Competence Regulation in Streptococcus pneumoniae and the Competence-targeted Anti-pneumococcal Strategies.

Natural transformation refers to the process in which bacteria acquire new traits by uptaking naked DNA from the environment and integrating it into their genome through homologous recombination when they are in the specialized physiological state of competence. The natural transformation was first described in Streptococcus pneumoniae. Since Frederick Griffith first described natural transformations in S. pneumoniae in 1928, this phenomenon has been studied extensively. Induction of competence before natural transformation has been reported to involve about 10% of the pneumococcal genome. In addition to natural transformation, multiple physiological processes are involved, including biofilm formation, bacteriocin production, and fratricide. In this review, we summarized current knowledge about natural transformation in S. pneumoniae and described its competence regulation mechanism. This review also introduces the development of novel drugs and vaccines against S. pneumoniae infection by utilizing the existing knowledge of competence and natural transformation.

Simulation study on electroporation of cancer cells in multicellular system.

Electroporation (EP) of the normal cell and cancer cell both in single-cell and multicellular models was investigated by the meshed transport network method (MTNM) in this paper. The simulation results suggest that the cancer cell undergoes faster and more significant local EP than that of the corresponding normal cell induced by nanosecond pulsed electric fields (nsPEFs) both in single-cell and multicellular models. Furthermore, the results of the multicellular model indicate that there is a unidirectional neighboring effect in the multicellular model, meaning that cells at the center are affected and their pore formation is significantly reduced, but this effect is very weak for cells at the edges of the system. This means that the electric field selectively kills cells in different distribution locations. This work can provide guidance for the selection of parameters for the cancer cell EP process.

Three-dimensional high-aspect-ratio microarray thick electrodes for high-rate hybrid supercapacitors.

Hybrid supercapacitors (HSCs) with facile integration and high process compatibility are considered ideal power sources for portable consumer electronics. However, as a crucial component for storing energy, traditional thin-film electrodes exhibit low energy density. Although increasing the thickness of thin films can enhance the energy density of the electrodes, it gives rise to issues such as poor mechanical stability and long electron/ion transport pathways. Constructing a stable three-dimensional (3D) ordered thick electrode is considered the key to addressing the aforementioned contradictions. In this work, a manufacturing process combining lithography and chemical deposition techniques is developed to produce large-area and high-aspect-ratio 3D nickel ordered cylindrical array (NiOCA) current collectors. Positive electrodes loaded with nickel-cobalt bimetallic hydroxide (NiOCA/NiCo-LDH) are constructed by electrodeposition, and HSCs are assembled with NiOCA/nitrogen-doped porous carbon (NiOCA/NPC) as negative electrodes. The HSCs exhibits 55% capacity retention with the current density ranging from 2 to 50 mA cm-2. Moreover, it maintains 98.2% of the initial capacity after long-term cycling of 15,000 cycles at a current density of 10 mA cm-2. The manufacturing process demonstrates customizability and favorable repeatability. It is anticipated to provide innovative concepts for the large-scale production of 3D microarray thick electrodes for high-performance energy storage system.

Research on Spatial Magnetic Field Distribution of Magnetic Fluids Based on Microstructure.

This study focuses on the spatial magnetic field distribution of magnetic fluids, an extraordinary class of fluids composed of magnetic nanoparticles (MNPs), employing the Monte Carlo method to simulate the microstructure of magnetic fluids under an external magnetic field. On that basis, a model was established through magnetic dipole theory to delve into the spatial magnetic field distribution of magnetic fluids. The findings reveal that the application of a magnetic field leads to the formation of chain-like structures within the magnetic fluids, resulting in inhomogeneous spatial magnetic field distribution. The size and concentration of MNPs are crucial determinants that significantly affect the microstructure of magnetic fluid and its spatial magnetic field distribution. Furthermore, environmental conditions such as external magnetic field strength or temperature can also regulate the positions of MNPs within magnetic fluids and the spatial magnetic field distribution of the magnetic fluids. These observations enrich the comprehension of the fundamental mechanisms of magnetic fluids and their response to diverse factors, advancing the growing comprehension on the characteristics and applications of these remarkable magnetic fluids.

Improving the Rechargeable Li-CO2 Battery Performances by Tailoring Oxygen Defects on Li-Ni-Co-Mn Multi-Metal Oxide Catalysts Recycled from Spent Ternary Lithium-Ion Batteries.

Rechargeable Li-CO2 batteries are considered as a promising carbon-neutral energy storage technology owing to their ultra-high energy density and efficient CO2 capture capability. However, the sluggish CO2 reduction/evolution kinetics impedes their practical application, which leads to huge overpotentials and poor cyclability. Multi-element transit metal oxides (TMOs) are demonstrated as effective cathodic catalysts for Li-CO2 batteries. But there are no reports on the integration of defect engineering on multi-element TMOs. Herein, the oxygen vacancy-bearing Li-Ni-Co-Mn multi-oxide (Re-NCM-H3) catalyst with the α-NaFeO2-type structure is first fabricated by annealing the NiCoMn precursor that derived from spent ternary LiNi0.8Co0.1Mn0.1O2 cathode, in H2 at 300 °C. As demonstrated by experimental results and theory calculations, the introduction of moderate oxygen vacancy has optimized electronic state near the Fermi level (Ef), eventually improving CO2 adsorption and charge transfer. Therefore, the Li-CO2 batteries with Re-NCM-H3 catalyst deliver a high capacity (11808.9 mAh g-1), a lower overpotential (1.54 V), as well as excellent stability over 216 cycles at 100 mA g-1 and 165 cycles at 400 mA g-1. This study not only opens up a sustainable application of spent ternary cathode, but also validates the potential of multi-element TMO catalysts with oxygen defects for high-efficiency Li-CO2 batteries.

Regional Pulmonary Ventilation Assessment Method and System Based on Impedance Sensing Information from the Pentapulmonary Lobes.

Regional lung ventilation assessment is a critical tool for the early detection of lung diseases and postoperative evaluation. Biosensor-based impedance measurements, known for their non-invasive nature, among other benefits, have garnered significant attention compared to traditional detection methods that utilize pressure sensors. However, solely utilizing overall thoracic impedance fails to accurately capture changes in regional lung air volume. This study introduces an assessment method for lung ventilation that utilizes impedance data from the five lobes, develops a nonlinear model correlating regional impedance with lung air volume, and formulates an approach to identify regional ventilation obstructions based on impedance variations in affected areas. The electrode configuration for the five lung lobes was established through numerical simulations, revealing a power-function nonlinear relationship between regional impedance and air volume changes. An analysis of 389 pulmonary function tests refined the equations for calculating pulmonary function parameters, taking into account individual differences. Validation tests on 30 cases indicated maximum relative errors of 0.82% for FVC and 0.98% for FEV1, all within the 95% confidence intervals. The index for assessing regional ventilation impairment was corroborated by CT scans in 50 critical care cases, with 10 validation trials showing agreement with CT lesion localization results.

Selective intrafascicular stimulation of myelinated and unmyelinated nerve fibers through a longitudinal electrode: A computational study.

Carbon nanotube (CNT) fiber electrodes have demonstrated exceptional spatial selectivity and sustained reliability in the context of intrafascicular electrical stimulation, as evidenced through rigorous animal experimentation. A significant presence of unmyelinated C fibers, known to induce uncomfortable somatosensory experiences, exists within peripheral nerves. This presence poses a considerable challenge to the excitation of myelinated Aß fibers, which are crucial for tactile sensation. To achieve nuanced tactile sensory feedback utilizing CNT fiber electrodes, the selective stimulation of Aß sensory afferents emerges as a critical factor. In confronting this challenge, the present investigation sought to refine and apply a rat sciatic-nerve model leveraging the capabilities of the COMSOL-NEURON framework. This approach enables a systematic evaluation of the influence exerted by stimulation parameters and electrode geometry on the activation dynamics of both myelinated Aß and unmyelinated C fibers. The findings advocate for the utilization of current pulses featuring a pulse width of 600 µs, alongside the deployment of CNT fibers characterized by a diminutive diameter of 10 µm, with an exclusively exposed cross-sectional area, to facilitate reduced activation current thresholds. Comparative analysis under monopolar and bipolar electrical stimulation conditions revealed proximate activation thresholds, albeit with bipolar stimulation exhibiting superior fiber selectivity relative to its monopolar counterpart. Concerning pulse waveform characteristics, the adoption of an anodic-first biphasic stimulation modality is favored, taking into account the dual criteria of activation threshold and fiber selectivity optimization. Consequently, this investigation furnishes an efficacious stimulation paradigm for the selective activation of touch-related nerve fibers, alongside provisioning a comprehensive theoretical foundation for the realization of natural tactile feedback within the domain of prosthetic hand applications.

CaSTH2 disables CaWRKY40 from activating pepper thermotolerance and immunity against Ralstonia solanacearum via physical interaction.

CaWRKY40 coordinately activates pepper immunity against Ralstonia solanacearum infection (RSI) and high temperature stress (HTS), forms positive feedback loops with other positive regulators and is promoted by CaWRKY27b/CaWRKY28 through physical interactions; however, whether and how it is regulated by negative regulators to function appropriately remain unclear. Herein, we provide evidence that CaWRKY40 is repressed by a SALT TOLERANCE HOMOLOG2 in pepper (CaSTH2). Our data from gene silencing and transient overexpression in pepper and epoptic overexpression in Nicotiana benthamiana plants showed that CaSTH2 acted as negative regulator in immunity against RSI and thermotolerance. Our data from BiFC, CoIP, pull down, and MST indicate that CaSTH2 interacted with CaWRKY40, by which CaWRKY40 was prevented from activating immunity or thermotolerance-related genes. It was also found that CaSTH2 repressed CaWRKY40 at least partially through blocking interaction of CaWRKY40 with CaWRKY27b/CaWRKY28, but not through directly repressing binding of CaWRKY40 to its target genes. The results of study provide new insight into the mechanisms underlying the coordination of pepper immunity and thermotolerance.

Mechanisms of action of Shizhenqing granules for eczema treatment: Network pharmacology analysis and experimental validation.

Background: Jiuwan decoction has been used to treat chronic eczema since the Qing Dynasty. According to clinical experience, Shizhenqing granules (SZQG), derived from the Jiuwan decoction, exert beneficial clinical effects on acute eczema and reduce recurrence. Therefore, we elucidated the underlying mechanisms of SZQG through network pharmacology, molecular docking, and experimental validation. Methods: The main chemical components of SZQG were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). And the targets of SZQG against eczema were screened out through online databases. Then, the regulatory network map of the "herbal compound-potential target" and the target protein-protein interaction (PPI) network was constructed. The Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using by R language. Additionally, the interaction between the active compounds and the targets was verified by molecular docking technology. Finally, an experiment in vivo was used to verify the effect and mechanism of SZQG on eczema. Results: Using UHPLC-MS/MS, 158 main chemical compounds of SZQG were identified, and 72 compounds were selected according to the criteria for further analysis. All 237 potential targets of SZQG in eczema were explored using multiple online databases. The network with 14 core targets was screened out, including STAT3, RELA, TNF, JUN, MAPK3, IL-6, PIK3CA, STAT1, MAPK14, MAPK1, IL-4, NFKBIA, IL1B, and MYC. KEGG analyses indicated that the therapeutic effects of SZQG on eczema were predominantly associated with cytokine-cytokine receptor interaction, TNF, MAPK, NF-κB, toll-like receptor, T cell receptor, and Th1 and Th2 cell differentiation signaling pathways. Furthermore, the good affinity between the core compounds and core targets was verified by molecular docking technology, particularly for RELA and MAPK. Animal experiments revealed that SZQG downregulated MAPK14, RELA, T-bet, and GATA3 mRNA expression, reduced immunoglobulin E (IgE) and interleukin-4 (IL-4) serum concentrations, and improved eczema-like lesions in model rats. Conclusion: This study identified potential targets and signaling pathways of SZQG in the treatment of eczema, whereby RELA and MAPK14 may constitute the main therapeutic targets of SZQG in cytokine regulation and reduction of inflammatory responses.

Development and validation of a nomogram for predicting the prognosis in children with spinal cord injuries.

AIMS: This research aims to construct and verify an accurate nomogram for forecasting the 3-, 5-, and 7-year outcomes in pediatric patients afflicted with spinal cord injury (SCI). METHODS: Pediatric patients with SCI from multiple hospitals in China, diagnosed between Jan 2005 and Jan 2020, were incorporated into this research. Half of these patients were arbitrarily chosen for training sets, and the other half were designated for external validation sets. The Cox hazard model was employed to pinpoint potential prognosis determinants related to the American Spinal Injury Association (ASIA) and Functional Independence Assessment (FIM) index. These determinants were then employed to formulate the prognostic nomogram. Subsequently, the bootstrap technique was applied to validate the derived model internally. RESULTS: In total, 224 children with SCI were considered for the final evaluation, having a median monitoring duration of 68.0 months. The predictive nomogram showcased superior differentiation capabilities, yielding a refined C-index of 0.924 (95% CI: 0.883-0.965) for the training cohort and a C-index of 0.863 (95% CI: 0.735-0.933) for the external verification group. Additionally, when applying the aforementioned model to prognostic predictions as classified by the FIM, it demonstrated a high predictive value with a C-index of 0.908 (95% CI: 0.863-0.953). Moreover, the calibration diagrams indicated a consistent match between the projected and genuine ASIA outcomes across both sets. CONCLUSION: The crafted and verified prognostic nomogram emerges as a dependable instrument to foresee the 3-, 5-, and 7-year ASIA and FIM outcomes for children suffering from SCI.

A nomogram for predicting the hospital-acquired infections in children with spinal cord injuries: a retrospective, multicenter, observational study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Hospital-acquired infections (HAIs) pose a significant risk for pediatric patients with spinal cord injuries (SCIs), potentially leading to extended hospital stays and increased morbidity. This study aims to identify patients at higher risk for HAIs. SETTING: Hospitals from multiple areas in China. METHODS: This retrospective study included 220 pediatric SCI patients from Jan 2005 to Dec 2023, divided into a training set (n = 154) and a validation set (n = 66). We conducted a multivariate logistic regression analysis to identify risk factors associated with HAIs and constructed a predictive nomogram. The model's performance was assessed using receiver operating characteristic (ROC) curves, area under the ROC curve (AUC) and calibration plots, while decision curve analysis was utilized to determine clinical utility. RESULTS: The nomogram incorporated age, time from injury to the hospital, history of urinary and pulmonary infections, urobilinogen positivity, damaged segments, and admission American Spinal Injury Association (ASIA) scores. The model demonstrated excellent discrimination in the training set (AUC = 0.957) and good discrimination in the validation set (AUC = 0.919). Calibration plots indicated an acceptable fit between predicted probabilities and observed outcomes. Decision curve analysis confirmed the model's net benefit over clinical decision thresholds in both sets. CONCLUSION: We developed and validated a predictive nomogram for HAIs in pediatric SCI patients that shows promise for clinical application. The model can assist healthcare providers in identifying patients at higher risk for HAIs, potentially facilitating early interventions and improved patient care strategies.

Open reduction after failed closed reduction following failed Pavlik harness treatment in developmental dysplasia of the hip: One- or two-stage?

INTRODUCTION: The current published evidence for the treatment of developmental dysplasia of the hip (DDH) with failed closed reduction (CR) following failed Pavlik harness (PH) treatment is still limited. This study aimed to determine whether an one-stage open reduction (OR) would lead to a similar outcome to a two-stage OR in these patients. Meanwhile, the occurrence of femoral head avascular necrosis (AVN) and further surgery (pelvic osteotomy, PO) within the follow-up period was investigated. MATERIALS AND METHODS: A consecutive series of DDH patients who failed CR following failed PH treatment and received OR finally between January 2008 and December 2020 were studied. The patients were divided into two groups. One group of which received OR immediately after failed CR (one-stage OR group, Group A), and the other received a delayed OR (two-stage OR group, Group B). The McKay's criteria, acetabular index (AI) and the degree of dislocation of the hips were evaluated for the final outcomes. RESULTS: At the last follow-up, 54 (84.4%) of the 64 hips in Group A and 26 (83.9%) of 31 hips in Group B were in excellent or good condition. Comparison between the two groups revealed that there were no differences in terms of McKay grading (P = 0.950), AI (P = 0.783), incidence of AVN (P = 0.745), and also incidence of PO (P = 1.000). However, a significant lower mean AI was found in Group A, when the OR was performed in Group B (31.06 ± 4.45° vs. 33.87 ± 4.12°, P = 0.004). CONCLUSION: Both of the one- and two-stage OR may acheive favorable outcomes. Moreover, one-stage OR is of without the general anesthesia risk associated with two-stage OR. We therefore advocate that an OR should be performed in appropriate DDH patients during the same session once a failed CR is detected.

Temperature-dependent action of pepper mildew resistance locus O 1 in inducing pathogen immunity and thermotolerance.

Plant diseases tend to be more serious under conditions of high-temperature/high-humidity (HTHH) than under moderate conditions, and hence disease resistance under HTHH is an important determinant for plant survival. However, how plants cope with diseases under HTHH remains poorly understood. In this study, we used the pathosystem consisting of pepper (Capsicum annuum) and Ralstonia solanacearum (bacterial wilt) as a model to examine the functions of the protein mildew resistance locus O 1 (CaMLO1) and U-box domain-containing protein 21 (CaPUB21) under conditions of 80% humidity and either 28 °C or 37 °C. Expression profiling, loss- and gain-of-function assays involving virus-induced gene-silencing and overexpression in pepper plants, and protein-protein interaction assays were conducted, and the results showed that CaMLO1 acted negatively in pepper immunity against R. solanacearum at 28 °C but positively at 37 °C. In contrast, CaPUB21 acted positively in immunity at 28 °C but negatively at 37 °C. Importantly, CaPUB21 interacted with CaMLO1 under all of the tested conditions, but only the interaction in response to R. solanacearum at 37 °C or to exposure to 37 °C alone led to CaMLO1 degradation, thereby turning off defence responses against R. solanacearum at 37 °C and under high-temperature stress to conserve resources. Thus, we show that CaMLO1 and CaPUB21 interact with each other and function distinctly in pepper immunity against R. solanacearum in an environment-dependent manner.

Suppressing the false magnetic field in beam-splitting Faraday rotation measurement.

In laser-plasma experiments, the beam-splitting Faraday rotation measurement is usually used for mapping the magnetic field. Due to the geometric characteristics of the beam-splitting configuration, the split beams are not always incident normally on the image plane, and their spots have different shapes and intensity distributions. Ignoring these issues will inevitably introduce errors in polarization calculation and then generate large false magnetic fields. We introduced the restoration method to recover the spots and suppress the false magnetic field. We applied this method to ZEMAX simulation data and Shenguang-II experimental data. Compared to the method of directly overlaying the spots, it can reduce the average false magnetic field by about 50%. And the false magnetic field at the edge of the spot is reduced by one order of magnitude. We can highly improve the accuracy of the magnetic field measurement with the Faraday rotation method.

Characterization of Chromatin Accessibility in Fetal Bovine Chondrocytes.

Despite significant advances of the bovine epigenome investigation, new evidence for the epigenetic basis of fetal cartilage development remains lacking. In this study, the chondrocytes were isolated from long bone tissues of bovine fetuses at 90 days. The Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) were used to characterize gene expression and chromatin accessibility profile in bovine chondrocytes. A total of 9686 open chromatin regions in bovine fetal chondrocytes were identified and 45% of the peaks were enriched in the promoter regions. Then, all peaks were annotated to the nearest gene for Gene Ontology (GO) and Kyoto Encylopaedia of Genes and Genomes (KEGG) analysis. Growth and development-related processes such as amide biosynthesis process (GO: 0043604) and translation regulation (GO: 006417) were enriched in the GO analysis. The KEGG analysis enriched endoplasmic reticulum protein processing signal pathway, TGF-ß signaling pathway and cell cycle pathway, which are closely related to protein synthesis and processing during cell proliferation. Active transcription factors (TFs) were enriched by ATAC-seq, and were fully verified with gene expression levels obtained by RNA-seq. Among the top50 TFs from footprint analysis, known or potential cartilage development-related transcription factors FOS, FOSL2 and NFY were found. Overall, our data provide a theoretical basis for further determining the regulatory mechanism of cartilage development in bovine.

Customizable Metal Micromesh Electrode Enabling Flexible Transparent Zn-Ion Hybrid Supercapacitors with High Energy Density.

Emerging flexible and wearable electronic products are placing a compelling demand on lightweight transparent energy storage devices. Owing to their distinguishing features of safety, high specific energy, cycling stability, and rapid charge/discharge advantages, Zn-ion hybrid supercapacitors are a current topic of discussion. However, the trade-off for optical transmittance and energy density remains a great challenge. Here, a high-performance Zn-ion hybrid supercapacitor based on the customizable ultrathin (5 µm), ultralight (0.45 mg cm-2 ), and ultra-transparent (87.6%) Ni micromesh based cathode and Zn micromesh anode with the highest figure of merit (84 843) is proposed. The developed flexible transparent Zn-ion hybrid supercapacitors reveal excellent cycle stability (no decline after 20 000 cycles), high areal energy density (31.69 µWh cm-2 ), and high power density (512 µW cm-2 ). In addition, the assembled solid flexible and transparent Zn-ion hybrid supercapacitor with polyacrylamide gel electrolyte shows extraordinary mechanical properties even under extreme bending and twisting operation. Furthermore, the full device displays a high optical transmittance over 55.04% and can be conformally integrated with diverse devices as a flexible transparent power supply. The fabrication technology offers seamless compatibility with industrial manufacturing, making it an ideal model for the advancement of portable and wearable devices.

Identification of cis-acting elements upstream of regR gene in streptococcus pneumoniae.

The identification and characterization of functional cis-acting elements is of fundamental importance for comprehending the regulatory mechanisms of gene transcription and bacterial pathogenesis. The transcription factor RegR has been demonstrated to control both competence and virulence in Streptococcus pneumoniae. Despite the clear contribution of RegR to these pathways, the mechanisms underlying its transcriptional regulation remain poorly understood. In this study, we conducted mutational analysis, gene dissection and luciferase activity assays to characterize the cis-elements situated upstream of the regR gene. Our findings revealed that a 311 bp 3'-terminal DNA sequence of the spd0300 gene represents a central region of the upstream cis-acting element of regR. Further investigations identified two structurally similar enhancer-like sequences within this region which feature prominently in the regulation of regR transcription. Furthermore, employing DNA pull-down assays allowed us to enrich the trans-acting factors with the potential to interact with these cis-acting elements. Notably, we found that the competence regulator ComE was implicated in the regulation of regR transcription, a finding which was corroborated by electrophoretic mobility shift assays (EMSA) and quantitative real-time PCR analyses (qRT-PCR). Taken together, our data thus provide fresh insight into the transcriptional regulation of regR.

Differential CaKAN3-CaHSF8 associations underlie distinct immune and heat responses under high temperature and high humidity conditions.

High temperature and high humidity (HTHH) conditions increase plant susceptibility to a variety of diseases, including bacterial wilt in solanaceous plants. Some solanaceous plant cultivars have evolved mechanisms to activate HTHH-specific immunity to cope with bacterial wilt disease. However, the underlying mechanisms remain poorly understood. Here we find that CaKAN3 and CaHSF8 upregulate and physically interact with each other in nuclei under HTHH conditions without inoculation or early after inoculation with R. solanacearum in pepper. Consequently, CaKAN3 and CaHSF8 synergistically confer immunity against R. solanacearum via activating a subset of NLRs which initiates immune signaling upon perception of unidentified pathogen effectors. Intriguingly, when HTHH conditions are prolonged without pathogen attack or the temperature goes higher, CaHSF8 no longer interacts with CaKAN3. Instead, it directly upregulates a subset of HSP genes thus activating thermotolerance. Our findings highlight mechanisms controlling context-specific activation of high-temperature-specific pepper immunity and thermotolerance mediated by differential CaKAN3-CaHSF8 associations.

The effect of the subthreshold oscillation induced by the neurons' resonance upon the electrical stimulation-dependent instability.

Repetitive electrical nerve stimulation can induce a long-lasting perturbation of the axon's membrane potential, resulting in unstable stimulus-response relationships. Despite being observed in electrophysiology, the precise mechanism underlying electrical stimulation-dependent (ES-dependent) instability is still an open question. This study proposes a model to reveal a facet of this problem: how threshold fluctuation affects electrical nerve stimulations. This study proposes a new method based on a Circuit-Probability theory (C-P theory) to reveal the interlinkages between the subthreshold oscillation induced by neurons' resonance and ES-dependent instability of neural response. Supported by in-vivo studies, this new model predicts several key characteristics of ES-dependent instability and proposes a stimulation method to minimize the instability. This model provides a powerful tool to improve our understanding of the interaction between the external electric field and the complexity of the biophysical characteristics of axons.

The eQTL colocalization and transcriptome-wide association study identify potentially causal genes responsible for economic traits in Simmental beef cattle.

BACKGROUND: A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle. To prioritize the putative variants and genes, we ran a comprehensive genome-wide association studies (GWAS) analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle. Then, we applied expression quantitative trait loci (eQTL) mapping between the genotype variants and transcriptome of three tissues (longissimus dorsi muscle, backfat, and liver) in 120 cattle. RESULTS: We identified 1,580 association signals for 21 beef agronomic traits using GWAS. We then illuminated 854,498 cis-eQTLs for 6,017 genes and 46,970 trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits. These cis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions. We observed an average of 43.5% improvement in cis-eQTL discovery using multi-tissue eQTL mapping. Fine-mapping analysis revealed that 111, 192, and 194 variants were most likely to be causative to regulate gene expression in backfat, liver, and muscle, respectively. The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits. Via the colocalization and Mendelian randomization analyses, we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues, which included genes, such as NADSYN1, NDUFS3, LTF and KIFC2 in liver, GRAMD1C, TMTC2 and ZNF613 in backfat, as well as TIGAR, NDUFS3 and L3HYPDH in muscle that could serve as the candidate genes for economic traits. CONCLUSIONS: The extensive atlas of GWAS, eQTL, fine-mapping, and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.