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The nuclear receptor, Nurr1, is critical for both the development and maintenance of midbrain dopamine neurons, representing a promising molecular target for Parkinson's disease (PD). We previously identified three Nurr1 agonists (amodiaquine, chloroquine and glafenine) that share an identical chemical scaffold, 4-amino-7-chloroquinoline (4A7C), suggesting a structure-activity relationship. Herein we report a systematic medicinal chemistry search in which over 570 4A7C-derivatives were generated and characterized. Multiple compounds enhance Nurr1's transcriptional activity, leading to identification of an optimized, brain-penetrant agonist, 4A7C-301, that exhibits robust neuroprotective effects in vitro. In addition, 4A7C-301 protects midbrain dopamine neurons in the MPTP-induced male mouse model of PD and improves both motor and non-motor olfactory deficits without dyskinesia-like behaviors. Furthermore, 4A7C-301 significantly ameliorates neuropathological abnormalities and improves motor and olfactory dysfunctions in AAV2-mediated α-synuclein-overexpressing male mouse models. These disease-modifying properties of 4A7C-301 may warrant clinical evaluation of this or analogous compounds for the treatment of patients with PD., (© 2023. The Author(s).)

64 Cu and 67 Cu are theragnostic pair radionuclides with promising application in the nuclear medicine. 64 Cu is PET nuclide for the non-invasive diagnosis and 67 Cu is beta emitter for therapy of various cancers. This study discusses optimization efforts in the production of these radioactive coppers carried out with 30 MeV cyclotron. Optimized conditions include target preparation, chemical separation, and quality control. The production routes of 64 Cu and 67 Cu were studied based on the nuclear reactions of 64 Ni(p,n) 64 Cu and 70 Zn(p,α) 67 Cu. The produced 64 Cu and 67 Cu have >99.9% of the radionuclidic purity. The yield at the end of bombardment (EOB) of 64 Cu and 67 Cu is 28.5 MBq/μAh and 67 Cu is 0.58 MBq/μAh, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Chae, Hur, Yang, Kong, Lee, Ju, Choi and Park.)

In imparting wetting properties, a fabrication process without the addition of new compounds and deposition of coating layers would be the most desirable because it does not introduce additional complexities. Hence, the ion beam irradiation technique is used as it enables the chemistry of materials to be modified through simple adjustments of irradiation parameters such as the type of accelerated particles, beam energy, and fluence. In this study, the hydrophilicity of alumina surfaces was weakened by irradiating He ion beams of different energy levels (200 keV and 20 MeV). These transitions become more pronounced as the total beam fluence increases. In low-energy irradiation, the effect of irradiation is predominant near the surface, and hydrophilicity is weakened by the increase in carbon adsorption and suppression of dissociative adsorption of water molecules owing to the introduction of oxygen vacancies. In contrast, nuclear transmutations are induced by irradiation with high-energy beams. Consequently, fluorine is generated, and hydrophobic functional groups are formed on the surface. By varying the beam conditions, the wetting properties of the target ceramic can be controlled to the desired level, which is required in various industries, via appropriate adjustments of the beam parameters. In addition, the beam irradiation technique may be applicable to all ceramic materials, including lattice oxygen and alumina.

Two commodity polymers, polystyrene (PS) and high-density polyethylene (HDPE), were irradiated by high-energy He ion beams at low fluence to examine the wettability changes at different fluences. The water contact angles of the PS and HDPE surfaces were reduced from 78.3° to 46.7° and 81.5° to 58.5°, respectively, upon increasing the fluence from 0 to 1 × 10 13 He 2+ /cm 2 for irradiation durations ≤4 min. Surface analyses were performed to investigate these wettability changes. Surface texture evaluations via scanning electron and atomic force microscopies indicated non-remarkable changes by irradiation. However, the chemical structures of the irradiated polymer surfaces were notable. The high-energy He ions induced nuclear transmutation of C to N, leading to C-N bond formation in the polymer chains. Further, C-O and C=O bonds were formed during irradiation in air because of polymer oxidation. Finally, amide and ester groups were generated by irradiation. These polar groups improved hydrophilicity by increasing surface energies. Experiments with other polymers can further elucidate the correlation between polymer structure and surface wettability changes due to high-energy low-fluence He ion irradiation. This method can realize simple and effective utilization of commercial cyclotrons to tailor polymer surfaces without compromising surface texture and mechanical integrity.

A durable and ready to use 68 Ge- 68 Ga generator column material is required for its routine use in radiopharmaceutical procedures. The present work comprises preliminary studies for development and evaluation of chitosan-TiO 2 based microsphere (C-TOM) composite towards its competence as a column material. The batch uptake studies showed higher distribution coefficients for 68 Ge vis-à-vis 68 Ga in the complete concentration range of HCl examined (0.01-1 mol.L -1 ). Furthermore, C-TOM showed enduring physical and chemical stability in 0.01 mol.L -1 HCl with persistent 68 Ga elution profiles (>95%) and negligible 68 Ge breakthrough (2 × 10 -4 %) for the preliminary evaluation period of ∼2 months. Overall, the studies indicated that, 68 Ga with high radionuclidic purity (≥99.99%) can be eluted routinely in a small volume (∼1.5 mL) of 0.01 mol.L -1 HCl proving its potentials as a novel solid phase extractant for 68 Ge/ 68 Ge generator system., (Copyright © 2019. Published by Elsevier Ltd.)

Biomimetic nanoparticles (NPs) have been actively studied for their biological compatibility due to its distinguished abilities viz. long-term circulation, low toxicity, ease for surface modification, and its ability to avoid phagocytosis of NPs by macrophages. Coating the NPs with a variety of cell membranes bearing the immune control proteins increases drug efficacy while complementing the intrinsic advantages of the NPs. In this study, efforts were made to introduce oxophilic radiometal 89 Zr with hollow mesoporous silica nanospheres (HMSNs) having abundant silanol groups and were bioengineered with red blood cell membrane (Rm) having cluster of differentiation 47 (CD47) protein to evaluate its long-term in vivo behavior. We were successful in demonstrating the increased in vivo stability of synthesized Rm-camouflaged, 89 Zr-labelled HMSNs with the markedly reduced 89 Zr release. Rm camouflaged 89 Zr-HMSNs effectively accumulated in the tumor by avoiding phagocytosis of macrophages. In addition, re-injecting the Rm isolated using the blood of the same animal helped to overcome the immune barrier. This novel strategy can be applied extensively to identify the long-term in vivo behavior of nano-drugs while enhancing their biocompatibility.

β-amyloid (Aβ) plaques in the brain are composed of Aβ40 and Aβ42 peptides, and are the defining pathological feature of Alzheimer's disease (AD). Fluorescent probes that can detect Aβ plaques have gained increasing interest as potential tools for in vitro and in vivo monitoring of the progression of AD. In this study, chalcone-mimic fluorescent probe 5 was designed and prepared. Probe 5 exhibited an approximately 50-fold increase in emission intensity after mixing with Aβ42 aggregates, a high affinity for Aβ42 aggregates (K D = 1.59 μM), and reasonable lipophilicity (log P value = 2.55). Probe 5 also exhibited specific staining of Aβ plaques in the transgenic mice (APP/PS1) brain sections. Ex vivo fluorescence imaging of the brain from normal and TG mice revealed that probe 5 was able to penetrate the BBB and stain the Aβ plaques. These results suggest that chalcone-mimic probe 5 possessed the requirements of a fluorescent probe for Aβ plaques and may be useful in AD research.

Direct metal-free C-4-selective indolation of pyridines is achieved for the first time using TEMPO and (Boc)2O. A variety of substituents on both indoles and pyridines are tolerated to give 3-(pyridin-4-yl)-1H-indole derivatives in moderate to excellent yields. This finding provides a novel approach for developing metal-free C-H functionalization of pyridines.

Phosphorus plays a pivotal role in plant growth and development. In this study, we isolated and characterized GmPTF1, a basic helix-loop-helix (bHLH) transcription factor (TF) gene from soybean (Glycine max) with tolerance to inorganic phosphate (Pi) starvation. Alignment analysis indicated that GmPTF1 and other reported bHLH TFs share significant similarity in the region of the bHLH domain. As with OsPTF1 and other homologous Pi starvation-related bHLH TFs (His-5, Glu-9, Arg-12, and Arg-13), all recognition motifs for the G-box (CACGTG) were present in the GmPTF1 domain. Prokaryotic expression in Escherichia coli strain BL21 (DE3) plysS showed that a novel 40-kDa polypeptide was expressed when cells containing GmPTF1 were induced. The subcellular localization in cells from onion epidermis and Arabidopsis roots demonstrated that the GmPTF1 protein was found in the nucleus. Furthermore, analysis of transcription activity in yeast revealed that full-length GmPTF1 and its N-terminal and C-terminal domains could activate the histidine, adenine, and uracil reporter genes. This suggested that the N-terminal and C-terminal peptides of GmPTF1 act as transcriptional activators. When real-time quantitative polymerase chain reaction was performed, the expression of GmPTF1 under conditions of phosphate starvation was significantly induced in soybean roots of the low-Pi-tolerant variety ZH15. Moreover, the relative level of expression was much higher there than in roots of the sensitive variety NMH from days 7 to 56 of low-Pi stress. These results imply that GmPTF1 is involved in conferring tolerance to phosphate starvation in soybean.

A general and efficient method for the cross-coupling of indoles with β-keto esters by using TEMPO/CuSO4·5H2O in air as oxidant has been developed. This reaction features high functional-group compatibility and an excellent selectivity. This methodology provides an alternative approach for the ketonization-olefination of indoles in moderate to good yields.

To investigate molecular epidemiology of DuCV in Cherry Valley ducks in China, the complete genomes of six DuCV strains, which were detected from Cherry Valley ducks in China between 2007 and 2008, were sequenced. Sequence and phylogenetic analysis were carried out to compare these six strains with another 27 DuCV strains from Mulard duck, Muscovy duck, Pekin ducks and Mule duck. The analysis showed that the six DuCV strains exhibited typical genetic features of the family of DuCV, such as a stem-loop structure, three major open reading frames (Rep, Cap and ORF3), four intergenic repeats and the conserved motifs for rolling circle replication and for the dNTP binding domain located in the Rep protein. Phylogenetic analysis of the nucleotide sequences of the complete genome and Cap gene of these strains together with those that have been previously published demonstrated two distinct DuCV genotypes. The DuCV strains with complete genomes containing 1988 and 1989 nucleotides clustered in genotype A, whereas the strains with complete genomes containing 1991, 1992, 1995 and 1996 nucleotides lay in genotype B. The six DuCV strains from Cherry Valley ducks were divided into the two groups. The results of the study provides some insight into the variation of DuCVs in Cherry Valley ducks.

The clinical symptoms of infectious coryza are multiple and include nasal discharge, facial swelling, lacrimation, and anorexia. In general, the disease is not fatal to chicken; so, in experiments where animals are infected with Avibacterium paragallinarum, there have been debates about conducting the challenge model and evaluating the clinical signs. In this experiment, 150 chickens, aged 30 days, were randomly divided into different groups. Some groups were infected with the 'in-contact' challenge model and others with the artificial intrasinus-injection-route model. The bacterial isolates used were three field isolates of different serogroups of A. paragallinarum, including Hpg-8 (Page serovar A), CCM6075 (Page serovar B) and Hpg-668 (Page serovar C). During this study, a scoring system was used to record the clinical signs of the infected birds and evaluate the pathogenic diversity of the two models. The final results indicated that the 'in-contact' challenge model of the three isolates showed a more reliable representation of the natural infection under field conditions than the artificial intrasinus-injection-route model. Thus, on carrying out animal experiments, the effect of 'in-contact' challenge model is more accurate than the artificial intrasinus-injection-route model., (Copyright 2009 Elsevier B.V. All rights reserved.)

The genomic DNA extracted from chicken embryo fibroblasts (CEF) of SPF chickens from three chicken farms was used as template to amplify the ALV proviral DNA by PCR with four pairs of primers, high positive detection rates of gag - gene (29/46), pol - gene (27/46), env - gene (24/46) and LTR fragment (31/46) were achieved. Eight continuous and overlapping fragments were amplified from one DNA sample with 8 pairs of primers according to published sequences, then cloned into the TA vector and se quenced. The complete sequence of the whole genome of ALV strain SD0501 was established and analyzed with DNAstar software. Comparisons of SD0501 sequence with that of other representative endogenous avian virus strains demonstrated that the genomes of ALV were relatively conservative, the nucleotide identity of all the strains was over 99.1%, and env - gene was over 98.5%. However, a low identity was demonstrated among the representative strains of different subgroups, especially, the env - gene showed obvious difference, the corresponding identity was as low as 56.3% - 91.5%.