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BackgroundThyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research.MethodsThe searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD.ResultsOverall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p

Abstract Background Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations. Methods This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations. Results Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p

By polymerization of gadolinium methacrylate (Gd (MAA)3), lead methacrylate (Pb(MAA)2) and methyl methacrylate (MMA), Gd and Pb were chemically bonded into polymers. The X-ray shielding performance was evaluated by Monte Carlo simulation method, and the results showed that the more metal functional organic monomer, the better the shielding performance of terpolymers. When the X-ray energy is 65 keV, Gd (MAA)3-containing polymers have better shielding performance than Pb(MAA)2-containing polymers. Gd could compensate for the weak absorption region of Pb. Therefore, polymers containing both Gd and Pb enhanced shielding efficiency against X-ray in various low-energy ranges. For obtaining terpolymers with uniform monomer compositions, the relationship between the monomer composition of the terpolymers and the conversion level was optimized by calculating the reactivity ratios. The value of reactivity ratios of r (Gd (MAA)3/Pb(MAA)2), r (Pb(MAA)2/Gd (MAA)3), r (Gd (MAA)3/MMA), r (MMA/Gd (MAA)3), r (Pb(MAA)2/MMA) and r (MMA/Pb(MAA)2) was 0.483, 0.004, 0.338, 2.508, 0.255, 0.029. The terpolymers with uniform monomer composition could be obtained by controlling the monomer compositions or conversion levels. The results can provide new radiation protection materials and contribute to the improvement in nuclear safety.

Summary: Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, and among the non-invasive tests, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) have shown better diagnostic performance in NAFLD. This meta-analysis aimed to evaluate the performance of CAP and LSM for assessing steatosis and fibrosis in NAFLD. Methods: We searched the PubMed, Web of Science, Cochrane Library, and Embase databases for relevant articles published up to February 13th, 2022, and selected studies that met the inclusion and exclusion criteria, and evaluated the quality of evidence. Then we pooled sensitivity (SE), specificity (SP), and area under receiver operating characteristic (AUROC) curves. A random effect model was applied regardless of heterogeneity. Meta-regression analysis and subgroup analysis were performed to explore heterogeneity, and Fagan plot analysis was used to evaluate clinical utility. This meta-analysis was completed in Nanjing, Jiangsu and registered on PROSPERO (CRD42022309965). Findings: A total of 10537 patients from 61 studies were included in our meta-analysis. The AUROC of CAP were 0·924, 0·794 and 0·778 for steatosis grades ≥ S1, ≥ S2 and = S3, respectively, and the AUROC of LSM for detecting fibrosis stages ≥ F1, ≥ F2, ≥ F3, and = F4 were 0·851, 0·830, 0·897 and 0·925, respectively. Subgroup analysis revealed that BMI ≥ 30 kg/m² had lower accuracy for diagnosing S ≥ S1, ≥ S2 than BMI

Abstract Transcription factor SP1 could manipulate pathways involved in ovarian cancer progression. LncRNAs are involved in SP1‐mediated tumorigenesis. LncRNA DANCR could promote metastasis of ovarian cancer. However, the regulatory function and involvement of SP1‐induced lncRNA DANCR in ovarian cancer remain elusive. Data from this study showed that SP1 was up‐regulated in ovarian cancer tissues and cells (CAOV3, SKOV3, A2780), and SP1 could bind to the promoter region of DANCR through chromatin immunoprecipitation and leuciferase activity assays. Therefore, DANCR was transcriptionally induced by SP1 in ovarian cancer tissues and cells (CAOV3, SKOV3, A2780). Functionally, reduced expression of DANCR suppressed cell viability, migration and invasion of CAOV3, while enhanced DANCR expression contributed to SKOV3 growth. Over‐expression of SP1 reversed the suppressive effects of DANCR interference on ovarian cancer progression. In conclusion, SP1‐induced DANCR contributed to oncogenic potential of ovarian cancer, suggesting a promising therapeutic target for ovarian cancer.

We consider the continuous Heisenberg spin chain equation S→t=α(t)S→×S→xx+β(t)S→x,S→⋅S→=1,where α(t)and β(t)are the parameters to describe the bilinear interaction, and the spin-transfer torque resulted from the spin-polarized current, respectively. We present explicitly the rogue wave solutions based on the gauge equivalence between the spin chain equation and a kind of nonlinear Schrödinger equation.

Abstract Background The five-year survival rate and therapeutic effect of malignant glioma is low. Identification of key/associated proteins and pathways in glioma is necessary for developing effective diagnosis and targeted therapy of glioma. In addition, Glioma involves hypoxia-specific microenvironment, whether hypoxia restriction influences the stoichioproteomic characteristics of expressed proteins is unknown. Methods In this study, we analyzed the most comprehensive immunohistochemical data from 12 human glioma samples and 4 normal cell types of cerebral cortex, identified differentially expressed proteins (DEPs), and researched the oxygen contents of DEPs, highly and lowly expressed proteins. Further we located key genes on human genome to determine their locations and enriched them for key functional pathways. Results Our results showed that although no difference was detected on whole proteome, the average oxygen content of highly expressed proteins is 6.65% higher than that of lowly expressed proteins in glioma. A total of 1480 differentially expressed proteins were identified in glioma, including 226 up regulated proteins and 1254 down regulated proteins. The average oxygen content of up regulated proteins is 2.56% higher than that of down regulated proteins in glioma. The localization of differentially expressed genes on human genome showed that most genes were on chromosome 1 and least on Y. The up regulated proteins were significantly enriched in pathways including cell cycle, pathways in cancer, oocyte meiosis, DNA replication etc. Functional dissection of the up regulated proteins with high oxygen contents showed that 51.28% of the proteins were involved in cell cycle and cyclins. Conclusions Element signature of oxygen limitation could not be detected in glioma, just as what happened in plants and microbes. Unsaved use of oxygen by the highly expressed proteins and DEPs were adapted to the fast division of glioma cells. This study can help to reveal the molecular mechanism of glioma, and provide a new approach for studies of cancer-related biomacromolecules. In addition, this study lays a foundation for application of stoichioproteomics in precision medicine.

Abstract Background Despite the medical importance of the genus Culex, the mitochondrial genome (mt genome) characteristics of Culex spp. are not well understood. The phylogeny of the genus and particularly the generic status of the genus Lutzia and the subgenus Culiciomyia remain unclear. Methods The present study sequenced and analyzed the complete mt genomes of Lutzia halifaxia, Lutzia fuscanus and Cx. (Culiciomyia) pallidothorax and assessed the general characteristics and phylogenetics of all known 16 mt genome sequences for species in the genera Culex and Lutzia. Results The complete mt genomes of Lt. halifaxia, Lt. fuscanus and Cx. pallidothorax are 15,744, 15,803 and 15,578 bp long, respectively, including 13 PCGs, 22 tRNAs, two tRNAs and a control region (CR). Length variations in the Culex and Lutzia mt genomes involved mainly the CR, and gene arrangements are the same as in other mosquitoes. We identified four types of repeat units in the CR sequences, and the poly-T stretch exists in all of these mt genomes. The repeat units of CR are conserved to different extent and provide information on their evolution. Phylogenetic analyses demonstrated that the Coronator and Sitiens groups are each monophyletic, whereas the monophyletic status of the Pipiens Group was not supported; Cx. pallidothorax is more closely related to the Sitiens and Pipiens groups; and both phylogenetics analysis and repeat unit features in CR show that Lutzia is a characteristic monophyletic entity, which should be an independent genus. Conclusions To our knowledge, this is the first comprehensive review of the mt genome sequences and taxonomic discussion based on the mt genomes of Culex spp. and Lutzia spp. The research provides general information on the mt genome of these two genera, and the phylogenetic and taxonomic status of Lutzia and Culiciomyia.

Abstract Background UDP-glycosyltransferase (UGT) is an important biotransformation superfamily of enzymes. They catalyze the transfer of glycosyl residues from activated nucleotide sugars to acceptor hydrophobic molecules, and function in several physiological processes, including detoxification, olfaction, cuticle formation, pigmentation. The diversity, classification, scaffold location, characteristics, phylogenetics, and evolution of the superfamily of genes at whole genome level, and their association and mutations associated with pyrethroid resistance are still little known. Methods The present study identified UGT genes in Anopheles sinensis genome, classified UGT genes in An. sinensis, Anopheles gambiae, Aedes aegypti and Drosophila melanogaster genomes, and analysed the scaffold location, characteristics, phylogenetics, and evolution of An. sinensis UGT genes using bioinformatics methods. The present study also identified the UGTs associated with pyrethroid resistance using three field pyrethroid-resistant populations with RNA-seq and RT-qPCR, and the mutations associated with pyrethroid resistance with genome re-sequencing in An. sinensis. Results There are 30 putative UGTs in An. sinensis genome, which are classified into 12 families (UGT301, UGT302, UGT306, UGT308, UGT309, UGT310, UGT313, UGT314, UGT315, UGT36, UGT49, UGT50) and further into 23 sub-families. The UGT308 is significantly expanded in gene number compared with other families. A total of 119 UGTs from An. sinensis, An. gambiae, Aedes aegypti and Drosophila melanogaster genomes are classified into 19 families, of which seven are specific for three mosquito species and seven are specific for Drosophila melanogaster. The UGT308 and UGT302 are proposed to main families involved in pyrethroid resistance. The AsUGT308D3 is proposed to be the essential UGT gene for the participation in biotransformation in pyrethroid detoxification process, which is possibly regulated by eight SNPs in its 3′ flanking region. The UGT302A3 is also associated with pyrethroid resistance, and four amino acid mutations in its coding sequences might enhance its catalytic activity and further result in higher insecticide resistance. Conclusions This study provides the diversity, phylogenetics and evolution of UGT genes, and potential UGT members and mutations involved in pyrethroid resistance in An. sinensis, and lays an important basis for the better understanding and further research on UGT function in defense against insecticide stress.

Abstract Background Eukaryotic cells contain a huge variety of internally specialized subcellular compartments. Stoichiogenomics aims to reveal patterns of elements usage in biological macromolecules. However, the stoichiogenomic characteristics and how they adapt to various subcellular microenvironments are still unknown. Results Here we first updated the definition of stoichiogenomics. Then we applied it to subcellular research, and detected distinctive nitrogen content of nuclear and hydrogen, sulfur content of extracellular proteomes. Specially, we found that acidic amino acids (AAs) content of cytoskeletal proteins is the highest. The increased charged AAs are mainly caused by the eukaryotic originated cytoskeletal proteins. Functional subdivision of the cytoskeleton showed that activation, binding/association, and complexes are the three largest functional categories. Electrostatic interaction analysis showed an increased electrostatic interaction between both primary sequences and PPI interfaces of 3D structures, in the cytoskeleton. Conclusions This study creates a blueprint of subcellular stoichiogenomic characteristics, and explains that charged AAs of the cytoskeleton increased greatly in evolution, which offer material basis for the eukaryotic cytoskeletal proteins to act in two ways of electrostatic interactions, and further perform their activation, binding/association and complex formation.

Therapeutic effects of anticancer medicines can be improved by targeting the specific receptors on cancer cells. Folate receptor (FR) targeting with antibody (Ab) is an effective tool to deliver anticancer drugs to the cancer cell. In this research project, a novel formulation of targeting drug delivery was designed, and its anticancer effects were analyzed. Folic acid-conjugated magnetic nanoparticles (MNPs) were used for the purification of folate receptors through a novel magnetic affinity purification method. Antibodies against the folate receptors and methotrexate (MTX) were developed and characterized with enzyme-linked immunosorbent assay and Western blot. Targeting nanomedicines (MNP-MTX-FR Ab) were synthesized by engineering the MNP with methotrexate and anti-folate receptor antibody (anti-FR Ab). The cytotoxicity of nanomedicines on HeLa cells was analyzed by calculating the % age cell viability. A fluorescent study was performed with HeLa cells and tumor tissue sections to analyze the binding efficacy and intracellular tracking of synthesized nanomedicines. MNP-MTX-FR Ab demonstrated good cytotoxicity along all the nanocomposites, which confirms that the antibody-coated medicine possesses the potential affinity to destroy cancer cells in the targeted drug delivery process. Immunohistochemical approaches and fluorescent study further confirmed their uptake by FRs on the tumor cells’ surface in antibody-mediated endocytosis. The current approach is a useful addition to targeted drug delivery for better management of cancer therapy along with immunotherapy in the future.

The mortality rate of acute severe intraventricular hematoma is extremely high, and the rate of disability in survivors is high. Intraventricular hematoma has always been a difficult problem for clinical treatment. Although minimally invasive endoscopic hematoma evacuation is widely used to treat this disease, the technique still has room for improvement. Equipment for the intra-neuroendoscopic technique (INET) consists of two of our patented inventions: a transparent sheath (Patent No. ZL 200820046232.0) and a hematoma aspirator (Patent No. ZL 201520248717.8). This study explored the safety and efficacy of INET by comparing it with extraventricular drainage in combination with urokinase thrombolytic therapy. This trial recruited 65 patients with severe intraventricular hemorrhage, including 35 (19 men and 16 women, aged 53.2 ± 8.7 years) in the INET group and 30 (17 men and 13 women, aged 51.5 ± 7.9 years) in the control group (extraventricular drainage plus urokinase thrombolytic therapy). Our results showed that compared with the control group, the INET group exhibited lower intraventricular hemorrhage volumes, shorter intensive care-unit monitoring and ventricular drainage-tube placement times, and fewer incidences of intracranial infection, secondary bleeding, and mortality. Thus, the prognosis of survivors had improved remarkably. These findings indicate that INET is a safe and efficient new method for treating severe intraventricular hematoma. This trial was registered with ClinicalTrials.gov (NCT02515903).

Anopheles sinensis is a major malarial vector in China and Southeast Asia. The mitochondria is involved in many important biological functions. Nuclear mitochondrial DNA segments (NUMTs) are common in eukaryotic organisms, but their characteristics are poorly understood. We sequenced and analyzed the complete mitochondrial (mt) genome of An. sinensis. The mt genome is 15,418 bp long and contains 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs and a large non-coding region. Its gene arrangement is similar to previously published mosquito mt genomes. We identified and analyzed the NUMTs of 19 mosquito species with both nuclear genomes and mt genome sequences. The number, total length and density of NUMTs are significantly correlated with genome size. About half of NUMTs are short (< 200 bp), but larger genomes can house longer NUMTs. NUMTs may help explain genome size expansion in mosquitoes. The expansion due to mitochondrial insertion segments is variable in different insect groups. PCGs are transferred to nuclear genomes at a higher frequency in mosquitoes, but NUMT origination is more different than in mammals. Larger-sized nuclear genomes have longer mt genome sequences in both mosquitoes and mammals. The study provides a foundation for the functional research of mitochondrial genes in An. sinensis and helps us understand the characteristics and origin of NUMTs and the potential contribution to genome expansion.

Abstract Background Anopheles sinensis is the major malaria vector in China and Southeast Asia. Vector control is one of the most effective measures to prevent malaria transmission. However, there is little transcriptome information available for the malaria vector. To better understand the biological basis of malaria transmission and to develop novel and effective means of vector control, there is a need to build a transcriptome dataset for functional genomics analysis by large-scale RNA sequencing (RNA-seq). Methods To provide a more comprehensive and complete transcriptome of An. sinensis, eggs, larvae, pupae, male adults and female adults RNA were pooled together for cDNA preparation, sequenced using the Illumina paired-end sequencing technology and assembled into unigenes. These unigenes were then analyzed in their genome mapping, functional annotation, homology, codon usage bias and simple sequence repeats (SSRs). Results Approximately 51.6 million clean reads were obtained, trimmed, and assembled into 38,504 unigenes with an average length of 571 bp, an N50 of 711 bp, and an average GC content 51.26%. Among them, 98.4% of unigenes could be mapped onto the reference genome, and 69% of unigenes could be annotated with known biological functions. Homology analysis identified certain numbers of An. sinensis unigenes that showed homology or being putative 1:1 orthologues with genomes of other Dipteran species. Codon usage bias was analyzed and 1,904 SSRs were detected, which will provide effective molecular markers for the population genetics of this species. Conclusions Our data and analysis provide the most comprehensive transcriptomic resource and characteristics currently available for An. sinensis, and will facilitate genetic, genomic studies, and further vector control of An. sinensis.

Pyrazinamide (PZA) is the only drug for the elimination of latent Mycobacterium tuberculosis (MTB) isolates. However, due to the increased number of PZA-resistance, the chances of the success of global TB elimination seems to be more prolonged. Recently, marine natural products (MNPs) as an anti-TB agent have received much attention, where some compounds extracted from marine sponge, Haliclona sp. exhibited strong activity under aerobic and hypoxic conditions. In this study, we screened articles from 1994 to 2019 related to marine natural products (MNPs) active against latent MTB isolates. The literature was also mined for the major regulators to map them in the form of a pathway under the dormant stage. Five compounds were found to be more suitable that may be applied as an alternative to PZA for the better management of resistance under latent stage. However, the mechanism of actions behind these compounds is largely unknown. Here, we also applied synthetic biology to analyze the major regulatory pathway under latent TB that might be used for the screening of selective inhibitors among marine natural products (MNPs). We identified key regulators of MTB under latent TB through extensive literature mining and mapped them in the form of regulatory pathway, where SigH is negatively regulated by RshA. PknB, RshA, SigH, and RNA polymerase (RNA-pol) are the major regulators involved in MTB survival under latent stage. Further studies are needed to screen MNPs active against the main regulators of dormant MTB isolates. To reduce the PZA resistance burden, understanding the regulatory pathways may help in selective targets of MNPs from marine natural sources.

A new flavonol glycoside together with five known phenolic compounds were isolated from the whole herb of Callianthemum taipaicum. The compounds were identified as isorhamnetin-3-O-α-L-arabinoside-7-O-β-D-glucoside (1), isorhamnetin-3-O-β-D-glucoside (2), dibutyl phthalate (3), (+)-1-hydroxylpinoresinol-4'-β-D-glucoside (4), pinoresinol-4'-O-β-D-glucoside (5) and 2-phenylethyl-β-primeveroside (6). Compound 1 was identified as a new flavonol glycoside. The compound 6 was isolated for the first time as natural product. All compounds were isolated for the first time from the Callianthemum genus. Furthermore, the 2D-NMR data of the four known compounds 2–5 are given for the first time in this paper. All the structures were identified on the basis of detailed spectral analysis. The compounds 1 and 4 exhibited certain antifungal activity.

OBJECTIVE This study aimed to explore the expression and significance of transforming growth factor β1(TGF-β1), extracellular signal-regulated kinases 1/2 (ERK1/2), and K-ras in colorectal cancer (CRC) using tissue microarray technology.METHODS The expressions of TGF-β1, ERK1/2, and K-ras in colon cancer cells taken from the specimens of 92 CRC patients (stage I: 16 cases, stage II: 28 cases, stage III: 24 cases, and stage IV: 24 cases) were analyzed using tissue microarray technology and immunohistochemistry, and compared with those of 20 normal colon tissue samples.RESULTS High immunoreactive scores (IRS) of TGF-β1, p-ERK1/2, and K-ras protein in CRC were obtained, which were 66.3% (61/92), 59.8% (55/92), and 48.9% (45/92), respectively, and those in normal epithelial cells of colon were 10% (2/20), 20% (4/20), and 30% (6/20), respectively (P0.05).CONCLUSION High level expressions of TGF-β1 and ERK1/2 are closely related to the clinical stages of colon cancer and crosstalk may exist between the 2 signal pathways.

The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.

The title compound, C17H12BrClN2O, was synthesized by oxidation of [3-(4-bromophenyl)-1-(4-chlorobenzyl)-1H-pyrazol-5-yl]methanol under mild conditions. The pyrazole ring makes dihedral angles of 3.29 (9) and 74.91 (4)°, respectively, with the bromophenyl and chlorophenyl rings.

In the title compound, C16H13N3O4, the imidazo[1,2-a]pyridine and benzene rings make a dihedral angle of 56.21 (2)°. The crystal packing is stabilized by weak π–π stacking interactions [centroid–centroid distances = 3.787 (2) Å] and C—H...O intermolecular hydrogen-bonding interactions.

Since the late 2010s, Artificial Intelligence (AI) including machine learning, boosted through deep learning, has boomed as a vital tool to leverage computer vision, natural language processing and speech recognition in revolutionizing zoological research. This review provides an overview of the primary tasks, core models, datasets, and applications of AI in zoological research, including animal classification, resource conservation, behavior, development, genetics and evolution, breeding and health, disease models, and paleontology. Additionally, we explore the challenges and future directions of integrating AI into this field. Based on numerous case studies, this review outlines various avenues for incorporating AI into zoological research and underscores its potential to enhance our understanding of the intricate relationships that exist within the animal kingdom. As we build a bridge between beast and byte realms, this review serves as a resource for envisioning novel AI applications in zoological research that have not yet been explored. [ABSTRACT FROM AUTHOR]

Background. Parkinson's disease (PD) is characterized as a neurodegenerative disease; however, the mechanisms regarding its pathogenesis have not been fully explored. Objectives. To explore the role of circular RNA homeodomain interacting protein kinase 3 (circHIPK3) in the progression of PD. Materials and methods. The circHIPK3 and microRNA-124 (miR-124) expression in human serum and cerebral fluid was detected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 92 PD patients and 95 controls. The circHIPK3 was overexpressed and/or silenced in cells to explore its molecular mechanisms and effects on neuroinflammation. The production of intracellular reactive oxygen species (ROS) was assessed using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Interleukin 6 (IL-6), IL-1β and tumor necrosis factor alpha (TNF-α) production in BV2 cells after the indicated treatment was measured using enzyme-linked immunosorbent assay (ELISA). The protein expression of microglia markers (cluster of differentiation molecule 11b (CD11b) and ionized calcium-binding adapter molecule 1 (Iba-1)), pyroptosis-related factors, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC), and caspase-1, signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) were examined using western blot analysis. Furthermore, the interaction between circHIPK3, miR-124 and STAT3 was predicted with bioinformatics and examined using fluorescence in situ hybridization (FISH), luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation (RIP). Results. The expression of circHIPK3 in human serum and cerebral fluids was significantly higher than in controls, whereas miR-124 expression was drastically reduced. In addition, lipopolysaccharide (LPS)- treated BV2 cells exhibited higher expression of circHIPK3 and lower miR-124 expression. The SH-SY5Y cells exhibited a significantly impaired viability and elevated apoptotic rate, along with an upregulation of circHIPK3 and a downregulation of miR-124 expression after being treated with supernatants collected from LPS-treated BV2 cells. The upregulation of circHIPK3 increased IL-6, IL-1β and TNF-α secretion in BV2 cells. The protein expressions of microglia markers (CD11b and Iba-1), as well as pyroptosis-related factors, NLRP3, caspase-1, and ASC, were also increased following the expression of circHIPK3. All these effects were reversed by the addition of miR-124. Conclusions. The circHIPK3 enhances neuroinflammation by sponging miR-124 and regulating the miR-124. [ABSTRACT FROM AUTHOR]

Actinide mononitrides as a promising advanced nuclear fuel have recently earned much attention. We herein studied the electronic and mechanical properties of the ternary actinide mixed mononitrides A0.5B0.5N (A, B=U, Np, and Pu) using the density functional theory +U method. It is found that in the studied ternary mixed mononitrides, the 5f electronic states of all actinide atoms maintain the local electronic character and do not overlap with each other. Compared with their corresponding binary mononitrides, the U-N bond becomes more ionic, where the Np-N and Pu-N bonds become more covalent in ternary actinide mixed mononitrides. The mechanical properties (such as bulk and shear moduli, Young’s modulus, and Poisson’s ratio) of three ternary actinide (U-Pu) mononitrides are found to be similar to that of their corresponding binary actinide mononitrides and thus are expected not to misbehave with actinide mononitrides in respect of mechanics. In addition, all the three ternary actinide mononitrides have no imaginary frequencies in their vibration curves and correspondingly satisfy the stability criteria for elastic constants of tetragonal structures. [ABSTRACT FROM AUTHOR]