A review of long non-coding RNAs in ankylosing spondylitis: pathogenesis, clinical assessment, and therapeutic targets.

Ankylosing spondylitis (AS) is a chronic immune-mediated type of inflammatory arthritis characterized by inflammation, bone erosion, and stiffness of the spine and sacroiliac joints. Despite great efforts put into the investigation of the disease, the pathogenesis of AS remains unclear, posing challenges in identifying ideal targets for diagnosis and treatment. To enhance our understanding of AS, an increasing number of studies have been conducted. Some of these studies reveal that long non-coding RNAs (lncRNAs) play crucial roles in the etiology of AS. Some certain lncRNAs influence the development of AS by regulating inflammatory responses, autophagy, apoptosis, and adipogenesis, as well as the proliferation and differentiation of cells. Additionally, some lncRNAs demonstrate potential as biomarkers, aiding in monitoring disease progression and predicting prognosis. In this review, we summarize recent studies concerning lncRNAs in AS to elucidate the underlying mechanisms in which lncRNAs are involved and their potential values as biomarkers for disease assessment and druggable targets for therapy.

Design, Synthesis, Nematicidal, and Fungicidal Activities of Novel Azo and Azoxy Compounds.

Bursaphelenchus xylophilus (B. xylophilus) and Meloidogyne are parasitic nematodes that have caused severe ecological and economic damage in pinewood and crops, respectively. Jietacins (jietacin A and B) were found to have excellent biological activity against B. xylophilus. Based on our tremendous demand for chemicals against B. xylophilus, a novel scaffold based on the azo and azoxy groups was designed, and a series of compounds were synthesized. In the bioassay, Ia, IIa, IIc, IId, and IVa exhibited higher activity against B. xylophilus in vitro than avermectin (LC50 = 2.43 µg·mL-1) with LC50 values of 1.37, 1.12, 0.889, 1.56, and 1.10 µg·mL-1, respectively. Meanwhile, Ib, Ic, IIc, and IVa showed good inhibition effects against Meloidogyne in vivo at the concentrations of 80 and 40 µg·mL-1 with inhibition rates of 89.0% and 81.6%, 95.6% and 75.7%, 96.3% and 41.2%, and 86.8% and 78.7%, respectively. In fungicidal activity in vitro, IIb and IVa exhibited excellent effect against Botryosphaeria dothidea with the inhibition of 82.59% and 85.32% at the concentration of 10 µg·mL-1, while the inhibition of Ia was 83.16% against Rhizoctonia solani at the concentration of 12.5 µg·mL-1. Referring to the biological activity against B. xylophilus, a 3D-QASR model was built in which the electron-donating group and small group at the 4-phenylhydrazine were favorable for the activity. In general, the novel azoxy compounds, especially IIc possess great potential for application in the prevention of B. xylophilus.

Predicting the mechanism of Tiannanxing-Shengjiang drug pair in treating pain using network pharmacology and molecular docking technology.

OBJECTIVE: This study aimed to analyze the potential targets and mechanism of Tiannanxing-Shengjiang drug pair in pain treatment using network pharmacology and molecular docking technology. METHODS: The active components and target proteins of Tiannanxing-Shengjiang were obtained from the TCMSP database. The pain-related genes were acquired from the DisGeNET database. The common target genes between Tiannanxing-Shengjiang and pain were identified and subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses on the DAVID website. AutoDockTools and molecular dynamics simulation analysis were used to assess the binding of the components with the target proteins. RESULTS: Ten active components were screened out, such as stigmasterol, ß-sitosterol, and dihydrocapsaicin. A total of 63 common targets between the drug and pain were identified. GO analysis showed that the targets were mainly associated with biological processes such as inflammatory response and forward regulation of the EKR1 and EKR2 cascade. KEGG analysis revealed 53 enriched pathways, including pain-related calcium signaling, cholinergic synaptic signaling, and serotonergic pathway. Five compounds and 7 target proteins showed good binding affinities. These data suggest that Tiannanxing-Shengjiang may alleviate pain through specific targets and signaling pathways. CONCLUSION: The active ingredients in Tiannanxing-Shengjiang might alleviate pain by regulating genes such as CNR1, ESR1, MAPK3, CYP3A4, JUN, and HDAC1 through the signaling pathways including intracellular calcium ion conduction, cholinergic prominent signaling, and cancer signaling pathway.

PIII -Directed Late-Stage Ligation and Macrocyclization of Peptides with Olefins by Rhodium Catalysis.

Transition metal-catalyzed C-H activation is a step-economical strategy for peptide functionalization. Herein, we report the method of late-stage peptide ligation and macrocyclization through rhodium-catalyzed alkylation of tryptophan residues at the C7 position. This method utilizes a N-Pt Bu2 directing group and tolerates various peptide and alkene substrates. Utilizing internal olefins, this study represents the first example of site-selective peptide C-H alkylation through deconjugative isomerization. Furthermore, our method provides access to peptide macrocycles with unique Trp(C7)-alkyl crosslinks and potent cytotoxicity towards cancer cells.

A hybrid XGBoost-ISSA-LSTM model for accurate short-term and long-term dissolved oxygen prediction in ponds.

Dissolved oxygen (DO) is one of the most critical factors to measure the water quality in ponds, which greatly impacts on healthy growth of aquatic organisms. To improve the prediction accuracy of DO and grasp its changing trends, a novel hybrid DO prediction model based on the long short-term memory network (LSTM) optimized by an improved sparrow search algorithm (ISSA) is proposed. Firstly, to discard redundant information and improve the calculation speed of the model, the key factors that have a greater correlation with DO are selected as the input parameters by extreme gradient boosting (XGBoost). Secondly, towards expanding the searching range of sparrows and balancing the global and local search, we introduce an adaptive factor exponential declining strategy for producers, and an arcsine decreasing strategy for scouters, which nonlinearly decreases with the increase of iterations. Besides, we also improve the position updating of scouters, making the sparrows gradually move to the best position. Finally, LSTM is optimized by ISSA to get the best initial weights and thresholds to construct an XGBoost-ISSA-LSTM DO prediction model. Specifically, we first analyze the method for water quality prediction, which can make short-term prediction (including about 1 h, 2 h) and long-term prediction (including about 12 h, 24 h) of DO. In 1-h prediction, the root mean square error (RMSE) of the model is 0.5571, the mean absolute error (MAE) is 0.2572, and the R2 is 0.9276. In 24 h prediction, RMSE of the model is 0.6310, MAE is 0.4562, and R2 is 0.9082. The experimental results show that the proposed model has better generalization performance and higher prediction accuracy compared with other common models. Therefore, the presented model based on XGBoost-ISSA-LSTM is more effective and could meet the actual demand of accurate prediction of DO.

Effect of storage states on stability of three organophosphorus insecticide residues on cowpea samples.

BACKGROUND: The stability of pesticide residues in stored samples is very important to ensure the quality of data about the residues. The evaluation of pesticide residues in food and environment samples is an important means to ensure food quality and protect consumers against potential dietary risks. Improper storage of pesticide residue samples may result in loss of pesticide and unreliable data, which could affect safety assessments. RESULTS: The influences of storage conditions, including temperature (-20 °C, 4 °C, and ambient temperature) and sample state (homogenized state and coarsely chopped state) on the storage stability of dichlorvos, malathion, and diazinon on cowpea were studied. Dichlorvos and malathion were more stable in an homogenized state than in a coarsely chopped state. At 4 °C, the residual dichlorvos in the coarsely chopped state and the homogenized state, respectively, was 12% and 69%; the residual malathion was 26% and 92%, respectively. Dichlorvos suffered a large loss of 89% and 59% for coarsely chopped and homogenized cowpea, even at -20 °C. It was obvious that the stability of dichlorvos and malathion were more affected by storage state than diazinon. The stability of diazinon was significantly affected by temperature. The effect of storage state and temperature on stability is likely to be correlated with enzymes in the matrix, such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). CONCLUSION: The optimal stable storage conditions for three organophosphorus insecticides residues on cowpea were in the homogenized state and under a lower temperature. © 2021 Society of Chemical Industry.

Efficacy and Safety of Chuanxiong Qingnao Granule in Patients with Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Chuanxiong Qingnao Granule (CQG) to treat migraine. METHOD: This study was a randomized, double-blind, placebo-controlled trial. All migraineurs were recruited and randomly assigned into a treatment group treated with CQG and a control group treated with a placebo. The whole research process included a 4-week baseline, 12-week intervention, and 12-week follow-up. The primary outcome was responder rate, defined as the percentage of migraineurs with 50% or more reduction in the frequency of migraine attack during treatment and posttreatment period compared with the baseline. The secondary outcomes were the number of migraine days, migraine attack frequency, visual analogue scale (VAS), Fatigue Severity Scale (FSS), Hamilton Depression Scale (HAMD), and Migraine Disability Assessment (MIDAS). RESULTS: A total of 346 migraineurs completed the research and were included in the intention-treatment analyses. The response rates differed significantly between the treatment group and the control group (71.5% vs. 12.1% at week 12 and 83.1% vs. 3.4% at week 24). Attack frequency, days of headache attack, VAS, FSS, HAMD, and MIDAS decreased at week 12 in both groups with more reduction in the treatment group (P < 0.001). No severe adverse events were observed in this trial. CONCLUSION: Chuanxiong Qingnao Granule can significantly improve headache symptoms in patients with migraine while improving disability, fatigue, and depression with a good safety profile.

The stability of four organophosphorus insecticides in stored cucumber samples is affected by additives.

The influence of some additives, including metal ions, antioxidants, enzyme inhibitors and organic solvents, on the storage stability of four organophosphorus pesticides in cucumber samples were investigated. It was found that metal ions, including Al3+, Fe3+, and Co2+, increased the stability of dichlorvos, malathion, and chlorpyrifos. Conversely, Al3+, Fe3+, Fe2+, and Co2+ caused catalytic degradation of diazinon. With the addition of organic solvents (CH2Cl2, CHCl3, CCl4, CH3OH and CH3COCH3), remaining of diazinon residues was higher (16-54%) after storage for seven days. CCl4 was associated with the highest retention of malathion, diazinon, and chlorpyrifos (33%, 48% and 44%, respectively) in samples. SDS also stabilized the pesticides since residues were, again, higher (13-38%) after seven days storage. Furthermore, addition of Al3+ and Fe3+ decreased peroxidase (POD) activity and inhibited degradation of dichlorvos and malathion. After 14 days, lyophilization increased the pesticide residues remaining by 36%, 29%, and 58% for diazinon, malathion and chlorpyrifos, respectively. Overall, the stability of these pesticides during storage is impacted by water content and addition of exogenous substances. This could ensure higher quality of pesticide residue data in samples.