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To compare the impact-sliding wear of different CAD/CAM resin-ceramic materials and tooth enamel, and explore the corresponding wear damage mechanism.Human tooth enamel (EN), Vita ENAMIC (Vita, VE), Lava Ultimate (3 M, LU), and GC CERASMART (GC, CS) were used in this study. The hardness, elastic modulus, and roughness values of the samples were measured. Further, impact-sliding wear tests were performed in a ball-on-flat configuration with spherical zirconia antagonists and the coefficients of friction (CoF) were recorded simultaneously. Additionally, a white light interferometer was used to determine the volume losses and scanning electron microscopy was used to observe the wear morphology of the wear scars and the damage feature in the vertical sections to clarify the damage mechanism during the impact-sliding wear test.EN exhibited the highest elastic modulus and CoF, followed by VE, LU, and CS. The hardness and roughness of EN and VE were similar and were higher than those of LU and CS. Throughout the wear tests, VE exhibited the highest volume loss, whereas CS exhibited the lowest. The wear damage characteristics of VE were similar to those of EN, displaying brittle fractures of inorganic substances and plastic deformation of organic substances in the impact part, exhibiting plough marks in the sliding parts. In the case of LU and CS, the entire wear areas displayed plastic deformation of the resin matrix, exfoliation of the filler particles, and plough marks.Enamel and polymer-infiltrated ceramic network materials exhibit similar wear damage modes. Additionally, the high-density nanocomposite resin material is the most resistant to impact-sliding wear from a tribological perspective.

Objective Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells. Methods A miR122 target (122T) sequence was incorporated into the 3′ untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined. Results The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells. Conclusion HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.

The major challenge of recombinant adeno-associated virus (rAAV) vectors is host immunological barriers. Compared to the neutralizing antibody and the cytotoxic T lymphocyte response, the host immune responses induced by unsatisfactory rAAV manufacturing were largely ignored previously. rAAV vector production usually requires large amounts of plasmid DNAs. The DNA are commonly isolated from the DH5α bacterial strain, which contains lipopolysaccharide (LPS) contamination. LPS, also named endotoxin, in plasmid DNA is intractable, and residual endotoxin in the subsequent rAAV vectors may result in substantial host immune response. Recently, a ClearColi K12 bacterial strain is commercially available, with genetically modified LPS that does not trigger endotoxic response in mammalian cells. Here, we produced rAAV-DJ vectors by plasmids yielded from either DH5α or ClearColi K12 bacterial strains. Our data indicated that the ClearColi K12 strain had satisfactory protection for the rAAV inverted terminal repeat (ITR) sequence. As expected, the ClearColi K12-derived rAAV-DJ vectors had lower endotoxin levels. The physical and biological equivalency of the purified viral stocks were confirmed by electron micrographs, Coomassie blue staining, and transduction assays. Most importantly, the ClearColi K12-derived rAAV-DJ vectors triggered reduced nuclear factor-kappa B (NF-κB) signaling pathway both in cell cultures in vitro and in C57BL/6 mice retinas in vivo. We believe that the use of the ClearColi K12 bacterial strain could eliminate the LPS in the purified vector stock at the source. Our data indicate its promising use in future clinical development.

Nowadays, with more and more WEEE (waste electrical and electronic equipment) being abandoned, WEEE recycling activities are increasingly popular. In this paper, we build a closed-loop supply chain model and focus on the recycling behaviors of the members in this supply chain, which contains two manufacturers, the retailer, and the consumer. In the reverse chain, we set up dual channels and design two recycling methods: sell-back method and trade-in method. We use classical backward induction to run the model. And then we analyze the stability of the system and the impacts of some essential parameters by numerical simulation. The speed of the manufacture’s decision adjustment has a significant effect on the stability of the model. Manufacturers should adopt a stable rather than radical price adjustment strategy in order to achieve stable profit growth in the whole supply chain and avoid a chaotic price war. Manufacturers should increase innovation investment in recycling technology to reduce the cost of remanufacturing products and improve the initiative in market competition. In the end, we adopt the parameter control method and the decision-making method to control chaos, and they both have a good control effect.

Nowadays, with a great number of household electrical appliances being discarded in every corner of the world every day, household electrical appliances recycling is attracting more attention. In this paper, we build a closed-loop supply chain that consists of a manufacturer and a third-party recycler based on the development of “Internet Plus” recovery platform. We thoroughly analyze the model and its evolution by chaos theory, complex dynamics theory, and numerical simulation and introduce the adaptive method to control the chaos of the system. We find that as the manufacturer increases the retail price, the stable area of the market becomes smaller. At the same time, when the manufacturers direct recycle price or the price adjustment range of the products recycled from the third party exceeds a certain threshold, all the recycle prices in the whole market will fluctuate, thus causing market chaos. Among them, as an adjustment decision method, delay strategy reduces the volatility of recycle price and makes it return to a stable state, which is an effective method to control system disorder. In addition, the third-party recycler will change the optimal subsidy model according to the government’s price subsidy level, while the manufacturer always prefers the price subsidy model.

Dysregulation of gut microbiota is implicated in the pathogenesis of various diseases, including metabolic diseases, inflammatory diseases, and cancer. To date, the link between gut microbiota and myeloid leukemia (ML) remains largely unelucidated. Herein, a total of 29 patients with acute myeloid leukemia (AML), 17 patients with chronic myeloid leukemia (CML), and 33 healthy subjects were enrolled, and gut microbiota were profiled via Illumina sequencing of the 16S rRNA. We evaluated the correlation between ML and gut microbiota. The microbial α‐diversity and β‐diversity exhibited significant differences between ML patients and healthy controls (HCs). Compared to healthy subjects, we found that at the phylum level, the relative abundance of Actinobacteria, Acidobacteria, and Chloroflexi was increased, while that of Tenericutes was decreased. Correspondingly, at the genus level in ML, Streptococcus were increased, especially in AML patients, while Megamonas (P = 0.02), Lachnospiraceae NC2004 group, and Prevotella 9 (P = 0.007) were decreased. Moreover, ML‐enriched species, including Sphingomonas, Lysobacyer, Helicobacter, Lactobacillus, Enterococcus, and Clostridium sensu stricto 1, were identified. Our results indicate that the gut microbiota was altered in ML patients compared to that of healthy subjects, which could contribute to the elucidation of microbiota‐related pathogenesis of ML, and the development of novel therapeutic strategies in the treatment of ML., The gut microbiota was altered in myeloid leukemia (ML). At the phylum level, the abundance of Actinobacteria, Acidobacteria, and Chloroflexi increased, while that of Tenericutes decreased compared to healthy subjects. At the genus level in ML, Streptococcus increased while Megamonas, Lachnospiraceae NC2004 group, and Prevotella 9 decreased. ML‐enriched species included Sphingomonas, Lysobacyer, Helicobacter, Lactobacillus, Enterococcus, and Clostridium sensu stricto 1.

Hematopoietic gene delivery, such as hematopoietic stem/progenitor cells (HSPCs), is a promising treatment for both inherited and acquired diseases, such as hemophilia. Recently, a combined strategy to achieve more than 90% transduction efficiency was documented using recombinant adeno-associated virus serotype 6 (rAAV6) vectors. However, the mechanisms of enhanced vector transduction efficiency in hematopoietic cells are largely unknown. In this manuscript, we first reported that proteasome inhibitors, which are well-known to facilitate rAAV intracellular trafficking in various cell types, are not effective in hematopoietic cells. From the screening of small molecules derived from traditional Chinese medicine, we demonstrated that shikonin, a potential reactive oxygen species (ROS) generator, significantly increased the in vitro and ex vivo transgene expression mediated by rAAV6 vectors in hematopoietic cells, including human cord blood-derived CD34 + HSPCs. Shikonin mainly targeted vector intracellular trafficking, instead of host cell entry or endonuclear single to double strand vector DNA transition, in a vector serotype-dependent manner. Moreover, a ROS scavenger completely prevented the capability of shikonin to enhance rAAV6 vector-mediated transgene expression. Taken together, these studies expand our understanding of rAAV6-mediated transduction in hematopoietic cells and are informative for improving rAAV6-based treatment of blood diseases.

The effect of polar monomer styrene content on the effectiveness of the performance of poly(octadecyl acrylate) (POA) pour-point depressant (PPD) was studied using the model waxy oils (MWOs) and Sh...

Thermodynamic equilibria of complexes of 1,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetic acid (DHPTA) with heavy lanthanides (Tb3+, Ho3+ and Lu3+) in aqueous solution have been investigated with potentiometry, spectrophotometry, luminescence spectroscopy and nuclear magnetic resonance spectroscopy (NMR). The results identified three 1:1 Ln/DHPTA (Ln: Tb3+, Ho3+ and Lu3+) complexes with different degrees of deprotonation, LnL−, Ln(H−1L)2−, and Ln(OH)(H−1L)3−, where H−1 represents the deprotonation of the hydroxyl group between two methyliminodiacetate groups in the DHPTA structure. The alkoxide form of the DHPTA hydroxyl group directly binds to the lanthanide atom, forming highly strong chelation. The complex of Ln(H−1L)2− could be present as a dimeric or polymeric complex in solution.

We report the observation of coherent oscillations in the relaxation dynamics of an exciton-polariton condensate that were driven by parametric scattering processes. As a result of the interbranch scattering scheme and the nonlinear polariton-polariton interactions, such parametric scatterings exhibit a high scattering efficiency that leads to the fast depletion of the polariton condensate and the periodic shut-off of the bosonic stimulation processes, eventually causing relaxation oscillations. Employing polariton-reservoir interactions, the oscillation dynamics in the time domain can be projected onto the energy space. In theory, our simulations using the open-dissipative Gross-Pitaevskii equation are in excellent agreement with experimental observations. Surprisingly, the oscillation patterns, including many excitation pulses, are clearly visible in our time-integrated images, implying the high stability of the relaxation oscillations driven by polariton parametric scatterings.

ObjectiveTo determine whether gut microbiota, fatty metabolism and cytokines were associated with immune thrombocytopenia (ITP).MethodsIn total, 29 preliminarily diagnosed ITP patients and 33 healthy volunteers were enrolled. Fecal bacterial were analyzed based on 16S rRNA sequencing. Plasma cytokines and motabolites were analyzed using flow cytometry and liquid chromatography-mass spectrometry (LC-MS), respectively.ResultsBacteroides, Phascolarctobacterium, and Lactobacillus were enriched at the genus level in ITP patients, while Ruminococcaceae UCG-002, Eubacterium coprostanoligeues, Megamonas, and Lachnospiraceae NC2004 were depleted. At the phylum level, the relative abundance of Proteobacteria and Chloroflexi increased in ITP patients, while Firmicutes, Actinobacteria, and the Firmicutes/Bacteroidetes ratio decreased. Plasma levels of 5-hydroxyeicosatetraenoic acid (5-HETE), 6-trans-12-epi-leukotriene B4 (6t,12e-LTB4), and resolvin D2 (RvD2) were upregulated, and stachydrine, dowicide A, dodecanoylcarnitine were downregulated in ITP patients. Furthermore, RvD2 is positively correlated with order Bacteroidetes VC2.1 Bac22, 5-HETE is positively correlated with genus Azospirillum, and 6t,12e-LTB4 is positively correlated with genus Cupriavidus. In addition, stachydrine is positively correlated with family Planococcaceae, dowicide A is positively correlated with class MVP-15, and dodecanoylcarnitine is positively correlated with order WCHB1-41. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were upregulated in ITP patients.ConclusionOur study revealed a relationship between microbiota and fatty metabolism in ITP. Gut microbiota may participate in the pathogenesis of ITP through affecting cytokine secretion, interfering with fatty metabolism.

As the most frequently occurring cancer worldwide, breast cancer (BC) is the leading cause of cancer-related death in women. The overexpression of HER2 (human epidermal growth factor receptor 2) is found in about 15% of BC patients, and it is often associated with a poor prognosis due to the effect on cell proliferation, migration, invasion, and survival. As a result of the heterogeneity of BC, molecular imaging with HER2 probes can non-invasively, in real time, and quantitatively reflect the expression status of HER2 in tumors. This will provide a new approach for patients to choose treatment options and monitor treatment response. Furthermore, radionuclide molecular imaging has the potential of repetitive measurements, and it can help solve the problem of heterogeneous expression and conversion of HER2 status during disease progression or treatment. Different imaging probes of targeting proteins, such as monoclonal antibodies, antibody fragments, nanobodies, and affibodies, are currently in preclinical and clinical development. Moreover, in recent years, HER2-specific peptides have been widely developed for molecular imaging techniques for HER2-positive cancers. This article summarized different types of molecular probes targeting HER2 used in current clinical applications and the developmental trend of some HER2-specific peptides.

Consider a dual-oligopoly game model of two manufacturers and consumers, where the government collects taxes from manufacturers based on their carbon emissions and the manufacturers can recycle waste products from consumers to reduce production cost and carbon emission taxes. Since manufactures are taking various strategies to achieve carbon abatement, models are also built under different circumstances. After solving the single phase equilibrium solution, a multi-period dynamic game model is further built. The complex characteristics, such as bifurcation, chaos and sensitivity are analyzed through 3-D stable state diagrams, parameter basin diagrams, and bifurcation diagrams. The results show that the system stability range, which is kept by the manufacturer's recovery price and its adjustment speed, reduces with the increase of carbon tax. Compared with manufacturer 1 who sells new products and recycles waste ones at the same time, the manufacturer 2 who only sells but not recycles has slighter influence on carbon emissions, and the sensitivity of consumers to price on the stability of the system is quite lower.

Recently, two-dimensional (2D) materials, especially transition-metal dichalcogenides (TMDCs), have attracted extensive interest owing to their potential applications in optoelectronics. Here, we demonstrate a hybrid 2D-zero-dimensional (0D) photodetector, which consists of a single-layer or few-layer molybdenum disulfide (MoS2) thin film and a thin layer of core/shell zinc cadmium selenide/zinc sulfide (ZnCdSe/ZnS) colloidal quantum dots (QDs). It is worth mentioning that the photoresponsivity of the hybrid 2D-0D photodetector is 3 orders of magnitude larger than the TMDC photodetector (from 10 to 104 A W-1). The detectivity of the hybrid structure detector is up to 1012 Jones, and the gain is up to 105. Due to an effective energy transfer from the photoexcited QD sensitizing layer to MoS2 films, light absorption is enhanced and more excitons are generated. Thus, this hybrid 2D-0D photodetector takes advantage of high charge mobility in the MoS2 layer and efficient photon absorption/exciton generation in the QDs, which suggests their promising applications in the development of TMDC-based optoelectronic devices.

Nowadays, with more and more WEEE (Waste Electrical and Electronic Equipment) being abandoned, WEEE recycling activities are increasingly popular. In this paper, we build a closed-loop supply chain model and focus on the recycling behaviors of the members in this supply chain, which contains two manufacturers, the retailer and the consumer. In the reverse chain, we set up dual channels and design two recycling methods: sell-back method and trade-in method. We use classical backward induction to run the model. And then we analyze the stability of the system and the impacts of some essential parameters by numerical simulation. The speed of the manufacture’s decision adjustment has a significant effect on the stability of the model. When the decision variables of manufacturers go into instability, the profits of both manufacturers and the retailer have a profit loss in multiple cycles on average. The lower production cost of manufacturer 1 will increase the retailer's profit and self-profit, while manufacturer 2's profit will decrease. And the smaller price coefficient of the retailer can bring higher profits but aggravate the chaotic condition, and the stability of the whole system will decrease. In the end, we adopt the parameter control method and the decision-making method to control chaos, and they both have a good control effect.

The major challenge of recombinant adeno-associated virus (rAAV) vectors is host immunological barriers. Compared to the neutralizing antibody and the cytotoxic T lymphocyte response, the host immune responses induced by unsatisfactory rAAV manufacturing were largely ignored previously. rAAV vector production usually requires large amounts of plasmid DNAs. The DNA are commonly isolated from the DH5α bacterial strain, which contains lipopolysaccharide (LPS) contamination. LPS, also named endotoxin, in plasmid DNA is intractable, and residual endotoxin in the subsequent rAAV vectors may result in substantial host immune response. Recently, a ClearColi K12 bacterial strain is commercially available, with genetically modified LPS that does not trigger endotoxic response in mammalian cells. Here, we produced rAAV-DJ vectors by plasmids yielded from either DH5α or ClearColi K12 bacterial strains. Our data indicated that the ClearColi K12 strain had satisfactory protection for the rAAV inverted terminal repeat (ITR) sequence. As expected, the ClearColi K12-derived rAAV-DJ vectors had lower endotoxin levels. The physical and biological equivalency of the purified viral stocks were confirmed by electron micrographs, Coomassie blue staining, and transduction assays. Most importantly, the ClearColi K12-derived rAAV-DJ vectors triggered reduced nuclear factor-kappa B (NF-κB) signaling pathway both in cell cultures in vitro and in C57BL/6 mice retinas in vivo. We believe that the use of the ClearColi K12 bacterial strain could eliminate the LPS in the purified vector stock at the source. Our data indicate its promising use in future clinical development., Graphical abstract, rAAV vector production requires large amounts of bacterial-derived plasmids, which may contain lipopolysaccharide contamination. In this manuscript, we used a genetically modified ClearColi K12 bacterial strain to generate rAAV vectors and showed that the vectors trigger lower endotoxic response in mammalian cells both in vitro and in vivo.

Neural tumors can generally be divided into central nervous system tumors and peripheral nervous tumors. Because this type of tumor is located in the nerve, even benign tumors are often difficult to remove by surgery. In addition, the majority of neural tumors are malignant, and it is particular the same for the central nervous system tumors. Even treated with the means such as chemotherapy and radiotherapy, they are also difficult to completely cure. In recent years, an increasingly number of studies have focused on the use of mRNA to treat tumors, representing an emerging gene therapy. The use of mRNA can use the expression of some functional proteins for the treatment of genetic disorders or tissue repair, and it can also be applied to immunotherapy through the expression of antigens, antibodies or receptors. Therefore, although these therapies are not fully-fledged enough, they have a broad research prospect. In addition, there are many ways to treat tumors using mRNA vaccines and exosomes carrying mRNA, which have drawn much attention. In this study, we reviewed the current research on the role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors, and examine the future research prospects of mRNA in neural tumors and the opportunities and challenges that will arise in the future application of clinical treatment.

Background Ischemic stroke (IS) is a serious global health burden. In order to improve our understanding of the risk factors associated with IS, we investigated the combined effect of the methylation of five genes related to the metabolism of homocysteine on developing IS. Methods Quantitative methylation‐specific PCR was used to measure the levels of promoter methylation in hypertensive and stroke patients. The cutoff value calculated by the maximum Youden index was used to classify the levels of gene methylation as hypomethylation and hypermethylation. Logistic regression was used to explore the relationship between gene methylation and IS. Results The methylation levels of the genes encoding methylenetetrahydrofolate dehydrogenase 1 [MTHFD1], cystathionine β‐synthase [CBS], and dihydrofolate reductase [DHFR] in hypertensive patients were higher than those in stroke patients (all p, A significant linear relationship between the number of elevated biomarkers and the risk of stroke.

To analyze the phenotype and genetic basis for a pedigree affected with hereditary coagulation factor XI deficiency.Activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), FXI activity (FXI:C) and the antigen of FXI (FXI:Ag) were determined for the proband and members from his pedigree. Sanger sequencing was used to analyze all exons, exon-intronic boundaries, as well as the 5'- and 3'- untranslated regions of the F11 gene. Suspected variants were verified in her family members and confirmed by reverse sequencing. The impact of the variants on the protein function was predicted by using PolyPhen-2 and SIFT software. The protein structure and amino acid interaction were analyzed by using Swiss-PdbViewer.The APTT, FXI:C and FXI:Ag of the proband and her sister were significantly reduced to 73.0 s, 10.0%, 15.0% and 87.1 s, 2.0% and 11.5%, respectively. APTT of some family members was slightly prolonged, and FXI:C and FXI:Ag also decreased to various extents. DNA sequencing revealed that the proband and her sister have carried compound heterozygous variants of c.738GA (p.Trp228stop) and c.938GT (p.Ser295Ile) respectively in exons 7 and 9 of the F11 gene. Her father, sister and daughter were heterozygous for the c.738GA (p.Trp228stop) variant, while her mother and nephew were heterozygous for the c.938GT (p.Ser295Ile). Both PolyPhen-2 and SIFT predicted that the p.Ser295Ile variant is likely to be deleterious and can affect the protein function. Modeling analysis indicated that the p.Ser295Ile variant may lead to disruption of a hydrogen bond, resulting in alteration of protein structure and instability.The compound heterozygous c.738GA (p.Trp228stop) and c.938GT (p.Ser295Ile) variants of the F11 gene probably underlie the decreased FXI level in this pedigree.

microRNAs (miRNAs) are important players in tumor suppression and oncogenesis. In this study, we aimed to explore the role of miR-4698 with its potential target tripartite motif-containing 59 (Trim59), a protein with oncogenic function, in hepatocellular carcinoma (HCC). The expression of miR-4698 was significantly lower in HCC tissues and HCC cell lines compared to normal tissues adjacent to tumors and in normal hepatic cell lines. Overexpression of miR-4698 in HCC cells by transfection of its mimic significantly inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), whereas its antisense oligonucleotides (ASOs) exerted the opposite effect. Trim59 was identified as a target of miR-4698 in miRDB, and consistent with this prediction, the expression of Trim59 was inversely correlated with that of miR-4698 in HCC, and miR-4698 overexpression led to a significant decrease in the luciferase activity of pRL-Trim59-3'-UTR but not mutant pRL-Trim59-3'-UTR. Moreover, the miR-4698 mimic inhibited the expression of Trim59. Overexpression of Trim59 abrogated the inhibitory effects of miR-4698. In conclusion, these data show that the miR-4698-Trim59 axis plays a tumor-suppressive role in HCC.

Fetal growth restriction (FGR) is the primary cause of infant morbidity and mortality. Although nutritional intervention is generally used to cure FGR, its effects on early- and late-onset FGR have not been reported. This study aimed to resolve this issue in a real-world setting. We collected the data of pregnant women whose fetuses were diagnosed with FGR and subsequently born at Nanshan Women and Children’s Care Hospital in Shenzhen, China. We conducted a MANOVA and series of Cox regression analyses to evaluate the effects of a prenatal nutritional intervention on early and late FGR after adjusting for potential confounders. Our results demonstrated that the average birth weights in the four sub-intervention groups were 50.36–160.05 g higher than those in the nonintervention group. These differences were insignificant with respect to early-onset FGR. In late-onset FGR, however, the interventions led to birth weight increases of 164.95–244.45 g greater than those in the nonintervention group, and these differences were significant. During early-onset FGR, four different nutritional interventions reduced the incidence of small-for-gestational age by 8.00–13.76% relative to the incidence in the nonintervention group, while in late-onset FGR, the incidence decreased by 11.37–17.39%. Our results based on a real-world setting reaffirmed that a prenatal nutritional intervention could improve the birth outcomes in cases of FGR and further suggested a better effectiveness on late-onset FGR.

Hypodysfibrinogenemia is the least frequently reported congenital fibrinogen disorder, characterized by both quantity and quality defects of fibrinogen. In this study, we investigated the molecular basis of hypodysfibrinogenemia in a Chinese family. Functional fibrinogen was measured by Clauss method, and the antigenic fibrinogen was measured by immunoturbidimetry assay. All the exons and exon-intron boundaries of fibrinogen genes (FGA, FGB and FGG) were analysed by direct DNA sequencing. To further evaluate its molecular and functional characterizations, fibrinogen was purified from the plasma of propositus, then SDS-PAGE, fibrin polymerization, clot lysis, and electron microscopy scanning were all performed. The propositus showed a slight decrease of immunologic fibrinogen (1.52 g/L) but dramatically reduced functional fibrinogen (0.3 g/L). DNA sequencing revealed a novel heterozygous CCTTTGATG deletion in the exon 8 of FGG, leading to the deletion of Ala289, Phe290, and Asp291 in fibrinogen γ-chain. The polymerization of the fibrinogen from the propositus was markedly impaired, with prolonged lag period and decreased final turbidity. The fibrinogen clottability showed a reduced fraction of participating clot formation. While the clot lysis showed normal. Scanning electron microscopy revealed that the fibers of the propositus were thicker than normal, with larger pores and curlier meshworks. We conclude that γAla289_Asp291del is responsible for the hypodysfibrinogenemia in this case.

Background Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignancies due to sophisticated genetic mutations and epigenetic dysregulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, are important regulators of gene expression in all biological processes, including leukemogenesis. Recently, miR-375 has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-leukemia activity in AML is largely unknown. Methods Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the expression of miR-375 and HOXB3 in leukemic cells and normal controls. Targets of miR-375 were confirmed by western blot and luciferase assay. Phenotypic effects of miR-375 overexpression and HOXB3 knockdown were assessed using viability (trypan blue exclusion assay), colony formation/replating, as well as tumor xenograft assays in vivo. Results The expression of miR-375 was substantially decreased in leukemic cell lines and primary AML blasts compared with normal controls, because DNA hypermethylation of precursor-miR-375 (pre-miR-375) promoter was discovered in leukemic cells but not in normal controls. Lower expression of miR-375 predicted poor outcome in AML patients. Furthermore, forced expression of miR-375 not only decreased proliferation and colony formation in leukemic cells but also reduced xenograft tumor size and prolonged the survival time in a leukemia xenograft mouse model. Mechanistically, overexpression of miR-375 reduced HOXB3 expression and repressed the activity of a luciferase reporter through binding 3′-untranslated regions (3’-UTR) of HOXB3 mRNA. Overexpression of HOXB3 partially blocked miR-375-induced arrest of proliferation and reduction of colony number, suggesting that HOXB3 plays an important role in miR-375-induced anti-leukemia activity. Knockdown of HOXB3 by short hairpin RNAs reduced the expression of cell division cycle associated 3 (CDCA3), which decreased cell proliferation. Furthermore, HOXB3 induced DNA methyltransferase 3B (DNMT3B) expression to bind in the pre-miR-375 promoter and enhanced DNA hypermethylation of pre-miR-375, leading to the lower expression of miR-375. Conclusions Collectively, we have identified a miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry which contributes to leukemogenesis and suggests a therapeutic strategy of restoring miR-375 expression in AML. Electronic supplementary material The online version of this article (10.1186/s12885-018-4097-z) contains supplementary material, which is available to authorized users.

With the purpose of researching the bullwhip effect when there is a callback center in the supply chain system, this paper establishes a new supply chain model with callback structure, which has a material supplier, a manufacture, and two retailers. The manufacture and retailers all employ AR(1) demand processes and use order-up-to inventory policy when they make order decisions. Moving average forecasting method is used to measure the bullwhip effect of each retailer and manufacture. We investigate the impact of lead-times of retailers and manufacture, forecasting precision, callback index, and marketing share on the bullwhip effect of both retailers and manufacture. Then we use the method of numerical simulation to indicate the different parameters in this supply chain. Furthermore, this paper puts forward some suggestions to help the enterprises to control the bullwhip effect in the supply chain with callback structure.