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Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder. A retrospective analysis predicted that the live birth prevalence of SRS in Estonia is 1:15,886 [Yakoreva et al., Eur J Hum Genet, 2019, 27(11), 1649-1658]. The most common causative genetic mechanism in the proband is loss of paternal methylation in the imprinted control region 1 (ICR1) at 11p15.5 chromosome. A few studies suggested that inherited or de novo loss-of-function alterations of the PLAG1 gene, including the whole-gene deletion and intragenic pathogenic variants, could cause a rare type of SRS. To date, less than 20 unrelated PLAG1-related SRS cases have been reported, and the clinical information about these cases is limited. We report the first prenatal case of SRS with 8q12 deletion (including the PLAG1 gene). The fetus presented with intrauterine growth retardation, small for gestational age, relative macrocephaly at birth, and a protruding forehead. Unlike classical SRS cases, the fetus had micrognathia and did not show body asymmetry. We hope that the literature review in this study provides new insights into genotype-phenotype relationships of PLAG1-related SRS. [ABSTRACT FROM AUTHOR]

Salvianolate (Sal) is a medicinal composition that is widely used in China for the treatment of coronary heart disease and angina pectoris. The aim of the present study was to investigate the potential macrophage-mediated pro-angiogenic effects of Sal in vitro. In addition, another aim was to explore the effects of Sal in a rat model of transient middle cerebral artery occlusion (tMCAO) along with the potential mechanism by which it promotes angiogenesis. In this study, human umbilical vein endothelial cells (HUVECs) and Raw264.7 macrophages in vitro, and a rat tMCAO model in vivo were used to detect the pro-angiogenic effect and mechanism of Sal. The results of in vitro experiments showed that the viability, migration and tube formation of HUVECs were promoted by the supernatant of Sal-treated Raw264.7 macrophages (s-Sal) but not by Sal alone. s-Sal also increased the levels of phosphorylated (p-)VEGFR-2, p-AKT and p-p38 MAPK in HUVECs while Sal alone did not. In vivo, treatment with Sal significantly reduced the cerebral infarction volume and neurological deficit scores in the rat tMCAO model. Similar to the mechanism observed in the in vitro experiments, Sal treatment upregulated the protein expression of VEGF and VEGFR-2, in addition to the phosphorylation of VEGFR-2, AKT and p38, in the brain tissues of the tMCAO model rats. In summary, the results of the present study suggest that the mechanism of Sal-mediated angiogenesis is associated with stimulation of the VEGF/VEGFR-2 signaling pathway by macrophages. This suggests the potential of Sal as a therapeutic option for the treatment of acute cerebral ischemic injury, which may act via the promotion of angiogenesis. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to analyze the clinical and pathological characteristics, treatment, and prognosis of de novo metastatic breast cancer (DnMBC). Information regarding 1,890 patients treated for advanced breast cancer at the Tianjin Medical University Cancer Hospital between January 2008 to December 2017 was collected. Clinicopathological characteristics, treatments and outcomes of these patients were compared using the chi-square test, log-rank test, and Cox regression analysis. A total of 171 patients were diagnosed with DnMBC. The median age at diagnosis was 53 years (range, 23-77). The percentage of T4 staging was higher (37.4%), 69.6% of patients were estrogen receptor (ER) positive, 59.1% were progesterone receptor positive, 29.8% had positive human epidermal growth factor receptor 2 (HER2) status, 68.4% had Ki-67 ≥20%, 55% had oligometastasis at the initial diagnosis, ~87.7% were treated with chemotherapy initially and 24% received palliative surgery for the primary tumor. After a median follow-up time of 26 months, the median progression-free survival (PFS) and overall survival (OS) among patients with DnMBC were 11 (8.7-13.3) months and 34 (27.9-40.1) months, respectively. In the multivariable model, ER status and sites of first metastasis (oligometastasis or polymetastasis) were identified to be independent predictors of PFS (P<0.05); ER status, primary tumor stage, and surgical treatment of primary tumors were identified to be independent predictors of OS (P<0.05). In conclusion, the clinicopathological characteristics of DnMBC are greater invasiveness and a higher risk of progression. Palliative surgical treatment may improve the prognosis of HR+/HER2-patients with oligometastasis. Therefore, individualized treatment as required is particularly important. [ABSTRACT FROM AUTHOR]

Calcium carbonate (CaCO3) biomineralization has been investigated due to its wide range of scientific and technological implications, however, the molecular mechanisms of this important geomicrobiological process are largely unknown. Here, a ureasepositive marine actinobacterium Brevibacterium linens BS258 was demonstrated to effectively form CaCO3 precipitates. Surprisingly, this bacterium could also dissolve the formed CaCO3 with the increase of the Ca2+ concentration. To disclose the mechanisms of biomineralization, the genome of B. linens BS258 was further completely sequenced. Interestingly, the expression of three carbonic anhydrases was significantly up-regulated along with the increase of Ca2+ concentration and the extent of calcite dissolution. Moreover, transcriptome analyses revealed that increasing concentration of Ca2+ induced KEGG pathways including quorum sensing (QS) in B. linens BS258. Notably, most up-regulated genes related to QS were found to encode peptide/nickel ABC transporters, which suggested that nickel uptake and its associated urease stimulation were essential to boost CaCO3 biomineralization. Within the genome of B. linens BS258, there are both cadmium and lead resistance gene clusters. Therefore, the sequestration abilities of Cd2C and Pb2+ by B. linens BS258 were checked. Consistently, Pb2+ and Cd2C could be effectively sequestered with the precipitation of calcite by B. linens BS258. To our knowledge, this is the first study investigating the microbial CaCO3 biomineralization from both genomic and transcriptomic insights, which paves the way to disclose the relationships among bacterial metabolisms and the biomineralization. [ABSTRACT FROM AUTHOR]

We investigated differences between goat and cow milk by exploring the factors influencing milk stability by testing the heat coagulation time. Heat-stable milk samples were characterized by a higher pH, a lower heating temperature, a lower calcium concentration, a higher concentrations of EDTA-2Na, phosphate and citrate. However the sucrose concentration caused different patterns of heat stability. The heat stability of milk increased as the sucrose concentration increased from 10% to 30%, then decreased as it rose above 30%. Compared with cow milk, goat milk is less stable to heat treatments being affected by pH, heating temperature, and the addition of calcium chloride, disodium EDTA, disodium hydrogen phosphate, and sucrose. After adding sodium citrate, the heat stability of goat milk was better than that of cow milk, with ANOVA results indicating a statistically significant difference. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) is an important pathogen that causes childhood and travelers' diarrhea. Here, we present the draft genomes of four ETEC isolates recovered from stool specimens of patients with diarrhea in Beijing, China and Dhaka, Bangladesh, respectively. Results: We obtained the draft genomes of ETEC strains CE516 and CE549 isolated in China, and E1777 and E2265 isolated in Bangladesh with a length of 5.1 Mbp, 4.9 Mbp, 5.1 Mbp, and 5.0 Mbp, respectively. Phylogenetic analysis indicated that the four strains grouped with the classical Escherichia coli phylogenetic groups A and B1 and three of them including a multi drug-resistant Chinese isolate (CE549) belonged to two major ETEC lineages distributed globally. The heat stable toxin (ST) structural gene (estA) was present in all strains except in strain CE516, and the heat labile toxin (LT) operon (eltAB) was present in all four genomes. Moreover, different resistance gene profiles were found between the ETEC strains. Conclusions: The draft genomes of the two isolates CE516 and CE549 represent the first genomes of ETEC reported from China. Though we revealed that ETEC is uncommon in Beijing, China, however, when it does occur, multi-drug resistance and ESBL positive isolates might pose a specific public health risk. Furthermore, this study advances our understanding of prevalence and antibiotic resistance of ETEC in China and adds to the number of sequenced strains from Bangladesh. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii is an important nosocomial pathogen that poses a serious health threat to immune-compromised patients. Due to its rapid ability to develop multidrug resistance (MDR), A. baumannii has increasingly become a focus of attention worldwide. To better understand the genetic variation and antibiotic resistance mechanisms of this bacterium at the genomic level, we reported high-quality draft genome sequences of 8 clinical isolates with various sequence types and drug susceptibility profiles. Results: We sequenced 7 MDR and 1 drug-sensitive clinical A. baumannii isolates and performed comparative genomic analysis of these draft genomes with 16 A. baumannii complete genomes from GenBank. We found a high degree of variation in A. baumannii, including single nucleotide polymorphisms (SNPs) and large DNA fragment variations in the AbaRlike resistance island (RI) regions, the prophage and the type VI secretion system (T6SS). In addition, we found several new AbaR-like RI regions with highly variable structures in our MDR strains. Interestingly, we found a novel genomic island (designated as GIBJ4) in the drug-sensitive strain BJ4 carrying metal resistance genes instead of antibiotic resistance genes inserted into the position where AbaR-like RIs commonly reside in other A. baumannii strains. Furthermore, we showed that diverse antibiotic resistance determinants are present outside the RIs in A. baumannii, including antibiotic resistance-gene bearing integrons, the blaOXA-23-containing transposon Tn2009, and chromosomal intrinsic antibiotic resistance genes. Conclusions: Our comparative genomic analysis revealed that extensive genomic variation exists in the A. baumannii genome. Transposons, genomic islands and point mutations are the main contributors to the plasticity of the A. baumannii genome and play critical roles in facilitating the development of antibiotic resistance in the clinical isolates. [ABSTRACT FROM AUTHOR]

We have observed electrical-field induced magneto-conductivity oscillations measured in Corbino samples made of a GaAs high-mobility two-dimensional electron gas, and found a consistent interpretation based on a semiclassical model of 2kF-selected orbital transitions between N and N + 1, 2, 3,..., Landau levels at respective local potentials, where kF is the Fermi wavevector. From the oscillation period, we deduce an effective mass value, which is consistent with the bare electron band mass of GaAs. In the same devices but with a vanishing electrical field and at elevated temperatures, we observed additional oscillation features, which can be attributed to cyclotron resonance by population of acoustic phonons. We thus demonstrate a method to determine the carrier effective mass and the sound velocity of host crystals by standard electrical transport. [ABSTRACT FROM AUTHOR]