Gansulinema gen. nov. and Komarkovaeasiopsis gen. nov.: Novel Oculatellacean genera (Cyanobacteria) isolated from desert soils and hot spring.

To increase the understanding of simple thin filamentous cyanobacteria in harsh environmental areas, we previously isolated and identified four strains (XN101, XN102, GS121, NX122) from desert soils and hot spring in China. As a result, two new Oculatellacean genera of these four strains, Gansulinema gen. nov. and Komarkovaeasiopsis gen. nov., are described based on a polyphasic approach. The ultrastructure of these strains showed a similar arrangement of peripheral thylakoids with three to four parallel layers, indicating that they belonged to the orders Nodosilineales, Oculatellales, or Leptolyngbyales. In the 16S rRNA gene phylogeny, two sequences of the Gansulinema strains and the two sequences of the Komarkovaeasiopsis strains formed two independent and robust clusters, within the order Oculatellales. The 16S rRNA gene sequences of strains of Komarkovaeasiopsis and Gansulinema showed low identity to each other (≤93.2%) and to other sequences of the Oculatellacean genera (≤94.5% and ≤93.3%, respectively). Furthermore, the 16S-23S internal transcribed spacer rRNA region secondary structures of strains of Komarkovaeasiopsis and Gansulinema were not consistent with all existing descriptions of Oculatellacean taxa. These data suggest that cyanobacterial communities are rich sources of new taxa in under-exploited areas, such as desert soils and hot spring in China.

Retraction of: Diagnostic Value of Exosomal miR-148a-3p in the Serum of Patients with Differentiated Thyroid Cancer.

This retracts the article DOI: 10.7754/Clin.Lab.2020.200519.

Construction of machine learning tools to predict threatened miscarriage in the first trimester based on AEA, progesterone and ß-hCG in China: a multicentre, observational, case-control study.

BACKGROUND: Endocannabinoid anandamide (AEA), progesterone (P4) and ß-human chorionic gonadotrophin (ß-hCG) are associated with the threatened miscarriage in the early stage. However, no study has investigated whether combing these three hormones could predict threatened miscarriage. Thus, we aim to establish machine learning models utilizing these three hormones to predict threatened miscarriage risk. METHODS: This is a multicentre, observational, case-control study involving 215 pregnant women. We recruited 119 normal pregnant women and 96 threatened miscarriage pregnant women including 58 women with ongoing pregnancy and 38 women with inevitable miscarriage. P4 and ß-hCG levels were detected by chemiluminescence immunoassay assay. The level of AEA was tested by ultra-high-performance liquid chromatography-tandem mass spectrometry. Six predictive machine learning models were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), accuracy and precision. RESULTS: The median concentration of AEA was significantly lower in the healthy pregnant women group than that in the threatened miscarriage group, while the median concentration of P4 was significantly higher in the normal pregnancy group than that in the threatened miscarriage group. Only the median level of P4 was significantly lower in the inevitable miscarriage group than that in the ongoing pregnancy group. Moreover, AEA is strongly positively correlated with threatened miscarriage, while P4 is negatively correlated with both threatened miscarriage and inevitable miscarriage. Interestingly, AEA and P4 are negatively correlated with each other. Among six models, logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) models obtained the AUC values of 0.75, 0.70 and 0.70, respectively; and their accuracy and precision were all above 0.60. Among these three models, the LR model showed the highest accuracy (0.65) and precision (0.70) to predict threatened miscarriage. CONCLUSIONS: The LR model showed the highest overall predictive power, thus machine learning combined with the level of AEA, P4 and ß-hCG might be a new approach to predict the threatened miscarriage risk in the near feature.

Preserved myocardial viability in patients with chronic total occlusion of a single coronary artery.

OBJECTIVE: To assess the benefits of coronary collateral circulation on myocardial perfusion, viability and function in patients with total occlusion of a single coronary artery using the 99mTc-sestamibi SPECT and 18F-fluorodeoxyglucose PET. METHODS: 164 Consecutive patients were included who underwent coronary angiography results exhibited total occlusion of a single coronary artery and received 99mTc-MIBI SPECT and 18F-FDG PET within 90 days of angiography. Myocardial perfusion and viability in patients with collateral circulation and those without it were compared. Long-term follow-up was performed through a review of patient clinical records. RESULTS: Collateral circulation was present in 56 patients (34%) and absent in 108 patients (66%). The total perfusion defect size in patients with collateral circulation decreased when compared to those without (30% ± 13% to 35% ± 14%, P < .05). The myocardial viability was 22% ± 12% in patients with collateral circulation, and 12% ± 9% in those without (P < .001). The left ventricular ejection fraction was higher, and the end-diastolic and end-systolic left ventricular volumes were lower in patients with collateral circulation (39% ± 11%, 138 ± 66, 89 ± 57) compared to patients without collateral circulation (31% ± 9%, 177 ± 55, 125 ± 48, all P < .001, respectively). Multi-factor logistic regression identified that concerning the variables of sex, age, viable myocardium, collateral circulation, treatment type and others, only treatment type was significantly associated with therapeutic effects (OR 3.872, 95% CI 1.915-7.830, P < .001). CONCLUSION: Collateral circulation can preserve resting myocardial blood perfusion and myocardial viability, and help maintain the function of the left ventricular myocardium. The appropriate treatment strategy will have a substantial impact on the therapeutic outcome.

Diagnostic Value of Exosomal miR-148a-3p in the Serum of Patients with Differentiated Thyroid Cancer.

BACKGROUND: The current study aims to evaluate the expression and diagnostic value of exosomal miR-148a-3p in the serum of DTC patients. METHODS: Exosomes were isolated from the serum of DTC patients and were identified using a transmission electron microscope. RT-PCR was performed to determine the level of exosomal miR-148a-3p in DTC patients. The possible target gene of miR-148a-3p was determined using dual luciferase reporter assay. ROC analysis was performed to determine the diagnostic value of exosomal miR-148a-3p in DTC patients. RESULTS: We identified a novel exosomal miRNA, exosomal miR-148a-3p, that was significantly decreased in the serum of DTC patients compared with that of benign thyroid tumor patients and healthy controls. Further study showed that exosomal miR-148a-3p was correlated with the malignant characteristics of DTC, including tumor diameter, lymph node metastasis (LNM), and higher TNM staging. Dual luciferase reporter assay indicated that IGF-1 was a target gene of miR-148a-3p. ROC analysis demonstrated that the AUC of exosomal miR-148a-3p was better than TgAb and Tg in DTC patients. More importantly, combined use of exosomal miR-148a-3p, TgAb, and Tg significantly enhanced the sensitivity and specificity, indicating exosomal miR-148a-3p is a sensitive biomarker in DTC patients. CONCLUSIONS: Altogether, reduced exosomal miR-148a-3p was associated with the risk of DTC and may be used as a biomarker for the diagnosis of DTC.

An Unusual Salt Effect in an Interfacial Nucleophilic Substitution Reaction.

This paper reports a kinetic characterization of the interfacial reaction of N-methylpyrrolidine with a self-assembled monolayer presenting an iodoalkyl group. SAMDI (self-assembled monolayers for matrix-assisted laser desorption/ionization) mass spectrometry was used to determine the extent of reaction for monolayers that were treated with a range of concentrations of the nucleophile for a range of times. These data revealed a second-order rate constant for the reaction that was approximately 100-fold greater than that for the analogous solution-phase reaction. However, addition of sodium iodide to the reaction mixture resulted in a 7-fold decrease in the reaction rate. Addition of bromide and chloride salts also gave slower rate constants for the reaction, but only at 100- and 1000-fold higher concentrations than was observed with iodide, respectively. The corresponding solution-phase reactions, by contrast, had rate constants that were unaffected by the concentration of halide salts. This work provides a well-characterized example illustrating the extent to which the kinetics and properties of an interfacial reaction can depart substantially from their better-understood solution-phase counterparts.

Meta-analysis shows that circulating tumor cells including circulating microRNAs are useful to predict the survival of patients with gastric cancer.

BACKGROUND: Circulating tumor cells (CTCs) are metastatic cells disseminated into the bloodstreams. They have been proposed to monitor disease progression for decades. However, the prognostic value of CTCs in gastric cancer (GC) remains controversial. We performed a meta-analysis to investigate the topic. METHODS: A systematic search was made for relevant studies in academic data bases, involving the Medline, Embase, and Science Citation Index. Data on prognosis of GC patients, such as recurrence-free survival (RFS) and overall survival (OS), were extracted when possible. The meta-analysis was performed with the random effects model and the pooled hazard ratios (HRs) and their associated 95% confident intervals (95%CIs) were computed as effect measures. RESULTS: Twenty six studies (including 40 subgroups) with peripheral blood samples of 1950 cases from 10 countries were included in the final analysis. The pooled results showed that GC patients with detectable CTCs (including circulating miRNAs) had a tendency to experience shortened RFS (HR=2.91, 95% CI [1.84-4.61], I2=52.18%, n=10). As for patient deaths, we found a similar association of CTC (including circulating miRNAs) presence with worse OS (HR=1.78, 95% CI [1.49-2.12], I2=30.71%, n=30). Additionally, subgroup analyses indicated strong prognostic powers of CTCs, irrespective of geographical, methodological, detection time and sample size differences of the studies. CONCLUSIONS: Our meta-analysis shows that CTCs (including circulating miRNAs) can predict the survival of GC patients. Large prospective studies are warranted to determine the best sampling time points, detection methods in homogeneous patients with GC in the future.

Prediction of EGFR-TP53 genes co-mutations in patients with lung adenocarcinoma (LUAD) by 18F-FDG PET/CT radiomics.

PURPOSE: This retrospective study was undertaken to assess the predictive efficacy of 18F-FDG PET/CT -derived radiomic features concerning the co-mutation status of epidermal growth factor receptor (EGFR) and TP53 in LUAD. METHODS: A cohort of 150 LUAD patients underwent pretreatment 18F-FDG PET/CT scans with known mutation status of EGFR and TP53 were collected. The feature extraction based on their PET/CT images utilized the Pyradiomics package based on the 3D Slicer. The optimal radiomic features were selected through correlation analysis and the Gradient Boosting Decision Tree (GBDT) algorithm, followed by the construction of the radiomic model. The clinical model incorporated meaningful clinical variables, whereas the complex model integrated both the radiomic and clinical models. The area under the receiver operating characteristic curve (AUC) facilitated the comparison of prediction performance across the three models. The DCA gauged the clinical utility of these models. RESULTS: The patient cohort was randomly allocated into a training set (n = 105) and a validation set (n = 45) in a 7:3 ratio. Eleven PET and eleven CT optimal radiomic features were selected to construct the radiomic model. The model showed a good ability to discriminate the co-occurrence of EGFR and TP53, with AUC equal to 0.850 in the training set, and 0.748 in the validation set, compared with 0.750 and 0.626 for the clinical model. The complex model exhibited the highest AUC values, with 0.880 and 0.794 in both sets, but there were no significant differences compared to the radiomic model. The DCA revealed favorable clinical value.

Peri- and intra-nodular radiomic features based on 18F-FDG PET/CT to distinguish lung adenocarcinomas from pulmonary granulomas.

Objective: To compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas. Methods: For this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1-5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Good and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model. Conclusion: When intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.

Steady-state of an enzymatic reaction is dependent on the density of reactant.

The post-translational modification of proteins is controlled by the relative activities of two opposing enzymes. For example, the extent of phosphorylation of tyrosine residues reflects the balance of a kinase and a phosphatase enzyme. The present article uses as a model system a self-assembled monolayer that presents a peptide that can be phosphorylated by Abl kinase and subsequently dephosphorylated by Lambda phosphatase. Treatment of monolayers with a reaction mixture containing both enzymes reveals that the steady-state level of peptide phosphorylation is dependent on the density of the peptide. Using identical reaction mixtures, surfaces that presented the substrate at high density led to a phosphorylated peptide at steady-state, whereas surfaces that presented the substrate at low density led to unphosphorylated peptide at steady-state. This dependence owes to an autocatalytic phosphorylation reaction that operates at high densities of substrate. This work provides an example of an interfacial reaction that has properties that have no analogue in the corresponding solution phase reaction. It also provides a model system that is relevant to understanding mechanisms that regulate signaling at the cellular membrane.

Sodium thiosulfate inhibits epithelial-mesenchymal transition in melanoma via regulating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Melanoma is the most common form of skin cancer. Given its high metastasis and high recurrence, its therapies are constantly updated. OBJECTIVE: The study aims to prove the efficacy of sodium thiosulfate (STS), an antidote to cyanide or nitroprusside poisoning, in melanoma treatment. METHODS: We tested the effect of STS by culturing melanoma cells (B16 and A375) in vitro and establishing melanoma mouse models in vivo. The proliferation and viability of melanoma cells were measured by the CCK-8 test, cell cycle assay, apoptosis analysis, wound healing assay, and transwell migration assay. The expression of apoptosis-related molecules, epithelial-mesenchymal transition (EMT)-associated molecules, and the Wnt/ß-catenin signaling pathway-related molecules were determined by Western blotting and immunofluorescence. RESULTS: The high metastasis of melanoma is considered to be linked to the EMT process. The scratch assay using B16 and A375 cells also showed that STS could inhibit the EMT process of melanoma. We demonstrated that STS inhibited the proliferation, viability, and EMT process of melanoma by releasing H2S. STS-mediated weakening of cell migration was related to the inhibition of the Wnt/ß-catenin signaling pathway. Mechanistically, we defined that STS inhibited the EMT process via the Wnt/ß-catenin signaling pathway. CONCLUSIONS: These results suggest that the negative effect of STS on melanoma development is mediated by the reduction of EMT via the regulation of the Wnt/ß-catenin signaling pathway, which provides a new clue to treating melanoma.

Evaluation of water quality and management of Hongze Lake and Gaoyou Lake along the Grand Canal in Eastern China.

Hongze Lake and Gaoyou Lake are the source of water for the Grand Canal and the eastern route of the South-to-North Water Transfer (SNWT) project. With the accelerating pace of construction of the SNWT and the initiative to achieve "World Heritage " status for the canal, the water quality and management of the lakes have gained attention in China. Based on analysis of water samples, monitoring data, and the content of heavy metal elements in surface sediments, the water quality of Gaoyou Lake and Hongze Lake have been examined. According to the analysis of the water samples taken in 2003, the content of the heavy metals met the water demands for Hongze Lake and Gaoyou Lake. However, monitoring data of 2004 indicate that the water quality of Hongze Lake and Gaoyou Lake both were worse than grade III which cannot meet the required standard. The heavy metal elements of sediment samples also were above the acceptable environmental standard values. Some projects were launched to promote the lake environment by controlling wastewater emissions, standardizing the types of boats and introducing regulations to protect the lakes. However, problems of vertical and horizontal fragmentation and insufficient public participation in the current management system still exist in the area. Considering the problems confronting the lakes, Integrated Water Resource Management is discussed as an effective approach to overcome the problems.

Rescue Protocol to Improve the Image Quality of 18F-FDG PET/CT Myocardial Metabolic Imaging.

PURPOSE: 18F-FDG PET myocardial metabolic imaging is used to estimate myocardial viability. However, poor image quality can affect the accurate quantification of viable myocardium. We assessed the feasibility of a rescue protocol that reinjected low-dose 18F-FDG with simultaneous 1 to 2 U of insulin injection and oral administration of 10 g of glucose to improve the image quality of 18F-FDG PET myocardial metabolic imaging. PATIENTS AND METHODS: Fifty-one consecutive patients with poor quality to uninterpretable 18F-FDG PET/CT myocardial metabolic images received the rescue protocol immediately after the initial image acquisition. The postrescue image acquisition was performed 1 hour later. The rescue image quality was compared with the initial image. The qualitative visual estimation of the images was graded as follows: grade 0, homogeneous, minimal uptake; grade 1, predominantly minimal or mild uptake; grade 2, moderate uptake; and grade 3, good uptake. The myocardium-to-blood pool activity ratio (M/B) was measured to assess the image quality quantitatively. RESULTS: The grades of 0 to 3 were observed in 24 (47%), 27 (53%), 0 (0%), and 0 (0%) patients, respectively, for the initial imaging, and in 0 (0%), 3 (5.9%), 4 (7.8%), and 44 (86.3%) patients for the rescue imaging (P < 0.001). The rescue M/B was significantly higher than the initial M/B (3.4 ± 1.4 vs 1.6 ± 0.6, respectively; P < 0.001). CONCLUSIONS: The rescue protocol successfully and rapidly improved the quality of myocardial 18F-FDG metabolic imaging.

Genetic Profiling of Breast Cancer with and Without Preexisting Metabolic Disease.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women. Various mechanisms are involved in the initiation and progression of breast cancer. Metabolic dysregulation has been associated with increasing breast cancer incidence and mortality. However, little is known about how metabolic disease regulates the development and progression of breast cancer at the molecular level. Here, using a hybridization capture-based panel including 124 cancer-associated genes, we performed targeted next-generation sequencing of tumor tissues and matched blood samples from 20 postmenopausal patients with primary breast cancer, in which 6 cases suffered from preexisting metabolic disorders including hypertension, type 2 diabetes, and coronary heart disease. We took only the protein-altering variants and identified 170 somatic mutations of 59 genes. Among these, 40 mutated genes were found in the metabolic disease group, and 33 mutated genes were found in the non-metabolic disease group. Importantly, nonsynonymous mutations of 26 genes (MSH3, BRAF, MLH3, MTOR, DDR2, ALK, etc.) were uniquely present in the metabolic disease group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to investigate biological functions and key pathways of somatic mutations. TP53, PIK3CA, and PTEN were the top three commonly mutated genes at a higher frequency compared with the Cancer Genome Atlas (TCGA) data, and several novel but infrequent mutations in other genes were also found. Although further studies are required to validate these variants, our results are the first to suggest a specific molecular profile of breast cancer with preexisting metabolic disease.

Catalpol regulates the proliferation and apoptosis of breast cancer MCF-7 cells through the FOXO3-FOXM1 signal axis / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨中药地黄提取物梓醇（Cat）对乳腺癌MCF-7细胞增殖与凋亡，以及裸鼠移植瘤生长的影响及其机制。方法：以不同质量浓度（0、5、25、50、100、200 μg/mL）Cat处理人乳腺癌MCF-7细胞，用MTT法筛选Cat给药浓度。将MCF-7细胞分为空白对照组、Cat低剂量组、Cat中剂量组、Cat高剂量组、Cat+sh-NC组和Cat+sh-FOXO3组，采用Edu细胞增殖实验、平板克隆实验、流式细胞术分别检测各组细胞的增殖与克隆形成能力、凋亡率和细胞周期，WB法检测各组细胞中FOXO3、FOXM1、caspase-3和caspase-8蛋白表达。构建乳腺癌MCF-7细胞裸鼠移植瘤模型，观察Cat对移植瘤生长的影响，WB法检测移植瘤组织中FOXO3和FOXM1蛋白表达。结果：Cat低（50 μg/mL）、中（100 μg/mL）、高（200 μg/mL）剂量处理的MCF-7细胞的增殖能力均显著下降（均P<0.05）。与空白对照组比较，Cat低、中、高剂量组Edu阳性细胞率、克隆形成数、S期与G2/M期细胞比例及FOXO3蛋白表达均显著降低（均P<0.05），细胞凋亡率、G0/G1期细胞比例及FOXM1、caspase-3、caspase-8蛋白表达均显著升高（均P<0.05）；与Cat+sh-NC组比较，Cat+sh-FOXO3组Edu阳性细胞率、克隆形成数、S期与G2/M期细胞比例及FOXO3蛋白表达均显著升高（均P<0.05），细胞凋亡率、G0/G1期细胞比例及FOXM1、caspase-3和caspase-8蛋白表达均显著下降（均P<0.05）。Cat组MCF-7细胞裸鼠移植瘤体积、质量和FOXO3蛋白表达均显著降低（均P<0.05），FOXM1的蛋白表达显著升高（P<0.05）。结论：Cat抑制乳腺癌MCF-7细胞增殖并促进凋亡，在体内抑制裸鼠移植瘤的生长，其机制可能与上调FOXO3、下调FOXM1的表达有关。

Myocardial Infarction in a Patient With Hypertrophic Cardiomyopathy but Normal Coronary Arteries.

A 57-year-old man with a history of hypertrophic cardiomyopathy diagnosed by echocardiography experienced atypical chest pain and dyspnea for 6 months. A rest Tc-MIBI myocardial SPECT imaging and a F-FDG myocardial PET/CT imaging were performed, which showed multiple matched myocardial perfusion/metabolism defects in the left ventricle, indicating scar tissue. Surprisingly, subsequent contrast coronary angiography revealed no significant coronary artery stenosis.

The Prognostic Value of Circulating Cell-Free DNA in Colorectal Cancer: A Meta-Analysis.

BACKGROUND: Circulating cell-free DNA (cfDNA) is a promising candidate biomarker for detection, monitoring and survival prediction of colorectal cancer (CRC). However, its prognostic significance for patients with CRC remains controversial. To derive a precise estimation of the prognostic significance of cfDNA, a meta-analysis was performed. METHODS: We made a systematic search in data base of the Science Citation Index Embase and Pubmed for studies reporting prognostic data of cfDNA in CRC patients. The data of cfDNA on recurrences-free survival (RFS) and overall survival (OS) were extracted and measured in hazard rates (HRs) and 95% confident intervals (CIs). Subgroup analyses were carried out as well. Finally, the meta-analysis is accompanied with nine studies including 19 subunits. RESULTS: The pooled HRs with 95% CIs revealed strong associations between cfDNA and RFS (HR [95%CI]=2.78[2.08-3.72], I(2)=32.23%, n=7) along with OS (HR [95%CI]=3.03[2.51-3.66], I(2)=29.24%, n=12) in patients with CRC. Entire subgroup analyses indicated strong prognostic value of cfDNA irrespective tumor stage, study size, tumor markers, detection methods and marker origin. CONCLUSIONS: All the results exhibits that appearance of cfDNA in blood is an indicator for adverse RFS and OS in CRC patients.

SAMDI Mass Spectrometry-Enabled High-Throughput Optimization of a Traceless Petasis Reaction.

Development of the self-assembled monolayer/MALDI mass spectrometry (SAMDI) platform to enable a high-throughput optimization of a traceless Petasis reaction is described. More than 1800 unique reactions were conducted simultaneously on an array of self-assembled monolayers of alkanethiolates on gold to arrive at optimized conditions, which were then successfully transferred to the solution phase. The utility of this reaction was validated by the efficient synthesis of a variety of di- and trisubstituted allenes.