Basis Of Function Research Articles

Anatomy and mobility in the adult cadaveric craniocervical junction

AbstractGenetic diseases with craniofacial malformations can be associated with anomalies of the craniocervical joint (CCJ). The functions of the CCJ are thus impaired, as mobility may be either limited by abnormal bone fusion causing headaches, or exaggerated in the case of hypermobility, which may cause irreparable damage to the spinal cord. Restoring the balance between mobility and stability requires surgical correction in children. The anatomy and biomechanics of the CCJ are quite unique, yet have been overlooked in the past decades. Pediatric evidence is so scarce, that investigating the adult CCJ is our best shot to disentangle the form‐function relationships of this anatomical region. The motivation of the present study was to understand the morphological and functional basis of motion in the CCJ, in the hope to find morphological features accessible from medical imaging able to predict mobility. To do so, we have quantified the in‐vitro kinematics of the CCJ in nine cadaveric asymptomatic adults, and estimated a wide range of mobility variables covering the complexity of spinal motion. We compared these variables with the shape of the occipital, the atlas and the axis, obtained using a dense geometric morphometric approach. Morphological joint congruence was also quantified. Our results suggest a strong relationship between bone shape and motion, with the overall geometry predicting best the primary movements, and the joint facets predicting best the secondary movements. We propose a functional hypothesis stating that the musculoligamental system determines movements of great amplitude, while the shape and congruence of joint facets determine the secondary and coupled movements, especially by varying the geometry of bone stops and the way ligaments are tensioned. We believe this work will provide valuable insights in understanding the biomechanics of the CCJ. Furthermore, it should help surgeons treating CCJ anomalies by enabling them to translate objectives of functional and clinical outcome into clear objectives of morphological outcome.

АНАЛІЗ ТА НАПРЯМИ ПІДВИЩЕННЯ ЕФЕКТИВНОСТІ УПРАВЛІНСЬКИХ РІШЕНЬ У СФЕРІ СТІЙКОСТІ БІЗНЕСУ В УМОВАХ КРИЗИ

The object of the study is the process of maintaining viability and ensuring the development of enterprises in crisis conditions. It was established that for such purposes, the formation and implementation of tools and means of anti-crisis management, aimed at strengthening the stability of the business entity in crisis conditions, becomes critically relevant. It is emphasized that in the conditions of a crisis caused by a full-scale war, the emphasis and prerogatives in the management of sustainability change for the sake of stability and orderliness of the functioning and development of economic entities. It is additionally argued that in crisis situations, the focus of attention shifts from issues of high efficiency to the task of preventing challenges and threats, when the subject of attention is the economic security of business, the relevant mechanisms and tools for ensuring it. Based on these principles, the purpose of the study is to analyze and identify directions for improving the effectiveness of management decisions in the field of business sustainability in crisis conditions. The implementation of the specified goal made it possible to develop a complex of means of improvement and development of anti-crisis management systems of domestic enterprises. According to the results of the survey of managers of domestic enterprises, their low activity in the field of business sustainability management and the concentration of measures in this field mainly only on monitoring the financial and economic condition of the enterprise were established, the current market situation and its changing trends, assortment, quality and price parameters of the products presented on the market. The leading factors that weaken the state of stability of domestic enterprises have been identified, which remain the unstable market conditions, in particular demand, pressure from competitors, insufficiently high level of development of the industry and related types of economic activity, underdevelopment of the product sales system, lack of material and technical and technical and technological support of enterprises. It has been proven that the difficulties of the war lead to the complication of the survival conditions of economic entities and, accordingly, require greater efforts of domestic enterprises to preserve their own financial and economic stability. The structural and functional basis for improving management in the field of managing the stability of domestic enterprises in crisis conditions through the rationalization of their strategic marketing management, which involves the implementation of measures of a financial-economic, organizational-production, intellectual-personnel, and socio-economic nature, is substantiated. An aggregated structural model of anti-crisis management in the area of guaranteeing the sustainability of domestic enterprises has been developed.

Reduced inhibitory synaptic transmission onto striatopallidal neurons may underlie aging-related motor skill deficits

Human beings are living longer than ever before and aging is accompanied by an increased incidence of motor deficits, including those associated with the neurodegenerative conditions, Parkinson's disease (PD) and Huntington's disease (HD). However, the biological correlates underlying this epidemiological finding, especially the functional basis at the synapse level, have been elusive. This study reveals that motor skill performance examined via rotarod, beam walking and pole tests is impaired in aged mice. This study, via electrophysiology recordings, further identifies an aging-related reduction in the efficacy of inhibitory synaptic transmission onto dorsolateral striatum (DLS) indirect-pathway medium spiny neurons (iMSNs), i.e., a disinhibition effect on DLS iMSNs. In addition, pharmacologically enhancing the activity of DLS iMSNs by infusing an adenosine A2A receptor (A2AR) agonist, which presumably mimics the disinhibition effect, impairs motor skill performance in young mice, simulating the behavior in aged naïve mice. Conversely, pharmacologically suppressing the activity of DLS iMSNs by infusing an A2AR antagonist, in order to offset the disinhibition effect, restores motor skill performance in aged mice, mimicking the behavior in young naïve mice. In conclusion, this study identifies a functional inhibitory synaptic plasticity in DLS iMSNs that likely contributes to the aging-related motor skill deficits, which would potentially serve as a striatal synaptic basis underlying age being a prominent risk factor for neurodegenerative motor deficits.

Bijective upsampling and learned embedding for point clouds correspondences

In this paper, we present a novel pipeline to compute and refine a data-driven solution for estimating the correspondence between 3D point clouds. Our method is compatible with the functional map framework, so it relies on a functional representation of the correspondence, but, differently from other similar approaches, this method is specifically designed to exploit this functional scenario for point cloud matching. Our new method merges a data-driven approach to compute functional basis and descriptors on the shape’s surface and a new refinement method designed for the learned basis. This refinement algorithm arises from a different way of converting functional operators into point-to-point correspondence, which we prove to promote bijectivity between maps, exploiting a theoretical result. Iterating this procedure and performing basis upsampling in the same way as other similar methods, ours increases the accuracy of the correspondence, leading to more bijective correspondences. Different from other approaches, our method allows us to train a functional basis, considering the refinement stage. Combining our new pipeline with an improved feature extractor, our solution outperforms previous methods in various evaluations and settings. We test our method over different datasets, comprising near-isometric and non-isometric pairs.

Cloud-based serverless computing enables accelerated monte carlo simulations for nuclear medicine imaging

Objective. This study investigates the potential of cloud-based serverless computing to accelerate Monte Carlo (MC) simulations for nuclear medicine imaging tasks. MC simulations can pose a high computational burden—even when executed on modern multi-core computing servers. Cloud computing allows simulation tasks to be highly parallelized and considerably accelerated. Approach. We investigate the computational performance of a cloud-based serverless MC simulation of radioactive decays for positron emission tomography imaging using Amazon Web Service (AWS) Lambda serverless computing platform for the first time in scientific literature. We provide a comparison of the computational performance of AWS to a modern on-premises multi-thread reconstruction server by measuring the execution times of the processes using between 105 and 2·1010 simulated decays. We deployed two popular MC simulation frameworks—SimSET and GATE—within the AWS computing environment. Containerized application images were used as a basis for an AWS Lambda function, and local (non-cloud) scripts were used to orchestrate the deployment of simulations. The task was broken down into smaller parallel runs, and launched on concurrently running AWS Lambda instances, and the results were postprocessed and downloaded via the Simple Storage Service. Main results. Our implementation of cloud-based MC simulations with SimSET outperforms local server-based computations by more than an order of magnitude. However, the GATE implementation creates more and larger output file sizes and reveals that the internet connection speed can become the primary bottleneck for data transfers. Simulating 109 decays using SimSET is possible within 5 min and accrues computation costs of about $10 on AWS, whereas GATE would have to run in batches for more than 100 min at considerably higher costs. Significance. Adopting cloud-based serverless computing architecture in medical imaging research facilities can considerably improve processing times and overall workflow efficiency, with future research exploring additional enhancements through optimized configurations and computational methods.

Abstract PO-020: ZBTB24 is a novel tumor suppressor and cooperates with CDKN2A to suppress B-cell lymphomagenesis

Abstract B-cell lymphoma is the most common hematological malignancy that accounts for the sixth highest mortality among all cancers. Despite recent improvements on combined chemotherapy and immunotherapy, treatments remain challenging due to complex genetic heterogeneity and molecular pathogenesis. To explore novel mechanisms in B-cell lymphomagenesis, we performed a genome-wide CRISPR knockout screen in the murine interleukin-3 (IL-3)-dependent Ba/F3 pro-B cell line and identified Zbtb24 as a putative target whose silencing leads to elevated proliferative signaling and reduced apoptosis, conferring IL-3-independent growth in Ba/F3 cells. Silencing of ZBTB24 also accelerated growth in multiple human B-cell lymphoma cell lines. ZBTB24 is a member of the zinc-finger and BTB domain containing transcription factor that is highly expressed in spleen and bone marrow. While it has been shown that ZBTB24 may play an important role in B-cell development and activation, its involvement in B-cell lymphoma has not been described. Analysis of publicly available datasets found that ZBTB24 copy number deletion occurs in various B-cell lymphomas, which frequently co-occurs with deletion of the tumor suppressor CDKN2A. Hence, we generated B-cell specific Zbtb24 single knockout and Zbtb24/Cdkn2a double knockout mice to explore the role of Zbtb24 in vivo. While Zbtb24 and Cdkn2a single knockout mice remained tumor-free or showed low penetrance of tumorigenesis, the double knockout mice developed lymphadenopathy and splenomegaly accompanied with accelerated mortality. Flow cytometry analysis of bone marrow, spleen, and lymph nodes revealed malignant B-cells. Subsequent transplantation of the splenic cells induced identical malignant B-cell lymphomagenesis and immunophenotype in athymic nude mice, further confirming its malignant identity. These results indicate that ZBTB24 is a novel tumor suppressor in B-cell malignancy. Ongoing studies are being conducted to understand the mechanistic basis for ZBTB24 tumor suppressive function that may involve transcriptional regulation of its target gene expression. This project is supported by the NIH R01CA232246, R01CA129536, and the John Colaizzi Endowment Fund. Citation Format: Rongrong Li, Namratha Sheshadri, Jianliang Shen, Junrong Yan, Jaeyong Jung, Muhammad Usama Tariq, Y Lynn Wang, Ping Xie, Wei-Xing Zong. ZBTB24 is a novel tumor suppressor and cooperates with CDKN2A to suppress B-cell lymphomagenesis [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-020.

Transformation to a geminal basis and stationary conditions for the exact wave function therein

We show the transformation from a one-particle basis to a geminal basis, transformations between different geminal bases demonstrate the Lie algebra of a geminal basis. From the basis transformations, we express both the wave function and Hamiltonian in the geminal basis. The necessary and sufficient conditions of the exact wave function expanded in a geminal basis are shown to be a Brillouin theorem of geminals. The variational optimization of the geminals in the antisymmetrized geminal power (AGP), antisymmetrized product of geminals (APG) and the full geminal product (FGP) wave function ansätze are discussed. We show that using a geminal replacement operator to describe geminal rotations introduce both primary and secondary rotations. The secondary rotations rotate two geminals in the reference at the same time due to the composite boson nature of geminals. Due to the completeness of the FGP, where all possible geminal combinations are present, the FGP is exact. The number of parameters in the FGP scale exponentially with the number of particles, like the full configuration interaction (FCI). Truncation in the FGP expansion can give compact representations of the wave function since the reference function in the FGP can be either the AGP or APG wave function.

Scalable chlorination of polypropylene for structural modification and flame retardancy as coating materials of insulation cable

ABSTRACT Chemical precipitation route has been demonstrated for in-situ chlorination of polypropylene and structural modification to integrate flame retardancy along with facile processing parameters, i.e. optimum melt flow index and mechanical properties. Thus, obtained chlorinated polypropylene (Cl-PP) was characterized for optimized composition and degree of chlorination, chemical structure, morphology, physical properties with the help of infra-red spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), melt flow index and other standard methods. The analytical results revealed the 74% chlorination of polypropylene chain increased with the molecular weight, comparable melt flow index and improved flame retardancy from V2 to V0 grade on UL-94 scale due to reduced heat release rate and improved limiting oxygen index from 17.5 to 27.1 due to structural changes and induced polycrystallinity. The evolved features of PP were explained on the basis of synergistic interaction, evolved crystallinity, size reduction and functionality during chemical treatments and reprecipitations. Further, the obtained Cl-PP was explored as the coating material for insulation of cables with electric insulation and durable properties.

Practical Approach to Nuclear Shelter Wall Thickness Estimation

Abstract In the complex situation in which we live, preventive measures are increasingly being taken against the threat of nuclear attack and ionizing radiation, nuclear shelters are being built for private and public purposes. The purpose of the authors is to provide a practical approach to quickly calculate the thickness of the concrete shelter wall for such cases. The shelter wall thickness is assessed on the basis of published data on radiation dose calculations, corroborated by field data from nuclear tests, and information or calculations of the dose attenuation in the shelter wall. Doses from nuclear tests or simulations are summarized in tables in relation to bomb yield and distance from the explosion point. A dose criterion is chosen as the acceptable dose behind the shield. Neutron dose transmission factors, defined as ratio of the dose criterion to the dose without shielding are calculated. The concrete wall thickness corresponding to the neutron dose transmission factor was taken from reference sources. For gamma rays, the shield thickness is calculated based on an analytical relationship between dose without shield, the dose criterion, and the shield thickness. Data tables are provided with the estimated concrete wall thickness in relation to bomb yield and distance.

CDC48A, an interactor of WOX2, is required for embryonic patterning in Arabidopsis thaliana

Key messageInteractor of WOX2, CDC48A, is crucial for early embryo patterning and shoot meristem stem cell initiation, but is not required for WOX2 protein turnover or subcellular localization.During Arabidopsis embryo patterning, the WUSCHEL HOMEOBOX 2 (WOX2) transcription factor is a major regulator of protoderm and shoot stem cell initiation. Loss of WOX2 function results in aberrant protodermal cell divisions and, redundantly with its paralogs WOX1, WOX3, and WOX5, compromised shoot meristem formation. To elucidate the molecular basis for WOX2 function, we searched for protein interactors by IP–MS/MS from WOX2-overexpression roots displaying reprogramming toward shoot-like cell fates. Here, we report that WOX2 directly interacts with the type II AAA ATPase molecular chaperone CELL DIVISION CYCLE 48A (CDC48A). We confirmed this interaction with bimolecular fluorescence complementation and co-immunoprecipitation and found that both proteins co-localize in the nucleus. We show that CDC48A loss of function results in protoderm and shoot meristem stem cell initiation defects similar to WOX2 loss of function. We also provide evidence that CDC48A promotes WOX2 activity independently of proteolysis or the regulation of nuclear localization, common mechanisms of CDC48A function in other processes. Our results point to a new role of CDC48A in potentiating WOX2 function during early embryo patterning.

Forest 3D Radar Reflectivity Reconstruction at X-Band Using a Lidar Derived Polarimetric Coherence Tomography Basis

Tomographic Synthetic Aperture Radar (SAR) allows the reconstruction of the 3D radar reflectivity of forests from a large(r) number of multi-angular acquisitions. However, in most practical implementations it suffers from limited vertical resolution and/or reconstruction artefacts as the result of non-ideal acquisition setups. Polarisation Coherence Tomography (PCT) offers an alternative to traditional tomographic techniques that allow the reconstruction of the low-frequency 3D radar reflectivity components from a small(er) number of multi-angular SAR acquisitions. PCT formulates the tomographic reconstruction problem as a series expansion on a given function basis. The expansion coefficients are estimated from interferometric coherence measurements between acquisitions. In its original form, PCT uses the Legendre polynomial basis for the reconstruction of the 3D radar reflectivity. This paper investigates the use of new basis functions for the reconstruction of X-band 3D radar reflectivity of forests derived from available lidar waveforms. This approach enables an improved 3D radar reflectivity reconstruction with enhanced vertical resolution, tailored to individual forest conditions. It also allows the translation from sparse lidar waveform vertical reflectivity information into continuous vertical reflectivity estimates when combined with interferometric SAR measurements. This is especially relevant for exploring the synergy of actual missions such as GEDI and TanDEM-X. The quality of the reconstructed 3D radar reflectivity is assessed by comparing simulated InSAR coherences derived from the reconstructed 3D radar reflectivity against measured coherences at different spatial baselines. The assessment is performed and discussed for interferometric TanDEM-X acquisitions performed over two tropical Gabonese rainforest sites: Mondah and Lopé. The results demonstrate that the lidar-derived basis provides more physically realistic vertical reflectivity profiles, which also produce a smaller bias in the simulated coherence validation, compared to the conventional Legendre polynomial basis.

Peran Media Sosial dalam Meningkatkan Partisipasi Politik Masyarakat di Desa Candirejo Kecamatan Biru-Biru Kabupaten Deli Serdang

This research discusses the role of social media in increasing community political participation in Candirejo village, Biru Biru subdistrict, Deli Serdang district. Social media is a potential tool for the government to shape public opinion and influence political participation. In the context of a democratic country like Indonesia, public opinion has a crucial role. because it is the basis for government functions, this research uses a qualitative descriptive method, the research stage is carried out by collecting data, interviews, observations and analysis, the results of the research show that social media plays a vital role in political participation and the formation of public opinion in the digital era, with an impact good and bad. Nevertheless, the government needs to monitor political activities in the modern social media era. Social media is not only a communication platform, but also a place for information seeking, discussion and networking. This research aims to find out how social media shapes political participation in society using a qualitative descriptive approach. The research results show that social media has a significant influence in engaging, connecting, and mobilizing political participation, although the receipt of political information via social media may vary between individuals.

Molecular basis for different substrate-binding sites and chaperone functions of the BRICHOS domain.

Proteins can misfold into fibrillar or amorphous aggregates and molecular chaperones act as crucial guardians against these undesirable processes. The BRICHOS chaperone domain, found in several otherwise unrelated proproteins that contain amyloidogenic regions, effectively inhibits amyloid formation and toxicity but can in some cases also prevent non-fibrillar, amorphous protein aggregation. Here, we elucidate the molecular basis behind the multifaceted chaperone activities of the BRICHOS domain from the Bri2 proprotein. High-confidence AlphaFold2 and RoseTTAFold predictions suggest that the intramolecular amyloidogenic region (Bri23) is part of the hydrophobic core of the proprotein, where it occupies the proposed amyloid binding site, explaining the markedly reduced ability of the proprotein to prevent an exogenous amyloidogenic peptide from aggregating. However, the BRICHOS-Bri23 complex maintains its ability to form large polydisperse oligomers that prevent amorphous protein aggregation. A cryo-EM-derived model of the Bri2 BRICHOS oligomer is compatible with surface-exposed hydrophobic motifs that get exposed and come together during oligomerization, explaining its effects against amorphous aggregation. These findings provide a molecular basis for the BRICHOS chaperone domain function, where distinct surfaces are employed against different forms of protein aggregation.

Trace amine associated receptor 1: predicted effects of single nucleotide variants on structure-function in geographically diverse populations

Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmaceutical target under investigation for the treatment of several neuropsychiatric conditions. TAAR1 single nucleotide variants (SNV) have been found in patients with schizophrenia and metabolic disorders. However, the frequency of variants in geographically diverse populations and the functional effects of such variants are unknown. In this study, we aimed to characterise the distribution of TAAR1 SNVs in five different WHO regions using the Database of Genotypes and Phenotypes (dbGaP) and conducted a critical computational analysis using available TAAR1 structural data to identify SNVs affecting ligand binding and/or functional regions. Our analysis shows 19 orthosteric, 9 signalling and 16 micro-switch SNVs hypothesised to critically influence the agonist induced TAAR1 activation. These SNVs may non-proportionally influence populations from discrete regions and differentially influence the activity of TAAR1-targeting therapeutics in genetically and geographically diverse populations. Notably, our dataset presented with orthosteric SNVs D1033.32N (found only in the South-East Asian Region and Western Pacific Region) and T1945.42A (found only in South-East Asian Region), and 2 signalling SNVs (V1253.54A/T2526.36A, found in African Region and commonly, respectively), all of which have previously demonstrated to influence ligand induced functions of TAAR1. Furthermore, bioinformatics analysis using SIFT4G, MutationTaster 2, PROVEAN and MutationAssessor predicted all 16 micro-switch SNVs are damaging and may further influence the agonist activation of TAAR1, thereby possibly impacting upon clinical outcomes. Understanding the genetic basis of TAAR1 function and the impact of common mutations within clinical populations is important for the safe and effective utilisation of novel and existing pharmacotherapies.

Scenario-based anticipatory failure determination and patent technology inspiration for product innovation design

Exploring opportunities of technologies for product is critical in the highly competitive market. Anticipatory failure determination (AFD) identifies likely failure modes of a product, which provides a tool to explore the technology opportunities for product improvement. The existing methods of AFD are limited in the failure analysis of system components and the acquisition of technical solutions for the failure cause is depending on designer experience. This research proposes an approach to product innovation design based on the scenario-based evolution of AFD and patent technology inspiration. Scenarios obtained based on the proposed scenario generation rules are used to form failure events from the product function level. The failure events are then used to explore technical opportunities based on the anticipatory failure determination. A word vector model is trained with the patent data to extract patent technology terms in combination with the semantic similarity of the functional basis. The Latent Dirichlet Allocation (LDA) is used to cluster patent technologies. The best technical solution is finally selected based on the relative technology maturity and technological distance. The TRIZ tool is used to resolve possible conflicting problems. A complete product innovation design process is proposed from the technology opportunity exploration to concept design formation.

Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies.

Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have been approved yet. The haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins of hPIV3 are major antigenic determinants. Here we describe naturally occurring potently neutralizing human antibodies directed against both surface glycoproteins of hPIV3. We isolated seven neutralizing HN-reactive antibodies and a pre-fusion conformation F-reactive antibody from human memory B cells. One HN-binding monoclonal antibody (mAb), designated PIV3-23, exhibited functional attributes including haemagglutination and neuraminidase inhibition. We also delineated the structural basis of neutralization for two HN and one F mAbs. MAbs that neutralized hPIV3 in vitro protected against infection and disease in vivo in a cotton rat model of hPIV3 infection, suggesting correlates of protection for hPIV3 and the potential clinical utility of these mAbs.

Molecular Basis of Energy Crops Functioning in Bioremediation of Heavy Metal Pollution

Heavy metal pollution is a gradually growing environmental issue that hinders the growth and development of plants, and also destabilizes soil. Consequently, eco-friendly phytoremediation methods have gained traction, with energy crops emerging as a particularly effective solution. Energy crops not only provide high-quality plant materials for detoxification and remediation of heavy metal pollution, but also possess energy properties conducive to biofuel production. Therefore, this paper delves into the tolerance mechanism of energy crops towards heavy metal toxicity, elucidating processes such as root complex-mediated inhibition of metal migration and response to reactive oxygen species (ROS) through heavy metal-related proteins, enzyme systems, reactive nitrogen species (RNS), and hormones. Moreover, it summarizes the heavy metals remediation mechanisms of energy crops, including uptake, translocation, chelation, immobilization, and sequestration. This paper explores applications of energy crops in heavy metal pollution remediation, emphasizing the methods for efficient biochar remediation and biofuel generation. Furthermore, potential challenges in using energy crops for heavy metal pollution remediation are outlined. By systematically examining the function mechanisms and prospective applications of energy crops in heavy metal pollution bioremediation, this paper serves as a valuable reference for both research and practical implementation in this field.

Target analyses by transcriptome sequencing in peripheral blood cells of grass carp: Potent immune responses in leukocytes and thrombocytes against bacterial and viral infections

Fishes provide abundant protein for humanity, while they are ravaging by bacterial and viral diseases. The defense based on peripheral blood cell immunity is an important means to resist pathogenic infections. However, the immune response of different blood cell communities to bacterial or viral infection remains largely unknown. In this study, grass carp (Ctenopharyngodon idella), the most productive fish in the world, was employed to comprehensively investigate the immune responses of erythrocytes, leukocytes, and thrombocytes after Aeromonas hydrophila or type II grass carp reovirus (GCRV-II) infection by transcriptome sequencing. The data of 45 samples with small intra-group and large inter-group differences were obtained. There were 3921, 15,378, 7019 DEGs in the infected erythrocytes, leukocytes, and thrombocytes, respectively. Through GO and KEGG analysis, they were mainly enriched in the items related to innate and adaptive immunity, including pattern recognition receptor signaling pathways and cytokine signaling pathways. Therefore, we conducted target analyses of vital immune families, including TLRs, RLRs, IFNs, IRFs, immune activators, and antigen presentation genes, systematically clarified the immune responses of blood cells to pathogenic infections. All the three types of blood cells expressed a large number of immune genes involved in anti-infection to varying degrees, among them leukocytes and thrombocytes responded aggressively. This study provides implications for the function of peripheral blood cells and the functional basis of immune genes in pathogenic infections.

Systematic Characterization of Triterpenoids in Ganoderma lucidum by UHPLC-Q/TOF MS

Background: Ganoderma lucidum, which is widely used as “Ganoderma” in China or other Asian countries (Japan, Korea, etc), exerts an important role in tonifying qi and calming the mind in clinical applications. Triterpenoids are the main active components in Ganoderma lucidum, with significant biological activities of hepatoprotective, anticancer, and anti-tumor, etc. However, the current analysis of triterpenoids in Ganoderma lucidum by mass spectrometry is limited, restricting its quality control and elucidation of its functional basis. Objective: This work aimed to systematically characterize the triterpenoids in Ganoderma lucidum. Methods: The Ganoderma lucidum powder was extracted by 50% ethanol/water and separated by Waters ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm). The data was obtained by Waters G2-Q-TOF mass spectrometry equipped with an electrospray ionization ion (ESI) source, and the MS data under positive and negative modes was acquired and analyzed. Results: A total of 43 triterpenoids were identified or tentatively characterized from the extracts of Ganoderma lucidum, including 32 known compounds and 11 potential new compounds. Among them, five triterpenoids were unambiguously identified by comparison with reference standards, including ganoderic acid A(28), ganoderic acid D(36), ganoderenic acid D(34), ganoderic acid F(43), and ganoderic acid G(16). The profiled triterpenoids could be divided into eight types according to the substituents at the C3, C7 and C15 positions of the parent structure. The mass fragmentation rules of Ganoderma lucidum triterpenoids were summarized. Under the positive ion mode, Ganoderma lucidum triterpenoids easily lost CH3 at the C10 position and H2O at C3, C7, and C15 positions, and the side chain bond at the C22(23) position was easily split. Under the negative ion mode, the split of the C and D rings was the characteristic feature. result: A total of 43 triterpenoids were identified or tentatively characterized from the extracts of Ganoderma lucidum, including 32 known compounds and 11 potential new compounds. Among them, five triterpenoids were unambitiously identified by comparison with reference standards, including ganoderic acid A(28), ganoderic acid D(36), ganoderenic acid D(34), ganoderic acid F(43), and ganoderic acid G(16). These triterpenoids could be divided into eight types according to the substituents at the C3, C7 and C15 positions of the parent structure. The mass fragmentation rules of Ganoderma lucidum triterpenoids were summarized. Under the positive ion mode, Ganoderma lucidum triterpenoids easily lost CH3 at the C10 position and H2O at C3, C7, C15 position, and the side chain bond at C22(23) position was easily cracked. Under the negative ion mode, the crack of the C and D rings was the characteristic feature. Conclusion: The mass fragmentation behaviors of Ganoderma lucidum triterpenoids under positive ion mode were summarized and emphasized, and reliable scientific data and methods for systematic characterization of Ganoderma lucidum triterpenoids were also supplied.

Unveiling the Druggable Landscape of Bacterial Peptidyl tRNA Hydrolase: Insights into Structure, Function, and Therapeutic Potential.

Bacterial peptidyl tRNA hydrolase (Pth) or Pth1 emerges as a pivotal enzyme involved in the maintenance of cellular homeostasis by catalyzing the release of peptidyl moieties from peptidyl-tRNA molecules and the maintenance of a free pool of specific tRNAs. This enzyme is vital for bacterial cells and an emerging drug target for various bacterial infections. Understanding the enzymatic mechanisms and structural intricacies of bacterial Pth is pivotal in designing novel therapeutics to combat antibiotic resistance. This review provides a comprehensive analysis of the multifaceted roles of Pth in bacterial physiology, shedding light on its significance as a potential drug target. This article delves into the diverse functions of Pth, encompassing its involvement in ribosome rescue, the maintenance of a free tRNA pool in bacterial systems, the regulation of translation fidelity, and stress response pathways within bacterial systems. Moreover, it also explores the druggability of bacterial Pth, emphasizing its promise as a target for antibacterial agents and highlighting the challenges associated with developing specific inhibitors against this enzyme. Structural elucidation represents a cornerstone in unraveling the catalytic mechanisms and substrate recognition of Pth. This review encapsulates the current structural insights of Pth garnered through various biophysical techniques, such as X-ray crystallography and NMR spectroscopy, providing a detailed understanding of the enzyme's architecture and conformational dynamics. Additionally, biophysical aspects, including its interaction with ligands, inhibitors, and substrates, are discussed, elucidating the molecular basis of bacterial Pth's function and its potential use in drug design strategies. Through this review article, we aim to put together all the available information on bacterial Pth and emphasize its potential in advancing innovative therapeutic interventions and combating bacterial infections.