Metabolites and metabolic pathway analysis of sulfadimidine in carp (Cyprinus carpio) based on UHPLC-Q-orbitrap HRMS.

Sulfadimidine (SM2) is an N-substituted derivative of p-aminobenzenesulfonyl structure. This study aimed to analyze the metabolism of SM2 in carp (Cyprinus carpio). The carps were fed with SM2 at a dose of 200 mg/(kg · bw) and then killed. The blood, muscle, liver, kidney, gill, other guts, and carp aquaculture water samples were collected. The UHPLC-Q-Exactive Plus Orbitrap-MS was adopted for determining the metabolites of SM2 in the aforementioned samples. Twelve metabolites, which were divided into metabolites in vivo and metabolites in vitro, were identified using Compound Discoverer software. The metabolic pathways in vivo of SM2 in carp included acetylation, hydroxylation, glucoside conjugation, glycine conjugation, carboxylation, glucuronide conjugation, reduction, and methylation. The metabolic pathways in vitro included oxidation and acetylation. This study clarified the metabolites and metabolic pathways of SM2 in carp and provided a reference for further pharmacodynamic evaluation and use in aquaculture.

Towards a structural and functional analysis of the immunoglobulin-fold proteome.

The immunoglobulin fold (Ig fold) domain is a super-secondary structural motif consisting of a sandwich with two layers of ß-sheets that is present in many proteins with very diverse biological functions covering a wide range of physiological processes. This domain presents a modular architecture built with ß strands connected by variable length loops that has a highly conserved structural core of four ß-strands and quite variable ß-sheet extensions in the two sandwich layers that enable both divergent and convergent evolutionary mechanisms in the known Ig fold proteome. The central role of this Ig fold's structural plasticity in the evolutionary success of antibodies in our immune system is well established. Nature has also utilized this Ig fold in all domains of life in many different physiological contexts that go way beyond the immune system. Here we will present a structural and functional overview of the utilization of the Ig fold in different biological processes and in different cellular contexts to highlight some of the innumerable ways that this structural motif can interact in multidomain proteins to enable their diversity of functions. This includes shareable specific protein structure visualizations behind those functions that serve as starting points for further explorations of the biomolecular interactions spanning the Ig fold proteome. This overview also highlights how this Ig fold is being utilized through natural adaptation, engineering, and even building from scratch for a range of biotechnological applications.

Database resources of the National Center for Biotechnology Information.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, SciENcv, the NIH Comparative Genomics Resource (CGR), NCBI Virus, SRA, RefSeq, foreign contamination screening tools, Taxonomy, iCn3D, ClinVar, GTR, MedGen, dbSNP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

Enhancing ion mobility spectrometry performance through a programmable ion swarm shaping method based on Bradbury-Nielsen gates.

The ion gate is a critical element in drift tube ion mobility spectrometry (IMS) as it directly influences the resolving power and sensitivity of the system. However, the conventional Bradbury-Nielsen gate (BNG) often leads to deformation of the ion swarm shape, resulting in reduced resolving power and significant discrimination effects. To address these limitations, we propose a novel method that incorporates a cutting phase following the gate opening. This approach effectively reduces trailing edge deformation, resulting in a maximum resolving power of over 100 and increased signal intensity. Additionally, this method maintains high resolving power even during longer gate opening times. Remarkably, this method not only significantly reduces the mobility discrimination effect but also enables the achievement of reverse discrimination by adjusting the duration of the cutting phase. Consequently, it demonstrates the potential to selectively amplify the peak height of target ions. Our method offers straightforward implementation across all IMS systems utilizing the BNG, thereby significantly improving system performance.

Hierarchical Style-Aware Domain Generalization for Remote Physiological Measurement.

The utilization of remote photoplethysmography (rPPG) technology has gained attention in recent years due to its ability to extract blood volume pulse (BVP) from facial videos, making it accessible for various applications such as health monitoring and emotional analysis. However, the BVP signal is susceptible to complex environmental changes or individual differences, causing existing methods to struggle in generalizing for unseen domains. This article addresses the domain shift problem in rPPG measurement and shows that most domain generalization methods fail to work well in this problem due to ambiguous instance-specific differences. To address this, the article proposes a novel approach called Hierarchical Style-aware Representation Disentangling (HSRD). HSRD improves generalization capacity by separating domain-invariant and instance-specific feature space during training, which increases the robustness of out-of-distribution samples during inference. This work presents state-of-the-art performance against several methods in both cross and intra-dataset settings.

Coal Structure Characteristics of the 2# Coal Seam in the Jiaozuo Mining Area and Its Geological Dependence.

To clarify the coal structure, spatial distribution, and controlling factors of the 2# coal seam in Jiaozuo mining, the drilling coal samples were collected to observe the coal type and coal structure. The coal macerals were identified by a MPVSP microscope photometer, and the spatial characteristics of the coal structure were obtained through interpreting deep lateral resistivity logging, natural gamma ray logging, density logging, and acoustic logging curves. The influence of coal properties, burial depth, geological stress, and faults on the coal structure were discussed correspondingly. The results exhibit that granulitic-mylonite coal was most developed in the 2# coal seam, followed by primary coal and cataclastic coal; the coal type was dominated by semibright coal, followed by clarain and semidull coal. Granulitic-mylonite, cataclastic, and primary coals were the main components of clarain, semibright coal, and semidull coal, respectively. Higher vitrinite and organic matter contents were conducive to the development of granulitic-mylonite. The coal structure combinations were spatially varied, and the granulitic-mylonite combinations were the most common. Granulitic-mylonite coal was developed in the east and south parts of the study area, and the coal structure was fragmented with a greater burial depth and larger thickness. The geological stress is the fundamental cause of coal structure damage as well as the cutting of faults.

Vision-Based Automated Recognition and 3D Localization Framework for Tower Cranes Using Far-Field Cameras.

Tower cranes can cover most of the area of a construction site, which brings significant safety risks, including potential collisions with other entities. To address these issues, it is necessary to obtain accurate and real-time information on the orientation and location of tower cranes and hooks. As a non-invasive sensing method, computer vision-based (CVB) technology is widely applied on construction sites for object detection and three-dimensional (3D) localization. However, most existing methods mainly address the localization on the construction ground plane or rely on specific viewpoints and positions. To address these issues, this study proposes a framework for the real-time recognition and localization of tower cranes and hooks using monocular far-field cameras. The framework consists of four steps: far-field camera autocalibration using feature matching and horizon-line detection, deep learning-based segmentation of tower cranes, geometric feature reconstruction of tower cranes, and 3D localization estimation. The pose estimation of tower cranes using monocular far-field cameras with arbitrary views is the main contribution of this paper. To evaluate the proposed framework, a series of comprehensive experiments were conducted on construction sites in different scenarios and compared with ground-truth data obtained by sensors. The experimental results show that the proposed framework achieves high precision in both crane jib orientation estimation and hook position estimation, thereby contributing to the development of safety management and productivity analysis.

3DVizSNP: a tool for rapidly visualizing missense mutations identified in high throughput experiments in iCn3D.

BACKGROUND: High throughput experiments in cancer and other areas of genomic research identify large numbers of sequence variants that need to be evaluated for phenotypic impact. While many tools exist to score the likely impact of single nucleotide polymorphisms (SNPs) based on sequence alone, the three-dimensional structural environment is essential for understanding the biological impact of a nonsynonymous mutation. RESULTS: We present a program, 3DVizSNP, that enables the rapid visualization of nonsynonymous missense mutations extracted from a variant caller format file using the web-based iCn3D visualization platform. The program, written in Python, leverages REST APIs and can be run locally without installing any other software or databases, or from a webserver hosted by the National Cancer Institute. It automatically selects the appropriate experimental structure from the Protein Data Bank, if available, or the predicted structure from the AlphaFold database, enabling users to rapidly screen SNPs based on their local structural environment. 3DVizSNP leverages iCn3D annotations and its structural analysis functions to assess changes in structural contacts associated with mutations. CONCLUSIONS: This tool enables researchers to efficiently make use of 3D structural information to prioritize mutations for further computational and experimental impact assessment. The program is available as a webserver at https://analysistools.cancer.gov/3dvizsnp or as a standalone python program at https://github.com/CBIIT-CGBB/3DVizSNP .

IEDB-3D 2.0: Structural data analysis within the Immune Epitope Database.

The Immune Epitope Database (IEDB) catalogs T cell, B cell, and major histocompatibility complex ligand information in the context of infectious disease, allergy, autoimmunity, and transplantation. An important component of this information is three-dimensional structural data on T cell receptors, antibodies, and pairwise residue interactions between immune receptors and antigens, which we refer to as IEDB-3D. Such data is highly valuable for mechanically understanding receptor:ligand interactions. Here, we present IEDB-3D 2.0, which comprises a complete overhaul of how we obtain and present 3D structural data. A new 3D viewer experience that utilizes iCn3D has been implemented to replace outdated java-based technology. In addition, we have designed a new epitope mapping system that matches each epitope available in the IEDB with its antigen structural data. Finally, immunogenicity data retrieved from the IEDB's ImmunomeBrowser can now be used to highlight immunogenic regions of an antigen directly in iCn3D. Overall, the IEDB-3D 2.0 provides an updated tool platform to visualize epitope data cataloged in the IEDB.

Database resources of the National Center for Biotechnology Information in 2023.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. New resources include the Comparative Genome Resource (CGR) and the BLAST ClusteredNR database. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, IgBLAST, GDV, RefSeq, NCBI Virus, GenBank type assemblies, iCn3D, ClinVar, GTR, dbGaP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo.

OBJECTIVE: Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy. METHODS: The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression. RESULTS: rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity. CONCLUSION: Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.

The conserved domain database in 2023.

NLM's conserved domain database (CDD) is a collection of protein domain and protein family models constructed as multiple sequence alignments. Its main purpose is to provide annotation for protein and translated nucleotide sequences with the location of domain footprints and associated functional sites, and to define protein domain architecture as a basis for assigning gene product names and putative/predicted function. CDD has been available publicly for over 20 years and has grown substantially during that time. Maintaining an archive of pre-computed annotation continues to be a challenge and has slowed down the cadence of CDD releases. CDD curation staff builds hierarchical classifications of large protein domain families, adds models for novel domain families via surveillance of the protein 'dark matter' that currently lacks annotation, and now spends considerable effort on providing names and attribution for conserved domain architectures. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment.

BACKGROUND: Helicobacter pylori ( H. pylori ) infection is an infectious disease with a prevalence rate of up to 50% worldwide. It can cause indigestion, gastritis, peptic ulcer, and gastric cancer. H. pylori eradication treatment can effectively control disease progression and reduce the risk of the above conditions. However, the escalating trend of antibiotic resistance presents a global challenge for H. pylori eradication. We aim to provide guidance on pharmacological treatment of H. pylori infection. METHODS: This clinical practice guideline is developed following the World Health Organization's recommended process, adopting Grading of Recommendations Assessment, Development and Evaluation in assessing evidence quality, and utilizing Evidence to Decision framework to formulate clinical recommendations, minimizing bias and increasing transparency of the clinical practice guideline development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. RESULTS: Though decreasing in developed countries, the prevalence of H. pylori remains high in developing countries, causing a major public health burden. This clinical practice guideline contains 12 recommendations concerning pharmacological treatment for H. pylori eradication. Among them, it is worth highlighting that bismuth preparations are inexpensive, safe, and effective, consequently making bismuth quadruple therapy a preferred choice for initial and rescue treatment. In empirical treatment, high-dose dual therapy is equally effective compared with bismuth quadruple therapy. CONCLUSIONS: The 12 recommendations in this clinical practice guideline are formed with consideration for stakeholders' values and preferences, resource use, feasibility, and acceptability. Recommendations are generalizable to resource limited settings with similar antibiotic resistance pattern as China, and lower middle-income countries facing comparable sociological and technical challenges. REGISTRATION: Guidelines International Network (GIN) website, https://guidelines.ebmportal.com/node/69996 .

Adsorption behavior and mechanism of CO2 in the Longmaxi shale gas reservoir.

CO2 is the main greenhouse gas in Earth's atmosphere, and has been causing global warming since the industrial revolution. Therefore, technologies to mitigate carbon emissions have attracted extensive research. Shale gas reservoirs could serve as potential sequestration space for CO2. This paper aims to gain insight in the CO2 adsorption behavior and mechanism in Longmaxi shale. The micropore filling theory is the best model for CO2 adsorption in the shale samples with the smallest MSR (Mean Square of Residual). This model fits better than that of the monolayer adsorption and multi-layer adsorption theories. Specifically, micropore filling adsorption mainly occurs in micropores, including the closed end of slit pores, capillary pores, and ink-shaped pores. Molecular layer adsorption mainly occurs in mesopores and macropores, including the open end of slit pores, plate pores, capillary pores, and ink-shaped pores. Moreover, the prediction model of CO2 storage quantity in deep shale gas reservoirs of China is established. This model shows that 91.5-388.89 × 1012 m3 of CO2 could in theory be stored in an adsorbed state. CO2 is mostly stored by an adsorbed state (higher than 95%) and a free state with good security and low leakage risk. The results from this work are of specific interest for global research on CO2 adsorption characteristics and adsorption mechanisms in different pore structures. Furthermore, it provides certain guidance for geological storage of CO2 in shale.

A model for superimposed coalbed methane, shale gas and tight sandstone reservoirs, Taiyuan Formation, Yushe-Wuxiang Block, eastern Qinshui Basin.

Superimposed accumulation mechanism and model of vertical source rock-reservoir system of coal-measure gas is crucial to evaluate the exploration potential, and also the basis of co-exploration and co-production of coal measure gas. This work investigates the formation mechanism of various types of reservoirs (coalbed methane, shale gas, tight sandstone) in the Taiyuan Formation (Yushe-Wuxiang Block, eastern Qinshui Basin). Source rocks (coal seams and coal-measure mudstones) in the study area are characterized by type III kerogen, organic rich and over-mature, and reach a gas generation peak during the Early to Late Cretaceous. Coalbed methane mainly adsorbs on the surface of micropores, shale gas mainly occurs in micropores, macropores and micro-factures in adsorbed and free states, and tight sandstone gas mainly occurs in macropores in a free state. The combinations of successions are identified, coalbed methane, shale gas, and tight sandstone gas horizons are divided into a mudstone-sandstone reservoir (combination I), a coal-mudstone-sandstone reservoir (combination II), and a coal-mudstone reservoir (combination III). This division occurs from top to bottom in the succession and is identified on the basis of lithology, total organic carbon content (TOC) of mudstones, gas logging, superimposition relationships, and the source rock-reservoir-caprock assemblage. The strata thickness, continuity, and gas logging results of combination III comprise the most favorable conditions for fairly good development potential, followed by combination I. The development potential of combination II is poor due to the small strata thickness and poor continuity. The identification of superimposed reservoirs can provide an engineering reference for the exploration of coal-measure gas.

Quantifying the immunological distinctiveness of emerging SARS-CoV-2 variants in the context of prior regional herd exposure.

The COVID-19 pandemic has seen the persistent emergence of immune-evasive SARS-CoV-2 variants under the selection pressure of natural and vaccination-acquired immunity. However, it is currently challenging to quantify how immunologically distinct a new variant is compared to all the prior variants to which a population has been exposed. Here, we define "Distinctiveness" of SARS-CoV-2 sequences based on a proteome-wide comparison with all prior sequences from the same geographical region. We observe a correlation between Distinctiveness relative to contemporary sequences and future change in prevalence of a newly circulating lineage (Pearson r = 0.75), suggesting that the Distinctiveness of emergent SARS-CoV-2 lineages is associated with their epidemiological fitness. We further show that the average Distinctiveness of sequences belonging to a lineage, relative to the Distinctiveness of other sequences that occur at the same place and time (n = 944 location/time data points), is predictive of future increases in prevalence (Area Under the Curve, AUC = 0.88 [95% confidence interval 0.86 to 0.90]). By assessing the Delta variant in India versus Brazil, we show that the same lineage can have different Distinctiveness-contributing positions in different geographical regions depending on the other variants that previously circulated in those regions. Finally, we find that positions that constitute epitopes contribute disproportionately (20-fold higher than the average position) to Distinctiveness. Overall, this study suggests that real-time assessment of new SARS-CoV-2 variants in the context of prior regional herd exposure via Distinctiveness can augment genomic surveillance efforts.

iCn3D: From Web-Based 3D Viewer to Structural Analysis Tool in Batch Mode.

iCn3D was initially developed as a web-based 3D molecular viewer. It then evolved from visualization into a full-featured interactive structural analysis software. It became a collaborative research instrument through the sharing of permanent, shortened URLs that encapsulate not only annotated visual molecular scenes, but also all underlying data and analysis scripts in a FAIR manner. More recently, with the growth of structural databases, the need to analyze large structural datasets systematically led us to use Python scripts and convert the code to be used in Node. js scripts. We showed a few examples of Python scripts at https://github.com/ncbi/icn3d/tree/master/icn3dpython to export secondary structures or PNG images from iCn3D. Users just need to replace the URL in the Python scripts to export other annotations from iCn3D. Furthermore, any interactive iCn3D feature can be converted into a Node. js script to be run in batch mode, enabling an interactive analysis performed on one or a handful of protein complexes to be scaled up to analysis features of large ensembles of structures. Currently available Node. js analysis scripts examples are available at https://github.com/ncbi/icn3d/tree/master/icn3dnode. This development will enable ensemble analyses on growing structural databases such as AlphaFold or RoseTTAFold on one hand and Electron Microscopy on the other. In this paper, we also review new features such as DelPhi electrostatic potential, 3D view of mutations, alignment of multiple chains, assembly of multiple structures by realignment, dynamic symmetry calculation, 2D cartoons at different levels, interactive contact maps, and use of iCn3D in Jupyter Notebook as described at https://pypi.org/project/icn3dpy.

KNOX II transcription factor HOS59 functions in regulating rice grain size.

Plant Knotted1-like homeobox (KNOX) genes encode homeodomain-containing transcription factors. In rice (Oryza sativa L.), little is known about the downstream target genes of KNOX Class II subfamily proteins. Here we generated chromatin immunoprecipitation (ChIP)-sequencing datasets for HOS59, a member of the rice KNOX Class II subfamily, and characterized the genome-wide binding sites of HOS59. We conducted trait ontology (TO) analysis of 9705 identified downstream target genes, and found that multiple TO terms are related to plant structure morphology and stress traits. ChIP-quantitative PCR (qPCR) was conducted to validate some key target genes. Meanwhile, our IP-MS datasets showed that HOS59 was closely associated with BELL family proteins, some grain size regulators (OsSPL13, OsSPL16, OsSPL18, SLG, etc.), and some epigenetic modification factors such as OsAGO4α and OsAGO4ß, proteins involved in small interfering RNA-mediated gene silencing. Furthermore, we employed CRISPR/Cas9 editing and transgenic approaches to generate hos59 mutants and overexpression lines, respectively. Compared with wild-type plants, the hos59 mutants have longer grains and increased glume cell length, a loose plant architecture, and drooping leaves, while the overexpression lines showed smaller grain size, erect leaves, and lower plant height. The qRT-PCR results showed that mutation of the HOS59 gene led to upregulation of some grain size-related genes such as OsSPL13, OsSPL18, and PGL2. In summary, our results indicate that HOS59 may be a repressor of the downstream target genes, negatively regulating glume cell length, rice grain size, plant architecture, etc. The identified downstream target genes and possible interaction proteins of HOS59 improve our understanding of the KNOX regulatory networks.