Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History.

We analyze whole-genome sequencing data from 141,431 Chinese women generated for non-invasive prenatal testing (NIPT). We use these data to characterize the population genetic structure and to investigate genetic associations with maternal and infectious traits. We show that the present day distribution of alleles is a function of both ancient migration and very recent population movements. We reveal novel phenotype-genotype associations, including several replicated associations with height and BMI, an association between maternal age and EMB, and between twin pregnancy and NRG1. Finally, we identify a unique pattern of circulating viral DNA in plasma with high prevalence of hepatitis B and other clinically relevant maternal infections. A GWAS for viral infections identifies an exceptionally strong association between integrated herpesvirus 6 and MOV10L1, which affects piwi-interacting RNA (piRNA) processing and PIWI protein function. These findings demonstrate the great value and potential of accumulating NIPT data for worldwide medical and genetic analyses.

Fast and accurate out-of-core PCA framework for large scale biobank data.

Principal component analysis (PCA) is widely used in statistics, machine learning, and genomics for dimensionality reduction and uncovering low-dimensional latent structure. To address the challenges posed by ever-growing data size, fast and memory-efficient PCA methods have gained prominence. In this paper, we propose a novel randomized singular value decomposition (RSVD) algorithm implemented in PCAone, featuring a window-based optimization scheme that enables accelerated convergence while improving the accuracy. Additionally, PCAone incorporates out-of-core and multithreaded implementations for the existing Implicitly Restarted Arnoldi Method (IRAM) and RSVD. Through comprehensive evaluations using multiple large-scale real-world data sets in different fields, we show the advantage of PCAone over existing methods. The new algorithm achieves significantly faster computation time while maintaining accuracy comparable to the slower IRAM method. Notably, our analyses of UK Biobank, comprising around 0.5 million individuals and 6.1 million common single nucleotide polymorphisms, show that PCAone accurately computes the top 40 principal components within 9 h. This analysis effectively captures population structure, signals of selection, structural variants, and low recombination regions, utilizing <20 GB of memory and 20 CPU threads. Furthermore, when applied to single-cell RNA sequencing data featuring 1.3 million cells, PCAone, accurately capturing the top 40 principal components in 49 min. This performance represents a 10-fold improvement over state-of-the-art tools.

Hi-BDiSCO: folding 3D mesoscale genome structures from Hi-C data using brownian dynamics.

The structure and dynamics of the eukaryotic genome are intimately linked to gene regulation and transcriptional activity. Many chromosome conformation capture experiments like Hi-C have been developed to detect genome-wide contact frequencies and quantify loop/compartment structures for different cellular contexts and time-dependent processes. However, a full understanding of these events requires explicit descriptions of representative chromatin and chromosome configurations. With the exponentially growing amount of data from Hi-C experiments, many methods for deriving 3D structures from contact frequency data have been developed. Yet, most reconstruction methods use polymer models with low resolution to predict overall genome structure. Here we present a Brownian Dynamics (BD) approach termed Hi-BDiSCO for producing 3D genome structures from Hi-C and Micro-C data using our mesoscale-resolution chromatin model based on the Discrete Surface Charge Optimization (DiSCO) model. Our approach integrates reconstruction with chromatin simulations at nucleosome resolution with appropriate biophysical parameters. Following a description of our protocol, we present applications to the NXN, HOXC, HOXA and Fbn2 mouse genes ranging in size from 50 to 100 kb. Such nucleosome-resolution genome structures pave the way for pursuing many biomedical applications related to the epigenomic regulation of chromatin and control of human disease.

vcfpp: a C++ API for rapid processing of the variant call format.

MOTIVATION: Given the widespread use of the variant call format (VCF/BCF) coupled with continuous surge in big data, there remains a perpetual demand for fast and flexible methods to manipulate these comprehensive formats across various programming languages. RESULTS: This work presents vcfpp, a C++ API of HTSlib in a single file, providing an intuitive interface to manipulate VCF/BCF files rapidly and safely, in addition to being portable. Moreover, this work introduces the vcfppR package to demonstrate the development of a high-performance R package with vcfpp, allowing for rapid and straightforward variants analyses. AVAILABILITY AND IMPLEMENTATION: vcfpp is available from https://github.com/Zilong-Li/vcfpp under MIT license. vcfppR is available from https://cran.r-project.org/web/packages/vcfppR.

Epigenetic Regulation of IL-23 by E3 Ligase FBXW7 in Dendritic Cells Is Critical for Psoriasis-like Inflammation.

Dendritic cells (DCs), a driver of psoriasis pathogenesis, produce IL-23 and trigger IL-23/IL-17 cytokine axis activation. However, the mechanisms regulating IL-23 induction remain unclear. In the current study, we found that mice with E3 ligase FBXW7 deficiency in DCs show reduced skin inflammation correlated with the reduction of IL-23/IL-17 axis cytokines in the imiquimod-induced psoriasis model. Fbxw7 deficiency results in decreased production of IL-23 in DCs. FBXW7 interacts with the lysine N-methyltransferase suppressor of variegation 39 homolog 2 (SUV39H2), which catalyzes the trimethylation of histone H3 Lys9 (H3K9) during transcription regulation. FBXW7 mediates the ubiquitination and degradation of SUV39H2, thus decreasing H3K9m3 deposition on the Il23a promoter. The Suv39h2 knockout mice displayed exacerbated skin inflammation with the IL-23/IL-17 axis overactivating in the psoriasis model. Taken together, our results indicate that FBXW7 increases IL-23 expression in DCs by degrading SUV39H2, thereby aggravating psoriasis-like inflammation. Inhibition of FBXW7 or the FBXW7/SUV39H2/IL-23 axis may represent a novel therapeutic approach to psoriasis.

Histone methyltransferase Suv39h1 regulates hepatic stellate cell activation and is targetable in liver fibrosis.

OBJECTIVE: Liver fibrosis is a prelude to a host of end-stage liver diseases. Hepatic stellate cells (HSCs), switching from a quiescent state to myofibroblasts, are the major source for excessive production of extracellular matrix proteins. In the present study, we investigated the role of Suv39h1, a lysine methyltransferase, in HSC-myofibroblast transition and the implication in liver fibrosis. DESIGN: HSC-specific or myofibroblast-specific Suv39h1 deletion was achieved by crossbreeding the Suv39h1 f/f mice to the Lrat-Cre mice or the Postn-CreERT2 mice. Liver fibrosis was induced by CCl4 injection or bile duct ligation. RESULTS: We report that Suv39h1 expression was universally upregulated during HSC-myofibroblast transition in different cell and animal models of liver fibrosis and in human cirrhotic liver tissues. Consistently, Suv39h1 knockdown blocked HSC-myofibroblast transition in vitro. HSC-specific or myofibroblast-specific deletion of Suv39h1 ameliorated liver fibrosis in mice. More importantly, Suv39h1 inhibition by a small-molecule compound chaetocin dampened HSC-myofibroblast transition in cell culture and mitigated liver fibrosis in mice. Mechanistically, Suv39h1 bound to the promoter of heme oxygenase 1 (HMOX1) and repressed HMOX1 transcription. HMOX1 depletion blunted the effects of Suv39h1 inhibition on HSC-myofibroblast transition in vitro and liver fibrosis in vivo. Transcriptomic analysis revealed that HMOX1 might contribute to HSC-myofibroblast transition by modulating retinol homeostasis. Finally, myofibroblast-specific HMOX1 overexpression attenuated liver fibrosis in both a preventive scheme and a therapeutic scheme. CONCLUSIONS: Our data demonstrate a previously unrecognised role for Suv39h1 in liver fibrosis and offer proof-of-concept of its targetability in the intervention of cirrhosis.

Liquid-liquid phase separation of amyloid-ß oligomers modulates amyloid fibrils formation.

Soluble amyloid-ß oligomers (AßOs) are proposed to instigate and mediate the pathology of Alzheimer's disease, but the mechanisms involved are not clear. In this study, we reported that AßOs can undergo liquid-liquid phase separation (LLPS) to form liquid-like droplets in vitro. We determined that AßOs exhibited an α-helix conformation in a membrane-mimicking environment of SDS. Importantly, SDS is capable of reconfiguring the assembly of different AßOs to induce their LLPS. Moreover, we found that the droplet formation of AßOs was promoted by strong hydrated anions and weak hydrated cations, suggesting that hydrophobic interactions play a key role in mediating phase separation of AßOs. Finally, we observed that LLPS of AßOs can further promote Aß to form amyloid fibrils, which can be modulated by (-)-epigallocatechin gallate. Our study highlights amyloid oligomers as an important entity involved in protein liquid-to-solid phase transition and reveals the regulatory role of LLPS underlying amyloid protein aggregation, which may be relevant to the pathological process of Alzheimer's disease.

Cobalt-Doping Induced Formation of Five-Coordinated Nickel Selenide for Enhanced Ethanol Assisted Overall Water Splitting.

To overcome the low efficiency of overall water splitting, highly effective and stable catalysts are in urgent need, especially for the anode oxygen evolution reaction (OER). In this case, nickel selenides appear as good candidates to catalyze OER and other substitutable anodic reactions due to their high electronic conductivity and easily tunable electronic structure to meet the optimized adsorption ability. Herein, an interesting phase transition from the hexagonal phase of NiSe (H-NiSe) to the rhombohedral phase of NiSe (R-NiSe) induced by the doping of cobalt atoms is reported. The five-coordinated R-NiSe is found to grow adjacent to the six-coordinated H-NiSe, resulting in the formation of the H-NiSe/R-NiSe heterostructure. Further characterizations and calculations prove the reduced splitting energy for R-NiSe and thus the less occupancy in the t2g orbits, which can facilitate the electron transfer process. As a result, the Co2 -NiSe/NF shows a satisfying catalytic performance toward OER, hydrogen evolution reaction, and (hybrid) overall water splitting. This work proves that trace amounts of Co doping can induce the phase transition from H-NiSe to R-NiSe. The formation of less-coordinated species can reduce the t2g occupancy and thus enhance the catalytic performance, which might guide rational material design.

Building a highly efficient Streptomyces super-chassis for secondary metabolite production by reprogramming naturally-evolved multifaceted shifts.

Streptomyces has an extensive array of bioactive secondary metabolites (SMs). Nevertheless, devising a framework for the heterologous production of these SMs remains challenging. We here reprogrammed a versatile plug-and-play Streptomyces super-chassis and established a universal pipeline for production of diverse SMs via understanding of the inherent pleiotropic effects of ethanol shock on jadomycin production in Streptomyces venezuelae. We initially identified and characterized a set of multiplex targets (afsQ1, bldD, bldA, and miaA) that contribute to SM (jadomycin) production when subjected to ethanol shock. Subsequently, we developed an ethanol-induced orthogonal amplification system (EOAS), enabling dynamic and precise control over targets. Ultimately, we integrated these multiplex targets into functional units governed by the EOAS, generating a universal and plug-and-play Streptomyces super-chassis. In addition to achieving the unprecedented titer and yield of jadomycin B, we also evidenced the potential of this super-chassis for production of diverse heterologous SMs, including antibiotic oxytetracycline, anticancer drug doxorubicins, agricultural herbicide thaxtomin A, and plant growth regulator guvermectin, all with the yields of >10 mg/g glucose in a simple mineral medium. Given that the production of SMs all required complexed medium and the cognate yields were usually much lower, our achievement of using a universal super-chassis and engineering pipeline in a simple mineral medium is promising for convenient heterologous production of SMs.

Regulatory role and translational potential of CCL11 in liver fibrosis.

BACKGROUND AND AIMS: Myofibroblasts are considered the major effector cell type of liver fibrosis and primarily derived from hepatic stellate cells (HSCs). In the present study, we investigated the contribution of C-C motif chemokine (CCL11) to HSC-myofibroblast trans -differentiation and its implication in liver fibrosis. APPROACH AND RESULTS: We report that CCL11 levels were elevated in HSCs, but not in hepatocytes or Kupffer cells, isolated from mice with liver fibrosis compared with the control mice. CCL11 levels were also up-regulated by 2 pro-fibrogenic growth factors TGF-ß and platelet derived growth factor in cultured HSCs. Mechanistically, zinc finger factor 281 bound to the CCL11 promoter and mediated CCL11 trans -activation in HSCs. Depletion of CCL11 attenuated whereas treatment with recombinant CCL11 promoted HSC activation. Further, global CCL11 deletion ( CCL11-/- ) or HSC/myofibroblast-specific CCL11 knockdown mitigated fibrogenesis in mice. RNA-sequencing revealed that CCL11 might regulate HSC activation by stimulating the transcription of Jagged 1. Reconstitution of Jagged 1 restored the fibrogenic response in CCL11-/- mice. Finally, several targeting strategies that aimed at blockading CCL11 signaling, either by administration of an antagonist to its receptor C-C motif chemokine receptor 3 or neutralizing antibodies against CCL11/C-C motif chemokine receptor 3, ameliorated liver fibrosis in mice. CONCLUSIONS: Our data unveil a previously unrecognized role for CCL11 in liver fibrosis and provide proof-of-concept evidence that targeting CCL11 can be considered as an effective therapeutic approach.

High-resolution iterative reconstruction at extremely low sampling rate for Fourier single-pixel imaging via diffusion model.

The trade-off between imaging efficiency and imaging quality has always been encountered by Fourier single-pixel imaging (FSPI). To achieve high-resolution imaging, the increase in the number of measurements is necessitated, resulting in a reduction of imaging efficiency. Here, a novel high-quality reconstruction method for FSPI imaging via diffusion model was proposed. A score-based diffusion model is designed to learn prior information of the data distribution. The real-sampled low-frequency Fourier spectrum of the target is employed as a consistency term to iteratively constrain the model in conjunction with the learned prior information, achieving high-resolution reconstruction at extremely low sampling rates. The performance of the proposed method is evaluated by simulations and experiments. The results show that the proposed method has achieved superior quality compared with the traditional FSPI method and the U-Net method. Especially at the extremely low sampling rate (e.g., 1%), an approximately 241% improvement in edge intensity-based score was achieved by the proposed method for the coin experiment, compared with the traditional FSPI method. The method has the potential to achieve high-resolution imaging without compromising imaging speed, which will further expanding the application scope of FSPI in practical scenarios.

Novel multi-target angiogenesis inhibitors as potential anticancer agents: Design, synthesis and preliminary activity evaluation.

Based on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cellswere 0.078 µmol/L and 0.068 µmol/L, respectively. The cytotoxicity evaluation indicated that TC9, TA11, TM4, and TH3 displayed good safety against HEK293T cells. TH2 and TH3 could induce apoptosis of MCF-7 cells. Molecular modeling and ADMET prediction results indicated that most of target compounds showed promising medicinal properties, which was consistent with the experimental results. Our findings provided new lead compounds for the structural optimization of multi-target angiogenesis inhibitors.

Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a Mendelian randomization study.

PURPOSE: Although studies have suggested that gut microbiota may be associated with intervertebral disk disease, their causal relationship is unclear. This study aimed to investigate the causal relationship between the gut microbiota and its metabolic pathways with the risk of intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica. METHODS: Genetic variation data for 211 gut microbiota taxa at the phylum to genus level were obtained from the MiBioGen consortium. Genetic variation data for 105 taxa at the species level and 205 metabolic pathways were obtained from the Dutch Microbiome Project. Genetic variation data for disease outcomes were obtained from the FinnGen consortium. The causal relationships between the gut microbiota and its metabolic pathways and the risk of IVDD, LBP, and sciatica were evaluated via Mendelian randomization (MR). The robustness of the results was assessed through sensitivity analysis. RESULTS: Inverse variance weighting identified 46 taxa and 33 metabolic pathways that were causally related to IVDD, LBP, and sciatica. After correction by weighted median and MR-PRESSO, 15 taxa and nine pathways remained stable. After FDR correction, only the effect of the genus_Eubacterium coprostanoligenes group on IVDD remained stable. Sensitivity analyses showed no evidence of horizontal pleiotropy, heterogeneity, or reverse causation. CONCLUSION: Some microbial taxa and their metabolic pathways are causally related to IVDD, LBP, and sciatica and may serve as potential intervention targets. This study provides new insights into the mechanisms of gut microbiota-mediated development of intervertebral disk disease.

First Report of Alternaria alternata Causing Leaf Spot on Oenothera biennis in China.

Oenothera biennis is a versatile plant that can be used for both ornamental and medicinal purposes. Its potential in treating a range of diseases is noteworthy and has been studied extensively (Bayles et al. 2009). In September 2022, leaf spot on O. biennis was first observed in a 0.2 ha plant experimental demonstration land in Libo County (25°23'24″N, 108°4'22″E), Guizhou Province, China. The incidence of all O. biennis was about 60% over the 0.2 ha surveyed. Initially, red round or irregular spots appeared on the leaves, which then gradually turned dry yellow. To identify the cause, diseased tissues (5 mm2) from the margin of the lesions were surface disinfected by immersion in 75% ethanol for 30 sec, and 7% sodium hypochlorite for 1 min, and then rinsed three times with sterile distilled water (Sun et al. 2022). The tissues were cultured in potato dextrose agar (PDA) at 25℃. After 7 days, further purification was performed by transferring onto the new PDA and potato carrot agar (PCA) by single-spore isolation. After 8 days, the colonies on PDA were 80 mm in diameter, cotton-like in texture, dark green in color and nearly circular in shape with a white edge. The conidia on the PCA were short-chains, pear-shaped or oval, pale brown, smooth surface, 15.3-30.8 × 8.3-12.6µm (n = 150). Beaks were columnar or conical, 0-6.0 × 0-4.0µm (n = 100). Conidiophores were solitary straight or flexuous less branched, dark brown, and measured 14.0-60.5 × 3.0-4.5µm. Based upon morphological observations, all these characteristics were consistent with those of Alternaria alternata (Simmons 2007). To further identify the fungal species, internal transcribed spacer (ITS) rDNA regions, glyceraldehyde-3-phosphate dehydrogenase (gpd), Alternaria major allergen (Alt a 1), RNA polymerase second largest subunit gene (RPB2) and translation elongation factor 1-alpha (TEF 1) were amplified and sequenced using the primers ITS4/ITS5, RPB2-5F/RPB2-7CR, gpd1/gpd2, EF1-728F/EF1-986R, and Alt-for/Alt-rev (Woudenberg et al. 2015). Sequences were deposited in GenBank (ITS: OM319523; RPB2: OM849249; gpd: OM296248; TEF1: OM238124; Alt a 1: OM649813). The similarity of the representative isolate YJC and the type strain CBS 595.93 (ITS: KP124320; RPB2: KP124788; gpd: KP124175; TEF1: KP125096; Alt a 1: JQ646399) on the phylogenetic tree was 98%. Therefore, the fungus was identified as A. alternata by morphology and phylogenetic analysis. To confirm pathogenicity, a spore suspension (1 × 106 conidia/ml) of the representative isolate YJC was sprayed on the leaves of six healthy plants and six plants sprayed with distilled water as controls. The plants used in the experiment were covered with plastic bags for 48 h (Luo et al. 2012). After 8 days, all inoculated plants exhibited symptoms of the disease, while the control plants remained symptom-free. The experiment was conducted twice using the same approach. The fungus that has been inoculated was reisolated from the leaves of the infected plants and identified as A. alternata through morphological observation, thus fulfilling Koch's postulates. To the best of our knowledge, this is the first documented case of O. biennis leaf spot caused by A. alternata. This pathogen could pose a threat to O. biennis yield and result in economic losses. For further development of specific control measures, it is important to confirm the identity.

First Report of Alternaria alternata Causing Leaf Blight on Elsholtzia ciliata in China.

Elsholtzia ciliata is an annual medicinal plant characterized to the family Lamiaceae Martinov. It is grown in most parts of China and has high economic value as a traditional Chinese medicine. In September of 2022, E. ciliata plants located at the planting base of traditional Chinses medicine in Daying county (30°35'40″N, 105°14 12″E), Sichuan Province, China, were recorded with leaf blight. The incidence of symptomatic plants was 15% (30 infected plants out of 200 surveyed). The symptoms included an irregular necrotic lesion at the tip of the leaf, which gradually expanded across the entire leaf. To elucidate the cause of the symptoms, 12 symptomatic leaves were sampled from four different plants and 5×5 mm section, including symptomatic and non-symptomatic tissue was excised. Tissue samples were disinfected in 75% ethanol for 30s, and 7% sodium hypochlorite for 1 min, and then rinsed three times with sterile distilled water (Sun et al. 2022). The sampled tissues were placed onto potato dextrose agar (PDA) and incubated at 25℃ in the dark. Seven days later, single spores were recovered onto fresh PDA (Zhu et al. 1992). Colonies on PDA initially appeared white, developing grayish-green conidia with white margins. Conidia (n=150) were collected and observed under the microscope. The conidia were smooth walled and dark brown, with pear-shaped, 12.1-31.4 × 5.0-9.4µm, with 3-5 transverse septa, 1-3 longitudinal or oblique septa. Conidiophores were thick, dark brown, simple with multiple conidial scars, 5.0-75.5 × 2.5.0-5.0µm. Based on morphological observations the 12 isolates were most similar to Alternaria alternata (Simmons 2007). The internal transcribed spacer (ITS) rDNA regions, glyceraldehyde-3-phosphate dehydrogenase (gpd), Alternaria major allergen (Alt a 1), RNA polymerase second largest subunit gene (RPB2) and translation elongation factor 1-alpha (TEF 1) were amplified and sequenced using the primers ITS4/ITS5, RPB2-5F/RPB2-7CR, gpd1/gpd2, EF1-728F/EF1-986R, and Alt-for/Alt-rev respectively (Woudenberg et al. 2015). The sequences of representative isolate (XR) were uploaded in GenBank (ITS: OM319521, RPB2: OM849248, gpd: OM296240, TEF1: OM238122, and Alt a 1: OM649814). The bootstrap value of the isolate and the type strain CBS 595.93 (ITS: KP124320, RPB2: KP124788, gpd: KP124175, TEF1: KP125096, and Alt a 1: JQ646399) on the phylogenetic tree was 99%. Therefore, based on morphology and phylogenetic analysis the fungus was identified as A. alternata. To verify pathogenicity, a spore suspension (1 × 106 conidia/ml) of the representative isolate XR was misted onto the foliage of six twenty-day-old non-symptomatic plants. Six additional plants were sprayed with distilled water and used as controls. The plants were covered with plastic bags for 48 h and incubated at a temperature of 28℃ in the dark. Eight days later, all inoculated plants demonstrated similar symptoms as recorded on the original source, while the control plants were symptomless. The experiment was repeated three times with similar results. A. alternata was re-isolated from the artificially inoculated plants, hence fulfilling Koch's postulates. To our best knowledge this is the first report of leaf blight caused by A. alternata in China on E. ciliate. The disease may be an economic threat and should be further monitored and studied.

[Clinical and genetic analysis of a child with Canavan disease due to compound heterozygous variants of ASPA gene].

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease. METHODS: A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c.556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION: The c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

Brownian dynamics simulations of mesoscale chromatin fibers.

The relationship between chromatin architecture and function defines a central problem in biology and medicine. Many computational chromatin models with atomic, coarse-grained, mesoscale, and polymer resolution have been used to shed light onto the mechanisms that dictate genome folding and regulation of gene expression. The associated simulation techniques range from Monte Carlo to molecular, Brownian, and Langevin dynamics. Here, we present an efficient Compute Unified Device Architecture (CUDA) implementation of Brownian dynamics (BD) to simulate chromatin fibers at the nucleosome resolution with our chromatin mesoscale model. With the CUDA implementation for computer architectures with graphic processing units (GPUs), we significantly accelerate compute-intensive hydrodynamic tensor calculations in the BD simulations by massive parallelization, boosting the performance a hundred-fold compared with central processing unit calculations. We validate our BD simulation approach by reproducing experimental trends on fiber diffusion and structure as a function of salt, linker histone binding, and histone-tail composition, as well as Monte Carlo equilibrium sampling results. Our approach proves to be physically accurate with performance that makes feasible the study of chromatin fibers in the range of kb or hundreds of nucleosomes (small gene). Such simulations are essential to advance the study of biological processes such as gene regulation and aberrant genome-structure related diseases.

Electronic Structure Modulation of Nickel Sites by Cationic Heterostructures to Optimize Ethanol Electrooxidation Activity in Alkaline Solution.

It is a good idea for efficient production of hydrogen to use ethanol oxidation reaction (EOR) in place of oxygen evolution reaction (OER) in water electrolysis process. Ni-based non-precious electrocatalysts are widely used in the conversion of ethanol to acetic acid. Here, different selenide heterostructures (NiCoSe, NiFeSe, and NiCuSe) are prepared in which Ni sites are regulated by transition metal. The valence state of Ni is NiCuSe < NiCoSe < NiFeSe in the three heterojunctions. NiCoSe shows the optimized charge distribution of Ni sites and outstanding catalytic activity. The effective modulations lead to optimized d-band center and facilitates both adsorption and desorption of reaction intermediates, which improves the kinetics of EOR. The results of this work prove that with appropriate designed catalyst it is possible to replace kinetically slow OER with faster EOR in water electrolysis to produce hydrogen.

High-speed real 3D scene acquisition and 3D holographic reconstruction system based on ultrafast optical axial scanning.

The lack of three-dimensional (3D) content is one of the challenges that have been faced by holographic 3D display. Here, we proposed a real 3D scene acquisition and 3D holographic reconstruction system based on ultrafast optical axial scanning. An electrically tunable lens (ETL) was used for high-speed focus shift (up to 2.5 ms). A CCD camera was synchronized with the ETL to acquire multi-focused image sequence of real scene. Then, the focusing area of each multi-focused image was extracted by using Tenengrad operator, and the 3D image were obtained. Finally, 3D holographic reconstruction visible to the naked eye can be achieved by the layer-based diffraction algorithm. The feasibility and effectiveness of the proposed method have been demonstrated by simulation and experiment, and the experimental results agree well with the simulation results. This method will further expand the application of holographic 3D display in the field of education, advertising, entertainment, and other fields.

Sildenafil Improves Pulmonary Vascular Remodeling in a Rat Model of Persistent Pulmonary Hypertension of the Newborn.

ABSTRACT: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by pulmonary arterial remodeling mainly because of apoptosis resistance and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Sildenafil is a phosphodiesterase-5 inhibitor. Some reports have shown that sildenafil exerts protective effects against PPHN. However, the function of sildenafil in PPHN and the underlying molecular mechanisms is not clear. Here, we revealed that sildenafil effectively suppressed hypoxia-induced PASMC proliferation and apoptosis inhibition ( P < 0.05). Also, sildenafil obviously reduced ventricular hypertrophy, and inhibited pulmonary vascular remodeling in the PPHN model ( P < 0.05). Moreover, sildenafil treatment significantly attenuated the induction of Notch3 and Hes1 induced by hypoxia treatment ( P < 0.05). Furthermore, overexpression of Notch3 abolished the reduction of PASMC proliferation and promotion of PASMC apoptosis induced by sildenafil under hypoxia ( P < 0.05), whereas knockdown of Notch3 had an opposite effect ( P < 0.05). Together, our study demonstrates that sildenafil shows a potential benefit against the development of PPHN by inhibiting Notch3 signaling, providing a strategy for treating PPHN in the future.