ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations.

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations; however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESCs), including a knockout and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR) and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-sequencing analyses in Zscan10-/- mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10.

TRPP2 is located in the primary cilia of human non-pigmented ciliary epithelial cells.

PURPOSE: Mechanosensitive channels (MSCs) and primary cilium possess a possible relevance for the sensation of intraocular pressure (IOP). However, there is only limited data on their expression and localization in the ciliary body epithelium (CBE). The purpose of this study was to characterize the expression and localization of TRPP2 in a human non-pigmented ciliary epithelial cell (HNPCE) line. METHODS: The expression of the TRPP2 was studied by quantitative (q)RT-PCR and in situ hybridization in rat and human tissue. Protein expression and distribution were studied by western blot analysis, immunohistochemistry, and immunoelectron microscopy. Cellular location of TRPP2 was determined in rat and human CBE by immunofluorescence and immunoblot analysis. Electron microscopy studies were conducted to evaluate where and with substructure TRPP2 is localized in the HNPCE cell line. RESULTS: The expression of TRPP2 in rat and human non-pigmented ciliary epithelium was detected. TRPP2 was mainly located in nuclei, but also showed a punctate distribution pattern in the cytoplasm of HNPCE of the tissue and the cell line. In HNPCE cell culture, primary cilia did exhibit different length following serum starvation and hydrostatic pressure. TRPP2 was found to be colocalized with these cilia in HNPCE cells. CONCLUSION: The expression of TRPP2 and the primary cilium in the CB may indicate a possible role, such as the sensing of hydrostatic pressure, for the regulation of IOP. Functional studies via patch clamp or pharmacological intervention have yet to clarify the relevance for the physiological situation or aqueous humor regulation.

DYT6 mutated THAP1 is a cell type dependent regulator of the SP1 family.

DYT6 dystonia is caused by mutations in the transcription factor THAP1. THAP1 knock-out or knock-in mouse models revealed complex gene expression changes, which are potentially responsible for the pathogenesis of DYT6 dystonia. However, how THAP1 mutations lead to these gene expression alterations and whether the gene expression changes are also reflected in the brain of THAP1 patients are still unclear. In this study we used epigenetic and transcriptomic approaches combined with multiple model systems [THAP1 patients' frontal cortex, THAP1 patients' induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic neurons, THAP1 heterozygous knock-out rat model, and THAP1 heterozygous knock-out SH-SY5Y cell lines] to uncover a novel function of THAP1 and the potential pathogenesis of DYT6 dystonia. We observed that THAP1 targeted only a minority of differentially expressed genes caused by its mutation. THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell type dependent manner. Comparing global differentially expressed genes detected in THAP1 patients' iPSC-derived midbrain dopaminergic neurons and THAP1 heterozygous knock-out rat striatum, we observed many common dysregulated genes and 61 of them were involved in dystonic syndrome-related pathways, like synaptic transmission, nervous system development, and locomotor behaviour. Further behavioural and electrophysiological studies confirmed the involvement of these pathways in THAP1 knock-out rats. Taken together, our study characterized the function of THAP1 and contributes to the understanding of the pathogenesis of primary dystonia in humans and rats. As SP1 family members were dysregulated in some neurodegenerative diseases, our data may link THAP1 dystonia to multiple neurological diseases and may thus provide common treatment targets.

Assessment of the Binding of Pseudallecin A to Human Serum Albumin with Multi-Spectroscopic Analysis, Molecular Docking and Molecular Dynamic Simulation.

The binding of pseudallecin A (PA), a potential antibiotic with strong inhibitory activities against Gram-positive Escherichia coli and Gram-negative Staphylococcus aureus, to human serum albumin (HSA) was explored. The interaction between them was assessed by multi-spectroscopic analysis, binding site competitive analysis, molecular docking and molecular dynamic simulation, showing the results as follows: PA effectively quenched the innate fluorescence of HSA by a static quenching process, formed a complex at a molar ratio of approximately 1 : 1 and performed an effective non-radiative energy transfer; the binding of PA to HSA was a spontaneous exothermic reaction driven by enthalpy with strong affinity and had a slight effect on the conformation of HSA; PA bound at site III of HSA and hydrogen bonds were the major binding forces to maintain the stability of the PA-HSA complex. Molecular dynamic simulation was performed to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF) and radius of gyration (Rg) for this complex and effectively supported the spectroscopic outcome. These results meant that the delivery and distribution of PA as a water-insoluble molecule can be efficiently accomplished via HSA in human blood and, it has a good potential for future drug application and pharmacological development.

Ameliorating SERS Sensitivity for Pesticide Malathion Detection with Synergistic Boosting Effect by Hydrogen Cations and Chloride Anions.

Although SERS has been widely recognized as one of the highly sensitive analytical methods that can be deployed in the field with high sensitivity and short analysis time, reports regarding the fast determination of malathion at low concentrations are still scarce. Here, in this work, the solution pH and various halogen co-adsorbates were explored to promote the SERS signal of malathion using the citrate-reduced Ag NPs. It was found that chloride anions were the most efficient signal booster among the three halogen ions screened. Further examination of the SERS profile of the malathion in the presence of different halogen species found that the stretching mode of the P-S bond shifted to a lower frequency with Cl-, which may imply closer (and stronger) binding of malathion to the Ag NPs. This concurs with literature reports that halogen ions could facilitate the adsorption of a certain analyte onto the SERS substrate. In addition, hydrogen ions showed a synergistic effect on SERS signal enhancement when combined with chloride anions. At optimum conditions, the malathion could be detected with a limit of detection (LOD) of 3 ppb. Malathion-spiked cherry tomatoes and oranges were analyzed, and the recovery rates were found to be within 85-100%.

Electrospun nanofibrous membrane with antibacterial and antiviral properties decorated with Myoporum bontioides extract and silver-doped carbon nitride nanoparticles for medical masks application.

Public health safety issues have been plaguing the world since the pandemic outbreak of coronavirus disease (COVID-19). However, most personal protective equipments (PPE) do not have antibacterial and anti- toxicity effects. In this work, we designed and prepared a reusable, antibacterial and anti-toxicity Polyacrylonitrile (PAN) based nanofibrous membrane cooperated with Ag/g-C3N4 (Ag-CN), Myoporum.bontioides (M. bontioides) plant extracts and Ag nanoparticles (NPs) by an electrospinning-process. The SEM and TEM characterization revealed the formation of raised, creased or wrinkled areas on the fiber surface caused by the Ag nanoparticles, the rough surface prevented the aerosol particles on the fiber surface from sliding and stagnating, thus providing excellent filtration performance. The PAN/M. bontioides/Ag-CN/Ag nanofibrous membrane could be employed as a photocatalytic bactericidal material, which not only degraded 96.37% of methylene blue within 150 min, but also exhibited the superior bactericidal effect of 98.65 ± 1.49% and 97.8 ± 1.27% against E. coli and S. aureus, respectively, under 3 hs of light exposure. After 3 cycles of sterilization experiments, the PAN/M. bontioides/Ag-CN/Ag nanofibrous membrane maintained an efficient sterilization effect. Molecular docking revealed that the compounds in M. bontioides extracts interacted with neo-coronavirus targets mainly on Mpro and RdRp proteins, and these compounds had the strongest docking energy with Mpro protein, the shortest docking radius, and more binding sites for key amino acids around the viral protein targets, which influenced the replication and transcription process of neo-coronavirus. The PAN/M.bontioides/Ag-CN/Ag nanofibrous membrane also performed significant inhibition of influenza A virus H3N2. The novel nanofiber membrane is expected to be applied to medical masks, which will improve human isolation and protection against viruses.

Static Retention of Dynamic Chiral Arrangements for Achiral Shear Thinning Metal-Organic Colloids.

Chiral compounds are known to be important not only because they are the fundamental components of living organisms, but also for their unique chiroptical properties. In recent years, scientists have fabricated several chiral organic supramolecular aggregates by using chiral physical fields, such as vortex flow. Herein, the relationship between dynamic chiroptical properties and rheological nature is discussed, suggesting the shear thinning properties of non-Newtonian fluids might help colloidal particles adopt a chiral arrangement in vortices. Furthermore, the storage modulus of colloids could be increased by adding a linking agent, which successfully kept the dynamic chiroptical properties in the static state. Moreover, the salt effect on the host-guest interaction involved in the colloids was studied, the results suggested a significant enhancement of the transferred dynamic circular dichroism for the achiral guest molecule.

Identification and Antifungal Activity of Compounds from the Mangrove Endophytic Fungus Aspergillus clavatus R7.

Two new coumarin derivatives, 4,4'-dimethoxy-5,5'-dimethyl-7,7'-oxydicoumarin (1), 7-(γ,γ-dimethylallyloxy)-5-methoxy-4-methylcoumarin (2), a new chromone derivative, (S)-5-hydroxy-2,6-dimethyl-4H-furo[3,4-g]benzopyran-4,8(6H)-dione (5), and a new sterone derivative, 24-hydroxylergosta-4,6,8(14),22-tetraen-3-one (6), along with two known bicoumarins, kotanin (3) and orlandin (4), were isolated from an endophytic fungus Aspergillusclavatus (collection No. R7), isolated from the root of Myoporum bontioides collected from Leizhou Peninsula, China. Their structures were elucidated using 1D- and 2D- NMR spectroscopy, and HRESIMS. The absolute configuration of compound 5 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Compound 6 significantly inhibited the plant pathogenic fungi Fusarium oxysporum, Colletotrichum musae and Penicillium italicum, compound 5 significantly inhibited Colletotrichum musae, and compounds 1, 3 and 4 greatly inhibited Fusarium oxysporum, showing the antifungal activities higher than those of the positive control, triadimefon.

Composite Hybrid Cluster Built from the Integration of Polyoxometalate and a Metal Halide Cluster: Synthetic Strategy, Structure, and Properties.

A step-by-step synthetic strategy, setting up a bridge between the polyoxometalate (POM) and metal halide cluster (MHC) systems, is demonstrated to construct an unprecedented composite hybrid cluster built up from one high-nuclearity cationic MHC [Cu8I6](2+) and eight Anderson-type anionic POMs [HCrMo6O18(OH)6](2-) cross-linked by a tripodal alcohol derivative.

Construction of High-Nuclearity Manganese-Cluster-Organic Frameworks by Using a Tripodal Alcohol Ligand.

Two novel cluster-organic frameworks based on the 12-nuclearity manganese-cluster secondary building unit (SBU), [MnIII4MnII8(L)4(Ac)8(MeO)2(µ5-O)2(H2O)4](Ac)2·16H2O (1) and [MnIII4MnII8(L)4(Ac)8(MeO)2(µ5-O)2(H2O)4](Ac)2·12H2O (2), where Ac = CH3COO- and MeO = CH3O, have been constructed from solvothermal reactions of the 3-nuclearity manganese cluster [Mn3(µ3-O)(Ac)6(py)3](ClO4) (Mn3, where py = pyridine) with a tripodal alcohol ligand containing a 4-pyridyl group. 1 and 2 represent the first examples of metal-organic frameworks containing 12-nuclearity manganese-cluster SBUs. In addition, 1 exhibits an integration of the porosity and magnetic properties from both the framework and cluster in a porous material.

Computational design of high efficiency nonplanar tri-s-triazine-based ambipolar host materials for phosphorescent blue emitters.

A series of nonplanar tri-s-triazine-based molecules were designed, and their optical, electronic, and charge transport properties as ambipolar host materials for blue electrophosphorescence emitters were explored by density functional theory. The influence of the linkage between tri-s-triazine and carbazole, diphenylamine and triphenylamine, as well as the influence of a series of electron-donating and electron-withdrawing substituents on triplet energy, energy level matching and charge transport of the designed molecules was discussed in detail. Our results reveal that the molecules under investigation can serve as host materials for blue electrophosphorescence emitters. We also predicted the mobility of designed molecules with better performance in the P1[combining macron] space group. Based on the investigated results, we proposed a rational way for the design of host materials for OLEDs, and also expanded the application field of tri-s-triazine.

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis.

Aim: To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making. Methods: A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis. Results: Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20. Conclusion: For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.

In-situ electrospinning PVB/Camellia oil/ZnO-TiO2 nanofibrous membranes with synergistic antibacterial and degradation of ethylene applied in fruit preservation.

This work utilizes a handheld electrospinning device to prepare a novel nanofibrous composite membrane in situ for packaging freshness. It can realize pick-and-pack and is easy to operate. The nanofibrous membrane is based on PVB as the matrix material, adding Camellia oil (CO) and ZnO-TiO2 composite nanoparticles (ZT) as the active material. The antimicrobial property of the CO and the photocatalytic activity of the nanoparticles give the material good antimicrobial and ethylene degradation functions. Meanwhile, this nanofibrous membrane has good mechanical properties, suitable moisture permeability and good optical properties. The nanofibrous membrane are suitable for both climacteric and non- climacteric fruits. Its use as a cling film extends the shelf life of strawberries by 4 days and significantly slows the ripening of small tomatoes. Therefore, this nanofibrous membrane has great potential for application in the field of fruit preservation.

Mechanistic insight into the catalytic oxidation of cyclohexane over carbon nanotubes: kinetic and in situ spectroscopic evidence.

As some of the most interesting metal-free catalysts, carbon nanotubes (CNTs) and other carbon-based nanomaterials show great promise for some important chemical reactions, such as the selective oxidation of cyclohexane (C6H12). Due to the lack of fundamental understanding of carbon catalysis in liquid-phase reactions, we have sought to unravel the role of CNTs in the catalytic oxidation of C6H12 through a combination of kinetic analysis, in situ spectroscopy, and density functional theory. The catalytic effect of CNTs originates from a weak interaction between radicals and their graphene skeletons, which confines the radicals around their surfaces. This, in turn, enhances the electron-transfer catalysis of peroxides to yield the corresponding alcohol and ketone.

Ozanimod-Dependent Activation of SIRT3/NF-κB/AIM2 Pathway Attenuates Secondary Injury After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is characterized by poor prognosis and high mortality rates. To date, satisfactory therapeutic approaches for ICH remain limited, so it is urgently needed to develop a safer and more effective prescription. Secondary inflammatory response has been acknowledged as an aggravating factor to neurological deterioration after ICH. As a component of inflammasome sensors, absent in melanoma 2 (AIM2) plays an important role in the neuroinflammation process. Here, ozanimod, a novel selective sphingosine 1-phosphate receptor modulator, has gained much attention, which alleviates the resultant neuroinflammation and improves functional recovery derived from ICH. In this study, ozanimod improved neurological functions of ICH mice via reduction of hematoma size. Furthermore, both microglial and AIM2 inflammasome activations were reversed by ozanimod, which are confirmed by the downregulation of related inflammatory proteins and cytokines (IL-1ß, IL-6, and TNF-α), coupled with the upregulation of SIRT3, by leveraging the Western blot and enzyme-linked immunosorbent assay. Additionally, we find that ozanimod decreases nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression. Notably, in vitro cell experiments induced by lipopolysaccharide confirms that the anti-inflammatory effect of ozanimod could be abolished by the SIRT3 inhibitor. In conclusion, these results indicate that ozanimod mitigates ICH-induced secondary inflammatory responses by modulating AIM2 inflammasome mediated by SIRT3/NF-κB/AIM2 pathway. This demonstrates ozanimod orchestrates ICH-induced neuroinflammation and could be a targeted therapy for improving prognosis of ICH.

A combined experimental and computational study on the interfacial distribution behavior in colloidal particle-surfactant co-stabilized Pickering emulsions.

Recently, co-stabilized Pickering emulsion (CPE) that stabilized by colloidal particles and surfactant has received increased research attention, owing to its improved stability and fluid properties comparing with conventional emulsions stabilized by particles or surfactants alone. Herein, the dynamic distribution behavior at multi-scale and the synergistic-competitive interfacial absorption in CPE co-stabilized by Tween20 (Tw20) and zein particles (Zp) were studied by experiment combined simulation method. The experimental studies identified the delicate synergistic-competitive stabilization phenomenon tuned by the molar ratio of Zp and Tw20. Meanwhile, dissipative particle dynamic (DPD) simulation was utilized to reveal the distribution and kinetic motion. Based on the two- and three-dimensional simulation on the formation of CPE, simulation revealed that Zp - Tw20 aggregates were formed when anchoring at the interface. The interfacial adsorption efficiency of Zp was improved at low Tw 20 concentration (0-1.0%wt), Tw20 inhibited the Brownian motion of Zp at the interface and competed them out at high concentrations (1.5-2.0%wt). Zp was departured from the interface 4.5 Å to 10 Å, as Tw20 increased from 1.06% to 5%. The study offers a novel approach to reveal the dynamic distribution behavior of surface active substances during the dynamic formation process of CEP, which will expand our current strategies for interface engineering of emulsions.

Inflammatory regulation by restraining M2 microglial polarization: Neurodestructive effects of Kallikrein-related peptidase 8 activation in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a cerebrovascular disease. Kallikrein-related peptidase 8 (KLK8) is a serine peptidase, while its role in ICH remains unclarified. Western blot (WB) showed that KLK8 was upregulated in rat perihematomal tissues 24 h following autologous blood injection. KLK8 overexpression aggravated behavioral deficits and increased water content and Fluoro-Jade B (FJB)-positive neuron numbers in brain tissue of rats. Immunofluorescence (IF) assay showed that overexpressed-KLK8 promoted Iba-1 and iNOS expression in perihematomal tissue of rats. Overexpressed-KLK8 increased COX-2, iNOS, and Arg-1 expression and the content of IL-6, IL-1ß, and TNF-α in perihematomal tissue of rats, confirmed by WB and ELISA. IF staining confirmed the expression of CCR5 was co-expressed with Iba-1, and the WB results shown increased CCR5 expression and decreased p-PKA and p-CREB expression in perihematomal tissue. Maraviroc (MVC, CCR5 inhibitor) administration rescued KLK8-induced behavioral deficits and brain injury (decreased water content and FJB-positive neuron numbers) in rats. Additionally, MVC suppressed p-PKA and p-CREB expression and the content of IL-6, IL-1ß, and TNF-α in perihematomal tissue, induced by overexpressed-KLK8. Co-IP confirmed the binding of CCR5 and CCL14 in HMC3 cells. Transwell assay shown that KLK8 plus CCL4 promoted the chemotactic activity of cells, which was rescued by MVC. The biological function of KLK8/CCL14/CCR5 axis in ICH injury was also proved by MVC administration in HMC3 cells. Overall, our work revealed that KLK8 overexpression aggravated ICH process and involved in microglial activation. KLK8 might activate CCL14 thereby turning on downstream CCR5/PKA/CREB pathway, providing a theoretical basis for future therapy.

Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage.

Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage (ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase VII into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell (BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3 (NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.

Simulating and Predicting the Part Warping in Fused Deposition Modeling by Thermal-Structural Coupling Analysis.

As the most commonly used additive manufacturing technology, fused deposition modeling (FDM) still faces some technical issues caused by temperature change-induced unsteady thermal stress and warping. These issues can further lead to the deformation of printed parts and even terminate the printing process. In response to these issues, this article established a numerical model of temperature field and thermal stress field for FDM by finite element modeling and "birth-death element" technique to predict the deformation of the part. What makes sense in this process is that the logic of elements sort based on ANSYS Parametric Design Language (APDL) was proposed to sort the meshed elements, which was aimed to perform FDM simulation quickly on the model. In this work, the effects of the sheets shape and infill line directions (ILDs) on the distortion during FDM were simulated and verified. From the analysis of stress field and deformation nephogram, the simulation results indicated that ILD had greater effects on the distortion. Moreover, the sheet warping became most serious when the ILD was aligned with the diagonal of the sheet. The simulation results matched well with the experimental results. Thus, the proposed method in this work can be used to optimize the printing parameters for FDM process.

Genetic polymorphisms of pri-let-7f, gene-environment and gene-gene interactions, and associations with ischemic stroke risk in Liaoning Province.

OBJECTIVE: The incidence of stroke has been rising annually and investigations into traditional risk factors have led to increased attention on genetic factors. In this study, we focused on the pri-let-7f gene, and investigated the association between pri-let-7f gene polymorphisms and ischemic stroke (IS). METHODS: This case-control study included 1803 patients and 1456 healthy controls of Han ethnicity living in Liaoning Province. We carried out genotyping analysis of two loci, pri-let-7f-1 rs10739971 and pri-let-7f-2 rs17276588, and performed statistical analysis controlling for confounding factors by logistic regression. RESULTS: The A alleles and AA genotypes of both loci were significantly associated with an increased risk of IS. Variant genotypes of rs17276588 may also increase the risk of IS in females with alcohol intake. Gene-gene interaction analysis showed combined effects of mutations in both these single nucleotide polymorphisms (SNPs). CONCLUSIONS: This study demonstrated an association between pri-let-7f SNPs and IS, providing potential latent biomarkers for the risk of IS. However, more detailed studies are needed to clarify these results.