NIEND: neuronal image enhancement through noise disentanglement.

MOTIVATION: The full automation of digital neuronal reconstruction from light microscopic images has long been impeded by noisy neuronal images. Previous endeavors to improve image quality can hardly get a good compromise between robustness and computational efficiency. RESULTS: We present the image enhancement pipeline named Neuronal Image Enhancement through Noise Disentanglement (NIEND). Through extensive benchmarking on 863 mouse neuronal images with manually annotated gold standards, NIEND achieves remarkable improvements in image quality such as signal-background contrast (40-fold) and background uniformity (10-fold), compared to raw images. Furthermore, automatic reconstructions on NIEND-enhanced images have shown significant improvements compared to both raw images and images enhanced using other methods. Specifically, the average F1 score of NIEND-enhanced reconstructions is 0.88, surpassing the original 0.78 and the second-ranking method, which achieved 0.84. Up to 52% of reconstructions from NIEND-enhanced images outperform all other four methods in F1 scores. In addition, NIEND requires only 1.6 s on average for processing 256 × 256 × 256-sized images, and images after NIEND attain a substantial average compression rate of 1% by LZMA. NIEND improves image quality and neuron reconstruction, providing potential for significant advancements in automated neuron morphology reconstruction of petascale. AVAILABILITY AND IMPLEMENTATION: The study is conducted based on Vaa3D and Python 3.10. Vaa3D is available on GitHub (https://github.com/Vaa3D). The proposed NIEND method is implemented in Python, and hosted on GitHub along with the testing code and data (https://github.com/zzhmark/NIEND). The raw neuronal images of mouse brains can be found at the BICCN's Brain Image Library (BIL) (https://www.brainimagelibrary.org). The detailed list and associated meta information are summarized in Supplementary Table S3.

[Effect of collagen sponge on the healing process of alveolar fossa after tooth extraction in rats].

PURPOSE: To investigate the effect of collagen sponge on early bone healing process of alveolar fossa after tooth extraction in rats. METHODS: A total of 16 healthy female SD rats were selected. Animal models with tooth extraction were established. The right alveolar fossa inserted with collagen sponge was as the experimental group, and the left alveolar fossa was as the control group with treatment. The rats were sacrificed 1, 2, 4 and 8 weeks after tooth extraction, and the osteogenesis of alveolar fossa was observed. Real-time quantitative PCR (qt-PCR) was used to detect the changes of osteogenesis related gene expression. SPSS 19.0 software package was used for statistical analysis. RESULTS: After surgery, alveolar cavity healing was significantly better in the experimental group than in the control group. Osterix, Runx2 and Vegf genes were expressed in the experimental group and the control group, and the expression levels of related genes in the experimental group were significantly higher than the control group 1, 2, 4 and 8 weeks after surgery(P＜0.05). CONCLUSIONS: Collagen sponge could promote early alveolar bone healing, possibly related to the expression level of osteogenic genes regulated by collagen sponge.

Full-Spectrum Neuronal Diversity and Stereotypy through Whole Brain Morphometry.

We conducted a large-scale study of whole-brain morphometry, analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We spatially registered 205 mouse brains and associated data from six Brain Initiative Cell Census Network (BICCN) data sources covering three major imaging modalities from five collaborative projects to the Allen Common Coordinate Framework (CCF) atlas, annotated 3D locations of cell bodies of 227,581 neurons, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1,891 neurons along with their axonal motifs, and detected 2.58 million putative synaptic boutons. Our analysis covers six levels of information related to neuronal populations, dendritic microenvironments, single-cell full morphology, sub-neuronal dendritic and axonal arborization, axonal boutons, and structural motifs, along with a quantitative characterization of the diversity and stereotypy of patterns at each level. We identified 16 modules consisting of highly intercorrelated brain regions in 13 functional brain areas corresponding to 314 anatomical regions in CCF. Our analysis revealed the dendritic microenvironment as a powerful method for delineating brain regions of cell types and potential subtypes. We also found that full neuronal morphologies can be categorized into four distinct classes based on spatially tuned morphological features, with substantial cross-areal diversity in apical dendrites, basal dendrites, and axonal arbors, along with quantified stereotypy within cortical, thalamic and striatal regions. The lamination of somas was found to be more effective in differentiating neuron arbors within the cortex. Further analysis of diverging and converging projections of individual neurons in 25 regions throughout the brain reveals branching preferences in the brain-wide and local distributions of axonal boutons. Overall, our study provides a comprehensive description of key anatomical structures of neurons and their types, covering a wide range of scales and features, and contributes to our understanding of neuronal diversity and its function in the mammalian brain.

Trait stacking simultaneously enhances provitamin A carotenoid and mineral bioaccessibility in biofortified Sorghum bicolor.

Vitamin A, iron, and zinc deficiencies are major nutritional inadequacies in sub-Saharan Africa and disproportionately affect women and children. Biotechnology strategies have been tested to individually improve provitamin A carotenoid or mineral content and/or bioaccessibility in staple crops including sorghum (Sorghum bicolor). However, concurrent carotenoid and mineral enhancement has not been thoroughly assessed and antagonism between these chemical classes has been reported. This work evaluated two genetically engineered constructs containing a suite of heterologous genes to increase carotenoid stability and pathway flux, as well as phytase to catabolize phytate and increase mineral bioaccessibility. Model porridges made from transgenic events were evaluated for carotenoid and mineral content as well as bioaccessibility. Transgenic events produced markedly higher amounts of carotenoids (26.4 µg g-1 DW) compared to null segregants (4.2 µg g-1 DW) and wild-type control (Tx430; 3.7 µg g-1 DW). Phytase activation by pre-steeping flour resulted in significant phytate reduction (9.4 to 4.2 mg g-1 DW), altered the profile of inositol phosphate catabolites, and reduced molar ratios of phytate to iron (16.0 to 4.1), and zinc (19.0 to 4.9) in engineered material, suggesting improved mineral bioaccessibility. Improved phytate : mineral ratios did not significantly affect micellarization and bioaccessible provitamin A carotenoids were over 23 times greater in transgenic events compared to corresponding null segregants and wild-type controls. A 200 g serving of porridge made with these transgenic events provide an estimated 53.7% of a 4-8-year-old child's vitamin A estimated average requirement. These data suggest that combinatorial approaches to enhance micronutrient content and bioaccessibility are feasible and warrant further assessment in human studies.

Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.

PURPOSE: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis. EXPERIMENTAL DESIGN: Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival formalin-fixed paraffin-embedded tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 494 of 541 patients (91.3%) had adequate tissue for analysis. A total of 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n = 360; 80.2%) was associated with significantly prolonged PFS [median: 8.5 vs. 4.4 months; HR, 0.73; 95% confidence interval (CI), 0.56-0.95; P = 0.02] and OS [median: 16.4 vs. 8.9 months; HR, 0.66 95% CI, 0.50-0.86; P = 0.002]. The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obtained by biopsy or surgical resection. CONCLUSIONS: High tumor AREG/EREG expression was associated with superior survival outcomes from anti-EGFR therapy in mCRC, including in right PTL disease. AREG/EREG IHC assessment could aid therapeutic decisions in routine practice. See related commentary by Randon and Pietrantonio, p. 4021.

Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway.

Objective: Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms. Methods: First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and ß-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and ß-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and ß-sitosterol on TNBC in vivo. The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis. Results: Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and ß-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and ß-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and ß-sitosterol produced similar outcomes. Conclusion: The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC.

Chronic urticaria patients are interested in apps to monitor their disease activity and control: A UCARE CURICT analysis.

BACKGROUND: Information/communication technologies such as mobile phone applications (apps) would enable chronic urticaria (CU) patients to self-evaluate their disease activity and control. Yet, recently Antó et al (2021) reported a global paucity of such apps for patients with CU. In this analysis, we assessed patient interest in using apps to monitor CU disease activity and control using questions from the chronic urticaria information and communication technologies (CURICT) study. METHODS: The methodology for CURICT has been reported. Briefly, a 23-item questionnaire was completed by 1841 CU patients from 17 UCAREs across 17 countries. Here, we analyzed patient responses to the CURICT questions on the use of apps for urticaria-related purposes. RESULTS: As previously published, the majority of respondents had chronic spontaneous urticaria (CSU; 63%; 18% chronic inducible urticaria (CIndU) [CIndu]; 19% with both), were female (70%) and in urban areas (75%). Over half of patients were very/extremely interested in an app to monitor disease activity (51%) and control (53%), while only ∼1/10 were not. Patients with both urticaria types versus those with CSU only (odds ratio [OR], 1.36 [1.03-1.79]) and females versus males (OR [95% CI], 1.47 [1.17-1.85]) were more likely to be very to extremely interested in an app to assess disease control. CONCLUSIONS: Overall, half of the patients with CU were very to extremely interested in using an app to assess their disease activity and control. Development of well-designed apps, specific to disease types (CSU, CIndU, CSU + CIndU, etc), validated by experts across platforms would help improve the management and possibly outcomes of CU treatment while providing important patient information to be used in future research.

The prevalence and year lived with disability of atopic dermatitis in China: Findings from the global burden of disease study 2019.

BACKGROUND: Atopic dermatitis (AD) is a chronic disease with growing prevalence and has become a global public health problem. However, little is known about the burden caused by AD in China. OBJECTIVE: To access the prevalence and burden of AD in China. METHODS: We estimated the prevalence and year lived with disability (YLD) of AD in China, by different age and sex groups. We also compared the burden of AD in China with other countries in the Group of Twenty (G20). We analyzed the changes in the number of AD patients and their YLDs by cause decomposition from 1990 to 2019. RESULTS: AD was the twenty-fourth leading cause of the burden of 369 diseases in China in 2019. From 1990 to 2019, the age-standardized prevalence and YLD rate of AD in China increased by 1.04% and 1.43% respectively, which were the second and the largest increase among the G20 and both higher than the global average (-4.29% and -4.14%). The number of patients with AD increased by 25.65%, of which 20.16% was due to population growth, 3.85% due to population aging, and 1.64% due to age-specific prevalence. Both the prevalence and YLD rate of AD were higher in 1 to 4 year-olds and 95+ years age group. Before the age of 10, the prevalence and YLD rate of AD in males were higher than those in females, while there was a marked sex shift at the ages of 10 to 14. CONCLUSION: AD is a serious public health problem in China. Substantial variations exist in burden due to AD between male and female, and in age groups. Considering these findings will be important for developing preventive strategies and treatments to reduce the burden of AD.

The Emerging Role of Mast Cells in Response to Fungal Infection.

Mast cells (MCs) have been considered as the core effector cells of allergic diseases. However, there are evidence suggesting that MCs are involved in the mechanisms of fungal infection. MCs are mostly located in the border between host and environment and thus may have easy contact with the external environmental pathogens. These cells express receptors which can recognize pathogen-associated molecular patterns such as Toll-like receptors (TLR2/4) and C-type Lectins receptors (Dectin-1/2). Currently, more and more data indicate that MCs can be interacted with some fungi (Candida albicans, Aspergillus fumigatus and Sporothrix schenckii). It is demonstrated that MCs can enhance immunity through triggered degranulation, secretion of cytokines and chemokines, neutrophil recruitment, or provision of extracellular DNA traps in response to the stimulation by fungi. In contrast, the involvement of MCs in some immune responses may lead to more severe symptoms, such as intestinal barrier function loss, development of allergic bronchial pulmonary aspergillosis and increased area of inflammatory in S. schenckii infection. This suggests that MCs and their relevant signaling pathways are potential treatment regimens to prevent the clinically unwanted consequences. However, it is not yet possible to make definitive statements about the role of MCs during fungal infection and/or pathomechanisms of fungal diseases. In our article, we aim to review the function of MCs in fungal infections from molecular mechanism to signaling pathways, and illustrate the role of MCs in some common host-fungi interactions.

How are patients with chronic urticaria interested in using information and communication technologies to guide their healthcare? A UCARE study.

BACKGROUND: Patients with chronic urticaria (CU) are increasingly using information and communication technologies (ICTs) to manage their health. What CU patients expect from ICTs and which ICTs they prefer remains unknown. We assessed why CU patients use ICTs, which ones they prefer, and what drives their expectations and choices. METHODS: In this cross-sectional study, 1841 patients across 17 countries were recruited at UCAREs (Urticaria Centers of Reference and Excellence). Patients with CU who were >12 years old completed a 23-item questionnaire. RESULTS: Most patients were interested in receiving disease information (87.3%), asking physicians about CU (84.1%), and communicating with other patients through ICTs (65.6%). For receiving disease information, patients preferred one-to-one and one-to-many ICTs, especially web browsers. One-to-one ICTs were also the ICTs of choice for asking physicians about urticaria and for communicating with other patients, and e-mail and WhatsApp were the preferred ICTs, respectively. Many-to-many ICTs such as Facebook, Instagram, LinkedIn, and Twitter were least preferred for all 3 purposes. Living in rural areas and higher education were linked to higher odds of being interested in receiving disease information, asking physicians, and communicating with patients through ICTs. CONCLUSIONS: Most patients and especially patients with higher education who live in rural areas are interested in using ICTs for their healthcare, but prefer different ICTs for different purposes, ie, web browsers for obtaining information, e-mail for asking physicians, and WhatsApp for communicating with other patients. Our findings may help to improve ICTs for CU.

Case Report: Omalizumab for Chronic Spontaneous Urticaria in Pregnancy.

Most chronic spontaneous urticaria (CSU) patients are female, and pregnancy can aggravate the disease activity of patients, but little is known about the efficacy and safety of omalizumab in pregnant CSU patients. We report two pregnant CSU patients treated with omalizumab and review the published information on omalizumab treatment during 11 pregnancies. The outcomes reported on patients with known pregnancies showed they had normal pregnancies and healthy babies as well as complete control of their CSU. The two new cases we reported support the view that omalizumab could be an effective and safe treatment option for pregnant and breastfeeding CSU patients. Further high-quality studies need to be carried out in order to obtain more information on the long-term efficacy and safety of the use of omalizumab during pregnancy in patients with chronic urticaria, including CSU.

Artificial Intelligence-Assisted Amphiregulin and Epiregulin IHC Predicts Panitumumab Benefit in RAS Wild-Type Metastatic Colorectal Cancer.

PURPOSE: High tumor mRNA levels of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are associated with anti-EGFR agent response in metastatic colorectal cancer (mCRC). However, ligand RNA assays have not been adopted into routine practice due to issues with analytic precision and practicality. We investigated whether AREG/EREG IHC could predict benefit from the anti-EGFR agent panitumumab. EXPERIMENTAL DESIGN: Artificial intelligence algorithms were developed to assess AREG/EREG IHC in 274 patients from the PICCOLO trial of irinotecan with or without panitumumab (Ir vs. IrPan) in RAS wild-type mCRC. The primary endpoint was progression-free survival (PFS). Secondary endpoints were RECIST response rate (RR) and overall survival (OS). Models were repeated adjusting separately for BRAF mutation status and primary tumor location (PTL). RESULTS: High ligand expression was associated with significant PFS benefit from IrPan compared with Ir [8.0 vs. 3.2 months; HR, 0.54; 95% confidence interval (CI), 0.37-0.79; P = 0.001]; whereas low ligand expression was not (3.4 vs. 4.4 months; HR, 1.05; 95% CI, 0.74-1.49; P = 0.78). The ligand-treatment interaction was significant (P interaction = 0.02) and remained significant after adjustment for BRAF-mutation status and PTL. Likewise, RECIST RR was significantly improved in patients with high ligand expression (IrPan vs. Ir: 48% vs. 6%; P < 0.0001) but not those with low ligand expression (25% vs. 14%; P = 0.10; P interaction = 0.01). The effect on OS was similar but not statistically significant. CONCLUSIONS: AREG/EREG IHC identified patients who benefitted from the addition of panitumumab to irinotecan chemotherapy. IHC is a practicable assay that may be of use in routine practice.

99mTc-3SPboroxime: A neutral 99mTc(III) radiotracer with high heart uptake and long myocardial retention.

BACKGROUND: 99mTc-3SPboroxime is a 99mTc(III) complex with high initial heart uptake comparable to that of 99mTc-Teboroxime, but with significantly longer myocardial retention in Sprague-Dawley rats. This study was performed to demonstrate its feasibility on myocardial perfusion imaging and myocardial blood flow quantification in swine models. METHODS: Dynamic single-photon emission computed tomography (SPECT) studies with 99mTc-3SPboroxime were performed in normal (with/without dipyridamole, n = 9) and acute myocardial infarction (AMI) swine (n = 3) in comparison with 99mTc-Teboroxime and 99mTc-Sestamibi. List-mode acquisitions were immediately started after injection and continued for 15 minutes. Regions of interest were drawn on heart (infarct and remote areas of AMI swine) and liver to generate time activity curves. Heart/liver and infarct/remote radioactivity ratios were calculated. One-tissue compartment model was implemented to obtain K1 and K2 values. RESULTS: The initial heart uptake of 99mTc-3SPboroxime was close to that of 99mTc-Teboroxime, but higher than that of 99mTc-Sestamibi. 99mTc-3SPboroxime had a myocardial retention longer than that of 99mTc-Teboroxime. The heart/liver ratio of 99mTc-3SPboroxime was higher than that of 99mTc-Teboroxime at later stage (13-15 minutes post-injection). The K1 value of 99mTc-3SPboroxime was much higher than that of 99mTc-Sestamibi, and the K2 value was significantly lower than that of 99mTc-Teboroxime both at rest and dipyridamole stress (rest K1: 0.63 ± 0.11 vs 0.40 ± 0.04 mL·min-1·g-1, P = 0.027; stress K1: 0.89 ± 0.05 vs 0.54 ± 0.08 mL·min-1·g-1, P = 0.031; rest K2: 0.22 ± 0.04 vs 0.33 ± 0.11 mL·min-1·g-1, P = 0.003; stress K2: 0.31 ± 0.03 vs 0.60 ± 0.30 mL·min-1·g-1, P = 0.047). High quality SPECT images could be obtained in any of the 5 minutes windows over the first 15 minutes after injection of 99mTc-3SPboroxime in normal and AMI swine models. Apical and anterior perfusion defects were clearly visualized in AMI swine. CONCLUSION: 99mTc-3SPboroxime is a promising radiotracer for future clinical translation considering its heart uptake, heart/liver ratio and SPECT image quality, as well as the advantage over 99mTc-Sestamibi in the definition of stress flow.

The usage, quality and relevance of information and communications technologies in patients with chronic urticaria: A UCARE study.

BACKGROUND: Chronic urticaria (CU) is characterized by itchy recurrent wheals, angioedema, or both for 6 weeks or longer. CU can greatly impact patients' physical and emotional quality of life. Patients with chronic conditions are increasingly seeking information from information and communications technologies (ICTs) to manage their health. The objective of this study was to assess the frequency of usage and preference of ICTs from the perspective of patients with CU. METHODS: In this cross-sectional study, 1800 patients were recruited from primary healthcare centers, university hospitals or specialized clinics that form part of the UCARE (Urticaria Centers of Reference and Excellence) network throughout 16 countries. Patients were >12 years old and had physician-diagnosed chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CIndU). Patients completed a 23-item questionnaire containing questions about ICT usage, including the type, frequency, preference, and quality, answers to which were recorded in a standardized database at each center. For analysis, ICTs were categorized into 3 groups as follows: one-to-one: SMS, WhatsApp, Skype, and email; one-to-many: YouTube, web browsers, and blogs or forums; many-to-many: Instagram, Twitter, Facebook, and LinkedIn. RESULTS: Overall, 99.6% of CU patients had access to ICT platforms and 96.7% had internet access. Daily, 85.4% patients used one-to-one ICT platforms most often, followed by one-to-many ICTs (75.5%) and many-to-many ICTs (59.2%). The daily ICT usage was highest for web browsers (72.7%) and WhatsApp (70.0%). The general usage of ICT platforms increased in patients with higher levels of education. One-to-many was the preferred ICT category for obtaining general health information (78.3%) and for CU-related information (75.4%). A web browser (77.6%) was by far the most commonly used ICT to obtain general health information, followed by YouTube (25.8%) and Facebook (16.3%). Similarly, for CU-specific information, 3 out of 4 patients (74.6%) used a web browser, 20.9% used YouTube, and 13.6% used Facebook. One in 5 (21.6%) patients did not use any form of ICT for obtaining information on CU. The quality of the information obtained from one-to-many ICTs was rated much more often as very interesting and of good quality for general health information (53.5%) and CU-related information (51.5%) as compared to the other categories. CONCLUSIONS: Usage of ICTs for health and CU-specific information is extremely high in all countries analyzed, with web browsers being the preferred ICT platform.

Analysis of nickel distribution by synchrotron radiation X-ray fluorescence in nickel-induced early- and late-phase allergic contact dermatitis in Hartley guinea pigs.

BACKGROUND: Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy. METHODS: Forty Hartley guinea pigs were divided into four groups according to the NiSO4 sensitizing concentration and the NiSO4 challenged concentration: the 5% NiSO4-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO4-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-µ-XRF) and micro X-ray absorption near-edge spectroscopy (µ-XANES). RESULTS: In each section, the nickel element concentration in both the 5% NiSO4-group and 10% NiSO4-group was significantly higher than that in the negative control group. In the upper 300-µm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (>200 µm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-µ-XRF. According to the XANES data for the 10% NiSO4 metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni aqueous ionic state but in the nickel-binding protein. CONCLUSIONS: This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.

68Ga-labeled dimeric and trimeric cyclic RGD peptides as potential PET radiotracers for imaging gliomas.

68Ga-labeled cyclic RGD dimers and trimer were evaluated as PET radiotracers. It was found that the linker group had little impact on αvß3 binding affinity of RGD dimers, which share similar αvß3 binding affinity with the RGD trimer despite of their different multiplicity. Biodistribution properties of 68Ga radiotracers depend on RGD peptides and radiometal chelates. Among the 68Ga radiotracers evaluated, 68Ga-I2P-RGD2 has the best tumor uptake with good tumor-to-background ratios, and is a good PET radiotracer for imaging gliomas.