EAA1 and EAA3, respectively (p < 0.001). Hydrophobic interactions of native helices correlated with water interactions of QTY- helices (rs = 0.4753, p < 0.001 for EAA1). QTY-variants underwent conformational changes resembling the outward-to-inward transition of native transporters. CONCLUSIONS: Water-soluble QTY-variants retain key structural properties of native glutamate transporters and mimic aspects of native lipid interactions, including conformational flexibility. This research provides valuable insights into the conformational changes and molecular mechanisms of glutamate transport, potentially offering a new approach for studying membrane protein dynamics and drug interactions.

Design, synthesis, and activity evaluation of water-soluble propofol derivatives as anesthetic drugs.

In this work, two series of water-soluble derivatives were designed and synthesized based on the structure of propofol as the lead compound. Furthermore, the anesthetic activities of the synthesized compounds were evaluated in vivo against mice, and the in vitro propofol release rate from five target compounds was determined. The findings of this study have shown that series II compounds which possess the structure feature of propofol + Î³-hydroxybutyric acid + α-aminoacetate or γ-aminobutyrate have higher therapeutic index than that of series I compounds which possess the structure feature of propofol + α-aminoacetate or ß-aminopropionate. In addition, the rate of propofol released from series II compounds was significantly better than that of series I compounds. Among series II compounds, compound II-20 had a therapeutic index of 5.6 (propofol = 2.7), a duration time of 571 s (propofol = 57 s), and no significant toxicity was observed in vivo, which made it valuable for further development.

Biodegradation of Water-Soluble Polymers by Wastewater Microorganisms: Challenging Laboratory Testing Protocols.

For water-soluble polymers (WSPs) that enter environmental systems at their end-of-life, biodegradability is a key functionality. For the development and regulation of biodegradable WSPs, testing methods that are both scientifically validated and economically practicable are needed. Here, we used respirometric laboratory tests to study the biodegradation of poly(amino acids), poly(ethylene glycol), and poly(vinyl alcohol), together with appropriate low-molecular-weight reference substrates. We varied key protocol steps of commonly used testing methods, which were originally established for small molecules and tested for effects on WSP biodegradation. We found that avoiding aeration of the wastewater inoculate prior to WSP addition, incubating WSP with filter-sterilized wastewater prior to biodegradation testing, and lowering the WSP concentration can increase biodegradation rates of WSPs. Combining the above-mentioned protocol variations substantially affected the results of the biodegradation testing for the two poly(amino acids) tested herein (i.e., poly(lysine) and poly(aspartic acid)). Our findings were consistent between microbial inocula derived from two municipal wastewater treatment plants. Our study presents promising biodegradation dynamics for poly(amino acids) and highlights the importance, strengths, and limitations of respirometric laboratory methods for WSP biodegradation testing.

Molecular Structure and Conformation of Biodegradable Water-Soluble Polymers Control Adsorption and Transport in Model Soil Mineral Systems.

Water-soluble polymers (WSPs) are used in diverse applications, including agricultural formulations, that can result in the release of WSPs to soils. WSP biodegradability in soils is desirable to prevent long-term accumulation and potential associated adverse effects. In this work, we assessed adsorption of five candidate biodegradable WSPs with varying chemistry, charge, and polarity characteristics (i.e., dextran, diethylaminoethyl dextran, carboxymethyl dextran, polyethylene glycol monomethyl ether, and poly-l-lysine) and of one nonbiodegradable WSP (poly(acrylic acid)) to sand and iron oxide-coated sand particles that represent important soil minerals. Combined adsorption studies using solution-depletion measurements, direct surface adsorption techniques, and column transport experiments over varying solution pH and ionic strengths revealed electrostatics dominating interactions of charged WSPs with the sorbents as well as WSP conformations and packing densities in the adsorbed states. Hydrogen bonding controls adsorption of noncharged WSPs. Under transport in columns, WSP adsorption exhibited fast and slow kinetic adsorption regimes with time scales of minutes to hours. Slow adsorption kinetics in soil may lead to enhanced transport but also shorter lifetimes of biodegradable WSPs, assuming more rapid biodegradation when dissolved than adsorbed. This work establishes a basis for understanding the coupled adsorption and biodegradation dynamics of biodegradable WSPs in agricultural soils.

Spectral Characteristics of Water-Soluble Rhodamine Derivatives for Laser-Induced Fluorescence.

We present a comprehensive fluorescence characterization of seven water-soluble rhodamine derivatives for applications in laser-induced fluorescence (LIF) techniques. Absorption and emission spectra for these dyes are presented over the visible spectrum of wavelengths (400 to 700 nm). Their fluorescence properties were also investigated as a function of temperature for LIF thermometry applications. Rhodamine 110 depicted the least fluorescence emission sensitivity to temperature at -0.11%/°C, while rhodamine B depicted the most with a -1.55%/°C. We found that the absorption spectra of these molecules are independent of temperature, supporting the notion that the temperature sensitivity of their emission only comes from changes in quantum yield with temperature. Conversely, these rhodamine fluorophores showed no change in emission intensities with pH variations and are, therefore, not suitable tracers for pH measurements. Similarly, fluorescent lifetime, which is also a property sensitive to local environmental changes in temperature, pH, and ion concentration, measurements were conducted for these fluorophores. It was found that rhodamine B and kiton red 620 have shorter fluorescence timescales compared to those of the other five rhodamine dyes, making them least suitable for applications where temporal changes in emission are monitored. Lastly, we conducted experiments to assess the physicochemical absorption characteristics of these dyes' molecules into polydimethylsiloxane (PDMS), the most common material for microfluidic devices. Rhodamine B showed the highest diffusion into PDMS substrates as compared to the other derivative dyes.

Chemical characterization and speciation of the soluble fraction of Arctic PM10.

The chemical composition of the soluble fraction of atmospheric particulate matter (PM) and how these components can combine with each other to form different species affect the chemistry of the aqueous phase dispersed in the atmosphere: raindrops, clouds, fog, and ice particles. The study was focused on the analysis of the soluble fraction of Arctic PM10 samples collected at Ny-Ålesund (Svalbard Islands, Norwegian Arctic) during the year 2012. The concentration values of Na+, K+, NH4+, Ca2+, Mg2+, Mn2+, Cu2+, Zn2+, Fe3+, Al3+, Cl-, NO2-, NO3-, SO42-, PO43-, formate, acetate, malonate, and oxalate in the water-soluble fraction of PM10 were determined by atomic spectroscopy and ion chromatography. Speciation models were applied to define the major species that would occur in aqueous solution as a function of pH (2-10). The model highlights that (i) the main cations such as Na+, K+, Mg2+, and Ca2+ occur in the form of aquoions in the whole investigated pH range; (ii) Cu2+, Zn2+, and, in particular, Fe3+ and Al3+ are mostly present in their hydrolytic forms; and (iii) Al3+, Fe3+, and Cu2+ form solid hydrolytic species that precipitate at pH values slightly higher than neutrality. These latter metals show interesting interactions with oxalate and sulfate ions, too. The speciation models were also calculated considering the seasonal variability of the concentration of the components and at higher concentration levels than those found in water PM extracts, to better simulate concentrations actually found in the atmospheric aqueous phase. The results highlight the role of oxalate as the main organic ligand in solution.

Water-Soluble Luminescent Polymers with Room-Temperature Phosphorescence Based on the α-Amino Acids.

Nonconventional luminophores have received increasing attention, owing to their fundamental importance, advantages in outstanding biocompatibility, easy preparation, environmental friendliness, and potential applications in sensing, imaging, and encryption. Purely organic molecules with outstanding fluorescence and room-temperature phosphorescence (RTP) have emerged as a new library of benign afterglow agents. However, the cost, toxicity, high reactivity, and poor stability of materials also limit their practical applications. Therefore, some natural products, synthetic compounds, and biomolecules have entered horizons of people. The as-designed exhibits sky blue and green fluorescence emission and green RTP emission (a lifetime of 343 ms and phosphorescence quantum of 15.3%) under air condition. This study presents an organic fluorescence for biological imaging and RTP for anti-counterfeiting and encryption based on amino acids, maleic anhydride and 4-vinylbenzenesulfonic acid sodium salt hydrate. This study provides a strategy for nonconventional luminophores in designing and synthesizing pure organic RTP materials.

Synthesis of New Glycine-Based Polymers and their Thermoresponsive Behavior in Water.

In this work, new glycine-derived polymers are developed that exhibit thermoresponsive properties in water. Therefore, a series of monomers containing one, two, or three amide functional groups and one terminal cyanomethyl group is synthesized. The resulting homopolymers, obtained by free radical polymerization (FRP) and reversible addition fragmentation chain transfer (RAFT) polymerization, display a sharp and reversible upper critical solution temperature (UCST)-type phase transition in water. Additionally, it is shown that the cloud point (TCP) can be adjusted over more than 60 °C by the number of glycyl groups present in the monomer structure and by the polymer's molar mass. These novel thermoresponsive polymers based on cyanomethylglycinamide enrich the range of nonionic UCST polymers and are promising to find applications in various fields.

Water-soluble vitamins and trace elements in children with chronic kidney disease stage 5d.

Children receiving maintenance dialysis (chronic kidney disease (CKD) stage 5d) have unique risk factors for micronutrient deficiency or toxicity. Children receiving chronic dialysis often require specialized diet plans that may provide more than the recommended daily allowance (RDA) of water-soluble vitamins and micronutrients, with or without the addition of a kidney-friendly vitamin. The following is a comprehensive review of current literature on disorders of micronutrients in this population including those of water-soluble vitamins (vitamin C and vitamin B complexes) and trace elements (copper, selenium, and zinc) and has three areas of focus: (1) the risk factors and clinical presentations of disorders of micronutrients, both deficiency and toxicity, (2) the tools to evaluate micronutrient status, and (3) the central role of renal dietitians in optimizing nutritional status from a micronutrient perspective.

Amino polycarboxylic acids-modified abiraterone derivatives as potential injectable anti-prostate cancer agents.

Abiraterone (Abi), an effective cytochrome oxidase P450 C17 (CYP17) inhibitor, inhibits androgen synthesis in testes, adrenal glands, and prostate tumors. However, their low bioavailability and dissolution rate due to their poor solubility and toxic side effects have hindered their clinical applications. In this study, water-soluble and injectable Abi derivatives were developed by introducing amino polycarboxylic acids into Abi, and their antiproliferation effects in vitro, mechanism of action, antitumor activities in vivo, pharmacokinetics, and toxicity were investigated. Compared to Abi, the water-soluble derivative Abi-DTPA exhibited excellent antitumor activity in vitro and in vivo. It decreased cell migration, invasion, and mitochondrial membrane potential. A mechanistic study revealed that it still targeted the CYP17 enzyme and increased the expression levels of apoptosis-related proteins, including cleaved caspase 9, cleaved PARP, and cleaved caspase 3. Abi-DTPA was the main form in the plasma and exhibited lower toxicity after intravenous administration. These findings suggest that Abi-DTPA can be used as a novel injectable anti-prostate cancer agent.

Size-resolved molecular characterization of water-soluble organic matter in atmospheric particulate matter from northern China.

Atmospheric particulate matter (PM) affects visibility, climate, biogeochemical cycles and human health. Water-soluble organic matter (WSOM) is an important component of PM. In this study, PM samples with size-resolved measurements at aerodynamic cut-point diameters (Dp) of 0.01-18 µm were collected in the rural area of Baoding and the urban area of Dalian, Northern China. Non-targeted analysis was adopted for the characterization of the molecule constitutes of WSOM in different sized particles using Fourier transform-ion cyclotron resonance mass spectrometry. Regardless of the location, the composition of WSOM in Aitken mode particles (aerodynamic diameter <0.05 µm) was similar. The WSOM in accumulation mode particles (0.05-2 µm) in Baoding was predominantly composed of CHO compounds (84.9%), which were mainly recognized as lignins and lipids species. However, S-containing compounds (64.2%), especially protein and carbohydrates species, accounted for most of the WSOM in the accumulation mode particles in Dalian. The CHO compounds (67.6%-79.7%) contributed the most to the WSOM in coarse mode particles (>2 µm) from both sites. Potential sources analysis indicated the WSOM in Baoding were mainly derived from biomass burning and oxidation reactions, while the WSOM in Dalian arose from coal combustion, oxidation reactions, and regional transport.