Kled: an ultra-fast and sensitive structural variant detection tool for long-read sequencing data.

Structural Variants (SVs) are a crucial type of genetic variant that can significantly impact phenotypes. Therefore, the identification of SVs is an essential part of modern genomic analysis. In this article, we present kled, an ultra-fast and sensitive SV caller for long-read sequencing data given the specially designed approach with a novel signature-merging algorithm, custom refinement strategies and a high-performance program structure. The evaluation results demonstrate that kled can achieve optimal SV calling compared to several state-of-the-art methods on simulated and real long-read data for different platforms and sequencing depths. Furthermore, kled excels at rapid SV calling and can efficiently utilize multiple Central Processing Unit (CPU) cores while maintaining low memory usage. The source code for kled can be obtained from https://github.com/CoREse/kled.

A Simplified Linearized Lattice Boltzmann Method for Acoustic Propagation Simulation.

A simplified linearized lattice Boltzmann method (SLLBM) suitable for the simulation of acoustic waves propagation in fluids was proposed herein. Through Chapman-Enskog expansion analysis, the linearized lattice Boltzmann equation (LLBE) was first recovered to linearized macroscopic equations. Then, using the fractional-step calculation technique, the solution of these linearized equations was divided into two steps: a predictor step and corrector step. Next, the evolution of the perturbation distribution function was transformed into the evolution of the perturbation equilibrium distribution function using second-order interpolation approximation of the latter at other positions and times to represent the nonequilibrium part of the former; additionally, the calculation formulas of SLLBM were deduced. SLLBM inherits the advantages of the linearized lattice Boltzmann method (LLBM), calculating acoustic disturbance and the mean flow separately so that macroscopic variables of the mean flow do not affect the calculation of acoustic disturbance. At the same time, it has other advantages: the calculation process is simpler, and the cost of computing memory is reduced. In addition, to simulate the acoustic scattering problem caused by the acoustic waves encountering objects, the immersed boundary method (IBM) and SLLBM were further combined so that the method can simulate the influence of complex geometries. Several cases were used to validate the feasibility of SLLBM for simulation of acoustic wave propagation under the mean flow.

Long-read sequencing settings for efficient structural variation detection based on comprehensive evaluation.

BACKGROUND: With the rapid development of long-read sequencing technologies, it is possible to reveal the full spectrum of genetic structural variation (SV). However, the expensive cost, finite read length and high sequencing error for long-read data greatly limit the widespread adoption of SV calling. Therefore, it is urgent to establish guidance concerning sequencing coverage, read length, and error rate to maintain high SV yields and to achieve the lowest cost simultaneously. RESULTS: In this study, we generated a full range of simulated error-prone long-read datasets containing various sequencing settings and comprehensively evaluated the performance of SV calling with state-of-the-art long-read SV detection methods. The benchmark results demonstrate that almost all SV callers perform better when the long-read data reach 20× coverage, 20 kbp average read length, and approximately 10-7.5% or below 1% error rates. Furthermore, high sequencing coverage is the most influential factor in promoting SV calling, while it also directly determines the expensive costs. CONCLUSIONS: Based on the comprehensive evaluation results, we provide important guidelines for selecting long-read sequencing settings for efficient SV calling. We believe these recommended settings of long-read sequencing will have extraordinary guiding significance in cutting-edge genomic studies and clinical practices.

Long-range assembly of sequences helps to unravel the genome structure and small variation of the wheat-Haynaldia villosa translocated chromosome 6VS.6AL.

Genomics studies in wild species of wheat have been limited due to the lack of references; however, new technologies and bioinformatics tools have much potential to promote genomic research. The wheat-Haynaldia villosa translocation line T6VS·6AL has been widely used as a backbone parent of wheat breeding in China. Therefore, revealing the genome structure of translocation chromosome 6VS·6AL will clarify how this chromosome formed and will help to determine how it affects agronomic traits. In this study, chromosome flow sorting, NGS sequencing and Chicago long-range linkage assembly were innovatively used to produce the assembled sequences of 6VS·6AL, and gene prediction and genome structure characterization at the molecular level were effectively performed. The analysis discovered that the short arm of 6VS·6AL was actually composed of a large distal segment of 6VS, a small proximal segment of 6AS and the centromere of 6A, while the collinear region in 6VS corresponding to 230-260 Mb of 6AS-Ta was deleted when the recombination between 6VS and 6AS occurred. In addition to the molecular mechanism of the increased grain weight and enhanced spike length produced by the translocation chromosome, it may be correlated with missing GW2-V and an evolved NRT-V cluster. Moreover, a fine physical bin map of 6VS was constructed by the high-throughput developed 6VS-specific InDel markers and a series of newly identified small fragment translocation lines involving 6VS. This study will provide essential information for mining of new alien genes carried by the 6VS·6AL translocation chromosome.

In-situ growth of electrically conductive MOFs in wood cellulose scaffold for flexible, robust and hydrophobic membranes with improved electrochemical performance.

Electrically conductive metal-organic frameworks (EC-MOFs) have attracted great attentions in electrochemical fields, but their practical application is limited by their hard-to-shape powder form. The aims was to integrate continuously nucleated EC-MOFs on natural wood cellulose scaffold to develop biobased EC-MOFs membrane with robust flexibility and improved electrochemical performance for wearable supercapacitors. EC-MOF materials (NiCAT or CuCAT) were successfully incorporated onto porous tempo-oxidized wood (TOW) scaffold to create ultrathin membranes through electrostatic force-mediated interfacial growth and simple room-temperature densification. The studies demonstrated the uniform and continuous EC-MOFs nanolayer on TOW scaffold and the interfacial bonding between EC-MOF and TOW. The densification of EC-MOF@TOW bulk yielded highly flexible ultrathin membranes (about 0.3 mm) with high tensile stress exceeding 180 MPa. Moreover, the 50 %-NiCAT@TOW membrane demonstrated high electrical conductivity (4.227 S·m-1) and hydrophobicity (contact angle exceeding 130°). Notably, these properties remained stable even after twisting or bending deformation. Furthermore, the electrochemical performance of EC-MOF@TOW membrane with hierarchical pores outperformed the EC-MOF powder electrode. This study innovatively anchored EC-MOFs onto wood through facile process, yielding highly flexible membranes with exceptional performance that outperforms most of reported conductive wood-based membranes. These findings would provide some references for flexible and functional EC-MOF/wood membranes for wearable devices.

Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment.

The brain and gut are intricately connected and respond to various stimuli. Stress-induced brain-gut communication is implicated in the pathogenesis and relapse of gut disorders. The mechanism that relays psychological stress to the intestinal epithelium, resulting in maladaptation, remains poorly understood. Here, we describe a stress-responsive brain-to-gut metabolic axis that impairs intestinal stem cell (ISC) lineage commitment. Psychological stress-triggered sympathetic output enriches gut commensal Lactobacillus murinus, increasing the production of indole-3-acetate (IAA), which contributes to a transferrable loss of intestinal secretory cells. Bacterial IAA disrupts ISC mitochondrial bioenergetics and thereby prevents secretory lineage commitment in a cell-intrinsic manner. Oral α-ketoglutarate supplementation bolsters ISC differentiation and confers resilience to stress-triggered intestinal epithelial injury. We confirm that fecal IAA is higher in patients with mental distress and is correlated with gut dysfunction. These findings uncover a microbe-mediated brain-gut pathway that could be therapeutically targeted for stress-driven gut-brain comorbidities.

Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.

Structural Variant Detection from Long-Read Sequencing Data with cuteSV.

Structural Variation (SV) represents genomic rearrangements and is strongly associated with human health and disease. Recently, long-read sequencing technologies provide the opportunity to more comprehensive identification of SVs at an ever-high resolution. However, under the circumstance of high sequencing errors and the complexity of SVs, there remains lots of technical issues to be settled. Hence, we propose cuteSV, a sensitive, fast, and scalable alignment-based SV detection approach to complete comprehensive discovery of diverse SVs. The benchmarking results indicate cuteSV is suitable for large-scale genome project since its excellent SV yields and ultra-fast speed. Here, we explain the overall framework for providing a detailed outline for users to apply cuteSV correctly and comprehensively. More details are available at https://github.com/tjiangHIT/cuteSV .

MicroRNA-126 engineered muscle-derived stem cells attenuates cavernosa injury-induced erectile dysfunction in rats.

BACKGROUND: Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury. METHODS: MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken. RESULTS: On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126. CONCLUSIONS: MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.

Role of treatment with human chorionic gonadotropin and clinical parameters on testicular sperm recovery with microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in 184 Klinefelter syndrome patients.

OBJECTIVE: To investigate whether preoperative human chorionic gonadotropin (hCG) treatment can help predict the outcomes of microdissection testicular sperm extraction (micro-TESE) and affect fertility outcomes in non-mosaic Klinefelter syndrome (KS) patients. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): A total of 184 non-mosaic KS patients who underwent micro-TESE with or without preoperative hCG treatment from January 2016 to July 2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm retrieval rate (SRR) with and without hCG treatment, logistic models analysis. RESULT(S): Eighty KS patients (43.5%) had successful sperm retrievals after micro-TESE. There was no statistically significant difference in the SRR between the group who received hCG treatment and the group that did not (44.0% vs. 43.3%). Logistic regression analyses demonstrated that the hCG treatment had no statistically significant effect on successful sperm retrieval. However, higher preoperative testosterone (T) levels seemed to be associated with a higher probability of successful sperm retrieval (multivariate adjusted odds ratio 1.09; 95% confidence interval [CI], 1.04-1.16). The prediction model for SRR on KS patients had an area under the curve of 67.3% (95% CI, 59.3-75.3%). In the hCG treatment group, the data indicated that the three parameters of testicular volume, pretreatment T level, and alterations of T were associated with the probability of successful sperm retrieval. Moreover, hCG therapy did not affect intracytoplasmic sperm injection (ICSI) outcomes. No differences in the pregnancy rate or live-birth rate were observed between the two groups. CONCLUSION(S): Therapy with hCG does not affect SRR or ICSI outcomes of non-mosaic KS patients. However, preoperative T levels, whether treated with hCG or not, can predict the chance of sperm retrieval with micro-TESE.

A malectin-like/leucine-rich repeat receptor protein kinase gene, RLK-V, regulates powdery mildew resistance in wheat.

Pattern recognition receptors (PRRs) can trigger plant immunity through the recognition of pathogen-associated molecular patterns. In this study, we report that a malectin-like/leucine-rich repeat receptor protein kinase gene, RLK-V, from Haynaldia villosa putatively acts as a PRR to positively regulate powdery mildew resistance caused by Blumeria graminis f. sp. tritici (Bgt) in wheat. RLK-V has two alternatively spliced transcripts corresponding to an intact RLK-V1.1 and a truncated RLK-V1.2 caused by intron retention. Expression analysis showed that both transcripts could be up-regulated by Bgt in resistant materials, whereas the functional RLK-V1.1 was expressed only after Bgt inoculation. Promoter activity assays indicated that RLK-V could respond to Bgt even in susceptible wheat. Silencing of RLK-V in Pm21-carrying resistant materials resulted in compromised resistance to Bgt. In addition, over-expression of RLK-V1.1 in Pm21-lacking susceptible Yangmai158 and SM-1 by single-cell transient expression and stable transformation in Yangmai158 could improve powdery mildew resistance. We propose that RLK-V regulates basal resistance to powdery mildew, which is also required for broad-spectrum resistance mediated by the Pm21 gene. Over-expression of RLK-V1.1 could trigger cell death in Nicotiana benthamiana, and RLK-V1.1 transgenic wheat accumulated more reactive oxygen species and displayed a stronger hypersensitive response than did the recipient, which led to enhanced Bgt resistance. However, constitutive activation of RLK-V1.1 resulted in the abnormal growth of transgenic plants.

A synthetic route to ultralight hierarchically micro/mesoporous Al(III)-carboxylate metal-organic aerogels.

Developing a synthetic methodology for the fabrication of hierarchically porous metal-organic monoliths that feature high surface area, low density and tunable porosity is imperative for mass transfer applications, including bulky molecule capture, heterogeneous catalysis and drug delivery. Here we report a versatile and facile synthetic route towards ultralight micro/mesoporous metal-organic aerogels based on the two-step gelation of metal-organic framework nanoparticles. Heating represents a key factor in the control of gelation versus crystallization of Al(III)-multicarboxylate systems. The porosity of the resulting metal-organic aerogels can be readily tuned, leading to the formation of well-ordered intraparticle micropores and aerogel-specific interparticle mesopores, thereby integrating the merits of both crystalline metal-organic frameworks and light aerogels. The hierarchical micro/mesoporosity of the Al-metal-organic aerogels is thoroughly evaluated by N2 sorption. The good accessibility of the micro/mesopores is verified by vapour/dye uptake, and their potential for utilization as effective fibre-coating absorbents is tested in solid-phase microextraction analyses.