Development of a Novel 99mTc-Labeled Folate Derivative Containing Phenyl Isonitrile to Target Folate Receptor with Reduced Renal Uptake.

The folate receptor has attracted much attention in the field of radiolabeled imaging agents due to the significant difference in its expression levels between tumor cells and most normal cells. However, the development of folate-based imaging agents has been limited by their high uptake in the kidney. In this study, to reduce the high renal uptake of radiolabeled folate-based tracers, a phenyl-isonitrile folate derivative (CNMBFA) was designed and labeled with technetium-99m. The complex obtained via the one-step kit labeling method had a high labeling yield (>95%) and high in vitro stability and hydrophilicity (log D7.4 = -1.72 ± 0.13). The results of the in vitro cell uptake and blocking studies and competitive binding experiments revealed that the [[99mTc]Tc-(CNMBFA)6]+ complex was specific for the folate receptor. Biodistribution and inhibition studies in KB tumor-bearing mice revealed moderate uptake and significant inhibition of the complex in tumors, whereas the renal uptake of [[99mTc]Tc-(CNMBFA)6]+ was significantly lower than that of previously reported tracers. Micro-SPECT/CT images further supported its ability to target the folate receptor for tumor imaging. Taken together, these results indicate that [[99mTc]Tc-(CNMBFA)6]+ is a potential tumor imaging agent that has good tumor-targeting properties with minimal radiation damage to the kidney.

NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation.

BACKGROUND: RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. METHODS: Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. RESULTS: As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. CONCLUSIONS: This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.

The coevolution of bullying and friendship networks.

The coevolution of bullying and friendship networks and the moderating effects of classroom bullying popularity norms were examined in a sample of 965 students (52.1% boys) in 22 fourth- and fifth-grade classes. Longitudinal social network analysis showed that children were more likely to bully their friends' victims (bully influence effect) and to be bullied by their friends' bullies (victim influence effect); two children bullying the same child were likely to be friends (bully selection effect), and two victims bullied by the same child were likely to be friends (victim selection effect). Bullying popularity norms served as moderators, and the bully selection effect was significant weaker in the context of low bullying popularity norms. This study adds understanding of bullying as a group process and provides implications for preventing school bullying.

Synthesis and Evaluation of [18F]SiFA-Conjugated Ligands for Fibroblast Activation Protein Imaging.

In recent years, fibroblast activation protein (FAP) has emerged as an important target for the diagnosis and therapy of various tumors due to its high expression on the cell surface of cancer-associated fibroblasts, which are the major components of the tumor stroma. In this study, we synthesized and evaluated 18F-labeled FAP inhibitors (FAPIs) for FAP imaging. Two silicon fluoride acceptor (SiFA)-conjugated FAPIs were synthesized: one containing a γ-carboxy-l-glutamic acid (Gla) residue (1) and another containing two Gla residues (2). Both ligands exhibited high binding affinities for FAP. 18F/19F exchange reactions on both ligands were performed in the presence of 2% water. This resulted in the formation of radioligands [18F]1 and [18F]2 in high radiochemical yields. Radioligand [18F]2, with a more favorable partition coefficient, was selected for the U87MG cell binding study, and the results showed FAP-specific binding of the radioligand to the cells. An ex vivo biodistribution study in U87MG tumor-bearing mice 60 min after injection demonstrated a 5.8-fold higher tumor accumulation of [18F]2 than that of [18F]1. Furthermore, PET and ex vivo biodistribution studies of [18F]2 in U87MG tumor-bearing mice showed high and persistent tumor uptake over time, which was significantly blocked by the preinjection of FAPI-04. Our results indicate that [18F]SiFA-(Gla)2-conjugated FAPI ([18F]2) has the potential for FAP imaging.

Serum perfluoroalkyl substances and growth and development in US adolescents: a nationally representative cross-sectional study.

Per- and polyfluoroalkyl substances (PFAS), synthetic organic chemicals, have been discovered in the blood of both humans and animals throughout the world. This has raised widespread concerns about its toxicity, especially for growing children and adolescents. Most research on growth and development to date has concentrated on children at birth and during the first two years, while few studies have analyzed weight, height, and Body Mass Index (BMI) changes in children later in life. The present study aims to assess the association between serum PFAS levels and growth and development in adolescents. Through multiple linear regression, we explored the relationship between serum PFAS levels and weight, height, and BMI in adolescents (aged 12 to 19 years) participating in the 2015-2018 National Health and Nutrition Examination Survey (NHANES). After covariate adjustment, serum perfluorooctane sulfonic acid (PFOS) was associated with decreased weight-for-age z-score in females (tertile 2 of PFOS: ß = - 0.22, 95% CI: -0.68, 0.23; tertile 3 of PFOS: ß = - 0.78, 95% CI: -1.20, - 0.36; P for trend = 0.009), while serum perfluorononanoic acid (PFNA) was associated with decreased weight-for-age z-score in males (tertile 2 of PFNA: ß = 0.09, 95% CI: -0.40, 0.58; tertile 3 of PFNA: ß = - 0.44, 95% CI: -0.86, - 0.03; P for trend = 0.018).In addition, serum PFOS was associated with decreased BMI z-score in all participants (tertile 2 of PFOS: ß = - 0.15, 95% CI: -0.46, 0.16; tertile 3 of PFOS: ß = - 0.63, 95% CI: -1.06, - 0.20; P for trend = 0.013). CONCLUSION: Our findings indicate a negative association between serum PFAS levels and weight, and BMI among adolescents, and we observed that the negative association was sex-specific in weight. WHAT IS KNOWN: • Wide exposure to PFAS has led to concerns about its adverse effects, especially for children during their growth and development. • So far, much research has evaluated the effects of prenatal PFAS exposures on children, and the current results are mixed, with some research showing that there are sex differences. WHAT IS NEW: • This study investigated the relationship between serum PFAS levels and height and weight in adolescents and is a good addition to current research. • Our study found that exposure to PFAS negatively affects adolescent growth and development and that this effect is sex-specific.

Long-wave infrared photothermoelectric detectors with ultrahigh polarization sensitivity.

Filter-free miniaturized polarization-sensitive photodetectors have important applications in the next-generation on-chip polarimeters. However, their polarization sensitivity is thus far limited by the intrinsic low diattenuation and inefficient photon-to-electron conversion. Here, we implement experimentally a miniaturized detector based on one-dimensional tellurium nanoribbon, which can significantly improve the photothermoelectric responses by translating the polarization-sensitive absorption into a large temperature gradient together with the finite-size effect of a perfect plasmonic absorber. Our devices exhibit a zero-bias responsivity of 410 V/W and an ultrahigh polarization ratio (2.5 × 104), as well as a peak polarization angle sensitivity of 7.10 V/W•degree, which is one order of magnitude higher than those reported in the literature. Full linear polarimetry detection is also achieved with the proposed device in a simple geometrical configuration. Polarization-coded communication and optical strain measurement are demonstrated showing the great potential of the proposed devices. Our work presents a feasible solution for miniaturized room-temperature infrared photodetectors with ultrahigh polarization sensitivity.

Five Tibetan patent medicines orally for ischemic stroke: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan Patent Medicines (TPMs) have unique advantages in the treatment of ischemic stroke (IS) with the features of multi-component, multi-channel, and multi-target. In China, five TPMs mainly consisting of precious medicinal materials such as gold, pearls, and agate are widely utilized to treat IS and have achieved good results according to the current clinical practice. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of the five TPMs orally in treating IS and provide a reference for future clinical application and research. MATERIALS AND METHODS: We searched the following 24 databases up to December 11, 2022: China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, Chinese Biomedical Database (CBM), PubMed, Embase, Web of Science, MEDLINE, Scopus, the Cochrane Library, ScienceDirect, etc. Comprehensive searches for randomized controlled trials (RCTs) of the five TPMs for IS were conducted. Outcome measures included clinical effective rate, neurological impairment score, activities of daily living (ADL), hematologic indices, and adverse events (AEs). The meta-regression, subgroup analyses, and sensitivity analyses were conducted to explore the sources of heterogeneity. We assessed the evidence grade of outcomes via the GRADE system. TSA software was used for trial sequential analyses of the clinical effective rate, neurological impairment score, and ADL. RESULTS: 17 RCTs (1603 patients) met our criteria. Compared with the control groups, the five TPMs showed greater improvement in clinical effective rate (RR = 1.23, 95% CI 1.17 to 1.29, P < 0.00001), neurological impairment score (SMD = -1.71, 95% CI -2.31 to -1.10, P < 0.00001), ADL (SMD = 1.97, 95% CI 1.26 to 2.68, P < 0.00001), hematocrit (MD = -1.56, 95% CI -2.83 to -0.29, P = 0.02), and hypersensitive-c-reactive-protein (MD = -2.96, 95% CI -3.30 to -2.61, P < 0.00001). AEs were reported in four RCTs and there was no statistical difference between groups (RD = -0.00, 95% CI -0.04 to 0.03, P = 0.82). The quality of evidence of the outcomes was rated as low to very low according to the GRADE system. The results of TSA provided firm evidence for the significant effect of the five TPMs on clinical effective rate, neurological impairment score, and ADL. CONCLUSIONS: This review showed that the five TPMs were beneficial in improving clinical effective rate, neurological impairment scores, and ADL. However, no definite conclusions for hematologic indices and AEs were drawn due to insufficient studies. Further high-quality clinical trials are required to confirm these findings.

Preparation and Bioevaluation of a Novel 99mTc-Labeled Glucose Derivative Containing Cyclohexane as a Promising Tumor Imaging Agent.

To develop novel tumor imaging agents with high tumor uptake and excellent tumor/non-target ratios, a glucose derivative containing cyclohexane (CNMCHDG) was synthesized and labeled with Tc-99m. [99mTc]Tc-CNMCHDG was prepared by a kit formulation that was straightforward to operate and fast. Without purification, [99mTc]Tc-CNMCHDG had a high radiochemical purity of over 95% and great in vitro stability and hydrophilicity (log P = -3.65 ± 0.10). In vitro cellular uptake studies showed that the uptake of [99mTc]Tc-CNMCHDG was significantly inhibited by pre-treatment with D-glucose and increased by pre-treatment with insulin. Preliminary cellular studies have demonstrated that the mechanism by which the complex enters into cells may be related to GLUTs. The results of biodistribution and SPECT imaging studies displayed high tumor uptake and good retention of [99mTc]Tc-CNMCHDG in A549 tumor-bearing mice (4.42 ± 0.36%ID/g at 120 min post-injection). Moreover, [99mTc]Tc-CNMCHDG exhibited excellent tumor-to-non-target ratios and a clean imaging background and is a potential candidate for clinical transformation.

The influence of social status on children's merit-based resource allocation: The potential explanation of expectation.

How 3- to 11-year-old children integrate recipients' merit and social status when allocating resources was examined in 2021 and 2022. Study 1 (Han Chinese, n = 309, 150 girls) showed that while children prioritized merit, they developed from favoring high-status recipients to favoring low-status recipients. Study 2 (n = 194, 98 girls) and Study 3 (n = 138, 68 girls) revealed that children held stereotypes about the relation between merit and social status which shifted with age from expecting high-status peers to expecting low-status peers to work harder, these expectations corresponded allocation decisions. These findings suggest children shift from perpetuating to rectifying inequity and changing stereotypes about people of different social status may serve an important function in the process.

Electrodeposited NaYF4:Yb3+, Er3+ up-conversion films for flexible neural device construction and near-infrared optogenetics.

Near-infrared optogenetics based on up-conversion materials provides a promising tool for the dissection of neural circuit functions in deep brain regions. However, it remains a challenge to combine near-infrared up-conversion optogenetic stimulation with high-density electrophysiological recording in a minimally invasive manner. Here, we develop a flexible device for simultaneous electrophysiological recording and near-infrared optogenetics. The flexible device is constructed by integrating polymer-based flexible recording microelectrodes with electrodeposited NaYF4:Yb3+, Er3+ up-conversion films that can convert deep-tissue-penetrating near-infrared light into visible light for optogenetic activation of C1V1-expressing neurons. The emission properties of the up-conversion films are optimized for green light emission to stimulate C1V1 opsins. Owing to their minimized surgical footprint and high mechanical compliance, chronically implanted devices enable simultaneous electrophysiological recording and near-infrared optogenetic modulation of neuronal activities in the brain.

A High-Affinity 64Cu-Labeled Ligand for PET Imaging of Hepsin: Design, Synthesis, and Characterization.

Hepsin, a cell surface serine protease, is a potential biomarker for the detection of prostate cancer due to its high expression in prostate cancer but not in normal prostate. This study aimed to develop a radioligand for positron emission tomography (PET) imaging of hepsin. Six leucine-arginine (Leu-Arg) dipeptide derivatives (two diastereomers for each of three ligands) were synthesized and evaluated for their binding affinities and selectivity for hepsin. Based on the binding assay, a natCu-1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA)-conjugated ligand (3B) was selected for the development of a PET radioligand. [64Cu]3B was synthesized by labeling the DOTA-conjugated compound 11B with [64Cu]CuCl2 at 80 °C for 20 min. The radioligand was evaluated for prostate cancer cell binding and PET imaging in a prostate tumor mouse model. The results demonstrated that [64Cu]3B exhibited high binding to LNCaP cells, intermediate binding to 22Rv1 cells, and low binding to PC3 cells. PET studies of [64Cu]3B in mice, implanted with 22Rv1 and PC3 cells on each flank, revealed that the radioligand uptake was high and persistent in the 22Rv1 tumors over time, whereas it was low in PC3 tumors. The results of this study suggest that [64Cu]3B is a promising PET radioligand for hepsin imaging.

CAMTA1 gene affects the ischemia-reperfusion injury by regulating CCND1.

Epigenetic modulations lead to changes in gene expression, including DNA methylation, histone modifications, and noncoding RNAs. In recent years, epigenetic modifications have been related to the pathogenesis of different types of cancer, cardiovascular disease, and other diseases. Emerging evidence indicates that DNA methylation could be associated with ischemic stroke (IS) and plays a role in pathological progression, but the underlying mechanism has not yet been fully understood. In this study, we used human methylation 850K BeadChip to analyze the differences in gene methylation status in the peripheral blood samples from two groups (3 IS patients vs. 3 healthy controls). According to their bioinformatics profiling, we found 278 genes with significantly different methylation levels. Seven genes with the most significant methylation modifications were validated in two expanded groups (100 IS patients vs. 100 healthy controls). The CAMTA1 gene had significantly different methylation changes in patients compared to the controls. To understand the CAMTA1 function in stroke, we generated CAMTA1 knockout in SH-SY5Y cells. RNA seq results in CAMTA1 knockout cells revealed the pathways and gene set enrichments involved in cellular proliferation and cell cycle. Furthermore, a series of experiments demonstrated that in the oxygen-glucose deprivation/re-oxygenation (OGD/R) model system, the expression of cyclin D1, an essential regulator of cell cycle progression, was increased in SH-SY5Y CAMTA1 KO cells. Increasing evidence demonstrated that ischemic stress could inappropriately raise cyclin D1 levels in mature neurons. However, the molecular signals leading to an increased cyclin D1 level are unclear. Our findings demonstrate for the first time that the CAMTA1 gene could regulate cyclin D1 expression and implicate their role in strokes.

Effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis: a multi-center, double-blind, randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis. METHODS: This was a multi-center, double-blind, double-dummy, positive-controlled, parallel randomized controlled clinical trial with 1? allocation. We recruited 404 patients with dizziness caused by cerebral arteriosclerosis (blood stasis symptom pattern) in 10 hospitals in China. GBE50 group received GBE50 and Naoxinqing tablet (NXQ) of mimetic agent, control group received NXQ and GBE50 of mimetic agent. The main outcome was Traditional Chinese Medicine (TCM) symptom pattern score of blood stasis after 6 weeks. The secondary outcomes were changes in the dizziness handicap inventory (DHI) score, vertigo visual analogue scale (VAS) score, the university of California vertigo questionnaire (UCLA-DQ) score and single-item symptom score of TCM from baseline to 2, 4 and 6 weeks. Safety indicators included the incidence of adverse events, severe adverse events and laboratory examination including blood routine, liver function, renal function, and so forth. RESULTS: The total effective rate of TCM symptom pattern score in the GBE50 group after 6 weeks of treatment was higher than that in the control group, the difference in rate was statistically significant (92.67% vs 83.07%, P = 0.004). Compared with the control group, there was no difference in the incidence of adverse reactions (9.95% vs 14.85%, P = 0.136). CONCLUSION: The treatment of dizziness caused by cerebral arteriosclerosis with GBE50 is effective, safe and reliable.

Preparation and Bioevaluation of 99mTc-Labeled FAP Inhibitors as Tumor Radiotracers to Target the Fibroblast Activation Protein.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts (CAFs) in a majority of human epithelial cancers. With low expression in normal organs, FAP has become a promising molecular target for tumor theranostics. To develop a lower cost and more widely available alternative to positron emission tomography (PET), two isocyanide-containing FAP inhibitors (CN-C5-FAPI and CN-PEG4-FAPI) were synthesized and radiolabeled with 99mTc to obtain [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ in high yields (>95%). They showed good stability in saline and mouse serum. The partition coefficient (log P) values of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were -0.86 ± 0.03 and -2.38 ± 0.07, respectively, indicating that they were good hydrophilic complexes. The low nanomolar IC50 values of CN-C5-FAPI and CN-PEG4-FAPI indicated that they had specificity to FAP. In vitro cellular uptake and blocking experiments implied a FAP-targeted uptake mechanism. The nanomolar Kd values from the saturation binding assay indicated that they had significantly high target affinity to FAP. The biodistribution and blocking study in BALB/c nude mice bearing U87MG tumors showed that both exhibited specific tumor uptake. [99mTc][Tc-(CN-PEG4-FAPI)6]+ showed a higher tumor uptake and a higher tumor/nontarget ratio than [99mTc][Tc-(CN-C5-FAPI)6]+. The results of micro-single-photon emission computed tomography (SPECT) imaging studies of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were in accordance with the biodistribution results, suggesting that [99mTc][Tc-(CN-PEG4-FAPI)6]+ is a promising tumor imaging agent for targeting FAP.

Epigenetic regulation mechanism of DNA methylation and miRNAs on the expression of the ALOX5AP gene in patients with ischemic stroke.

5-lipoxygenase-activating protein (FLAP), encoded by the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene, can adjust the biogenesis of proinflammatory leukotrienes to increase the adhesion and permeability of the vascular internal wall. Moreover, it participates in the process of atherosclerosis and is closely associated with ischemic stroke (IS). Accumulating evidence has shown that the expression levels of the ALOX5AP gene are upregulated in patients with IS. However, the mechanism of ALOX5AP action in IS remain elusive. The present study hypothesized that epigenetic regulation, including DNA methylation and microRNA (miR/miRNA) regulation, affects the expression levels of the ALOX5AP gene. Therefore, 200 patients with a first diagnosis of acute IS and 200 healthy control subjects were enrolled in the present study. Initially, the mRNA expression levels of the ALOX5AP gene were examined by reverse transcription-quantitative PCR. It was found that the mRNA levels of ALOX5AP gene in the IS group were significantly higher compared with controls (P<0.05). Subsequently, the methylation status of 17 CpG sites located in the promoter region of ALOX5AP was assessed by MethyTarget sequencing. However, the levels of methylation exhibited no significant differences between IS and control groups (P>0.05). Moreover, the expression levels of miR-335 and miR-495 were examined as two potential miRNAs targeting the ALOX5AP gene. The expression levels of miR-335 and miR-495 in the IS group were significantly lower compared with the control group (P<0.05). Finally, the luciferase assay results indicated that the luciferase activity of the experimental group following co-transfection of miRNA mimic and wild-type reporter gene plasmid was significantly lower compared with the other experimental groups (P<0.05), suggesting that miR-335 and miR-495 could specifically bind to the 3'-untranslated region of the ALOX5AP gene, thereby downregulating its expression. The present study provided preliminary evidence demonstrating that epigenetic regulation affects the expression of the ALOX5AP gene in patients with IS.

Preparation and Evaluation of Novel Folate Isonitrile 99mTc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors.

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specific tumor uptake. Compared with [99mTc]Tc-CN5FA, the tumor/muscle ratios of [99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two 99mTc complexes have potential as tumor imaging agents to target folate receptors.

Investigation of α-Synuclein Species in Plasma Exosomes and the Oligomeric and Phosphorylated α-Synuclein as Potential Peripheral Biomarker of Parkinson's Disease.

α-Synuclein (α-syn), especially its abnormal oligomeric and phosphorylated form, plays a critical role in the pathogenesis of Parkinson's disease (PD). Plasma exosomal α-syn species have been shown to be a promising PD biomarker. However, whether different α-syn species in plasma exosomes (the oligomeric α-syn and the Ser129 phosphorylated α-syn (p-α-syn)) which represent the PD pathogenesis in the brain could be specific peripheral PD biomarker haven't been well elucidated. In this study, we successfully extracted and identified the human plasma exosomes, and the CNS-derived exosomes were detected. The different aggregation status, localization and degradation characteristics of α-syn and p-α-syn in the plasma exosomes between PD patients and healthy controls were further analyzed. The results suggested that α-syn and p-α-syn in the plasma exosomes of PD patients showed poor solubility after protease K (PK) treatment. Aggregated α-syn and p-α-syn existed both inside and on the membrane surface of plasma exosomes. The Receiver operating characteristic (ROC) performance of α-syn oligomer/total α-syn in exosomes was moderately helpful in PD diagnosis (AUC = 0.71, sensitivity = 60.5%, specificity = 59.4%), and the ratio of p-α-syn oligomer/total p-α-syn showed similar result (AUC = 0.69, sensitivity = 60.0%, specificity = 59.5%). This study indicates that the oligomeric α-syn/total α-syn and oligomeric p-α-syn/total p-α-syn ratio in plasma exosomes may be applied to assist the PD diagnosis, which needs further research.

Radiolabeling and evaluation of a novel [99mTcN]2+ complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging.

In order to find a 99mTc-labeled deferoxamine radiotracer for bacterial infection imaging, deferoxamine dithiocarbamate (DFODTC) was successfully synthesized and it was radiolabeled with [99mTcN]2+ core to prepare the 99mTcN(DFODTC)2 complex. 99mTcN(DFODTC)2 was obtained with high radiochemical purity without further purification. The complex was lipophilic and exhibited good in vitro stability. According to the result of bacterial binding study, the binding of 99mTcN(DFODTC)2 to bacteria was specific. Biodistribution in mice study indicated that 99mTcN(DFODTC)2 had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses at 120 min after injection, which showed that the radiotracer could differentiate between bacterial infection and sterile inflammation. SPECT/CT images showed that there was a clear accumulation in infection sites, suggesting that 99mTcN(DFODTC)2 could be a potential bacterial infection imaging radiotracer.

Material and relational asymmetry: The role of receivers' wealth and power status in children's resource allocation.

Asymmetries in social status, specifically social status related to wealth and relational power, appear to influence the ways in which children allocate resources. However, the impact of wealth and relational power status on children's resource allocation decisions has yet to be examined among children developing within a Chinese cultural context. In addition, how children weight the relative importance of these factors when they exist concurrently is not well understood. In Study 1, we examined the impact of recipients' wealth and relational power status on Chinese children's (3- to 8-year-olds; N = 199) allocation decisions. We found that across both categories of social status, 3- and 4-year-olds gave more to high-status individuals, whereas 7- and 8-year-olds gave more to low-status individuals, despite younger children also showing a strong egalitarian preference when the resources could be allocated equally. In Study 2, we investigated how children (3- to 8-year-olds; N = 219) weigh the relative importance of these two types of social status in situations where the level of recipients' wealth and relational power were either consistent or in conflict. When they needed to allocate the resources unequally, the youngest children were found to place greater emphasis on wealth over relational power and favored the high-status individual, whereas older children tended to favor the low-status individual and placed greater importance on relational power over wealth. Overall, we found a consistent age-related shift from favoring high-status individuals toward compensating low-status individuals, suggesting a developing concern for social equity.

Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents.

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [99mTc][Tc(I)]+ core to obtain [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF were specific to bacteria. Compared with [99mTc]Tc-CN4NF, biodistribution studies of [99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.