The blockade of aberrant hedgehog (Hh) signaling has shown promise for therapeutic intervention in cancer. A cell-based phenotypic high-throughput screen was performed, and the lead structure (1) was ...identified as an inhibitor of the Hh pathway via antagonism of the Smoothened receptor (Smo). Structure−activity relationship studies led to the discovery of a potent and specific Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4′-(trifluoromethoxy)biphenyl-3-carboxamide (5m, NVP-LDE225), which is currently in clinical development.
H9N2 avian influenza viruses are widely prevalent in birds and pose an increasing threat to humans because of their enhanced virulence and transmissibility in mammals. Active surveillance on the ...prevalence and evolution of H9N2 viruses in different avian hosts will help develop eradication measures. We isolated 16 H9N2 viruses from chickens, green peafowls, and wild birds in eastern China from 2017 to 2019 and characterized their comparative genetic evolution, receptor-binding specificity, antigenic diversity, replication, and transmission in chickens and mice. The phylogenetic analysis indicated that the green peafowl viruses and swan reassortant shared the same ancestor with the poultry H9N2 viruses prevalent in eastern China, while the seven wild bird viruses belonged to wild bird lineage. The chicken, peafowl, and swan H9N2 viruses that belonged to the poultry lineage preferentially recognized α-2, 6-linked sialic acids (human-like receptor), but the wild bird lineage viruses can bind both α-2, 3 (avian-like receptor) and human-like receptor similarly. Interestingly, the H9N2 viruses of poultry lineage replicated well and transmitted efficiently, but the viruses of wild bird lineage replicated and transmitted with low efficiency. Importantly, the H9N2 viruses of poultry lineage replicated in higher titer in mammal cells and mice than the viruses of wild birds lineage. Altogether, our study indicates that co-circulation of the H9N2 viruses in poultry, wild birds, and ornamental birds increased their cross-transmission risk in different birds because of their widespread dissemination.
The gut microbiota is highly symbiotic with the host, and the microbiota and its metabolites are essential for regulating host health and physiological functions.
, as a feed additive, can improve ...animal immunity. However, the effects of
root powder on the rumen microbiota and their metabolites in lambs are not apparent. In this study, thirty healthy Hu sheep lambs with similar body weights (17.42 ± 2.02 kg) were randomly selected for the feeding experiment. Lambs were fed diets supplemented with 0.3%
root powder, and the rumen microbiota density and metabolome were measured to determine the effects of
on the health of lambs in the rumen. The results showed that the relative abundance of
(
),
(
),
(
), and
(
) in the rumen was increased in the
group (
< 0.01), and metabolic profiling showed that the metabolites, such as L-lyrosine and L-leucine, were upregulated in the
group (
< 0.01). KEGG functional annotation revealed that upregulated metabolites were mainly enriched in the pathways of amino acid metabolism, lipid metabolism, fatty acid biosynthesis, and bile secretion in the
group, and downregulated metabolites were enriched in the pathways of methane metabolism and other pathways. Correlation analysis revealed that butyric acid was positively correlated with
and
(
< 0.05) and negatively correlated with
(
< 0.05). Thus, by analyzing the interactions of
root powder with the density of rumen microorganisms and their metabolites in lambs, it was shown that
root powder could improve the structure of rumen microbiota and their metabolites and then participate in the regulation of amino acid metabolism, lipid metabolism, immune metabolism, and other pathways to improve the efficiency of energy absorption of the lambs.
Aim
This study aimed to explore the level and influencing factors of fatigue in patients with rheumatoid arthritis.
Methods
This cross‐sectional study was conducted in 243 patients with rheumatoid ...arthritis from April 2016 to March 2017. The Bristol Rheumatoid Arthritis Fatigue Multi‐Dimensional Questionnaire, Arthritis Self‐Efficacy Scale‐8, Visual Analogue Scale for pain, physical function subscale of Short Form 36‐Item Health Survey, Hospital Anxiety and Depression Scale, Perceived Social Support Scale, Pittsburgh Sleep Quality Index and a self‐designed demographic and disease‐related information questionnaire were used to collect the data. Stepwise linear multiple regression was used to clarify the impact of statistically significant variables (P < 0.05) in the independent sample t test, one‐way ANOVA and correlation analysis on the level of fatigue.
Results
Stepwise linear multiple regression analyses showed that disease activity, self‐efficacy, physical function, pain, depression, duration of morning stiffness and anxiety were major factors influencing fatigue in patients with rheumatoid arthritis, which explained 59.5% of the total variance.
Conclusion
Our study demonstrated a moderate level of fatigue in Chinese patients with rheumatoid arthritis. In clinical practice, nurses should explore individualized intervention programmes based on related predictors of fatigue to help patients relieve fatigue.
Summary statement
What is already known about this topic?
Fatigue is a common problem in patients with rheumatoid arthritis (RA).
Little research has investigated what factors are associated with fatigue in patients with RA.
Nurses need to understand the factors that potentially influence fatigue in patients with RA, in order to improve the quality of life.
What this paper adds?
Fatigue is moderate in Chinese patients with RA, which is lower than the results of western countries.
Disease activity, self‐efficacy, physical function, pain, depression, duration of morning stiffness and anxiety are important factors affecting fatigue in patients with RA.
The implications of this paper:
Special attention should be paid to the RA patients with high level of fatigue.
The findings of this study highlight the need to develop effective strategies to alleviate fatigue and eventually improve the quality of life in patients with RA.
Key message
Fifteen candidate reference genes were selected from the dove tree genome. Their performance as internal controls for RT-qPCR analysis was assessed in bracts at different developmental ...stages, normal and abortive seeds, and leaves of different colors. The applicability of the candidate reference genes was validated through detection of the expression levels of three target genes normalized by different reference genes.
Dove tree (
Davidia
) is a relic species and has some unique traits in its reproductive organs. The molecular mechanisms underlying the development of these organs have attracted increasing attention. RT-qPCR is a powerful tool for gene expression pattern detection, which is critical for studies on gene function or regulation. However, information regarding suitable reference genes, which ensures reliable RT-qPCR results, is absent in dove tree. Based on our previously obtained
Davidia
transcriptome data, 15 reference genes, including eight traditional and seven novel reference genes, were selected for this study. Using geNorm, NormFinder and BestKeeper software, the stability and applicability of these candidate reference genes were assessed with regard to different aspects including bract development, seed abortion and leaf color. The candidate reference genes were ranked by the software programs, and the most suitable and unsuitable genes for different situations were determined. In addition, the expression levels of three
Davidia
genes of interest involved in bract development, seed abortion and leaf color, respectively, were normalized with high-ranking and low-ranking reference genes. The comparison results demonstrated that the selection of “good” or “bad” reference genes led to differing conclusions.
This paper focuses on the comparison between two fusion methods, namely early fusion and late fusion. The former fusion is carried out at kernel level, also known as multiple kernel learning, and in ...the latter, the modalities are fused through logistic regression at classifier score level. Two kinds of multilayer fusion structures, differing in the quantities of feature/kernel groups in a lower fusion layer, are constructed for early and late fusion systems, respectively. The goal of these fusion methods is to put each of various features into effect and mine redundant information of the combination of them, and then to develop a generic and robust semantic indexing system to bridge semantic gap between human concepts and these low-level visual features. Performance evaluated on both TRECVID2009 and TRECVID2010 datasets demonstrates that the systems with our proposed multilayer fusion methods at kernel level perform more stably to reach the goal than the classification-score-level fusion; the most effective and robust one with highest MAP score is constructed by early fusion with two-layer equally weighted composite kernel learning.
Ankyrin 1 (
ANK1
) gene has been demonstrated to be a functional candidate gene for meat quality that helps to constitute and maintain the structure of the cell skeleton. In this study, three ...contiguous
ANK1
regions from yak were analyzed using polymerase chain reaction-single-stranded conformational polymorphism (PCR
–
SSCP). As a result, nine single-nucleotide polymorphisms (SNPs) were identified, four of them in the coding region and three (c.179 C/A, c.250 G/C, and c.313 C/T) putatively resulting in amino acid changes (p. Ala 60 Glu, p. Asp 84 His, and p. Pro 105 Ser). Some SNPs in promoter region were located within or nearby the putative transcription factor binding sites, such as Sp1 and GATA, which might have an impact on the expression of the yak
ANK1
gene. The presence of
C
1
–D
3
and
C
1
–A
3
were associated with an increased hot carcass weight (
p
= 0.0045) and a decreased drip loss rate (
p
= 0.0046). The presence of
B
1
–B
3
,
C
1
–A
3
and
C
1
–D
3
had decreased Warner–Bratzler shear force (
p
= 0.0066,
p
= 0.0343 and
p
= 0.0004). The presence of one and two copies of
B
1
–B
3
and
C
1
–A
3
had decreased Warner–Bratzler shear force (
p
= 0.0005 and
p
= 0.0443), and
C
1
–A
3
had also decreased drip loss rate (
p
= 0.0164). These findings indicated that genetic variations of the
ANK1
gene would be a preferable biomarker for the improvement of yak meat quality.
The plasmonic Ag nanoparticles match with vertically aligned N-doped TiO sub(2) nanotube arrays, which display improving photoelectrochemical performance. N-doped anatase nanotube arrays are ...fabricated firstly, and then cubic Ag nanoparticles of diameter 5 nm are deposited on TiO sub(2) nanotubes without organic additives at room temperature. X-ray photoelectron spectroscopy shows that the oxygen vacancies and N impurity are revealed in N-doped TiO sub(2). The electrical properties of samples are investigated by systematic photoelectrochemical measurement. The charge transfer ability of TiO sub(2), N-doped TiO sub(2) and Ag/N-doped TiO sub(2) is presented directly by Electrochemical impedance spectroscopy and Mott-Schottky measurement, respectively. The carrier density of Ag/N-doped TiO sub(2) is higher 2 orders of magnitude enhancement of TiO sub(2). Furthermore, its photocurrent responds rapidly with illumination owing to fast photoelectron transport. And photocurrent density is 0.14 mA cm super(-2) at 1.23 V sub(RHE). which is the highest among samples. Finally, the mechanism of improving photoelectrochemical activity is schematically displayed. The plasmonic Ag/N-doped TiO sub(2) composties are favorable for the separation for photoelectron-hole pairs and increasing electron transfer, leading to a considerably photoelectrochemical performance under sunlight. The modified nanotube arrays provide potential application in photoelectrochemical cell.
Acoustic tweezers, capable of complicated manipulation of bioparticles by acoustic radiation forces using a noninvasive and noncontact approach, are an innovative technology for patterning assemble ...organoids. Hence, acoustic tweezers exhibit considerable potential for forming programmable patterning of organoids with specific spatial structures. Furthermore, heterogeneous assembloids with complex arrangement patterns can be built through sequential assembling and culturing to explore polarized tissue development or disease metastasis in multiple organs. This study focuses on the structural assembly of organoids using an ultrasonic 2D matrix array to generate real‐time switching of different acoustic fields. In addition, a local renal injured assembloid is fabricated to study and verify its application in tissue engineering and disease modeling.
An ultrasonic phase array‐based online structural‐assembling platform that integrates precise selection, movement, rotation, and accurate assembly of organoids using multiplexing functional holographic acoustic fields noninvasively is investigated. Hence, the patterning of heterogeneous kidney assembloids to mimic acute kidney injury in vivo is programmed. This is the pioneer demonstration of programmable assembloids in tissue engineering and disease modeling.
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