Exploring Transformer Model in Longitudinal Pharmacokinetic/Pharmacodynamic Analyses and Comparing with Alternative Natural Language Processing Models.

There remains a substantial need for a comprehensive assessment of various natural language processing (NLP) algorithms in longitudinal pharmacokinetic/pharmacodynamic (PK/PD) modeling despite recent advances in machine learning in the space of quantitative pharmacology. We herein investigated the application of the transformer model and further compared the performance among several different NLP models, including long short-term memory (LSTM) and neural-ODE (Ordinary Differential Equation) in analyzing longitudinal PK/PD data using virtual data containing three different regimens. Results suggested that LSTM and neural-ODE, along with their respective variants provide a strong performance when predicting from training-included (seen) regimens, albeit with slight information loss for training-excluded (unseen) regimens.

Genomic and Transcriptomic Survey Provides Insights into Molecular Basis of Pathogenicity of the Sunflower Pathogen .

(teleomorph ) is the causal agent of sunflower ( L.) black stem. In order to investigate the molecular basis for the pathogenicity of , genomic and transcriptomic analyses were performed.

[Development of the iGEM high school track].

The international genetically engineered machine (iGEM) competition is a global top college academic competition in synthetic biology. The iGEM competition has exhibited extensive international influence and attracted teams from more than 40 countries and regions around the world to participate in. The annual iGEM outputs have attracted the attention of top academic journals or international media such as , , , , (BBC), etc.

RNAi machinery regulates nutrient metabolism and fluconazole resistance in the pathogenic fungus Cryptococcus deneoformans.

The RNAi machinery has been extensively studied in plant and animal cells for their crucial roles in the regulation of genome function. However, the potential roles of RNAi in controlling fungal growth and development have been poorly studied, especially in the basidiomycetous yeast Cryptococcus deneoformans. To characterize the biological functions of RNAi in the pathogenic fungus, a comparative analysis of mRNA profiles using high-throughput sequencing technology was performed for the wild type and the RNAi mutants of C.

Prevalence of smoking among nurses and its association with blood pressure: A cross-sectional study in 11 cities of China.

Aim: Smoking is harmful to human health. However, the relationship between smoking and blood pressure (BP) has not been consistent. This study aimed to analyse nurses' smoking behaviours and their relationship with BP.

A cross-sectional study of the interaction between night shift frequency and age on hypertension prevalence among female nurses.

Night shift is a common work schedule. This study aimed to analyze the interaction between age and frequency of night shift on the hypertension prevalence. A census questionnaire was conducted in 512 medical institutions in 11 cities of Hebei Province.

Acquiring novel chemicals by overexpression of a transcription factor DibT in the dibenzodioxocinone biosynthetic cluster in Pestalotiopsis microspora.

The endophytic fungus Pestalotiopsis microspora has drawn attention due to its production of dibenzodioxocinones which are a new class of inhibitors of cholesterol ester transfer protein (CETP). Previous studies showed that the pks8 gene cluster is responsible for the biosynthesis of dibenzodioxocinones in P. microspora.

Transcription Factors Pmr1 and Pmr2 Cooperatively Regulate Melanin Biosynthesis, Conidia Development and Secondary Metabolism in .

Melanins are the common fungal pigment, which contribute to stress resistance and pathogenesis. However, few studies have explored the regulation mechanism of its synthesis in filamentous fungi. In this study, we identified two transcription factors, Pmr1 and Pmr2, in the filamentous fungus .

The optimal spacing interval between principal shelterbelts of the farm-shelter forest network.

The farm-shelter forest network is a complex grid protection system, with a windbreak that is distinctly different from that of the single shelterbelt. We selected the farm-shelter forest network of a jujube field in the Tarim Basin of northwest China and used a combination of field measurements and wind tunnel tests to determine the optimal spacing interval between principal shelterbelts. The wind speed reductive curve of the farm-shelter forest network showed a gradual wind speed tendency to stability.

A Putative CH Transcription Factor CgTF6, Controlled by CgTF1, Negatively Regulates Chaetoglobosin A Biosynthesis in .

Gα signaling pathway as well as the global regulator LaeA were demonstrated to positively regulate the biosynthesis of chaetoglobosin A (ChA), a promising biotic pesticide produced by . Recently, the regulatory function of ZnCys binuclear finger transcription factor that lies within the ChA biosynthesis gene cluster has been confirmed. However, was not merely a pathway specific regulator.

A Rapid, Visible, and Highly Sensitive Method for Recognizing and Distinguishing Invasive Fungal Infections via CCP-FRET Technology.

Invasive fungal infection (IFI) is one of the leading causes of death in the intensive care unit (ICU) due to its high morbidity and mortality among immunocompromised patients. Early diagnosis of IFI is typically infeasible because of the lack of clinical signs and symptoms. By virtue of the cationic conjugated polymer-based fluorescence resonance energy transfer (CCP-FRET) technology, we develop a rapid, visible, simple, and sensitive method for simultaneous detection and discrimination of three types of pathogens, including (), (), and ().

Deletion of a Rare Fungal PKS CgPKS11 Promotes Chaetoglobosin A Biosynthesis, Yet Defers the Growth and Development of .

We previously reported that chaetoglobosin A (ChA) exhibits a great potential in the biocontrol of nematodes and pathogenic fungi. To improve the production of ChA, a CRISPR-Cas9 system was created and applied for eliminating potential competitive polyketide products. One of the polyketide synthase encoding genes, , which is putatively involved in the biosynthesis of chaetoglocin A, was disrupted.

Epigenetic regulation of virulence and the transcription of ribosomal protein genes involves a YEATS family protein in Cryptococcus deneoformans.

Epigenetic marks or post-translational modifications on histones have important regulatory roles in gene expression in eukaryotic organisms. The epigenetic regulation of gene expression in the pathogenic yeast Cryptococcus deneoformans remains largely undetermined. The YEATS domain proteins are readers of crotonylated lysine residues in histones.

Effect of frequency and pattern of night shift on hypertension risk in female nurses: a cross-sectional study.

Objectives: Understanding the effect of night shift on hypertension risk in nurses is important to improve the health of nurses and ensure patient safety. This study aimed to evaluate the effect of the frequency and pattern of night shift on hypertension risk and the interaction of them in female nurses.

Methods: This cross-sectional study constituted 84 697 female nurses in 13 cities in China.

A Fungal Diterpene Synthase Is Responsible for Sterol Biosynthesis for Growth.

A conserved open reading frame, , is described in , sharing a remarkable similarity with fungal diterpene synthases whose function is less studied. Loss-of-function approach manifested that was necessary for the growth and the development of the fungus. A deletion strain, Δ, showed a fundamental retardation in growth, which could deliberately be restored by the addition of exogenous sterols to the media.

An effective method to produce 7-epitaxol from taxol in HCO.

It is known that 7-epitaxol has much stronger cytotoxicity than taxol does. However, the content of 7-epitaxol in yew is much less than taxol, which makes it more costly to obtain. We describe here a method to effectively convert taxol to 7-epitaxol.

A Gene Cluster for the Biosynthesis of Dibenzodioxocinons in the Endophyte , a Taxol Producer.

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in .

Regulation of the Gα-cAMP/PKA signaling pathway in cellulose utilization of Chaetomium globosum.

Background: The canonical heterotrimeric G protein-cAMP/PKA pathway regulates numerous cellular processes in filamentous fungi. Chaetomium globosum, a saprophytic fungus, is known for producing many secondary metabolites, including cytotoxic chaetoglobosin A (ChA), as well as abundant cellulase and xylanase.

Results: Here we report on the functional characterization of this signaling pathway in C.

Role of the fungus-specific flavin carrier Flc1 in antifungal resistance in the fungal pathogen Cryptococcus neoformans.

FLC family, a conserved fungus-specific family of integral membrane proteins, has been demonstrated to play important roles in flavin transport, growth, and virulence in several fungi but not yet in Cryptococcus neoformans. In this study, we have identified the single homologue of flavin adenine dinucleotide transporter in the opportunistic pathogen C. neoformans.

A MYST Histone Acetyltransferase Modulates Conidia Development and Secondary Metabolism in Pestalotiopsis microspora, a Taxol Producer.

Reverse genetics is a promising strategy for elucidating the regulatory mechanisms involved in secondary metabolism and development in fungi. Previous studies have demonstrated the key role of histone acetyltransferases in transcriptional regulation. Here, we identified a MYST family histone acetyltransferase encoding gene, mst2, in the filamentous fungus Pestalotiopsis microspora NK17 and revealed its role in development and secondary metabolism.

Gα-cAMP/PKA pathway positively regulates pigmentation, chaetoglobosin A biosynthesis and sexual development in Chaetomium globosum.

Sensing the environmental signals, the canonical Gα-cAMP/PKA pathway modulates mycelial growth and development, and negatively regulates some secondary metabolism in filamentous fungi, e.g. aflatoxin in Aspergillus nidulans.

Distinct Roles of Velvet Complex in the Development, Stress Tolerance, and Secondary Metabolism in Pestalotiopsis microspora, a Taxol Producer.

The velvet family proteins have been shown to play critical roles in fungal secondary metabolism and development. However, variations of the roles have been observed in different fungi. We report here the observation on the role of three velvet complex components VeA, VelB, and LaeA in , a formerly reported taxol-producing fungus.

Genome-Wide Identification of circRNAs in Pathogenic Basidiomycetous Yeast Cryptococcus neoformans Suggests Conserved circRNA Host Genes over Kingdoms.

Circular RNAs (circRNAs), a novel class of ubiquitous and intriguing noncoding RNA, have been found in a number of eukaryotes but not yet basidiomycetes. In this study, we identified 73 circRNAs from 39.28 million filtered RNA reads from the basidiomycete JEC21 using next-generation sequencing (NGS) and the bioinformatics tool circular RNA identification (CIRI).

The AMP-Activated Protein Kinase Homolog Snf1 Concerts Carbon Utilization, Conidia Production and the Biosynthesis of Secondary Metabolites in the Taxol-Producer Pestalotiopsis microspora.

Highly conserved, the Snf1/AMPK is a central regulator of carbon metabolism and energy production in the eukaryotes. However, its function in filamentous fungi has not been well established. In this study, we reported functional characterization of Snf1/AMPK in the growth, development and secondary metabolism in the filamentous fungus .

Identification of a basidiomycete-specific Vilse-like GTPase activating proteins (GAPs) and its roles in the production of virulence factors in Cryptococcus neoformans.

Cryptococcus neoformans is a basidiomycetous pathogenic yeast that causes fatal infections in both immunocompetent and immunocompromised patients. Regulation on the production of its virulence factors is not fully understood. Here we reported the characterization of a gene, named CVH1(CNA06260), encoding a Drosophila Vilse-like RhoGAP homolog, which is hallmarked by three conserved functional domains: WW, MyTH4 and RhoGAP.