Feasibility and Diagnostic Performance of Functional SYNTAX Score Derived From Dynamic CT Myocardial Perfusion Imaging.

BACKGROUND: Computed tomography (CT) fractional flow reserve (FFR)-derived functional SYNTAX score (FSSCT-FFR) is a valuable method for guiding treatment strategy in patients with multivessel coronary artery disease. Dynamic CT myocardial perfusion imaging (CT-MPI) demonstrates higher diagnostic accuracy than CT-FFR in identifying hemodynamically significant coronary artery disease. We aimed to evaluate the feasibility of CT-MPI-derived FSS (FSSCT-MPI) with reference to invasive FSS. METHODS: In this retrospective study, patients with multivessel coronary artery disease who underwent dynamic CT-MPI+ coronary CT angiography and invasive coronary angiography or FFR within 4 weeks were consecutively included. Invasive (FSSinvasive) and noninvasive FSS (FSSCT-MPI and FSSCT-FFR) were calculated by an online calculator, which assigned points to lesions with hemodynamic significance (defined as FFRinvasive ≤0.80, invasive coronary angiography diameter stenosis ≥90%, CT-FFR ≤0.80, and myocardial ischemia on CT-MPI). Weighted κ value and net reclassification index were calculated to determine the consistency and incremental discriminatory power of FSSCT-MPI. Receiver operating characteristic curve analysis was used for the comparison of FSSCT-MPI and FSSCT-FFR in detecting intermediate- to high-risk patients. RESULTS: A total of 119 patients (96 men; 64.6±10.6 years) with 305 obstructive lesions were included. The average FSSCT-MPI, FSSCT-FFR, and FSSinvasive were 15.58±13.03, 16.18±13.30, and 13.11±12.22, respectively. The agreement on risk classification based on the FSSCT-MPI tertiles was good (weighted κ, 0.808). With reference to FSSinvasive, FSSCT-MPI correctly reclassified 27 (22.7%) patients from the intermediate- to high SYNTAX score group to the low-score group (net reclassification index, 0.30; P<0.001). In patients with severe calcification, FSSCT-MPI had better diagnostic value than FSSCT-FFR in detecting intermediate- to high-risk patients when compared with FSSinvasive (area under the curve, 0.976 versus 0.884; P<0.001). CONCLUSIONS: Noninvasive FSS derived from CT-MPI is feasible and has strong concordance with FSSinvasive. It allows accurate categorization of FSS in patients with multivessel coronary artery disease, in particular with severe calcification.

Diagnostic and prognostic performance of artificial intelligence-based fully-automated on-site CT-FFR in patients with CAD.

Currently, clinically available coronary CT angiography (CCTA) derived fractional flow reserve (CT-FFR) is time-consuming and complex. We propose a novel artificial intelligence-based fully-automated, on-site CT-FFR technology, which combines the automated coronary plaque segmentation and luminal extraction model with reduced order 3 dimentional (3D) computational fluid dynamics. A total of 463 consecutive patients with 600 vessels from the updated China CT-FFR study in Cohort 1 undergoing both CCTA and invasive fractional flow reserve (FFR) within 90 d were collected for diagnostic performance evaluation. For Cohort 2, a total of 901 chronic coronary syndromes patients with index CT-FFR and clinical outcomes at 3-year follow-up were retrospectively analyzed. In Cohort 3, the association between index CT-FFR from triple-rule-out CTA and major adverse cardiac events in patients with acute chest pain from the emergency department was further evaluated. The diagnostic accuracy of this CT-FFR in Cohort 1 was 0.82 with an area under the curve of 0.82 on a per-patient level. Compared with the manually dependent CT-FFR techniques, the operation time of this technique was substantially shortened by 3 times and the number of clicks from about 60 to 1. This CT-FFR technique has a highly successful (> 99%) calculation rate and also provides superior prediction value for major adverse cardiac events than CCTA alone both in patients with chronic coronary syndromes and acute chest pain. Thus, the novel artificial intelligence-based fully automated, on-site CT-FFR technique can function as an objective and convenient tool for coronary stenosis functional evaluation in the real-world clinical setting.

Prognostic implications of pre-transcatheter aortic valve replacement computed tomography-derived coronary plaque characteristics and stenosis severity.

OBJECTIVES: The study aimed to investigate the prognostic value of pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) in assessing physiological stenosis severity (CTA-derived fractional flow reserve (CT-FFR)) and high-risk plaque characteristics (HRPC). MATERIALS AND METHODS: Among TAVR patients who underwent pre-procedure CTA, the presence and number of HRPCs (minimum lumen area of < 4 mm2, plaque burden ≥ 70%, low-attenuating plaques, positive remodeling, napkin-ring sign, or spotty calcification) as well as CT-FFR were assessed. The risk of vessel-oriented composite outcome (VOCO, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) was compared according to the number of HRPC and CT-FFR categories. RESULTS: Four hundred and twenty-seven patients (68.4% were male) with 1072 vessels were included. Their mean age was 70.6 ± 10.6 years. Vessels with low CT-FFR (≤ 0.80) (41.7% vs. 15.8%, adjusted hazard ratio (HRadj) 1.96; 95% confidence interval (CI): 1.28-2.96; p = 0.001) or lesions with ≥ 3 HRPC (38.7% vs. 16.0%, HRadj 1.81; 95%CI 1.20-2.71; p = 0.005) demonstrated higher VOCO risk. In the CT-FFR (> 0.80) group, lesions with ≥ 3 HRPC showed a significantly higher risk of VOCO than those with < 3 HRPC (34.7% vs. 13.0%; HRadj 2.04; 95%CI 1.18-3.52; p = 0.011). However, this relative increase in risk was not observed in vessels with positive CT-FFR (≤ 0.80). CONCLUSIONS: In TAVR candidates, both CT-FFR and the presence of ≥ 3 HRPC were associated with an increased risk of adverse clinical events. However, the value of HRPC differed with the CT-FFR category, with more incremental predictability among vessels with negative CT-FFR but not among vessels with positive CT-FFR. CLINICAL RELEVANCE STATEMENT: In transcatheter aortic valve replacement (TAVR) candidates, pre-TAVR CTA provided the opportunity to assess coronary physiological stenosis severity and high-risk plaque characteristics, both of which are associated with worse clinical outcomes. KEY POINTS: • The current study investigated the prognostic value of coronary physiology significance and plaque characteristics in transcatheter aortic valve replacement patients. • The combination of coronary plaque vulnerability and physiological significance showed improved accuracy in predicting clinical outcomes in transcatheter aortic valve replacement patients. • Pre-transcatheter aortic valve replacement CT can be a one-stop-shop tool for coronary assessments in clinical practice.

Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex.

BACKGROUND: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear. METHODS: Given the known role of Ptpn23 (protein tyrosine phosphatase, nonreceptor type 23) in regulating membrane deformation, its expression in patients with dilated cardiomyopathy was determined. Taking advantage of Cre/Loxp, CRISPR/Cas9, and adeno-associated virus 9 (AAV9)-mediated in vivo gene editing, we generated cardiomyocyte-specific Ptpn23 and Actn2 (α-actinin-2, a major component of Z-discs) knockout mice. We also perturbed the DGC by using dystrophin global knockout mice (DmdE4*). MM 4-64 and Di-8-ANEPPS staining, Cav3 immunofluorescence, and transmission electron microscopy were performed to determine T-tubule structure in isolated cells and intact hearts. In addition, the assembly of the DGC with Ptpn23 and dystrophin loss of function was determined by glycerol-gradient fractionation and SDS-PAGE analysis. RESULTS: The expression level of Ptpn23 was reduced in failing hearts from dilated cardiomyopathy patients and mice. Genetic deletion of Ptpn23 resulted in disorganized T-tubules with enlarged diameters and progressive dilated cardiomyopathy without affecting sarcomere organization. AAV9-mediated mosaic somatic mutagenesis further indicated a cell-autonomous role of Ptpn23 in regulating T-tubule formation. Genetic and biochemical analyses showed that Ptpn23 was essential for the integrity of costameres, which anchor the T-tubule membrane to Z-discs, through interactions with α-actinin and dystrophin. Deletion of α-actinin altered the subcellular localization of Ptpn23 and DGCs. In addition, genetic inactivation of dystrophin caused similar T-tubule defects to Ptpn23 loss-of-function without affecting Ptpn23 localization at Z-discs. Last, inducible Ptpn23 knockout at 1 month of age showed Ptpn23 is also required for the maintenance of T-tubules in adult cardiomyocytes. CONCLUSIONS: Ptpn23 is essential for cardiac T-tubule formation and maintenance along Z-discs. During postnatal heart development, Ptpn23 interacts with sarcomeric α-actinin and coordinates the assembly of the DGC at costameres to sculpt T-tubule spatial patterning and morphology.

Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode.

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

Dual-Catalyzed Stereodivergent Electrooxidative Homocoupling of Benzoxazolyl Acetate.

The development of a reliable strategy for stereodivergent radical reactions that allows convenient access to all stereoisomers of homocoupling adducts with multiple stereogenic centers remains an unmet goal in organic synthesis. Herein, we describe a dual-catalyzed electrooxidative C(sp3)-H/C(sp3)-H homocoupling with complete absolute and relative stereocontrol for the synthesis of molecules with contiguous quaternary stereocenters in a general and predictable manner. The stereodivergent electrooxidative homocoupling reaction is achieved by synergistically utilizing two distinct chiral catalysts that convert identical racemic substrates into inherently distinctive reactive chiral intermediates, dictate enantioselective radical addition, and allow access to the full complement of stereoisomeric products via simple catalyst permutation. The successful execution of the dual-electrocatalytic strategy programmed via electrooxidative activation provides a significant conceptual advantage and will serve as a useful foundation for further research into cooperative stereocontrolled radical transformations and diversity-oriented synthesis.

Integrated CO2 capture and conversion via H2-driven CO2 biomethanation: Cyclic performance and microbial community response.

This study investigated the use of H2-driven CO2 biomethanation for integrated CO2 capture and conversion (iCCC). Anaerobic chambers containing Na2CO3-amended microbial growth medium provided with H2 were inoculated with anaerobic granular sludge. Microorganisms were enriched that could regenerate carbonate by using the bicarbonate formed from CO2 absorption to generate methane. Multiple absorption-regeneration cycles were performed and effective restoration of CO2 absorption capacity and stable carbonate recycling via CO2 biomethanation were observed for CO2 absorbents adjusted to three different pH values (9.0, 9.5, and 10.0). The pH = 10.0 group had the highest CO2 absorption capacity; 65.3 mmol/L in the 5th cycle. A slight alkaline inhibition of acetoclastic methanogenesis occurred near the end of regeneration, but had limited impact on the cyclic performance of the iCCC process. Microbial communities were dominated by H2-utilizing and alkali-tolerant species that could participate in CO2 biomethanation and survive under alternating neutral and alkaline conditions.

Rosellosides A and B, two phenyloxazole glycosides from Glycyrrhiza inflata-derived fungus Rosellinia sp. Glinf021.

Two new chlorinated phenyloxazole glycosides, named rosellosides A (1) and B (2), were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata (Leguminosae). Both compounds were rare chlorinated polyketide glycosides bearing an oxazole moiety. Their structures were elucidated by analysis of the NMR and HRESIMS data, and their absolute configurations were determined by quantum chemical ECD calculations and X-ray crystallography.

Corrigendum: Case Report: Surgical treatment of a primary giant epithelioid hemangioendothelioma of the spine with total en-bloc spondylectomy.

[This corrects the article DOI: 10.3389/fonc.2023.1109643.].

Automatic epicardial adipose tissue segmentation in pulmonary computed tomography venography using nnU-Net.

Background: Epicardial adipose tissue (EAT) is a key aspect in the investigation of cardiac pathophysiology. We sought to develop a deep learning (DL) model for fully automatic extraction and quantification of EAT through pulmonary computed tomography venography (PCTV) images. Methods: In this retrospective study, we included 128 patients with atrial fibrillation and PCTV from 2 hospitals. A DL model for automated EAT segmentation was developed from a training set of 51 patients and a validation set of 13 patients from hospital A. The algorithm was further validated using an internal test set of 16 patients from hospital A and an external test set of 48 patients from hospital B. The consistency and measurement agreement of EAT quantification were compared between the DL model and the conventional manual protocol using the Dice score coefficient (DSC), Hausdorff distance (HD95), Pearson correlation coefficient, and Bland-Altman plot. Results: In the internal and external test set, automated segmentation with DL was successful in all cases. The total analysis time was shorter for DL than for manual reconstruction (5.43±2.52 vs. 106.20±15.90 min; P<0.001). The EAT segmented with the DL model had good consistency with manual segmentation (the DSC of the internal and external test sets were 0.92±0.02 and 0.88±0.03, respectively). The quantification of EAT evaluated with the 2 methods showed excellent correlation (all correlation coefficients >0.9; all P values <0.001) and minimal measurement difference. Conclusions: The proposed DL model achieved fully automatic quantification of EAT from PCTV images. The yielded results were highly consistent with those of manual quantification.

Microvascular Myocardial Ischemia in Patients With Diabetes Without Obstructive Coronary Stenosis and Its Association With Angina.

OBJECTIVE: To investigate the incidence of microvascular myocardial ischemia in diabetic patients without obstructive coronary artery disease (CAD) and its relationship with angina. MATERIALS AND METHODS: Diabetic patients and an intermediate-to-high pretest probability of CAD were prospectively enrolled. Non-diabetic patients but with an intermediate-to-high pretest probability of CAD were retrospectively included as controls. The patients underwent dynamic computed tomography-myocardial perfusion imaging (CT-MPI) and coronary computed tomography angiography (CCTA) to quantify coronary stenosis, myocardial blood flow (MBF), and extracellular volume (ECV). The proportion of patients with microvascular myocardial ischemia, defined as any myocardial segment with a mean MBF ≤ of 100 mL/min/100 mL, in patients without obstructive CAD (Coronary Artery Disease-Reporting and Data System [CAD-RADS] grade 0-2 on CCTA) was determined. Various quantitative parameters of the patients with and without diabetes without obstructive CAD were compared. Multivariable analysis was used to determine the association between microvascular myocardial ischemia and angina symptoms in diabetic patients without obstructive CAD. RESULTS: One hundred and fifty-two diabetic patients (mean age: 59.7 ± 10.7; 77 males) and 266 non-diabetic patients (62.0 ± 12.3; 167 males) were enrolled; CCTA revealed 113 and 155 patients without obstructive CAD, respectively. For patients without obstructive CAD, the mean global MBF was significantly lower for those with diabetes than for those without (152.8 mL/min/100 mL vs. 170.4 mL/min/100 mL, P < 0.001). The mean ECV was significantly higher for diabetic patients (27.2% vs. 25.8%, P = 0.009). Among the patients without obstructive CAD, the incidence of microvascular myocardial ischemia (36.3% [41/113] vs. 10.3% [16/155], P < 0.001) and interstitial fibrosis (69.9% [79/113] vs. 33.3% [8/24], P = 0.001) were significantly higher in diabetic patients than in the controls. The presence of microvascular myocardial ischemia was independently associated with angina symptoms (adjusted odds ratio = 3.439, P = 0.037) in diabetic patients but without obstructive CAD. CONCLUSION: Dynamic CT-MPI + CCTA revealed a high incidence of microvascular myocardial ischemia in diabetic patients without obstructive CAD. Microvascular myocardial ischemia is strongly associated with angina.

A robust and efficient AI assistant for breast tumor segmentation from DCE-MRI via a spatial-temporal framework.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows screening, follow up, and diagnosis for breast tumor with high sensitivity. Accurate tumor segmentation from DCE-MRI can provide crucial information of tumor location and shape, which significantly influences the downstream clinical decisions. In this paper, we aim to develop an artificial intelligence (AI) assistant to automatically segment breast tumors by capturing dynamic changes in multi-phase DCE-MRI with a spatial-temporal framework. The main advantages of our AI assistant include (1) robustness, i.e., our model can handle MR data with different phase numbers and imaging intervals, as demonstrated on a large-scale dataset from seven medical centers, and (2) efficiency, i.e., our AI assistant significantly reduces the time required for manual annotation by a factor of 20, while maintaining accuracy comparable to that of physicians. More importantly, as the fundamental step to build an AI-assisted breast cancer diagnosis system, our AI assistant will promote the application of AI in more clinical diagnostic practices regarding breast cancer.

Enhanced bone regeneration via local low-dose delivery of PTH1-34 in a composite hydrogel.

Introducing bone regeneration-promoting factors into scaffold materials to improve the bone induction property is crucial in the fields of bone tissue engineering and regenerative medicine. This study aimed to develop a Sr-HA/PTH1-34-loaded composite hydrogel system with high biocompatibility. Teriparatide (PTH1-34) capable of promoting bone regeneration was selected as the bioactive factor. Strontium-substituted hydroxyapatite (Sr-HA) was introduced into the system to absorb PTH1-34 to promote the bioactivity and delay the release cycle. PTH1-34-loaded Sr-HA was then mixed with the precursor solution of the hydrogel to prepare the composite hydrogel as bone-repairing material with good biocompatibility and high mechanical strength. The experiments showed that Sr-HA absorbed PTH1-34 and achieved the slow and effective release of PTH1-34. In vitro biological experiments showed that the Sr-HA/PTH1-34-loaded hydrogel system had high biocompatibility, allowing the good growth of cells on the surface. The measurement of alkaline phosphatase activity and osteogenesis gene expression demonstrated that this composite system could promote the differentiation of MC3T3-E1 cells into osteoblasts. In addition, the in vivo cranial bone defect repair experiment confirmed that this composite hydrogel could promote the regeneration of new bones. In summary, Sr-HA/PTH1-34 composite hydrogel is a highly promising bone repair material.

SALL4 promotes angiogenesis in gastric cancer by regulating VEGF expression and targeting SALL4/VEGF pathway inhibits cancer progression.

BACKGROUND: Spalt-like protein 4 (SALL4) is a stemness-related transcription factor whose abnormal re-expression contributes to cancer initiation and progression. However, the role of SALL4 in cancer angiogenesis remains unknown. METHODS: Analyses of clinical specimens via TCGA datasets were performed to determine the expression level and clinical significance of SALL4 in STAD (Stomach Adenocarcinoma). SALL4 knockdown, knockout, and overexpression were achieved by siRNA, CRISPR/Cas9, and plasmid transfection. The effects of conditioned medium (CM) from SALL4 knockdown or overexpression of gastric cancer cells on endothelial cell proliferation, migration, and tube formation were investigated by CCK-8 assay, transwell migration assay, and tube formation assay. The regulation of VEGF gene expression by SALL4 was studied by qRT-PCR, western blot, chromatin immunoprecipitation (ChIP) assay, and electrophoretic mobility shift assay (EMSA). Engineered exosomes from 293T cells loaded with si-SALL4-B and thalidomide were produced to test their therapeutic effect on gastric cancer progression. RESULTS: SALL4 expression was increased in STAD and positively correlated with tumor progression and poor prognosis. SALL4-B knockdown or knockout decreased while over-expression increased the promotion of human umbilical vein endothelial cells (HUVEC) cell proliferation, migration, and tube formation by gastric cancer cell-derived CM. Further investigation revealed a widespread association of SALL4 with angiogenic gene transcription through the TCGA datasets. Additionally, SALL4-B knockdown reduced, while over-expression enhanced the expression levels of VEGF-A, B, and C genes. The results of ChIP and EMSA assays indicated that SALL4 could directly bind to the promoters of VEGF-A, B, and C genes and activate their transcription, which may be associated with increased histone H3-K79 and H3-K4 modifications in their promoter regions. Furthermore, si-SALL4-B and thalidomide-loaded exosomes could be efficiently uptaken by gastric cancer cells and significantly reduced SALL4-B and Vascular Endothelial Growth Factor (VEGF) expression levels in gastric cancer cells, thus inhibiting the pro-angiogenic role of their derived CM. CONCLUSION: These findings suggest that SALL4 plays an important role in angiogenesis by transcriptionally regulating VEGF expression. Co-delivery of the functional siRNA and anticancer drug via exosomes represents a useful approach to inhibiting cancer angiogenesis by targeting SALL4/VEGF pathway.

Vps4a Regulates Autophagic Flux to Prevent Hypertrophic Cardiomyopathy.

Autophagy has stabilizing functions for cardiomyocytes. Recent studies indicate that an impairment in the autophagy pathway can seriously affect morphology and function, potentially leading to heart failure. However, the role and the underlying mechanism of the endosomal sorting complex required for transport (ESCRT) family protein, in particular the AAA-ATPase vacuolar protein sorting 4a (Vps4a), in regulating myocardial autophagy remains unclear. In the present study, cardiomyocyte-specific Vps4a knockout mice were generated by crossing Vps4aflox/flox (Vps4afl/fl) with Myh6-cre transgenic mice. As a result, we observed a partially dilated left ventricular (LV) chamber, a significant increase in heart weight to body weight ratio (HW/BW), and heart weight to tibial length ratio (HW/TL), hypertrophic cardiomyopathy and early lethality starting at 3 months of age. Hematoxylin-eosin (HE), immunofluorescence assay (IFA), and Western blot (WB) revealed autophagosome accumulation in cardiomyocytes. A transcriptome-based analysis and autophagic flux tracking by AAV-RFP-GFP-LC3 showed that the autophagic flux was blocked in Vps4a knockout cardiomyocytes. In addition, we provided in vitro evidence demonstrating that Vps4a and LC3 were partially co-localized in cardiomyocytes, and the knockdown of Vps4a led to the accumulation of autophagosomes in cardiomyocytes. Similarly, the transfection of cardiomyocytes with adenovirus (Adv) mCherry-GFP-LC3 further indicated that the autophagic flux was blocked in cells with deficient levels of Vps4a. Finally, an electron microscope (EM) showed that the compromised sealing of autophagosome blocked the autophagic flux in Vps4a-depleted cardiomyocytes. These findings revealed that Vps4a contributed to the sealing of autophagosomes in cardiomyocytes. Therefore, we demonstrated that Vps4a deletion could block the autophagic flux, leading to the accumulation of degradation substances and compromised cardiac function. Overall, this study provides insights into a new theoretical basis for which autophagy may represent a therapeutic target for cardiovascular diseases.

Host shift promotes divergent evolution between closely related holoparasitic species.

Distinct hosts have been hypothesized to possess the potential for affecting species differentiation and genome evolution of parasitic organisms. However, what host shift history is experienced by the closely related parasites and whether disparate evolution of their genomes occur remain largely unknown. Here, we screened horizontal gene transfer (HGT) events in a pair of sister species of holoparasitic Boschniakia (Orobanchaceae) having obligate hosts from distinct families to recall the former host-parasite associations and performed a comparative analysis to investigate the difference of their organelle genomes. Except those from the current hosts (Ericaceae and Betulaceae), we identified a number of HGTs from Rosaceae supporting the occurrence of unexpected ancient host shifts. Different hosts transfer functional genes which changed nuclear genomes of this sister species. Likewise, different donors transferred sequences to their mitogenomes, which vary in size due to foreign and repetitive elements rather than other factors found in other parasites. The plastomes are both severely reduced, and the degree of difference in reduction syndrome reaches the intergeneric level. Our findings provide new insights into the genome evolution of parasites adapting to different hosts and extend the mechanism of host shift promoting species differentiation to parasitic plant lineages.

The bioavailability, metabolism and microbial modulation of curcumin-loaded nanodelivery systems.

Curcumin (Cur), the major bioactive component of turmeric (Curcuma longa) possesses many health benefits. However, low solubility, stability and bioavailability restricts its applications in food. Recently, nanocarriers such as complex coacervates, nanocapsules, liposomes, nanoparticles, nanomicelles, have been used as novel strategies to solve these problems. In this review, we have focused on the delivery systems responsive to the environmental stimuli such as pH-responsive, enzyme-responsive, targeted-to-specific cells or tissues, mucus-penetrating and mucoadhesive carriers. Besides, the metabolites and their biodistribution of Cur and Cur delivery systems are discussed. Most importantly, the interaction between Cur and their carriers with gut microbiota and their effects of modulating the gut health synergistically were discussed comprehensively. In the end, the biocompatibility of Cur delivery systems and the feasibility of their application in food industry is discussed. This review provided a comprehensive review of Cur nanodelivery systems, the health impacts of Cur nanocarriers and an insight into the application of Cur nanocarriers in food industry.

Financial and clinical outcomes of CT myocardial perfusion imaging and coronary CT angiography-guided versus coronary CT angiography-guided strategy.

OBJECTIVES: To compare the financial and clinical outcomes of CT myocardial perfusion imaging (CT-MPI) + coronary CT angiography (CCTA)-guided versus CCTA-guided strategy in patients suspected of chronic coronary syndrome (CCS). MATERIALS AND METHODS: This study retrospectively included consecutive patients suspected of CCS and referred for CT-MPI+CCTA-guided and CCTA-guided treatment. The details of medical costs within 3 months after index imaging, including downstream invasive procedures, hospitalization, and medications, were recorded. All patients were followed up for major adverse cardiac events (MACE) at a median time of 22 months. RESULTS: A total of 1335 patients (559 in the CT-MPI+CCTA group and 776 in the CCTA group) were finally included. In the CT-MPI+CCTA group, 129 patients (23.1%) underwent ICA and 95 patients (17.0%) received revascularization. In the CCTA group, 325 patients (41.9%) underwent ICA whereas 194 patients (25.0%) received revascularization. An addition of CT-MPI in the evaluation strategy remarkably reduced the healthcare expenditure, compared with CCTA-guided strategy (USD 1441.36 vs. USD 232.91, p < 0.001). After adjustment for potential cofounders after inverse probability weighting, the CT-MPI+CCTA strategy was significantly associated with lower medical expenditure [adjusted cost ratio (95% CI) for total costs: 0.77 (0.65-0.91), p < 0.001]. In addition, there was no significant difference regarding the clinical outcome between the two groups (adjusted HR= 0.97; p = 0.878). CONCLUSIONS: CT-MPI+CCTA considerably reduced medical expenditures in patients suspected of CCS, compared to the CCTA strategy alone. Moreover, CT-MPI+CCTA led to a lower rate of invasive procedures with a similar long-term prognosis. CLINICAL RELEVANCE STATEMENT: CT myocardial perfusion imaging + coronary CT angiography-guided strategy reduced medical expenditure and invasive procedure rate. KEY POINTS: • CT-MPI+CCTA strategy yielded significantly lower medical expenditure than did the CCTA strategy alone in patients with suspected CCS. • After adjustment for potential confounders, the CT-MPI+CCTA strategy was significantly associated with lower medical expenditure. • No significant difference was observed regarding the long-term clinical outcome between the two groups.

The new advance of SALL4 in cancer: Function, regulation, and implication.

SALL4 (split-like protein 4) is a member of the mammalian homologs of the Drosophila homoeotic gene spalt (sal) and acts as a zinc finger transcription factor to govern the self-renewal and pluripotency of embryonic stem cells. SALL4 expression gradually decreases during development and is even absent in most adult tissues. However, increasing evidence suggests that SALL4 expression is restored in human cancers and its aberrant expression is associated with the progression of many hematopoietic malignancies and solid tumors. The potent roles of SALL4 in regulating cancer cell proliferation, apoptosis, metastasis, and drug resistance have been reported. SALL4 plays a dual role in epigenetic modulation by acting as either an activator or a repressor of its target genes. Furthermore, SALL4 interacts with other partners to control the expression of many downstream genes and the activation of various key signaling transduction pathways. SALL4 is considered as a promising diagnostic and prognostic biomarker and therapeutic target for cancer. In this review, we highlighted the major advances in the roles and mechanisms of SALL4 in cancer and the therapeutic strategies for targeting SALL4 to treat cancer.

The incremental value of CCTA-derived myocardial radiomics signature for ischemia diagnosis with reference to CT myocardial perfusion imaging.

OBJECTIVES: To explore the incremental value of myocardial radiomics signature derived from static coronary computed tomography angiography (CCTA) for identifying myocardial ischemia based on stress dynamic CT myocardial perfusion imaging (CT-MPI). METHODS: Patients who underwent CT-MPI and CCTA were retrospectively enrolled from two independent institutions, one used as training and the other as testing. Based on CT-MPI, coronary artery supplying area with relative myocardial blood flow (rMBF) value <0.8 was considered ischemia. Conventional imaging features of target plaques which caused the most severe narrowing of the vessel included area stenosis, lesion length (LL), total plaque burden, calcification burden, non-calcification burden, high-risk plaque (HRP) score, and CT fractional flow reserve (CT-FFR). Myocardial radiomics features were extracted at three vascular supply areas from CCTA images. The optimized radiomics signature was added to the conventional CCTA features to build the combined model (radiomics + conventional). RESULTS: There were 168 vessels from 56 patients enrolled in the training set, and the testing set consisted of 135 vessels from 45 patients. From either cohort, HRP score, LL, stenosis ≥50% and CT-FFR ≤0.80 were associated with ischemia. The optimal myocardial radiomics signature consisted of nine features. The detection of ischemia using the combined model was significantly improved compared with conventional model in both training and testing set (AUC 0.789 vs 0.608, p < 0.001; 0.726 vs 0.637, p = 0.045). CONCLUSIONS: Myocardial radiomics signature extracted from static CCTA combining with conventional features could provide incremental value to diagnose specific ischemia. ADVANCES IN KNOWLEDGE: Myocardial radiomics signature extracted from CCTA may capture myocardial characteristics and provide incremental value to detect specific ischemia when combined with conventional features.