A second-generation M1-polarized CAR macrophage with antitumor efficacy.

Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner. Here we engineered induced pluripotent stem cell-derived macrophages (iMACs) with toll-like receptor 4 intracellular toll/IL-1R (TIR) domain-containing CARs resulting in a markedly enhanced antitumor effect over first-generation CAR-macrophages. Moreover, the design of a tandem CD3ζ-TIR dual signaling CAR endows iMACs with both target engulfment capacity and antigen-dependent M1 polarization and M2 resistance in a nuclear factor kappa B (NF-κB)-dependent manner, as well as the capacity to modulate the tumor microenvironment. We also outline a mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we provide a second-generation CAR-iMAC with an ability for orthogonal phagocytosis and polarization and superior antitumor functions in treating solid tumors relative to first-generation CAR-macrophages.

Rational Design of the Alkali Metal Sn-Based Mixed Halides with Large Birefringence and Wide Transparent Range.

Birefringent materials are widely used in various advanced optical systems, owing to their vital role in creating and controlling polarized light. Currently, Sn2+-based compounds containing stereochemically active lone-pair (SCALP) cations are extensively investigated and considered as one class of promising birefringent materials. To solve the problem of relatively narrow bandgap of Sn2+-based compounds, alkali metals and multiple halogens are introduced to widen the bandgap during the research. Based on this strategy, four new Sn2+-based halides, A2Sn2F5Cl and ASnFCl2 (A = Rb and Cs), with large birefringence, short ultraviolet (UV) cutoff edge, and wide transparent range are successfully found. The birefringences of A2Sn2F5Cl (A = Rb and Cs) are 0.31 and 0.28 at 532 nm, respectively, which are among the largest in Sn-based halide family. Remarkably, A2Sn2F5Cl possess relatively shorter UV cutoff edge (<300 nm) and broad infrared (IR) transparent range (up to 16.6 µm), so they can become promising candidates as birefringent materials applied in both UV and IR regions. In addition, a comprehensive analysis on crystal structures and structure-property relationship of metal Sn2+-based halides is performed to fully understand this family. Therefore, this work provides insights into designing birefringent materials with balanced optical properties.

Phylogenomics of mulberries (Morus, Moraceae) inferred from plastomes and single copy nuclear genes.

Mulberries (genus Morus), belonging to the order Rosales, family Moraceae, are important woody plants due to their economic values in sericulture, as well as for nutritional benefits and medicinal values. However, the taxonomy and phylogeny of Morus, especially for the Asian species, remains challenging due to its wide geographical distribution, morphological plasticity, and interspecific hybridization. To better understand the evolutionary history of Morus, we combined plastomes and a large-scale nuclear gene analyses to investigate their phylogenetic relationships. We assembled the plastomes and screened 211 single-copy nuclear genes from 13 Morus species and related taxa. The plastomes of Morus species were relatively conserved in terms of genome size, gene content, synteny, IR boundary and codon usage. Using nuclear data, our results elucidated identical topologies based on coalescent and concatenation methods. The genus Morus was supported as monophyletic, with M. notabilis as the first diverging lineage and the two North American Morus species, M. microphylla and M. rubra, as sister to the other Asian species. In the Asian Morus species, interspecific relationships were completely resolved. However, cyto-nuclear discordances and gene tree-species tree conflicts were detected in the phylogenies of Morus, with multiple evidences supporting hybridization/introgression as the main cause of discordances between nuclear and plastid phylogenies, while gene tree-species tree conflicts were mainly caused by ILS.

Oral-gut microbial transmission promotes diabetic coronary heart disease.

BACKGROUND: Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia-reperfusion injury (MIRI). METHODS: We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice. RESULTS: Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI. CONCLUSION: Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.

Stent-specific fat attenuation index is associated with target vessel revascularization after PCI.

OBJECTIVES: To explore the clinical relevance of stent-specific perivascular fat attenuation index (FAI) in patients with stent implantation. METHODS: A total of 162 consecutive patients who underwent coronary computed tomography angiography (CCTA) following stent implantation were retrospectively included. The stent-specific FAI at 2 cm adjacent to the stent edge was calculated. The endpoints were defined as target vessel revascularization (TVR) on the stented vessel after CCTA and readmission times due to chest pain after stent implantation. Binary logistic regression analysis for TVR and ordinal regression models were conducted to identify readmission times (0, 1, and ≥ 2) with generalized estimating equations on a per-stent basis. RESULTS: On a per-stent basis, 9 stents (4.5%) experienced TVR after PCI at a median 30 months' follow-up duration. Stent-specific FAI differed significantly among subgroups of patients with stent implantation and different readmission times (p = 0.002); patients with at least one readmission had higher stent-specific FAI than those without readmission (p < 0.001). Bifurcated stents (odds ratio [OR]: 11.192, p = 0.001) and stent-specific FAI (OR: 1.189, p = 0.04) were independently associated with TVR. With no readmission as a reference, stent-specific FAI (OR: 0.984, p = 0.007) was an independent predictor for hospital readmission times ≥ 2 (p = 0.003). CONCLUSION: Non-invasive stent-specific FAI derived from CCTA was found to be associated with TVR, which was a promising imaging marker for functional assessment in patients who underwent stent implantation. CLINICAL RELEVANCE STATEMENT: Noninvasive fat attenuation index adjacent to the stents edge derived from CCTA, an imaging marker reflecting the presence of inflammation acting on the neointimal tissue at the sites of coronary stenting, might be relevant clinically with target vessel revascularization. KEY POINTS: • Non-invasive stent-specific FAI derived from CCTA was associated with TVR (OR: 1.189 [95% CI: 1.007-1.043], p = 0.04) in patients who underwent stent implantation. • Stent-specific FAI significantly differed among a subgroup of patients with chest pain after stent implantation and with different readmission times (p = 0.002); the patients with at least one readmission had higher stent-specific FAI than those without readmission (p < 0.001). • Non-invasive stent-specific FAI derived from CCTA could be used as an imaging maker for the functional assessment of patients following stent implantation.

AX·(H2SeO3)n (A = K, Cs; X = Cl, Br; n = 1, 2): A Series of Ionic Cocrystals as Promising UV Birefringent Materials with Large Birefringence and Wide Band Gap.

The design and syntheses of new birefringent crystals will be of great importance in commercial applications and materials science. A series of ultraviolet (UV) birefringent crystals, AX·(H2SeO3)n (A = K, Cs; X = Cl, Br; n = 1, 2), with large sizes up to 23 × 6 × 3 mm3, was successfully synthesized by simple aqueous solution method. These four compounds belong to three different space groups. Isomorphic KCl·(H2SeO3)2 and CsCl·(H2SeO3)2 crystallize in the P1¯ space group, while CsBr·(H2SeO3)2 and CsCl·H2SeO3 crystallize in the P21/m and P21/c space groups, respectively. They exhibit cocrystal structures composed of [2(H2SeO3)]∞ and [AX]∞ frameworks, ingeniously inheriting the large optical anisotropy of selenite and the wide band gap of alkali metal halide. And it proves that these compounds indeed possess large birefringence (0.1-0.17 at 532 nm) and short UV cutoff edges (227-239 nm), achieving a balance of optical properties. This research affords a simple and viable strategy for the design and syntheses of new UV birefringent crystals. Besides, it is also found that the n value and ionic size (A and X ions) have important influences on the crystal structures and optical properties of AX·(H2SeO3)n. And this will promote further understanding of the alkali metal halide selenite family.

Na3K6(CO3)3(NO3)2X·6H2O (X = NO3, Cl, Br): Exploring High-Performance UV Birefringent Crystals Induced by Coplanar π-Conjugated CO3 and NO3 Groups.

Planar π-conjugated groups, like CO3, NO3, and BO3 triangles, are ideal functional units for designing birefringent materials due to their large optical anisotropy and wide band gap. The key point for designing birefringent crystals is to select appropriate functional building blocks (FBBs) and the proper arrangement mode. It is well known that the substitution strategy has proven to be a promising and accessible approach. In this work, alkali metals were chosen to regulate and control two different π-conjugated groups, CO3 and NO3, to build new compounds with large birefringence. Subsequently, three new compounds, Na3K6(CO3)3(NO3)2X·6H2O (X = NO3, Cl, Br), were successfully synthesized using the hydrothermal method. The aliovalent substitution between the [NO3]- anionic group and halogen anions [Cl]-/[Br]- has been achieved in these compounds. Na3K6(CO3)3(NO3)2X·6H2O feature the well-coplanar CO3 and NO3 groups in their crystal structure. This coplanar arrangement mode may effectively enhance the anisotropic polarizability of Na3K6(CO3)3(NO3)2X·6H2O. And their experimental birefringence can reach 0.094-0.131 at 546 nm. Diffuse reflectance spectra demonstrate that these compounds exhibit short ultraviolet (UV) absorption edges of ∼235 nm. Meanwhile, Na3K6(CO3)3(NO3)2X·6H2O also have an easily grown capacity under facile conditions. This work not only reports three new potential UV birefringent crystals but also provides a strategy to make the π-conjugated MO3 group coplanar.

Artificial Intelligence to Predict Lymph Node Metastasis at CT in Pancreatic Ductal Adenocarcinoma.

Background Although deep learning has brought revolutionary changes in health care, reliance on manually selected cross-sectional images and segmentation remain methodological barriers. Purpose To develop and validate an automated preoperative artificial intelligence (AI) algorithm for tumor and lymph node (LN) segmentation with CT imaging for prediction of LN metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Materials and Methods In this retrospective study, patients with surgically resected, pathologically confirmed PDAC underwent multidetector CT from January 2015 to April 2020. Three models were developed, including an AI model, a clinical model, and a radiomics model. CT-determined LN metastasis was diagnosed by radiologists. Multivariable logistic regression analysis was conducted to develop the clinical and radiomics models. The performance of the models was determined on the basis of their discrimination and clinical utility. Kaplan-Meier curves, the log-rank test, or Cox regression were used for survival analysis. Results Overall, 734 patients (mean age, 62 years ± 9 [SD]; 453 men) were evaluated. All patients were split into training (n = 545) and validation (n = 189) sets. Patients who had LN metastasis (LN-positive group) accounted for 340 of 734 (46%) patients. In the training set, the AI model showed the highest performance (area under the receiver operating characteristic curve [AUC], 0.91) in the prediction of LN metastasis, whereas the radiologists and the clinical and radiomics models had AUCs of 0.58, 0.76, and 0.71, respectively. In the validation set, the AI model showed the highest performance (AUC, 0.92) in the prediction of LN metastasis, whereas the radiologists and the clinical and radiomics models had AUCs of 0.65, 0.77, and 0.68, respectively (P < .001). AI model-predicted positive LN metastasis was associated with worse survival (hazard ratio, 1.46; 95% CI: 1.13, 1.89; P = .004). Conclusion An artificial intelligence model outperformed radiologists and clinical and radiomics models for prediction of lymph node metastasis at CT in patients with pancreatic ductal adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chu and Fishman in this issue.

Multi-stable dye-doped dual-frequency twisted nematic liquid crystal smart window.

In this study, a novel, to the best of our knowledge, dye-doped dual-frequency liquid crystal multi-stable smart window is proposed. A chiral dopant with appropriate content was introduced into dye-doped dual-frequency liquid crystals to achieve an initial 180° twisted state. These liquid crystals can be switched to a nematic phase or a 360° twisted state by controlling the magnitude and frequency of the applied voltage. These nematic phase and 360° twisted states can exist stably for a long time because of the backflow effect and the anisotropic nature of the dual-frequency liquid crystal material. Due to the optical waveguide effect of dye-doped liquid crystals in the long-pitch state, the transmittance was different in nematic phase, 180°, and 360° twisted three zero-field stabilized absorption states. Finally, a multi-stable smart window is developed to switch between three zero-field stabilized absorption and scattering states.

Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation.

Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.

Replacing secretin-enhanced MRCP with MRI radiomics model based on a fully automated pancreas segmentation for assessing pancreatic exocrine function in chronic pancreatitis.

OBJECTIVES: To develop and validate a radiomics nomogram based on a fully automated pancreas segmentation to assess pancreatic exocrine function. Furthermore, we aimed to compare the performance of the radiomics nomogram with the pancreatic flow output rate (PFR) and conclude on the replacement of secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) by the radiomics nomogram for pancreatic exocrine function assessment. METHODS: All participants underwent S-MRCP between April 2011 and December 2014 in this retrospective study. PFR was quantified using S-MRCP. Participants were divided into normal and pancreatic exocrine insufficiency (PEI) groups using the cut-off of 200 µg/L of fecal elastase-1. Two prediction models were developed including the clinical and non-enhanced T1-weighted imaging radiomics model. A multivariate logistic regression analysis was conducted to develop the prediction models. The models' performances were determined based on their discrimination, calibration, and clinical utility. RESULTS: A total of 159 participants (mean age [Formula: see text] standard deviation, 45 years [Formula: see text] 14;119 men) included 85 normal and 74 PEI. All the participants were divided into a training set comprising 119 consecutive patients and an independent validation set comprising 40 consecutive patients. The radiomics score was an independent risk factor for PEI (odds ratio = 11.69; p < 0.001). In the validation set, the radiomics nomogram exhibited the highest performance (AUC, 0.92) in PEI prediction, whereas the clinical nomogram and PFR had AUCs of 0.79 and 0.78, respectively. CONCLUSION: The radiomics nomogram accurately predicted pancreatic exocrine function and outperformed pancreatic flow output rate on S-MRCP in patients with chronic pancreatitis. KEY POINTS: • The clinical nomogram exhibited moderate performance in diagnosing pancreatic exocrine insufficiency. • The radiomics score was an independent risk factor for pancreatic exocrine insufficiency, and every point rise in the rad-score was associated with an 11.69-fold increase in pancreatic exocrine insufficiency risk. • The radiomics nomogram accurately predicted pancreatic exocrine function and outperformed the clinical model and pancreatic flow output rate quantified by secretin-enhanced magnetic resonance cholangiopancreatography on MRI in patients with chronic pancreatitis.

RbCl·(H2SeO3)2: A Salt-Inclusion Selenite Featuring Short UV Cut-Off Edge and Large Birefringence.

Birefringent materials are key components to control the light polarization in laser science and technology as well as optical communication. However, the performance of current commercial birefringent materials has been limited by the magnitude of birefringence, optical transparency range, or the attainability of large-scale single crystals. To explore new birefringent materials, we strategically incorporated a lone pair cation (Se4+) with large optical anisotropy, an alkali metal, and halogen ions (Rb+ and Cl-) with superior UV transparent capacity; thus a new compound, RbCl·(H2SeO3)2, was successfully discovered with the aid of the facile hydrothermal method. Interestingly, Rb-Cl chains locate in the [H2SeO3]∞ skeleton, which makes RbCl·(H2SeO3)2 a salt-inclusion selenite. Millimeter-sized single crystals (up to 4 × 2 × 1 mm3) were obtained, and the transmittance spectrum revealed that its UV cut-off edge can be as low as 230 nm. In addition, the calculated birefringence of RbCl·(H2SeO3)2 is 0.14 at 589 nm that is similar to the birefringent value of famous α-BaB2O4. Wide UV transparency, large birefringence, and feasible crystal growth make RbCl·(H2SeO3)2 a new member of birefringent materials for UV light applications.

Liver X receptor agonists exert antitumor effects against hepatocellular carcinoma via inducing REPS2 expression.

Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1-0.5 µM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.

Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1ß and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.

Hydrodeoxygenation of Oxygen-Containing Aromatic Plastic Wastes to Liquid Organic Hydrogen Carriers.

To address the global plastic pollution issues and the challenges of hydrogen storage and transportation, we report a system, based on the hydrodeoxygenation (HDO) of oxygen-containing aromatic plastic wastes, from which organic hydrogen carriers (LOHCs) can be derived. We developed a catalytic system comprised of Ru-ReOx /SiO2 +HZSM-5 for direct HDO of polycarbonate (PC), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyphenylene oxide (PPO), and their mixtures, to cycloalkanes as LOHCs, with high yields up to 99 %, under mild reaction conditions. The theoretical hydrogen storage capacity reaches ca. 5.74 wt%. The reaction pathway involves depolymerization of PC into C15 aromatics and C15 monophenols by direct hydrogenolysis of the C-O bond between the benzene ring and ester group, and subsequent parallel hydrogenation of C15 aromatics and HDO of C15 monophenols. HDO of cyclic alcohol is the rate-determining step. The active site is Ru metallic nanoparticles with partially covered ReOx species. The excellent performance is attributed to the synergetic effect of oxophilic ReOx species and Ru metallic sites for C-O hydrogenolysis and hydrogenation, and the promotion effect of HZSM-5 for dehydration of cyclic alcohol. The highly efficient and stable dehydrogenation of cycloalkanes over Pt/γ-Al2 O3 confirms that HDO products can act as LOHCs.

Two nomograms for differentiating mass-forming chronic pancreatitis from pancreatic ductal adenocarcinoma in patients with chronic pancreatitis.

OBJECTIVES: To develop and validate a CT nomogram and a radiomics nomogram to differentiate mass-forming chronic pancreatitis (MFCP) from pancreatic ductal adenocarcinoma (PDAC) in patients with chronic pancreatitis (CP). METHODS: In this retrospective study, the data of 138 patients with histopathologically diagnosed MFCP or PDAC treated at our institution were retrospectively analyzed. Two radiologists analyzed the original cross-sectional CT images based on predefined criteria. Image segmentation, feature extraction, and feature reduction and selection were used to create the radiomics model. The CT and radiomics models were developed using data from a training cohort of 103 consecutive patients. The models were validated in 35 consecutive patients. Multivariable logistic regression analysis was conducted to develop a model for the differential diagnosis of MFCP and PDAC and visualized as a nomogram. The nomograms' performances were determined based on their differentiating ability and clinical utility. RESULTS: The mean age of patients was 53.7 years, 75.4% were male. The CT nomogram showed good differentiation between the two entities in the training (area under the curve [AUC], 0.87) and validation (AUC, 0.94) cohorts. The radiomics nomogram showed good differentiation in the training (AUC, 0.91) and validation (AUC, 0.93) cohorts. Decision curve analysis showed that patients could benefit from the CT and radiomics nomograms, if the threshold probability was 0.05-0.85 and > 0.05, respectively. CONCLUSIONS: The two nomograms reasonably accurately differentiated MFCP from PDAC in patients with CP and hold potential for refining the management of pancreatic masses in CP patients. KEY POINTS: • A CT nomogram and a computed tomography-based radiomics nomogram reasonably accurately differentiated mass-forming chronic pancreatitis from pancreatic ductal adenocarcinoma in patients with chronic pancreatitis (CP). • The two nomograms can monitor the cancer risk in patients with CP and hold promise to optimize the management of pancreatic masses in patients with CP.

CCTA-derived strain analysis in detection of regional myocardial dysfunction in coronary artery disease patients with preserved left ventricular ejection fraction: A feasibility study.

OBJECTIVES: To evaluate the feasibility of using coronary computed tomography angiography (CCTA)-derived strain to detect regional myocardial dysfunction in coronary artery disease (CAD) patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 1,580 segments from 101 patients who underwent stressed CT myocardial perfusion imaging (CT-MPI) and CCTA were retrospectively enrolled in this study. The CT-derived global and segmental strain values were evaluated using the feature tracking technique. Segments with myocardial blood flow (MBF) < 125 ml/min/100 ml and 95 ml/min/100 ml were categorized as ischemic and infarcted, respectively. RESULTS: Segmental radial strain (SRS) and segmental circumferential strain (SCS) in the abnormal segments (including all segments with MBF < 125 ml/min/100 ml) were significantly lower than those in the normal segments (14.81±8.65% vs 17.17±9.13%, p < 0.001; -10.21±5.79% vs -11.86±4.52%, p < 0.001, respectively). SRS and SCS values in infarcted segments were significantly impaired compared with the ischemic segments (12.43±8.03% vs. 15.32±8.71%, p = 0.038; -7.72±5.91% vs. -10.67±5.66%, p = 0.010, respectively). The AUCs for SRS and SCS in detecting infarcted segments were 0.622 and 0.698, respectively (p < 0.05). CONCLUSIONS: It is feasible for using CCTA-derived strain parameters to detect regional myocardial dysfunction in CAD patients with preserved LVEF. Segmental radial and circumferential strain have the potential ability to distinguish myocardial ischemia from infarction, and normal from ischemic myocardium.

Metabolomics of red-light-induced stomatal opening in Arabidopsis thaliana: Coupling with abscisic acid and jasmonic acid metabolism.

Environmental stimuli-triggered stomatal movement is a key physiological process that regulates CO2 uptake and water loss in plants. Stomata are defined by pairs of guard cells that perceive and transduce external signals, leading to cellular volume changes and consequent stomatal aperture change. Within the visible light spectrum, red light induces stomatal opening in intact leaves. However, there has been debate regarding the extent to which red-light-induced stomatal opening arises from direct guard cell sensing of red light versus indirect responses as a result of red light influences on mesophyll photosynthesis. Here we identify conditions that result in red-light-stimulated stomatal opening in isolated epidermal peels and enlargement of protoplasts, firmly establishing a direct guard cell response to red light. We then employ metabolomics workflows utilizing gas chromatography mass spectrometry and liquid chromatography mass spectrometry for metabolite profiling and identification of Arabidopsis guard cell metabolic signatures in response to red light in the absence of the mesophyll. We quantified 223 metabolites in Arabidopsis guard cells, with 104 found to be red light responsive. These red-light-modulated metabolites participate in the tricarboxylic acid cycle, carbon balance, phytohormone biosynthesis and redox homeostasis. We next analyzed selected Arabidopsis mutants, and discovered that stomatal opening response to red light is correlated with a decrease in guard cell abscisic acid content and an increase in jasmonic acid content. The red-light-modulated guard cell metabolome reported here provides fundamental information concerning autonomous red light signaling pathways in guard cells.

Protein docking model evaluation by 3D deep convolutional neural networks.

MOTIVATION: Many important cellular processes involve physical interactions of proteins. Therefore, determining protein quaternary structures provide critical insights for understanding molecular mechanisms of functions of the complexes. To complement experimental methods, many computational methods have been developed to predict structures of protein complexes. One of the challenges in computational protein complex structure prediction is to identify near-native models from a large pool of generated models. RESULTS: We developed a convolutional deep neural network-based approach named DOcking decoy selection with Voxel-based deep neural nEtwork (DOVE) for evaluating protein docking models. To evaluate a protein docking model, DOVE scans the protein-protein interface of the model with a 3D voxel and considers atomic interaction types and their energetic contributions as input features applied to the neural network. The deep learning models were trained and validated on docking models available in the ZDock and DockGround databases. Among the different combinations of features tested, almost all outperformed existing scoring functions. AVAILABILITY AND IMPLEMENTATION: Codes available at http://github.com/kiharalab/DOVE, http://kiharalab.org/dove/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.