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Six iridium complexes were designed and studied using the DFT approach, (ppy) 2 Ir(pic) (1), (f 4 ppy) 2 Ir(pic) (2), (ppy) 2 Ir(tmd) (3), (f 4 ppy) 2 Ir(tmd) (4), (ppy) 2 Ir(tpip) (5) and (f 4 ppy) 2 Ir(tpip) (6). Here ppy denotes phenylpyridine, f 4 ppy denotes 2-(2,3,4,5-tetrafluorophenyl) pyridine, pic denotes benzoic acid, tmd denotes 5-hydroxy-2,2,6,6-tetramethylhept-4-en-3-one and tpip denotes tetraphenylimido-diphosphinate. The geometries, absorptions, emissions, frontier molecular orbitals, and spin-orbit coupling (SOC) constants of the 6 complexes were evaluated. An intriguing phenomenon was observed during the excitation process of these molecules. It was discovered that, in the ground state, the Frontier Molecular Orbitals (FMOs) of these molecules were loosely arranged throughout the molecule. However, in the Lowest Unoccupied Molecular Orbitals (LUMO) of the triplet excited state, the FMOs become concentrated around the metal core and a maximum of two ligands. Furthermore, the analysis of the energy difference between the lowest singlet excited state and the lowest triplet excited state (Δ E S 1 T 1 ) of these complexes in conjunction with their spin-orbit coupling performance indicated that complex 1 exhibits characteristics consistent with Thermally Activated Delayed (TAD) fluorescence. We hope that this research can serve as a reference for practical experimental synthesis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Although the pathogenesis of osteoarthritis (OA) is unclear, inflammatory cytokines are related to its occurrence. However, few studies focused on the therapeutic strategies of regulating joint homeostasis by simultaneously remodeling the anti-inflammatory and immunomodulatory microenvironments. Fibroblast growth factor 18 (FGF18) is the only disease-modifying OA drug (DMOAD) with a potent ability and high efficiency in maintaining the phenotype of chondrocytes within cell culture models. However, its potential role in the immune microenvironment remains unknown. Besides, information on an optimal carrier, whose interface and chondral-biomimetic microenvironment mimic the native articular tissue, is still lacking, which substantially limits the clinical efficacy of FGF18. Herein, to simulate the cartilage matrix, chondroitin sulfate (ChS)-based nanoparticles (NPs) are integrated into poly(D, L-lactide)-poly(ethylene glycol)-poly(D, L-lactide) (PLEL) hydrogels to develop a bionic thermosensitive sustainable delivery system. Electrostatically self-assembled ChS and ε-poly-l-lysine (EPL) NPs are prepared for the bioencapsulation of FGF18. This bionic delivery system suppressed the inflammatory response in interleukin-1β (IL-1β)-mediated chondrocytes, promoted macrophage M2 polarization, and inhibited M1 polarization, thereby ameliorating cartilage degeneration and synovitis in OA. Thus, the ChS-based hydrogel system offers a potential strategy to regulate the chondrocyte-macrophage crosstalk, thus re-establishing the anti-inflammatory and immunomodulatory microenvironment for OA therapy., (© 2024 Wiley‐VCH GmbH.)

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single-component dual-functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)-generated HOCl. A representative prodrug (DHU-CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU-CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU-CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase-2 (COX-2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX-2. Downstream prostaglandins E 2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU-CBA2 promotes infiltration and function of CD8 + T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single-component dual-functional prodrug activated by TME-specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX-2 inhibitor., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (β = 1400.230 mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (β = -0.006 mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale and Objectives: Clinicians must precisely pinpoint the etiology of low back pain as the number of people suffering from it increases to provide targeted care. The purpose of this paper was to use MR imaging radiomics based on lumbar soft tissue to analyze changes in the lumbar fascia of patients with low back pain., Materials and Methods: We retrospectively analyzed the lumbar MRI of 197 patients with low back pain. Patients were randomly assigned to either the training (n = 138) or validation (n = 59) cohorts. Multivariate logistic regression analysis was used to create radiomics model and combined nomogram model and their predictive performance were evaluated using receiver operating characteristic curves., Results: Seven radiomics features based on lumbar soft tissue MRI images were established, which performed well in distinguishing between low back pain patients with fascial changes and normal individuals demonstrated an excellent ability to identify differences, with an Area Under Curve (AUC) of 0.92 (95% CI, 0.88-0.96) in the training cohort and 0.84 (95% CI, 0.73-0.96) in the validation cohort, which performed better than the clinical model significantly only., Conclusion: The nomogram based on clinical features and radiomics features of MR images had a good predictive ability to differentiate fascial alterations in patients with low back pain from normal subjects. It had the potential to be used as a decision support tool to assist clinicians in determining the etiology of patients with lower back pain and managing patients promptly, particularly in the early stage of the fasciitis when significant abnormalities on imaging were difficult to detect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The luminescence characteristics of small molecule excited B 40 have not been studied yet, and it may have a potential application value in quantum dot luminescence. Herein, the adsorption and fluorescence emission spectra of small molecules (pyridine, pyrazine and benzene) adsorbed on B 40 are studied using first-principles. The results show that the absorption of pyridine and pyrazine on B 40 can form stable chemisorption structures pyridine-B 40 and pyrazine-B 40 , while benzene adsorption can form physisorption structure benzene-B 40 . Moreover, the adsorbed pyridine can enhance the intensity of emission spectra of B 40 . And the pyrazine adsorbed can obviously enhance the intensity of absorption and emission spectra of B 40 and cause the spectra to redshift to the visible light range. And the adsorption of benzene has almost no enhancement effect on absorption and emission spectra of B 40 . In addition, the influence of different computational basis sets on spectra characteristics has also been discussed and the results show that the main peaks of absorption and emission spectra calculated by the diffuse function augmented basis sets are redshifted relatively. This finding provides a strategy for quantum dot luminescence and a theoretical reference for experimental research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Trichinella spiralis is a zoonotic parasite with worldwide distribution that can seriously harm human health and animal husbandry. Ornithine decarboxylase is a component of the acid resistance (AR) system in Escherichia coli. The aim of this study was to investigate the role that T. spiralis ornithine decarboxylase (TsODC) plays in the acid resistance mechanism of T. spiralis. This study involved assessing the transcription and expression of TsODC in worms under acidic conditions. According to mRNA sequences published by NCBI and the results of molecular biology experiments, the complete TsODC sequence was cloned and expressed. rTsODC had good immunogenicity, and immunofluorescence analysis revealed that TsODC was principally localized on the surface tissues of the nematode, especially at the head and tail. qRT‒PCR and Western blotting analysis indicated that the relative expression levels of TsODC mRNA and protein were highest when cultured at pH 2.5 for 2 h. The muscle larvae (ML) of T. spiralis were treated with curcumin and rapamycin, as well as arginine and TsODC polyantisera. The expression levels of TsODC mRNA and protein were significantly increased by arginine and suppressed by curcumin and rapamycin. After reducing the amount of TsODC, the relative expression of TsODC mRNA and the survival rate of T. spiralis ML were both reduced when compared to these values in the phosphate-buffered saline (PBS) group. The results indicated that TsODC is a member of the T. spiralis AR system and different treatments on TsODC have different effects; thus, these treatments might be a new way to prevent T. spiralis infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The factors affecting membrane fouling are very complex. In this study, the membrane fouling process was revealed from the perspective of ion environment changes, which affected the whey protein structure during ultrafiltration. It was found that the concentrations of Ca 2+ and Na + were overall increased and the concentrations of K + , Mg 2+ and Zn 2+ were decreased at an ultrafiltration time of 11 min, which made more hydrophilic groups buried inside and increased the content of α-helix, leading to more protein aggregation. The relatively higher K + ratio in retention could lead to an antiparallel β-sheet configuration, aspartic acid, glutamic acid and tryptophan increased, which resulted in more protein aggregation and deposition on the membrane surface at 17 min. When the ion concentration and ratio restored the balance and were close to the initial state in retention, the protein surface tension decreased, and the hydrophilic ability increased at 21-24 min., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Accurate target volume delineation is the premise for the implementation of precise radiotherapy. Inadequate target volume delineation may diminish tumor control or increase toxicity. Although several clinical target volume (CTV) delineation guidelines for rectal cancer have been published in recent years, significant interobserver variation (IOV) in CTV delineation still exists among radiation oncologists. However, proper education may serve as a bridge that connects complex guidelines with clinical practice., Aim: To examine whether an education program could improve the accuracy and consistency of preoperative radiotherapy CTV delineation for rectal cancer., Methods: The study consisted of a baseline target volume delineation, a 150-min education intervention, and a follow-up evaluation. A 42-year-old man diagnosed with stage IIIC (T3N2bM0) rectal adenocarcinoma was selected for target volume delineation. CTVs obtained before and after the program were compared. Dice similarity coefficient (DSC), inclusiveness index (IncI), conformal index (CI), and relative volume difference [ΔV (%)] were analyzed to quantitatively evaluate the disparities between the participants' delineation and the standard CTV. Maximum volume ratio (MVR) and coefficient of variation (CV) were calculated to assess the IOV. Qualitative analysis included four common controversies in CTV delineation concerning the upper boundary of the target volume, external iliac area, groin area, and ischiorectal fossa., Results: Of the 18 radiation oncologists from 10 provinces in China, 13 completed two sets of CTVs. In quantitative analysis, the average CTV volume decreased from 809.82 cm 3 to 705.21 cm 3 ( P = 0.001) after the education program. Regarding the indices for geometric comparison, the mean DSC, IncI, and CI increased significantly, while ΔV (%) decreased remarkably, indicating improved agreement between participants' delineation and the standard CTV. Moreover, an 11.80% reduction in MVR and 18.19% reduction in CV were noted, demonstrating a smaller IOV in delineation after the education program. Regarding qualitative analysis, the greatest variations in baseline were observed at the external iliac area and ischiorectal fossa; 61.54% (8/13) and 53.85% (7/13) of the participants unnecessarily delineated the external iliac area and the ischiorectal fossa, respectively. However, the education program reduced these variations., Conclusion: Wide variations in CTV delineation for rectal cancer are present among radiation oncologists in mainland China. A well-structured education program could improve delineation accuracy and reduce IOVs., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Voltage-driven stochastic magnetization switching in a nanomagnet has attracted more attention recently with its superiority in achieving energy-efficient artificial neuron. Here, a novel pure voltage-driven scheme with ∼27.66 aJ energy dissipation is proposed, which could rotate magnetization vector randomly using only a pair of electrodes covered on the multiferroic nanomagnet. Results show that the probability of 180° magnetization switching is examined as a sigmoid-like function of the voltage pulse width and magnitude, which can be utilized as the activation function of designed neuron. Considering the size errors of designed neuron in fabrication, it's found that reasonable thickness and width variations cause little effect on recognition accuracy for MNIST hand-written dataset. In other words, the designed pure voltage-driven spintronic neuron could tolerate size errors. These results open a new way toward the realization of artificial neural network with low power consumption and high reliability., (© 2022 IOP Publishing Ltd.)

Toxoplasma gondii is an obligate intracellular protozoan parasite, which has a worldwide distribution and can infect a large number of warm-blooded animals and humans. T. gondii must colonize and proliferate inside the host cells in order to maintain its own survival by securing essential nutrients for the development of the newly generated tachyzoites. The type II fatty acid biosynthesis pathway (FASII) in the apicoplast is essential for the growth and survival of T. gondii . We investigated whether deletion of genes in the FASII pathway influences the in vitro growth and in vivo virulence of T. gondii . We focused on beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) and oxidoreductase, short chain dehydrogenase/reductase family proteins ODSCI and ODSCII. We constructed T. gondii strains deficient in FabZ, ODSCI , and ODSCII using CRISPR-Cas9 gene editing technology. The results of immunofluorescence assay, plaque assay, proliferation assay and egress assay showed that in RHΔ FabZ strain the apicoplast was partly lost and the growth ability of the parasite in vitro was significantly inhibited, while for RHΔ ODSCI and RHΔ ODSCII mutant strains no similar changes were detected. RHΔ FabZ exhibited reduced virulence for mice compared with RHΔ ODSCI and RHΔ ODSCII , as shown by the improved survival rate. Deletion of FabZ in the PRU strain significantly decreased the brain cyst burden in mice compared with PRUΔ ODSCI and PRUΔ ODSCII . Collectively, these findings suggest that FabZ contributes to the growth and virulence of T. gondii , while ODSCI and ODSCII do not contribute to these traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Elsheikha, Liu, Zhang, Sun, Liang, Song and Zhu.)

Exorista civilis Rondani (Diptera:Tachinidae) is an excellent dominant parasitic enemy all over the world. But there has been a lack of research on the molecular regulation of diapause in E. civilis. To investigate the important diapause-associated genes and metabolic pathways in E. civilis, we can provide a theoretical basis for clarifying the molecular mechanism of diapause at the transcriptome level. The Illumina HiSeq. 2000 platform was used to perform transcriptome sequencing and bioinformatics analysis of the non-diapause and diapause pupae of E. civilis. 58,050 unigenes were successfully assembled, in which 4355 upregulated and 3158 downregulated unigenes were differentially expressed. Moreover, by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, 896 kinds of the differentially expressed genes were specifically analyzed and showed that diapause-associated genes were related to be involved in the pathways of cold resistance, amino acid metabolism, and energy metabolism. Furthermore, these upregulated five genes showed the same trends of expression patterns between quantitative real-time polymerase chain reaction and RNA-Seq. This study provides a theoretical basis for the further study of the diapausing molecular mechanisms of E. civilis., (© 2021 Wiley Periodicals LLC.)

Coronocyclus labiatus and Cylicodontophorus bicoronatus are two significant horse parasitic nematodes which are classified into subfamily Cyathostominae, family Strongylidae, however, the classification of these nematodes has been controversial for more than a century. Mitochondrial (mt) genomes are considered valuable sources for parasite taxonomy, population genetics, and systematics studies. In the present study, the mt genomes of Co. labiatus and Cd. bicoronatus (type species) were determined and subsequently compared with those from closely related species by phylogenetic analysis based on concatenated datasets of amino acid sequences predicted from mt protein-coding genes. The complete mt genomes of Co. labiatus and Cd. bicoronatus were circular with 13,827 bp and 13,753 bp in size, respectively. Both mt genomes consisted of a total of 12 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and two non-coding regions. All protein coding genes were transcribed in the same direction, and the gene order in both mt genomes belonged to the gene arrangement type 3 (GA3). There were 19 intergenic spacers with 1 bp to 35 bp and one overlap with 4 bp in mt genome of Co. labiatus, and 22 intergenic spacers with 1-29 bp in size but no overlap in the mt genome of Cd. bicoronatus. The A + T content of Co. labiatus and Cd. bicoronatus mt genomes were 75.87 % and 75.16 %, respectively. Similar to mt genones of other Strongylidae species published in GenBank, they also exhibited a strong A + T bias not only in the nucleotide composition but also in codon usage. Comparative analyses of mt genomes nucleotide sequence showed that mt genomes of Co. labiatus and Cd. bicoronatus had higher identities to that of Cylicostephanus goldi (90.3 % and 86.9 %, respectively), followed by those of two Cyathostomum species (89.9∼90.0 %; 86.4 %), respectively. Phylogenetic analyses using mt genomes of 26 Strongyloidea nematodes revealed that Co. labiatus was closely related to Cyathostomum species, and Cd. bicoronatus formed a distinct branch with Cyathostominae species, which was closer to Triodontophorus than Poteriostomum imparidentatum. We concluded Coronocyclus might be closely related with Cyathostomum but represent a distinct genus based on comparative mt genome sequences and phylogenetic analyses. The availability of complete mt genome sequences of Co. labiatus and Cd. bicoronatus provides new and useful genetic markers for further studies on Strongylidae nematodes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Due to the decrease of estrogen and estrogen receptor (ER) in postmenopausal women, they have a higher risk of intervertebral disc degeneration (IDD) than men. This study aims to explore how ERα and ERb interact with CCN5 and protect IDD., Patients and Methods: We used Chromatin immunoprecipitation (ChIP) and Luciferase reporter assay to determine whether the ERα/b protein binds to CCN5 promoter and activates its expression. We used TNF-α to induce nucleus pulposus (NP) cell degeneration to simulate the IDD process. The change of the expression of ERα/β and CCN5 was measured in the degenerated NP cells. To understand the function of ERα/β in the NP cells degeneration, we upregulated the ERα/b gene expression by vector transfection or 17b-estradiol (E2) stimulation. Besides, we also used the CCN5 gene-silenced NP cells by siRNA transfection as a comparison to determine the role of CCN5. We tested the cell proliferation and principal components of the extracellular matrix (ECM) to value the degree of NP cell degeneration., Results: ERα and ERβ protein can bind to the same promoter regions of CCN5 and activate its expression, respectively. TNF-α degraded NP cells with a reduction of cell proliferation, collagen II, ACAN, ERα, ERβ, and CCN5 expression, and increased collagen I/III, and MMP-13 expression. Upregulated ERα or ERβ resulted in the maintains of CCN5 and alleviated the NP cell degeneration. Besides, 17β-E2 supplement increased the ERα, ERβ, and CCN5 expression, as well as stable NP cells phenotype. However, it was partly abolished by the silencing of CCN5., Conclusions: Upregulation of ERα and ERβ protects the NP cell degeneration during IDD through the activation of CCN5 by binding to its promoter.

Background: Surgery is often indicated for patients with massively prolapsed intervertebral disc herniation. The interlaminar endoscopic spine system (iLESSYS) Delta 6-mm working channel endoscope has advantages over other systems. The aim of this study was to explore the benefits and complications of using the iLESSYS Delta for the treatment of massively prolapsed intervertebral disc herniation., Aim: To explore the clinical benefits of treating massively prolapsed lumbar intervertebral disc herniation with the iLESSYS Delta endoscope., Methods: In this study, the data of 37 patients who underwent surgery with the iLESSYS Delta endoscope at The Affiliated Hospital of Qingdao University were retrospectively analyzed. Intraoperative blood loss, operation time, and complications were collected. The visual analog scale (VAS), oswestry disability index (ODI), and modified MacNab criteria were determined before and at 1 d, 3 mo, and 6 mo after surgery., Results: The mean intraoperative blood loss was 20.4 ± 1.2 mL. The mean operation time was 97.3 ± 12.4 min. The VAS scores for leg and back pain decreased from 68.0 ± 7.3, 34.4 ± 8.5 before operation to 2.5 ± 1.7, 5.5 ± 1.9 at 6 mo after surgery, respectively. The ODI also decreased from 60.2 ± 7.3 to 17.9 ± 3.4 at 6 mo after surgery. The improvement rate of the MacNab score was 86.4%, which was considered excellent. No spinal dural injury, nerve root injury, secondary protrusion of intervertebral disc, or myeloid hypertension was found during follow-up., Conclusion: The iLESSYS Delta 6-mm working channel endoscope has several advantages in terms of clinical and functional benefits, complications, and low risk of residual vertebral pulp in treating patients with massively prolapsed intervertebral disc herniation., Competing Interests: Conflict-of-interest statement: The authors of this work have nothing to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Based on the potent antidepressant and anticonvulsant activities of the triazole-containing quinolinones reported in our previous work, a series of ring-opened derivatives of them were designed, synthesized in this work. Their antidepressant and anticonvulsant activities were screened using the forced swimming test (FST) and the maximal electroshock seizure test (MES), respectively. The results showed that compounds 4a, 5a, 6c-6e, 6g-6i, and 7 led to significant reductions in the accumulated immobility time in the FST at a dose of 50 mg/kg. Especially compound 7 exhibited higher levels of efficacy than the reference standard fluoxetine in the FST and the tail suspension test. The results of an open field test excluded the possibility of central nervous stimulation of 7, which further confirmed its antidepressant effect. Meanwhile, compounds 6a-6i and 7 showed different degrees of anticonvulsant activity in mice at the doses range from 300 to 30 mg/kg in the MES. Among them, compounds 6e and 7 displayed the ED 50 of 38.5 and 32.7 mg/kg in the MES, and TD 50 of 254.6 and 245.5 mg/kg, respectively. No one showed neurotoxicity at the dose of 100 mg/kg. The preliminary investigation forward to their mechanism indicated that regulation of GABAergic system might contribute to their anticonvulsive and anti-depressive action., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cyathostomins are one kind of the most important parasites in equids. Cylicostephanus minutus is a member of the subfamily Cyathostominae. In the present study, we determined the complete mitochondrial (mt) genomes from four Cs. minutus isolates and reconstructed the phylogenetic relationship of Strongylidae to test the hypothesis that Cs. minutus represents a species complex. The complete mt genome sequences of Cs. minutus were 13,772-13,822 bp in length, and contained 36 genes (12 protein coding genes, 22 tRNA genes, two rRNA genes), and two non-coding regions (NCRs). The intraspecific identity of nucleotide sequences and amino acid sequences in Cs. minutus (1-4) were 89.3-97.9% and 97.0-98.8%, respectively. Two operational taxonomic units (OTUs) were determined based on the mt genome sequences, OTU 2 (Csm 1 and Csm 2) and OTU 3 (Csm 3 and Csm 4). Sequence analysis showed the divergence between OTU 2 and OTU 3 was 8.9-10.7%. Pairwise comparisons of 12 protein coding genes between OTU 2 and OTU 3 showed a difference of 3.0-13.3% at the nucleotide level and 0-6.7% at the amino acid level. Phylogenetic analysis showed the separation of Cs. minutus isolates from the same host into different distinct clades based on mt genomes. Comparisons of partial mt cox1, nad5, and cytb and ITS2 sequences from 20 Cs. minutus isolates from the same host and the same geographical location with other Cs. minutus sequences available in GenBank revealed significant nucleotide differences. Phylogenetic analysis showed a separation of Cs. minutus into three distinct clades. Thus, the comparative and phylogenetic analyses of mtDNA datasets indicated that Cs. minutus represents a complex of at least three species. Our results have further confirmed the existence of a cryptic Cs. minutus species, and provides a reference for the taxonomical, population genetics, and systematics studies of other cyathostomin species., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Trichinella infection can induce macrophages into the alternatively activated phenotype, which is primarily associated with the development of a polarized Th2 immune response. In the present study, we examined the immunomodulatory effect of T. spiralis thioredoxin peroxidase-2 (TsTPX2), a protein derived from T. spiralis ES products, in the regulation of Th2 response through direct activation of macrophages. The location of TsTPX2 was detected by immunohistochemistry and immunofluorescence analyses. The immune response in vivo induced by rTsTPX2 was characterized by analyzing the Th2 cytokines and Th1 cytokines in the peripheral blood. The rTsTPX2-activated macrophages (M rTsTPX2 ) were tested for polarization, their ability to evoke naïve CD4 + T cells, and resistance to the larval infection after adoptive transfer in BALB/c mice. The immunolocalization analysis showed TsTPX2 in cuticles and stichosome of T. spiralis ML. The immunostaining was detected in cuticles and stichosome of T. spiralis Ad3 and ML, as well as in tissue-dwellings around ML after the intestines and muscle tissues of infected mice were incubated with anti-rTsTPX2 antibody. Immunization of BALB/c mice with rTsTPX2 could induce a Th1-suppressing mixed immune response given the increased levels of Th2 cytokines (IL-4 and IL-10) production along with the decreased levels of Th1 cytokines (IFN-γ, IL-12, and TNF-α). In vitro studies showed that rTsTPX2 could directly drive RAW264.7 and peritoneal macrophages to the M2 phenotype. Moreover, M rTsTPX2 could promote CD4 + T cells polarized into Th2 type in vitro . Adoptive transfer of M rTsTPX2 into mice suppressed Th1 responses by enhancing Th2 responses and exhibited a 44.7% reduction in adult worm burden following challenge with T. spiralis infective larval, suggesting that the TsTPX2 is a potential vaccine candidate against trichinosis. Our study showed that TsTPX2 would be at least one of the molecules to switch macrophages into the M2 phenotype during T. spiralis infection, which provides a new therapeutic approach to various inflammatory disorders like allergies or autoimmune diseases., (Copyright © 2020 Jin, Zhang, Li, Qin, Liu, Ohiolei, Niu, Yan, Li, Jia, Song and Fu.)

In this article, we propose a hybrid artificial bee colony (ABC) algorithm to solve a parallel batching distributed flow-shop problem (DFSP) with deteriorating jobs. In the considered problem, there are two stages as follows: 1) in the first stage, a DFSP is studied and 2) after the first stage has been completed, each job is transferred and assembled in the second stage, where the parallel batching constraint is investigated. In the two stages, the deteriorating job constraint is considered. In the proposed algorithm, first, two types of problem-specific heuristics are proposed, namely, the batch assignment and the right-shifting heuristics, which can substantially improve the makespan. Next, the encoding and decoding approaches are developed according to the problem constraints and objectives. Five types of local search operators are designed for the distributed flow shop and parallel batching stages. In addition, a novel scout bee heuristic that considers the useful information that is collected by the global and local best solutions is investigated, which can enhance searching performance. Finally, based on several well-known benchmarks and realistic industrial instances and via comprehensive computational comparison and statistical analysis, the highly effective performance of the proposed algorithm is favorably compared against several algorithms in terms of both solution quality and population diversity.

At present,the production equipment and process of Chinese patent medicines still have many problems including high energy consumption,low efficiency,high pollution,and low intelligence,which seriously hinder the transformation,upgrading and modernized development of traditional Chinese medicine industry. With the emergence of various new pharmaceutical technologies and the application of technologies of other fields in traditional Chinese medicine industry,the development of Chinese patent medicine has ushered in new opportunities. The processes such as pulverization,mixing,extraction,separation,concentration,drying and sterilization are unique for the production of Chinese patent medicine. These main features can be distinguished from the manufacturing process of chemical drugs,determining the characteristics of the production process and equipment of Chinese patent medicine. In this paper,each operation unit was mentioned to summarize and analyze the new equipment and new technologies with advantages and characteristics in recent years from the perspectives of definition,principle,classification and application. Among them,the automatic spray device of the mixer,the extraction and separation equipment of volatile oil,and the crane basket-type circulation extraction technology,composite multi-layer spiral vibration countercurrent drying,and vibration sterilization equipment all have rapid development in recent years,with great prospects in the production of Chinese patent medicines. In this paper,we also analyzed some problems existing in the production equipment and technology of Chinese patent medicine and the key factors restricting the development of Chinese patent medicine,discussed the transformation of Chinese patent medicine production from traditional to modern and from semi-automatic to intelligent,and put forward three suggestions to help Chinese patent medicine achieve the goal of improving quality,efficiency and green manufacturing in production.

A novel series of benzoxazole derivatives containing 1,2,4-triazolone (5a-m) was designed. These compounds were synthesized in order to screen their anticonvulsant activities by the maximal electroshock seizure (MES) model and the subcutaneous pentylenetetrazole (sc-PTZ) seizure model in mice. The rotarod test was used to evaluate their neurotoxicities. Most of the compounds showed anti-MES activities at 100 and 300 mg/kg. Compound 5f, which showed potential anticonvulsant activity in the MES model with ED 50 values of 22.0 mg/kg, was considered as the most promising one in this study. It exhibited greater safety than that of carbamazepine and valproate regarding neurotoxicity. The efficacy of compound 5f in inhibiting the tonic seizures and death induced by the convulsants 3-mercaptopropionic acid and BIC was also verified. In an enzyme-linked immunosorbent assay, compound 5f and the positive drug phenytoin significantly increased the γ-aminobutyric acid (GABA) level in the mouse brain. Further, pretreatment with an inhibitor of the GABA synthesizing enzyme dramatically raised the ED 50 value of 5f in the MES model. These results confirmed that the compound 5f plays its anticonvulsive action via regulating the GABA function in the brain. Also, a docking study of the compound 5f in the benzodiazepine (BZD) binding site of the GABA A receptor confirmed possible binding of the compound 5f with BZD receptors., (© 2019 Deutsche Pharmazeutische Gesellschaft.)

Background: In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected., Methods: We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy. We also initiated a heightened surveillance program in the same hospital to screen for other patients who presented with fever, headache, and a history of tick bites. We used reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and cell-culture assays to detect the pathogen and immunofluorescence and neutralization assays to determine the levels of virus-specific antibodies in serum specimens from the patients., Results: We found that the index patient was infected with a previously unknown segmented RNA virus, which we designated Alongshan virus (ALSV) and which belongs to the jingmenvirus group of the family Flaviviridae. ALSV infection was confirmed by RT-PCR assay in 86 patients from Inner Mongolia and Heilongjiang who presented with fever, headache, and a history of tick bites. Serologic assays showed that seroconversion had occurred in all 19 patients for whom specimens were available from the acute phase and the convalescent phase of the illness., Conclusions: A newly discovered segmented virus was found to be associated with a febrile illness in northeastern China. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China.)., (Copyright © 2019 Massachusetts Medical Society.)

Epilepsy is one of the common diseases seriously threatening life and health of human. More than 50 million people are suffering from this condition and anticonvulsant agents are the main treatment. However, side effects and intolerance, and a lack of efficacy limit the application of the current anticonvulsant agents. The search for new anticonvulsant agents with higher efficacy and lower toxicity continues to be the focus and task in medicinal chemistry. Numbers of triazole derivatives as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have proved the importance of this heterocyclic nucleus in drug design and discovery. Recently many endeavours were made to involve the triazole into the anticonvulsants design, which have brought lots of active compounds. This work is an attempt to systematically review the research of triazole derivatives in the design and development of anticonvulsant agents during the past two decades.

We adopted an ingenious method that cut out the DA alternating oligomers from the corresponding DA alternating copolymers. From analyzing the orbital compositions of the HOMOs and LUMOs as well as the reorganization energies, we found the level of charge transfer is increased with the increasing of D/A ratio, but ionization potentials and electron affinities show a contrary trend. Moreover, with the greater ratio, the trend in the nearness of two transitions results in broadening the absorption band in the visible range. That is why experimentally improving the ratio is beneficial for the copolymers used as the p-type materials in the BHJ solar cells. This method is impossible to take the real copolymer system, however, it could provide a strategy to avoid the limitation of the theory level and perform reliable result to study the intrinsic properties of DA alternating copolymers, which can provide a guidance to experimental works., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, a novel series of 4-(2-(alkylthio)benzo[ d ]oxazol-5-yl)-2,4-dihydro-3 H -1,2,4-triazol-3-ones ( 4a - m ) was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The neurotoxicity of these compounds was evaluated using the rotarod neurotoxicity test. The majority of compounds showed anti-MES activities at 100 or 300 mg/kg. Compound 4g was considered to be the most promising, based on its potency against MES- and PTZ-induced seizures with ED 50 values of 23.7 and 18.9 mg/kg, respectively. The TD 50 value of 4g was 284.0 mg/kg, which resulted in a higher protective index (PI = TD 50 /ED 50 ) value than that of carbamazepine and valproate. In an ELISA test, compound 4g significantly increased the γ-aminobutyric acid (GABA) content in mouse brain. In addition, pretreatment with thiosemicarbazide (an inhibitor of the GABA synthesizing enzyme) significantly decreased the activity of 4g in the MES model, which suggests that the mechanism through which compound 4g elicits its anticonvulsive action is at least in part through increasing the GABA level in the brain., Competing Interests: The authors declare no conflict of interest.

Wheat straws were modified by 3-chloro-2-hydroxypropyl trimethylammonium chloride (CTA) to obtain aminated wheat straw St-N'. The optimum synthetic conditions were determined to be NaOH with 30% mass fraction, CTA of 100 mL, reaction temperature of 80℃, and reaction time of 3 h, which was verified by orthogonal experiments. Nano-sized hydrous zirconium oxides (HZO) were immobilized into St-N' by an in situ precipitation method to obtain the nanocomposite St-N'-Zr. The SEM, TEM, XRD, and BET results indicated that the nano-sized HZO with 50-100 nm sizes were uniformly loaded onto the inner surface of the biomass-based carrier St-N' that was amorphous in nature. A Langmuir adsorption isotherm fitted the adsorption process well, and the maximum adsorption amount was calculated to be 33.90 mg·g -1 . The optimal pH range was 1.8-6.0, displaying good removal capacity of phosphate in acidic waters. In the presence of high levels of competing anions, the phosphate adsorption still retained more than 70% of the original amount, showing the higher preference of St-N'-Zr towards phosphate than towards the commercial anion exchanger D-201. After 10 cycles of adsorption-desorption, the removal efficiency remained stable, confirming the good regeneration ability and potential application of St-N'-Zr.

High-fluorescent p-X-ferrites (XFe 2 O 4 ; XFO; X = Fe, Cr, Mn, Co, or Ni) embedded in n-hematite (Fe 2 O 3 ) surfaces were successfully fabricated via a facile bio-approach using Shewanella oneidensis MR-1. The results revealed that the X ions with high/low work functions modify the unpaired spin Fe 2+ -O 2- orbitals in the XFe 2 O 4 lattices to become localized paired spin orbitals at the bottom of conduction band, separating the photovoltage response signals (73.36~455.16/-72.63~-32.43 meV). These (Fe 2 O 3 )-O-O-(XFe 2 O 4 ) interfacial coupling behaviors at two fluorescence emission peaks (785/795 nm) are explained via calculating electron-hole effective masses (Fe 2 O 3 -FeFe 2 O 4 17.23 × 10 -31  kg; Fe 2 O 3 -CoFe 2 O 4 3.93 × 10 -31  kg; Fe 2 O 3 -NiFe 2 O 4 11.59 × 10 -31  kg; Fe 2 O 3 -CrFe 2 O 4 -4.2 × 10 -31  kg; Fe 2 O 3 -MnFe 2 O 4 -11.73 × 10 -31  kg). Such a system could open up a new idea in the design of photovoltage response biosensors.

High-photostability fluorescent (XZn)Fe 2 O 4 (X=Mg, Mn or Ni) embedded in BiFeO 3 spinel-perovskite nanocomposites were successfully fabricated via a novel bio-induced phase transfer method using shewanella oneidensis MR-1. These nanocomposites have the near-infrared fluorescence response (XZn or Fe)-O-O-(Bi) interfaces (785/832nm), and the (XZn)Fe 2 O 4 /BiFeO 3 lattices with high/low potentials (572.15-808.77meV/206.43-548.1meV). Our results suggest that heavy metal ion (Cr 3+ , Cd 2+ , Co 2+ and Pb 2+ ) d↓ orbitals hybridize with the paired-spin X-Zn-Fe d↓-d↓-d↑↓ orbitals to decrease the average polarization angles (-29.78 to 44.71°), qualitatively enhancing the photovoltage response selective potentials (39.57-487.84meV). The fluorescent kinetic analysis shows that both first-order and second-order equilibrium adsorption isotherms are in line and meet the Langmuir and Freundlich modes. Highly selective fluorescence detection of Co 2+ , Cr 3+ and Cd 2+ can be achieved using Fe 3 O 4 -BiFeO 3 (Langmuir mode), (MgZn)Fe 2 O 4 -BiFeO 3 and (MnZn)Fe 2 O 4 -BiFeO 3 (Freundlich mode), respectively. Where the corresponding max adsorption capacities (q max ) are 1.5-1.94, 35.65 and 43.7 multiple, respectively, being more competitive than that of other heavy metal ions. The present bio-synthesized method might be relevant for high-photostability fluorescent spinel-perovskite nanocomposites, for design of heavy metal ion sensors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Due to the rapidly growing bacterial resistance to antibiotics and the scarcity of novel agents under development, bacterial infections are still a pressing global problem, making new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, urgently needed. In this paper, seven series of N -arylsulfonylindole analogs 5 - 11 bearing rhodanine moieties were synthesized, characterized, and evaluated for antibacterial activity. According to the in vitro antimicrobial results, half of the synthesized compounds showed potent inhibition against four Gram-positive bacteria, with MIC values in the range of 0.5-8 µg/mL. For multidrug-resistant strains, compounds 6a and 6c were the most potent, with MIC values of 0.5 µg/mL, having comparable activity to gatifloxacin, moxiflocaxin and norfloxacin and being 128-fold more potent than oxacillin (MIC = 64 µg/mL) and 64-fold more active than penicillin (MIC = 32 µg/mL) against Staphylococcus aureus ATCC 43300 ., Competing Interests: The authors declare no conflict of interest.

Electron-donating molecules play an important role in the development of organic solar cells. (Z)-2-(2-Phenylhydrazinylidene)acenaphthen-1(2H)-one (PDAK), C 18 H 12 N 2 O, was synthesized by a Schiff base reaction. The crystal structure shows that the molecules are planar and are linked together forming `face-to-face' assemblies held together by intermolecular C-H...O, π-π and C-H...π interactions. PDAK exhibits a broadband UV-Vis absorption (200-648 nm) and a low HOMO-LUMO energy gap (1.91 eV; HOMO is the highest occupied molecular orbital and LUMO is the lowest unoccupied molecular orbital), while fluorescence quenching experiments provide evidence for electron transfer from the excited state of PDAK to C 60 . This suggests that the title molecule may be a suitable donor for use in organic solar cells.

Background: Epilepsy and depression are two of the common diseases seriously threatening life and health of human. A shared neurobiological substrate led to the bidirectional relationship and high comorbid occurrence of the two disorders. Recently, an increasing number of patients with epilepsy (PWE) require some form of antidepressant medication. However, most of the available antidepressants are inadequate for PWE for some reasons. So, the search for novel and increasingly effective drugs with anticonvulsant and antidepressant activities is necessary., Methods: A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles (5a-p) were designed and synthesized. Their anticonvulsant activities were evaluated using maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. Their antidepressant activities were screened with the forced swimming test (FST)., Results: All the compounds showed anti-MES activities in different degree, among which 5g and 5j were the most promising one with ED50 value of 31.7 and 12.7 mg/kg, respectively. What's more, 5g and 5j also exhibited nice anti-scPTZ activities and low neurotoxicity. Interestingly, these compounds also showed good antidepressant activities in FST. And the efficacy of 5g were also confirmed by a tail suspension test and a open field test. The pretreatment of thiosemicarbazide (an inhibitor of γ- aminobutyric acid synthesis enzyme) significantly increased the ED50 of 5g in MES and reversed the reductions in the immobility time of 5g in FST., Conclusion: Triazole-containing benzo[d]oxazole is a good skeleton to develop compounds with both anticonvulsant and antidepressant activities. We have got the compound 5g, which display remarkable antidepressant and anticonvulsant activities, and the GABAergic system was involved in the action mechanism of 5g., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Ferrites-bismuth ferrite is an intriguing option for medical diagnostic imaging device due to its magnetoelectric and enhanced near-infrared fluorescent properties. However, the embedded XFO nanoparticles are randomly located on the BFO membranes, making implementation in devices difficult. To overcome this, we present a facile bio-approach to produce XFe 2 O 4 -BiFeO 3 (XFO-BFO) (X = Cr, Mn, Co, or Ni) membranes using Shewanella oneidensis MR-1. The perovskite BFO enhances the fluorescence intensity (at 660 and 832 nm) and surface potential difference (-469 ~ 385 meV and -80 ~ 525 meV) of the embedded spinel XFO. This mechanism is attributed to the interfacial coupling of the X-Fe (e - or h + ) and O-O (h + ) interfaces. Such a system could open up new ideas in the design of environmentally friendly fluorescent membranes.

Giardia duodenalis is one of the most common enteric parasites of humans and animals, including companion animals, livestock and wildlife. To date, the information about the prevalence and molecular characterization of G. duodenalis infection in white yaks was limited. In the present study, a total of 208 white yak fecal samples were collected from Tianzhu Tibetan Autonomous County (TTAC) between September 2013 and March 2014. Of the 208 white yak fecal samples, four samples (1.92%, all collected in March 2014) tested G. duodenalis-positive by PCR amplification of triosephosphate isomerase (tpi) gene. Sequence analysis confirmed the presence of G. duodenalis assemblage E. The present study revealed the presence and genotype of G. duodenalis in white yaks for the first time, and extended the host range of G. duodenalis. These results provided useful information for further genotyping or subtyping studies of G. duodenalis in white yaks.

We elucidated a number of facets regarding glutathione (GSH)-bismuth ferrite (BiFeO3, BFO) interactions and reactivity that have previously remained unexplored on a molecular level. In this approach, the cation-modified reduced GSH (or oxidised glutathione (GS·)) formed on the (111)-oriented BiFeO3 membrane (namely BFO-(111)) can serve as an efficient quencher, and the luminescence mechanism is explained in aqueous conditions. Notably, we suggest the use of Fe(2+)↓ ion as an electron donor and K(+) ion as an electron acceptor to exert a "gluing" effect on the glutamic acid (Glu) and glycine (Gly) side chains, producing an exposed sulfhydryl (-SH) configuration. This method may enable the rational design of a convenient platform for biosensors.

The microbial resistance has become a global hazard with the irrational use of antibiotics. Infection of drug-resistant bacteria seriously threatens human health. Currently, there is an urgent need for the development of novel antimicrobial agents with new mechanisms and lower levels of toxicity. In this paper, a series of (S ,Z)-4-methyl-2-(4-oxo-5-((5-substitutedphenylfuran-2-yl) methylene)-2-thioxothiazolidin-3-yl)pentanoic acids via a Knoevenagel condensation were synthesized and evaluated for their antibacterial activity in - vitro. The synthesized compounds were characterized by IR, (1)H NMR and MS. The antibacterial test in - vitro showed that all of the synthesized compounds had good antibacterial activity against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 2-4 µg/mL. Especially compounds 4c, 4d, 4e and 4f were the most potent, with MIC values of 2 µg/mL against four multidrug-resistant Gram-positive bacterial strains.

Understanding how plutonium (Pu) doping affects the crystalline zircon structure is very important for risk management. However, so far, there have been only a very limited number of reports of the quantitative simulation of the effects of the Pu charge and concentration on the phase transition. In this study, we used density functional theory (DFT), virtual crystal approximation (VCA), and two-dimensional correlation analysis (2D-CA) techniques to calculate the origins of the structural and electronic transitions of Zr1-cPucSiO4 over a wide range of Pu doping concentrations (c=0-10mol%). The calculations indicated that the low-angular-momentum Pu-fxy-shell electron excites an inner-shell O-2s(2) orbital to create an oxygen defect (VO-s) below c=2.8mol%. This oxygen defect then captures a low-angular-momentum Zr-5p(6)5s(2) electron to form an sp hybrid orbital, which exhibits a stable phase structure. When c>2.8mol%, each accumulated VO-p defect captures a high-angular-momentum Zr-4dz electron and two Si-pz electrons to create delocalized Si(4+)→Si(2+) charge disproportionation. Therefore, we suggest that the optimal amount of Pu cannot exceed 7.5mol% because of the formation of a mixture of ZrO8 polyhedral and SiO4 tetrahedral phases with the orientation (10-1). This study offers new perspective on the development of highly stable zircon-based solid solution materials., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To explore the effect of Bushen Huoxue Compound (BHC) on lactate dehydrogenase (LDH) leakage, expressions of vascular endothelial growth factor (VEGF) and VEGF mRNA in retinal Muller cells under high glucose condition or advanced glycosylation end products (AGEs) condition by using serum pharmacological method., Methods: The retinal Müller cells of 5-7 days post-natal Sprague Dawley (SD) rats were cultured with modified enzyme-digestion method. Purified retinal Muller cells were cultured in normal conditions, high glucose condition (50 mmol/L) or AGEs (50 mg/L and 100 mg/L) conditions, and BHC-containing serum was added to culture medium. The LDH leakage and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the relative expression of VEGF mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR)., Results: Compared with the normal control group, expressions of VEGF and VEGF mRNA were significantly increased in the high glucose group, the low dose AGEs group and the high dose AGEs group (all P < 0.01). The LDH leakage was obviously increased in the high dose AGEs group, when compared with the normal control group and the high glucose group (P < 0.01). The LDH leakage, expressions of VEGF and VEGF mRNA were obviously decreased by BHC-containing serum both in high glucose and AGEs conditions (P < 0.05, P < 0.01). BHC-containing serum had no significant effect on the LDH leakage and expressions of VEGF and VEGF mRNA in normal conditions (P > 0.05)., Conclusions: AGEs intervention could obviously lower the stability of Müller cell membrane. Up-regulated expressions of VEGF and VEGF mRNA in cultured Müller cells could be induced by AGEs or high glucose. BHC-containing serum could stabilize the stability of Müller cell membrane, inhibit the transcription of VEGF mRNA and decrease the protein expression of VEGF, which might be one of important mechanisms for preventing and treating diabetic retinopathy.

H5N1 and H9N2 viruses are important causes of avian influenza in China. H5N1 is typically associated with severe to fatal disease in poultry, while H9N2 is usually associated with mild disease. Differences in viral virulence prompted us to investigate whether innate immune responses would be differentially regulated following infection by H5N1 and H9N2 viruses. To address this hypothesis, expression of a panel of innate immune-related genes including IFN-α, IFN-β, Mx1, OASL, ISG12, IFIT5, IRF7, USP18, SST, and KHSRP in immortal DF-1 cells following H5N1 and H9N2 infection was analyzed and compared by real-time quantitative RT-PCR. Cells infected by either virus overall exhibited a similar expression profile for four ISGs (Mx1, OASL, ISG12, and IFIT5), IFN-α, IFN-β, and SST gene. However, two immune-regulatory genes (IRF7 and KHSRP) were not responsive to highly pathogenic H5N1 infection but were strongly up-regulated in DF-1 cells infected with low pathogenic H9N2 infection. The subtype-dependent host response observed in this study offers new insights into the potential roles of IRF7 and KHSRP in control and modulation of the replication and virulence of different subtypes or strains of avian influenza A virus.

Understanding how temperature affects the electronic transitions of BFO is important for design of BiFeO3 (BFO)-based temperature-sensitive device. Hitherto, however, there have been only very limited reports of the quantitative simulation. Here, we used density functional theory (DFT) and two-dimensional correlation analysis (2D-CA) techniques to calculate the systematic variations in electronic transitions of BFO crystal, over a range of temperature (50~1500 K). The results suggest that the heat accumulation accelerates the O-2p(4) orbital splitting, inducing the Fe(3+)-3d(5) → Fe(2+)-3d(5)d(0) charge disproportionation. The origin is observed as the temperature-dependent electron transfer process changes from threefold degeneracy to twofold degeneracy. Additionally, the crystallographic orientation (111) can be used to control the 2p-hole-induced electronic transition as O → unoccupied Fe(3+)-3d(5), in comparison to the O → Bi-6p(3) + Fe(3+)-3d(5)d(0) on the orientations (001) and (101). This study offers new perspective on the improvement of BFO-based temperature-sensitive device.

A series of heteroleptic cyclometalated Ir (III) complexes for OLEDs application have been investigated theoretically to explore their electronic structures and spectroscopic properties. The geometries, electronic structures, and the lowest-lying singlet absorptions and triplet emissions of (piq)₂Ir(acac) (labeled 1) and theoretically designed models (piq)₂Ir(dpis) (labeled 2), (4Fpiq)₂Ir(dpis) (labeled 3), (4F5M-piq)₂Ir(dpis) (labeled 4), (4,5-2F-piq)₂Ir(dpis) (labeled 5) and (5-F-piq)₂Ir(dpis) (labeled 6) were investigated with density functional theory (DFT)-based approaches, where, piq=1-phenylisoquinolato, acac=acetylacetonate and dpis=diphenylimidodisilicate. Their structures in the ground and excited states have been optimized at the DFT/B3LYP/LANL2DZ and TDDFT/B3LYP/LANL2DZ levels, and the lowest absorptions and emissions were evaluated at B3LYP and M062X level of theory, respectively. Furthermore, the energy-transfer mechanism of these complexes also be analyzed here, and the result shown that the complexes 1-6 are having the low efficiency roll-off property. Except that, the oscillator strength analyze shown that the complexes 2-6, which were designed by theory, are suitable for OLED since their high oscillator strength property., (Copyright © 2014 Elsevier B.V. All rights reserved.)

An avian influenza virus (AIV) strain belonging to the H4 subtype and provisionally designated as A/duck/China/J1/2012(H4N6) was isolated from diseased ducks with respiratory disease at a commercial poultry farm in Shandong, China, in 2012. The genomic coding sequences of all eight segments of this J1 isolate were determined and used for subsequent analysis. Phylogenetic analysis of all eight segments showed that this duck H4N6 virus was of Eurasian lineage and not American lineage. The results show that the virus probably emerged because of a reassortment event involving other avian H4N6 and H6N1 viruses. Interestingly, this H4N6 virus had all the conserved features common to low-pathogenic AIVs, including the HA cleavage sequence, receptor-binding sequences for the 2,3-linked sialic acid receptor in avian species, and the PB2 627E motif. These results suggest that the duck H4N6 isolate could not cross the species barrier to infect and replicate in mammals, including humans. In addition, screening of the duck serum samples showed that only 0.57 % (2/352) of the individuals had weak but measurable hemagglutination inhibition (HI) antibody titers. The low antibody prevalence data were also supported by the failure to detect H4N6 virus (0/56) in clinical nasal swabs of the ducks. These data indicate an alternate reservoir for the H4N6 virus.

Herein, we report the design, syntheses and in vitro anti-microbial activity of two series of rhodanines with chalcone moiety. Anti-microbial tests showed that some of the synthesized compounds exhibited good inhibition (MIC = 1-8 µg/mL) against multi-drug-resistant Gram-positive organisms, including methicillin resistant and quinolone-resistant Staphylococcus aureus, in which the compound 4g was found to be the most potent with minimum inhibitory concentration (MIC) value of 1 µg/mL against two methicillin-resistant S. aureus.

A series of arylhydrazone derivatives bearing a rhodanine moiety have been synthesized, characterized, and evaluated as antibacterial agents. Some of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, IIk and IIIk were identified as the most effective, with minimum inhibitory concentration values of 2-4 μg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL.

Two series of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4]thiazepine derivatives (6a-q and 7a-q) were synthesized and evaluated for their anticonvulsant activity using the maximal electroshock (MES) method. All of the compounds prepared were effective in the MES screens. Among which, compound 7j was considered as the most promising one with an ED50 value of 26.3 mg/kg and a superior protective index value of 12.6. The potency of compound 7j against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid and bicuculline suggested that two different mechanisms of action might potentially be involved in its anticonvulsant activity, including the inhibition of voltage-gated ion channels and the modulation of GABAergic activity. A computational study was also conducted to predict the pharmacokinetic properties of the compounds prepared, with the results supporting the use of these compounds as a group of promising antiepileptic agents.

Epilepsy is the most frequent nearological affiction and afflicts 1% about of the world's population. Currently there is an urgent need for the development of novel anticonvulsants with higher levels of potency and lower levels of toxicity. In this paper, a series of new 6-(substituted-phenyl)thiazolo[3,2-b][1,2,4]triazole derivatives were synthesized and tested for their anticonvulsant activities using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (PTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. In these compounds, 6-(4-fluorophenyl)thiazolo[3,2-b][1,2,4]triazole (3c) showed selective protection against the MES seizures with an ED50 value of 49.1 mg/Kg and a TD50 value of 94.1 mg/Kg, which provided compound 3c a protective index (PI = TD50/ED50) of 1.9 in the MES test. 6-(4-Propoxyphenyl)thiazolo[3,2-b][1,2,4]triazole (5b) was found to be active in both models, i.e. MES test and PTZ test. In the PTZ screen, compound 5b gave an ED50 of 63.4 mg/Kg and a TD50 of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine.

A series of 1-substituted-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydroquinolin-2(1H)-ones were designed, synthesized, and screened for their antidepressant and anticonvulsant activities. Interestingly, compounds 5i, 5j, 5m, and 5n led to significant reductions in the immobility time in the forced swimming test at a dose of 50 mg/kg, and exhibited higher levels of efficacy than the reference standard fluoxetine. In addition, compound 5i exhibited greater efficacy than fluoxetine in the tail suspension test. The results of an open field test further confirmed that compound 5i provided a good antidepressant effect. In the maximal electroshock seizure screen, compounds 5c and 5d showed moderate levels of anticonvulsant activity and protected 100% of the animals at a dose of 100 mg/kg. None of the synthesized compounds showed any neurotoxicity in the rotarod test at a dose of 100 mg/kg., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

A series of 7-alkoxy-4,5-dihydro-[1,2,4]oxadiazolo[4,3-a]quinolin-1-ones was synthesized and their negative inotropic effects were evaluated by measuring the left atrium stroke volume in isolated rabbit heart preparations. All compounds moderated the cardiac workload by decreasing heart rate and contractility (inotropic effects). Among them, compound 6 was found to be best potent with a -28.89 ± 1.91 % decrease in the stroke volume at a concentration of 3 × 10(-5) M in our in vitro study.

Three series of rhodanine derivatives bearing a quinoline moiety (6a-h, 7a-g, and 8a-e) have been synthesized, characterized, and evaluated as antibacterial agents. The majority of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, 6g and 8c were identified as the most effective with minimum inhibitory concentration (MIC) values of 1 μg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus (MRSA and QRSA, respectively). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL. The cytotoxic activity assay showed that compounds 6g, 7g and 8e exhibited in vitro antibacterial activity at non-cytotoxic concentrations. Thus, these studies suggest that rhodanine derivatives bearing a quinoline moiety are interesting scaffolds for the development of novel Gram-positive antibacterial agents., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Two series of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. The majority of the derivatives exhibited better in vitro activity than the existing drug, milrinone, and 6-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)tetrazolo[5,1-a]phthalazine. 8 m in particular was identified as the most potent with an increased stroke volume of 12.02 ± 0.20% (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10(-5)  m. The chronotropic effects of the compounds that exhibited good potency were also evaluated., (© 2013 John Wiley & Sons A/S.)