Preferences in Clinical Care of Individuals With Differences of Sex Development.

OBJECTIVES: To identify the most important attributes related to the process of achieving, and outcomes associated with, successful care for differences of sex development (DSD). METHODS: We developed a best-worst scaling survey administered to 520 DSD stakeholders, including individuals or family members of those with DSD, health care specialists, and patient support and advocacy representatives. Fourteen process-related attributes and 16 outcome-related attributes were identified through qualitative research. We estimated relative importance scores and coefficients from regression analysis to understand the relative importance of attributes and conducted latent class analysis to explore heterogeneity in preferences. RESULTS: The 3 most important process attributes were (1) good communication between care team and patient/family, (2) care team educated patient/family about condition, and (3) care team incorporates the values of patient/family. The 3 most important outcome attributes were (1) patient satisfaction, (2) patient mental health, and (3) treatment maintains physical health. Latent class analyses showed that respondents had heterogeneous preferences. For process-related attributes, we identified 3 respondent groups: "Patient autonomy and support" (46% of respondents), "Education and care transitions" (18%), and "Shared decision-making" (36%). For outcome-related attributes, we identified 2 respondent groups: "Preserving function and appearance" (59% of respondents) and "Patient health and satisfaction" (41%). CONCLUSIONS: Outcomes such as patient satisfaction and health were the most important outcome attributes, and good communication and education from the care team were the most important process attributes. Respondents expressed heterogeneous preferences for selected DSD care attributes that providers should consider to improve satisfaction with and quality of DSD care.

Gadolinium Doping Modulates the Enzyme-like Activity and Radical-Scavenging Properties of CeO2 Nanoparticles.

Their unique physicochemical properties and multi-enzymatic activity make CeO2 nanoparticles (CeO2 NPs) the most promising active component of the next generation of theranostic drugs. When doped with gadolinium ions, CeO2 NPs constitute a new type of contrast agent for magnetic resonance imaging, possessing improved biocatalytic properties and a high level of biocompatibility. The present study is focused on an in-depth analysis of the enzyme-like properties of gadolinium-doped CeO2 NPs (CeO2:Gd NPs) and their antioxidant activity against superoxide anion radicals, hydrogen peroxide, and alkylperoxyl radicals. Using an anion-exchange method, CeO2:Gd NPs (~5 nm) with various Gd-doping levels (10 mol.% or 20 mol.%) were synthesized. The radical-scavenging properties and biomimetic activities (namely SOD- and peroxidase-like activities) of CeO2:Gd NPs were assessed using a chemiluminescent method with selective chemical probes: luminol, lucigenin, and L-012 (a highly sensitive luminol analogue). In particular, gadolinium doping has been shown to enhance the radical-scavenging properties of CeO2 NPs. Unexpectedly, both bare CeO2 NPs and CeO2:Gd NPs did not exhibit SOD-like activity, acting as pro-oxidants and contributing to the generation of reactive oxygen species. Gadolinium doping caused an increase in the pro-oxidant properties of nanoscale CeO2. At the same time, CeO2:Gd NPs did not significantly inhibit the intrinsic activity of the natural enzyme superoxide dismutase, and CeO2:Gd NPs conjugated with SOD demonstrated SOD-like activity. In contrast to SOD-like properties, peroxidase-like activity was observed for both bare CeO2 NPs and CeO2:Gd NPs. This type of enzyme-like activity was found to be pH-dependent. In a neutral medium (pH = 7.4), nanoscale CeO2 acted as a prooxidant enzyme (peroxidase), while in an alkaline medium (pH = 8.6), it lost its catalytic properties; thus, it cannot be regarded as a nanozyme. Both gadolinium doping and conjugation with a natural enzyme were shown to modulate the interaction of CeO2 NPs with the key components of redox homeostasis.

Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

Association Between Alcohol Use Disorder and Hospital Readmission Rates and Outcomes in Cancer Survivors: A Population Cohort Study.

BACKGROUND: Alcohol use disorder (AUD) is the most common substance use disorder and is characterized by heavy alcohol use and the inability to control drinking. This study sought to compare the rate, timing, length, and total costs of hospital readmissions among cancer survivors with and without AUD. METHODS: We used the Nationwide Readmissions Database in 2017 and 2018 in this cohort study. Cancer survivors with an AUD diagnosis during their index hospitalization were included in the exposure group. Propensity score matching was used to identify cancer survivors without AUD for the control group. The primary outcome was all-cause readmission, and secondary outcomes included days to, length of, and total cost of readmission. Outcomes were measured after 90 and 180 days of follow-up. Logistic regression was used to measure the likelihood of readmission, and negative binomial regression and gamma regression were used for the other outcomes. RESULTS: Of 485,962 cancer survivors, 13,953 (2.9%) had co-occurring AUD. Cancer survivors with AUD had slightly higher odds of 90-day (odds ratio, 1.14; 95% CI, 1.06-1.22) and 180-day (odds ratio, 1.11; 95% CI, 1.05-1.18) readmission compared with those without AUD. Cancer survivors with AUD who were readmitted after 90 days also had higher readmission costs ($3,785 vs $3,376; P=.03). No differences in time to and length of readmission were observed between groups. The odds of readmission were higher among cancer survivors with AUD irrespective of age and type of cancer. Male, but not female, cancer survivors with AUD were more likely than those without AUD to be readmitted in both follow-up periods. CONCLUSIONS: This population-based cohort study of cancer survivors in the United States found that AUD is associated with higher 90- and 180-day readmission rates and higher related health care costs after 90 days of follow-up. Hospitalized cancer survivors with AUD may benefit from addiction treatment and discharge planning that addresses their co-occurring AUD.

NaGaPO4F - a KTiOPO4-structured solid sodium-ion conductor.

Advanced ionic conductors are crucial for a large variety of contemporary technologies spanning solid state ion batteries, fuel cells, gas sensors, water desalination, etc. In this work, we report on a new member of KTiOPO4-structured materials, NaGaPO4F, with sodium-ion conductivity. NaGaPO4F has been obtained for the first time via a facile two-step synthesis consisting of a hydrothermal preparation of an ammonia-based precursor, NH4GaPO4F, followed by an ion exchange reaction with NaNO3. Its crystal structure was precisely refined using a combination of synchrotron X-ray powder diffraction and electron diffraction tomography. The material is thermally stable upon 450 °C showing no significant structural transformations or degradation but only a ∼1% cell volume expansion. Na-ion mobility in NaGaPO4F was investigated by a joint experimental and computational approach comprising solid-state nuclear magnetic resonance (NMR) and density functional theory (DFT). DFT and bond-valence site energy (BVSE) calculations reveal 3D diffusion of sodium in the [GaPO4F] framework with migration barriers amounting to 0.22 and 0.44 eV, respectively, while NMR yields 0.3-0.5 eV that, being coupled with a calculated bandgap of ∼4.25 eV, makes NaGaPO4F a promising fast Na-ion conductor.

Influence of the Synthesis Scheme of Nanocrystalline Cerium Oxide and Its Concentration on the Biological Activity of Cells Providing Wound Regeneration.

In the ongoing search for practical uses of rare-earth metal nanoparticles, cerium dioxide nanoparticles (nanoceria) have received special attention. The purpose of this research was to study the biomedical effects of nanocrystalline forms of cerium oxide obtained by different synthesis schemes and to evaluate the effect of different concentrations of nanoceria (from 10-2 to 10-6 M) on cells involved in the regeneration of skin cell structures such as fibroblasts, mesenchymal stem cells, and keratinocytes. Two different methods of nanoceria preparation were investigated: (1) CeO-NPs-1 by precipitation from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid and (2) CeO-NPs-2 by hydrolysis of ammonium hexanitratocerate (IV) under conditions of thermal autoclaving. According to the X-ray diffraction, transmission electron microscopy, and dynamic light scattering data, CeO2-1 consists of individual particles of cerium dioxide (3-5 nm) and their aggregates with diameters of 60-130 nm. CeO2-2 comprises small aggregates of 8-20 nm in diameter, which consist of particles of 2-3 nm in size. Cell cultures of human fibroblasts, human mesenchymal stem cells, and human keratinocytes were cocultured with different concentrations of nanoceria sols (10-2, 10-3, 10-4, 10-5, and 10-6 mol/L). The metabolic activity of all cell types was investigated by MTT test after 48 and 72 h, whereas proliferative activity and cytotoxicity were determined by quantitative cell culture counting and live/dead test. A dependence of biological effects on the method of nanoceria preparation and concentration was revealed. Data were obtained with respect to the optimal concentration of sol to achieve the highest metabolic effect in the used cell cultures. Hypotheses about the mechanisms of the obtained effects and the structure of a fundamentally new medical device for accelerated healing of skin wounds were formulated. The method of nanoceria synthesis and concentration fundamentally and significantly change the biological activity of cell cultures of different types-from suppression to pronounced stimulation. The best biological activity of cell cultures was determined through cocultivation with sols of citrate nanoceria (CeO-NPs-1) at a concentration of 10-3-10-4 M.

Synergistic Antimicrobial Effect of Cold Atmospheric Plasma and Redox-Active Nanoparticles.

Cold argon plasma (CAP) and metal oxide nanoparticles are well known antimicrobial agents. In the current study, on an example of Escherichia coli, a series of analyses was performed to assess the antibacterial action of the combination of these agents and to evaluate the possibility of using cerium oxide and cerium fluoride nanoparticles for a combined treatment of bacterial diseases. The joint effect of the combination of cold argon plasma and several metal oxide and fluoride nanoparticles (CeO2, CeF3, WO3) was investigated on a model of E. coli colony growth on agar plates. The mutagenic effect of different CAP and nanoparticle combinations on bacterial DNA was investigated, by means of a blue-white colony assay and RAPD-PCR. The effect on cell wall damage, using atomic force microscopy, was also studied. The results obtained demonstrate that the combination of CAP and redox-active metal oxide nanoparticles (RAMON) effectively inhibits bacterial growth, providing a synergistic antimicrobial effect exceeding that of any of the agents alone. The combination of CAP and CeF3 was shown to be the most effective mutagen against plasmid DNA, and the combination of CAP and WO3 was the most effective against bacterial genomic DNA. The analysis of direct cell wall damage by atomic force microscopy showed the combination of CAP and CeF3 to be the most effective antimicrobial agent. The combination of CAP and redox-active metal oxide or metal fluoride nanoparticles has a strong synergistic antimicrobial effect on bacterial growth, resulting in plasmid and genomic DNA damage and cell wall damage. For the first time, a strong antimicrobial and DNA-damaging effect of CeF3 nanoparticles has been demonstrated.

Calcein-Modified CeO2 for Intracellular ROS Detection: Mechanisms of Action and Cytotoxicity Analysis In Vitro.

Cerium oxide nanoparticles (CeO2 NPs) are metal-oxide-based nanozymes with unique reactive oxygen species (ROS) scavenging abilities. Here, we studied new CeO2 NPs modified with calcein (CeO2-calcein) as an intracellular ROS inactivation/visualization theranostic agent. The molecular mechanisms of the CeO2-calcein intracellular activity, allowing for the direct monitoring of ROS inactivation in living cells, were studied. CeO2-calcein was taken up by both normal (human mesenchymal stem cells, hMSc) and cancer (human osteosarcoma, MNNG/Hos cell line) cells, and was easily decomposed via endogenous or exogenous ROS, releasing brightly fluorescent calcein, which could be quantitatively detected using fluorescence microscopy. It was shown that the CeO2-calcein has selective cytotoxicity, inducing the death of human osteosarcoma cells and modulating the expression of key genes responsible for cell redox status as well as proliferative and migration activity. Such cerium-based theranostic agents can be used in various biomedical applications.

Hybrid Polyelectrolyte Capsules Loaded with Gadolinium-Doped Cerium Oxide Nanoparticles as a Biocompatible MRI Agent for Theranostic Applications.

Layer-by-layer (LbL) self-assembled polyelectrolyte capsules have demonstrated their unique advantages and capability in drug delivery applications. These ordered micro/nanostructures are also promising candidates as imaging contrast agents for diagnostic and theranostic applications. Magnetic resonance imaging (MRI), one of the most powerful clinical imaging modalities, is moving forward to the molecular imaging field and requires advanced imaging probes. This paper reports on a new design of MRI-visible LbL capsules, loaded with redox-active gadolinium-doped cerium oxide nanoparticles (CeGdO2-x NPs). CeGdO2-x NPs possess an ultrasmall size, high colloidal stability, and pronounced antioxidant properties. A comprehensive analysis of LbL capsules by TEM, SEM, LCSM, and EDX techniques was carried out. The research demonstrated a high level of biocompatibility and cellular uptake efficiency of CeGdO2-x-loaded capsules by cancer (human osteosarcoma and adenocarcinoma) cells and normal (human mesenchymal stem) cells. The LbL-based delivery platform can also be used for other imaging modalities and theranostic applications.

Boron Nanoparticle-Enhanced Proton Therapy for Cancer Treatment.

Proton therapy is one of the promising radiotherapy modalities for the treatment of deep-seated and unresectable tumors, and its efficiency can further be enhanced by using boron-containing substances. Here, we explore the use of elemental boron (B) nanoparticles (NPs) as sensitizers for proton therapy enhancement. Prepared by methods of pulsed laser ablation in water, the used B NPs had a mean size of 50 nm, while a subsequent functionalization of the NPs by polyethylene glycol improved their colloidal stability in buffers. Laser-synthesized B NPs were efficiently absorbed by MNNG/Hos human osteosarcoma cells and did not demonstrate any remarkable toxicity effects up to concentrations of 100 ppm, as followed from the results of the MTT and clonogenic assay tests. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell death under irradiation by a 160.5 MeV proton beam. The irradiation of MNNG/Hos cells at a dose of 3 Gy in the presence of 80 and 100 ppm of B NPs led to a 2- and 2.7-fold decrease in the number of formed cell colonies compared to control samples irradiated in the absence of NPs. The obtained data unambiguously evidenced the effect of a strong proton therapy enhancement mediated by B NPs. We also found that the proton beam irradiation of B NPs leads to the generation of reactive oxygen species (ROS), which evidences a possible involvement of the non-nuclear mechanism of cancer cell death related to oxidative stress. Offering a series of advantages, including a passive targeting option and the possibility of additional theranostic functionalities based on the intrinsic properties of B NPs (e.g., photothermal therapy or neutron boron capture therapy), the proposed concept promises a major advancement in proton beam-based cancer treatment.

Novel thienocycloalkylpyridazinones as useful scaffolds for acetylcholinesterase inhibition and serotonin 5-HT6 receptor interaction.

A library of eighteen thienocycloalkylpyridazinones was synthesized for human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibition and serotonin 5-HT6 receptor subtype interaction by following a multitarget-directed ligand approach (MTDL), as a suitable strategy for treatment of Alzheimer's disease (AD). The novel compounds featured a tricyclic scaffold, namely thieno[3,2-h]cinnolinone, thienocyclopentapyridazinone and thienocycloheptapyridazinone, connected through alkyl chains of variable length to proper amine moieties, most often represented by N-benzylpiperazine or 1-(phenylsulfonyl)-4-(piperazin-1-ylmethyl)-1H-indole as structural elements addressing AChE and 5-HT6 interaction, respectively. Our study highlighted the versatility of thienocycloalkylpyridazinones as useful architectures for AChE interaction, with several N-benzylpiperazine-based analogues emerging as potent and selective hAChE inhibitors with IC50 in the 0.17-1.23 µM range, exhibiting low to poor activity for hBChE (IC50 = 4.13-9.70 µM). The introduction of 5-HT6 structural moiety phenylsulfonylindole in place of N-benzylpiperazine, in tandem with a pentamethylene linker, gave potent 5-HT6 thieno[3,2-h]cinnolinone and thienocyclopentapyridazinone-based ligands both displaying hAChE inhibition in the low micromolar range and unappreciable activity towards hBChE. While docking studies provided a rational structural explanation for AChE/BChE enzyme and 5-HT6 receptor interaction, in silico prediction of ADME properties of tested compounds suggested further optimization for development of such compounds in the field of MTDL for AD.

Discovery of novel arylpiperazine-based DA/5-HT modulators as potential antipsychotic agents - Design, synthesis, structural studies and pharmacological profiling.

Schizophrenia is a mental disorder with a complex pathomechanism involving many neurotransmitter systems. Among the currently used antipsychotics, classical drugs acting as dopamine D2 receptor antagonists, and drugs of a newer generation, the so-called atypical antipsychotics, can be distinguished. The latter are characterized by a multi-target profile of action, affecting, apart from the D2 receptor, also serotonin receptors, in particular 5-HT2A and 5-HT1A. Such profile of action is considered superior in terms of both efficacy in treating symptoms and safety. In the search for new potential antipsychotics of such atypical receptor profile, an attempt was made to optimize the arylpiperazine based virtual hit, D2AAK3, which in previous studies displayed an affinity for D2, 5-HT1A and 5-HT2A receptors, and showed antipsychotic activity in vivo. In this work, we present the design of D2AAK3 derivatives (1-17), their synthesis, and structural and pharmacological evaluation. The obtained compounds show affinities for the receptors of interest and their efficacy as antagonists/agonists towards them was confirmed in functional assays. For the selected compound 11, detailed structural studies were carried out using molecular modeling and X-ray methods. Additionally, ADMET parameters and in vivo antipsychotic activity, as well as influence on memory and anxiety processes were evaluated in mice, which indicated good therapeutic potential and safety profile of the studied compound.

Vestibular and visual brain areas in the medial cortex of the human brain.

Self-motion perception involves an interaction between vestibular and visual brain regions. In the lateral brain, it includes the parietoinsular vestibular cortex and the posterior insular cortex. In the medial cortex, the cingulate sulcus visual (CSv) area is known to process visual-vestibular cues. Here, we show that the vestibular-visual network of the medial cortex extends beyond area CSv. We examined brain activations of 36 healthy right-handed participants by functional magnetic resonance imaging (fMRI) during stimulation with caloric vestibular, thermal, or visual motion cues. Consistent with previous research, we found that area CSv responded to both vestibular and visual cues but not to thermal cues. Moreover, the V6 complex and the precuneus motion (PcM) area responded primarily to (laminar-translational) visual motion cues. However, we also observed a region inferior to CSv within the pericallosal sulcus (vicinity of anterior retrosplenial) that primarily responded to vestibular cues. This vestibular pericallosal sulcus (vPCS) region did not respond to either visual or thermal cues. It was also distinct from a more posterior motion-sensitive region in the retrosplenial complex (mRSC) that responded to (radial) visual motion but not to vestibular and thermal cues. Together, our results suggest that the vestibular-visual network in the medial cortex not only includes areas CSv, PcM, and the V6 complex but also two additional brain regions adjacent to the callosum. These two brain regions exhibit similarities in terms of their locations and responses to vestibular and visual cues with self-motion-related brain regions recently described in nonhuman primates.NEW & NOTEWORTHY Self-motion perception involves several vestibular and visual cortical regions. Within the medial cortex, the cingulate sulcus visual (CSv) area, the precuneus motion (PcM) area, and the V6 complex respond selectively to self-motion cues. Here, we show that vestibular information is also processed in the pericallosal sulcus (vPCS), whereas (radial) visual motion information is associated with activation in the retrosplenial cortex (mRSC).

Evidence of target enhancement and distractor suppression in early visual areas.

Although the mechanisms of target enhancement and distractor suppression have been investigated along the visual processing hierarchy, there remains some unknown as to the role of perceptual load on the competition between different task-related information as attention deployment is manipulated. We present an fMRI spatial cueing paradigm, in which 32 participants had to attend to either a left or a right hemifield location and to indicate the orientation of the target Gabor that was presented simultaneously to a noise patch distractor. Critically, the target could appear at either the cued, valid location or at the uncued, invalid location; in the latter, the noise patch distractor appeared at the cued location. Perceptual load was manipulated by the presence or absence of high-contrast Gabor patches close to the fixation cross, which acted as lateral masks. Behavioural results indicated that participants performed more efficiently in validly cued trials compared to invalidly cued trials and under low compared to high load. Enhancement effects for targets and suppression effects for noise patches were greater in early visual areas at high load, that is in the presence of lateral masks. These results are in line with the hypothesis that attention results in both target enhancement and distractor suppression, and that these effects are most marked under high perceptual load. Theoretical implications of these results for different models of attention are discussed.

Heavily Gd-Doped Non-Toxic Cerium Oxide Nanoparticles for MRI Labelling of Stem Cells.

Recently, human mesenchymal stem cells (hMSc) have attracted a great deal of attention as potential therapeutic agents in the treatment of socially significant diseases. Despite substantial advances in stem-cell therapy, the biological mechanisms of hMSc action after transplantation remain unclear. The use of magnetic resonance imaging (MRI) as a non-invasive method for tracking stem cells in the body is very important for analysing their distribution in tissues and organs, as well as for ensuring control of their lifetime after injection. Herein, detailed experimental data are reported on the biocompatibility towards hMSc of heavily gadolinium-doped cerium oxide nanoparticles (Ce0.8Gd0.2O2-x) synthesised using two synthetic protocols. The relaxivity of the nanoparticles was measured in a magnetic field range from 1 mT to 16.4 T. The relaxivity values (r1 = 11 ± 1.2 mM-1 s-1 and r1 = 7 ± 1.2 mM-1 s-1 in magnetic fields typical of 1.5 and 3 T MRI scanners, respectively) are considerably higher than those of the commercial Omniscan MRI contrast agent. The low toxicity of gadolinium-doped ceria nanoparticles to hMSc enables their use as an effective theranostic tool with improved MRI-contrasting properties.

Mitogen-like Cerium-Based Nanoparticles Protect Schmidtea mediterranea against Severe Doses of X-rays.

Novel radioprotectors are strongly demanded due to their numerous applications in radiobiology and biomedicine, e.g., for facilitating the remedy after cancer radiotherapy. Currently, cerium-containing nanomaterials are regarded as promising inorganic radioprotectors due to their unrivaled antioxidant activity based on their ability to mimic the action of natural redox enzymes like catalase and superoxide dismutase and to neutralize reactive oxygen species (ROS), which are by far the main damaging factors of ionizing radiation. The freshwater planarian flatworms are considered a promising system for testing new radioprotectors, due to the high regenerative potential of these species and an excessive amount of proliferating stem cells (neoblasts) in their bodies. Using planarian Schmidtea mediterranea, we tested CeO2 nanoparticles, well known for their antioxidant activity, along with much less studied CeF3 nanoparticles, for their radioprotective potential. In addition, both CeO2 and CeF3 nanoparticles improve planarian head blastema regeneration after ionizing irradiation by enhancing blastema growth, increasing the number of mitoses and neoblasts' survival, and modulating the expression of genes responsible for the proliferation and differentiation of neoblasts. The CeO2 nanoparticles' action stems directly from their redox activity as ROS scavengers, while the CeF3 nanoparticles' action is mediated by overexpression of "wound-induced genes" and neoblast- and stem cell-regulating genes.

Hydrodeoxygenation of Lignin-Based Compounds over Ruthenium Catalysts Based on Sulfonated Porous Aromatic Frameworks.

Bifunctional catalysts are a major type of heterogeneous catalytic systems that have been widely investigated for biomass upgrading. In this work, Ru-catalysts based on sulfonated porous aromatic frameworks (PAFs) were used in the hydrodeoxygenation (HDO) of lignin-derived compounds: guaiacol, veratrole, and catechol. The relationship between the activity of metal nanoparticles and the content of acid sites in synthesized catalysts was studied. Herein, their synergy was demonstrated in the Ru-PAF-30-SO3H/5-COD catalyst. The results revealed that this catalytic system promoted partial hydrogenation of lignin-based compounds to ketones without any further transformations. The design of the Ru-PAF-30-SO3H/5-COD catalytic system opens a promising route to the selective conversion of lignin model compounds to cyclohexanone.

Redox-Active Cerium Fluoride Nanoparticles Selectively Modulate Cellular Response against X-ray Irradiation In Vitro.

Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells-hMSC) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSC from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in hMSC, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 h after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA-repair system after X-ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of hMSC from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.