The neovascularization network of pannus formation plays a crucial role in the development of rheumatoid arthritis (RA). Annexin a2 (Axna2) is an important mediating agent that induces angiogenesis in vascular diseases. The correlation between Axna2 and pannus formation has not been studied. Here, we provided evidence that compared to osteoarthritis (OA) patients and healthy people, the expression of Axna2 and Axna2 receptor (Axna2R) were up-regulated in patients with RA. Joint swelling, inflammation and neovascularization were increased significantly in mice with collagen-induced arthritis (CIA) that were exogenously added Axna2. Cell experiments showed that Axna2 promoted HUVEC proliferation by binding Axna2R, and could activate Hedgehog (HH) signaling and up-regulate the expression of Ihh and Gli. Besides, expression of Ihh, Patched (Ptc), Smoothened (Smo) and Gli and matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), angiogenic growth factor of HH signaling downstream, were down-regulated after inhibition of expression Axna2R on HUVEC. Together, our research definitely observed that over-expression of Axna2 could promote the development of CIA, especially during the process of pannus formation for the first time. Meanwhile, Axna2 depended on combining Axna2R to activate and enlarge HH signaling and the expression of its downstream VEGF, Ang-2 and MMP-2 to promote HUVEC proliferation, and eventually caused to angiogenesis. Therefore, the role of Axna2 is instructive for understanding the development of RA, suppress the effect of Axna2 might provide a new potential measure for treatment of RA.

Cypermethrin (CYP) is an insecticide in the pyrethroid family and is used widely in agriculture and for public health purposes. However, CYP has been shown to have negative impacts on reproduction, immunity and nerves in mammals. In this study, a monoclonal antibody (mAb) against CYP was prepared and used to establish an indirect competitive immunosorbent assay (ic-ELISA) and colloidal gold lateral flow immunoassay (LFIA) for the quantitative and qualitative determination of CYP residues in agricultural products. The half inhibition concentration of the ic-ELISA was 2.49 ng/mL, and the cut-off value and visual limit of detection of the LFIA were 0.6 and 0.3 μg/mL, respectively. The recovery rates of the ic-ELISA ranged from 78.8% to 87.6% in tomato, cabbage and romaine lettuce. The qualitative results of LFIA and quantitative results of ic-ELISA and HPLC were in good agreement in blind samples. Overall, the established ic-ELISA and LFIA proved to be accurate and rapid methods for the determination of CYP in agricultural products.

Chrysanthemum is one kind of ornamental plant well-known and widely used in the world. However, its quality and production were severely affected by low temperature conditions in winter and early spring periods. Therefore, we used the RNA-Seq platform to perform a de novo transcriptome assembly to analyze chrysanthemum (Dendranthema grandiflorum) transcription response to low temperature.

βΒ2-crystallin (CRYBB2) is expressed at an increased level in the postnatal lens cortex and is associated with cataracts. Improved understanding of the underlying biology of cataracts is likely to be critical for the development of early detection strategies and new therapeutics. The present study aimed to identify long non-coding RNAs (lncRNAs) and mRNAs associated with CRYBB2 knockdown (KO)-induced cataracts. RNAs from 3 non-treated mice and 3 CRYBB2 KO mice were analyzed using the Affymetrix GeneChip Mouse Gene 2.0 ST array. A total of 149 lncRNAs and 803 mRNAs were identified to have upregulated expression, including Snora73b, Klk1b22 and Rnu3a, while the expression levels of 180 lncRNAs and 732 mRNAs were downregulated in CRYBB2 KO mice, including Snord82, Snhg9 and Foxn3. This lncRNA and mRNA expression profile of mice with CRYBB2 KO provides a basis for studying the genetic mechanisms of cataract progression.

β-crystallin B2 (CRYBB2) knockout mice exhibit morphological and functional abnormalities in the ovary. Long non‑coding RNAs (lncRNAs) regulate gene transcription and translation, and epigenetic modification of genomic DNA. The present study investigated the role of lncRNAs in mediating the effects of CRYBB2 in the regulation of ovary development in mice. In the current study, ovary tissues from wild‑type (WT) and CRYBB2 knockout mice were subjected to lncRNA and mRNA microarray profiling. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to group the differentially expressed lncRNAs into regulated gene pathways and functions. The correlation matrix method was used to establish a network of lncRNA and mRNA co‑expression. Quantitative reverse transcription-polymerase chain reaction (RT‑qPCR) was used to verify expression of a number of these differentially expressed lncRNAs and mRNAs. There were 157 differentially expressed lncRNAs and 1,085 differentially expressed mRNAs between ovary tissues from WT and CRYBB2 knockout mice. The GO and KEGG analyses indicated that these differentially expressed lncRNAs and mRNAs were important in Ca2+ signaling and ligand and receptor interactions. The correlation matrix method established an lncRNA and mRNA co‑expression network, consisting of 53 lncRNAs and 45 mRNAs with 98 nodes and 75 connections. RT‑qPCR confirmed downregulation of lncRNA A‑30‑P01019163 expression, which further downregulated its downstream gene purinergic receptor P2X, ligand‑gated ion channel, 7 (P2rx7) expression in ovary tissues from CRYBB2 knockout mice. In conclusion, CRYBB2 regulates expression of different lncRNAs to influence ovary development. lncRNA A‑30‑P01019163 may affect ovarian cell cycle and proliferation by regulating P2rx7 expression in the ovary.

Phormium tenax is a kind of drought resistant garden plant with its rich and colorful leaves. To clarify the molecular mechanism of drought resistance in Phormium tenax, transcriptome was sequenced by the Illumina sequencing technology under normal and drought stress, respectively. A large number of contigs, transcripts and unigenes were obtained. Among them, only 30,814 unigenes were annotated by comparing with the protein databases. A total of 4,380 genes were differentially expressed, 2,698 of which were finally annotated under drought stress. Differentially expression analysis was also performed upon drought treatment. In KEGG pathway, the mechanism of drought resistance in Phormium tenax was explained from three aspects of metabolism and signaling of hormones, osmotic adjustment and reactive oxygen species metabolism. These results are helpful to understand the drought tolerance mechanism of Phormium tenax and will provide a precious genetic resource for drought-resistant vegetation breeding and research.

Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-κB transcriptional factor p50, apart from the well-known HIF 1α. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia.

The biological mechanism of a recent discovered association of type 2 diabetes with the ACAA-insertion/deletion polymorphism at the 3'UTR of the IGF2R gene has remained unclear. A very recently emerging novel polymorphic control layer by microRNAs (miRNAs) makes it possible to elucidate this issue. In this study, a prediction by web tools MicroInspector and miRanda demonstrated that DNA sequence polymorphism (DSPs) ACAA-insertion/deletion in IGF2R 3'UTR is located within the hsa-miR-657 and hsa-miR-453 binding sites. And luciferase reporter assay revealed that hsa-miR-657 acts directly at the 3'UTR of the IGF2R. Furthermore, ACAA-deletion exerted a further repression compared with ACAA-insertion, indicating that hsa-miR-657 regulates IGF2R gene expression in a polymorphic control manner. Importantly, we also demonstrated that hsa-miR-657 can translationally regulate the IGF2R expression levels in Hep G2 cells. Thus, our findings testify the possibility that the ACAA-insertion/deletion polymorphism may result in the change of IGF2R expression levels at least in part by hsa-miR-657-mediated regulation, contributing to the elucidation for the pathogenesis of type 2 diabetes and raise the possibility that miRNAs or in combination with functional DNA sequence polymorphism may be valuable in the treatment of human type 2 diabetes.

The usage of quaternary ammonium compounds (QACs) as disinfectants has increased dramatically since the outbreak of COVID-19 pandemic, leading to potentially accelerated emergence of antibiotic resistance. Long-term exposure to subinhibitory level QACs can lead to multidrug resistance, but the contribution of mutagenesis to resistance evolution is obscure. In this study, we subcultured E. coli K-12 under subinhibitory (0.25 × and 0.5 × Minimum Inhibitory Concentration, MIC) or inhibitory (1 × and 2 × MIC) concentrations of benzalkonium chloride (BAC, mono-chained) or didecyldimethylammonium chloride (DDAC, twin-chained) for 60 days. The sensitivity of QAC-adapted cells to five typical antibiotics decreased significantly, and in particular, the MIC of rifampicin increased by 85 times. E. coli adapted faster to BAC but developed 20-167% higher antibiotic resistance with 56% more mutations under DDAC exposure. The broader mutations induced by QACs, including negative regulators (acrR, marR, soxR, and crp), outer membrane proteins and transporters (mipA and sbmA), and RNA polymerase (rpoB and rpoC), potentially contributed to the high multi-drug resistance. After QACs stresses were removed, the phenotypic resistance induced by subinhibitory concentrations of QACs was reversible, whereas that induced by inhibitory concentrations of QACs was irreversible. The different patterns and molecular mechanism of antibiotic resistance induced by BAC and DDAC is informative to estimating the risks of broader QACs present at varied concentrations in the environment.

Chrysanthemum dichrum is an important wild species in the family Asteraceae. However, because of a lack of genetic information, there has been relatively little research conducted on the molecular mechanisms in C. dichrum. There is no report describing the transcriptome and metabolome of C. dichrum flowers and leaves at different developmental stages. In this study, high-throughput sequencing and RNA-seq analyses were used to investigate the transcriptome of C. dichrum leaves, flower buds, and blooming flowers. Additionally, these three tissues also underwent a metabolomics analysis. A total of 447,313,764 clean reads were assembled into 77,683 unigenes, with an average length of 839 bp. Of the 44,204 annotated unigenes, 42,189, 28,531, 23,420, and 17,599 were annotated using the Nr, Swiss-Prot, KOG, and KEGG databases, respectively. Furthermore, 31,848 differentially expressed genes (DEGs) were detected between the leaves and flower buds, whereas 23,197 DEGs were detected between the leaves and blooming flowers, and 11,240 DEGs were detected between the flower buds and blooming flowers. Finally, a quantitative real-time Polymerase Chain Reaction (qRT-PCR) assay was conducted to validate the identified DEGs. The metabolome data revealed several abundant metabolites in C. dichrum leaves, flower buds, and blooming flowers, including raffinose, 1-kestose, asparagine, glutamine, and other medicinal compounds. The expression patterns of significant DEGs revealed by the transcriptome analysis as well as the data for the differentially abundant metabolites in three C. dichrum tissues provide important genetic and metabolic information relevant for future investigations of the molecular mechanisms in C. dichrum. Moreover, the results of this study may be useful for the molecular breeding, development, and application of C. dichrum resources.

Drought is an important abiotic factor that threatens the growth and development of plants. Verbena bonariensis is a widely used landscape plant with a very high ornamental value. We found that Verbena has drought tolerance in production practice, so in order to delve into its mechanism of drought resistance and screen out its drought-resistance genes, we used the RNA-Seq platform to perform a de novo transcriptome assembly to analyze Verbena transcription response to drought stress. By high-throughput sequencing with Illumina Hiseq Xten, a total of 44.59 Gb clean data was obtained from T01 (control group) and T02 (drought experiment group). After assembly, 111,313 unigenes were obtained, and 53,757 of them were annotated by compared databases. In this study, 4829 differentially expressed genes were obtained, of which 4165 were annotated. We performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses, and explored a lot of differently expressed genes related to plant energy production, hormone synthesis, cell signal transduction, and metabolism to understand the stress response of Verbena in drought stress. In addition, we also found that a series of TFs related to drought-resistance of Verbena and provide excellent genetic resources for improving the drought tolerance of crops.

Multiple mechanisms underlying the development of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi-omics data on PVTTs in HCCs have made it possible to investigate whether PVTTs originate from the corresponding primary tumors (Ts).

Acute lung injury (ALI) is a life-threatening disorder related to serious pulmonary inflammation. Narciclasine exhibits strong anti-inflammation activity and attenuates the reactive oxygen species (ROS) production. The present study aims to investigate the underlying mechanism related to the effect of narciclasine on the pathogenesis of neonatal acute lung injury (ALI). Narciclasine attenuated LPS-induced pathological injury and pulmonary edema. In addition, narciclasine suppressed the secretion of inflammatory cytokines, including necrosis factor-α (TNF-α), Interleukin (IL-6), IL-1β, monocyte chemotactic protein-1 (MCP-1) in serum, and inhibited the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in lung tissues of neonatal ALI rats. Furthermore, narciclasine alleviated oxidative stress and apoptosis in lung tissues. Importantly, narciclasine exerted an inhibition effect on NF-κB nuclear translocation and activation of Toll-like Receptor 4 (TLR4)/Nuclear factor (NF)-κB/Cyclooxygenase 2 (Cox2) signaling pathway. Taken together, narciclasine protected against lung injury via inhibition effect on excessive inflammation, oxidative stress and apoptosis, hence, narciclasine may be considered as an effective and novel agent for clinical therapeutic strategy of ALI Treatment.

Splicing factor 3b subunit 4 (SF3B4) is a splicing factor and potential oncogene in hepatocellular carcinoma (HCC); however, its regulatory mechanism is yet unclear. We aimed to determine the role of SF3B4 in HCC and the underlying mechanism.

The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors, including hepatocellular carcinoma (HCC). Small nucleolar RNAs (snoRNAs) regulate ribosome biogenesis by guiding the modification of ribosomal RNAs (rRNAs). However, the underlying mechanism of this process in HCC remains elusive.

The chrysanthemum DgLsL gene, homologous with tomato Ls, is one of the earliest expressed genes controlling axillary meristem initiation. In this study, the wild-type chrysanthemum (CW) and DgLsL-overexpressed line 15 (C15) were used to investigate the regulatory mechanism of axillary bud development in chrysanthemum. Transcriptome sequencing was carried out to detect the differentially expressed genes of the axillary buds 0 h, 24 h and 48 h after decapitation. The phenotypic results showed that the number of axillary buds of C15 was significantly higher than CW. A total of 9,224 DEGs were identified in C15-0 vs. CW-0, 10,622 DEGs in C15-24 vs. CW-24, and 8,929 DEGs in C15-48 vs. CW-48.GO and KEGG pathway enrichment analyses showed that the genes of the flavonoid, phenylpropanoids and plant hormone pathways appeared to be differentially expressed, indicating their important roles in axillary bud germination. DgLsL reduces GA content in axillary buds by promoting GA2ox expression.These results confirmed previous studies on axillary bud germination and growth, and revealed the important roles of genes involved in plant hormone biosynthesis and signal transduction, aiding in the study of the gene patterns involved in axillary bud germination and growth.

To improve the early diagnosis of hepatocellular carcinoma (HCC), more effective diagnostic biomarkers are needed. A combination of biomarkers is reported to distinguish individuals with early-stage HCC from at-risk individuals.

Immobilizing metal atoms by multiple nitrogen atoms has triggered exceptional catalytic activity toward many critical electrochemical reactions due to their merits of highly unsaturated coordination and strong metal-substrate interaction. Herein, atomically dispersed Fe-NC material with precise sulfur modification to Fe periphery (termed as Fe-NSC) was synthesized, X-ray absorption near edge structure analysis confirmed the central Fe atom being stabilized in a specific configuration of Fe(N3)(N-C-S). By enabling precisely localized S doping, the electronic structure of Fe-N4 moiety could be mediated, leading to the beneficial adjustment of absorption/desorption properties of reactant/intermediate on Fe center. Density functional theory simulation suggested that more negative charge density would be localized over Fe-N4 moiety after S doping, allowing weakened binding capability to *OH intermediates and faster charge transfer from Fe center to O species. Electrochemical measurements revealed that the Fe-NSC sample exhibited significantly enhanced oxygen reduction reaction performance compared to the S-free Fe-NC material (termed as Fe-NC), showing an excellent onset potential of 1.09 V and half-wave potential of 0.92 V in 0.1 M KOH. Our work may enlighten relevant studies regarding to accessing improvement on the catalytic performance of atomically dispersed M-NC materials by managing precisely tuned local environments of M-Nx moiety.