Search

Abstract: FePt films were prepared by RF sputtering using Ne, Ar, and Kr as sputtering gas. The effects of sputtering gas on the microstructure and magnetic properties were studied. Both magnetic and crystallographic properties show that Kr gas promotes the formation of L10 phase. The films prepared by using Ar and Ne gas have random orientation, whereas the films prepared by using Kr gas show preferential c-axis perpendicular to the film plane orientation. [Copyright &y& Elsevier]

Abstract: Patterned magnetic media have been considered as one of the promising candidates for future ultra-high-density magnetic recording. In this paper, a new kind of patterned medium based on hexagonal ferrite have been studied. We have successfully fabricated strontium ferrite dot arrays by electron beam lithography. Their magnetic properties are evaluated by magnetic force microscopy (MFM) and superconducting quantum interference device (SQUID). The results show the dot arrays have perpendicular anisotropy. Dots with the lateral size larger than 500nm show multidomain magnetization configuration in the initial magnetization state. However, with dot size decreased to 500nm, all the dots have single-domain configuration both in the initial magnetization state and remanent magnetization state. [Copyright &y& Elsevier]

Abstract: A new technique, which utilizes the interlayer diffusion, for preparation of self-assembled nanodot magnetic structures has been proposed. L10-phase Pt/FeCu and Pt/FeAg films have been successfully synthesized by this technique. Both the coercivity of Pt/FeCu and Pt/FeAg films exhibited, respectively 4.1 and 8.0kOe in perpendicular direction. Pt/Fe and Pt/FeAg films show positive values, while Pt/FeCu shows negative value in δm plot. The results indicate that the exchange coupling between the grains has been decoupled in the self-assembled nanodot structure in Pt/FeCu film. [Copyright &y& Elsevier]

Abstract: TiN thin film is prepared by DC reactive sputtering in Ar+N2 atmosphere and its suitability as underlayer and overlayer for TbFeCo perpendicular recording media as well as its effect on the magnetic properties of the latter have been studied. Only 5nm TiN overlayer and 20nm under layer can successfully protect the TbFeCo film from oxidation. Initially the coercivity is increased sharply from about 2 to 6kOe for an increase of underlayer thickness to 60nm then the increasing rate of coercivity becomes very slow. The saturation magnetization remains almost constant with the underlayer thickness. The remanent squareness ratio remains constant at 1.0 with the underlayer thickness up to 60nm then decreases. [Copyright &y& Elsevier]

Thrombocytopenia is a disease in which the number of platelets in the peripheral blood decreases. It can be caused by multiple genetic factors, and numerous challenges are associated with its treatment. In this study, the effects of alnustone on megakaryocytes and platelets were investigated, with the aim of developing a new therapeutic approach for thrombocytopenia. Random forest algorithm was used to establish a drug screening model, and alnustone was identified as a natural active compound that could promote megakaryocyte differentiation. The effect of alnustone on megakaryocyte activity was determined using cell counting kit-8. The effect of alnustone on megakaryocyte differentiation was determined using flow cytometry, Giemsa staining, and phalloidin staining. A mouse model of thrombocytopenia was established by exposing mice to X-rays at 4 Gy and was used to test the bioactivity of alnustone in vivo. The effect of alnustone on platelet production was determined using zebrafish. Network pharmacology was used to predict targets and signaling pathways. Western blotting and immunofluorescence staining determined the expression levels of proteins. Alnustone promoted the differentiation and maturation of megakaryocytes in vitro and restored platelet production in thrombocytopenic mice and zebrafish. Network pharmacology and western blotting showed that alnustone promoted the expression of interleukin-17A and enhanced its interaction with its receptor, and thereby regulated downstream MEK/ERK signaling and promoted megakaryocyte differentiation. Alnustone can promote megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway and thus provides a new therapeutic strategy for the treatment of thrombocytopenia. The graphical abstract illustrates the virtual screening process of alnustone, the potential mechanism of promoting megakaryocyte differentiation, and the role of alnustone in enhancing platelet production in thrombocytopenic mice and zebrafish. [Display omitted] [ABSTRACT FROM AUTHOR]

Magnetic skyrmions are topological quasiparticles with nanoscale size and high mobility, which have potential applications in information storage and spintronic devices. Here, we computationally investigate the dynamics of isolated skyrmions in a ferromagnetic racetrack, where magnetic properties of the edges are enhanced and modified, forming a channel with lower magnetic anisotropy for skyrmion motion. It is found that the rectangular notch at the edge can have a pinning effect on the skyrmion and enrich the dynamics of the skyrmion. Based on the racetrack with modified edges and the notch, we design a racetrack that realizes the skyrmionic logic AND, OR, and NOT gates as well as the diode in the same magnetic racetrack. It is found that the driving current density could be much smaller than those used in previous designs of skyrmion-based logic gates. By slightly altering the shape of the racetrack, we also design the NAND and NOR gates. Finally, we study the feasibility of our design at finite temperatures. Our results may contribute to the design of nonvolatile spintronic devices with integrated multiple functions and ultra-low energy consumption. [ABSTRACT FROM AUTHOR]

Introduction: This post hoc analysis applies a fixed dosing stratification approach to patient-level brolucizumab data from the phase III HAWK and HARRIER trials to determine the proportion of patients who would have been assigned to fixed dosing regimens with treatment intervals of 8, 12, or 16 weeks (q8w, q12w, or q16w) based on the presence/absence of disease activity (DA) following the loading phase. The analysis also simulates central subfield thickness (CSFT) data to estimate the anatomical outcomes if the patients had been thus assigned. Of note, the limitations of this analysis include the post hoc nature of the work and the inability to directly compare HAWK and HARRIER with TENAYA and LUCERNE due to the differences in design. Design: This study was a post hoc modelling analysis of patient-level data. Methods: Using patient-level data from HAWK and HARRIER, patients (n = 730) were allocated to a fixed q16w, q12w, or q8w regimen based on assessment of DA at weeks 16 and 20. Two definitions of DA were used: DA 1, based on a phase II study of faricimab, and DA 2, a definition derived from common clinical consideration including visual acuity and anatomical changes. CSFT simulations were performed using a pharmacokinetic/pharmacodynamic model describing CSFT response to anti-VEGF treatment. Outcome measures were modelled patient allocation to fixed regimens and mean CSFT reduction. Results: Using DA definitions 1 and 2, respectively, 78% and 76% of patients in the brolucizumab arm were allocated to a greater than or equal to q12w regimen, and 56% and 52% were allocated to a q16w regimen. Mean reduction in CSFT was similar between the two study drugs with both DA definition assumptions. Conclusions: This analysis demonstrates the potential durability of action and effectiveness of brolucizumab. [ABSTRACT FROM AUTHOR]

Digital data, generated by corporate and individual users, is growing day by day due to a vast range of digital applications. Magnetic hard disk drives (HDDs) currently fulfill the demand for storage space, required by this data growth. Although flash memory devices are replacing HDDs in applications like mobile phones, laptops, and desktops, HDDs cover the majority of digital data stored in the cloud and servers. Since the capacity growth of HDDs is slowing down, it is essential to look for a potential alternative. One such alternative is domain wall (DW) memory, where magnetic domains in the form of two-dimensional or three-dimensional wires are used to store the information. DW memory (DWM) devices should satisfy the four basic operations, such as writing (nucleating domains or inserting DWs in memory element), storing (stabilizing DWs), shifting (moving DWs), and reading (reading magnetization direction). An external magnetic field or spin-transfer torque can be used to write the information. Spin–orbit torque or electric field may be used for shifting the DWs. The information can be read using tunneling magnetoresistance. The domains may be stored along the tracks using artificial pinning potentials. The absence of moving parts makes the DWM consume less power as compared to HDDs, and be more robust. The potential to stack many layers to store information in three dimensions makes them potentially a large storage capacity device. In addition to memory, DW devices also offer a route for making synaptic devices for neuromorphic computing. Despite these potential advantages of DWM, significant advances in research are needed before DWM could become commercially viable. One of the major challenges associated with DWM is DW dynamics. Many problems, such as controlled DW motion, the stability of domains, reducing the dimensions of the DW devices are still to be addressed. Artificial pinning sites fabricated through either geometrical or non-geometrical methods have been proposed for controlling DW motion. This review paper presents a survey of the investigations carried out so far and the future perspective of such devices. [ABSTRACT FROM AUTHOR]

Background: Infectious bovine rhinotracheitis (IBR) caused by bovine alphaherpesvirus 1 (BoHV-1) is one of the most important contagious diseases in bovine. This is one of the most common infectious disease of cattle. This has led to high economic losses in the cattle farming industry. BoHV-1 can potentially be transmitted via semen during natural or artificial insemination (AI). Therefore, testing methods for the early diagnosis of BoHV-1 infection are urgently needed for international trade of ruminant semen. In this study, we developed a novel droplet digital PCR (ddPCR) assay for the detection of BoHV-1 DNA in semen samples. Results: The ddPCR results showed that the detection limit was 4.45 copies per reaction with high reproducibility. The established method was highly specific for BoHV-1 and did not show cross-reactivity with specify the organisms (BTV, BVDV, Brucella, M. bovis). The results of clinical sample testing showed that the positivity rate of ddPCR (87.8%) was higher than that of qPCR (84.1%). Conclusions: The ddPCR assay showed good accuracy for mixed samples and could be a new added diagnostic tool for detecting BoHV-1. [ABSTRACT FROM AUTHOR]

Transparent and flexible multilayer films are fabricated based on the alternating assembly of cellulose acetate (CA) and layered double hydroxide (LDH) nanoplatelets followed by thermal annealing treatment. The films exhibit tremendously enhanced oxygen barrier properties. The oxygen transmission rate (OTR) of the resulting (CA/LDH) n multilayer films can be tuned by changing the aspect ratio of high-crystalline LDH nanoplatelets from 20 to 560. The (CA/LDH)20 film displays excellent oxygen-barrier behavior with an OTR equal to or below the detection limit of commercial instrumentation (<0.005 cm3 m−2 day−1), much superior to the previously reported inorganic flake-filled barrier film. Molecular dynamics simulations reveal that a hydrogen bonding network occurs at the interface of highly oriented LDH nanoplatelets and CA molecules, accounting for the suppression of oxygen transportation and the resulting largely improved barrier behavior. In addition, the durability of (CA/LDH) n films against humidity, temperature, and light irradiation is successfully demonstrated, which would guarantee their practical application. Therefore, this work provides a facile and cost-effective strategy for the fabrication of an LDH-based oxygen barrier material, which could potentially be used in flexible displays and drug and food packaging. [ABSTRACT FROM AUTHOR]

The influenza A virus (IAV) is a ubiquitous and continuously evolving respiratory pathogen. The intranasal vaccination mimicking natural infections is an attractive strategy for controlling IAVs. Multiepitope vaccines accurately targeting multiple conserved domains have the potential to broaden the protective scope of current seasonal influenza vaccines and reduce the risk of generating escape mutants. Here, multiple linear epitopes from the matrix protein 2 ectodomain (M2e) and the hemagglutinin stem domain (HA2) are fused with the Helicobacter pylori ferritin, a self-assembled nanocarrier and mucosal adjuvant, to develop a multiepitope nanovaccine. Through intranasal delivery, the prokaryotically expressed multiepitope nanovaccine elicits long-lasting mucosal immunity, broad humoral immunity, and robust cellular immunity without any adjuvants, and confers complete protection against H3N2 and H1N1 subtypes of IAV in mice. Importantly, this intranasal multiepitope nanovaccine triggers memory B-cell responses, resulting in secretory immunoglobulin A (sIgA) and serum immunoglobulin G (IgG) levels persisting for more than five months post-immunization. Therefore, this intranasal ferritin–based multiepitope nanovaccine represents a promising approach to combating respiratory pathogens. [Display omitted] • Developed an intranasal multiepitope influenza nanovaccine using the Helicobacter pylori ferritin nanoplatform. • The Helicobacter pylori ferritin is a safe and effective mucosal adjuvant. • Insertion of up to 170 amino acids does not affect the self-assembly ability of ferritin in Escherichia coli. • Mucosal immunity induced by the multiepitope nanovaccine lasts for 6 months. • The intranasal nanovaccine represents a compelling strategy against respiratory pathogens. [ABSTRACT FROM AUTHOR]

Topological spin textures can serve as non-volatile information carriers. Here we study the current-induced dynamics of an isolated magnetic skyrmion on a nanoscale square-grid pinning pattern formed by orthogonal defect lines with reduced magnetic anisotropy. The skyrmion on the square grid can be pixelated with a quantized size of the grid. We demonstrate that the position, size, and shape of skyrmion on the square grid are electrically configurable. The skyrmion center is quantized to be on the grid and the skyrmion may show a hopping motion instead of a continuous motion. We find that the skyrmion Hall effect can be perfectly prohibited due to the pinning effect of the grid. The pixelated skyrmion can be harnessed to build future programmable racetrack memory, multistate memory, and logic computing device. Our results will be a basis for digital information storage and computation based on pixelated topological spin textures on artificial pinning patterns. Skyrmions are particle-like magnetic structures which could form an important component of future spintronic devices but greater control over their physical characteristics must first be achieved. Here, using micromagnetic simulations, the authors report pixelated skyrmions showing how to engineer their position, size, and shape using a current pulse. [ABSTRACT FROM AUTHOR]

Purpose: Cefmetazole (CMZ) has received attention as a pharmaceutical intervention for extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) infections. This study aimed to investigate the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of CMZ against ESBL-EC. Methods: The susceptibility and time-killing activity of CMZ against clinically isolated ESBL-EC (EC9 and EC19) were determined in vitro. The optimal PK/PD index and its target value were calculated based on the results of a PK study in healthy mice and PD study in neutropenic murine thigh infection model mice. Results: The minimum inhibitory concentrations (MICs) of CMZ against EC9 and EC19 were 2.0 and 1.0 µg/mL, respectively. Time–kill studies showed that colony-forming units decreased in a time-dependent manner at CMZ concentrations in the range of 4–64 × MIC. In in vivo PK/PD studies, the antibacterial effect of CMZ showed the better correlation with the time that the free drug concentration remaining above the MIC (fT>MIC), with the target values for a static effect and 1 log10 kill reduction calculated as 57.6% and 69.6%, respectively. Conclusion: CMZ possesses time-dependent bactericidal activities against ESBL-EC and is required to achieve "fT>MIC" ≥ 69.6% for the treatment of ESBL-EC infections. [ABSTRACT FROM AUTHOR]

Introduction Impulsivity in intertemporal choice has been operationalized as 'delay discounting', referring to the preference for a sooner, smaller reward. FK506 binding protein 5 ( FKBP5) is a co-chaperone of the glucocorticoid receptor ( GR). FKBP5 overexpression causes GR resistance, resulting in increased plasma cortisol levels. High cortisol levels are associated with low impulsivity in intertemporal choice. The aim of this study was to explore the effect of single nucleotide polymorphisms ( SNPs) in FKBP5 on delay discounting. Methods The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9 ± 6.9 years). Each participant completed Kirby's monetary choice questionnaire ( MCQ) and donated a whole blood sample. Five SNPs in FKBP5 were genotyped using the DigiTag2. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time-discount rate ( k). Results Two SNPs were excluded from analysis because of their low minor allelic frequencies. The SNP rs1360780 showed a significant association; participants with more minor alleles ( T) were less impulsive in intertemporal choice for delayed gain (multiplicity-corrected P = 0.047). Discussion The significant SNP rs1360780 is located in the region adjacent to the hormone response element ( HRE)-binding sequence where transcription factors bind and alter the transcription of FKBP5. A minor allele ( T) of rs1360780, which causes FKBP5 overexpression, may reduce impulsivity in intertemporal choice (i.e. delay discounting) via GR resistance and the subsequent high cortisol levels. This is the first study to demonstrate an association between FKBP5 and impulsivity in intertemporal choice. [ABSTRACT FROM AUTHOR]

A method of introducing pinning sites in TbFeCo film by the using of focused ion beam was presented. The formed bulges in the film surface by discontinuous scan of light-dose focused ion beam have been proved to enhance the film's coercivity effectively. Coercivity increases almost linearly with the bulge density, giving the evidence of pinning effect contributed from those bulges predicted by domain wall pinning mechanism. Compared with the traditional way of etching the film for adjusting the coercivity, the method presented here shows superiority on reducing magnetic damage to film caused by the focused ion beam irradiation. [ABSTRACT FROM PUBLISHER]

Self-assembled Ni-Co-Sn substituted strontium ferrite dot array was formed on the outer surface of functionalized multiwalled carbon nanotubes (MWCNTs) by means of hetero-coagulation. The structural properties were evaluated by X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), Mössbauer spectroscopy, and field emission scanning electron microscopy. The obtained results indicate that the single phase strontium ferrite dot array was deposited with almost constant dot spacing on MWCNTs. It was found that the substitution cations preferentially occupy the 12 k sites. Vibrating sample magnetometer (VSM) graphs confirmed that the values of saturation magnetization and coercivity have strong correlation with the volume percentage of MWCNTs. Reflection loss and permittivity values of nanocomposite were also enhanced by increasing the volume percentage of carbon nanotubes in the absorbing media. [ABSTRACT FROM PUBLISHER]

Magnetic multiwalled carbon nanotube (MWCNTs) nanocomposites have been created by the assembly of Mg-Ni-Ti substituted barium ferrite nanoparticles onto surface of MWCNTs. X-ray diffraction (XRD) and transmission electron microscope (TEM) were used to demonstrate the successful attachment of ferrite nanoparticles to MWCNTs. Vibrating sample magnetometer (VSM) confirms the relatively strong dependence of saturation of magnetization and coercivity with the volume percentage of MWCNTs. Reflection loss evaluations indicated that the nanocomposites display a great potential application as wide-band electromagnetic wave absorbers. [ABSTRACT FROM AUTHOR]

Substituted strontium ferrite (\SrFe12-x{(\Cr0.5\Al0.5)}_x\O19) thin films were formed along the surface of multiwalled carbon nanotubes (MWCNTs). Mössbauer spectroscopy indicates that the substituted cations preferentially occupy the 12k sites. X-ray diffraction (XRD), transmission electron microscope (TEM), field emission scanning electron microscope (FE-SEM), vibrating sample magnetometer (VSM), and vector network analyzer were used to analyze the structure, static, and high-frequency magnetic properties of the prepared samples. It was found that with an increase in substitution content, the saturation of magnetization decreases while the coercivity increases. The CNTs could enhance the real and imaginary parts of permittivity of ferrites. With an increase in volume percentage of MWCNTs, the reflection loss values were increased. [ABSTRACT FROM AUTHOR]

Abstract: Strontium ferrite (SrM) thin films were prepared by dc magnetron sputtering system on thermally oxidized silicon wafer (SiO2/Si), single-crystal sapphire with (00l) orientation and single-crystal MgO with (111) orientation and the effect of Au and Pt underlayers on morphology and magnetic properties was studied. Experimental results revealed that with the application of underlayers, the crystallization temperature of SrM was reduced. Strontium ferrite thin films with uniaxial anisotropy were formed on all substrate specimens. Comparison of the results obtained on all thin films indicated that the maximum saturation magnetization and coercivity in the perpendicular direction were 0.377T and 0.382MAm−1, respectively, for thin films with Au underlayer and SiO2/Si substrate. [ABSTRACT FROM AUTHOR]

Abstract: The bacteriophage phiSASD1, isolated from a failed industrial avermectin fermentation, belongs to the Siphoviridae family. Its four predominant structural proteins, which include the major capsid, portal and two tail-related proteins, were separated and identified by SDS-PAGE and N-terminal sequence analysis. The entire double-stranded DNA genome of phiSASD1 consists of 37,068bp, with 3''-protruding cohesive ends of nine nucleotides. Putative biological functions have been assigned to 24 of the 43 potential open reading frames. Comparative analysis shows perfect assembly of three “core” gene modules: the morphogenesis and head module, the tail module and the right arm gene module, which displays obvious similarity to the right arm genes of Streptomyces phage phiC31 in function and arrangement. Meanwhile, structural module flexibility within phiSASD1 suggests that assignment of phage taxonomy based on comparative genomics of structural genes will be more complex than expected due to the exchangeability of functional genetic elements. [Copyright &y& Elsevier]

Abstract: Strontium ferrite (SrM) thin films were deposited on thermally oxidized silicon wafer with Au underlayer. Gold underlayers were prepared at various substrate temperatures by using a magnetron sputtering system. C-axis oriented SrM perpendicular films and preferred (111) orientation of underlayer have confirmed by X-ray diffraction patterns. The intensity of (111) diffraction line for Au and that of (00 l) diffraction line for strontium ferrite decrease with increase in substrate temperature (T u) The maximum coercivity and remanent squareness ratio in perpendicular direction, at T u of 500°C, are 5.4kOe and 0.68, respectively. The strength of the intergranular interaction of SrM magnetic particles is described by the parameter Δm. The SrM/Au films prepared at T u above 100°C have smaller Δm peak values than that for SrM/Au films prepared at T u of room temperature. This behavior is related to low magnetostatic coupling between the magnetic particles separated by the non-magnetic amorphous phase. [Copyright &y& Elsevier]

Abstract: Strontium ferrite (SrM) thin films on Au nano-dots were deposited on single-crystal sapphire with (00 l) orientation (Al2O3 (00 l)), single crystal MgO with (111) orientation (MgO (111)) and Corning glass by employing dc magnetron sputtering system. In order to improve the crystalline orientation for Au nano-dots, an attempt to use the single crystal as the substrate has been carried out. The effects of the substrates and underlayer on grain orientation, magnetic properties, and microstructure of SrM thin films were studied. The SrM grows with its c-axis oriented perpendicularly to the film. The maximum of coercivity and remanent squareness ratio in perpendicular direction for single crystal Al2O3 (00 l) substrate is 3.0kOe and 0.51, respectively. It is found that the magnetic interaction between SrM grains deposited on Au nano-dots is less than that for the continuous film. [Copyright &y& Elsevier]

Abstract: Strontium ferrite (SrM) thin films deposited on thermally oxidized silicon wafer (SiO2/Si) and single crystal sapphire with (00 l) orientation (Al2O3(00 l)) substrate using Pt underlayer were prepared by DC magnetron sputtering system. It was found that the intensity of (111) line for Pt and that of (00 l) diffraction line for SrM increases with increasing substrate temperature, Tu . The c-axis dispersion angle, Δθ 50, of SrM(008) depends on that of Pt underlayer. Both dispersion angle of Pt(111) and SrM(008) decrease with increasing temperature. It was observed that the saturation magnetization of SrM/Pt deposited on SiO2/Si is higher than that of Al2O3 substrate. The coercivity and remanent squareness ratio in perpendicular direction are higher than that in in-plane direction. The maximum of coercivity in perpendicular direction of SrM/Pt films deposited on single crystal Al2O3 is about 4.2kOe. [Copyright &y& Elsevier]

Strontium ferrite (SrFe[sub12]O[sub19]) thin films have been deposited on thermally oxidized silicon wafer with Au underlayer by using DC magnetron sputtering system. Crystallization of the strontium hexaferrite phase on Au underlayer is achieved for deposition temperature as low as 475 °C. The intensity of (111) diffraction line for Au and that of (00l) diffraction line for strontium ferrite decreases with increasing substrate temperature of underlayer. The maximum of coercivity and remanent squareness ratio in perpendicular direction are 5.7 kOe and 0.86, respectively, at substrate temperature of underlayer of 200 °C. [ABSTRACT FROM AUTHOR]

Abstract: Strontium ferrite SrFe12O19 (SrM) thick films have been synthesized using a spinning coating sol–gel process. The coating sol was formed from SrFe12O19 powders dispersed in the strontium ferrite raw sol. XRD, TEM, SEM, vibrating sample magnetometer (VSM) and ac susceptometer were employed to evaluate the structure, composition and magnetic properties of SrFe12O19 thick films. The results indicated that a uniform and crack-free coating of Strontium ferrite with ∼15μm thickness can be produced with a good deal of consistency. The magnetization hysteresis loops were almost the same for magnetic fields both applied in parallel and perpendicular. [Copyright &y& Elsevier]

Key message: A dwarfism gene LacDWARF1 was mapped by combined BSA-Seq and comparative genomics analyses to a 65.4 kb physical genomic region on chromosome 05. Dwarf architecture is one of the most important traits utilized in Cucurbitaceae breeding because it saves labor and increases the harvest index. To our knowledge, there has been no prior research about dwarfism in the sponge gourd. This study reports the first dwarf mutant WJ209 with a decrease in cell size and internodes. A genetic analysis revealed that the mutant phenotype was controlled by a single recessive gene, which is designated Lacdwarf1 (Lacd1). Combined with bulked segregate analysis and next-generation sequencing, we quickly mapped a 65.4 kb region on chromosome 5 using F2 segregation population with InDel and SNP polymorphism markers. Gene annotation revealed that Lac05g019500 encodes a gibberellin 3β-hydroxylase (GA3ox) that functions as the most likely candidate gene for Lacd1. DNA sequence analysis showed that there is an approximately 4 kb insertion in the first intron of Lac05g019500 in WJ209. Lac05g019500 is transcribed incorrectly in the dwarf mutant owing to the presence of the insertion. Moreover, the bioactive GAs decreased significantly in WJ209, and the dwarf phenotype could be restored by exogenous GA3 treatment, indicating that WJ209 is a GA-deficient mutant. All these results support the conclusion that Lac05g019500 is the Lacd1 gene. In addition, RNA-Seq revealed that many genes, including those related to plant hormones, cellular process, cell wall, membrane and response to stress, were significantly altered in WJ209 compared with the wild type. This study will aid in the use of molecular marker-assisted breeding in the dwarf sponge gourd. [ABSTRACT FROM AUTHOR]

Antiferromagnets are promising materials for future spintronic applications due to their unique properties including zero stray fields, robustness vs external magnetic fields, and ultrafast dynamics, which have attracted extensive interest in recent years. In this work, we investigate the dynamics of isolated skyrmions in an antiferromagnetic nanotrack with a voltage-gated region. It is found that the skyrmion can be jointly controlled by the driving current and the voltage-controlled magnetic anisotropy gradient. We further propose a design of logic computing gates based on the manipulation of antiferromagnetic skyrmions, which is numerically realized combining several interactions and phenomena, including the spin Hall effect, voltage-controlled magnetic anisotropy effect, skyrmion–skyrmion interaction, and skyrmion–edge interaction. The proposed logic gates can perform the basic Boolean operations of the logic AND, OR, NOT, NAND, and NOR gates. Our results may have a great impact on fundamental physics and be useful for designing future nonvolatile logic computing devices with ultra-low energy consumption and ultra-high storage density. [ABSTRACT FROM AUTHOR]

• Leflunomide could be a therapeutic candidate for MG treatment. • The germinal center response in EAMG rats was reduced by leflunomide. • Leflunomide rebuilds the balance of CD4+ Th cells by suppressing Th1 cells and promoting Treg cells. • Leflunomide inhibits Tfh cells through the IL-21/STAT3 pathway. Leflunomide, an immunosuppressive disease-modifying anti-rheumatic drug (DMARD), is widely used in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PA) as well as multiple sclerosis. However, its role in myasthenia gravis (MG) has not yet been clearly explored. Here, we investigated the effect of leflunomide on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. The results demonstrated that leflunomide alleviated the severity of EAMG associated with reduced serum total anti-acetylcholine receptor (AChR) IgG levels. During the development of EAMG, the increase of follicular helper T cells (Tfh) 1, Tfh 17 cells and decrease of follicular regulatory T cells (Tfr) were reversely altered after leflunomide administration. Our work further found that leflunomide might inhibit Tfh cells through the IL-21/STAT3 pathway to reduce the secretion of antibodies by B cells. In addition, leflunomide rebuilt the balance of Th1/Th2/Th17/Treg subsets. These results suggested that leflunomide ameliorated EAMG severity by regulating humoral immune responses and Th cell profiles thereby providing a novel effective treatment strategy for MG. [ABSTRACT FROM AUTHOR]

Missing or erroneous information is a common problem in the analysis of pharmacokinetic (PK) data. This may present as missing or inaccurate dose level or dose time, drug concentrations below the analytical limit of quantification, missing sample times, or missing or incorrect covariate information. Several methods to handle problematic data have been evaluated, although no single, broad set of recommendations for commonly occurring errors has been published. In this tutorial, we review the existing literature and present the results of our simulation studies that evaluated common methods to handle known data errors to bridge the remaining gaps and expand on the existing knowledge. This tutorial is intended for any scientist analyzing a PK data set with missing or apparently erroneous data. The approaches described herein may also be useful for the analysis of nonclinical PK data. [ABSTRACT FROM AUTHOR]

The response of surface radiation and water-heat flux to soil moisture is a critical mechanism in drought, desertification and other effects of climate change. This study analyzed soil moisture data and four-component radiation data during the summers (June, July and August) from 2010 to 2018 in a desert steppe environment of Inner Mongolia. The influence of soil moisture on the radiation flux and water-heat flux under dry, intermediate and wet conditions were quantified through correlation analysis. Radiation and water-heat fluxes showed obvious diurnal changes under different soil moisture conditions. Net longwave radiation and soil heat flux showed the largest differences in diurnal variation followed by net surface radiation, total flux and albedo. Net radiation, net longwave radiation, surface received longwave radiation, soil heat flux and total flux all increased with increasing soil moisture, while surface reflection ability decreased. Soil moisture during wet intervals (16.57-28%) showed a stronger correlation with fluxes than dry and intermediate intervals (9.78-16.46%). This indicates that soil moisture exerts a stronger influence on surface flux under moist conditions. Soil moisture showed a negative correlation with surface reflecting longwave radiation (P<0.01) and a positive correlation with net longwave radiation, net surface radiation and total flux (P<0.01). The research shows that soil moisture interacts with the atmospheric system through its influence on total flux (sensible heat and latent heat) and surface net radiation. [ABSTRACT FROM AUTHOR]

We show a topological spin texture called "bimeronium" in magnets with in-plane magnetization. It is a topological counterpart of skyrmionium in perpendicularly magnetized magnets and can be seen as a combination of two bimerons with opposite topological charges. We report the static structure and spin-orbit-torque-induced dynamics of an isolated bimeronium in a magnetic monolayer with frustrated exchange interactions. We study the anisotropy and magnetic field dependences of a static bimeronium. We also explore the bimeronium dynamics driven by the damping-like spin-orbit torque. We find that the bimeronium shows steady rotation when the spin polarization direction is parallel to the easy axis. Moreover, we demonstrate the annihilation of the bimeronium when the spin polarization direction is perpendicular to the easy axis. Our results are useful for understanding the fundamental properties of bimeronium structures and may offer an approach to build bimeronium-based spintronic devices. [ABSTRACT FROM AUTHOR]

Heat stress (HS) has a negative impact on animal health. A modified chitosan-gentamicin conjugate (CS-GT) was prepared to investigate its potential protective effects and mechanism of action on heat stress-induced intestinal mucosa injury in IPEC-J2 cells and mouse 3D intestinal organs in a mouse model. CS-GT significantly (P < 0.01) reversed the decline in transmembrane resistance and increased the FITC-dextran permeability of the IPEC-J2 monolayer fusion epithelium caused by heat stress. Heat stress decreased the expression of the tight binding proteins occludin, claudin1, and claudin2. However, pretreatment with CS-GT significantly increased (P < 0.01) the expression of these tight binding proteins. Mechanistically, CS-GT inhibited the activation of the TLR4/STAT6/MYLK signaling pathway induced by heat stress. Molecular docking showed that CS-GT can bind effectively with TLR4. In conclusion, CS-GT alleviates heat stress-induced intestinal mucosal damage both in vitro and in vivo. This effect is mediated, at least partly, by the inhibition of the TLR4/STAT6/MYLK signaling pathway and upregulation of tight junction proteins. These findings suggest that CS-GT may have therapeutic potential in the prevention and treatment of heat stress-related intestinal injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Mitral annular calcification (MAC) is a risk factor for cardiac surgery, but there is limited study on the prognosis value and the impact for valve function of MAC based on computed tomography (CT) diagnosis after myectomy for hypertrophic obstructive cardiomyopathy (OHCM). Consecutive OHCM patients underwent septal myectomy were compared according to the existence of MAC and its severity in preoperative CT scans. The survival data were evaluated and compared by Kaplan Meier analysis and log rank test. Cox regression analysis was used to evaluate the impact of MAC on endpoint events. From the entire cohort of 1035 patients, 10.8% had MAC. In multivariate regression, female (OR = 2.23), age (OR = 1.07), aortic annular calcification (OR = 2.52), aortic calcification (OR = 2.56), systolic anterior motion of the mitral valve (SAM) (OR = 0.42), mitral valve thickening (OR = 2.13), and tricuspid regurgitation (OR = 3.12) were independent predictors of MAC. All-cause mortality (3.57% vs. 1.08%, p = 0.031), major adverse cardiovascular and cerebrovascular events (MACCE) (23.32% vs. 13.65%, p = 0.014), recurrent MR > 2+ (8.04% vs. 2.49%, p = 0.001) and NYHA III-IV (11.61% vs. 5.53%, p = 0.012) were more frequent in OHCM patients with MAC after myectomy. MAC was discovered to be an independent predictor of postoperative recurrent MR > 2+ after other risk factors were taken into account (HR 2.47, 95% CI 1.08–5.67, p = 0.0329). Moderate-to-severe MAC was an independent risk factor (HR 2.03, 95% CI 1.09–3.75, p = 0.0244) for long-term major adverse cardiovascular and cerebrovascular events (MACCE). MAC was detected in one-tenth of OHCM patients in preoperative CT scanning and is mainly associated with aging and atherosclerosis. OHCM patients with MAC had a worse prognosis and more recurrent mitral valve regurgitation than those without MAC after septal myectomy. • The incidence of mitral annulus calcification in patients who had septal myectomy for hypertrophic obstructive cardiomyopathy was 10.8% in this large-scale CT diagnostic research. • There were the following baseline predictors of mitral annulus calcification: female, older age, aortic annular calcification, aortic calcification, systolic anterior motion of the mitral valve, mitral valve thickening, and preoperative tricuspid regurgitation. • In long-term follow-up, patients with mitral annulus calcification have a worse prognosis. Moderate-to-severe MAC was the risk factor for MACCE, and MAC was the risk factor of recurrent mitral regurgitation. • To reduce the risk posed by operating on calcified annulus, we used multiple surgical techniques. [ABSTRACT FROM AUTHOR]

Understanding the sources and composition of organic aerosol (OA) in indoor environments requires rapid measurements, since many emissions and processes have short timescales. However, real‐time molecular‐level OA measurements have not been reported indoors. Here, we present quantitative measurements, at a time resolution of five seconds, of molecular ions corresponding to diverse aerosol‐phase species, by applying extractive electrospray ionization mass spectrometry (EESI‐MS) to indoor air analysis for the first time, as part of the highly instrumented HOMEChem field study. We demonstrate how the complex spectra of EESI‐MS are screened in order to extract chemical information and investigate the possibility of interference from gas‐phase semivolatile species. During experiments that simulated the Thanksgiving US holiday meal preparation, EESI‐MS quantified multiple species, including fatty acids, carbohydrates, siloxanes, and phthalates. Intercomparisons with Aerosol Mass Spectrometer (AMS) and Scanning Mobility Particle Sizer suggest that EESI‐MS quantified a large fraction of OA. Comparisons with FIGAERO‐CIMS shows similar signal levels and good correlation, with a range of 100 for the relative sensitivities. Comparisons with SV‐TAG for phthalates and with SV‐TAG and AMS for total siloxanes also show strong correlation. EESI‐MS observations can be used with gas‐phase measurements to identify co‐emitted gas‐ and aerosol‐phase species, and this is demonstrated using complementary gas‐phase PTR‐MS observations. [ABSTRACT FROM AUTHOR]

Purpose: Although flomoxef (FMOX) has attracted substantial attention as an antibiotic against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-producing E. coli), the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of FMOX against ESBL-producing E. coli is unclear. The aim of this study was to determine the PK/PD index of FMOX against ESBL-producing E. coli. Methods: In vitro time-kill curve studies and in vivo PK/PD experiments were carried out. Results: Time–kill curves exhibited a unique bactericidal activity: time-dependent activity at low concentrations and concentration-dependent activity at high concentrations. In neutropenic murine thigh infection experiments, the antibacterial activity of FMOX correlated with the time that the free drug concentration remaining above the minimum inhibitory concentration (MIC) (fT>MIC) and the ratio of the area under the free drug concentration–time curve for a 24 h period to the MIC (fAUC24/MIC). However, the burden of ESBL producing E. coli significantly reduced when the time intervals for administration were shorter among three dosage regimens with same magnitude of fAUC24/MIC, indicating that fT>MIC is significant PK/PD index. The target value of fT>MIC for 1 log10 kill reduction was 35.1%. Conclusions: fT>MIC is the most significant PK/PD index of FMOX against ESBL-producing E. coli and its target value is ≥ 40%. [ABSTRACT FROM AUTHOR]

Because exclusive use of echinocandins can induce the drug-resistant strains, appropriate use of azoles and polyenes is still necessary in the treatment of candidemia. In this study, we conducted a meta-analysis of randomized controlled trials regarding the efficacy and safety of azole and polyene antifungals in the treatment of candidemia. MEDLINE and the Cochrane Register of Controlled Trials were used as reference databases, and papers published up to June 10, 2019 were searched. The search results were carefully scrutinized, duplicate references were removed, and the study was ultimately carried out using three reports. Among azole antifungals, fluconazole and voriconazole were extracted, however; only conventional amphotericin B (AMPH-B) was extracted among polyene antifungals. Treatment successes with the use of azoles and AMPH-B were compared, and findings showed that AMPH-B was significantly superior (RR = 0.90, 95% CI 0.82–1.00, p = 0.04). However, there was no significant difference in mortality (RR = 0.87, 95% CI 0.72–1.07, p = 0.19). Analysis of adverse events showed that renal disorders were significantly less common with azoles than with AMPH-B (RR = 0.26, 95% CI 0.10–0.68, p = 0.006). In conclusion, AMPH-B were superior to azoles in terms of efficacy, but had a risk of causing renal disorders. [ABSTRACT FROM AUTHOR]

Echinocandins are frequent use antifungals in the treatment of invasive candidiasis, and it is important to update information on their efficacy and safety for optimal antifungal drug treatment. The aim of this study is to clarify whether echinocandins are superior to non-echinocandins for the treatment of invasive candidiasis. We conducted a meta-analysis of RCTs of echinocandins and non-echinocandins for adult invasive candidiasis. The MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov databases before June 2019 were used. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method random-effects model. We identified 14,846 articles and screened, and five studies were included meta-analysis. The treatment success ratio for echinocandins was significantly higher than that for non-echinocandins (RR = 1.14, 95% CI 1.06–1.22, p = 0.0003). In regard to adverse events, there was no significant difference between the two treatment groups. A subgroup analysis showed that the treatment success ratio for echinocandins was significantly higher than that for azoles (RR = 1.20, 1.08–1.34, p = 0.001), whereas no significant differences were observed between echinocandins and polyenes. In safety analysis, the incidence ratio of electrolyte disorder (RR = 0.50, 0.33–0.76, p = 0.001), renal disorder (RR = 0.19, 0.09–0.40, p < 0.0001), and fever (RR = 0.46, 0.23–0.93, p = 0.03) were significantly lower in patients receiving echinocandins than in those receiving polyenes. This meta-analysis based on RCTs was first to show that use of echinocandins was associated with improved clinical success. Echinocandins may be useful as a first-line drug for invasive candidiasis. [ABSTRACT FROM AUTHOR]

Background: With evidence of warming climates, it is important to understand the effects of heat stress in farm animals in order to minimize production losses. Studying the changes in the brain proteome induced by heat stress may aid in understanding how heat stress affects brain function. The hypothalamus is a critical region in the brain that controls the pituitary gland, which is responsible for the secretion of several important hormones. In this study, we examined the hypothalamic protein profile of 10 pigs (15 ± 1 kg body weight), with five subjected to heat stress (35 ± 1 °C; relative humidity = 90%) and five acting as controls (28 ± 3 °C; RH = 90%). Result: The isobaric tags for relative and absolute quantification (iTRAQ) analysis of the hypothalamus identified 1710 peptides corresponding to 360 proteins, including 295 differentially expressed proteins (DEPs), 148 of which were up-regulated and 147 down-regulated, in heat-stressed animals. The Ingenuity Pathway Analysis (IPA) software predicted 30 canonical pathways, four functional groups, and four regulatory networks of interest. The DEPs were mainly concentrated in the cytoskeleton of the pig hypothalamus during heat stress. Conclusions: In this study, heat stress significantly increased the body temperature and reduced daily gain of body weight in pigs. Furthermore, we identified 295 differentially expressed proteins, 147 of which were down-regulated and 148 up-regulated in hypothalamus of heat stressed pigs. The IPA showed that the DEPs identified in the study are involved in cell death and survival, cellular assembly and organization, and cellular function and maintenance, in relation to neurological disease, metabolic disease, immunological disease, inflammatory disease, and inflammatory response. We hypothesize that a malfunction of the hypothalamus may destroy the host physical and immune function, resulting in decreased growth performance and immunosuppression in heat stressed pigs. [ABSTRACT FROM AUTHOR]

In this research work, ferrite nanoparticles with composition of SrFe12-x(Ni0.5Co0.5Ti)x/2O19 (x = 0-2.5 in a step of 0.5) were synthesized by a reverse micelle. Multiwalled carbon nanotubes (MWCNT) were also functionalized by employing poly(acrylic acid). Then the ferrite nanoparticles were deposited on the functionalized surface of carbon nanotubes by hetero-coagulation process. The volume percentage of carbon nanotubes was kept constant at 8 vol. % for synthesizing nanocomposites. The site preference of substituted cations in ferrite crystal structure was determined by 57Fe Mössbauer spectroscopy. It was proved that the substituted cations were distributed in 12 k crystallographic sites. The morphology of ferrite dot array on carbon nanotubes was studied by field emission scanning electron microscopy (FESEM). Quantum Device MPMS-5S SQUID magnetometer was used to probe the variation of magnetization with applied magnetic field. It was found that with an increase in substitution content, the saturation of magnetization and coercivity decrease. [ABSTRACT FROM AUTHOR]

By introducing artificial pinning sites to locally modify coercivity in perpendicularly magnetized TbFeCo wires, strip domains were constructed without expense of specimen damage. The construction of strip domains with well-defined shape and controllable number enables a determination of magneto-resistance contributing from singe domain wall. Contrast to crystalline materials, a rather high domain wall magneto-resistance ratio near 20% was found at room temperature, indicating the amorphous TbFeCo is a potential candidate for spintronic devices. [ABSTRACT FROM AUTHOR]

Large-scale carbon nanotubes (CNTs)/substituted strontium ferrite nanocomposites have been fabricated by hetero-coagulation. The structure and morphology of nanoparticles and nanocomposites were evaluated by high-resolution transmission electron microscopy (HRTEM). HRTEM confirmed that strontium ferrite was successfully attached to carbon nanotubes. The vibrating sample magnetometer (VSM) confirmed the relatively strong dependence of saturation magnetization with the volume percentage of multi-walled carbon nanotubes (MWCNTs). Reflection loss of nanocomposites at 12-18 GHz was evidently enhanced, as compared to that of strontium ferrite nanoparticles. The maximum reflection loss increased significantly with an increase in volume percentage of MWCNTs. It was proved that the microwave absorbing bandwidth was modulated simply by manipulating the thickness of nanocomposites. Reflection loss evaluations indicate that the nanocomposites display a great potential application as wide-band electromagnetic wave absorbers. [ABSTRACT FROM AUTHOR]

In this research work, magnetic multi-walled carbon nanotube (MWCNTs) nanocomposites have been created by the assembly of Mn-Co-Ti-substituted barium ferrite nanoparticles onto the surface of MWCNTs. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used to demonstrate the successful attachment of ferrite nanoparticles to MWCNTs. Vibrating sample magnetometry (VSM) confirmed the relatively strong dependence of saturation magnetization on the volume percentage of MWCNTs. Microwave absorption of the MWCNTs/doped barium ferrite (BaM) nanocomposites is evidently enhanced compared to that of pure MWCNTs and ferrite nanoparticles. The maximum reflection loss increased significantly with an increase in volume percentage of MWCNTs in nanocomposites. [ABSTRACT FROM AUTHOR]

Magnetic skyrmionium can be used as a nanometer-scale non-volatile information carrier, which shows no skyrmion Hall effect due to its special structure carrying zero topological charge. Here, we report the static and dynamic properties of an isolated nanoscale skyrmionium in a frustrated magnetic monolayer, where the skyrmionium is stabilized by competing interactions. The frustrated skyrmionium has a size of about 10 nm, which can be further reduced by tuning perpendicular magnetic anisotropy or the magnetic field. It is found that the nanoscale skyrmionium driven by the damping-like spin-orbit torque shows directional motion with a favored Bloch-type helicity. A small driving current or magnetic field can lead to the transformation of an unstable Néel-type skyrmionium to a metastable Bloch-type skyrmionium. A large driving current may result in the distortion and collapse of the Bloch-type skyrmionium. Our results are useful for the understanding of frustrated skyrmionium physics, which also provide guidelines for the design of spintronic devices based on topological spin textures. [ABSTRACT FROM AUTHOR]

The naturally occurring quercetin flavonoid, dihydroquercetin, is widely distributed in plant tissues and has a variety of biological activities. Herein, a magnetic molecularly imprinted solid‐phase extraction was tailor made for selective determination of dihydroquercetin in Larix griffithiana using high‐performance liquid chromatography. Amino‐functionalized core‐shell magnetic nanoparticles were prepared and characterized using scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, and infrared spectroscopy. The polymer had an average diameter of 250 ± 2.56 nm and exhibited good stability and adsorption for template molecule, which is enriched by hydrogen bonding interaction. Multiple factors for extraction, including loading, washing, elution solvents, and extraction time, were optimized. The limit of detection was 1.23 μg/g. The precision determined at various concentration of dihydroquercetin was less than 4% and the mean recovery was between 74.64 and 101.80%. It has therefore been shown that this protocol can be used as an alternative extraction to quantify dihydroquercetin in L. griffithiana and purify quercetin flavonoid from other complex matrices. [ABSTRACT FROM AUTHOR]

Supplemental arginine has shown promise as a safe therapeutic option to improve endogenous nitric oxide (NO) regulation in cardiovascular diseases associated with endothelial dysfunction. In clinical studies in adults, l-arginine, an endogenous amino acid, was reported to improve cardiovascular function in hypertension, pulmonary hypertension, preeclampsia, angina, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome. l-citrulline, a natural precursor of l-arginine, is more bioavailable than l-arginine because it avoids hepatic first-pass metabolism and has a longer circulation time. Although not yet well-studied, arginine/citrulline has immense therapeutic potential in some life-threatening diseases in children. However, the optimal clinical development of arginine or citrulline in children requires more information about pharmacokinetics and exposure–response relationships at appropriate ages and under relevant disease states. This article summarizes the preclinical and clinical studies of arginine/citrulline in both adults and children, including currently available pharmacokinetic information. The pharmacology of arginine/citrulline is confounded by several patient-specific factors such as variations in baseline arginine/citrulline due to developmental ages and disease states. Currently available pharmacokinetic studies are insufficient to inform the optimal design of clinical studies, especially in children. Successful bench-to-bedside clinical translation of arginine supplementation awaits information from well-designed pharmacokinetic/pharmacodynamic studies, along with pharmacometric approaches. [ABSTRACT FROM AUTHOR]

Background: RIPK1 (receptor-interacting protein kinase-1) plays a role in cancer development, whereas no clear studies focused on the cervical cancer. The objective of this study was to evaluate the relationship between RIPK1 polymorphisms and cervical cancer risk among the Uyghur population.Methods: We performed a case-control study including 342 cervical cancer patients and 498 age-matched healthy controls. Four RIPK1 genetic variants (rs6907943, rs2077681, rs9503400 and rs17548629) were genotyped with Agena MassARRAY platform. The associations between RIPK1 polymorphisms and cervical cancer risk were assessed under Binary logistic regression models. False discovery rate (FDR) was used to improve the results reliability.Results: The results showed rs2077681 was significantly associated with cervical cancer risk under various genetic models (codominant: OR = 3.14, 95% CI = 1.40-7.07, p = 0.006, FDR-p = 0.018; recessive: OR = 3.20, 95% CI = 1.43-7.16, p = 0.005, FDR-0.018). The stratified analysis indicated that the relationships of rs6907946, rs9503400 and rs17548629 with cervical cancer risk were statistically significant in the subgroup of clinical stage (p < 0.05).Conclusion: Our findings demonstrated that RIPK1 polymorphisms were associated with cervical cancer susceptibility among the Uyghur population in China, and RIPK1 polymorphisms might be involved in the development of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Genetic testing has been conducted in patients with prostate cancer (PCa) using multigene panels, but no centralized guidelines for genetic testing exist. To overcome this limitation, we investigated the demographic and clinical characteristics of patients with pathogenic variants.Methods: We sequenced eight genes associated with hereditary PCa in 7636 unselected Japanese patients with PCa and 12 366 male, cancer-free control individuals. We assigned clinical significance for all 1456 variants using the American College of Medical Genetics and Genomics guidelines and ClinVar. We compared the frequency of carriers bearing pathogenic variants between cases and control participants with calculated PCa risk in each gene and documented the demographic and clinical characteristics of patients bearing pathogenic variants. All statistical tests were two-sided.Results: We identified 136 pathogenic variants, and 2.9% of patients and 0.8% of control individuals had a pathogenic variant. Association with PCa risk was statistically significant for variants in BRCA2 (P < .001, odds ratio [OR] = 5.65, 95% confidence interval [CI] = 3.55 to 9.32), HOXB13 (P < .001, OR = 4.73, 95% CI = 2.84 to 8.19), and ATM (P < .001, OR = 2.86, 95% CI = 1.63 to 5.15). We detected recurrent new pathogenic variants such as p.Gly132Glu of HOXB13. Patients with pathogenic variants were 2.0 years younger at diagnosis and more often had smoking and alcohol drinking histories as well as family histories of breast, pancreatic, lung, and liver cancers.Conclusions: This largest sequencing study of PCa heredity provides additional evidence supporting the latest consensus among clinicians for developing genetic testing guidelines for PCa. [ABSTRACT FROM AUTHOR]

Background: Copy number variants (CNVs) have been reported to be associated with diseases, traits, and evolution. However, it is hard to determine which gene should have priority as a target for further functional experiments if a CNV is rare or a singleton. In this study, we attempted to overcome this issue by using two approaches: by assessing the influences of gene dosage sensitivity and gene expression sensitivity. Dosage sensitive genes derived from two-round whole-genome duplication in previous studies. In addition, we proposed a cross-sectional omics approach that utilizes open data from GTEx to assess the effect of whole-genome CNVs on gene expression. Methods: Affymetrix Genome-Wide SNP Array 6.0 was used to detect CNVs by PennCNV and CNV Workshop. After quality controls for population stratification, family relationship and CNV detection, 287 patients with narcolepsy, 133 patients with essential hypersomnia, 380 patients with panic disorders, 164 patients with autism, 784 patients with Alzheimer disease and 1280 healthy individuals remained for the enrichment analysis. Results: Overall, significant enrichment of dosage sensitive genes was found across patients with narcolepsy, panic disorders and autism. Particularly, significant enrichment of dosage-sensitive genes in duplications was observed across all diseases except for Alzheimer disease. For deletions, less or no enrichment of dosage-sensitive genes with deletions was seen in the patients when compared to the healthy individuals. Interestingly, significant enrichments of genes with expression sensitivity in brain were observed in patients with panic disorder and autism. While duplications presented a higher burden, deletions did not cause significant differences when compared to the healthy individuals. When we assess the effect of sensitivity to genome dosage and gene expression at the same time, the highest ratio of enrichment was observed in the group including dosage-sensitive genes and genes with expression sensitivity only in brain. In addition, shared CNV regions among the five neuropsychiatric diseases were also investigated. Conclusions: This study contributed the evidence that dosage-sensitive genes are associated with CNVs among neuropsychiatric diseases. In addition, we utilized open data from GTEx to assess the effect of whole-genome CNVs on gene expression. We also investigated shared CNV region among neuropsychiatric diseases. [ABSTRACT FROM AUTHOR]

Summary: Anthocyanin fruit (Aft) and atroviolacea (atv) were characterized in wild tomato and can enhance anthocyanin content in tomato fruit. However, the gene underlying the Aft locus and the mechanism by which Aft and atv act remain largely unknown.In this study, the Aft locus was fine‐mapped to an approximately 145‐kb interval on chromosome 10, excluding SlAN2 (Solyc10g086250), SlANT1 (Solyc10g086260) and SlANT1‐like (Solyc10g086270), which have previously been suggested as candidates. Thus, the R2R3‐MYB transcription factor SlAN2‐like (Solyc10g086290) was considered the best candidate gene for Aft.The CRISPR/Cas9‐mediated SlAN2‐like mutants show a much lower accumulation of anthocyanins associated with the downregulation of multiple anthocyanin‐related genes compared to the wild‐type tomato, indicating that SlAN2‐like is responsible for the Aft phenotype. The repressive function of SlMYBATV also was confirmed through the CRISPR/Cas9 approach. A yeast‐two‐hybrid assay revealed that SlMYBATV interacts with the bHLH protein SlJAF13. Furthermore, yeast‐one‐hybrid and dual‐luciferase transient expression assays showed that Aft directly binds to the SlMYBATV promoter and activates its expression.The results herein provide candidate genes to enhance anthocyanin content in tomato fruit. This research also provides insight into a mechanism involving the Aft‐SlMYBATV pathway that fine‐tunes anthocyanin accumulation in tomato fruit. [ABSTRACT FROM AUTHOR]