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Background: IVS-II-5 G>C (HBB: c.315+5 G>C) is a rare β-thalassemia mutation. However, there is no clear evidence regarding the effect of this defect or co-inheritance of other β-thalassemia mutations on phenotypes. Methods: The clinical phenotypes associated with compound heterozygosity for the IVS-II-5 G>C mutation and other β-thalassemia mutations, together with the genetic modifiers' potential effect of the genetic modifiers α-thalassemia, were studied in 13 patients. In addition, analyses of red cell indices, hemoglobin component, iron status, and α-globin genes were carried out in 19 heterozygotes. Results: Next-generation sequencing of 24 undiagnosed patients with transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) identified 13 carriers of the IVS-II-5 G>C mutation. There was a wide spectrum of phenotypic severity in compound heterozygotes and 6 (46.2%) of 13 were transfusion dependent. Analysis of 19 heterozygotes indicated that most were hematologically normal without appreciable microcytosis or hypochromia, and approximately half had normal hemoglobin A2 levels at the same time. Conclusion: Compound heterozygotes for IVS-II-5 G>C and other severe β-thalassemia mutations are phenotypically severe enough to necessitate appropriate therapy and counselling. Coinheritance of this nucleotide substitution with other β-thalassemia mutations may account for a considerable portion of the incidence of undiagnosed patients with NTDT and TDT in Guangxi. Therefore, the IVS-II-5 G>C mutation can pose serious difficulties in screening and counselling. [ABSTRACT FROM AUTHOR]

The Otindag sandland, located at the boundary of the East Asian monsoon area, is sensitive to climate change and is therefore an ideal place to investigate past environmental evolution. Due to frequent volcanic eruptions that have occurred since the Cenozoic, numerous interbeds of multi-stage basalt and sand exist in the stratigraphic sequence, which allowed older sand to be preserved due to the protective effect of the overlying rock. Previous studies of climate change in the sandland mainly focused on the time interval since the last glacial period, and information is lacking regarding climate change over longer timescales and younger volcanic activity. The key reason for this is that suitable geological carriers are rare, which prevents the expansion of the desired sediment chronological scale. In order to establish the chronological framework, samples of the sandy paleosoil, aeolian sand, lacustrine sand and volcanic baked layer were collected and dated by the optically stimulated luminescence (OSL) method. The conventional SAR, TT-OSL and pIRIR(200,290) procedures were used to obtain equivalent doses of quartz and feldspar. To ensure the accuracy of the dating data, the age of the feldspar dating of the oldest aeolian sand sample (TBB) was compared with the quartz result, and the quartz and feldspar ages were found to be consistent with each other within the error range. Considering the error of the age measured by TTOSL (384.2±68.0 ka) exceeded 10%, the age measured by the pIRIR(200,290) method (321.2±11.5 ka) was adopted to represent the deposition age of the aeolian sand sample. In addition, the age of the oldest sand deposition in the three sections of the Otindag sandland may reach 300 ka, mainly due to the different thermal history and provenance from other areas such as Loess Plateau, resulting in the different saturation dose and dose rate lever of quartz or feldspar. The sedimentary age framework established by OSL dating enabled the reconstruction of the evolution process of the Otindag Sandland. The climate was cold and dry during the periods corresponding to 321.2, 160.3-151.6 and 4.4 ka, and the Aeolian sand material quickly accumulated during these times, as dunes were activated and the sandland expanded. During the periods corresponding to 5.0 ka and 2.4-1.3 ka, sandy soil developed efficiently, implying the dunes were fixed. The oldest lacustrian sand age is 320.4±16.0 ka for quartz dated by the SAR method. Hence, aeolian sand and lacustrine sand developed in the same period, which indicates that there was a landscape where dunes and lakes coexisted around 320.4 ka, such as at present. The Optical Stimulated Luminescence dating results of the volcanic baking layer and the underlying coarse sand layer confirm that volcanic activity occurred around 321.2 and 155.0 ka. Combined with results of previous research, this study indicates that the northeast and northwestward basement faults of the northern margin of the North China Craton and the Central Asian orogenic belt are characterized by extensional tectonic properties in the background setting of plate subduction, and relative uplift and settlement occur in the sandland formation zone. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests that hepatitis C virus (HCV) contributes to hepatocellular carcinoma (HCC) by directly modulating oncogenic signaling pathways. Protein phosphatase magnesium-dependent 1A (PPM1A) has recently emerged as an important tumor suppressor as it can block a range of tumor-centric signaling pathways through protein dephosphorylation. However, the role and regulatory mechanisms of PPM1A in HCV-infected cells have not been reported. Methods: Total, cytoplasmic, and nuclear PPM1A protein after HCV infection or overexpression of HCV nonstructural protein 3 (NS3) were detected by western blotting. The expression of PPM1A in normal liver and HCV-related HCC tissues was quantified by immunohistochemistry. The effects of HCV infection and NS3 expression on the PPM1A protein level were systematically analyzed, and the ubiquitination level of PPM1A was determined by precipitation with anti-PPM1A and immunoblotting with either anti-ubiquitin or anti-PPM1A antibody. Finally, the roles of NS3 and PPM1A in hepatoma cell migration and invasion were assessed by wound healing and transwell assays, respectively. Results: HCV infection and replication decreased PPM1A abundance, mediated by NS3, in hepatoma cells. Compared to normal liver tissues, the expression of PPM1A was significantly decreased in the HCC tumor tissues and adjacent non-tumor tissues. NS3 directly interacted with PPM1A to promote PPM1A ubiquitination and degradation, which was dependent on its protease domain. Blockade of PPM1A through small interfering RNA significantly promoted HCC cell migration, invasion, and epithelial mesenchymal transition (EMT), which were further intensified by TGF-β1 stimulation, in vitro. Furthermore, restoration of PPM1A abrogated the NS3-mediated promotion of HCC migration and invasion to a great extent, which was dependent on its protein phosphatase function. Conclusions: Our findings demonstrate that the HCV protein NS3 can downregulate PPM1A by promoting its ubiquitination and proteasomal degradation, which might contribute to the migration and invasion of hepatoma cells and may represent a new strategy of HCV in carcinogenesis. [ABSTRACT FROM AUTHOR]

We obtain an estimate on the rate of convergence of Durrmeyer-Bézier operaters for functions of bounded variation by means of some probabilistic methods and inequality techniques. Our estimate improves the result of Zeng and Chen (2000). [ABSTRACT FROM AUTHOR]

In this paper, the singular perturbation of nonlinear differential equation system with nonlinear boundary conditions is discussed. Under suitable assumptions, with the asymptotic method of Lyusternik-Vishik[1] and fixed point theory, the existence of the solution of the perturbation problem is proved and its uniformly valid asymptotic expansion of higher order is derived. [ABSTRACT FROM AUTHOR]

Background: ((1-triphenylaminebenzo[c][1,2,5] thiadiazole-4-yl) styryl)-1-methylpyridin methylpyridin-1-ium iodide salt (TBZPy) is a novel photosensitizer that displays excellent photodynamic properties. However, There are few reports on the mechanism of action of the TBZPy photodynamic. Previous studies revealed that photodynamic therapy (PDT) could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum. Therefore, in this study, we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus (HR-HPV) infection and their underlying mechanisms. Methods: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with TBZPy-PDT. Cell migration, invasion, and colony-forming ability were evaluated using wound-healing, Transwell invasion, and colonyforming assays, respectively. Through western blot analysis, we determined the level of expression of the PI3K/AKT and PERK/eIF2α pathway proteins and the proteins associated with calcium trafficking and apoptosis. The calcium levels in the cytoplasm were detected via flow cytometry. Results: The result shows that TBZPy-PDT could inhibite the migration, invasion, and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro. And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2α pathway. Moreover, TBZPy-PDT increased the levels of calcium and calmodulin, while decreasing the levels of endoplasmic reticulum calcium-binding proteins. Conclusions: TBZPy-PDT is effective on treating human papillomavirus-infected cells. Targeting the PI3K/AKT and PERK/eIF2α pathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection. [ABSTRACT FROM AUTHOR]

The sustained-release properties of the biodegradable nano-drug delivery systems were used to improve the residence time of the chemotherapeutic agent in the body. These drug delivery systems were widely used to deliver chemotherapeutic drugs.The 5-fluorouracil loaded chitosan nanoparticles prepared in this paper have the above advantage. Here, we found that when the mass ratio of 5-fluorouracil and chitosan was 1:1, the maximum drug loading of nanoparticles was 20.13 ± 0.007%, the encapsulation efficiency was 44.28 ± 1.69%, the particle size was 283.9 ± 5.25 nm and the zeta potential was 45.3 ± 3.23 mV. The prepared nanoparticles had both burst-release and sustained-release phases in vitro release studies. In addition, the inhibitory effect of the prepared nanoparticles on gastric cancer SGC-7901 cells was similar to that of 5-fluorouracil injection and the blank vector had no obvious inhibitory effect on SGC-7901 cells. In the pharmacokinetic study of rats in vivo, we found that AUC (0-t), MRT (0-t) and t1/2z of nanoparticles were significantly increased in vivo compared with 5-fluorouracil solution, indicating that the prepared nanoparticles can play a role in sustained-release. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the molecular mechanism governing the regulation of transcription factor Oct4 and embryonic stem cells. Observation regarding the repressive effect of Oct4 on Nanog promoter is revealed. The function of forkhead box D3 antibody as an activator of Nanog is described. The failure of Oct4 and Nanog in sustaining the self-renewal of mouse embryonic stem cells is revealed.

A Pd-catalyzed site-selective C(sp2)–H activation/cycloimidoylation of 2-isocyano-2,3-diarylpropanoates to construct diverse cyclic imine products has been developed. Six-membered 3,4-dihydroisoquinolines containing a C3 quaternary carbon center were generated dominantly by using bulky Ad2Pn-Bu as a ligand, while five-membered 1,1-disubstituted 1H-isoindoles were formed preferentially in the presence of bidentate phosphine ligand DPPB. The selectivity for 1H-isoindole formation was enhanced by using steric hindered aryl iodides. DFT calculations suggested that the experimentally observed ligand-controlled selectivity was a result of trans effect. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. It has been speculated that plant MMPs are involved in plant growth, development, and stress response. However, the biological function of MMPs in higher plants still remains elusive. In the present study, a MMP gene Gm2-MMP was isolated and characterized. It encoded a 357 amino acids protein and contained a common domain structure of MMPs. Subcellular localization of Gm2-MMP-GFP fusion protein indicated thatGm2-MMP was located in plasma membrane. Gm2-MMP was found to show higher expression levels in mature seeds, mature leaves, or old leaves than in other organs and was continuously expressed from seed development to maturation stage. Additionally, Gm2-MMP participated in response to HTH stress in leaves and developing seeds (R7 period) of soybean. The overexpression of Gm2-MMP in Arabidopsis affected the growth and development of leaves, enhanced the tolerance to HTH stress in leaves and developing seeds, and improved the vitality of seed. Twenty-eight candidate proteins interacted with Gm2- MMP were identified from the cDNA library of soybean developing seed under HTH stress by yeast two-hybrid (Y2H) screen. Our results suggested that Gm2-MMP is related to growth and development and confers enhanced HTH stress tolerance in plants. This will be helpful for us in further understanding of the biological functions of MMP family in plant. [ABSTRACT FROM AUTHOR]

The AgSbF6-catalyzed cyclization of 2-diazo-3,5-dioxo-6-ynoates (ynones, ynamide) in alcoholic solvents affords γ-pyrones, whereas the AgOAc-catalyzed cyclization in 1,2-dichloroethane (DCE) produces 3(2H)-furanones. The cyclization reactions proceeded cleanly under mild reaction conditions, and the desired γ-pyrones or 3(2H)-furanones were obtained in excellent yield. It was observed for the first time that both the catalyst and solvent play key roles in the selective formation. This unique method for the reversal of regioselectivity proved to be highly efficient except for substrates with aliphatic and Me3Si groups at the triple bond position. [ABSTRACT FROM AUTHOR]

The incidence of acute myeloid leukemia (AML) increases with age. Elderly patients with AML are less tolerant to high-intensity consolidation therapy than younger patients, with significantly worse prognoses. Induction and consolidation therapy combined with allogeneic hematopoietic stem cell microtransplantation may improve the prognosis of elderly patients with AML. The present study reports the effect of maintenance therapy with low-dose chemotherapy treatment combined with microtransplantation in elderly patients with AML following consolidation. Between January 2011 and April 2014, three elderly patients (>55 years old), including one 58-year-old patient with acute mixed lineage leukemia (AMLL) and two patients with AML aged 59 years and 62 years, underwent microtransplantation maintenance therapy. Following a complete response to induction chemotherapy and consolidation chemotherapy with two to four cycles of medium dose Ara-c (auto transplantation was performed in the patient with AMLL), maintenance therapy was performed using low-dose Ara-c combined with human leukocyte antigen haploidentical allogeneic hematopoietic stem cell microtransplantation, which was repeated every 3 to 6 months. The patients were followed up for 27, 20 and 16 months, respectively, and all three patients achieved disease-free survival. The bone marrow Wilms' tumor suppression gene (WT1) level of the case with AMLL was dynamically monitored. The results showed that the WT1 level was abnormally high prior to microtransplantation and gradually declined to normal levels subsequent to the process. None of the patients suffered from graft versus host disease during the microtransplantation process. In conclusion, microtransplantation maintenance therapy following consolidation therapy is feasible in elderly patients with AML, and is expected to be able to further remove residual lesions and improve treatment efficacy. A large-scale clinical trial is required to confirm the effect of maintenance therapy in elderly patients with AML. [ABSTRACT FROM AUTHOR]

Interferon (IFN)-γ is a potent proinflammatory molecule. However, few studies have investigated the expression levels of IFN-γ during pelvic organ prolapse (POP). In the present study, the expression levels and tissue localization of IFN-γ and its pathway.associated genes were detected in the vaginal walls of premenopausal females with POP and asymptomatic controls using quantitative polymerase chain reaction and immunohistochemistry. When compared with the matched controls, an 8.6-fold increase in IFN-γ, 3.8-fold increase in IFN-γ receptor (IFNGR)1, 2.6-fold increase in IFNGR2, 3.4-fold increase in signal transducer and activator of transcription-1, 2.2-fold increase in janus kinase-1 and 5.1-fold increase in nuclear factor (NF)-κB mRNA expression levels were observed in the females with premenopausal POP. In all the females with POP, higher mRNA expression levels of IFN-γ and its receptors were observed when compared with the controls. Expression levels of all the proteins were detected by immunohistochemistry, and the results demonstrated higher staining for IFN-γ, IFNGRs and pathway-associated genes in females with POP. Therefore, the results indicated that IFN-γ may be used as an inflammatory marker for POP development, and is associated with NF-κB. [ABSTRACT FROM AUTHOR]

Paleoflood slackwater deposits (SWDs) of the Holocene were found at many sites along the Jin-Shaan Gorges in the middle Yellow River basin. A set of four paleoflood SWD beds was identified at the Pingduguan (PDG) sites and studied by field observations and laboratory analysis including particle-size distribution and Optically Stimulated Luminescence (OSL) dating. Hydrological reconstruction using the HEC-RAS model shows that the paleoflood peak discharges were between 39,000 and 50,220m³s-1. They are about double the largest gauged flood (24,000m³s-1) that has occurred since 1976 along the Jin-Shaan Gorges. These extraordinary flood events were OSL dated to between 1800 and 1600yr BP during which climatic deterioration and disasters were documented over the Yellow River basin. Various evidences show that severe flood and drought disasters during the episode resulted in frequent harvest failures, famines, social upheavals, and population reduction, invasions by nomads, and even the fall and replacement of the dynasties. Climate decline documented by proxy records such as tree-rings, stalagmites, ice-cores and lake sediments from over the world is in agreement with the paleoflood events identified along the Jin-Shaan Gorges. These mean that the extraordinary paleoflood events are closely related to increased climatic variability and instability. This result provides solid evidence for understanding the response of hydroclimatic system to global climate change in the semi-arid and sub-humid regions of the world. [ABSTRACT FROM AUTHOR]

Previous palaeoclimatic studies in the northeastern Qinghai-Tibetan Plateau (NETP) during the Holocene, mainly using lake sediments, have deepened our understanding of the climatic system in this remote region. The timing and forcing mechanisms of climatic change in this region are still controversial, however. Aeolian sand and silt deposits, which are widely distributed in the NETP, can be readily dated by optically stimulated luminescence (OSL) techniques and reveal the sensitive response of the landscape to climatic change. In this study, aeolian sand and loess at six sites around Qinghai Lake were studied to reconstruct millennial-scale climatic changes during the Holocene. Multiproxy data along with 24 OSL age determinations show that low effective moisture and aeolian activity occurred at c. 13 ka, 10—9.1 ka, and 8.9—7.8 ka. Periods of greater effective moisture may have occurred at ~11 ka and 9 ka, and there is evidence for a previously undocumented wet climate at 4—3 ka. These results show that millennial-scale Holocene palaeoclimatic changes in the NETP cannot be explained simply as direct responses to changes in monsoon precipitation forced by summer insolation. We suggest that changes in effective moisture were determined by the balance between monsoon-induced rainfall and evaporation loss (mainly controlled by temperature). Thus, climatic change in the NETP may have been influenced by complex interactions between the monsoon circulation and local convection/evaporation effects, in addition to large-scale change in the Asian monsoon and the westerlies. [ABSTRACT FROM AUTHOR]