It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis.

Asthma is a common chronic airway disease with increasing prevalence. MicroRNAs act as vital regulators in cell progressions and have been identified to play crucial roles in asthma. The objective of the present study is to clarify the molecular mechanism of miR-203a-3p in the development of asthma. The expression of miR-203a-3p and Sine oculis homeobox homolog 1 (SIX1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of SIX1, fibronectin, E-cadherin, vimentin, phosphorylated-drosophila mothers against decapentaplegic 3 (p-Smad3) and Smad3 were measured by Western blot. The interaction between miR-203a-3p and SIX1 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. MiR-203a-3p was down-regulated and SIX1 was up-regulated in asthma serums, respectively. Transforming growth factor-β1 (TGF-β1) treatment induced the reduction of miR-203a-3p and the enhancement of SIX1 in BEAS-2B and 16HBE cells in a time-dependent manner. Subsequently, functional experiments showed the promotion of epithelial-mesenchymal transition (EMT) induced by TGF-β1 treatment could be reversed by miR-203a-3p re-expression or SIX1 deletion in BEAS-2B and 16HBE cells. SIX1 was identified as a target of miR-203a-3p and negatively regulated by miR-203a-3p. Then rescue assay indicated that overexpressed miR-203a-3p ameliorated TGF-β1 induced EMT by regulating SIX1 in BEAS-2B and 16HBE cells. Moreover, miR-203a-3p/SIX1 axis regulated TGF-β1 mediated EMT process in bronchial epithelial cells through phosphorylating Smad3. These results demonstrated that MiR-203a-3p modulated TGF-β1-induced EMT in asthma by regulating Smad3 pathway through targeting SIX1.

The transforming growth factor type-β (TGF-β) has been demonstrated to play an important role in the development of atherosclerosis through binding to the serine/threonine kinase transmembrane type I and type II receptors. However, as a key type I receptor for TGF-β, the exact role and the underlying mechanism of Activin receptor-like kinase 5 (ALK5) on macrophage activation involved in atherogenesis remain unclear. In the present study, enhanced ALK5 expression was found in bone marrow derived macrophages (BMDMs) upon OX-LDL stimulation tested by RT-PCR and Western blot, which was further verified by co-immunofluorescence staining. Next, the loss-of-function of ALK5 used AdshALK5 transfection was performed to test the effect of ALK5 on macrophage activation. We observed that ALK5 silencing inhibited pro-inflammatory but promoted anti-inflammatory macrophage markers expression. Moreover, decreased foam cell formation was found in ALK5 knockdown macrophages accompanied by increased cholesterol efflux. Mechanistically, ALK5 knockdown significantly increased KLF4 expression that was responsible for the attenuated macrophage activation induced by ALK5 knockdown. Collectively, these findings suggested that neutralization of ALK5 may act as a promising strategy for the management of atherosclerosis.

Overexpression of S100P promotes breast cancer metastasis in animals and elevated levels in primary breast cancers are associated with poor patient outcomes. S100P can differentially interact with nonmuscle myosin (NM) isoforms (IIA > IIC > IIB) leading to the redistribution of actomyosin filaments to enhance cell migration. Using COS-7 cells which do not naturally express NMIIA, S100P is now shown to interact directly with α,β-tubulin in vitro and in vivo with an equilibrium Kd of 2-3 × 10-7 M. The overexpressed S100P is located mainly in nuclei and microtubule organising centres (MTOC) and it significantly reduces their number, slows down tubulin polymerisation and enhances cell migration in S100P-induced COS-7 or HeLa cells. It fails, however, to significantly reduce cell adhesion, in contrast with NMIIA-containing S100P-inducible HeLa cells. When taxol is used to stabilise MTs or colchicine to dissociate MTs, S100P's stimulation of migration is abolished. Affinity-chromatography of tryptic digests of α and β-tubulin on S100P-bound beads identifies multiple S100P-binding sites consistent with S100P binding to all four half molecules in gel-overlay assays. When screened by NMR and ITC for interacting with S100P, four chemically synthesised peptides show interactions with low micromolar dissociation constants. The two highest affinity peptides significantly inhibit binding of S100P to α,β-tubulin and, when tagged for cellular entry, also inhibit S100P-induced reduction in tubulin polymerisation and S100P-enhancement of COS-7 or HeLa cell migration. A third peptide incapable of interacting with S100P also fails in this respect. Thus S100P can interact directly with two different cytoskeletal filaments to independently enhance cell migration, the most important step in the metastatic cascade.

Endocytosis of the amyloid precursor protein (APP) is critical for generation of β-amyloid, aggregating in Alzheimer's disease. APP endocytosis depending on the intracellular NPTY motif is well investigated, whereas involvement of the YTSI (also termed BaSS) motif remains controversial. Here, we show that APP lacking the YTSI motif (ΔYTSI) displays reduced localization to early endosomes and decreased internalization rates, similar to APP ΔNPTY. Additionally, we show that the YTSI-binding protein, PAT1a interacts with the Rab5 activator RME-6, as shown by several independent assays. Interestingly, knockdown of RME-6 decreased APP endocytosis, whereas overexpression increased the same. Similarly, APP ΔNPTY endocytosis was affected by PAT1a and RME-6 overexpression, whereas APP ΔYTSI internalization remained unchanged. Moreover, we could show that RME-6 mediated increase of APP endocytosis can be diminished upon knocking down PAT1a. Together, our data identify RME-6 as a novel player in APP endocytosis, involving the YTSI-binding protein PAT1a.

A wheat protein phosphatase PP2C-a10, which interacted with TaDOG1L1 and TaDOG1L4, promoted seed germination and decreased drought tolerance of transgenic Arabidopsis. Seed dormancy and germination are critical to plant fitness. DELAY OF GERMINATION 1 (DOG1) is a quantitative trait locus for dormancy in Arabidopsis thaliana. Some interactions between DOG1 and the type 2C protein phosphatases (PP2Cs) have been reported in Arabidopsis. However, the research on molecular functions and regulations of DOG1Ls and group A PP2Cs in wheat (Triticum aestivum. L), an important crop plant, is rare. In this study, the whole TaDOG1L family was identified. Expression analysis revealed that TaDOG1L2, TaDOG1L4 and TaDOG1L-N2 specially expressed in wheat grains, while others displayed distinct expression patterns. Yeast two-hybrid analysis of TaDOG1Ls and group A TaPP2Cs revealed interaction patterns differed from those in Arabidopsis, and TaDOG1L1 and TaDOG1L4 interacted with TaPP2C-a10. The qRT-PCR analysis showed that TaPP2C-a10 exhibited the highest transcript level in wheat grains. Further investigation showed that ectopic expression of TaPP2C-a10 in Arabidopsis promoted seed germination and decreased sensitivity to ABA during germination stage. Additionally, TaPP2C-a10 transgenic Arabidopsis exhibited decreased tolerance to drought stress. Finally, the phylogenetic analysis indicated that TaPP2C-a10 gene was conserved in angiosperm during evolutionary process. Overall, our results reveal the role of TaPP2C-a10 in seed germination and abiotic stress response, as well as the functional diversity of TaDOG1L family.

To assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI (mpMRI, BI-RADS 4, and BI-RADS 5).

Due to the growing number of liver transplantations (LTs), there is an increasing number of patients requiring retransplantation (reLT). Data on the use of grafts from extended criteria donors (ECD), especially donation after circulatory death (DCD), for reLT are lacking. We aimed to assess the outcome of patients undergoing reLT using a DCD graft in the Netherlands between 2001 and July 2018. Propensity score matching was used to match each DCD-reLT with three DBD-reLT cases. Primary outcomes were patient and graft survival. Secondary outcome was the incidence of biliary complications, especially nonanastomotic strictures (NAS). 21 DCD-reLT were compared with 63 matched DBD-reLTs. Donors in the DCD-reLT group had a significantly lower BMI (22.4 vs. 24.7 kg/m2 , P-value = 0.02). Comparison of recipient demographics and ischemia times yielded no significant differences. Patient and graft survival rates were comparable between the two groups. However, the occurrence of nonanastomotic strictures after DCD-reLT was significantly higher (38.1% vs. 12.7%, P-value = 0.02). ReLT with DCD grafts does not result in inferior patient and graft survival compared with DBD grafts in selected patients. Therefore, DCD liver grafts should not routinely be declined for patients awaiting reLT.

In the present study, a homogenous polysaccharide (DFPW) was isolated and purified from the dried rhizome of Drynaria fortunei, and its protective effect against osteoporosis was investigated in ovariectomized (OVX) rats. Histological analysis indicated that oral administration of DFPW (100 and 400 mg/kg) for 12 weeks significantly improved trabecular bone mass, as demonstrated by the increase in trabecular area, trabecular thickness and its number in OVX rats. Furthermore, the decline of bone mineral density and bone mineral content including Ca, P and Mg induced by OVX was reversed by the DFPW administration. This function was achieved by the decreased levels of the bone turnover markers, such as serum ALP, urinary deoxypyridinoline (DPD), Ca and P excretions. Besides, DFPW improved biomechanical parameters (maximum load, energy, Young's, modulus and maximum stress) to strengthen the hardness and strength femoral diaphysis in OVX rats. These results strongly suggested that DFPW might be a hopeful alternative therapeutics to treat postmenopausal osteoporosis.

Lactate measurements have proven utility as a triage tool, therapeutic guide, and prognostic indicator, with broad use in Acute Care and transplantation. Its value in guiding therapy and predicting outcomes following liver resection is less well-defined. This systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines assessed the relationship between peri-operative lactate levels and morbidity and mortality after liver resection. Seven relevant studies comprising 2573 patients in total were identified. Six studies assessed intra-operative or early postoperative lactate levels, one publication examined pre-operative levels. All studies demonstrated a significant association between peri-operative lactate levels and adverse outcomes. The influence of pre-operative diabetes and cirrhosis on postoperative lactate levels was shown in one study each, no study assessed the association of lactate with post-hepatectomy liver failure according to defined criteria. The heterogeneity of study measurements and end-points precluded a meta-analysis from being performed. Early postoperative lactate >3-3.7 mmol/L is associated with mortality but validation of clear cut-off levels for outcome prediction is pending. Literature suggests lactate is a useful predictive marker for outcomes post liver surgery, especially when measured in the early postoperative phase. Further research is required to standardize the use of lactate measurements in a meaningful therapeutic manner.

Shine-Dalgarno (SD) motifs are thought to play an important role in translational initiation in bacteria. Paradoxically, ribosome profiling studies in E. coli show no correlation between the strength of an mRNA's SD motif and how efficiently it is translated. Performing profiling on ribosomes with altered anti-Shine-Dalgarno sequences, we reveal a genome-wide correlation between SD strength and ribosome occupancy that was previously masked by other contributing factors. Using the antibiotic retapamulin to trap initiation complexes at start codons, we find that the mutant ribosomes select start sites correctly, arguing that start sites are hard-wired for initiation through the action of other mRNA features. We show that A-rich sequences upstream of start codons promote initiation. Taken together, our genome-wide study reveals that SD motifs are not necessary for ribosomes to determine where initiation occurs, though they do affect how efficiently initiation occurs.

Toxoplasma gondii, a protozoan parasite, undergoes a complex and poorly understood developmental process that is critical for establishing a chronic infection in its intermediate hosts. Here, we applied single-cell RNA-sequencing (scRNA-seq) on >5,400 Toxoplasma in both tachyzoite and bradyzoite stages using three widely studied strains to construct a comprehensive atlas of cell-cycle and asexual development, revealing hidden states and transcriptional factors associated with each developmental stage. Analysis of SAG1-related sequence (SRS) antigenic repertoire reveals a highly heterogeneous, sporadic expression pattern unexplained by measurement noise, cell cycle, or asexual development. Furthermore, we identified AP2IX-1 as a transcription factor that controls the switching from the ubiquitous SAG1 to rare surface antigens not previously observed in tachyzoites. In addition, comparative analysis between Toxoplasma and Plasmodium scRNA-seq results reveals concerted expression of gene sets, despite fundamental differences in cell division. Lastly, we built an interactive data-browser for visualization of our atlas resource.

Chlorthalidone is currently recommended as the preferred thiazide diuretic to treat hypertension, but no trials have directly compared risks and benefits.

Incidence rates of cardiomyopathies, which are a common cause of heart failure in young people, have increased during the last decades. An association between body weight in adolescence and future cardiomyopathy among men was recently identified. Whether or not this holds true also for women is unknown. The aim was therefore to determine whether for young women being overweight or obese is associated with a higher risk of developing cardiomyopathy.

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The main active component in Angelica sinensis, ligustilide, has been reported to have the protective effect on AD. Whether ligustilide could protect against age-induced dementia is still unknown. In this study, we used an aging model, SAMP8 mice to investigate the neuroprotective effect of ligustilide. The behavioral tests (Morris water maze, object recognition task, open field test and elevated plus maze) results showed that ligustilide could improve the memory deficit in SAMP8 mice. For mechanism study, we found that the protein level of P-Drp1 (fission) was decreased and the levels of Mfn1 and Mfn2 (fusion) were increased after ligustilide treatment in animals and cells. Ligustilide increased P-AMPK and ATP levels. Malondialdehyde and superoxide dismutase activity results indicated that ligustilide exerts antioxidant effects by reducing the level of oxidative stress markers. In addition, ligustilide improved neural function and alieved apoptosis and neuroinflammation. These findings have shown that ligustilide treatment improves mitochondrial function in SAMP8 mice, and improves memory loss.

Tourette Syndrome (TS) is characterized by the presence of tics and sensory phenomena, such as premonitory urges, and is often accompanied by significant obsessive-compulsive symptoms (OCS). The goal of this exploratory study was to determine the association between functional connectivity and the different symptom domains of TS, as little is currently known about how they differ. Resting-state functional magnetic resonance imaging was performed in 39 patients with TS and 20 matched healthy controls. Seed-based functional connectivity of the supplementary motor area (SMA), orbitofrontal cortex (OFC), insula, caudate and putamen were compared between the groups, and correlated with clinical measures within the patient group. When compared to controls, patients with TS exhibited greater connectivity between the temporal gyri, insula and putamen, and between the OFC and cingulate cortex. Tic severity was associated with greater connectivity between the putamen and the sensorimotor cortex; OCS severity was associated with less connectivity between the SMA and thalamus and between the caudate and precuneus; and premonitory urge severity was associated with less connectivity between the OFC and sensorimotor cortex and between the inferior frontal gyrus and the putamen and insula seeds. Functional connectivity within sensorimotor processing regions were associated with all of the investigated symptom domains, including OCS, suggesting dysfunctions in the sensorimotor system may explain most of the observed symptoms in TS, and not just tics.

The addition of budesonide (Bud) 0.25 mg/kg to surfactant decreased the lung and systemic responses to mechanical ventilation in preterm sheep and the rates and severity of bronchopulmonary dysplasia (BPD) in preterm infants. We hypothesized that lower budesonide concentrations in surfactant will decrease injury while decreasing systemic corticosteroid exposure.

Hardy kiwifruits (Actinidia arguta Planch.) have high amounts of antioxidants, including ascorbic acid (vitamin C) and phenolics. The anti-cholinesterase activity and neuroprotective effects of three different cultivars of hardy kiwifruits, cv. Mansu (A. arguta × A. deliciosa), cv. Haeyeon (A. arguta), and cv. Chiak (A. arguta), on PC-12 and SH-SY5Y cells were evaluated. Extraction of phenolics and vitamin C was carried out using 80% (v/v) aqueous ethanol and metaphosphoric acid assisted with homogenization, respectively. Hardy kiwifruit of cv. Mansu showed higher total phenolic, total flavonoid, and vitamin C contents and antioxidant capacity compared to the other tw°Cultivars of hardy kiwifruits, cv. Haeyeon and cv. Chiak. Analysis of high-performance liquid chromatography results revealed the presence of procyanidin B2, (?)-epicatechin, neochlorogenic acid, cryptochlorogenic acid, rutin, hyperoside, isoquercitrin, and astragalin in hardy kiwifruits. The three cultivars of hardy kiwifruits had a wide range of vitamin C content of 55.2?130.0 mg/100 g fresh weight. All three cultivars of hardy kiwifruits had protective effects on neuronal PC-12 and SHSY5Y cells exposed to hydrogen peroxide by increasing cell viability and reducing intracellular oxidative stress. Furthermore, the hardy kiwifruits inhibited acetylcholinesterase and butyrylcholinesterase. Collectively, these results suggest that hardy kiwifruits rich in antioxidants like phenolics and vitamin C have good potential as functional materials in neuroprotective applications.

Exercise has been reported to induce autophagy. We hypothesized that exercise preconditioning (EP)-related autophagy in cardiomyocytes could be attributed to intermittent ischemia-hypoxia, allowing the heart to be protected for subsequent high-intensity exercise (HE). We applied approaches, chromotrope-2R brilliant green (C-2R BG) staining and plasma cTnI levels measuring, to characterize two periods of cardioprotection after EP: early EP (EEP) and late EP (LEP). Further addressing the relationship between ischemia-hypoxia and autophagy, key proteins, Beclin1, LC3, Cathepsin D, and p62, were determined by immunohistochemical staining, western blotting, and by their adjacent slices with C-2R BG. Results indicated that exercise-induced ischemia-hypoxia is a key factor in Beclin1-dependent autophagy. High-intensity exercise was associated with the impairment of autophagy due to high levels of LC3II and unchanged levels of p62, intermittent ischemia-hypoxia by EP itself plays a key role in autophagy, which resulted in more favorable cellular effects during EEP-cardioprotection compared to LEP.

There is a growing body of evidences indicating iNOS has involved in the pathogenesis of SLE. However, the role of iNOS in SLE is inconsistency. This systematic review was designed to evaluate the association between iNOS and SLE.