Species-specific cleavage of cGAS by picornavirus protease 3C disrupts mitochondria DNA-mediated immune sensing.

RNA viruses cause numerous infectious diseases in humans and animals. The crosstalk between RNA viruses and the innate DNA sensing pathways attracts increasing attention. Recent studies showed that the cGAS-STING pathway plays an important role in restricting RNA viruses via mitochondria DNA (mtDNA) mediated activation. However, the mechanisms of cGAS mediated innate immune evasion by RNA viruses remain unknown. Here, we report that seneca valley virus (SVV) protease 3C disrupts mtDNA mediated innate immune sensing by cleaving porcine cGAS (pcGAS) in a species-specific manner. Mechanistically, a W/Q motif within the N-terminal domain of pcGAS is a unique cleavage site recognized by SVV 3C. Three conserved catalytic residues of SVV 3C cooperatively contribute to the cleavage of pcGAS, but not human cGAS (hcGAS) or mouse cGAS (mcGAS). Additionally, upon SVV infection and poly(dA:dT) transfection, pcGAS and SVV 3C colocalizes in the cells. Furthermore, SVV 3C disrupts pcGAS-mediated DNA binding, cGAMP synthesis and interferon induction by specifically cleaving pcGAS. This work uncovers a novel mechanism by which the viral protease cleaves the DNA sensor cGAS to evade innate immune response, suggesting a new antiviral approach against picornaviruses.

Pseudorabies virus tegument protein UL13 recruits RNF5 to inhibit STING-mediated antiviral immunity.

Pseudorabies virus (PRV) has evolved various immune evasion mechanisms that target host antiviral immune responses. However, it is unclear whether and how PRV encoded proteins modulate the cGAS-STING axis for immune evasion. Here, we show that PRV tegument protein UL13 inhibits STING-mediated antiviral signaling via regulation of STING stability. Mechanistically, UL13 interacts with the CDN domain of STING and recruits the E3 ligase RING-finger protein 5 (RNF5) to promote K27-/K29-linked ubiquitination and degradation of STING. Consequently, deficiency of RNF5 enhances host antiviral immune responses triggered by PRV infection. In addition, mutant PRV lacking UL13 impaired in antagonism of STING-mediated production of type I IFNs and shows attenuated pathogenicity in mice. Our findings suggest that PRV UL13 functions as an antagonist of IFN signaling via a novel mechanism by targeting STING to persistently evade host antiviral responses.

Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors.

Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with anti-tumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/ refractory mature B-cell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase II dose (RP2D) (clinicaltrials gov. Identifier: NCT02857998). Overall, 134 Chinese patients were enrolled (dose escalation, N=27; dose expansion, N=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d.), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d.. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% confidence interval: 37.5- 64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the dose-expansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased dose-proportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed anti-tumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.

A single-center, multi-factor, retrospective study to improve the diagnostic accuracy of primary prostate cancer using [68Ga]Ga-PSMA-11 total-body PET/CT imaging.

PURPOSE: To improve the diagnostic accuracy of initial detection in patients with suspected primary prostate cancer (PCa). METHODS: Eighty-four patients who underwent Gallium-68-labeled prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) total-body positron emission tomography/computed tomography (PET/CT) imaging before treatment in our department were enrolled. The maximum standard uptake value (SUVmax) of the prostate (SUVmax-PSMA), liver (SUVmax-PSMA-L), and mediastinal blood pool (SUVmax-PSMA-M) was measured using [68Ga]Ga-PSMA-11 total-body PET/CT imaging. The [68Ga]Ga-PSMA-11 derived metabolic tumor volume (MTV), the total lesion (TLP), and the cross-sectional areas of focal concentration in the prostate (CAP) were also determined. Besides, the prostate-specific antigen (PSA) levels and the above imaging characteristics were analyzed using receiver operating characteristic curves to identify the cutoff value to improve the diagnostic accuracy of suspected PCa. Finally, a multivariate regression analysis was conducted to discover the independent predictor to improve the diagnostic accuracy on [68Ga]Ga-PSMA-11 total-body imaging. RESULTS: There was no significant difference between the PCa and Non-PCa groups in age, height, weight, injected dose, except for the PSA levels, the SUVmax-PSMA, TLP, MTV, and CAP. Besides, the SUVmax-PSMA-T/L and SUVmax-PSMA-T/M derived from SUVmax-PSMA were both significantly different. In addition, the areas under the curve of PSA levels, SUVmax-PSMA, SUVmax-PSMA-T/L, SUVmax-PSMA-T/M, TLP, MTV, and CAP to predict PCa on [68Ga]Ga-PSMA-11 imaging were 0.620 (95% confidence interval (CI) 0.485-0.755), 0.864 (95% CI 0.757-0.972), 0.819 (95% CI 0.704-0.935), 0.876 (95% CI 0.771-0.980), 0.845 (95% CI 0.741-0.949), 0.820 (95% CI 0.702-0.938), 0.627 (95% CI 0.499-0.754), respectively. However, a multivariate regression analysis showed that SUVmax-PSMA was an independent predictor, with a cutoff value of 11.5 and an odds ratio of 1.221. CONCLUSION: The SUVmax-PSMA with a cutoff value of 11.5 was an independent predictor to improve the diagnostic accuracy of PCa on [68Ga]Ga-PSMA-11 total-body imaging.

Genome-wide association studies reveal genetic basis of ionomic variation in cassava.

As one of the most important food crops, cassava (Manihot esculenta) is the main dietary source of micronutrients for about 1 billion people. However, the ionomic variation in cassava and the underlying genetic mechanisms remain unclear so far. Herein, genome-wide association studies were performed to reveal the specific single nucleotide polymorphisms (SNPs) that affect the ionomic variation in cassava. We identified 164 SNPs with P-values lower than the threshold located in 88 loci associated with divergent ionomic variations. Among them, 13 SNPs are related to both calcium (Ca) and magnesium (Mg), and many loci for different ionomic traits seem to be clustered on specific chromosome regions. Moreover, we identified the peak SNPs in the promoter regions of Sc10g003170 (encoding methionyl-tRNA synthetase [MetRS]) and Sc18g015190 (encoding the transcriptional regulatory protein AlgP) for nitrogen (N) and phosphorus (P) accumulation, respectively. Notably, these two SNPs (chr10_32807962 and chr18_31343738) were directly correlated with the transcript levels of Sc10g003170 (MetRS) and Sc18g015190 (AlgP), which positively modulated N accumulation and P concentration in cassava, respectively. Taken together, this study provides important insight into the genetic basis of cassava natural ionomic variation, which will promote genetic breeding to improve nutrient use and accumulation of elements in cassava.

Prediction and Structure-Activity Relationship Analysis on Ready Biodegradability of Chemical Using Machine Learning Method.

Persistent contaminants from different industries have already caused significant risks to the environment and public health. In this study, a data set containing 1306 not readily biodegradable (NRB) and 622 readily biodegradable (RB) chemicals was collected and characterized by CORINA descriptors, MACCS fingerprints, and ECFP_4 fingerprints. We utilized decision tree (DT), support vector machine (SVM), random forest (RF), and deep neural network (DNN) to construct 34 classification models that could predict the biodegradability of compounds. The best model (model 5F) built using a Transformer-CNN algorithm had a balanced accuracy of 86.29% and a Matthews correlation coefficient of 0.71 on the test set. By analyzing the top 10 CORINA descriptors used for modeling, the properties containing solubility, π/σ atom charges, rotatable bonds number, lone pair/π/σ atom electronegativities, molecular weight, and number of nitrogen atom based hydrogen bonding acceptors were determined to be critical for biodegradability. The substructure investigations confirmed earlier studies that the presence of aromatic rings and nitrogen or halogen substitutions in a molecule will hinder the biodegradation of the compound, while the ester groups and carboxyl groups promote biodegradability. We also identified the representative fragments affecting biodegradability by analyzing the frequency differences of substructural fragments between the NRB and RB compounds. The results of the study can provide excellent guidance for the discovery and design of compounds with good chemical biodegradability.

The genome of Areca catechu provides insights into sex determination of monoecious plants.

The areca palm (Areca catechu) has a monoecious spadix, with male flowers on the apical side and females on the basal side. Here, we applied multiomics analysis to investigate sex determination and floral organ development in areca palms. We generated a chromosome-level reference genome of A. catechu with 16 pseudochromosomes, composed of 2.73 Gb and encoding 31 406 genes. Data from RNA-seq and ATAC-seq (assay for transposase accessible chromatin sequencing) suggested that jasmonic acid (JA) synthesis and signal transduction-related genes were differentially expressed between female and male flowers via epigenetic modifications. JA concentration in female flowers was c. 10 times than that in males on the same inflorescence, while JA concentration in hermaphroditic flowers of abnormal inflorescences was about twice that in male flowers of normal inflorescences. JA promotes the development of female flower organs by decreasing the expression of B-function genes, including AGL16, AP3, PIb and PIc. There is also a region on pseudochromosome 15 harboring sex-related genes, including CYP703, LOG, GPAT, AMS and BiP. Among them, CYP703, AMS and BiP were specifically expressed in male flowers.

Short-time total-body dynamic PET imaging performance in quantifying the kinetic metrics of 18F-FDG in healthy volunteers.

PURPOSE: To investigate the performance of short-time dynamic imaging in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG). METHODS: Dynamic total-body positron emission tomography (PET) imaging was performed in 11 healthy volunteers for 75 min. The data were divided into 30-, 45- and 75-min groups. Nonlinear regression (NLR) generated constant rates (k1 to k3) and NLR-based Ki in various organs. The Patlak method calculated parametric Ki images to generate Patlak-based Ki values. Paired samples t-test or the Wilcoxon signed-rank test compared the kinetic metrics between the groups, depending on data normality. Deming regression and Bland-Altman analysis assessed the correlation and agreement between NLR- and Patlak-based Ki. A two-sided P < 0.05 was considered statistically significant. RESULTS: The 45- and 75-min groups were similar in NLR-based kinetic metrics. The relative difference ranges were as follows: k1, from 3.4% (P = 0.627) in the spleen to 57.9% (P = 0.130) in the white matter; k2, from 6.0% (P = 0.904) in the spleen to 60.7% (P = 0.235) in the left ventricle (LV) myocardium; k3, from 45.6% (P = 0.302) in the LV myocardium to 96.3% (P = 0.478) in the liver; Ki, from 14.0% (P = 0.488) in the liver to 77.8% (P = 0.067) in the kidney. Patlak-based Ki values were also similar between these groups in all organs, except the grey matter (9.6%, P = 0.029) and cerebellum (14.4%, P = 0.002). However, significant differences in kinetic metrics were found between the 30-min and 75-min groups in most organs both in NLR- and Patlak-based analyses. The NLR- and Patlak-based Ki values significantly correlated, with no bias in any of the organs. CONCLUSION: Dynamic imaging using a high-sensitivity total-body PET scanner for a shorter time of 45 min could achieve relevant kinetic metrics of 18F-FDG as done by long-time imaging.

PP2C1 fine-tunes melatonin biosynthesis and phytomelatonin receptor PMTR1 binding to melatonin in cassava.

Melatonin is an important molecule in both animals and plants, regulating circadian rhythms and stress responses. Therefore, the improvement of melatonin accumulation not only strengthens the function of melatonin but also improves stress resistance in crops. Although melatonin biosynthetic enzymes have been identified through reverse genetics previously, an investigation of melatonin level-related genes through forward genetics in plants has yet to be performed. In this study, a genome-wide association study using cassava natural population of 298 genetic resources identified melatonin accumulation 1 (MA1), which regulates the natural variation of melatonin levels in cassava. We found that MA1 encodes type 2C protein phosphatase 1 (PP2C1), which serves as a negative regulator of melatonin levels in cassava. MePP2C1 physically interacts with MeRAV1/2 and MeWRKY20 and dephosphorylates them at serine (S) 35 residue, S34 residue, and S176 residue, respectively, thereby hindering their transcriptional activation on downstream melatonin biosynthetic genes. Notably, MePP2C1 interacts with phytomelatonin receptor MePMTR1 and dephosphorylates it at S11 residue, repressing its binding to melatonin. In summary, this study demonstrates that MePP2C1 as MA1 plays dual roles in negatively regulating both melatonin accumulation and signaling, extending the understanding of the molecular mechanism underlying melatonin accumulation and signaling through forward genetics in plants.

Role of 18F-FDG PET/CT imaging in cardiac and pericardial masses.

BACKGROUND: Considering the few reported cardiac masses, PET/CT in the imaging workup of cardiac masses is not well established. This retrospective study analyzed the role of 18F-FDG PET/CT imaging in cardiac/pericardial masses. METHODS AND RESULTS: Fifty-nine patients with newly diagnosed cardiac/pericardial masses who underwent PET/CT and transthoracic echocardiography (TTE) were recruited. Echocardiographic and PET/CT characteristics were evaluated for predictive value in differentiating malignant and non-malignant lesions using histologic confirmation as the gold standard. The McNemar test was used to test the differences in sensitivity between PET/CT and TTE. 18F-FDG PET/CT had higher sensitivity in determining the malignancy of cardiac/pericardial masses compared to TTE (sensitivity, 96.6% vs 72.4%, P = .039). However, when pericardial masses were excluded from the analysis, the difference in sensitivity between the two was not statistically significant (sensitivity, 95.6% vs 78.3%, P = .219). 18F-FDG PET/CT identified two malignant pericardial masses missed on TTE, changed the diagnostic orientation of TTE in 15 patients, and found seven patients with extracardiac lesions in 29 malignant patients. CONCLUSIONS: PET/CT was an effective additional image modality in patients with suspected malignant cardiac mass for further confirmation and to screen for potential metastasis.

Fluorine 18 Fluorodeoxyglucose PET/CT Findings in Gorlin-Goltz Syndrome.

Online supplemental material is available for this article.

Computational determination of gene age and characterization of evolutionary dynamics in human.

Genes originate at different evolutionary time scales and possess different ages, accordingly presenting diverse functional characteristics and reflecting distinct adaptive evolutionary innovations. In the past decades, progresses have been made in gene age identification by a variety of methods that are principally based on comparative genomics. Here we summarize methods for computational determination of gene age and evaluate the effectiveness of different computational methods for age identification. Our results show that improved age determination can be achieved by combining homolog clustering with phylogeny inference, which enables more accurate age identification in human genes. Accordingly, we characterize evolutionary dynamics of human genes based on an extremely long evolutionary time scale spanning ~4,000 million years from archaea/bacteria to human, revealing that young genes are clustered on certain chromosomes and that Mendelian disease genes (including monogenic disease and polygenic disease genes) and cancer genes exhibit divergent evolutionary origins. Taken together, deciphering genes' ages as well as their evolutionary dynamics is of fundamental significance in unveiling the underlying mechanisms during evolution and better understanding how young or new genes become indispensable integrants coupled with novel phenotypes and biological diversity.

Ultra-low-activity total-body dynamic PET imaging allows equal performance to full-activity PET imaging for investigating kinetic metrics of 18F-FDG in healthy volunteers.

PURPOSE: To investigate the feasibility of ultra-low-activity total-body positron emission tomography (PET) dynamic imaging for quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in normal organs and to verify its clinical relevance with full-activity imaging. METHODS: Dynamic total-body PET imaging was performed in 20 healthy volunteers, with eight using full activity (3.7 MBq/kg) of 18F-FDG and 12 using 10× activity reduction (0.37 MBq/kg). Image contrast, in terms of liver-to-muscle ratio (LMR), liver-to-blood ratio (LBR), and blood-to-muscle ratio (BMR) of radioactivity concentrations were assessed. A two-tissue compartment model was fitted to the time-to-activity curves in organs based on regions of interest (ROIs) delineation using PMOD, and constant rates (k1, k2, and k3) were generated. Kinetic constants, corresponding coefficients of variance (CoVs), image contrast, radiation dose, prompt counts, and data size were compared between full- and low-activity groups. RESULTS: All constant rates, corresponding CoVs, and image contrast in different organs were comparable with none significant differences between full- and ultra-low-activity groups. PET images in the ultra-low-activity group generated significantly lower effective radiation dose (median, 0.419 vs. 4.886 mSv, P < 0.001), reduced prompt counts (median, 2.79 vs. 55.68 billion, P < 0.001), and smaller data size (median, 71.11 vs. 723.18 GB, P < 0.001). CONCLUSION: Total-body dynamic PET imaging using 10× reduction of injected activity could achieve relevant kinetic metrics of 18F-FDG and comparable image contrast with full-activity imaging. Activity reduction results in significant decrease of radiation dose and data size, rendering it more acceptable and easier for data reconstruction, transmission, and storage for clinical practice.

Total-body PET/CT using half-dose FDG and compared with conventional PET/CT using full-dose FDG in lung cancer.

PURPOSE: The purpose was to explore the effects of total-body PET/CT with half-dose 18F-FDG activity on image quality, compared with those of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer. METHODS: Fifty-six primary lung cancer patients who underwent total-body PET/CT on a uEXPLORER scanner with half-dose (1.85 MBq/kg) 18F-FDG activity before treatment were retrospectively studied; among them, 28 patients were confirmed by postoperative pathologic examination and 28 patients by biopsy. After matching with the pathological study results, the other 28 patients with lung cancer who underwent surgery were selected for the full-dose (3.70 MBq/kg) group. Patients in the full-dose group were studied with a conventional uM780 PET/CT scanner. The acquisition time of the half-dose group was 15 min, split into 4-min and 2-min duration groups, which were all referred to as G15, G4 and G2, respectively. The PET/CT scanning speed in the full-dose group was 2 min/bed. Image quality was evaluated by subjective and objective analyses. The subjective analysis method was carried out with a 5-point scale (5-excellent, 1-poor). Objective analysis indicators of PET image quality included the SUVmax, SUVmean and signal-to-noise ratio (SNR) of the liver; the SUVmax and SUVmean of the blood pool; and the SUVmax and tumour-to-background ratio (TBR) of the lesions. G15 served as the reference for G2 and G4 to test lesion detectability. RESULTS: Image quality scores in G2 (4.3 ± 0.7) were significantly higher than those in the full-dose group (3.7 ± 0.6) (p = 0.004). The mean and SD of the image quality scores in G4 and G15 were 4.9 ± 0.2 and 5.0 ± 0.0, respectively. The liver SNR in G2 was significantly higher than that in the full-dose group; the corresponding SNR were 11.7 ± 1.5 and 8.3 ± 1.2 (p < 0.001), respectively. The liver SNR significantly increased with the time of acquisition among G2, G4 and G15 (11.1 ± 1.7, 15.2 ± 3.4 and 30.5 ± 6.0, all p < 0.05). G15 served as the reference, and all these lesions (100%) could be identified by G2 and G4. CONCLUSION: Total-body PET/CT with half-dose 18F-FDG activity in G2 and G4 achieved comparable image quality to conventional PET/CT, and its image quality was better than that of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer.

Characterization and identification of long non-coding RNAs based on feature relationship.

MOTIVATION: The significance of long non-coding RNAs (lncRNAs) in many biological processes and diseases has gained intense interests over the past several years. However, computational identification of lncRNAs in a wide range of species remains challenging; it requires prior knowledge of well-established sequences and annotations or species-specific training data, but the reality is that only a limited number of species have high-quality sequences and annotations. RESULTS: Here we first characterize lncRNAs in contrast to protein-coding RNAs based on feature relationship and find that the feature relationship between open reading frame length and guanine-cytosine (GC) content presents universally substantial divergence in lncRNAs and protein-coding RNAs, as observed in a broad variety of species. Based on the feature relationship, accordingly, we further present LGC, a novel algorithm for identifying lncRNAs that is able to accurately distinguish lncRNAs from protein-coding RNAs in a cross-species manner without any prior knowledge. As validated on large-scale empirical datasets, comparative results show that LGC outperforms existing algorithms by achieving higher accuracy, well-balanced sensitivity and specificity, and is robustly effective (>90% accuracy) in discriminating lncRNAs from protein-coding RNAs across diverse species that range from plants to mammals. To our knowledge, this study, for the first time, differentially characterizes lncRNAs and protein-coding RNAs based on feature relationship, which is further applied in computational identification of lncRNAs. Taken together, our study represents a significant advance in characterization and identification of lncRNAs and LGC thus bears broad potential utility for computational analysis of lncRNAs in a wide range of species. AVAILABILITY AND IMPLEMENTATION: LGC web server is publicly available at http://bigd.big.ac.cn/lgc/calculator. The scripts and data can be downloaded at http://bigd.big.ac.cn/biocode/tools/BT000004. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comparison of post-therapeutic sequential 131I whole-body scans in the detection of metastatic thyroid cancer.

BACKGROUND: The aim was to compare the detect ability of three sequential 131I whole-body scans (tri-WBS) on the second, third, and fourth day after 131I therapy for metastatic thyroid cancer. METHODS: Differentiated thyroid cancer patients who received oral high-dose 131I therapy underwent routinely tri-WBS on the second, third, and fourth day after total or near-total thyroidectomy in Zhongshan Hospital, Fudan University. We enrolled 137 patients with 261 tri-WBSs in this study between January 2015 and November 2017. The inclusion criteria was that at least one metastasis was found in the tri-WBS. We classified radioactive uptake of metastatic lesions by visual assessment into three grades: grade 0 = no uptake, grade 1= suspicious uptake, and grade 2 = definite uptake. The fourth day 131I WBS images were also compared with concurrent pre-therapeutic 99mTc-pertechnetate WBS images when available. We also analyzed the serum Tg levels of probably statistical difference in the patients with only lymph node, lung, bone, and multiple metastases when they underwent the first radioiodine ablation. RESULTS: A total of 722 metastatic accumulations were identified in the final decisions, including 293 lymph node metastases, 261 nodular pulmonary metastases, 49 diffuse bilateral pulmonary metastases, 106 bone metastases, and 13 other metastases. The differences of intensity of uptake in sequential three day images were significant in visualization of lymph node metastasis (χ2=124.432, P<0.001), nodular pulmonary metastasis (χ2=160.334, P<0.001), diffuse bilateral pulmonary metastasis (χ2=41.710, P<0.001), and bone metastasis (χ2=22.118, P<0.001) in our study. Compared to the second day scans, the fourth day scans detected 87 (29.70%) more metastatic lymph nodes, 111 (42.53%) more nodular pulmonary metastases, 26 (53.06%) more diffuse bilateral pulmonary metastases and 17 (16.95%) more bone metastases. The differences of intensity of uptake between 99mTc-pertechnetate WBS and the fourth day 131I WBS were significant in visualization of lymph node metastasis (χ2=172.624, P<0.001), nodular pulmonary metastasis (χ2=111.004, P<0.001), diffuse bilateral pulmonary metastasis (χ2=17.400, P<0.001) and bone metastasis (χ2=46.298, P<0.001). The means of RTg in the patients with only lymph node, lung, bone metastasis, and multiple metastases were 47.20, 76.58, 89.00, and 91.56, respectively. The differences of serum Tg levels in the patients with only lymph node, lung, bone metastasis, and multiple metastases were significant (χ2=35.850, P<0.001). CONCLUSIONS: The detect ability of tri-WBS was significantly different even for consecutive three-day images on the second, third, and fourth day after 131I therapy for metastatic thyroid cancer. There was a linear trend of increasing 131I uptake from the second to fourth day 131I WBS. The pre-therapy 99mTc-pertechnetate WBS demonstrated a poor ability to detect metastatic thyroid cancer compared to 131I WBS. There was an increasing trend of the means of RTg in patients with more extensive metastases.

A cross-sectional study of job burnout, psychological attachment, and the career calling of Chinese doctors.

BACKGROUND: The main objectives of this study were as follows: (1) evaluate the prevalence of burnout syndrome among doctors, (2) establish associations with demographic factors in China, and (3) examine the mediating role of psychological attachment in the relationship between job burnout and career calling. METHODS: This cross-sectional survey was conducted by administering an online questionnaire in May 2016. The survey was performed across Thirty provinces. In total, A total of 3016 Chinese doctors were selected as participants, of which 2617 completed valid questionnaires (effective response rate: 86.77%). RESULTS: The overall prevalence of burnout symptoms among Chinese doctors was 85.79%. Little variance was reported for burnout symptoms according to age (Waldχ2 = 6.843, P < 0.05, OR < 1), professional title (Waldχ2 = 13.110, P < 0.05, OR > 1), and daily working hours (Waldχ2 = 7.226, P < 0.05, OR > 1). However, the burnout of Chinese doctors was found to be associated with psychological attachment (B = - 0.6433, P < 0.0001) and career calling (B = 0.3653, P < 0.0001); furthermore, psychological attachment (B = 0.2350, P < 0.001) mediated the relationship between job burnout and career calling. CONCLUSION: Burnout symptoms among Chinese doctors were prevalent and associated with age, professional title, and long working hours. Chinese doctors aged 20-30 experienced a much higher level of burnout symptoms. The longer hours doctors worked, the more likely they were at risk of burnout symptoms, especially among attending physicians. Doctors who endured high-level burnout tended to exhibit decreasing psychological attachment, which threatened their sense of career calling. Finally, this paper proposed related explanations for the function mechanisms based on both theoretical and practical perspectives.

The value of 18 F-FDG PET/CT in diagnosing and localising deep sternal wound infection to guide surgical debridement.

Deep sternal wound infection (DSWI) is a severe complication in patients after open heart surgery (OHS). But there is a lack of appropriate imaging tool to detect the infection sites, which may lead to incomplete debridement. The present study aims to investigate the value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in comparison with CT scan in diagnosing and localising DSWI. A total of 102 patients with DSWI after OHS were retrospectively collected from January 2012 to December 2017 in our hospital. All the patients had surgical debridements for DSWI with pretreatment imaging of either 18 F-FDG PET/CT or CT scan. The sensitivity, specificity, and accuracy of localising infection sites were compared between PET/CT and CT groups, with surgical, microbiological, and histopathological findings as the gold standard. The length of hospital stays and the rate of recurrence were also compared. Ten patients in the PET/CT group had a follow-up PET/CT scan after debridement, and the correlations between the changes of PET/CT findings and surgical outcomes were analysed. 18 F-FDG PET/CT is more accurate than CT in diagnosing and localising DSWI after OHS, which leads to a more successful surgical debridement with a lower rate of recurrence and a shorter length of hospital stay. In addition, follow-up PET/CT after debridement could evaluate the treatment effect.

Psidin, a conserved protein that regulates protrusion dynamics and cell migration.

Dynamic assembly and disassembly of actin filaments is a major driving force for cell movements. Border cells in the Drosophila ovary provide a simple and genetically tractable model to study the mechanisms regulating cell migration. To identify new genes that regulate cell movement in vivo, we screened lethal mutations on chromosome 3R for defects in border cell migration and identified two alleles of the gene psidin (psid). In vitro, purified Psid protein bound F-actin and inhibited the interaction of tropomyosin with F-actin. In vivo, psid mutations exhibited genetic interactions with the genes encoding tropomyosin and cofilin. Border cells overexpressing Psid together with GFP-actin exhibited altered protrusion/retraction dynamics. Psid knockdown in cultured S2 cells reduced, and Psid overexpression enhanced, lamellipodial dynamics. Knockdown of the human homolog of Psid reduced the speed and directionality of migration in wounded MCF10A breast epithelial monolayers, whereas overexpression of the protein increased migration speed and altered protrusion dynamics in EGF-stimulated cells. These results indicate that Psid is an actin regulatory protein that plays a conserved role in protrusion dynamics and cell migration.

Fatty acids promote bovine skeletal muscle satellite cell differentiation by regulating ELOVL3 expression.

Fatty acids (FAs) play essential roles in regulating differentiation and proliferation by affecting gene expression in various cell types. However, their potential functions in bovine cells remain unclear. Herein, we examine the differentiation and proliferation of bovine skeletal muscle-derived satellite cells (MDSCs) after incubation with three types of representative FAs (palmitic acid, oleic acid and docosahexaenoic acid) by western blotting, immunofluorescence assays, flow cytometry analysis and EdU incorporation assays. The myotube fusion rate, myotube length and expression levels of muscle differentiation-related gene myogenin (MYOG) and myosin heavy chain 3 (MYH3) increased significantly, although the FAs did not affect proliferation. Additionally, FA-induced bovine MDSC differentiation increased ELOVL3 expression and relocation of ELOVL3 to cytoplasmic lipid droplets in the differentiation of bovine MDSCs. Moreover, the effect of FAs on bovine MDSC differentiation was inhibited upon ELOVL3 downregulation. Collectively, these data indicate that FAs promote bovine MDSC differentiation by regulating ELOVL3 expression.