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Scientific Reports Jul 2024The design and radiosynthesis of [F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach...
The design and radiosynthesis of [F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach that led to the radiosynthesis of [F]NT376 in a good radiochemical yield, (17.0 ± 3%, decay corrected), high radiochemical purity (> 97%) and relatively high molar activity of 185.0 GBq/µmol (> 5.0 Ci/µmol). The repositioning of the F-radiolabel into a phenyl ring (F-Fluoro-aryl) of the class-IIa HDAC inhibitor avoided the shortcomings of the direct radiolabeling of the 5-trifluoromethyl-1,2,4-oxadiazole moiety that was reported by us previously and was associated with low molar activity (0.74-1.51 GBq/µmol, 20-41 mCi/µmol). This radiochemical approach could find a wider application for radiolabeling similar molecules with good radiochemical yield and high molar activity.
Topics: Histone Deacetylase Inhibitors; Fluorine Radioisotopes; Radiopharmaceuticals; Drug Design; Humans; Radiochemistry; Oxadiazoles
PubMed: 38956204
DOI: 10.1038/s41598-024-65668-z -
Scientific Reports Jul 2024We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with...
We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.
Topics: Excipients; Polysorbates; Vitamin E; Surface-Active Agents; Pyrrolidines; Molecular Dynamics Simulation; Thermodynamics; Hot Melt Extrusion Technology; Vinyl Compounds
PubMed: 38956156
DOI: 10.1038/s41598-024-65978-2 -
ACS Applied Materials & Interfaces Jul 2024In the development of back electrodes for perovskite solar cells (PSCs), the major challenges are stability and cost. To address this, we present an innovative approach:...
In the development of back electrodes for perovskite solar cells (PSCs), the major challenges are stability and cost. To address this, we present an innovative approach: Simultaneous evaporation of two independently controlled sources of metal materials was performed to achieve a uniform distribution of the alloy electrodes. In this study, Ag-Cu alloys (the molar ratio of Ag/Cu is 7/3) with a high-index crystal face (111) and a work function matching perovskite were prepared using a codeposition technique. These properties mitigate nonradiative carrier recombination at the interface and reduce the energy barrier for carrier migration. Consequently, compared to Ag based PSCs (22.77%), the implementation of Ag-Cu alloy (Ag/Cu is 7/3)-based PSCs resulted in a power conversion efficiency of 23.72%. In a 1500 h tracking test in ambient air, the Ag-Cu alloy (Ag/Cu is 7/3)-based PSCs maintained their initial efficiency of 86%. This can be attributed to almost no migration of elements from the Ag-Cu alloy electrode to the perovskite layer. Our work presents a vital strategy for improving the stability of PSCs and reducing the costs associated with the back electrode in PSCs.
PubMed: 38955805
DOI: 10.1021/acsami.4c07144 -
Caries Research Jul 2024The purpose of this study was to investigate the effects of nitrate and nitrite on the pH-lowering activity of human plaque, the nitrite-producing and -degrading...
INTRODUCTION
The purpose of this study was to investigate the effects of nitrate and nitrite on the pH-lowering activity of human plaque, the nitrite-producing and -degrading activities of human plaque, and their correlation.
METHODS
Nitrate and nitrite were added to human plaque suspensions collected from the buccal aspect of maxillary molars of patients visiting a general dental clinic, and changes in pH were measured with and without glucose addition. Nitrite-producing and -degrading activities were evaluated by adding nitrate and nitrite to the plaque suspension and measuring the increase and decrease in nitrite with Griess reagent, respectively.
RESULTS
The addition of nitrate inhibited both endogenous and glucose-induced plaque pH lowering. The addition of glucose enhanced the production of nitrite from nitrate by about 3.3-fold. The addition of nitrite also inhibited endogenous plaque pH-lowering, but the addition of glucose promoted nitrite degradation by only about 1.1-fold. Nitrite-producing activity was positively correlated with age, but not with nitrite-degrading activity.
CONCLUSION
This study revealed that nitrite was produced from nitrate and inhibited the pH-lowering activity of human plaque, which may contribute to caries control. Both nitrite-producing and -degrading activities occurred in human plaque, but no correlation was found between them. Furthermore, nitrite production was enhanced by glucose metabolism, which may function as a self-regulatory mechanism (resilience) to prevent excessive acidification by glucose metabolism.
PubMed: 38955172
DOI: 10.1159/000540017 -
Waste Management (New York, N.Y.) Jul 2024This work outlines the first microwave (MW)-assisted protocol for the production of biofuel precursor furfural (FF) from the raw agricultural waste almond hull (AH),...
This work outlines the first microwave (MW)-assisted protocol for the production of biofuel precursor furfural (FF) from the raw agricultural waste almond hull (AH), olive stone (OS), and the winemaking-derived grape stalk (GS), grape marc (GM) and exhausted grape marc (EGM) through a one-pot synthesis process. To enhance the overall yield, a catalytic process was firstly developed from xylose, major constituent of hemicellulose present in lignocellulosic biomass. This method afforded FF with 100 % selectivity, yielding over 85 % in isolated product when using HSO, as opposed to a 37 % yield with AlCl·6HO, at 150 °C in only 10 min. For both catalysts, the developed methodology was further validated, proving adaptable and efficient in producing the targeted FF from the aforementioned lignocellulosic raw materials. More specifically, the employment of AlCl·6HO resulted in the highest selectivity (up to 89 % from GM) and FF yield (42 % and 39 % molar from OS and AH, respectively), maintaining notable selectivity for the latter (61 and 48 % from AH and OS). At this regard, and considering the environmental factor of sustainability, it is important to point out the role of AlCl·6HO in contrast to HSO, thus mitigating detrimental substances. This study provides an important management of agricultural waste through sustainable practises for the development of potential bio-based chemicals, aligning with Green Chemistry and process intensification principles.
PubMed: 38954920
DOI: 10.1016/j.wasman.2024.06.009 -
Journal of Human Evolution Jul 2024The superfamily Cercopithecoidea had a broad spatial distribution and occupied a wide variety of habitats across Europe from the Late Miocene until the Middle...
The superfamily Cercopithecoidea had a broad spatial distribution and occupied a wide variety of habitats across Europe from the Late Miocene until the Middle Pleistocene. Cercopithecines, such as macaques, showed more flexibility in habitat preferences, whereas colobines tended to be more sensitive to environmental differences. In Romania, only a few Pliocene and Pleistocene fossil sites have yielded primate remains. In this paper, we revise selected specimens previously listed in site reviews, and we describe several unpublished specimens from the Plio-Pleistocene fossil localities of Berești (Mammal Neogene [MN], MN14-MN15), Mălușteni (MN14), Ciuperceni-2 (MN15b), and Betfia (MN18). For each, we provide detailed descriptions, comparisons to other relevant material, and updated taxonomic assignments. We also present an updated biochronology and provide a paleoenvironmental reconstruction based on the taxonomic composition of the faunal assemblages described from these primate localities. The colobine monkey Dolichopithecus ruscinensis, from Berești, Mălușteni, and Ciuperceni-2, was present during the Early Pliocene in Romania. Mesopithecus monspessulanus is also known from Mălușteni, as is Paradolichopithecus sp. The Early Pleistocene site Betfia yielded a molar germ (in crypt; Betfia-XIII) and a deciduous premolar (Betfia-IX), both belonging to a Macaca sylvanus subspecies. Macaca sylvanus ssp. occurrences from Betfia-XIII and Betfia-IX offer an important perspective for understanding the chronostratigraphic range and geographic distribution of this species during the Early Pleistocene. The paleoenvironmental descriptions from Ciuperceni-2 show that primates were distributed in a mosaic habitat, with open and forested areas and a warm Mediterranean climate. This differs from Mălușteni, Berești, and Betfia, where a dry continental phase with an open landscape is inferred. Our review of paleoenvironmental conditions of Romanian primate localities provides a paleoecological framework for understanding the habitat preferences of extinct primates.
PubMed: 38954897
DOI: 10.1016/j.jhevol.2024.103544 -
Forensic Science International Jul 2024To summarize recent cases of fatal insulin poisoning both domestically and internationally, thereby offering valuable insights for the forensic identification of insulin...
PURPOSE
To summarize recent cases of fatal insulin poisoning both domestically and internationally, thereby offering valuable insights for the forensic identification of insulin overdose cases.
METHODS
Literature published since 2000 on fatal insulin overdose were systematically searched and screened. Data encompassing variables such as year, age, sex, cause of death, scene conditions, occupations, medical histories of victims and perpetrators, autopsy timing, dosage and administration methods, forensic pathology, and toxicological analysis, were compiled for rigorous statistical analysis.
RESULTS
Among the 29 fatal cases of insulin poisoning, suicides and homicides accounted for 55.2 % and 41.4 %, respectively. Precisely 34.5 % of victims or perpetrators were associated with the medical industry, 27.6 % had diabetes, and 24.1 % had mental illnesses such as depression. Intravenous injection resulted in quicker death than did subcutaneous injection. In some cases, immunohistochemical staining of insulin and protamine at injection sites yielded positive results. The average molar ratio of insulin to C-peptide in post-mortem blood was 13.76 ± 5.167, indicating a significant diagnostic value for insulin poisoning.
CONCLUSION
Assessment of cases of fatal insulin overdose should be thorough, incorporating case investigation, scene examination, medical records review, autopsy findings, pathological examinations, and laboratory tests, alongside considering the condition of the body and timing of death autopsy. Using mass spectrometry to detect insulin proves valuable, particularly in cases of poor body preservation.
PubMed: 38954875
DOI: 10.1016/j.forsciint.2024.112126 -
Glycoconjugate Journal Jul 2024A glucosyl-rich pectin, JMMP-3 (M, 2.572 × 10 g/mol, O-methyl % = 3.62%), was isolated and purified from the pericarp of the immature fruit of Juglans...
A glucosyl-rich pectin, JMMP-3 (M, 2.572 × 10 g/mol, O-methyl % = 3.62%), was isolated and purified from the pericarp of the immature fruit of Juglans mandshurica Maxim. (QingLongYi). The structure of JMMP-3 was studied systematically by infrared spectroscopy, monosaccharide compositions, methylation analysis, partial acid hydrolysis, and 1/2D-NMR. The backbone of JMMP-3 possessed a smooth region (→ GalA →) and a hairy region (→ GalA → Rha →) with a molar ratio of 2: 5. The substitution of four characteristic side chains (R-R) occurs at C-4 of → 2,4)-α-Rhap-(1→, where R is composed of → 5)-α-Araf-(1→, R is composed of → 4)-β-Galp-(1 → and β-Galp-(1→, R is composed of α-Glcp-(1→, →4)-α-Glcp-(1 → and → 4,6)-α-Glcp-(1→, and R is composed of → 5)-α-Araf-(1→, β-Galp-(1→, → 4)-β-Galp-(1→, → 3,4)-β-Galp-(1→, → 4,6)-β-Galp-(1 → and → 2,4)-β-Galp-(1 → . In addition, the antitumor activity of JMMP-3 on HepG2 cells was preliminarily investigated.
PubMed: 38954268
DOI: 10.1007/s10719-024-10156-9 -
Nano-micro Letters Jul 2024The impedance matching of absorbers is a vital factor affecting their microwave absorption (MA) properties. In this work, we controllably synthesized Material of...
The impedance matching of absorbers is a vital factor affecting their microwave absorption (MA) properties. In this work, we controllably synthesized Material of Institute Lavoisier 88C (MIL-88C) with varying aspect ratios (AR) as a precursor by regulating oil bath conditions, followed by one-step thermal decomposition to obtain carbon-coated iron-based composites. Modifying the precursor MIL-88C (Fe) preparation conditions, such as the molar ratio between metal ions and organic ligands (M/O), oil bath temperature, and oil bath time, influenced the phases, graphitization degree, and AR of the derivatives, enabling low filler loading, achieving well-matched impedance, and ensuring outstanding MA properties. The MOF-derivatives 2 (MD)/polyvinylidene Difluoride (PVDF), MD/PVDF, and MD/PVDF absorbers all exhibited excellent MA properties with optimal filler loadings below 20 wt% and as low as 5 wt%. The MD/PVDF (5 wt%) achieved a maximum effective absorption bandwidth (EAB) of 5.52 GHz (1.90 mm). The MD/PVDF (10 wt%) possessed a minimum reflection loss (RL) value of - 67.4 at 12.56 GHz (2.13 mm). A symmetric gradient honeycomb structure (SGHS) was constructed utilizing the high-frequency structure simulator (HFSS) to further extend the EAB, achieving an EAB of 14.6 GHz and a RL of - 59.0 dB. This research offers a viable inspiration to creating structures or materials with high-efficiency MA properties.
PubMed: 38954048
DOI: 10.1007/s40820-024-01435-z -
Expert Opinion on Biological Therapy Jul 2024Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations.... (Review)
Review
INTRODUCTION
Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life.
AREAS COVERED
This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained release devices, reservoirs for intravitreal delivery, and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed.
EXPERT OPINION
The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes. demonstrating promise in expanding treatment durability.
PubMed: 38953649
DOI: 10.1080/14712598.2024.2374869