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Background The IQ-SPECT system is equipped with multifocal collimators and uses ordered-subset conjugate gradient minimization (OSCGM) as its reconstruction algorithm, achieving a shorter acquisition time than conventional SPECT. Left ventricular ejection fraction (LVEF) is overestimated by conventional SPECT in patients with small heart size. In this study, we compared IQ-SPECT with conventional SPECT and cardiovascular magnetic resonance (CMR) for the estimation of LVEF in patients with small hearts (males: EDV ≤ 60 ml, ESV ≤ 25 ml; females: EDV ≤ 45 ml, ESV ≤ 20 ml). Methods The study consisted of 49 consecutive patients (20 normal and 29 with small heart size) undergoing gated myocardial perfusion imaging (GMPI) with a 99mTc-labelled agent during stress or rest to assess the risk of coronary artery disease (CAD). The data were reconstructed using filtered back-projection (FBP) for conventional SPECT and OSCGM for IQ-SPECT. ESV, EDV, and LVEF were calculated using quantitative gated SPECT (QGS). To determine the optimal ordered-subset reconstruction parameters, we compared the LVEF from SPECT to the corresponding measurement from CMR. Results EDV, ESV, and LVEF values obtained from IQ-SPECT and conventional SPECT showed that the results of these two forms of SPECT were significantly correlated, although the EDV and ESV obtained by IQ-SPECT were higher than those obtained by conventional SPECT. IQ-SPECT yielded lower LVEF measurements than conventional SPECT (normal heart size: 50.6 ± 4.3% vs. 73.4 ± 8.4%, P = 0.002; small heart size: 62.1 ± 7.8% vs. 75.0 ± 11.4%, P 0.05; small heart size: 62.1 ± 7.8% vs. 64.6 ± 8.8%, P > 0.05). Five subsets (S) and 12 iterations (I) did not differ significantly in LVEF between CMR and IQ-SPECT for patients with small hearts (64.6 ± 8.8% vs. 62.1 ± 7.8%, P = 0.120), while 3 S and 10 I were the best parameters for patients with normal heart size (50.6 ± 4.3% vs. 53.1 ± 5.8%, P = 0.117). Conclusion With CMR as the standard, IQ-SPECT yields more reliable LVEF values than conventional SPECT for populations with small heart size. The best reconstruction parameters from IQ-SPECT were 5 S and 12 I for patients with small hearts.

Purpose Recently, a “U” hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar “U” curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%). Methods Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated 13 N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose–response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan–Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome. Results An inverted “U” curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF n = 106) (57.9% vs 54.5% vs 34.3%, p p p p = 0.01). Conclusions Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.

Berberine is an extensively used pharmaceutical benzylisoquinoline alkaloid (BIA) derived from plants. Microbial manufacturing has emerged as a promising approach to source valuable BIAs. Here, we demonstrated the complete biosynthesis of berberine in Saccharomyces cerevisiae by engineering 19 genes including 12 heterologous genes from plants and bacteria. Overexpressing bottleneck enzymes, fermentation scale-up, and heating treatment after fermentation increased berberine titer by 643-fold to 1.08 mg L-1. This pathway also showed high efficiency to incorporate halogenated tyrosine for the synthesis of unnatural BIA derivatives that have higher therapeutical potentials. We firstly demonstrate the in vivo biosynthesis of 11-fluoro-tetrahydrocolumbamine via nine enzymatic reactions. The efficiency and promiscuity of our pathway also allow for the simultaneous incorporation of two fluorine-substituted tyrosine derivatives to 8, 3’-di-fluoro-coclaurine. This work highlights the potential of yeast as a versatile microbial biosynthetic platform to strengthen current pharmaceutical supply chain and to advance drug development.

Human beings have a fundamental need to belong. Evaluating and dealing with social exclusion and social inclusion events, which represent negative and positive social interactions, respectively, are closely linked to our physical and mental health. In addition to traditional paradigms that simulate scenarios of social interaction, images are utilized as effective visual stimuli for research on socio-emotional processing and regulation. Since the current mainstream emotional image database lacks social stimuli based on a specific social context, we introduced an open-access image database of social inclusion/exclusion in young Asian adults (ISIEA). This database contains a set of 164 images depicting social interaction scenarios under three categories of social contexts (social exclusion, social neutral, and social inclusion). All images were normatively rated on valence, arousal, inclusion score, and vicarious feeling by 150 participants in Study 1. We additionally examined the relationships between image ratings and the potential factors influencing ratings. The importance of facial expression and social context in the image rating of ISIEA was examined in Study 2. We believe that this database allows researchers to select appropriate materials for socially related studies and to flexibly conduct experimental control.

Background Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD. Methods We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis. Results A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR−/− mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-β, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway. Conclusions We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway.

Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant natural products with extensive pharmacological properties, but the yield of BIAs from plant is limited. The understanding of BIA biosynthetic mechanism in plant and the development of synthetic biology enable the possibility to produce BIAs through microbial fermentation, as an alternative to agriculture-based supply chains. In this review, we discussed the engineering strategies to synthesize BIAs in Saccharomyces cerevisiae (yeast) and improve BIA production level, including heterologous pathway reconstruction, enzyme engineering, expression regulation, host engineering and fermentation engineering. We also highlight recent metabolic engineering advances in the production of BIAs in yeast.

Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) could markedly attenuate MI-reperfusion (MIR) injury. In this study, we aimed to assess its effects on cardiac sympathetic innervation and metabolism. Transient myocardial ischemia is induced by ligature of the left anterior descending coronary artery (LAD) in male Sprague–Dawley rats, and in vivo cardiac 2-[18F]FDG and [11C]mHED PET scans were performed at 14–15 days after ischemia. RIPerc was induced by three cycles of 5-min-long unilateral hind limb ischemia and intermittent 5 min of reperfusion during LAD occlusion period. The PET quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional radioactive quantification in deficit regions to remote areas. The ex vivo radionuclide distribution was additionally identified using autoradiography. Myocardial neuron density (tyrosine hydroxylase positive staining) and chondroitin sulfate proteoglycans (CSPG, inhibiting neuron regeneration) expression were assessed by immunohistochemistry. There was no significant difference in the mean hypometabolism 2-[18F]FDG uptake ratio (44.6 ± 4.8% vs. 45.4 ± 4.4%) between MIR rats and MIR + RIPerc rats (P > 0.05). However, the mean [11C]mHED nervous activity of denervated myocardium was significantly elevated in MIR + RIPerc rats compared to the MIR rats (35.9 ± 7.1% vs. 28.9 ± 2.3%, P P

Background Cervical cancer is the fourth most common malignancy in women, which is threatening female reproductive tract health. Chemotherapy can be used for neoadjuvant therapy of locally advanced cervical cancer and postoperative adjuvant therapy for patients with high-risk factors, so as to reduce the focus, sensitize radiotherapy, and reduce recurrence. The current first-line treatment is paclitaxel combined with platinum. Many literature studies have found that As2O3 alone or in combination with platinum drugs have good efficacy in a variety of tumors both in vivo and in vitro. Moreover, our research group has verified that the efficacy of As2O3 combined with platinum drugs in the treatment of cervical cancer is not inferior to the traditional first-line regimen at the cellular and animal levels, and paclitaxel is more expensive than As2O3. Hence, we aim to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. Methods Sixty participants in the IB2, IIA2, and IIB stages of cervical cancer will be recruited in this study. After excluding patients who did not meet the criteria, they were randomly assigned to two groups in a 1:1 ratio. All patients underwent colposcopic biopsies to confirm the diagnosis and detailed clinical examinations. Eligible patients will receive either 2 cycles of paclitaxel and carboplatin or As2O3 and carboplatin every 3 weeks. Patients were assessed for clinical efficacy after the second cycle of chemotherapy. Patients who had disease stable or disease progression at these time points will receive concurrent chemotherapy and radiation directly, while responders will receive PiverRutledge grade III radical hysterectomy and bilateral pelvic lymphadenectomy. Both groups of patients undergoing radical hysterectomy were given adjuvant therapy as per protocol-defined criteria. The efficacy and toxicity of the two groups were evaluated according to WHO acute and subacute toxicity classification standards. Discussion This is the first single-center, prospective, two-arm design, open-label randomized control trial that will evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. Trial registration ChineseClinicalTrialRegistryChiCTR1900023822. Registered on 13 June 2019.

Dispersibility and magnetic response characteristics of magnetic nanoparticles is crucial to the sensitivity and stability of flexible magnetic field sensors. To improve the performance of magnetic nanoparticles, this paper reported a preparation method of the fullerene-coated ferric oxide (C60@Fe3O4) magnetic nanocomposites. The TEM results showed that the C60@Fe3O4 has uniform dispersion and consistent particle size, and C60 particles are distributed on the surface of Fe3O4, forming a coating structure. The X-ray diffraction, Fourier transform infrared spectroscopy, and energy dispersion spectroscopy results further proved that the compositions of the nanomaterials are Fe3O4 and C60. The VSM hysteresis loop of the nanocomposites showed good performance in magnetic response. Then, styrene ethylene butylene Styrene (SEBS), the C60@Fe3O4 magnetic nanoparticles, and CNTs, which were used as flexible substrate, magnetic sensitive unit, and conductive networks, respectively, composed the flexible magnetic field sensor. The measurement results of the flexible magnetic field sensor showed its high sensitivity (2.1 T−1) and good stability. The mechanism of the sensor was explored at last.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is routinely used in diffuse large B cell lymphoma (DLBCL) for staging, assessment of remission and recurrence, and estimation of therapeutic efficacy. In this study, we aimed to assess the role of an early interim PET/computed tomography (CT) in the evaluation of response in DLBCL. Sixty primary DLBCL patients (31 females) were analyzed. Baseline and follow-up 18F-FDG PET/CT was performed in patients after one cycle (n = 30) and two cycles (n = 30) of chemotherapy. The ΔSUVmax% was calculated. Patients were additionally evaluated using the conventional Deauville five-point scale (D-5PS) system. Fluorescence in situ hybridization (FISH) was employed to characterize the MYC gene status. We determined the optimum cutoff value of ΔSUVmax% using receiver operating characteristic (ROC) analysis. Kaplan–Meier analysis was applied to test for the influence of prognostic values. The optimal cutoff for the prediction of treatment outcome was a ΔSUVmax% of 57% (after one cycle) and 63% (after two cycles); we could not detect a difference in accuracy with respect to a PET scan performed after one cycle and two cycles of chemotherapy (P > 0.05). The ΔSUVmax% and the D-5PS (score 5) showed the highest prognostic value compared to a score of 3 and/or 4 (both after one cycle and two cycles). No significant difference in sensitivity, specificity, accuracy, or the area of under the curve (AUC) of ΔSUVmax% and D-5PS (score 5) was observed between PETs performed after one cycle or two cycles of therapy (P > 0.05). ΔSUVmax%, D-5PS (score 5), and MYC gene rearrangement correlated significantly (P

The trajectory data of taxies containing time dimensional and spatial dimensional information is an important kind of traffic data. How to obtain valuable information from these data has become a hot topic in the field of intelligent transportation. Existing trajectory clustering algorithms can only compute similarities using partial characteristics of the trajectory data, leading to clustering results are not accurate. This study proposes a novel trajectory clustering algorithm named GLTC, which can obtain more accurate number of clusters based on the global and local characteristics of trajectories. This study intuitively displays the laws and knowledge in clustering results using visualization techniques. Experimental results reveal that the GLTC algorithm can discover more accurate clustering results, effectively display spatial-temporal change trends in GPS data, and better assist in analyzing the flow law of urban citizens and urban traffic conditions using visualization methods.

The exposition of phosphatidylserine (PS) from the cell membrane is associated with most cell death programs (apoptosis, necrosis, autophagy, mitotic catastrophe, etc.), which makes PS an attractive target for overall cell death imaging. To this end, zinc(II) macrocycle coordination complexes with cyclic polyamine units as low-molecular-weight annexin mimics have a selective affinity for biomembrane surfaces enriched with PS, and are therefore useful for detection of cell death. In the present study, a 11C-labeled zinc(II)–bis(cyclen) complex (11C-CyclenZn2) was prepared and evaluated as a new positron emission tomography (PET) probe for cell death imaging. 11C-CyclenZn2 was synthesized by methylation of its precursor, 4-methoxy-2,5-di-[10-methyl-1,4,7,10-tetraazacyclododecane-1,4,7-tricarboxylic acid tri-tert-butyl ester] phenol (Boc-Cyclen2) with 11C-methyl triflate as a prosthetic group in acetone, deprotection by hydrolysis in aqueous HCl solution, and chelation with zinc nitrate. The cell death imaging capability of 11C-CyclenZn2 was evaluated using in vitro cell uptake assays with camptothecin-treated PC-3 cells, biodistribution studies, and in vivo PET imaging in Kunming mice bearing S-180 fibrosarcoma. Starting from 11C-methyl triflate, the total preparation time for 11C-CyclenZn2 was ~40 min, with an uncorrected radiochemical yield of 12 ± 3% (based on 11C-CH3OTf, n = 10), a radiochemical purity of greater than 95%, and the specific activity of 0.75–1.01 GBq/μmol. The cell death binding specificity of 11C-CyclenZn2 was demonstrated by significantly different uptake rates in camptothecin-treated and control PC-3 cells in vitro. Inhibition experiments for 18F-radiofluorinated Annexin V binding to apoptotic/necrotic cells illustrated the necessity of zinc ions for zinc(II)–bis(cyclen) complexation in binding cell death, and zinc(II)–bis(cyclen) complexe and Annexin V had not identical binding pattern with apoptosis/necrosis cells. Biodistribution studies of 11C-CyclenZn2 revealed a fast clearance from blood, low uptake rates in brain and muscle tissue, and high uptake rates in liver and kidney, which provide the main metabolic route. PET imaging using 11C-CyclenZn2 revealed that cyclophosphamide-treated mice (CP-treated group) exhibited a significant increase of uptake rate in the tumor at 60 min postinjection, compared with control mice (Control group). The results indicate that the ability of 11C-CyclenZn2 to detect cell death is comparable to Annexin V, and it has potential as a PET tracer for noninvasive evaluation and monitoring of anti-tumor chemotherapy.

We propose a heterogeneous multi-task learning framework for human pose estimation from monocular images using a deep convolutional neural network. In particular, we simultaneously learn a human pose regressor and sliding-window body-part and joint-point detectors in a deep network architecture. We show that including the detection tasks helps to regularize the network, directing it to converge to a good solution. We report competitive and state-of-art results on several datasets. We also empirically show that the learned neurons in the middle layer of our network are tuned to localized body parts.

Small-molecular probe 18F-labeled bis(zinc(II)-dipicolylamine) complex (18F-FB-DPAZn2) was evaluated for PET imaging of sterile inflammation. In comparison with 18F-2-deoxy-β-d-glucose (18F-FDG), 18F-radiolabeled Annexin V (18F-FB-Annexin V) showed rapid clearance of radioactivity from the kidney and low uptake in most tissues. Both the lower radioactivity accumulation in brain and heart and the higher uptakes in the lung, liver, and intestine were observed for the biodistribution of 18F-FB-DPAZn2. In PET imaging, 18F-FDG showed significantly higher tumor and inflammation uptake than did of 18F-FB-DPAZn2 and 18F-FB-Annexin V in the S-180 fibrosarcoma mouse model and sterile inflammation mouse model. Both 18F-FB-DPAZn2 and 18F-FB-Annexin V performed the specifically localization in inflammation, and the ratios of inflammatory lesion-to-muscle and tumor-to-muscle were 1.83 ± 0.20 and 0.90 ± 0.12 (P 0.05) for 18F-FB-Annexin V, respectively. Terminal deoxynucleotide end-labeling (TUNEL) assays performed on the dissected tissues showed the significantly more TUNEL-positive nuclei in the inflammatory muscle than in tumor and normal muscle, and these TUNEL results correlated with the uptake of 18F-FB-DPAZn2 in dissected tissues. Biodistribution and PET imaging studies showed that the 18F-FB-DPAZn2 is suitable for imaging sterile inflammation in vivo and is capable of the differentiating tumor from inflammation.

The aim of this study was to compare the properties and feasibility of the glucose analog, 2-18F-fluoro-2-deoxy-D-glucose (18F-FDG), three short 18F-labeled carboxylic acids, 18F-fluoroacetate (18F-FAC), 2-18F-fluoropropionic acid (18F-FPA) and 4-(18F)fluorobenzoic acid (18F-FBA), for differentiating tumors from inflammation. Biodistributions of 18F-FAC, 18F-FPA and 18F-FBA were determined on normal Kunming mice, and positron emission tomography (PET) imaging with these tracers were performed on the separate tumor-bearing mice model and inflammation mice model in comparison with 18F-FDG. Biodistribution results showed that 18F-FAC and 18F-FPA had similar biodistribution profiles and the slow radioactivity clearance from most tissues excluding the in vivo defluorination of 18F-FAC, and 18F-FBA demonstrated a lower uptake and fast clearance in most tissues. PET imaging with 18F-FDG, 18F-FAC and 18F-FPA revealed the high uptake in both tumor and inflammatory lesions. The ratios of tumor-to-inflammation were 1.63 ± 0.28 for 18F-FDG, 1.20 ± 0.38 for 18F-FAC, and 1.41 ± 0.33 for 18F-FPA at 60 min postinjection, respectively. While clear tumor images with high contrast between tumor and inflammation lesion were observed in 18F-FBA/PET with the highest ratio of tumor-to-inflammation (1.98 ± 0.15). Our data demonstrated 18F-FBA is a promising PET probe to distinguish tumor from inflammation. But the further modification of 18F-FBA structure is required to improve its pharmacokinetics.

In this review, we focus mainly on the clinical applications of myocardial perfusion imaging (MPI) with single-photon emission CT (SPECT) and metabolic imaging in clinical practice. Important advances have been made in the clinical applications of MPI, including its role in stratifying risk and guiding management decisions. The impact of incomplete and complete myocardial ischemia correction on long-term outcomes was analyzed and compared with complete and incomplete diseased vessel intervention. Importantly, a new pharmacologic stress testing agent—higenamine—was developed and has completed phase III clinical trials. Ventricular synchrony was assessed by phase analysis of gated MPI in healthy Chinese subjects and in patients with or without left ventricular (LV) dysfunction. Finally, the clinical value of technetium (99mTc) sestamibi SPECT and fludeoxyglucose (18F-FDG) positron emission tomography (PET) in patients with LV aneurysms was deeply investigated. Viability of LV aneurysm in patients with ischemic cardiomyopathy was a negative independent predictor of survival. The diagnostic accuracy of LV parameters analyzed by both gated SPECT and gated PET was investigated in patients with LV aneurysm, who revealed severe perfusion defects and LV remodeling. Additionally, end-systolic volume measured by gated PET was the only independent predictor of cardiac death among all the LV functional parameters evaluated by gated SPECT, gated PET, cardiac magnetic resonance imaging, and echocardiography.