The GRAS transcription factor CsTL regulates tendril formation in cucumber.

Cucumber (Cucumis sativus, Cs) tendrils are slender vegetative organs that typically require manual removal to ensure orderly growth during greenhouse cultivation. Here, we identified cucumber tendril-less (tl), a Tnt1 retrotransposon-induced insertion mutant lacking tendrils. Map-based cloning identified the mutated gene, CsaV3_3G003590, which we designated as CsTL, which is homologous to Arabidopsis thaliana LATERAL SUPPRESSOR (AtLAS). Knocking out CsTL repressed tendril formation but did not affect branch initiation, whereas overexpression of CsTL resulted in the formation of two or more tendrils in one leaf axil. Although expression of two cucumber genes regulating tendril formation, Tendril (CsTEN) and Unusual Floral Organs (CsUFO), was significantly decreased in CsTL knockout lines, these two genes were not direct downstream targets of CsTL. Instead, CsTL physically interacted with CsTEN, an interaction that further enhanced CsTEN-mediated expression of CsUFO. In Arabidopsis, the CsTL homolog AtLAS acts upstream of REVOLUTA (REV) to regulate branch initiation. Knocking out cucumber CsREV inhibited branch formation without affecting tendril initiation. Furthermore, genomic regions containing CsTL and AtLAS were not syntenic between the cucumber and Arabidopsis genomes, whereas REV orthologs were found on a shared syntenic block. Our results revealed not only that cucumber CsTL possesses a divergent function in promoting tendril formation but also that CsREV retains its conserved function in shoot branching.

TARGET OF EAT3 (TOE3) specifically regulates fruit spine initiation in cucumber (Cucumis sativus L.).

The presence or absence of spines is an important economic trait of cucumber fruit. Spines are believed to be a type of specialized trichome on the fruit surface, and all the identified cucumber trichome-less mutants lack fruit spines. However, genes that specifically regulate fruit spine initiation remain to be identified. Here, we found that knocking out cucumber TARGET OF EAT3 homolog (CsTOE3), belonging to the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) family, affected flower development and, more interestingly, inhibited cucumber fruit spine initiation. On analyzing expression patterns by quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization assay, CsTOE3 was found to be highly expressed in male and female flowers, and its mRNA accumulated in the tips of sepal and petal primordia and in the cells of fruit spines and peels. Biochemical analyses indicated that CsTOE3 directly interacts with GLABRA1 (CsGL1) and TRANSPARENT TESTA GLABRA1 (CsTTG1), which are positive regulators of trichome formation. In addition, RNA-seq showed that the transcription levels of eight ERFs were significantly upregulated in CsTOE3 knockout lines. Phytohormone content analysis also revealed a significant increase in the amount of ethylene released by CsTOE3 knockout line, and treatment with the ethylene synthesis inhibitor aminoethoxyvinyl-glycine partly restored the spineless phenotype. Our results suggest that CsTOE3 specifically regulates fruit spine initiation but does not affect the formation of trichomes on other organs in cucumber. Our findings may have a far-reaching significance for cucumber germplasm improvement and quality breeding using fruit spines as the target trait.

GRAS family member LATERAL SUPPRESSOR regulates the initiation and morphogenesis of watermelon lateral organs.

The lateral organs of watermelon (Citrullus lanatus), including lobed leaves, branches, flowers, and tendrils, together determine plant architecture and yield. However, the genetic controls underlying lateral organ initiation and morphogenesis remain unclear. Here, we found that knocking out the homologous gene of shoot branching regulator LATERAL SUPPRESSOR in watermelon (ClLs) repressed the initiation of branches, flowers, and tendrils and led to developing round leaves, indicating that ClLs undergoes functional expansion compared with its homologs in Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and tomato (Solanum lycopersicum). Using ClLs as the bait to screen against the cDNA library of watermelon, we identified several ClLs-interacting candidate proteins, including TENDRIL (ClTEN), PINOID (ClPID), and APETALA1 (ClAP1). Protein-protein interaction assays further demonstrated that ClLs could directly interact with ClTEN, ClPID, and ClAP1. The mRNA in situ hybridization assay revealed that the transcriptional patterns of ClLs overlapped with those of ClTEN, ClPID, and ClAP1 in the axillary meristems and leaf primordia. Mutants of ClTEN, ClPID, and ClAP1 generated by the CRISPR/Cas9 gene editing system lacked tendrils, developed round leaves, and displayed floral diapause, respectively, and all these phenotypes could be observed in ClLs knockout lines. Our findings indicate that ClLs acts as lateral organ identity protein by forming complexes with ClTEN, ClPID, and ClAP1, providing several gene targets for transforming the architecture of watermelon.

Cucumber NUCLEAR FACTOR-YC2/-YC9 target translocon component CsTIC21 in chloroplast photomorphogenesis.

Light signals promote photomorphogenesis and photosynthesis, allowing plants to establish photoautotrophic growth. Chloroplasts are organelles responsible for photosynthesis in which light energy is converted into chemical energy and stored as organic matter. However, how light regulates chloroplast photomorphogenesis remains unclear. Here, we isolated a cucumber (Cucumis sativus L.) mutant albino seedling (as) from an ethyl methane sulfonate mutagenesis library with an albino phenotype. Map-based cloning revealed that the mutation occurred in a component of cucumber translocon at the inner membrane of chloroplasts (CsTIC21). Subsequently, virus-induced gene silencing and CRISPR/Cas9 analyses confirmed the association between the mutant gene and the as phenotype. Loss-of-function of CsTIC21 induces malformation of chloroplast formation, leading to albinism and death in cucumber. Notably, CsTIC21 transcription was very low in etiolated seedlings grown in the dark and was upregulated by light, with expression patterns similar to those of Nuclear factor-YC (NF-YC) genes. Here, 7 cucumber NF-YC family genes (CsNF-YC) were identified, among which the expression of 4 genes (CsNF-YC1, -YC2, -YC9, and -YC13) responded to light. Gene silencing of all CsNF-YC genes in cucumber indicated that CsNF-YC2, -YC9, -YC11-1, and -YC11-2 induced distinct etiolated growth and decreased chlorophyll content. Interaction studies verified that CsNF-YC2 and CsNF-YC9 target the CsTIC21 promoter directly and promote gene transcription. These findings provide mechanistic insights on the role of the NF-YCs-TIC21 module in chloroplast photomorphogenesis promoted by light in cucumber.

Computer-based facial recognition as an assisting diagnostic tool to identify children with Noonan syndrome.

BACKGROUND: Noonan syndrome (NS) is a rare genetic disease, and patients who suffer from it exhibit a facial morphology that is characterized by a high forehead, hypertelorism, ptosis, inner epicanthal folds, down-slanting palpebral fissures, a highly arched palate, a round nasal tip, and posteriorly rotated ears. Facial analysis technology has recently been applied to identify many genetic syndromes (GSs). However, few studies have investigated the identification of NS based on the facial features of the subjects. OBJECTIVES: This study develops advanced models to enhance the accuracy of diagnosis of NS. METHODS: A total of 1,892 people were enrolled in this study, including 233 patients with NS, 863 patients with other GSs, and 796 healthy children. We took one to 10 frontal photos of each subject to build a dataset, and then applied the multi-task convolutional neural network (MTCNN) for data pre-processing to generate standardized outputs with five crucial facial landmarks. The ImageNet dataset was used to pre-train the network so that it could capture generalizable features and minimize data wastage. We subsequently constructed seven models for facial identification based on the VGG16, VGG19, VGG16-BN, VGG19-BN, ResNet50, MobileNet-V2, and squeeze-and-excitation network (SENet) architectures. The identification performance of seven models was evaluated and compared with that of six physicians. RESULTS: All models exhibited a high accuracy, precision, and specificity in recognizing NS patients. The VGG19-BN model delivered the best overall performance, with an accuracy of 93.76%, precision of 91.40%, specificity of 98.73%, and F1 score of 78.34%. The VGG16-BN model achieved the highest AUC value of 0.9787, while all models based on VGG architectures were superior to the others on the whole. The highest scores of six physicians in terms of accuracy, precision, specificity, and the F1 score were 74.00%, 75.00%, 88.33%, and 61.76%, respectively. The performance of each model of facial recognition was superior to that of the best physician on all metrics. CONCLUSION: Models of computer-assisted facial recognition can improve the rate of diagnosis of NS. The models based on VGG19-BN and VGG16-BN can play an important role in diagnosing NS in clinical practice.

Gene regulatory network controlling carpel number variation in cucumber.

The WUSCHEL-CLAVATA3 pathway genes play an essential role in shoot apical meristem maintenance and floral organ development, and under intense selection during crop domestication. The carpel number is an important fruit trait that affects fruit shape, size and internal quality in cucumber, but the molecular mechanism remains elusive. Here, we found that CsCLV3 expression was negatively correlated with carpel number in cucumber cultivars. CsCLV3-RNAi led to increased number of petals and carpels, whereas overexpression of CsWUS resulted in more sepals, petals and carpels, suggesting that CsCLV3 and CsWUS function as a negative and a positive regulator for carpel number variation, respectively. Biochemical analyses indicated that CsWUS directly bound to the promoter of CsCLV3 and activated its expression. Overexpression of CsFUL1A , a FRUITFULL-like MADS-box gene, resulted in more petals and carpels. CsFUL1A can directly bind to the CsWUS promoter to stimulate its expression. Furthermore, we found that auxin participated in carpel number variation in cucumber through interaction of CsARF14 with CsWUS. Therefore, we have identified a gene regulatory pathway involving CsCLV3, CsWUS, CsFUL1A and CsARF14 in determining carpel number variation in an important vegetable crop - cucumber.

TINY BRANCHED HAIR functions in multicellular trichome development through an ethylene pathway in Cucumis sativus L.

The fruit trichomes of Cucurbitaceae are widely desired in many Asian countries and have been a key determinant of cucumber (Cucumis sativus L.) cultivar selection for commercial production and breeding. However, our understanding of the initiation and development of cucumber trichomes is still limited. Here, we found that the cucumber TINY BRANCHED HAIR (TBH) gene is preferentially expressed in multicellular trichomes. Overexpression of CsTBH in tbh mutants restored the trichome phenotype and increased the percentage of female flowers, whereas silencing of CsTBH in wild-type plants resulted in stunted trichomes with a lower rate of female flowers. Furthermore, we provide evidence that CsTBH can directly bind to the promoters of cucumber 1-Aminocyclopropane-1-Carboxylate Synthase (CsACS) genes and regulate their expression, which affects multicellular trichome development, ethylene accumulation, and sex expression. Two cucumber acs mutants with different trichome morphology and sex morphs compared with their near-isogenic line further support our findings. Collectively, our study provides new information on the molecular mechanism of CsTBH in regulating multicellular trichome development and sex expression through an ethylene pathway.

CsBRC1 inhibits axillary bud outgrowth by directly repressing the auxin efflux carrier CsPIN3 in cucumber.

Shoot branching is an important agronomic trait that directly determines plant architecture and affects crop productivity. To promote crop yield and quality, axillary branches need to be manually removed during cucumber production for fresh market and thus are undesirable. Auxin is well known as the primary signal imposing for apical dominance and acts as a repressor for lateral bud outgrowth indirectly. The TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) family gene BRANCHED1 (BRC1) has been shown to be the central integrator for multiple environmental and developmental factors that functions locally to inhibit shoot branching. However, the direct molecular link between auxin and BRC1 remains elusive. Here we find that cucumber BRANCHED1 (CsBRC1) is expressed in axillary buds and displays a higher expression level in cultivated cucumber than in its wild ancestor. Knockdown of CsBRC1 by RNAi leads to increased bud outgrowth and reduced auxin accumulation in buds. We further show that CsBRC1 directly binds to the auxin efflux carrier PIN-FORMED (CsPIN3) and negatively regulates its expression in vitro and in vivo. Elevated expression of CsPIN3 driven by the CsBRC1 promoter results in highly branched cucumber with decreased auxin levels in lateral buds. Therefore, our data suggest that CsBRC1 inhibits lateral bud outgrowth by direct suppression of CsPIN3 functioning and thus auxin accumulation in axillary buds in cucumber, providing a strategy to breed for cultivars with varying degrees of shoot branching grown in different cucumber production systems.

Initial Clinical Experience with the Biodegradable AbsnowTM Device for Percutaneous Closure of Atrial Septal Defect: A 3-Year Follow-Up.

OBJECTIVE: We reported the 3-year follow-up results of initial clinical experience with the AbsnowTM device, a novel biodegradable occluder for percutaneous closure of atrial septal defect (ASD). BACKGROUND: The AbsnowTM device is a total biodegradable septal occluder with double-disc poly-L-lactic acid (PLLA) framework and PLLA membranes intergraded into the device to ensure its biodegradability, clinical safety, and efficacy. METHODS: Five pediatric patients were enrolled from May to June 2018 in our institution and were followed up for 3 years. A clinical evaluation and transthoracic echocardiography were performed at 24 hr, 1 month, 3 months, 6 months, 12 months, and yearly after implantation. Primary endpoints were a composite clinical success, comprising of clinical closure success and safety at the 36-month follow-up evaluation. Secondary endpoints included technical success, procedure success, closure success, and safety at each of the follow-up visits. RESULTS: The median subject age was 3.6 years (range 3.1-6.5 years). The mean ASD diameter was (13.7 ± 2.9) mm. The median device size was 20 mm (range 14 to 24 mm). Technical and procedure success was achieved in 100% (5/5) of the patients. At 2-year follow-up, 3 of the 5 patients developed new-onset residual shunts and 2 of them reached a moderate degree. At 3-year follow-up, the residual shunt size increased over time in all the 3 patients, and 1 of them had right ventricular enlargement. All of the 5 patients were free from serious adverse events during the 3-year follow-up, with no device embolization, thromboembolization, or reintervention to the target defect. CONCLUSION: This 3-year follow-up result of initial experience with the biodegradable AbsnowTM device has demonstrated acceptable safety with no procedural complications. Notably, the high rate of residual shunt significantly affected its efficacy. The long-term safety and efficacy of the device should be further evaluated in a large cohort of patients in future studies.

Nutrition and metabolism status alteration in advanced hepatocellular carcinoma patients treated with anti-PD-1 immunotherapy.

PURPOSE: The aim of this study was to evaluate the nutrition and metabolism status alteration during immunotherapy in advanced hepatocellular carcinoma (HCC) patients. METHODS: Patients with advanced HCC who participated in the clinical trials of single-agent anti-PD-1 immunotherapy or sorafenib were retrospectively included. We analyzed self-comparison of the nutritional and metabolic indices of patients in the anti-PD-1 and sorafenib treatment group. We conducted mutual-comparison of the mentioned indices between the disease progression group and disease control group among anti-PD-1 treatment patients. We further analyzed those indices with statistical differences by partial correlation and survival analysis. RESULTS: Both self-comparison before and after treatment in the anti-PD-1 group and mutual-comparison of disease progression and the control group showed significant differences in multiple indices, but we did not observe significant differences in the sorafenib group. Strikingly, albumin (ALB)/prognostic nutritional index (PNI, calculated by serum albumin and lymphocyte count) decreased distinctly in the immunotherapy disease progression group patients. However, changes in ALB/PNI were not significant in disease progression patients from the sorafenib group or in the disease control patients with immunotherapy. Partial correlation analysis suggested that ALB and PNI were positively correlated with the efficacy of immunotherapy. Furthermore, survival analysis showed that the median progression-free survival and median overall survival of patients in the ALB/PNI decreased group were significantly shorter than those of patients from the ALB/PNI increased group. CONCLUSION: Anti-PD-1 immunotherapy might alter the nutritional and metabolic status in advanced HCC patients. We also should pay attention to the nutritional and metabolic status of patients when drug resistance is detected.

δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages.

δ-Tocotrienol, an important component of vitamin E, has been reported to possess some physiological functions, such as anticancer and anti-inflammation, however their molecular mechanisms are not clear. In this study, δ-tocotrienol was isolated and purified from rice bran. The anti-inflammatory effect and mechanism of δ-tocotrienol against lipopolysaccharides (LPS) activated pro-inflammatory mediator expressions in RAW264.7 cells were investigated. Results showed that δ-tocotrienol significantly inhibited LPS-stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-α, IFN-γ, IL-1ß and IL-6) production and blocked the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2). δ-Tocotrienol repressed the transcriptional activations and translocations of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), which were closely related with downregulated cytokine expressions. Meanwhile, δ-tocotrienol also affected the PPAR signal pathway and exerted an anti-inflammatory effect. Taken together, our data showed that δ-tocotrienol inhibited inflammation via mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR) signalings in LPS-stimulated macrophages.

Mycoplasma gallisepticum MGA_0676 is a membrane-associated cytotoxic nuclease with a staphylococcal nuclease region essential for nuclear translocation and apoptosis induction in chicken cells.

Mycoplasma gallisepticum can infect a wide variety of birds including the commercial poultry. M. gallisepticum MGA_0676 is a putative lipoprotein, which is similar to bacterial thermostable nucleases. But the possible pathogenic effect of M. gallisepticum MGA_0676 has not been investigated so far. In the present study, we cloned the MGA_0676 gene after deletion of the amino-terminal signal sequence and mutagenesis of the Mycoplasma TGA tryptophan codons to TGG and expressed recombinant MGA_0676 protein in Escherichia coli. We identified and characterized MGA_0676 as a Ca(2+)-dependent cytotoxic nuclease of M. gallisepticum with a staphylococcal nuclease (SNc) region that displays the hallmarks of nucleases. Membrane protein immunoblot analysis and immunogold electron microscopy revealed that MGA_0676 locates on the membrane surface of M. gallisepticum. Furthermore, apoptosis assay using annexin V-FITC and propidium iodide (annexin V/PI) indicated that MGA_0676 played significant roles in apoptosis induction and pathological damages in chicken cells. Moreover, confocal microscopy showed that MGA_0676 localizes in the nuclei of host cells. Besides, after the SNc region was deleted, MGA_0676 lost its ability of nuclear localization, nuclease activity, and cytotoxicity, which revealed that the SNc region is essential for nuclear translocation and induction of apoptosis in chicken cells. The above results suggest that MGA_0676 is an important virulence factor in cellular pathology and may play a unique role in the life cycle events of M. gallisepticum.

Enzyme linked aptamer assay: based on a competition format for sensitive detection of antibodies to Mycoplasma bovis in serum.

Mycoplasma bovis (M. bovis) is a major, but often overlooked, pathogen that causes respiratory disease, mastitis, and arthritis in cattle. It has been widespread in China since 2008. In this study, single-stranded DNA (ssDNA) aptamers with high affinity and specificity against the P48 protein of M. bovis were selected using microplates as the matrix. Of nine candidates, aptamer WKB-14 showed the best affinity in an indirect enzyme-linked aptamer assay (ELAA) and good specificity by dot blotting. To the best of our knowledge, this is the first time that an aptamer has been used in a competitive ELAA for the serological detection of M. bovis. The percent inhibition (PI) cutoff value of the indirect competitive ELAA (ic-ELAA) was 40%, assessed using 20 negative sera. In a comparative study of different detection methods, ic-ELAA with dc-ELISA and dot blotting had a higher positive detection rate than the other two commercial indirect ELISA kits.

[Levels of histone H3 acetylation in peripheral blood mononuclear cells of acute cerebral infarction patients].

OBJECTIVE: To observe the co-variation of acetylated histone H3 levels of peripheral blood mononuclear cells (PBMCs) and onset time of acute ischemic stroke and examine the histone H3 acetylation levels in PBMCs of acute cerebral infarction patients with different stroke subtypes and injury degrees. METHODS: The peripheral blood samples 2 ml from patients at different timepoints (1, 3, 5, 7, 14 d) from April 2013 to July 2013 and normal controls were collected to observe the dynamic change of Ac-H3 levels of PBMCs in cerebral infarction patients. Also between April 2013 and October 2013, blood samples from 103 patients within 7 d after acute ischemic stroke were collected. Global histone was extracted by assay kit and differential histone H3 acetylation levels were determined by Western blot. All patients were measured by the Oxfordshire Community Stroke Project (OCSP) classification and National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: The levels of acetylated histone H3 in PBMCs of acute cerebral infarction patients started to decrease as early as 1 d and remained below those normal controls for at least 7 d after stroke. It fulfilled the minimum at 3 d after infarction (P < 0.001). Acetylated histone H3 levels of PBMCs differed in OCSP classification (P < 0.05) and reached a nadir in TACI group. Histone H3 acetylation levels of PBMCs were major affecting factors of neurological injury severity and negatively correlated with it through multiple regressive analysis (ß = -0.297, P = 0.001). CONCLUSION: Histone H3 acetylation level in PBMCs of acute cerebral infarction patients is lower than healthy persons. And it decreases markedly in TACI group and patients with severe neurological dysfunction.

A critical review of the bioactive ingredients and biological functions of camellia oleifera oil.

Camellia oleifera oil is a pure and natural high-grade oil prevalent in South China. Camellia oleifera oil is known for its richness in unsaturated fatty acids and high nutritional value. There is increasing evidence indicating that a diet rich in unsaturated fatty acids is beneficial to health. Despite the widespread production of Camellia oleifera oil and its bioactive components, reports on its nutritional components are scarce, especially regarding systematic reviews of extraction methods and biological functions. This review systematically summarized the latest research on the bioactive components and biological functions of Camellia oleifera oil reported over the past decade. In addition to unsaturated fatty acids, Camellia oleifera oil contains six main functional components contributing to its antioxidant, antibacterial, anti-inflammatory, antidiabetic, anticancer, neuroprotective, and cardiovascular protective properties. These functional components are vitamin E, saponins, polyphenols, sterols, squalene, and flavonoids. This paper reviewed the biological activity of Camellia oleifera oil and its extraction methods, laying a foundation for further development of its bioactive components.

Discrepancy between arterial oxygen saturation and pulse oximetry measurement in a Chinese pediatric patient cohort.

Background: Increasing evidence suggest a racial bias in pulse oximetry measurement, but this was under investigated in Asian pediatric populations. Methods: Via the Pediatric Intensive Care database, this retrospective study included pediatric patient records of arterial oxygen saturation (SaO2) and oxygen saturation on pulse oximetry (SpO2) measured within 10 min. Discrepancy was examined, and potential predictors of occult hypoxemia (defined as SaO2 <88% with the paired SpO2 ≥92%) as well as its association with outcomes were explored by logistic regression. Results: A total of 390 patients were included with 454 pairs of SaO2-SpO2 readings. The study population consisted of Han Chinese (99.0%) and 43.6% were female. Occult hypoxemia was observed in 20.0% of the patients, with a mean SaO2 of 71.4 ± 15.8%. Potential predictors of occult hypoxemia included female, being first admitted to cardiac ICU, congenital heart disease, increased heart rate, while patients with prior surgery records were less likely to experience occult hypoxemia. Patients with occult hypoxemia had numerically higher in-ICU mortality (16.7% versus 10.9%) and in-hospital mortality (17.9% versus 10.9%), but the associations were not statistically significant. Conclusions: There was a substantial proportion of hypoxemia that was not detected by pulse oximetry in the Chinese pediatric patients, which might be predicted by several characteristics and seemed to associate with mortality.

Echocardiographic characteristics and clinical outcomes in fetuses with pulmonary stenosis or pulmonary atresia with intact ventricular septum.

OBJECTIVE: To summarize echocardiographic characteristics of the anatomy and hemodynamic and clinical outcomes in fetuses with isolated pulmonary stenosis (PS) or pulmonary atresia with intact ventricular septum (PA/IVS). METHODS: This was a single-center retrospective study of fetuses with isolated PS or PA/IVS. Echocardiographic variables and clinical outcomes after delivery were evaluated and compared. RESULTS: Between 2016 and 2021, 115 livebirths with isolated PS or PA/IVS were included. Proportion of fetuses with mild, moderate and critical PS and PA/IVS was 41.7 %, 18.3 %, 26.1 % and 13.9 %. Fetuses with more severe PS had worse anatomic and hemodynamic profiles. Specifically, the cardiothoracic ratio, pulmonary valve (PV) velocity, degree and velocity of tricuspid regurgitation increased as PS severity increased; and the pulmonary artery/aorta ratio, right ventricle/left ventricle long-axis (TV/MV) ratio, tricuspid valve/mitral valve annulus (TV/MV) ratio, and tricuspid valve inflow duration/cardiac cycle ratio decreased as PS severity increased (P <0.001 for all). PV velocity ≥2 m/s predicted PV pressure ≥40 mm Hg after delivery, with an AUC of 0.81; TV/MV ratio combined with RV/LV ratio predicted clinical outcomes, with an AUC of 0.88. Live births with more severe PS had higher mortality rate (mild 0 vs. moderate 0 vs. critical 11 % vs. PA-IVS 36 %) and lower rate of developing bi-ventricles (mild 100 % vs. moderate 95 % vs. critical 89 % vs. PA-IVS 36 %). CONCLUSION: Findings of this study help better understand the anatomy and hemodynamic and clinical outcomes in fetuses with isolated PS or PA/IVS, which could have implications for prenatal counseling and prediction of fetal outcome.

A Comprehensive Review of Health-Benefiting Components in Rapeseed Oil.

Rapeseed oil is the third most consumed culinary oil in the world. It is well-known for its high content of unsaturated fatty acids, especially polyunsaturated fatty acids, which make it of great nutritional value. There is increasing evidence that a diet rich in unsaturated fatty acids offers health benefits. Although the consumption of rapeseed oil cuts across many areas around the world, the nutritional elements of rapeseed oil and the exact efficacy of the nutrients remain unclear. In this review, we systematically summarized the latest studies on functional rapeseed components to ascertain which component of canola oil contributes to its function. Apart from unsaturated fatty acids, there are nine functional components in rapeseed oil that contribute to its anti-microbial, anti-inflammatory, anti-obesity, anti-diabetic, anti-cancer, neuroprotective, and cardioprotective, among others. These nine functional components are vitamin E, flavonoids, squalene, carotenoids, glucoraphanin, indole-3-Carbinol, sterols, phospholipids, and ferulic acid, which themselves or their derivatives have health-benefiting properties. This review sheds light on the health-benefiting effects of rapeseed oil in the hope of further development of functional foods from rapeseed.

The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma.

PURPOSE: The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. METHODS: Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. RESULTS: In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). CONCLUSIONS: Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.

The role of TMEM26 in disrupting tight junctions and activating NF-κB signaling to promote epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

OBJECTIVES: Metastasis is one of the biggest challenges in the management of Esophageal Squamous Cell Carcinoma (ESCC), of which molecular mechanisms remain elusive. The present study aimed to explore the roles and underlying mechanisms of Transmembrane protein 26 (TMEM26) in ESCC. METHOD: TMEM26 expressions in tumorous and adjacent tissues from patients with ESCC and in normal esophageal epithelial and ESCC cell lines were detected by immunostaining and western blotting, respectively. The Epithelial-Mesenchymal Transition (EMT), a critical process during metastasis, was investigated by wound healing and Transwell assays, and EMT-related proteins were examined after the TMEM26 alteration in ESCC cell lines. NF-κB signaling activation and Tight Junction (TJ) protein expression were analyzed by western blotting and immunofluorescence, respectively. In vivo verification was performed on the liver metastatic murine model. RESULTS: Compared with non-cancerous esophageal tissues and cells, the TMEM26 expression level was higher in ESCC samples and cell lines, where the plasma membrane localization of TMEM26 was observed. The EMT-related processes of ESCC cells were suppressed by RNAi depletion of TMEM26 but aggravated by TMEM26 overexpression. Mechanistically, TMEM26 promoted NF-κB signaling to accelerate EMT in ESCC cells. The plasma membrane presentation and assembly of TJ proteins were impaired by TMEM26. CONCLUSION: Overall, TMEM26 acts as a critical determinant for EMT in ESCC cells by disrupting TJ formation and promoting NF-κB signaling, which may be a potential therapeutic target for treating metastatic ESCC.