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A scientific and rational evaluation of teaching is essential for personalized learning. In the current teaching assessment model that solely relies on Grade Point Average (GPA), learners with different learning abilities may be classified as the same type of student. It is challenging to uncover the underlying logic behind different learning patterns when GPA scores are the same. To address the limitations of pure GPA evaluation, we propose a data-driven assessment strategy as a supplement to the current methodology. Firstly, we integrate self-paced learning and graph memory neural networks to develop a learning performance prediction model called the self-paced graph memory network. Secondly, inspired by outliers in linear regression, we use a t-test approach to identify those student samples whose loss values significantly differ from normal samples, indicating that these students have different inherent learning patterns/logic compared to the majority. We find that these learners' GPA levels are distributed across different levels. Through analyzing the learning process data of learners with the same GPA level, we find that our data-driven strategy effectively addresses the shortcomings of the GPA evaluation model. Furthermore, we validate the rationality of our method for student data modeling through protein classification experiments and student performance prediction experiments, it ensuring the rationality and effectiveness of our method., (© 2023. The Author(s).)

Interleukin-17A (IL-17A) levels are elevated in patients with asthma. Ferroptosis has been identified as the non-apoptotic cell death type associated with asthma. Data regarding the relation of ferroptosis with asthma and the effect of IL-17A on modulating ferroptosis in asthma remain largely unclear. The present work focused on investigating the role of IL-17A in allergic asthma-related ferroptosis and its associated molecular mechanisms using public datasets, clinical samples, human bronchial epithelial cells, and an allergic asthma mouse model. We found that IL-17A was significantly upregulated within serum in asthma cases. Adding IL-17A significantly increased ferroptosis within human bronchial epithelial cells (BEAS-2B). In ovalbumin (OVA)-induced allergic asthmatic mice, IL-17A regulated and activated lipid peroxidation induced ferroptosis, whereas IL-17A knockdown effectively inhibited ferroptosis in vivo by protection of airway epithelial cells via the xCT-GSH-GPX4 antioxidant system and reduced airway inflammation. Mouse mRNA sequencing results indicated that the tumor necrosis factor (TNF) pathway was the differential KEGG pathway in the OVA group compared to healthy controls and the OVA group compared to the IL-17A knockout OVA group. We further used N-acetylcysteine (TNF inhibitor) to inhibit the TNF signaling pathway, which was found to protect BEAS-2B cells from IL-17A induced lipid peroxidation and ferroptosis damage. Our findings reveal a novel mechanism for the suppression of ferroptosis in airway epithelial cells, which may represent a new strategy for the use of IL-17A inhibitors against allergic asthma., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The prevalence of food allergies (FA) has been steadily increasing over 2 to 3 decades, showing diverse symptoms and rising severity. These long-term outcomes affect children's growth and development, possibly linking to inflammatory bowel disease. However, the cause remains unclear. Previous studies reveal that early infancy significantly impacts FA development through gut microbiota. Yet, a consistent view on dysbiosis characteristics and its connection to future allergies is lacking. We explored how early-life gut microbiota composition relates to long-term clinical signs in children with FA through longitudinal research., Methods: We employed high-throughput 16S rDNA gene sequencing to assess gut microbiota composition in early-life FA children in southern Zhejiang. Follow-up of clinical manifestations over 2 years allowed us to analyze the impact of early-life gut microbiota dysbiosis on later outcomes., Results: While the diversity of gut microbiota in FA children remained stable, there were shifts in microbiota abundance. Abundant Akkermansia, Parabacteroides, Blautia, and Escherichia-Shigella increased, while Bifidobacterium and Clostridium decreased. After 2 years, two of ten FA children still showed symptoms. These two cases exhibited increased Escherichia-Shigella and reduced Bifidobacterium during early childhood. The other eight cases experienced symptom remission., Conclusions: Our study suggests that FA and its prognosis might not correlate with early-life gut microbiota diversity. Further experiments are needed due to the small sample size, to confirm these findings., (© 2023. The Author(s).)

Purpose: Recent studies had shown that gut microbiota played a significant role in the development of the immune system and may affect the course of airway allergic disease. We conducted this study to determine unique gut microbial associated with allergic disease in children by shotgun gene sequencing., Methods: We collected fecal samples from children with allergic asthma (n = 23) and allergic rhinitis (n = 18), and healthy control (n = 19). The gut microbiota of specimens was analyzed by high-throughput metagenomic shotgun gene sequencing., Results: The intestinal microbiota of children with allergic asthma and allergic rhinitis was characterized by increased microbial richness and diversity. Simpson and Shannon were significantly elevated in children with allergic asthma. Principal coordinates analysis (PCoA) showed that the gut microbial communities cluster patterns of children with asthma or rhinitis were significantly different from those of healthy controls. However, no significant difference was found between asthma group and rhinitis group At the phylum level, higher relative abundance of Firmicutes was found in the allergic rhinitis group and allergic asthma group, while the level of Bacteroidetes was significantly lower. At the genus level, Corynebacterium, Streptococcus, Dorea, Actinomyces, Bifidobacterium, Blautia, and Rothia were significantly enriched in the allergic asthma group. Finally, a random forest classifier model selected 16 general signatures to discriminate the allergic asthma group from the healthy control group., Conclusion: In conclusion, children in the allergic rhinitis group and allergic asthma group had altered gut microbiomes in comparison with the healthy control group. Compared to healthy children, the gut microbiome in children with allergic diseases has higher pro-inflammatory potential and increased production of pro-inflammatory molecules., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Wan et al.)

Purpose: To compare the anxiety, depression and sleep quality of mothers of healthy control children and mothers of children with atopic dermatitis (AD) of varying severity, both before and after treatment., Methods: A total of 120 parent-child dyads participated in the study. These dyads were divided into four subgroups of 30 patients each: mild AD, moderate AD, severe AD, and control groups. The children's symptoms, their mothers' psychological status, and their mothers' sleep quality were evaluated using the Scoring of Atopic Dermatitis (SCORAD), the Hospital Anxiety and Depression Scale (HADS), and the Pittsburgh Sleep Quality Index (PSQI), respectively, before and after a one-month comprehensive treatment., Results: SCORAD, representing differences in severity of children's AD, decreased significantly after one month's treatment ( p < 0.001). Anxiety in mothers significantly decreased in all AD severity groups after treatment ( p < 0.05). However, for depression, only the mothers in the mild and moderate AD groups showed a decrease after treatment ( p < 0.05). The PSQI total score also decreased in the mild AD group after treatment ( p < 0.05)., Conclusion: The most severe effect was seen in the psychology and sleep quality of mothers of children with severe AD. After one month of treatment, the psychological health and sleep quality of the mothers in the mild AD group significantly improved, while those of mothers in the moderate and severe AD groups showed partial improvement., 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., (© 2023 Song et al.)

The nuclear receptor (NR) superfamily is one of the largest groups of transcription factors in living organisms. Oestrogen related receptor (ERR) is a class of nuclear receptors closely related to oestrogen receptors (ERs). In this study, the Nilaparvata lugens (N. lugens) ERR2 (NlERR2) was cloned, and the expression of NlERR2 was detected by qRT-PCR to explore the distribution of NlERR2 during development and in different tissues. Using RNAi and qRT-PCR, the interaction between NlERR2 and related genes of the 20-hydroxyecdysone (20E) and juvenile hormone (JH) signalling pathways was studied. The results showed that topical application of 20E and juvenile hormone III (JHIII) affected the expression of NlERR2, and NlERR2 could affect the expression of genes related to 20E and JH signalling pathways. Furthermore, NlERR2 and JH/20E hormone signalling-related genes affect moulting and ovarian development. NlERR2 and NlE93/NlKr-h1 affect the transcriptional expression of Vg-related genes. In summary, NlERR2 is related to hormone signalling pathways, which is also related to the expression of Vg and Vg related genes. Brown planthopper is one of the most important rice pests. This study provides an important basis for mining new targets for pest control., (© 2023 Royal Entomological Society.)

Nanoparticles can play valuable roles in delivering nucleic acids, including microRNAs (miRNA), which are small, non-coding RNA segments. In this way, nanoparticles may exert post-transcriptional regulatory influences on various inflammatory conditions and bone disorders. This study used biocompatible, core-cone-structured, mesoporous silica nanoparticles (MSN-CC) to deliver miRNA-26a to macrophages in order to influence osteogenesis in vitro. The loaded nanoparticles (MSN-CC-miRNA-26) showed low-level toxicity towards macrophages (RAW 264.7 cells) and were internalized efficiently, causing the reduced expression of pro-inflammatory cytokines, as seen via real-time PCR and cytokine immunoassays. The conditioned macrophages created a favorable osteoimmune environment for MC3T3-E1 preosteoblasts, driving osteogenic differentiation with enhanced osteogenic marker expression, alkaline phosphatase (ALP) production, extracellular matrix formation, and calcium deposition. An indirect co-culture system revealed that direct osteogenic induction and immunomodulation by MSN-CC-miRNA-26a synergistically increased bone production due to the crosstalk between MSN-CC-miRNA-26a-conditioned macrophages and MSN-CC-miRNA-26a-treated preosteoblasts. These findings demonstrate the value of nanoparticle delivery of miR-NA-26a using MSN-CC for suppressing the production of pro-inflammatory cytokines with macrophages and for driving osteogenic differentiation in preosteoblasts via osteoimmune modulation.

Asthma is a common chronic inflammatory disease of the airway. Intestinal flora, a significant risk factor for asthma, has become a widespread concern in the pathogenesis of asthma. To review the literature related to intestinal flora in asthma, summarize research direction, and report trends, this study used CiteSpace to perform bibliometric statistics and analysis on the research papers of intestinal flora and asthma collected in the Web of science core collection from 2001 to 2021. Eventually, a total of 613 articles were included. The results demonstrated that research on gut flora and asthma continued to heat up, with article numbers increasing, especially in the last decade. Moreover, analysis of the keywords showed that the research topics of intestinal flora and asthma range from confirming the link between intestinal flora and asthma to investigating mechanisms and then to asthma treatment. According to the summary of research hotspots, we expand on three emerging issues that require attention in the intestinal flora and asthma research, including (regulatory T)Treg cells, probiotics, and chain fatty acid. Evidence illustrated that Treg cells play a crucial role in the pathogenesis of asthma caused by dysbiosis of the gut flora. Furthermore, in contrast to probiotic supplements, which do not reduce the risk of developing asthma, short-chain fatty acids supplements do. Overall, the research direction in the field of intestinal flora and asthma has recently evolved from macro to micro with depth broadened. As a robust scientific evaluation, our study provided a comprehensive overview of the area, particularly for research focus, which could more precisely direct scholars on future research and clinical diagnosis, therapy, and individualized prevention., Competing Interests: The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be explained as a potential conflict of interest., (© 2023 Zheng et al.)

Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic and progressive inflammatory joint diseases that affect a large population worldwide. Intra-articular administration of various therapeutics is applied to alleviate pain, prevent further progression, and promote cartilage regeneration and bone remodeling in both OA and RA. However, the effectiveness of intra-articular injection with traditional drugs is uncertain and controversial due to issues such as rapid drug clearance and the barrier afforded by the dense structure of cartilage. Nanoparticles can improve the efficacy of intra-articular injection by facilitating controlled drug release, prolonged retention time, and enhanced penetration into joint tissue. This review systematically summarizes nanoparticle-based therapies for OA and RA management. Firstly, we explore the interaction between nanoparticles and joints, including articular fluids and cells. This is followed by a comprehensive analysis of current nanoparticles designed for OA/RA, divided into two categories based on therapeutic mechanisms: direct therapeutic nanoparticles and nanoparticles-based drug delivery systems. We highlight nanoparticle design for tissue/cell targeting and controlled drug release before discussing challenges of nanoparticle-based therapies for efficient OA and RA treatment and their future clinical translation. We anticipate that rationally designed local injection of nanoparticles will be more effective, convenient, and safer than the current therapeutic approach., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chun Xu reports financial support was provided by U21., (© 2023 The Authors. Published by Elsevier Ltd.)

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide health threat and has already tormented humanity during its long history, creating an urgent need for the development of new classes of antibacterial agents. In this study, twenty-one novel sulfonylurea derivatives containing phenyl-5-vinyl and pyrimidinyl-4-aryl moieties were designed and synthesized, among which, nine compounds exhibited inhibitory potencies against Gram-positive bacterial strains: MRSA (Chaoyang clinical isolates), S. aureus ATCC6538, vancomycin-resistant Enterococci -309 (VRE-309), and Bacillus subtilis ATCC 6633. Especially, 9i and 9q demonstrated inhibitory activities against the four bacterial strains with minimum inhibitory concentrations (MICs) of 0.78-1.56 μg/mL, and quite a few of other MRSA clinical strains with MICs of 0.78 μg/mL, superior to those of the positive controls vancomycin (MIC of 1 μg/mL) and methicillin (MIC of >200 μg/mL). This is the very first time that sulfonylurea derivatives have been identified as promising inhibitors against different MRSA clinical isolates. In addition, all the MIC values of the synthesized compounds against Candida albicans were greater than 100 μg/mL. Since the reported anti- Candida activities of sulfonylureas were due to acetohydroxyacid synthase (AHAS) inhibition, the molecular target against MRSA for the target sulfonylureas was thought to be a different mode of action. Density functional theory (DFT) calculations were finally performed to understand the structure-activity relationships, based on which, significant differences were observed between their HOMO maps for compounds with strong antibacterial activities and weak anti-MRSA effects. The present results hence provide valuable guidance for the discovery of novel agents to treat bacterial infections, especially against MRSA.

Introduction: Allergen immunotherapy (AIT) is considered to be the only treatment that may change the natural process of allergic diseases. Subcutaneous immunotherapy (SCIT) is a type of allergen immunotherapy that is commonly used in clinical practice. However, SCIT has inconsistent effects on individuals, and it is yet unclear what factors affect therapeutic efficacy. In recent years, vitamin D levels have been speculated as a potential factor influencing SCIT efficacy., Objective: To investigate the effect of serum vitamin D level on the SCIT efficacy in children with allergic rhinitis and/or asthma caused by dust mite allergy., Methods: According to the panel consensus, children with asthma and/or allergic rhinitis who received SCIT were divided into the vitamin D deficiency group (<12 ng/ml), vitamin D insufficiency group (12-20 ng/ml), and vitamin D sufficiency group (>20 ng/ml). Serum 1-25(OH) D3, blood eosinophil, total IgE, dermatophagoides pteronyssinus (Dp), and dermatophagoides farina (Df) specific IgE (sIgE) were detected, and questionnaires of symptom and medication scores were collected before and after one year of treatment., Results: After one year of SCIT treatment, the symptom and medication score significantly decreased ( P  < 0.05), but there was no difference between the efficacy in different groups ( P  > 0.05). Our study found a statistical difference in Dp sIgE level between the vitamin D deficiency and the sufficiency groups ( P  = 0.024), and vitamin D levels become lower with children's growth (Y = -0.8981*X + 34.26, P  = 0.0025)., Conclusions: No difference was found between the efficacy of one-year SCIT and serum vitamin D levels based on symptom and medication scores. Nevertheless, higher vitamin D levels may be associated with a decreased indicator of Dp allergy., 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., (© 2022 Jia, Zheng, Yan, Dai and Xiang.)

Micro-ribonucleic acid (miRNA)-based therapies show advantages for bone regeneration but need efficient intracellular delivery methods. Inorganic nanoparticles such as mesoporous bioactive glass nanoparticles (MBGN) and mesoporous silica nanoparticles (MSN) have received growing interest in the intracellular delivery of nucleic acids. This study explores the capacity of MBGN and MSN for delivering miRNA to bone marrow mesenchymal stem cells (BMSC) for bone regenerative purposes, with a focus on comparing the two in terms of cell viability, transfection efficiency, and osteogenic actions. Spherical MBGN and MSN with a particle size of ~200 nm and small-sized mesopores were prepared using the sol-gel method, and then the surface was modified with polyethyleneimine for miRNA loading and delivery. The results showed miRNA can be loaded into both nanoparticles within 2 h and was released sustainedly for up to 3 days. Confocal laser scanning microscopy and flow cytometry analysis indicated a high transfection efficiency (>64%) of both nanoparticles without statistical difference. Compared with MSN, MBGN showed stronger activation of alkaline phosphatase and activation of osteocalcin genes. This translated to a greater osteogenic effect of MBGN on BMSC, with Alizarin red staining showing greater mineralization compared with the MSN group. These findings show the potential for MBGN to be used in bone tissue engineering.

Rationale: The imbalance of T helper (Th17) cell and regulatory T (Treg) cell are involved in allergic asthma pathogenesis. We hypothesized that ICS/LABA could modulate the Th17/Treg imbalance and that subcutaneous immunotherapy (SCIT) could coordinate with ICS/LABA to rebalance the dysfunction of Th17/Treg., Methods: Thirty house dust mites (HDM) allergic asthmatic children and fifteen healthy control subjects were enrolled in this study. Fifteen asthmatic children were treated by ICS/LABA powder inhalation, while the other fifteen asthmatic children were treated by ICS/LABA powder inhalation combined with HDM-SCIT. Asthmatic subjects were followed up for 6 months, but 2 asthmatics treated with ICS/LABA were lost to follow-up. Flow cytometry was used to determine the proportions of Th17 and Treg in CD4 + T cells from peripheral blood mononuclear cells (PBMCs). Serum levels of IL-17A and IL-10 were assessed by ELISA., Result: ICS/LABA treatment significantly reduced the percentage of Th17 cells (1.252 ± 0.134% vs. 2.567 ± 0.386%), serum IL-17A (49.42 ± 2.643 pg/ml vs. 66.75 ± 3.442 pg/ml) and Th17/Treg ratio (0.194 ± 0.025 vs. 0.439 ± 0.072) compared to baseline (P<0.01). The ICS/LABA+HDM-SCIT treatment group showed similar reduction in the percentage of Th17 cells (1.11 ± 0.114% vs. 2.654 ± 0.276%), serum IL-17A (49.23 ± 2.131 pg/ml vs. 66.41 ± 2.616 pg/ml) and the Th17/Treg ratio (0.133 ± 0.015 vs. 0.4193 ± 0.050) (P<0.01). ICS/LABA+HDM-SCIT treatment group demonstrated elevated Treg percentages (8.483 ± 0.408% vs. 6.549 ± 0.299%) and serum IL-10 levels (127.4 ± 4.423 pg/ml vs. 93.15 ± 4.046 pg/ml), resulting in a lower Th17/Treg ratio than the ICS/LABA group., Conclusion: ICS/LABA treatment regulates Th17/Treg imbalance mainly by mitigating Th17-induced inflammation in asthma patients. The addition of SCIT further enhanced such effect by upregulating Treg cells., 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 © 2022 Dai, Zheng, Wang, Wan, Tong, Zhao and Zhang.)

A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 μmol·L -1 , respectively. Compounds 9-12 also showed good cellular antioxidant activities with CAA 50 values of 12.23, 23.11, 5.31 and 16.04 μmol·L -1 , respectively. Molecular docking between COVID-19 M pro and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods., (Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl 4 )-induced acute liver injury mouse model., Methods: High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O 2 ∙- , OH ∙ , DPPH ∙ , and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl 4 . Hepatoprotective effects of GTP were evaluated in a CCl 4 -induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot., Results: GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl 4 -exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl 4 -exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01)., Conclusion: GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.

A diffusive epidemic model with two delays subjecting to Neumann boundary conditions is considered. First we obtain the existence and the stability of the positive constant steady state. Then we investigate the existence of Hopf bifurcations by analyzing the distribution of the eigenvalues. Furthermore, we derive the normal form on the center manifold near the Hopf bifurcation singularity. Finally, some numerical simulations are carried out to illustrate the theoretical results.

Background: The prevalence of food allergy (FA) has increased worldwide. In China, the prevalence of FA in infants and school-aged children is well known, but the prevalence in preschool children is unknown., Methods: A total of 4151 preschool children aged 3 to 6 years in urban Wenzhou, China, were recruited for this cross-sectional study. Their parents completed a preliminary screening questionnaire, and a detailed FA questionnaire was given to parents whose children had suspected FA according to the preliminary screening. According to the results of the detailed FA questionnaires, some children underwent a skin prick test (SPT) and specific IgE (sIgE) measurement. Children with abnormal SPT and/or sIgE results who did not meet the diagnostic criteria and those with negative SPT and sIgE results whose histories strongly supported FA underwent an oral food challenge (OFC)., Results: Of the 4151 children's parents who completed the surveys, 534 (12.86%) indicated a positive medical history of FA. Among the 40 children who underwent an OFC, 24 were positive. According to SPT and sIgE measurements, 11 children were diagnosed with FA. The prevalence of FA was at least 0.84%; children who dropped out during the study were considered FA-negative. Among the 35 children with FA, the most common allergic manifestation was skin symptoms. The most common allergic foods were egg, fish and shrimp., Conclusions: The parent-reported rate of FA in preschool children in urban Wenzhou was 12.86%. The prevalence of FA was at least 0.84%. Among all cases, the most common allergic food was eggs, and the most common allergic manifestation was skin symptoms., Trial Registration: NCT03974555, registered on 30 May 2019 (www.clinicaltrials.gov).

Two new meroterpenoid compounds (1 and 2) together with five known meroterpenoid derivatives (3-7) were isolated from solid culture of mushroom Panus lecomtei. The structures of new compounds were confirmed by the analysis of NMR and HR-ESI-MS spectroscopic data. The biosynthetic pathway of 1-7 was postulated. All isolated compounds were evaluated for antibacterial activities against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Bacillus Calmette-Guérin. Compound 3 exhibited weak antibacterial activity against Bacillus Calmette-Guérin with the inhibition rate of 83.6% at 100 μmol·L -1 . Other compounds showed no antibacterial activities against all tested pathogens at 100 μmol·L -1 ., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Atropa belladonna seedlings were used as experimental materials and cultivated by soil culture method. Different concentrations(0,0.05,0.1,0.2,0.5 mmol·L~(-1))of NO donor sodium nitroprusside(SNP) were sprayed on the leaves. The effects of different concentrations of SNP and different treatment time(4,8,12,16 d) on nitrogen metabolism, secondary metabolite content, precursor content of tropane alkaloid synthesis pathway and expression of key enzyme genes under 100 mmol·L~(-1) NaCl stress were studied. The results showed that with the prolongation of salt stress, the nitrogen metabolism and the accumulation of secondary metabolites of A. belladonna were inhibited to some extent. After treatment with different concentrations of exogenous SNP, the ammonium nitrogen content decreased dramatically, and the contents of nitrate nitrogen, free amino acid, soluble protein and the activities of key enzymes of nitrogen metabolism(NR, GS, GDH) were all greatly improved; the contents of precursor amino acids(ornithine, arginine) and polyamines(Put, Spd, Spm) in the secondary metabolic pathway have increased to varying degrees. The qRT-PCR analysis showed that exogenous SNP treatment can effectively promote the high expression of key enzyme genes PMT, TRⅠ and H6H in the secondary metabolic pathway of A. belladonna, and the production of hyoscyamine and scopolamine were increased notably. In summary, the application of appropriate concentration of SNP can effectively alleviate the inhibition of salt stress on the nitrogen metabolism and secondary metabolism of Atropa belladonna, and enhance its salt tolerance. Overall, 0.1 mmol·L~(-1) and 0.2 mmol·L~(-1) SNP treatment achieved the most remarkable effect.

According to the data of Pinellia ternate transcriptome,two calmodulin genes were cloned and named as Pt Ca M1 and PtCa M2 respectively. The results of bioinformatics analysis showed that Pt Ca Ms genes contained a 450 bp open reading frame,encoding149 amino acids.The identity of the coding sequences was 80%,and the identity of amino acids sequence was 91%. Pt Ca Ms genes contained EF-hand structure domain,belonging to the Ca M families. The Real-time PCR analysed the expression patterns of Pt Ca Ms in different tissues and different treatments. RESULTS:: showed that Pt Ca M1 and Pt Ca M2 gene were the highest expression level in tuber. Under Ca Cl2 treatment,the expressions of Pt Ca Ms were significantly higher than the control. Under EGTA,La Cl3 and TFP treatments,the expression level of Pt Ca Ms decreased gradually. In this study,the Pt Ca Ms gene were successfully cloned from P. ternate,which laid a foundation for the functional characteristic of Pt Ca Ms gene and the synthesis of alkaloids from P. ternata for further study.

Background: Urinary DcR2 (uDcR2) is a biomarker for the early detection the tubulointerstitial injury (TII) in patients with chronic kidney disease (CKD), but the high-dose hook effect may lead to falsely low or even negative results when using an enzyme-linked immunosorbent assay (ELISA). This study aimed to investigate if the high-dose hook effect exists with ELISA testing, and to uncover a potential approach for reducing this effect., Methods: 72 CKD patients were recruited and categorized into four groups based on TII scores. uDcR2 was measured in undiluted and serially diluted (two-, four-, eight- and 16-fold dilutions) urine using an ELISA kit. The results from the assay were normalized to urinary creatinine. We evaluated the correlation between uDcR2/cre levels at different dilutions and renal histological parameters. Receiver operating characteristic (ROC) curves were generated to examine the value of uDcR2/cre for predicting TII., Results: uDcR2/cre levels in the undiluted urine were significantly higher in patients with CKD than those in the control. However, higher TII scores did not yield higher levels of uDcR2/cre in the undiluted urine. After serial dilution, uDcR2/cre levels were highest with the four-fold dilution. A positive correlation was found between uDcR2/cre levels at different dilutions and TII scores, with the highest correlation coefficient and the largest AUC being observed at the four-fold dilution., Conclusions: The high-dose hook effect was apparent during ELISA testing of uDcR2 in CKD patients, yet dilution of the urine samples neutralized this effect. However, the use of a four-fold dilution of urine for uDcR2/cre testing may eliminate the high-dose hook effect and make it possible to effectively monitor the severity of TII in CKD patients., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: The tripartite motif 66(TRIM66) is an important member of the TRIM protein superfamily, which can participate in the expression of multiple proteins, and is closely associated with the behaviors of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the effect of TRIM66 in this process in vitro using NSCLC cell lines, and the role of TRIM66 in regulating epithelial-mesenchymal transition(EMT) in NSCLC., Methods: Western blotting was used to detect the TRIM66 protein expression levels in NSCLC cell lines and normal lung epithelial cells BEAS-2B. We silenced its expression in A549 cells by transient siRNA transfection to ascertain the function of TRIM66 in NSCLC cells. Western blotting was used to detect the expression of EMT-related proteins., Results: TRIM66 protein content was highest in NSCLC cell line A549, compared with BEAS-2B, it showed that the TRIM66-siRNA group lung cancer cell proliferation was significantly reduced after knockdown of TRIM66, and knockdown of TRIM66 also suppressed invasion, migration and clonogenic ability of A549 cells. Finally, we found that siRNA-mediated TRIM66 silencing suppressed EMT by downregulating expression of N-cadherin and vimentin and upregulating that of E-cadherin in NSCLC cells, which could effectively reduce the invasive, migratory, and proliferative capacities of lung cancer cells., Conclusion: Silence TRIM66 expression suppressed NSCLC cell proliferation, invasion, and migration. The siRNA-mediated TRIM66 silencing could block the occurrence of EMT. TRIM66 could be a promising novel target for future NSCLC treatments., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients who were diagnosed by renal biopsy. uDcR2 levels were measured by ELISA, and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2 and renal functional parameters were evaluated. Receiver operating characteristics (ROC) curve analyzed area under the curve (AUC) of uDcR2 for assessing TII. Double staining was undertaken for renal DcR2 with proximal and distal tubular markers; senescent markers p16, p21, and senescence-associated β-galactosidase (SA-β-gal); and fibrotic markers collagen I and IV. We found DcR2 was primarily expressed in renal proximal tubules; uDcR2 levels were elevated per albuminuria stratum and correlated with renal functional parameters in diabetics and were associated with percentage of tubular DcR2 and TII score in DN. The uDcR2 had an AUC of 0.909 for assessing TII in DN by ROC analysis. Almost all tubular DcR2 was coexpressed with p16 and p21, and nearly more than one-half of tubular DcR2 was positive for SA-β-gal, primarily in collagen I- and IV-positive regions of DN. Our results indicate uDcR2 could potentially serve as a novel biomarker for TII and may reflect senescence of renal proximal tubular cells in DN pathogenesis., (Copyright © 2017 the American Physiological Society.)

Objective: To study the protective effect of Sanhuangyinchi Fang drug serum (SF) against hydrogen peroxide-mediated DNA oxidative damage in LO2 cells., Methods: The LO2 cells were randomly divided into the control group, H(2)O(2) group, SF groups (5%, 10%, and 15%) and vitE group. The morphological features of the treated LO2 cells were observed under inverted microscope. The viability of the treated cells was assessed with CCK-8 method, and the activity of SOD, CAT and GSH-PX were detected biochemically. Reactive oxygen species (ROS) levels, the content of 8-OHdG, and DNA damage of the cells were evaluated by flow cytometry, ELISA, and Comet assay, respectively., Results: Compared with H(2)O(2) group, the cells in SF groups (10% and 15%) and vitE group showed higher cell survival rate (P<0.05) and higher SOD, CAT, GSH-PX (P<0.05) and ROS scavenging activities (P<0.01) with markedly decreases the content of 8-OHdG (P<0.01) and reduced tailing ratio, tail length, tail moment and Olive tail moment (P<0.05)., Conclusion: SF drug serum, especially at the concentration of 15%, can protect LO2 cells from H(2)O(2)-mediated DNA oxidative damage.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have caused an increasing mortality rate, which means that antibiotic resistance is becoming an important health issue. In the course to screen new agents for resistant bacteria, we identified that a series of isatin-β-thiosemicarbazones (IBTs) could inhibit the growth of MRSA and VRE. This was the first time that the "familiar" IBT compounds exhibited significant anti Gram-positive pathogen activity. Against a clinical isolated MRSA strain, 20 of the 51 synthesized compounds showed minimum inhibitory concentration (MIC) data of 0.78 mg/L and another 12 novel compounds had MICs of 0.39 mg/L. Moreover, these compounds also inhibited Enterococcus faecalis and VRE at similar levels, indicating that IBTs might have different mode of action compared with vancomycin. For these IBTs, comparative field analysis (CoMFA) models were further established to understand the structure-activity relationships in order to design new compounds from steric and electrostatic contributions. This work has suggested that IBTs can be considered as potential lead compounds to discover antibacterial inhibitors to combat drug resistance., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Gluconobacter oxydans DSM2003 was used to catalyze the oxidation of racemic 1-phenyl-1,2-ethanediol (PED) for the production of (S)-enantiomer. The oxidative product mandelic acid produced strong inhibition to this reaction and largely reduced the activity of biocatalyst, which was the key problem in the reaction. In order to overcome this bottleneck, an anion exchange resin was selected and introduced as adsorbent for the in situ removal of the inhibitor from the reaction system. This method increased the substrate concentration from 12 to 60 g/L and the yield of (S)-PED by approximately five times from 4.9 g/L, on the premise that the enantiomeric excess (ee) value of (S)-PED remained above 96% and the reaction time was no more than 20 h. Moreover, the final space-time yield was over 1.2g/L/h, which was higher than that reported from previous studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A Gram-positive, aerobic, non-motile actinobacterium, designated strain Ms392A(T), was isolated from an ocean-sediment sample collected from the South China Sea. The isolate contained chemical markers that supported chemotaxonomic assignment to the genus Amycolatopsis. On the basis of an analysis of 16S rRNA gene sequence similarities, strain Ms392A(T) represents a novel subclade within the genus Amycolatopsis, with Amycolatopsis palatopharyngis 1BDZ(T) as its closest phylogenetic neighbour (99.4 % similarity). However, DNA-DNA hybridization demonstrated that strain Ms392A(T) was distinct from A. palatopharyngis AS 4.1729(T) (48.6 % relatedness). The polyphasic analysis demonstrated that the ocean isolate can be clearly distinguished from recognized species of the genus Amycolatopsis. Therefore, strain Ms392A(T) represents a novel species of the genus Amycolatopsis, for which the name Amycolatopsis marina sp. nov. is proposed. The type strain is Ms392A(T) (=CGMCC 4.3568(T) =NBRC 104263(T)).