18F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease.

INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.

Corrigendum: Diagnostic value of striatal 18F-FP-DTBZ PET in Parkinson's disease.

[This corrects the article DOI: 10.3389/fnagi.2022.931015.].

Diagnostic value of striatal 18F-FP-DTBZ PET in Parkinson's disease.

Background: 18F-FP-DTBZ has been proven as a biomarker for quantifying the concentration of presynaptic vesicular monoamine transporter 2 (VMAT2). However, its clinical application is still limited. Objectives: To evaluate the difference in dopaminergic integrity between patients with Parkinson's disease (PD) and healthy controls (HC) using 18F-FP-DTBZ PET in vivo and to determine the diagnostic value of standardized uptake value ratios (SUVRs) using the Receiver Operating Characteristic (ROC) curve. Methods: A total of 34 PD and 31 HC participants were enrolled in the PET/MR derivation cohort, while 89 PD and 18 HC participants were recruited in the PET/CT validation cohort. The Hoehn-Yahr Scale and the third part of the MDS-Unified Parkinson's Disease Rating Scale (MDSUPDRS-III) were used to evaluate the disease staging and severity. All assessments and PET scanning were performed in drug-off states. The striatum was segmented into five subregions as follows: caudate, anterior dorsal putamen (ADP), anterior ventral putamen (AVP), posterior dorsal putamen (PDP), and posterior ventral putamen (PVP) using automatic pipeline built with the PMOD software (version 4.105). The SUVRs of the targeted subregions were calculated using the bilateral occipital cortex as the reference region. Results: Regarding the diagnostic value, ROC curve and blind validation showed that the contralateral PDP (SUVR = 3.43) had the best diagnostic accuracy (AUC = 0.973; P < 0.05), with a sensitivity of 97.1% (95% CI: 82.9-99.8%), specificity of 100% (95% CI: 86.3-100%), positive predictive value (PPV) of 100% (95% CI: 87.0-100%), negative predictive value (NPV) of 96.9% (95% CI: 82.0-99.8%), and an accuracy of 98.5% for the diagnosis of PD in the derivation cohort. Blind validation of 18F-FP-DTBZ PET imaging diagnosis was done using the PET/CT cohort, where participants with a SUVR of the PDP <3.43 were defined as PD. Kappa test showed a consistency of 0.933 (P < 0.05) between clinical diagnosis and imaging diagnosis, with a sensitivity of 98.9% (95% CI: 93.0-99.9%), specificity of 94.4% (95% CI: 70.6-99.7%), PPV of 98.9% (95% CI: 93.0-99.9%), NPV of 94.4% (95% CI: 70.6-99.7%), and a diagnostic accuracy of 98.1%. Conclusions: Our results showed that an SUVR threshold of 3.43 in the PDP could effectively distinguish patients with PD from HC.

Brain microglia activation and peripheral adaptive immunity in Parkinson's disease: a multimodal PET study.

BACKGROUND: Abnormal activation of immune system is an important pathogenesis of Parkinson's disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear. OBJECTIVES: To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity. METHODS: In this case-control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson's disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET. RESULTS: Compared to healthy controls, patients with Parkinson's disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson's disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed. CONCLUSION: Parkinson's disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.

Synthesis of functional dicationic ionic liquids for the treatment of lignocellulosic biomass.

Mono-cationic ionic liquids (MILs) have been widely utilized for the treatment of lignocelluloses. However, the hydrophilic property of MILs increases the difficulty of isolating sugars and their reuse, which limits their industrial application. In the present study, a series of dicationic ionic liquids (DILs) were synthesized with totally different di-cations and di-anions. An alternating miscibility of DILs with water was observed depending on the dealing temperature. The functional DILs exhibiting hydrophobic and acidic properties were investigated for the treatment of corn stalk. High yields of sugars were achieved as 27.8% and 31.6% with DIL3 and DIL4, respectively. Cellulosic materials were obtained as 74.3% and 77.8% with DIL1 and DIL2 and 61.2% and 65.7% with DIL3 and DIL4, respectively. Enzymatic reaction was successfully performed with cellulosic materials after the DIL treatment. DILs were recycled and reused with no significant reduction in sugar yields. Hydrophobic DILs are a potentially effective approach to enable the successful decomposition and degradation of lignocellulosic biomass.

Characterization and synthesis of indole-3-acetic acid in plant growth promoting Enterobacter sp.

Indole-3-acetic acid (IAA) plays an important role in the growth and development of plants. In this study, a series of predominant strains were isolated and identified as Enterobacter sp. with remarkable IAA-producing capabilities. The IAA-producing strains are mainly tryptophan-dependent and have significantly high yields of IAA (3477 µg mL-1 and 3378 µg mL-1). The ipdC gene encoding indole-3-pyruvate decarboxylase was identified by genomic analysis and RT-qPCR analysis, indicating the involvement of the indole-3-pyruvic acid (IPyA) pathway of IAA biosynthesis. The IPyA pathway was also confirmed by the intermediate assay. The IAA product of microbial metabolites was isolated, purified and characterized. These microbes exhibiting IAA production significantly promoted the growth of maize, increasing root length, plant height, fresh weight and dry weight. Thus, Enterobacter sp. with high IAA production has great prospects in agricultural and industrial applications.

Diurnal Regulation of Plant Epidermal Wax Synthesis through Antagonistic Roles of the Transcription Factors SPL9 and DEWAX.

Plant surface waxes form an outer barrier that protects the plant from many forms of environmental stress. The deposition of cuticular waxes on the plant surface is regulated by external environmental changes, including light and dark cycles. However, the underlying molecular mechanisms controlling light regulation of wax production are still poorly understood, especially at the posttranscriptional level. In this paper, we report the regulation of cuticular wax production by the miR156-SPL9 (SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9) module in Arabidopsis (Arabidopsis thaliana). When compared with wild-type plants, miR156 and SPL9 mutants showed significantly altered cuticular wax amounts in both stems and leaves. Furthermore, it was found that SPL9 positively regulates gene expression of the alkane-forming enzyme ECERIFERUM1 (CER1), as well as the primary (1-) alcohol-forming enzyme ECERIFERUM4 (CER4), to enhance alkane and 1-alcohol synthesis, respectively. Our results indicate that complex formation of SPL9 with a negative regulator of wax synthesis, DEWAX, will hamper SPL9 DNA binding ability, possibly by interfering with SPL9 homodimerization. Combined with their diurnal gene and protein expressions, this dynamic repression-activation transcriptional module defines a dynamic mechanism that may allow plants to optimize wax synthesis during daily cycles. These findings provide a regulatory framework for environmental signal integration in the regulation of wax synthesis.

The association between peroxisome proliferator-activated receptor Δ rs3777744, rs3798343, and rs6922548 and coronary artery disease.

Objective: The aim of the present study is to investigate the association between the single nucleotide polymorphism (SNP) sites of peroxisome proliferator-activated receptor Δ (PPARD) and the risk of coronary artery disease (CAD). To this end, a prospective observational single-center study of the clinical data from 880 subjects in a Chinese population was conducted. Methods: A total of 880 subjects, including 609 CAD patients and 271 control subjects, were selected for the present study. All inpatients had 4 ml of venous blood drawn after 12 h of fasting, and then clinical tests were conducted to obtain the biochemical parameters. CAD patients and Controls were distinguished by coronary angiography. Statistical analysis was conducted with SPSS software (ver 16.0). Results: A significant association between the G-alleles of PPARD rs3777744 and rs3798343 and a decreased risk for CAD was found. Moreover, we found an interaction between high fasting high-density lipoprotein cholesterol (HDL-C) serum levels, low serum glucose levels and their genotypes, ultimately decreasing the risk of CAD. Haplotype analysis was conducted on the three SNP sites, rs3777744 and rs3798343 to form a block [r2 = 0.79, D' = 0.99). The A-C haplotypes were associated with an increased risk of CAD (odds ratio (OR), 95% confidence interval (CI): 1.321 (1.060-1.647), P=0.013], and the G-G haplotypes were associated with a decreased risk [OR, 95% CI: 0.714 (0.567-0.849), P=0.004]. Conclusions: Our study indicates a significant association between the G-alleles of PPARD rs3777744 and rs3798343 and a decreased CAD risk. In addition, genotypes interact with high serum HDL-C levels and low serum glucose levels, resulting in decreased prevalence of CAD.

Insight into the effects of modifying chromophores on the performance of quinoline-based dye-sensitized solar cells.

A series of organic dyes based on quinoline as an electron-deficient π-linker, were designed and synthesized for dye sensitized solar cells (DSSC) application. These push-pull conjugated dyes, sharing same anchoring group with distinctive electron-rich donating groups such as N,N-diethyl (DEA-Q), 3,6-dimethoxy carbazole (CBZ-Q), bis(4-butoxyphenyl)amine (BPA-Q), were synthesized by Riley oxidation of CH3 followed by Knoevenagel condensation of the corresponding aldehyde precursors 2a-c with cyanoacrylic acid. The optical, electrochemical, theoretical calculation and photovoltaic properties with these three dyes were systematically investigated. Compared to DEA-Q and CBZ-Q, BPA-Q possesses better light harvesting properties with regard to extended conjugate length, red-shifted intramolecular charge transfer band absorption and broaden light-responsive IPCE spectrum, resulting in a greater short circuit photocurrent density output. BPA-Q also has improved open-circuit voltage due to the apparent large charge recombination resistance. Consequently, assembled with iodine redox electrolytes, the device with BPA-Q achieved the best overall conversion efficiency value of 3.07% among three dyes under AM 1.5G standard conditions. This present investigation demonstrates the importance of various N-substituent chromophores in the prevalent D-π-A type organic sensitizers for tuning the photovoltaic performance of their DSSCs.

De novo Assembly and Characterization of the Fruit Transcriptome of Idesia polycarpa Reveals Candidate Genes for Lipid Biosynthesis.

Idesia polycarpa, is a valuable oilseed-producing tree of the Flacourtiaceae family that has the potential to fulfill edible oil production and is also a possible biofuel feedstock. The fruit is unique in that it contains both saturated and unsaturated lipids present in pericarp and seed, respectively. However, triglyceride synthesis and storage in tissues outside of the seeds has been poorly studied in previous researches. To gain insight into the unique properties of I. polycarpa fruit lipid synthesis, biochemical, and transcriptomic approaches were used to compare the lipid accumulation between pericarp and seed of the fruit. Lipid accumulation rates, final lipid content and composition were significantly different between two tissues. Furthermore, we described the annotated transcriptome assembly and differential gene expression analysis generated from the pericarp and seed tissues. The data allowed the identification of distinct candidate genes and reconstruction of lipid pathways, which may explain the differences of oil synthesis between the two tissues. The results may be useful for engineering alternative pathways for lipid production in non-seed or vegetative tissues.

Seventeen-year follow-up study on chromosomal aberrations in five victims accidentally exposed to several Gy of 60Co gamma-rays.

On 25 June 1990, a radiation accident occurred in a (60)Co source radiation unit in Shanghai, due to violations in operation regulations. This accident resulted in the exposure of seven individuals to acute high-dose and dose-rate whole-body external irradiation. Conventional chromosomal aberration analysis, G-banding automatic karyotype analysis and/or fluorescent in situ hybridization (FISH) painting methods were used to analyze chromosomal aberrations in peripheral blood lymphocytes from five of the victims 24 h to 17 years after accidental exposure to 1.9-5.1 Gy of (60)Co gamma-rays. The frequency of unstable chromosomal aberrations (dicentrics and rings) remained at constant levels 1 month after exposure. Three months after exposure, the frequency was reduced by 20-40% in three victims, while no reduction was seen in the other two victims. Twelve years after exposure, the number of dicentrics and rings decreased by more than 90%, and did not reveal a dose-dependent relationship. However, even at 12-17 years after exposure, stable chromosome aberrations, dominated by translocations, remained at a high level in a dose-dependent manner. The frequency of stable chromosomal aberrations detected by FISH showed a similar dose-dependent relationship as that detected by karyotype analysis of G-banding chromosomes. The G-banding analysis also suggested that the pattern of chromosome breakpoints is random. The FISH data showed a decreasing tendency with time for chromosome translocation frequency in the peripheral lymphocytes, and the rate of reduction varied among different individuals. It is likely that the higher dose the victim received, the lesser the translocation frequency decreased with time. The G-banding data also showed that the rate of reduction of translocations is different among individuals. From 5 to 17 years after accidental irradiation, a very small reduction (approximately 10%) of translocation frequency was observed in victims C and D, while there was about a 35% reduction (the highest among the victims) for victim G who received the smallest dose (1.9 Gy). These observations can be used to validate the existence of chromosomal aberrations in peripheral blood lymphocytes as a biological dosimeter for radiation exposures.