Infection with SARS-CoV2, which is responsible for COVID-19, can lead to differences in disease development, severity and mortality rates depending on gender, age or the presence of certain diseases. Considering that existing studies ignore these differences, this study aims to uncover potential differences attributable to gender, age and source of sampling as well as viral load using bioinformatics and multi-omics approaches. Differential gene expression analyses were used to analyse the phenotypic differences between SARS-CoV-2 patients and controls at the mRNA level. Pathway enrichment analyses were performed at the gene set level to identify the activated pathways corresponding to the differences in the samples. Drug repurposing analysis was performed at the protein level, focusing on host-mediated drug candidates to uncover potential therapeutic differences. Significant differences (i.e. the number of differentially expressed genes and their characteristics) were observed for COVID-19 at the mRNA level depending on the sample source, gender and age of the samples. The results of the pathway enrichment show that SARS-CoV-2 can be combated more effectively in the respiratory tract than in the blood samples.
Taking into account the different sample sources and their characteristics, different drug candidates were identified. Evaluating disease prediction, prevention and/or treatment strategies from a personalised perspective is crucial. In this study, we not only evaluated the differences in COVID-19 from a personalised perspective, but also provided valuable data for further experimental and clinical efforts. Our findings could shed light on potential pandemics.
Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse biological activities, holds promise as a protective agent against Candida albicans (C. albicans) infection. This study aims to investigate the potential of LA to safeguard vaginal epithelial cells (VECs) from C. albicans infection and elucidate the underlying molecular mechanisms. To simulate VVC in vitro, VK2-E6E7 cells were infected with C. albicans. Candida albicans biofilm formation, C.
albicans adhesion to VK2-E6E7 cells, and C. albicans-induced cell damage and inflammatory responses were assessed by XTT reduction assay, fluorescence assay, LDH assay, and ELISA. CCK-8 assay was performed to evaluate the cytotoxic effects of LA on VK2-E6E7 cells. Western blotting assay was performed to detect protein expression. LA dose-dependently hindered C. albicans biofilm formation and adhesion to VK2-E6E7 cells. Furthermore, LA mitigated cell damage, inhibited the Bax/Bcl-2 ratio, and attenuated the secretion of pro-inflammatory cytokines in C.
albicans-induced VK2-E6E7 cells. The investigation into LA's impact on the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway revealed that LA downregulated TLR4 expression and inhibited NF-κB activation in C.
albicans-infected VK2-E6E7 cells. Furthermore, TLR4 overexpression partially abated LA-mediated protection, further highlighting the role of the TLR4/NF-κB pathway. LA holds the potential to safeguard VECs against C. albicans infection, potentially offering therapeutic avenues for VVC management.
The maturation of infant gut microbiota has lifelong implications
on health, which has been proposed as the major events
during the first year of life. However, little is known about
their dynamic colonization and influencing elements among
the first two-year infancy as well as into the adulthood. So
based on the 16S rRNA sequencing data among 30 healthy
breast-feeding mother-infant pairs with normal ranges of
growth and development indicators from birth to two years
old, the dynamic colonization of gut microbiota and its influencing
factors were discussed using this birth cohort. Among
these, we identified that the diversity of gut microbiota was
significantly increased from six-month to two-year subgroups.
The significantly dynamic trends of gut microbiota at the phylum
(genus) level were that the percents of Firmicutes (Faecalibacterium,
Blautia, Enterococcus, Subdoligranulum, Agathobacter,
unidentified_Erysipelotrichaceae, Staphylococcus,
unidentified_Ruminococcaceae, and Fusicatenibacter), Bacteroidetes
and Verrucomicrobia were increased, while Actinobacteria
(Bifidobacterium) and Proteobacteria (unidentified-
Enterobacteriaceae and Klebsiella) were decreased with
the increased ages from six months to two years old, which
might simultaneously modulate the host pathways, such as
the higher percents of chemoheterotrophy and fermentation,
and lower percentages of nitrate_reduction, aerobic_chemoheterotrophy
and so on. Furthermore, there were significant
associations between maternal (milk microbiota, pre-pregnancy
BMI, BMI increment during the pregnancy)/infant
characteristics (BMI at birth and BMI gain), and the compositions
of gut microbiota. However, no differences of gut
microbiota were shown between the different sex and productive
mode subgroups. Overall, the colonization of gut microbiota
is significantly matured into the adulthood with the
increased ages to two-years old and regulated by the above
maternal/infant characteristics, which will provide a new direction
for the host-gut microbiota interplay during the first
two years of life.
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Oligopeptides with functional activities are of current interest
in the nutraceutical and medical sectors. The development of
the biosynthetic process of oligopeptides through a nonribosomal
peptide synthetase (NRPS) system has become more
challenging. To develop a production platform for nonribosomal
peptides (NRPs), reprogramming of transcriptional
regulation of the acv gene encoded ACV synthetase (ACVS)
was implemented in Aspergillus oryzae using the CRISPRCas9
system. Awakening silent acv expression was successfully
achieved by promoter substitution. Among the three exchanged
promoters, AoPgpdA, AoPtef1, and PtPtoxA, the
replacement of the native promoter with AoPgpdA led to the
highest ACV production in A. oryzae. However, the ACV production
of the AoPGpdA strain was also dependent on the
medium composition, in which urea was the best nitrogen
source, and a C:N ratio of 20:1 was optimal for tripeptide production.
In addition to cell growth, magnesium ions are an
essential element for ACV production and might participate
in ACVS activity. It was also found that ACV was the growthassociated
product of the engineered strain that might be a result of constitutive transcriptional control by the AoPgpdA
promoter. This study offers a potential strategy for nonribosomal
ACV production using the fungal system, which is applicable
for redesigning bioactive oligopeptides with industrial
relevance.
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The environment is under siege from a variety of pollution
sources. Fecal pollution is especially harmful as it disperses
pathogenic bacteria into waterways. Unraveling origins of
mixed sources of fecal bacteria is difficult and microbial
source tracking (MST) in complex environments is still a
daunting task. Despite the challenges, the need for answers
far outweighs the difficulties experienced. Advancements in
qPCR and next generation sequencing (NGS) technologies
have shifted the traditional culture-based MST approaches
towards culture independent technologies, where communitybased
MST is becoming a method of choice. Metagenomic
tools may be useful to overcome some of the limitations of
community-based MST methods as they can give deep insight
into identifying host specific fecal markers and their association
with different environments. Adoption of machine
learning (ML) algorithms, along with the metagenomic based
MST approaches, will also provide a statistically robust and
automated platform. To compliment that, ML-based approaches
provide accurate optimization of resources. With the
successful application of ML based models in disease prediction,
outbreak investigation and medicine prescription,
it would be possible that these methods would serve as a
better surrogate of traditional MST approaches in future.
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Two unknown Gram-stain-positive, catalase- and oxidasenegative,
non-motile, and coccus-shaped bacteria, designated
MN-17T and MN-09, were isolated from yaks faeces (Bos
grunniens) in the Qinghai-Tibet Plateau of China. 16S rRNA
gene sequence-based comparative analyses revealed that the
two strains were grouped within the genus Vagococcus, displaying
the highest similarity with Vagococcus xieshaowenii
CGMCC 1.16436T (98.6%) and Vagococcus elongatus CCUG
51432T (96.4%). Both strains grew optimally at 37°C and pH
7.0 in the presence of 0.5% (w/v) NaCl. The complete genome
of MN-17T comprises 2,085 putative genes with a total
of 2,190,262 bp and an average G + C content of 36.7 mol%.
The major fatty acids were C16:0 (31.2%), C14:0 (28.5%), and
C18:1ω9c (13.0%); the predominant respiratory quinone was
MK-7 (68.8%); the peptidoglycan type was A4α(L-Lys-DAsp);
and the major polar lipid was diphosphatidylglycerol.
Together, these supported the affiliation of strain MN-17T
to the genus Vagococcus. In silico DNA-DNA hybridization
and the average nucleotide identity values between MN-17T
and all recognized species in the genus were 21.6–26.1%
and 70.7–83.0%, respectively. MN-17T produced acid from
D-cellobiose, D-fructose, glycerol, D-glucose, N-acetyl-glucosamine,
gentiobiose, D-mannose, D-maltose, D-ribose, Dsaccharose,
salicin, D-trehalose, and D-xylose. These results
distinguished MN-17T and MN-09 from closely related species
in Vagococcus. Thus, we propose that strains MN-17T
and MN-09 represent a novel species in the genus Vagococcus,
with the name Vagococcus zengguangii sp. The type strain
is MN-17T (= CGMCC 1.16726T = GDMCC 1.1589T = JCM
33478T).
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Enterovirus D68 (EVD68) is an emerging pathogen that recently
caused a large worldwide outbreak of severe respiratory
disease in children. However, the relationship between
EVD68 and host cells remains unclear. Caspases are involved
in cell death, immune response, and even viral production.
We found that caspase-3 was activated during EVD68 replication
to induce apoptosis. Caspase-3 inhibitor (Z-DEVDFMK)
inhibited viral production, protected host cells from
the cytopathic effects of EVD68 infection, and prevented
EVD68 from regulating the host cell cycle at G0/G1. Meanwhile,
caspase-3 activator (PAC-1) increased EVD68 production.
EVD68 infection therefore activates caspase-3 for virus
production. This knowledge provides a potential direction
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Multidrug efflux pumps play an important role in antimicrobial
resistance and pathogenicity in bacteria. Here, we report
the functional characterization of the RND (resistance-nodulation-
division) efflux pump, AcrAB, in Acinetobacter nosocomialis.
An in silico analysis revealed that homologues of the
AcrAB efflux pump, comprising AcrA and AcrB, are widely
distributed among different bacterial species. Deletion of acrA
and/or acrB genes led to decreased biofilm/pellicle formation
and reduced antimicrobial resistance in A. nosocomialis. RNA
sequencing and mRNA expression analyses showed that expression
of acrA/B was downregulated in a quorum sensing
(QS) regulator (anoR)-deletion mutant, indicating transcriptional
activation of the acrAB operon by AnoR in A. nosocomialis.
Bioassays showed that secretion of N-acyl homoserine
lactones (AHLs) was unaffected in acrA and acrB deletion
mutants; however, AHL secretion was limited in a deletion
mutant of acrR, encoding the acrAB regulator, AcrR.
An in silico analysis indicated the presence of AcrR-binding
motifs in promoter regions of anoI (encoding AHL synthase)
and anoR. Specific binding of AcrR was confirmed by electrophoretic
mobility shift assays, which revealed that AcrR
binds to positions -214 and -217 bp upstream of the translational
start sites of anoI and anoR, respectively, demonstrating
transcriptional regulation of these QS genes by AcrR.
The current study further addresses the possibility that AcrAB
is controlled by the osmotic stress regulator, OmpR, in A.
nosocomialis. Our data demonstrate that the AcrAB efflux
pump plays a crucial role in biofilm/pellicle formation and
antimicrobial resistance in A. nosocomialis, and is under the
transcriptional control of a number of regulators. In addition,
the study emphasizes the interrelationship of QS and AcrAB
efflux systems in A. nosocomialis.
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Endophytes colonize tissues of healthy host plants and play
a crucial role in plant growth and development. However,
little attention has been paid to the endophytes of tuber crops
such as cassava, which is used as a staple food by approximately
800 million people worldwide. This study aimed to
elucidate the diversity and composition of endophytic bacterial
and fungal communities in different cassava cultivars
using high-throughput sequencing. Although no significant
differences in richness or diversity were observed among the
different cassava cultivars, the community compositions were
diverse. Two cultivars (SC124 and SC205) tolerant to root rot
exhibited similar community compositions, while two other
cultivars (SC10 and SC5), which are moderately and highly
susceptible to root rot, respectively, harboured similar community
compositions. Proteobacteria, Firmicutes, and Ascomycota
dominated the endophyte assemblages, with Weissella,
Serratia, Lasiodiplodia, Fusarium, and Diaporthe being the
predominant genera. The differentially abundant taxonomic
clades between the tolerant and susceptible cultivars were
mainly rare taxa, such as Lachnoclostridium_5, Rhizobium,
Lampropedia, and Stenotrophomonas. These seemed to be key
genera that affected the susceptibility of cassava to root rot.
Moreover, the comparison of KEGG functional profiles revealed
that ‘Environmental adaptation’ category was significantly
enriched in the tolerant cultivars, while ‘Infectious
diseases: Parasitic’ category was significantly enriched in the
susceptible cultivars. The present findings open opportunities
for further studies on the roles of endophytes in the susceptibility
of plants to diseases.
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Severe fever with thrombocytopenia syndrome (SFTS) is being
reported annually in South Korea since its first detection
there in 2010. The causal agent is a negative-strand RNA
virus 80–100 nm in diameter. It causes fever, thrombocytopenia,
leukocytopenia, gastrointestinal symptoms, and neural
symptoms. The mortality rate of SFTS was 32.6% among 172 case s reported from 2012 to 2015 in South Korea. Thus, is
necessary to develop an effective diagnostic method that selectively
identifies the isolates circulating in South Korea. The
real-time reverse transcription loop-mediated isothermal amplification
(RT-LAMP) assay is a simple, rapid, and sensitive
approach for molecular diagnosis. Here, we designed novel
primers for this assay and found that the technique had very
high specificity, sensitivity, and efficiency. This real-time RTLAMP
approach using the novel primers developed herein
can be applied for early diagnosis of SFTSV strains in South
Korea to reduce the mortality rate of SFTS.
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Balancing soil microbial diversity and abundance is critical
to sustaining soil health, and understanding the dynamics of
soil microbes in a monocropping system can help determine
how continuous monocropping practices induce soil sickness
mediated by microorganisms. This study used previously
constructed gradient continuous monocropping plots and
four varieties with different monocropping responses were
investigated. The feedback responses of their soil fungal communities
to short-term and long-term continuous monocropping
were tracked using high-throughput sequencing techniques.
The analyses indicated that soil samples from 1 and
2 year monocropped plots were grouped into one class, and
samples from the 11 and 12 year plots were grouped into another,
regardless of variety. At the species level, the F. solani,
Fusarium oxysporum, Neocosmospora striata, Acrophialophora
levis, Aspergillus niger, Aspergillus corrugatus, Thielavia
hyrcaniae, Emericellopsis minima, and Scedosporium
aurantiacum taxa showed significantly increased abundances
in the long-term monocropping libraries compared to
the short-term cropping libraries. In contrast, Talaromyces
flavus, Talaromyces purpureogenus, Mortierella alpina, Paranamyces
uniporus, and Volutella citrinella decreased in
the long-term monocropping libraries compared to the shortterm
libraries. This study, combined with our previous study,
showed that fungal community structure was significantly
affected by the length of the monocropping period, but peanut
variety and growth stages were less important. The increase
in pathogen abundances and the decrease in beneficial
fungi abundances seem to be the main cause for the yield decline
and poor growth of long-term monocultured peanut.
Simplification of fungal community diversity could also contribute
to peanut soil sickness under long-term monocropping.
Additionally, the different responses of peanut varieties
to monocropping may be related to variations in their
microbial community structure.
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A Gram-negative aerobic bacterium, designated RR4-38T,
was isolated from a biofilter in a seawater recirculating aquaculture
system (RAS) in Busan, South Korea. The bacteria
were irregular, short, rod-shaped, non-motile, oxidase-positive,
and catalase-negative. Growth of the strain RR4-38T
was observed at 15–35°C (optimum, 25–30°C), pH 5.5–9.5
(optimum, pH 8.0), and in the presence of 0–5% (w/v) NaCl
(optimum, 3%). Phylogenetic analysis based on the 16S rRNA
gene sequences showed that the strain RR4-38T formed a distinct
lineage with close genera Ulvibacter (≤ 95.01% 16S rRNA
gene sequence similarity), Aureitalea (94.74%), Aureisphaera
(≤ 93.27%), and Jejudonia (93.07%) that all belong to the
family Flavobacteriaceae. Whole-genome sequence comparison
revealed that the ANI (average nucleotide identity) and
digital DDH (DNA-DNA hybridization) values between strain
RR4-38T and the two closest strains, Ulvibacter antarcticus
DSM 23424T and Aureitalea marina S1-66T, were 68.96–
69.88% and 17.4–19%, respectively. The genome analysis
revealed that the strain might be involved in biodegradation
of organic debris produced by farmed fish in aquaculture
systems. The predominant respiratory quinone was menaquinone
MK-6 and the major cellular fatty acids were iso-
C15:0 (26.5%), iso-C17:0 3-OH (16.4%), iso-C15:1 G (15%), and
iso-C16:0 3-OH (9.6%). The major cellular polar lipids were
diphosphatidylglycerol, phosphatidylethanolamine, unidentified
aminolipids, and glycolipids. Based on phenotypic, chemotaxonomic,
and phylogenetic features, strain RR4-38T represents
a novel genus and species in the family Flavobacteriaceae,
for which the name Pukyongia salina gen. nov., sp.
nov. is proposed. The type strain is RR4-38T (= KCTC 52651T
= DSM 108068T).
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in the world has caused serious environmental problems.
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of using white rot fungi for bioremediation at contaminated
sites. Based on tolerance experiment results, Phlebia brevispora
and Phlebia lindtneri had the highest tolerance to lindane
and were screened by degradation tests. After 25 days of
incubation, P. brevispora and P. lindtneri degraded 87.2 and
73.3% of lindane in low nitrogen medium and 75.8 and 64.9%
of lindane in high nitrogen medium, respectively. Several unreported
hydroxylation metabolites, including monohydroxylated,
dehydroxylated, and trihydroxylated products, were detected
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two fungi after 60 days of incubation, and the mineralization
was slightly promoted by the addition of glucose. Additionally,
the degradation of lindane and the formation of metabolites
were efficiently inhibited by piperonyl butoxide, demonstrating
that cytochrome P450 enzymes are involved in the fungal
transformation of lindane. The present study showed that
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hence, they can be applied in the bioremediation process
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