ABSTRACT
Natural language processing (NLP) has become an essential technique in various fields, offering a wide range of possibilities for analyzing data and developing diverse NLP tasks. In the biomedical domain, understanding the complex relationships between compounds and proteins is critical, especially in the context of signal transduction and biochemical pathways. Among these relationships, protein-protein interactions (PPIs) are of particular interest, given their potential to trigger a variety of biological reactions. To improve the ability to predict PPI events, we propose the protein event detection dataset (PEDD), which comprises 6823 abstracts, 39 488 sentences and 182 937 gene pairs. Our PEDD dataset has been utilized in the AI CUP Biomedical Paper Analysis competition, where systems are challenged to predict 12 different relation types. In this paper, we review the state-of-the-art relation extraction research and provide an overview of the PEDD's compilation process. Furthermore, we present the results of the PPI extraction competition and evaluate several language models' performances on the PEDD. This paper's outcomes will provide a valuable roadmap for future studies on protein event detection in NLP. By addressing this critical challenge, we hope to enable breakthroughs in drug discovery and enhance our understanding of the molecular mechanisms underlying various diseases.
Subject(s)
Drug Discovery , Natural Language Processing , Signal TransductionABSTRACT
Marek's disease virus (MDV) vaccines were the first vaccines that protected against cancer. The avirulent turkey herpesvirus (HVT) was widely employed and protected billions of chickens from a deadly MDV infection. It is also among the most common vaccine vectors providing protection against a plethora of pathogens. HVT establishes latency in T-cells, allowing the vaccine virus to persist in the host for life. Intriguingly, the HVT genome contains telomeric repeat arrays (TMRs) at both ends; however, their role in the HVT life cycle remains elusive. We have previously shown that similar TMRs in the MDV genome facilitate its integration into host telomeres, which ensures efficient maintenance of the virus genome during latency and tumorigenesis. In this study, we investigated the role of the TMRs in HVT genome integration, latency, and reactivation in vitro and in vivo. Additionally, we examined HVT infection of feather follicles. We generated an HVT mutant lacking both TMRs (vΔTMR) that efficiently replicated in cell culture. We could demonstrate that wild type HVT integrates at the ends of chromosomes containing the telomeres in T-cells, while integration was severely impaired in the absence of the TMRs. To assess the role of TMRs in vivo, we infected one-day-old chickens with HVT or vΔTMR. vΔTMR loads were significantly reduced in the blood and hardly any virus was transported to the feather follicle epithelium where the virus is commonly shed. Strikingly, latency in the spleen and reactivation of the virus were severely impaired in the absence of the TMRs, indicating that the TMRs are crucial for the establishment of latency and reactivation of HVT. Our findings revealed that the TMRs facilitate integration of the HVT genome into host chromosomes, which ensures efficient persistence in the host, reactivation, and transport of the virus to the skin.
Subject(s)
Chickens , Marek Disease , Telomere , Virus Integration , Virus Latency , Animals , Chickens/virology , Telomere/genetics , Telomere/virology , Marek Disease/virology , Marek Disease/immunology , Marek Disease/prevention & control , Genetic Vectors , Herpesvirus 1, Meleagrid/genetics , Herpesvirus 1, Meleagrid/immunology , Marek Disease Vaccines/immunology , Marek Disease Vaccines/genetics , Genome, Viral , Herpesvirus 2, Gallid/genetics , Herpesvirus 2, Gallid/immunology , Repetitive Sequences, Nucleic Acid , Poultry Diseases/virology , Poultry Diseases/immunology , Poultry Diseases/prevention & controlABSTRACT
Ferroelectricity, which has diverse important applications such as memory elements, capacitors, and sensors, was first discovered in a molecular compound, Rochelle salt, in 1920 by Valasek. Owing to their superiorities of lightweight, biocompatibility, structural tunability, mechanical flexibility, etc., the past decade has witnessed the renaissance of molecular ferroelectrics as promising complementary materials to commercial inorganic ferroelectrics. Thus, on the 100th anniversary of ferroelectricity, it is an opportune time to look into the future, specifically into how to push the boundaries of material design in molecular ferroelectric systems and finally overcome the hurdles to their commercialization. Herein, we present a comprehensive and accessible review of the appealing development of molecular ferroelectrics over the past 10 years, with an emphasis on their structural diversity, chemical design, exceptional properties, and potential applications. We believe that it will inspire intense, combined research efforts to enrich the family of high-performance molecular ferroelectrics and attract widespread interest from physicists and chemists to better understand the structure-function relationships governing improved applied functional device engineering.
ABSTRACT
Information exchange between neurons and astrocytes mediated by extracellular vesicles (EVs) is known to play a key role in the pathogenesis of central nervous system diseases. A key driver of epilepsy is the dysregulation of intersynaptic excitatory neurotransmitters mediated by astrocytes. Thus, we investigated the potential association between neuronal EV microRNAs (miRNAs) and astrocyte glutamate uptake ability in epilepsy. Here, we showed that astrocytes were able to engulf epileptogenic neuronal EVs, inducing a significant increase in the glutamate concentration in the extracellular fluid of astrocytes, which was linked to a decrease in glutamate transporter-1 (GLT-1) protein expression. Using sequencing and gene ontology (GO) functional analysis, miR-181c-5p was found to be the most significantly upregulated miRNA in epileptogenic neuronal EVs and was linked to glutamate metabolism. Moreover, we found that neuronal EV-derived miR-181c-5p interacted with protein kinase C-delta (PKCδ), downregulated PKCδ and GLT-1 protein expression and increased glutamate concentrations in astrocytes both in vitro and in vivo. Our findings demonstrated that epileptogenic neuronal EVs carrying miR-181c-5p decrease the glutamate uptake ability of astrocytes, thus promoting susceptibility to epilepsy.
Subject(s)
Epilepsy , Extracellular Vesicles , MicroRNAs , Humans , Astrocytes/metabolism , Protein Kinase C-delta/metabolism , Epilepsy/genetics , Epilepsy/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neurons/metabolism , Extracellular Vesicles/metabolism , Glutamic Acid/metabolism , Amino Acid Transport System X-AG/metabolismABSTRACT
Metal halide perovskites (MHPs) have garnered significant attention due to their distinctive optical and electronic properties, coupled with excellent processability. However, the thermal characteristics of these materials are often overlooked, which can be harnessed to cater to diverse application scenarios. We showcase the efficacy of lowering the congruent melting temperature (Tm) of layered 2D MHPs by employing a strategy that involves the modification of flexible alkylammonium through N-methylation and I-substitution. Structural-property analysis reveals that the N-methylation and I-substitution play pivotal roles in reducing hydrogen bond interactions between the organic components and inorganic parts, lowering the rotational symmetry number of the cation and restricting the residual motion of the cations. Additional I···I interactions enhance intermolecular interactions and lead to improved molten stability, as evidenced by a higher viscosity. The 2D MHPs discussed in this study exhibit low Tm and wide melt-processable windows, e.g., (DMIPA)2PbI4 showcasing a low Tm of 98 °C and large melt-processable window of 145 °C. The efficacy of the strategy was further validated when applied to bromine-substituted 2D MHPs. Lowering the Tm and enhancing the molten stability of the MHPs hold great promise for various applications, including glass formation, preparation of high-quality films for photodetection, and fabrication of flexible devices.
ABSTRACT
BACKGROUND: Studies have shown that hepatitis B virus (HBV)-associated B-cell non-Hodgkin lymphoma (NHL) constitutes a unique subgroup with distinct clinical features. It still leaves open the question of whether the integration of HBV DNA into the B-cell genome is a causal mechanism in the development of lymphoma. METHODS: Using the hybridisation capture-based next generation sequencing and RNA sequencing, we characterised the HBV integration pattern in 45 HBV-associated B-cell NHL tumour tissues. RESULTS: A total of 354 HBV integration sites were identified in 13 (28.9%) samples, indicating the relatively low integration frequency in B-cell NHLs. High plasma HBV DNA loads were not associated with the existence of HBV integration. The insertion sites distributed randomly across all the lymphoma genome without any preferential hotspot neither at the chromosomal level nor at the genetic level. Intriguingly, most HBV integrations were nonclonal in B-cell NHLs, implying that they did not confer a survival advantage. Analysis of the paired diagnosis-relapse samples showed the unstable status of HBV integrations during disease progression. Furthermore, transcriptomic analysis revealed the limited biological impact of HBV integration. CONCLUSION: Our study provides an unbiased HBV integration map in B-cell NHLs, revealing the insignificant role of HBV DNA integration in B-cell lymphomagenesis.
ABSTRACT
Lung cancer has a high incidence rate and requires more effective treatment strategies and drug options for clinical patients. EGFR is a common genetic alteration event in lung cancer that affects patient survival and drug strategy. Our study discovered aberrant aldolase A (ALDOA) expression and dysfunction in lung cancer patients with EGFR mutations. In addition to investigating relevant metabolic processes like glucose uptake, lactate production, and ATPase activity, we examined multi-omics profiles (transcriptomics, proteomics, and pull-down assays). It was observed that phosphodiesterase 3A (PDE3A) enzyme and ALDOA exhibit correlation, and furthermore, they impact M2 macrophage polarization through ß-catenin and downstream ID3. In addition to demonstrating the aforementioned mechanism of action, our experiments discovered that the PDE3 inhibitor trequinsin has a substantial impact on lung cancer cell lines with EGFR mutants. The trequinsin medication was found to decrease the M2 macrophage polarization status and several cancer phenotypes, in addition to transduction. These findings have potential prognostic and therapeutic applications for clinical patients with EGFR mutation and lung cancer.
Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Fructose-Bisphosphate Aldolase/genetics , beta Catenin/genetics , beta Catenin/metabolism , Signal Transduction/genetics , Cyclic Nucleotide Phosphodiesterases, Type 3/genetics , Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism , Cell Line, Tumor , Mutation , ErbB Receptors/genetics , ErbB Receptors/metabolism , Neoplasm Proteins/metabolism , Inhibitor of Differentiation Proteins/geneticsABSTRACT
LiNO3 has attracted intensive attention as a promising electrolyte additive to regulate Li deposition behavior as it can form favorable Li3N, LiNxOy species to improve the interfacial stability. However, the inferior solubility in carbonate-based electrolyte restricts its application in high-voltage Li metal batteries. Herein, an artificial composite layer (referred to as PML) composed of LiNO3 and PMMA is rationally designed on Li surface. The PML layer serves as a reservoir for LiNO3 release gradually to the electrolyte during cycling, guaranteeing the stability of SEI layer for uniform Li deposition. The PMMA matrix not only links the nitrogen-containing species for uniform ionic conductivity but also can be coordinated with Li for rapid Li ions migration, resulting in homogenous Li-ion flux and dendrite-free morphology. As a result, stable and dendrite-free plating/stripping behaviors of Li metal anodes are achieved even at an ultrahigh current density of 20 mA cm-2 (>570 h) and large areal capacity of 10 mAh cm-2 (>1200 h). Moreover, the Li||LiFePO4 full cell using PML-Li anode undergoes stable cycling for 2000 cycles with high-capacity retention of 94.8%. This facile strategy will widen the potential application of LiNO3 in carbonate-based electrolyte for practical LMBs.
ABSTRACT
Photon blockade (PB) is one of the effective methods to generate single-photon sources. In general, both the PB effect with the significant sub-Poissonian statistics and a large mean photon number are desired to guarantee the brightness and the purity of single-photon sources. Here, we propose to obtain the PB effect at the cavity dark-state polariton (DSP) using a cavity Λ-type electromagnetically induced transparency (EIT) system with and without the two-photon dissipation (TPD). In the Raman resonance case, the PB effect at the DSP could by realized by using the TPD process in the weak or intermediate coupling regime, which accompanies with near unity transmission, i.e., very high photon occupation. In the slightly detuned Raman resonance case, the excited state is induced into the components of the DSP, and the atomic dissipation path is added into the two-photon excitation paths. Thus, the PB effect at the DSP can be obtained due to the quantum destructive interference (QDI) in the strong coupling regime, which can be further enhanced using the TPD process. Due to the slight detuning, the PB effect still remains high photon occupation and has highly tunability. This work provides an alternative way to manipulate the photon statistics by the PB effect and has potential applications in generating single-photon sources with high brightness and purity.
ABSTRACT
Multifarious molecular ferroelectrics with multipolar axial characteristics have emerged in recent years, enriching the scenarios for energy harvesting, sensing, and information processing. The increased polar axes have enhanced the urgency of distinguishing different polarization states in material design, mechanism exploration, etc. However, conventional methods hardly meet the requirements of in situ, fast, microscale, contactless, and nondestructive features due to their inherent limitations. Herein, SHG polarimetry is introduced to probe the multioriented polarizations on a nanosized multiaxial molecular ferroelectric, i.e., TMCM-CdCl3 nanoplates, as an example. Combined with the analysis of the second-order susceptibility tensor, SHG polarimetry could serve as an effective method to detect the polarization orders and domain distributions of molecular ferroelectrics. Profiting from the full-optical feature, SHG polarimetry can even be performed on samples covered by transparent mediums, 2D materials, or thin metal electrodes. Our research might spark further fundamental studies and expand the application boundaries of next-generation ferroelectric materials.
ABSTRACT
Piezoelectric materials that enable electromechanical conversion have great application value in actuators, transducers, sensors, and energy harvesters. Large piezoelectric (d33) and piezoelectric voltage (g33) coefficients are highly desired and critical to their practical applications. However, obtaining a material with simultaneously large d33 and g33 has long been a huge challenge. Here, we reported a hybrid perovskite ferroelectric [Me3NCH2Cl]CdBrCl2 to mitigate and roughly address this issue by heavy halogen substitution. The introduction of a large-size halide element softens the metal-halide bonds and reduces the polarization switching barrier, resulting in excellent piezoelectric response with a large d33 (â¼440 pC/N), which realizes a significant optimization compared with that of previously reported [Me3NCH2Cl]CdCl3 (You et al. Science2017, 357, 306-309). More strikingly, [Me3NCH2Cl]CdBrCl2 simultaneously shows a giant g33 of 6215 × 10-3 V m/N, far exceeding those of polymers and conventional piezoelectric ceramics. Combined with simple solution preparation, easy processing of thin films, and a high Curie temperature of 373 K, these attributes make [Me3NCH2Cl]CdBrCl2 promising for high-performance piezoelectric sensors in flexible, wearable, and biomechanical devices.
ABSTRACT
BACKGROUND AND AIMS: Hepatitis B immunoglobulin (HBIG) has been routinely applied in the liver transplantation setting to block HBV reinfection of grafts. However, new monoclonal anti-HBV surface antibodies have been developed to replace HBIG. The epitopes of such monoclonal antibodies may affect the emergence of escape variants and deserve study. APPROACH AND RESULTS: The conformational epitope of sLenvervimab, a surrogate form of Lenvervimab, which is a monoclonal anti-HBsAg antibody currently under phase 3 trial, was investigated by selecting escape mutants from a human liver chimeric mouse. HBV-infected chimeric mice treated with sLenvervimab monotherapy showed an initial decline in circulating HBsAg levels, followed by a quick rebound in 1 month. Sequencing of circulating or liver HBV DNA revealed emerging variants, with replacement of amino acid E164 or T140, two residues widely separated in HBsAg. E164 HBV variants strongly resisted sLenvervimab neutralization in cell culture infection, and the T140 variant moderately resisted sLenvervimab neutralization. Natural HBV variants with amino-acid replacements adjacent to E164 were constructed and examined for sLenvervimab neutralization effects. Variants with K160 replacement also resisted neutralization. These data revealed the conformational epitope of sLenvervimab. CONCLUSIONS: Selection of antibody-escape HBV variants in human chimeric mice works efficiently. Analysis of such emerging variants helps to identify anchor amino-acid residues of the conformational epitope that are difficult to discover by conventional approaches.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B , Animals , Antibodies, Monoclonal , Epitopes , Hepatitis B/drug therapy , Hepatitis B Antibodies , Hepatitis B virus/genetics , MiceABSTRACT
OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease. Src homology 2 domain containing protein tyrosine phosphatase (SHP2) is a member of the protein tyrosine phosphatases (PTPs) family. To date, relationship between SHP2 and SLE pathogenesis is not elucidated. METHOD: We measured plasma levels of SHP2 in 328 SLE patients, 78 RA patients, 80 SS patients and 79 healthy controls by ELISA, and discussed association of SHP2 in SLE patients, potential of plasma SHP2 as a SLE biomarker. Moreover, histological and serological changes were evaluated by flow cytometry, HE/Masson examination, immunofluorescence test in pristane-induced lupus mice after SHP2 inhibitor injection to reveal role of SHP2 in lupus development. RESULTS: Results indicated that SHP2 plasma levels were upregulated in SLE patients and correlated with some clinical, laboratory characteristics such as proteinuria, pyuria, and may be a potential biomarker for SLE. After SHP2 inhibitor treatment, hepatosplenomegaly and histological severity of the kidney in lupus mice were improved. SHP2 inhibitor reversed DCs, Th1, and Th17 cells differentiation and downregulated inflammatory cytokines (IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) and autoantibodies (ANA, anti-dsDNA) production in pristane-lupus mice. CONCLUSION: In summary, SHP2 correlated with SLE pathogenesis and promoted the development of lupus.
Subject(s)
Autoimmune Diseases , Lupus Erythematosus, Systemic , Animals , Mice , Terpenes/adverse effects , Cytokines/metabolism , BiomarkersABSTRACT
OBJECTIVE: Clinical evaluation of systemic lupus erythematosus (SLE) disease activity is limited and inconsistent, and high disease activity significantly, seriously impacts on SLE patients. This study aims to generate a machine learning model to identify SLE patients with high disease activity. METHOD: A total of 1014 SLE patients with low disease activity and 453 SLE patients with high disease activity were included. A total of 94 clinical, laboratory data and 17 meteorological indicators were collected. After data preprocessing, we use mutual information and multisurf to evaluate and select the importance of features. The selected features are used for machine learning modeling. Performance of the model is evaluated and verified by a series of binary classification indicators. RESULTS: We screened out hematuria, proteinuria, pyuria, low complement, precipitation, sunlight and other features for model construction by integrated feature selection. After hyperparameter optimization, the LGB has the best performance (ROC: AUC = 0.930; PRC: AUC = 0.911, APS = 0.913; balance accuracy: 0.856), and the worst is the naive bayes (ROC: AUC = 0.849; PRC: AUC = 0.719, APS = 0.714; balance accuracy: 0.705). Finally, the selection of features has good consistency in the composite feature importance bar plot. CONCLUSION: We identify SLE patients with high disease activity by a simple machine learning pipeline, especially the LGB model based on the characteristics of proteinuria, hematuria, pyuria and other feathers screened out by collective feature selection.
Subject(s)
Lupus Erythematosus, Systemic , Pyuria , Humans , Hematuria , Bayes Theorem , Lupus Erythematosus, Systemic/diagnosis , Machine Learning , ProteinuriaABSTRACT
3-O-ß-Glucuronide triterpenes are plant-derived compounds. Some of them have been used as herbal medicine and in pharmaceuticals, such as chikusetsu saponins and Quillaja saponins. However, the demand for these materials has remained largely a challenge owing to their natural scarcity and low-yielding purification process. Therefore, a chemical triterpene 3-O-glucuronidation was conducted in this study to alleviate the surging demand on natural source. Various glucuronyl imidate donors and oleanane-type triterpene acceptors were synthesized, and the relative reactivity values (RRV) and acceptor nucleophilic constants (Aka) were systematically measured to study their influence on glucuronidation yield. As a result, applying donors in higher RRV value generally improved the production of 3-O-glucuronide triterpenes. Meanwhile, a bulky pivaloyl group was an ideal 2-O-protection to provide ß-selectivity and prevented side reactions, including orthoester formation and acyl-transfer reaction. Collectively, a positive correlation was observed between reactive donors/acceptors and improved glucuronidation yields. These findings offered insights on the influence of donors' and acceptors' reactivities on 3-O-ß-glucuronide triterpenes synthesis, and this knowledge would help to access saponins of interest to address future needs.
Subject(s)
Plants, Medicinal , Saponins , Triterpenes , Triterpenes/chemistry , Glucuronides , Plants, Medicinal/chemistry , Saponins/chemistry , Plant Extracts/chemistryABSTRACT
BACKGROUND: Aflatoxin B1 (AFB1), one of the most prevalent contaminants in human and animal food, impairs the immune system, but information on the mechanisms of AFB1-mediated macrophage toxicity is still lacking. METHODS AND RESULTS: In this study, for the first time, we employed whole transcriptome sequencing technology to explore the molecular mechanism by which AFB1 affects the growth of porcine alveolar macrophages (PAM). We found that AFB1 exposure reduced the proliferative capacity of PAM and prevented cell cycle progression. Based on whole transcriptome analysis, RT-qPCR, ICC and RNAi, we verified the role and regulatory mechanism of the competing endogenous RNA (ceRNA) network in the process of AFB1 exposure affecting the growth of PAM. CONCLUSIONS: We found that AFB1 induced MSTRG.43,583, MSTRG.67,490, MSTRG.84,995, and MSTRG.89,935 to competitively bind miR-219a, miR-30b-3p, and miR-30c-1-3p, eliminating the inhibition of its target genes CACNA1S, RYR3, and PRKCG. This activated the calcium signaling pathway to regulate the growth of PAM. These results provide valuable information on the mechanism of AFB1 exposure induced impairment of macrophage function in humans and animals.
Subject(s)
Aflatoxin B1 , MicroRNAs , Humans , Animals , Swine , Aflatoxin B1/toxicity , Aflatoxin B1/metabolism , Macrophages, Alveolar/metabolism , Calcium Signaling , Macrophages/metabolism , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on ß-cyclodextrin (ß-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for "supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects" in "advanced yeast particles", but also provided strong theoretical support multi-effect therapy for UC.
Subject(s)
Colitis, Ulcerative , Curcumin , Animals , Mice , Saccharomyces cerevisiae , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Curcumin/pharmacology , Reactive Oxygen Species , Inflammation/drug therapy , Disease Models, AnimalABSTRACT
Immunoassays are currently not available in commercial kits for the quantification of valproic acid, vigabatrin, pregabalin, and gabapentin, which also cannot suffer the limitations of interferences of substances with similar structures. Chromatography is a good alternative to immunoassay. In this study, a simple and robust non-derivatization gas chromatography-mass spectrometry method for simultaneous determination of the above four drugs in human plasma was developed and validated for therapeutic drug monitoring purposes. This method employed benzoic acid as the internal standard with hydrochloric acid for plasma acidification and ACN for precipitate protein. The supernatant was directly injected into gas chromatography-mass spectrometry for analysis. Good linearity was obtained with linear correlation coefficients of the four analytes of 0.9988-0.9996. Extraction recoveries of valproic acid, vigabatrin, pregabalin, and gabapentin were respectively in the ranges of 91.3%-94.5%, 90.0%-90.9%, 90.0%-92.1%, and 88.0%-92.2% with the relative standard deviation values less than 12.6%. Intra- and inter-batch precision and accuracy, and stability assays were all acceptable. Taken together, the novel method developed in this study provided easy plasma pretreatment, good extraction yield, and high chromatographic resolution, which has been successfully validated through the quantification of valproic acid in the plasma of 46 patients with epilepsy.
Subject(s)
Cyclohexanecarboxylic Acids , Vigabatrin , Humans , Gabapentin/analysis , Vigabatrin/analysis , Pregabalin/analysis , Valproic Acid/analysis , Anticonvulsants , Gas Chromatography-Mass Spectrometry/methods , gamma-Aminobutyric Acid , Amines/analysis , Cyclohexanecarboxylic Acids/analysis , Cyclohexanecarboxylic Acids/chemistryABSTRACT
The gut microbiota plays an integral role in the metabolism and immunity of animal hosts, and provides insights into the health and habitat assessment of threatened animals. The skywalker hoolock gibbon (Hoolock tianxing) is a newly described gibbon species, and is considered an endangered species. Here, we used 16S rRNA amplicon sequencing to describe the fecal bacterial community of skywalker hoolock gibbons from different habitats and in captivity. Fecal samples (n = 5) from two captive gibbons were compared with wild populations (N = 6 gibbons, n = 33 samples). At the phylum level, Spirochetes, Proteobacteria, Firmicutes, Bacteroidetes dominated in captive gibbons, while Firmicutes, Bacteroidetes, and Tenericutes dominated in wild gibbons. At the genus level, captive gibbons were dominated by Treponema-2, followed by Succinivibrio and Cerasicoccus, while wild gibbons were dominated by Anaeroplasma, Prevotellaceae UCG-001, and Erysipelotrichaceae UCG-004. Captive rearing was significantly associated with lower taxonomic alpha-diversity, and different relative abundance of some dominant bacteria compared to wild gibbons. Predicted Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that captive gibbons have significantly lower total pathway diversity and higher relative abundance of bacterial functions involved in "drug resistance: antimicrobial" and "carbohydrate metabolism" than wild gibbons. This study reveals the potential influence of captivity and habitat on the gut bacterial community of gibbons and provides a basis for guiding the conservation management of captive populations.
Subject(s)
Gastrointestinal Microbiome , Hylobatidae , Animals , Hylobates , RNA, Ribosomal, 16S/genetics , Hylobatidae/genetics , Ecosystem , Bacteria/geneticsABSTRACT
Dispensing errors play a crucial role in various medical errors, unfortunately emerging as the third leading cause of death in the United States. This alarming statistic has spurred the World Health Organization (WHO) into action, leading to the initiation of the Medication Without Harm Campaign. The primary objective of this campaign is to prevent dispensing errors from occurring and ensure patient safety. Due to the rapid development of deep learning technology, there has been a significant increase in the development of automatic dispensing systems based on deep learning classification to avoid dispensing errors. However, most previous studies have focused on developing deep learning classification systems for unpackaged pills or drugs with the same type of packaging. However, in the actual dispensing process, thousands of similar drugs with diverse packaging within a healthcare facility greatly increase the risk of dispensing errors. In this study, we proposed a novel two-stage induced deep learning (TSIDL)-based system to classify similar drugs with diverse packaging efficiently. The results demonstrate that the proposed TSIDL method outperforms state-of-the-art CNN models in all classification metrics. It achieved a state-of-the-art classification accuracy of 99.39%. Moreover, this study also demonstrated that the TSIDL method achieved an inference time of only 3.12 ms per image. These results highlight the potential of real-time classification for similar drugs with diverse packaging and their applications in future dispensing systems, which can prevent dispensing errors from occurring and ensure patient safety efficiently.