Benchmarking spatial clustering methods with spatially resolved transcriptomics data.

Spatial clustering, which shares an analogy with single-cell clustering, has expanded the scope of tissue physiology studies from cell-centroid to structure-centroid with spatially resolved transcriptomics (SRT) data. Computational methods have undergone remarkable development in recent years, but a comprehensive benchmark study is still lacking. Here we present a benchmark study of 13 computational methods on 34 SRT data (7 datasets). The performance was evaluated on the basis of accuracy, spatial continuity, marker genes detection, scalability, and robustness. We found existing methods were complementary in terms of their performance and functionality, and we provide guidance for selecting appropriate methods for given scenarios. On testing additional 22 challenging datasets, we identified challenges in identifying noncontinuous spatial domains and limitations of existing methods, highlighting their inadequacies in handling recent large-scale tasks. Furthermore, with 145 simulated data, we examined the robustness of these methods against four different factors, and assessed the impact of pre- and postprocessing approaches. Our study offers a comprehensive evaluation of existing spatial clustering methods with SRT data, paving the way for future advancements in this rapidly evolving field.

pH Mapping of Gliomas Using Quantitative Chemical Exchange Saturation Transfer MRI: Quasi-Steady-State, Spillover-, and MT-Corrected Omega Plot Analysis.

BACKGROUND: Quantitative in-situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH-dependent exchange rate (ksw ), the reliable quantification of ksw in glioma remains constrained due to technical challenges. PURPOSE: To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis. STUDY TYPE: Prospective. PHANTOMS/ANIMAL MODEL/SUBJECTS: Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas. FIELD STRENGTH/SEQUENCE: 11.7 T, 7.0 T, CEST imaging, T2 -weighted (T2 W) imaging, and T1 -mapping. ASSESSMENT: Omega plot analysis, quasi-steady-state (QUASS) analysis, multi-pool Lorentzian fitting, amine and amide concentration-independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis. STATISTICAL TESTS: Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters. RESULTS: In vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH-4.198) ; lysates: ksw = 185.1 + 0.101 × 10(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω1 2 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s-1 vs. 403.54 ± 51.01 s-1 , P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data. DATA CONCLUSION: Utilizing QUASS-based, spillover-, and MT-corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 1.

Assessment of early anthracycline-induced cardiotoxicity and liver injury with T2 and T2* mapping in rabbit models.

OBJECTIVES: To evaluate the early prevalence of anthracycline-induced cardiotoxicity (AIC) and anthracycline-induced liver injury (AILI) using T2 and T2* mapping and to explore their correlations. MATERIALS AND METHODS: The study included 17 cardiotoxic rabbits that received weekly injections of doxorubicin and magnetic resonance imaging (MRI) every 2 weeks for 10 weeks. Cardiac function and T2 and T2* values were measured on each period. Histopathological examinations for two to five rabbits were performed after each MRI scan. The earliest sensitive time and the threshold of MRI parameters for detecting AIC and AILI based on these MRI parameters were obtained. Moreover, the relationship between myocardial and liver damage was assessed. RESULTS: Early AIC could be detected by T2 mapping as early as the second week and focused on the 7th, 11th, and 12th segments of left ventricle. The cutoff value of 46.64 for the 7th segment had the best diagnostic value, with an area under the curve (of 0.767, sensitivity of 100%, and specificity of 52%. T2* mapping could detect the change in iron content for early AIC at the middle interventricular septum and AILI as early as the sixth week (p = 0.014, p = 0.027). The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver (r = 0.39, p = 0.002). CONCLUSION: T2 and T2* mapping showed value one-stop assessment of AIC and AILI and could obtain the earliest MRI diagnosis point and optimal parameter thresholds for these conditions. CLINICAL RELEVANCE STATEMENT: Anthracycline-induced cardiotoxicity could be detected by T2 mapping as earlier as the second week, mainly focusing on the 7th, 11th, and 12th segments of left ventricle. Combined with T2* mapping, hepatoxicity and supplementary cardiotoxicity were assessed by one-stop scan. KEY POINTS: • MRI screening time of cardiotoxicity was as early as the second week with focusing on T2 values of the 7th, 11th, and 12th segments of left ventricle. • T2* mapping could be used as a complement to T2 mapping to evaluate cardiotoxicity and as an effective index to detect iron change in the early stages of chemotherapy. • The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver, indicating that iron content in the liver and heart increased with an increase in the chemotherapeutic drugs.

Accelerated 3D MR neurography of the brachial plexus using deep learning-constrained compressed sensing.

OBJECTIVES: To explore the use of deep learning-constrained compressed sensing (DLCS) in improving image quality and acquisition time for 3D MRI of the brachial plexus. METHODS: Fifty-four participants who underwent contrast-enhanced imaging and forty-one participants who underwent unenhanced imaging were included. Sensitivity encoding with an acceleration of 2 × 2 (SENSE4x), CS with an acceleration of 4 (CS4x), and DLCS with acceleration of 4 (DLCS4x) and 8 (DLCS8x) were used for MRI of the brachial plexus. Apparent signal-to-noise ratios (aSNRs), apparent contrast-to-noise ratios (aCNRs), and qualitative scores on a 4-point scale were evaluated and compared by ANOVA and the Friedman test. Interobserver agreement was evaluated by calculating the intraclass correlation coefficients. RESULTS: DLCS4x achieved higher aSNR and aCNR than SENSE4x, CS4x, and DLCS8x (all p < 0.05). For the root segment of the brachial plexus, no statistically significant differences in the qualitative scores were found among the four sequences. For the trunk segment, DLCS4x had higher scores than SENSE4x (p = 0.04) in the contrast-enhanced group and had higher scores than SENSE4x and DLCS8x in the unenhanced group (all p < 0.05). For the divisions, cords, and branches, DLCS4x had higher scores than SENSE4x, CS4x, and DLCS8x (all p ≤ 0.01). No overt difference was found among SENSE4x, CS4x, and DLCS8x in any segment of the brachial plexus (all p > 0.05). CONCLUSIONS: In three-dimensional MRI for the brachial plexus, DLCS4x can improve image quality compared with SENSE4x and CS4x, and DLCS8x can maintain the image quality compared to SENSE4x and CS4x. CLINICAL RELEVANCE STATEMENT: Deep learning-constrained compressed sensing can improve the image quality or accelerate acquisition of 3D MRI of the brachial plexus, which should be benefit in evaluating the brachial plexus and its branches in clinical practice. KEY POINTS: •Deep learning-constrained compressed sensing showed higher aSNR, aCNR, and qualitative scores for the brachial plexus than SENSE and CS at the same acceleration factor with similar scanning time. •Deep learning-constrained compressed sensing at acceleration factor of 8 had comparable aSNR, aCNR, and qualitative scores to SENSE4x and CS4x with approximately half the examination time. •Deep learning-constrained compressed sensing may be helpful in clinical practice for improving image quality and acquisition time in three-dimensional MRI of the brachial plexus.

A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling.

The genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive behaviors, without confounding comorbidities of abnormal motor function and heightened anxiety. Brain structural changes in the frontal cortex, hippocampus and cerebellar cortex were observed in Shank1 R882H-KI mice via structural magnetic resonance imaging. These key brain regions also showed severe and consistent downregulation of mGluR1-IP3R1-calcium signaling, which subsequently affected the release of intracellular calcium. Corresponding cellular structural and functional changes were present in Shank1 R882H-KI mice, including decreased spine size, reduced spine density, abnormal morphology of postsynaptic densities, and impaired hippocampal long-term potentiation and basal excitatory transmission. These findings demonstrate the causative role of SHANK1 in ASD and elucidate the underlying biological mechanism of core symptoms of ASD. We also provide a reliable model of ASD with core symptoms for future studies, such as biomarker identification and therapeutic intervention studies.

Retrograde percutaneous coronary intervention of chronic total occlusion via discontinuous septal channels.

OBJECTIVES: The study aims to investigate the safety and feasibility of retrograde CTO intervention via collateral connection grade 0 (CC-0) septal channel and to identify predictors of collateral tracking failure. BACKGROUND: Guidewire crossing a collateral channel is a critical step for successful retrograde percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). METHODS: Retrograde PCI was attempted in 122 cases of CTO with CC-0 septal collaterals from December 2018 to May 2021. A hydrophilic polymer coating guidewire was used for crossing all intended CC-0 collaterals. A multivariable logistic regression analysis was performed to identify the predictors of guidewire tracking failure via the CC-0 collaterals. RESULTS: Successful guidewire tracking via CC-0 septal channel was achieved in 98 (80.3%) of 122 cases. The independent predictors of CC-0 septal channel guidewire tracking failure included well-developed non-septal collateral (OR: 5.297, 95% CI: 1.107-25.353, p = 0.037) and the ratio length of posterior descending artery (PDA) versus the distance of PDA ostium to cardiac apex ≤2/3 (OR: 3.970, 95% CI: 1.454-10.835, p = 0.007). Collateral perforation, target vessel perforation, and cardiac tamponade occurred in 5 (4.1%), 3 (2.5%), and 6 (4.9%) cases, respectively. There were no complications requiring emergency cardiac surgery or revascularization of nontarget vessel. CONCLUSIONS: Retrograde PCI via CC-0 septal channels with a hydrophilic polymer-coated guidewire is feasible and safe in patients with CTO. Well-developed nonseptal collaterals and short PDA length influence the procedure success and the risk of guidewire tracking failure via CC-0 septal channels.

Sleep duration, brain structure, and psychiatric and cognitive problems in children.

Low sleep duration in adults is correlated with psychiatric and cognitive problems. We performed for the first time a large-scale analysis of sleep duration in children, and how this relates to psychiatric problems including depression, to cognition, and to brain structure. Structural MRI was analyzed in relation to sleep duration, and psychiatric and cognitive measures in 11,067 9-11-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study, using a linear mixed model, mediation analysis, and structural equation methods in a longitudinal analysis. Dimensional psychopathology (including depression, anxiety, impulsive behavior) in the children was negatively correlated with sleep duration. Dimensional psychopathology in the parents was also correlated with short sleep duration in their children. The brain areas in which higher volume was correlated with longer sleep duration included the orbitofrontal cortex, prefrontal and temporal cortex, precuneus, and supramarginal gyrus. Longitudinal data analysis showed that the psychiatric problems, especially the depressive problems, were significantly associated with short sleep duration 1 year later. Further, mediation analysis showed that depressive problems significantly mediate the effect of these brain regions on sleep. Higher cognitive scores were associated with higher volume of the prefrontal cortex, temporal cortex, and medial orbitofrontal cortex. Public health implications are that psychopathology in the parents should be considered in relation to sleep problems in children. Moreover, we show that brain structure is associated with sleep problems in children, and that this is related to whether or not the child has depressive problems.

Preferential Targeting Cerebral Ischemic Lesions with Cancer Cell-Inspired Nanovehicle for Ischemic Stroke Treatment.

The poor drug delivery to cerebral ischemic regions is a key challenge of ischemic stroke treatment. Inspired by the intriguing blood-brain barrier (BBB)-penetrating ability of 4T1 cancer cells upon their brain metastasis, we herein designed a promising biomimetic nanoplatform by camouflaging a succinobucol-loaded pH-sensitive polymeric nanovehicle with a 4T1 cell membrane (MPP/SCB), aiming to promote the preferential targeting of cerebral ischemic lesions to attenuate the ischemia/reperfusion injury. In transient middle cerebral artery occlusion (tMCAO) rat models, MPP/SCB could be preferentially delivered to the ischemic hemisphere with a 4.79-fold higher than that in the normal hemisphere. Moreover, MPP/SCB produced notable enhancement of microvascular reperfusion in the ischemic hemisphere, resulting in a 69.9% reduction of infarct volume and showing remarkable neuroprotective effects of tMCAO rats, which was superior to the counterpart uncamouflaged nanovehicles (PP/SCB). Therefore, this design provides a promising nanoplatform to target the cerebral ischemic lesions for ischemic stroke therapy.

Resveratrol, an Inhibitor Binding to VEGF, Restores the Pathology of Abnormal Angiogenesis in Retinopathy of Prematurity (ROP) in Mice: Application by Intravitreal and Topical Instillation.

Retinopathy of prematurity (ROP) is a severe eye disease leading to blindness. Abnormal vessel formation is the pathological hallmark of neovascular ROP. In forming vessels, vascular endothelial growth factor (VEGF) is an important stimulator. The current anti-ROP therapy has focused on bevacizumab, a monoclonal antibody against VEGF, and pazopanib, a tyrosine kinase inhibitor on the VEGF receptor (VEGFR). Several lines of evidence have proposed that natural compounds may be more effective and safer for anti-VEGF function. Resveratrol, a common natural compound, binds to VEGF and blocks its interaction with VEGFR, thereafter suppressing angiogenesis. Here, we evaluate the efficacy of intravitreal injection, or topical instillation (eye drops), of resveratrol into the eyes of mice suffering from oxygen-induced retinopathy, i.e., developing ROP. The treatment of resveratrol significantly relieved the degree of vascular distortion, permeability and hyperplasia; the efficacy could be revealed by both methods of resveratrol application. In parallel, the treatments of resveratrol inhibited the retinal expressions of VEGF, VEGFR and CD31. Moreover, the applied resveratrol significantly relieved the damage caused by oxygen radicals through upregulating the level of superoxide dismutase (SOD) and downregulating the level of malondialdehyde (MDA) in the retina. Taken together, the potential therapeutic benefit of resveratrol in pro-angiogenic diseases, including retinopathy, can be considered.

Preliminary demonstration of in vivo quasi-steady-state CEST postprocessing-Correction of saturation time and relaxation delay for robust quantification of tumor MT and APT effects.

PURPOSE: Chemical exchange saturation transfer (CEST) MRI is versatile for measuring the dilute labile protons and microenvironment properties. However, the use of insufficiently long RF saturation duration (Ts) and relaxation delay (Td) may underestimate the CEST measurement. This study proposed a quasi-steady-state (QUASS) CEST analysis for robust CEST quantification. METHODS: The CEST signal evolution was modeled as a function of the longitudinal relaxation rate during Td and spin-lock relaxation rate during Ts, from which the QUASS-CEST effect is derived. Numerical simulation and in vivo rat glioma MRI experiments were conducted at 11.7 T to compare the apparent and QUASS-CEST results obtained under different Ts/Td of 2 seconds/2 seconds and 4 seconds/4 seconds. Magnetization transfer and amide proton transfer effects were resolved using a multipool Lorentzian fitting and evaluated in contralateral normal tissue and tumor regions. RESULTS: The simulation showed the dependence of the apparent CEST effect on Ts and Td, and such reliance was mitigated with the QUASS algorithm. Animal experiment results showed that the apparent magnetization transfer and amide proton transfer effects and their contrast between contralateral normal tissue and tumor regions increased substantially with Ts and Td. In comparison, the QUASS magnetization transfer and amide proton transfer effects and their difference between contralateral normal tissue and tumor exhibited little dependence on Ts and Td. In addition, the apparent magnetization transfer and amide proton transfer were significantly smaller than the corresponding QUASS indices (P < .05). CONCLUSION: The QUASS-CEST algorithm enables robust CEST quantification and offers a straightforward approach to standardize CEST experiments.

Pointwise encoding time reduction with radial acquisition in subtraction-based magnetic resonance angiography to assess saccular unruptured intracranial aneurysms at 3 Tesla.

PURPOSE: To investigate the clinical utility of pointwise encoding time reduction with radial acquisition in subtraction-based magnetic resonance angiography (PETRA-MRA) and time-of-flight magnetic resonance angiography (TOF-MRA) to evaluate saccular unruptured intracranial aneurysms (UIAs). METHODS: A total of 49 patients with 54 TOF-MRA-identified saccular UIAs were enrolled. The morphologic parameters, contrast-to-noise-ratios (CNRs), and sharpness of aneurysms were measured using PETRA-MRA and TOF-MRA. Two radiologists independently evaluated subjective image scores, focusing on aneurysm signal homogeneities and sharpness depictions using a 4-point scale: 4, excellent; 3, good; 2, poor; 1, not assessable. PETRA-MRA and TOF-MRA acoustic noises were measured. RESULTS: All aneurysms were detected with PETRA-MRA. The morphologic parameters of 15 patients evaluated with PETRA-MRA were more closely correlated with those receiving computed tomography angiography over those receiving TOF-MRA. No significant differences between PETRA-MRA and TOF-MRA parameters were seen in the 54 UIAs (p > 0.10), excluding those with inflow angles (p < 0.05). In four patients with inflow angles on PETRA-MRA, the angles were more closely related to those of digital subtraction angiography than those of TOF-MRA. CNRs between TOF-MRA and PETRA-MRA were comparable (p = 0.068), and PETRA-MRA sharpness values and subjective image scores were significantly higher than those of TOF-MRA (p < 0.001). Inter-observer agreements were excellent for both PETRA-MRA and TOF-MRA (intraclass correlation coefficients were 0.90 and 0.97, respectively). The acoustic noise levels of PETRA-MRA were much lower than those of TOF-MRA (59 vs.73 dB, p < 0.01). CONCLUSIONS: PETRA-MRA, with better visualization of aneurysms and lower acoustic noise levels than TOF-MRA, showed a superior diagnostic performance for depicting saccular UIAs.

Systematic analysis of the basic/helix-loop-helix (bHLH) transcription factor family in pummelo (Citrus grandis) and identification of the key members involved in the response to iron deficiency.

BACKGROUND: Iron (Fe) deficiency is a common problem in citrus production. As the second largest superfamily of transcription factors (TFs), the basic/helix-loop-helix (bHLH) proteins have been shown to participate in the regulation of Fe homeostasis and a series of other biological and developmental processes in plants. However, this family of members in citrus and their functions in citrus Fe deficiency are still largely unknown. RESULTS: In this study, we identified a total of 128 CgbHLHs from pummelo (Citrus grandis) genome that were classified into 18 subfamilies by phylogenetic comparison with Arabidopsis thaliana bHLH proteins. All of these CgbHLHs were randomly distributed on nine known (125 genes) and one unknown (3 genes) chromosomes, and 12 and 47 of them were identified to be tandem and segmental duplicated genes, respectively. Sequence analysis showed detailed characteristics of their intron-exon structures, bHLH domain and conserved motifs. Gene ontology (GO) analysis suggested that most of CgbHLHs were annotated to the nucleus, DNA-binding transcription factor activity, response to abiotic stimulus, reproduction, post-embryonic development, flower development and photosynthesis. In addition, 27 CgbHLH proteins were predicted to have direct or indirect protein-protein interactions. Based on GO annotation, RNA sequencing data in public database and qRT-PCR results, several of CgbHLHs were identified as the key candidates that respond to iron deficiency. CONCLUSIONS: In total, 128 CgbHLH proteins were identified from pummelo, and their detailed sequence and structure characteristics and putative functions were analyzed. This study provides comprehensive information for further functional elucidation of CgbHLH genes in citrus.

Potential α-glucosidase inhibitor from Hylotelephium erythrostictum.

In light of the adequate sources for Hylotelephium erythrostictum, its active components have aroused research interest. 2-(3',4'-dihydroxyphenyl)-2,3-dihydro-4,6-dihydroxy-2-(methoxy)- 3-benzofuranone(1), apigenin(2), diosmetin(3), kaempferol(4), kaempferide(5), rhamnocitrin(6), quercetin(7), and gallic acid(8) were isolated from H. erythrostictum. Rarely occurring naturally, 1 is 2-methoxybenzofuranone type compound against α-glucosidase and exhibits a potential inhibitory effect on α-glucosidase(IC50 = 1.8 µM), with a Ki value of 709 nM. In silico molecular docking was performed for the investigation of the inhibition mechanism. H. erythrostictum is a potential source of antidiabetic agent. This information is useful in finding more potent antidiabetic candidates from medicinal plants for the clinical development of therapeutics.

Selective C-H dithiocarbamation of arenes and antifungal activity evaluation.

This paper discloses a transition metal-free selective C-H dithiocarbamation of drug skeletons using disulfiram (DSF) in the presence of KI/K2S2O8 in DMF/H2O. Drug skeletons, including 5-aminopyrazoles, indoles, pyrroloquinoline, and Julolidine, underwent C-H dithiocarbamation smoothly to afford a variety of drug-like molecules in moderate to good yields. It was found that the in situ formed 5-aminopyrazole iodide is the key intermediate for the dithiocarbamation. Bioassay results show that some of these N-heterocyclic dithiocarbamate derivatives exhibit good antifungal activity against Colletotrichum gloeosprioides and Fusarium oxysporum, F. proliferatum, Fusarium solani, Geotrichum candidum, Penicillium digitatum, Penicillium italicum, Phyricularia grisea.

Cough maneuver is superior to Valsalva maneuver for detecting mild-extent right-to-left shunt.

Objective: The purpose of this study was to explore the different provocative maneuvers in detecting right-to-left shunt during contrast transthoracic echocardiography (cTTE). Methods: We evaluated 378 patients for right-to-left shunt detection by cTTE at the quiet respiration, during Valsalva maneuver (blowing into a face mask connected to a sphygmomanometer at 40 mmHg for 10 s), and during cough maneuver, performed in random order, and the degree of right-to-left shunt as the number of microbubbles in the left atrium per frame after each provocative maneuver was recorded. Results: The detection rates of right-to-left shunt for quiet respiration, Valsalva maneuver, and cough maneuver were 16%, 33%, and 38%, respectively (p < .001). The detection rate for cough maneuver was significantly higher than that for Valsalva maneuver (p < .001). There was no significant difference between Valsalva maneuver and cough maneuver in terms of detecting moderate- or severe-extent right-to-left shunt (p > .05), but cough maneuver was significantly better than Valsalva maneuver at detecting mild-extent right-to-left shunt (p = .001). Conclusions: Cough maneuver is an effective alternative to Valsalva maneuver, with a higher detection rate for mild-extent right-to-left shunt during cTTE, maybe due to its own mechanical characteristics.

Noninvasive detection of coronary artery stents by transthoracic echocardiography postprocessing subtraction technique.

AIM: To explore the feasibility and value of transthoracic echocardiography (TTE) postprocessing subtraction technique in the detection of a stent in the coronary artery. METHOD: Transthoracic echocardiography was used to examine 46 coronary artery stents in 30 patients by two-dimensional ultrasound postprocessing subtraction technique. The shape of each stent and its flow patency were observed. The patency was assessed according to blood flow and mosaic flow in the stent. Then, the results were compared with those of percutaneous coronary intervention (PCI) records and coronary angiography (CAG). RESULTS: Transthoracic echocardiography detected 36 stents among 46 stents (two in the LMCA, 23 in the LAD, seven in the RCA, and two in the LCX); the detection rate was 78.3%. The average length of the stents was 21.8 ± 4.1 mm, and the average diameter was 2.4 ± 0.5 mm; both are shorter than those from PCI records (P < .001). Of the 36 stents, blood flow could be observed in 27. Compared with the results of CAG, TTE had 75% feasibility and 92.6% accuracy in detecting flow patency in the stents. CONCLUSION: Transthoracic echocardiography postprocessing subtraction technique could be a noninvasive method for detecting a coronary artery stent and, although the measurements of stent length and diameter were shorter than those of PCI records, an accurate detection of flow patency in the stents was achieved.

Whole-transcriptome RNA sequencing reveals the global molecular responses and ceRNA regulatory network of mRNAs, lncRNAs, miRNAs and circRNAs in response to copper toxicity in Ziyang Xiangcheng (Citrus junos Sieb. Ex Tanaka).

BACKGROUND: Copper (Cu) toxicity has become a potential threat for citrus production, but little is known about related mechanisms. This study aims to uncover the global landscape of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in response to Cu toxicity so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) and to provide valuable knowledge pertinent to Cu response in citrus. RESULTS: Tolerance of four commonly used rootstocks to Cu toxicity was evaluated, and 'Ziyang Xiangcheng' (Citrus junos) was found to be the most tolerant genotype. Then the roots and leaves sampled from 'Ziyang Xiangcheng' with or without Cu treatment were used for whole-transcriptome sequencing. In total, 5734 and 222 mRNAs, 164 and 5 lncRNAs, 45 and 17 circRNAs, and 147 and 130 miRNAs were identified to be differentially expressed (DE) in Cu-treated roots and leaves, respectively, in comparison with the control. Gene ontology enrichment analysis showed that most of the DEmRNAs and targets of DElncRNAs and DEmiRNAs were annotated to the categories of 'oxidation-reduction', 'phosphorylation', 'membrane', and 'ion binding'. The ceRNA network was then constructed with the predicted pairs of DEmRNAs-DEmiRNAs and DElncRNAs-DEmiRNAs, which further revealed regulatory roles of these DERNAs in Cu toxicity. CONCLUSIONS: A large number of mRNAs, lncRNAs, circRNAs, and miRNAs in 'Ziyang Xiangcheng' were altered in response to Cu toxicity, which may play crucial roles in mitigation of Cu toxicity through the ceRNA regulatory network in this Cu-tolerant rootstock.

Biodiversity and antifouling activity of fungi associated with two soft corals from the South China Sea.

Bacteria in corals have been studied in detail in the past decades. However, the biodiversity and bioactivity of fungi in corals are still poorly understood. This study investigated the biodiversity and antifouling activity of fungi in soft corals Cladiella krempfi and Sarcophyton tortuosum from the South China Sea. A high diverse and abundant fungal community was found in the two soft corals. Furthermore, five isolates shared 83-95% similarity with their closest relatives, indicating that they might be novel species in genera Phaeoshaeria and Mucor. In addition, approximately 50% of the representative isolates exhibited distinct antifouling activity. In particular, isolates Fungal sp. SCAU132 and Fungal sp. SCAU133 displayed very strong antifouling activity against Bugula neritina, suggesting they can provide a potential resource for further investigation on isolation of novel antifouling metabolites. To our knowledge, this study is the first report to investigate the biodiversity and antifouling activity of fungi in C. krempfi and S. tortuosum.

Value of the cough maneuver for detecting right-to-left shunt during contrast transthoracic echocardiography.

AIM: To explore the value of cough maneuver (CM) in detecting right-to-left (RLS) during contrast transthoracic echocardiography (cTTE) and its mechanism. METHOD: We enrolled 196 patients with a high level of clinical suspicion of RLS underwent cTTE for RLS detection. Valsalva maneuver (VM) (blowing into a face mask connected to a sphygmomanometer at 40 mm Hg for 10 seconds) and CM were performed to provoke RLS, respectively. A comparison of the two provocative maneuvers in terms of the RLS-detection rate, the degree of RLS, the mobility of septum primum was done. RESULTS: The detection rates of RLS for CM were significantly higher than that for VM (38.3% vs 32.1%), (P < 0.001). There was no significant difference between VM and CM in terms of detecting moderate- or severe-extent RLS (P > 0.05), however, CM was significantly better than VM in detecting mild-extent RLS (P = 0.004). CM caused a greater mobility of septum primum than VM (20.1 ± 0.2 mm vs 6.3 ± 0.1 mm), (P < 0.001). CONCLUSION: Cough maneuver had a higher detection rate for RLS than VM during cTTE, maybe due to its greater mobility of septum primum than VM caused.

Increased CEST specificity for amide and fast-exchanging amine protons using exchange-dependent relaxation rate.

Chemical exchange saturation transfer (CEST) imaging of amides at 3.5 ppm and fast-exchanging amines at 3 ppm provides a unique means to enhance the sensitivity of detection of, for example, proteins/peptides and neurotransmitters, respectively, and hence can provide important information on molecular composition. However, despite the high sensitivity relative to conventional magnetic resonance spectroscopy (MRS), in practice, CEST often has relatively poor specificity. For example, CEST signals are typically influenced by several confounding effects, including direct water saturation (DS), semi-solid non-specific magnetization transfer (MT), the influence of water relaxation times (T1w ) and nearby overlapping CEST signals. Although several editing techniques have been developed to increase the specificity by removing DS, semi-solid MT and T1w influences, it is still challenging to remove overlapping CEST signals from different exchanging sites. For instance, the amide proton transfer (APT) signal could be contaminated by CEST effects from fast-exchanging amines at 3 ppm and intermediate-exchanging amines at 2 ppm. The current work applies an exchange-dependent relaxation rate (Rex ) to address this problem. Simulations demonstrate that: (1) slowly exchanging amides and fast-exchanging amines have distinct dependences on irradiation powers; and (2) Rex serves as a resonance frequency high-pass filter to selectively reduce CEST signals with resonance frequencies closer to water. These characteristics of Rex provide a means to isolate the APT signal from amines. In addition, previous studies have shown that CEST signals from fast-exchanging amines have no distinct features around their resonance frequencies. However, Rex gives Lorentzian lineshapes centered at their resonance frequencies for fast-exchanging amines and thus can significantly increase the specificity of CEST imaging for amides and fast-exchanging amines.