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BackgroundLatent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA.MethodsThis randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up.ResultsA total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG.ConclusionsDry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months.Trial registrationRegistered in the Chinese Clinical Trial Registry (www.chictr.org.cn) in 17/11/2017 with the following code: ChiCTR-INR-17013432.

IntroductionLower limb dysfunction is among the common sequelae of patients who had a poststroke and often results in the reduction of the quality of life. This study aims to assess the short and interim-term efficacy of dry needling (DN) intervention on lower extremity function, balance and gait in lower limb dysfunction after stroke.Methods and analysisThis protocol entails an assessor and statistician-blinded, single-centre study with a randomised controlled trial. Forty-four patients who had a poststroke will be randomly allocated (1:1) to either the conventional treatment group (n=22) or the DN group (n=22). The conventional treatment group will receive conventional rehabilitation treatment once a day for 40 min each time. The treatment will be performed five times a week for 2 weeks. In the DN group, participants will be treated with DN on the basis of the conventional treatment. The intervention will be performed thrice a week for 2 weeks. The primary outcome that determines the efficacy of lower limb dysfunction will be the change in the Fugl-Meyer Assessment of Lower Extremity scale. The secondary indicators include the range of motion of knee and ankle joints, limits of stability, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, Modified Ashworth Scale and Barthel Index. Results will be evaluated at baseline, at 24 hours after intervention, at 2 weeks after intervention and at 3-month follow-up. Data will be released after the completion of the study. Adverse events will be reported.Ethics and disseminationThe experiment was approved by the Ethical Committee of Shanghai Tong Ren Hospital in October 2021 (approval number: 202105702). The results of this study will be published in peer-reviewed journals.Trial registration numberChiCTR2000040754.

An efficient and general method for the catalytic installation of azido and thiocyanato groups via remote C(sp3)–H activation is described. The copper-catalyzed reaction proceeds through a cascade of single-electron transfer, favorable 1,5-hydrogen atom transfer, and C–N/C–S cross-coupling, thus providing the distal azido and thiocyanato alkylamines. This reaction could be applicable to primary, secondary, tertiary, and benzylic C(sp3)–H functionalization, as well as demonstrating excellent site-selectivity and functional-group compatibility.

Background Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Besides, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. Results The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. Conclusion In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity study inferred that the "no-observed adverse effect level" (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of the PSO. This article is protected by copyright. All rights reserved.

Objective The objective of this study was to conduct an updated systematic review of diagnostic criteria for myofascial trigger points (MTrPs) used in clinical trials of physical therapy interventions from 2007 to 2019. Methods MEDLINE and Physiotherapy Evidence Database (PEDro) were searched using the following MeSH keywords: "trigger points," "trigger point," "myofascial trigger point," "myofascial trigger points," "myofascial pain," and "myofascial pain syndrome." The MeSH keywords were combined by using Boolean operators "OR"/"AND." All physiotherapy clinical trials including patients with musculoskeletal conditions characterized by at least 1 active MTrP or latent MTrP in any body area were selected. We pooled data from an individual criterion and criteria combinations used to diagnose MTrPs. The protocol was developed in accordance with the PRISMA-P guidelines. Results Of 478 possibly relevant publications, 198 met the inclusion criteria. Of these 198 studies, 129 studies (65.1%) stated specifically the diagnostic criteria used for MTrPs in the main text, 56 studies (28.3%) failed to report any method whereby MTrP was diagnosed, and 13 studies (6.6%) adopted expert-based definitions for MTrPs without specification. Of 129 studies, the 6 criteria applied most commonly were: "spot tenderness" (n=125, 96.9%), "referred pain" (95, 73.6%), "local twitch response" (63, 48.8%), pain recognition (59, 45.7%), limited range of motion" (29, 22.5%), and "jump sign" (10, 7.8%). Twenty-three combinations of diagnostic criteria were identified. The most frequently used combination was "spot tenderness," "referred pain," and "local twitch response" (n=28 studies, 22%). Conclusions A number of the included studies failed in properly reporting the MTrP diagnostic criteria. Moreover, high variability in the use of MTrP diagnostic was also observed. Spot tenderness, referred pain, and local twitch response were the 3 most popular criteria (and the most frequently used combination). A lack of transparency in the reporting of MTrP diagnostic criteria is present in the literature. Registry This systematic review was registered under the Centre for Reviews and Dissemination, PROSPERO number: CRD42018087420.

Here we report a method for the site-selective intermolecular C(sp3)–H amination of carboxamides by merging transition-metal catalysis and the hydrogen atom transfer strategy. The reaction proceeds...

Inefficient utilization of flavonoid resources from agricultural waste has caused serious pollution of the ecological environment. Isoquercitrin, a natural and rare flavonoid, shows obvious pharmacological activities. Abandoned rutin from plant could be used to produce isoquercitrin by the employment of the rhamnose hydrolysis. This study reported an efficient preparation process of isoquercitrin using the conversion of rutin catalyzed by whole-cell catalysts in a polyvinylidene fluoride (PVDF) membrane reactor coupled with reaction and separation. The PVDF hollow fibre membrane with filtration precision of 0.1 μm was selected as the membrane module. Recombinant Escherichia coli whole cells were used as catalysts. And the effects of the extractant-substrate volume ratio, reaction temperature, pH and substrate concentration on the yield were investigated. The results showed that the isoquercitrin yield of the coupling system with an extractant increased within 0–8 h and reached a maximum yield of 82.2 ± 2.3% at 8 h. The maximum isoquercitrin yield of 87.92 ± 2.93% was obtained under the optimum reaction conditions as follows: a temperature of 40 °C, a ratio of extractant: substrate of 3:4, a pH value of 5.5, and a substrate concentration of 0.02 g/L. After five-successive cycles, the relative enzyme activity of the whole-cell catalysts was maintained above 50%. The flux of the membrane used for 10 h was restored to 75% when washed seven times with a 1% (v/v) aqueous HCl solution. Thus, the PVDF membrane reactor coupled with reaction and separation could be used in the industrial application of biocatalysis due to the increase of reaction efficiency and the decrease of product inhibition.

A visible-light-driven iminyl radical-mediated C–C bond cleavage and functionalization of cycloketone oxime esters have been accomplished. This protocol is simple and does not require expensive and toxic photoredox and/or transition-metal catalysis, providing a novel catalyst-free strategy for alkylation, allylation, vinylation and alkynylation through addition of C(sp3)-centered radicals to various unsaturated acceptors. The commercially available and photoactive Hantzsch ester effectively serves as an electron donor, as well as a hydrogen atom source.

BACKGROUND: Whole‐cell catalysis has been widely used because the steps of extracting pure enzyme are omitted and the cost would be greatly saved. However, the efficiency of the whole‐cell catalyst can be limited by the existence of the cell membrane. In the present study, to enhance the binding between an intracellular enzyme and a substrate, ionic liquids (ILs) and deep eutectic solvents (DESs) were used to treat Escherichia coli BL21‐pET21a‐rhaB1 cells for isoquercitrin production by the biotransformation of rutin. RESULTS: The whole‐cell catalyst exhibited the highest catalytic activity with 6% choline chloride‐urea (ChCl/U) after treatment with different concentrations. The ChCl/U‐treated whole‐cell catalyst was more stable than the crude rhaB1, because its optimum pH was closer to neutral and it demonstrated higher temperature tolerance. Under the best conditions of rutin concentration 0.05 g L–¹, pH 6.5 and 40 °C, the isoquercitrin yield reached a maximum of 93.05 ± 1.3%. Additionally, the whole‐cell catalyst retained >52% enzyme activity after five repeated uses. CONCLUSION: These results show that using ChCl/U to increase cell permeability improves the catalytic performance of the whole‐cell catalyst of E. coli BL21‐pET21a‐rhaB1. This approach has promising potential for the utilization of natural flavonoids. © 2019 Society of Chemical Industry

Based on the modern anatomy and physiology, the referred pain of myofascial trigger points of each muscle is integrated; compared with the twelve meridians as well as conception vessel and governor vessel, the similarity of their position and running course is observed. With the current research progress of myofascial trigger points and fasciology, based on the running course of referred pain of trigger points, combined with fascia mechanics, nerve and vascular, the location of acupoints and meridians, as well as the relationship between acupoints and meridians, are discussed.在现代解剖生理学基础上，将各个肌肉的肌筋膜触发点牵涉痛区域进行整合，对比传统经络的十二经脉和任督二脉，观察二者位置和走行的相似性；并通过目前肌筋膜触发点和筋膜学的研究进展，在触发点牵涉痛路径的基础上，结合筋膜力学、神经和血管思路深入理解穴位的定位和经络，以及穴位和经络的关系。.

Tobacco smoke is the major risk factor for developing chronic obstructive pulmonary disease (COPD). Viral infection is a major cause of COPD exacerbation, which lacks effective drug treatments. In the present study, to mimic the pathogenesis of COPD, we employed a TLR3 ligand [Poly (I:C), PIC] to mimic viral infection to determine whether it enhances the effects of cigarette smoke (CS)-induced airway inflammation and remodeling. Our results showed that PIC enhanced the effects of cigarette smoke extract (CSE)-induced inflammatory cytokine IL-1β, TNF-α and IL-8 mRNA expression and remodeling factor E-cadherin, α-SMA and TGF-β1 mRNA expression with TLR3 upregulation and EGFR phosphorylation in pulmonary epithelial NCI–H292 cells. These responses were inhibited by a TLR3/dsRNA complex inhibitor (TLR3i) or a tyrosine kinase inhibitor icotinib (Ico). Similarly, in the PIC-enhanced CS-induced airway inflammation and remodeling mouse model, treatment with TLR3i or Ico reduced the mRNA and protein expression of the inflammatory cytokines IL-1β and TNF-α and keratinocyte chemoattractant (KC) and the remodeling factors α-SMA, TGF-β1, MMP-9 and MUC5AC, while increasing E-cadherin mRNA and protein expression. Furthermore, we found that TLRi and Ico can attenuate the airway hyperreactivity induced by PIC, which is enhanced by CS. Finally, PIC enhanced the effects of CS on TLR3 upregulation and EGFR phosphorylation and significantly increased Erk1/2 and P38 phosphorylation, whereas TLR3i and Ico markedly suppressed TLR3 upregulation and EGFR, Erk1/2 and P38 phosphorylation in the model. Our findings suggest that TLR3/EGFR may be a potential target for the treatment of airway inflammation and remodeling in COPD.

Ginger has been used as a flavoring agent and traditional medicine for a long time in Asian countries. Pharmacological studies showed that it has antiemetic, anti-inflammatory and analgesic effects, which is attributed to its chemical constituents. The aim of the present study is to investigate the anti-rheumatoid arthritis properties of cedrol (CE) found in ginger. In an in vivo anti-RA study, CE remarkably alleviated the paw swelling and arthritis score in CE-treated CIA mice compared with the model group. The neutrophil count and the productions of TNF-α and IL-1β were inhibited, and the expressions of Rankl, Cox-1 and Cox-2 were down-regulated at the mRNA level. Radiologic evaluation, histopathological analysis and immunohistochemistry indicated that CE ameliorated inflammatory cell infiltration, synovial hyperplasia, and bone and cartilage damage, and exhibited an immunotherapeutic effect. The MTT assay demonstrated that CE (10-10-10-5 M) had no cytotoxicity on fibroblast-like synoviocytes (FLSs), and exhibited an inhibitory effect on the proliferation of LPS-induced FLSs at concentrations of 10-6 M and 10-5 M. Mechanism research showed that the suppressed expressions of pivotal inflammatory mediators including COX-1 and COX-2 subsequently reduced the production of PGE2, thereby causing the secretions of pro-inflammatory cytokines, ultimately attenuating the progression of inflammation. Meanwhile, the reduction in the mRNA levels of Mmp-13 and Mcp-1 responsible for osteoclastogenesis resistance was detected. This illustrated that CE showed anti-rheumatoid arthritis properties via blocking the phosphorylation of ERK/MAPK and p65/NF-κB signaling pathways in LPS-activated FLSs. The current research suggested that CE is an important functional component in ginger, which may be a promising candidate drug for RA therapy.

Li-Hui Li,1,2 Qiang-Min Huang,1 Marco Barbero,2 Lin Liu,3 Thi-Tham Nguyen,4 Matteo Beretta-Piccoli,2 An-Le Xu,1 Li-Juan Ji1 1Department of Sport Medicine and Rehabilitation Center, Shanghai University of Sport, Shanghai, China; 2Rehabilitation Research Laboratory 2rLab, Department of Business Economics Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland; 3Nanjing Sport Institute, Sport and Health Science Department, Nanjing, China; 4Faculty of Sport Science, Ton Duc Thang University, Ho Chi Minh City, Vietnam Background: Proteomics analysis may provide important information regarding the pathogenesis of chronic myofascial pain and the mechanisms underlying the treatment effects of dry needling. Materials and methods: This study used a rat model of myofascial trigger points (MTrPs) to perform a proteomics analysis. Three biological replicate experiments were used to compare the proteomes of healthy control rats, a rat model of MTrP, MTrP model rats following dry needling of MTrPs, and MTrP model rats following dry needling of non-MTrPs. Tandem mass tag (TMT) labeling technology based on nanoscale liquid chromatography-tandem mass spectrometry was used. Hierarchical clustering, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein–protein interaction network analysis were performed to characterize the proteins. To validate the TMT results, three candidate biomarker proteins were verified using parallel reaction monitoring and Western blot analysis. Results: A total of 2,635 proteins were identified. GO and KEGG enrichment analyses showed that the glycolysis/gluconeogenesis pathways played dominant roles in the pathogenesis of chronic myofascial pain. The three candidate biomarker proteins were the pyruvate kinase muscle isozyme (encoded by the PKM gene), the muscle isoform of glycogen phosphorylase (encoded by the PYGM gene), and myozenin 2 (encoded by the MYOZ2 gene). The validation results were consistent with the TMT results.Conclusion: This is the first proteomics study that has investigated the pathogenesis of chronic myofascial pain and the mechanisms underlying the treatment effects of dry needling in an in vivo rat model of MTrPs, which might promote our understanding of the molecular mechanisms underlying chronic myofascial pain. Keywords: musculoskeletal pain, acupuncture, bioinformatics, mass spectrometry, tandem mass tag, parallel reaction monitoring

Here we report an efficient copper-catalysed selective C–C bond cleavage/amination of cyclobutanone oxime esters. This reaction protocol is operationally simple and conducted at ambient temperature, allowing access to a wide range of functionalized 4-(arylamino)butanenitriles in moderate to excellent yields. This transformation shows high chemo-selectivity and wide functional-group compatibility and can be easily scaled up to the gram level with a useful yield. A mechanism involving copper-catalysed capture of alkyl radical intermediates by amine nucleophiles is proposed.

Here we report a method for the site-selective intermolecular C(sp

MicroRNA are significant regulators of neuropathic pain development. Neuroinflammation contributes a lot to the progression of neuropathic pain. miR-381 is involved in various pathological processes. However, the role of miR-381 in neuropathic pain development remains barely understood. Therefore, in our study, we aimed to investigate the effects of miR-381 on the process of neuropathic pain progression by establishing a rat model using chronic sciatic nerve injury (CCI). Here, we observed that miR-381 was dramatically decreased in CCI rats. Up-regulation of miR-381 strongly reduced neuropathic pain behaviors including mechanical and thermal hyperalgesia. In addition, inflammatory cytokine expression, including IL-6, IL-10 and TNF-α were significantly repressed by overexpression of miR-381. High mobility group box 1 protein (HMGB1) and Chemokine CXC receptor 4 (CXCR4) participate in neuropathic pain development. In our present study, HMGB1 and CXCR4 were predicted as direct targets of miR-381 by employing bioinformatics analysis. Overexpression of miR-381 was able to restrain the expression of HMGB1 and CXCR4 greatly. The direct correlation between HMGB1 and CXCR4 and miR-381 was confirmed in our research. Furthermore, we found that HMGB1 and CXCR4 were increased in CCI rats time-dependently. Moreover, it was demonstrated that silence of HMGB1 and CXCR4 in CCI rats depressed neuropathic pain progression greatly. In conclusion, it was indicated that miR-381could inhibit neuropathic pain development through targeting HMGB1 and CXCR4.

Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs, however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly up-regulated in the airway epithelia of children with asthma or mouse models with allergic airway disease. Specifically, airway-specific SMO loss of function significantly suppresses allergen-induced goblet cell phenotypes, whereas an airway-specific SMO gain of function markedly enhances the goblet cell phenotypes in mouse models with allergic airway disease. Notably, intratracheal administration with SHH- neutralizing antibody or cyclopamine robustly attenuates goblet cell phenotypes in mouse models with allergic airway disease. Finally, we identify that Muc5AC gene encoding MUC5AC mucin serves as a direct target of GLI transcriptional factors in response to SHH, whereas the SAM pointed domain-containing ETS transcription factor and Forkhead box A2, critical transcriptional factors for goblet cell phenotypes, both function as the effectors of GLIs in response to SHH stimulation. Together, the up-regulation of SHH expression in allergic bronchial epithelia contributes to goblet cell metaplasia; thus, blockage of SHH signaling is a rational approach in a therapeutic intervention of epithelial remodeling in chronic airway diseases.

To increase the reuse of food residues, multifrequency countercurrent ultrasonic treatment was used to enhance the extraction yield of defatted mulberry seed protein (DMSP), and sweet-flavored peptides from DMSP hydrolysates (DMSPHs) were obtained for the first time. Here, the DMSP yield was increased by 16.2% (p 0.05) while the power density was halved compared with single-frequency ultrasonic treatment. According to Fick's second law, a molecular diffusion dynamics model was developed to be suitable for predicting the pretreatment conditions (R

Tertiary alcohols bearing a trifluoromethyl group are of considerable medicinal interest. Using an umpolung strategy, we herein report the first intermolecular reductive cross-coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines with the aid of a Brønsted acid catalyst upon visible-light irradiation. This metal-free reaction is operationally simple and performed at ambient temperature, allowing access to desired tertiary alcohols with tri-/difluoromethyl groups in moderate to excellent yields. The commercially available and easily handled Hantzsch ester effectively serves as an electron donor, as well as a hydrogen atom source.

Objective To investigate the histopathological nature of myofascial trigger points (MTrPs) or spots (MTrSs) at different stages of recovery from injury in a rat model. Methods Forty Sprague–Dawley rats were randomly divided into two groups: a control group (CG) and experimental group (EG). The CG was further randomly subdivided into CG1 and CG2 subgroups. The CG2 was used for palpating the taut band and CG1 as a blank. EG was subdivided into three groups according to recovery times: 4 weeks (4W), 8 weeks (8W) and 12 weeks (12W); these groups consisted of eight rats each. All CG rats received no intervention, whereas the intervention in EG rats was by a blunt strike to the vastus medialis and eccentric exercise for 8 weeks. The taut bands with spontaneous electrical activity were then detected in the muscle to guide a muscle biopsy. The histopathological findings were investigated under optical and electron microscopes in all groups. Results Under optical microscopy, the differently augmented sizes of round fibres (contracture knots) with deep staining in the transverse section and fusiform shapes in a longitudinal view were clearly seen in CG2 and EGs with a large diameter; the number of contracture knots was significantly more in EGs than in CGs. Under an electron microscope, the mitochondria in EGs significantly decreased with abnormal structures. The sarcomeres were significantly shortened in the 8W and 12W EGs. Conclusion An injury can cause activation of MTrSs in a muscle and an activated level of MTrPs depending on the number of contracture knots in muscle with impaired energy production.

Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched. In the present study, we studied whether GSE provided protection against bleomycin (BLM)-induced mouse pulmonary fibrosis. ICR strain mice were treated with BLM in order to establish pulmonary fibrosis models. GSE was given daily via intragastric administration for three weeks starting at one day after intratracheal instillation. GSE at 50 or 100mg/kg significantly reduced BLM-induced inflammatory cells infiltration, proinflammatory factor protein expression, and hydroxyproline in lung tissues, and improved pulmonary function in mice. Additionally, treatment with GSE also significantly impaired BLM-induced increases in lung fibrotic marker expression (collagen type I alpha 1 and fibronectin 1) and decreases in an anti-fibrotic marker (E-cadherin). Further investigation indicated that the possible molecular targets of GSE are matrix metalloproteinases-9 (MMP-9) and TGF-β1, given that treatment with GSE significantly prevented BLM-induced increases in MMP-9 and TGF-β1 expression in the lungs. Together, these results suggest that supplementation with GSE may improve the quality of life of lung fibrosis patients by inhibiting MMP-9 and TGF-β1 expression in the lungs.

The mitochondrial genome is widely used for phylogenetic analyses and evolutionary biology. The complete mitochondrial genome of Thitarodes sejilaensis (Lepidoptera: Hepialidae) was sequenced and analyzed in this study. This mitogenome is a typical circular molecule of 15,290bp, with the gene content, orientation and order identical to other insects in the family Hepialidae. The genome nucleotide composition is heavily biased towards As and Ts, accounting for 80.87% of total nucleotide content. The major strand shows a positive AT-skew and negative GC-skew. All 13 protein-coding genes (PCG) are initiated by the canonical putative start codons ATN, except for COI and ND1 that use the initiation codons CGA and TTG, respectively. Nine PCGs share the complete termination codons TAA, while the remaining PCGs use an incomplete termination codon T. Additionally, the codon distribution and Relative Synonymous Codon Usage of all PCGs in the T. sejilaensis mitogenome are consistent with other Hepialidae mitogenomes. Among 22 transfer RNAs, 21 have the typical clover-leaf structure, while tRNASer(AGN) does not possess the dihydrouridine (DHU) arm and could not form a stable stem-loop structure. The secondary structures of 2 ribosomal RNA genes broadly conform to the proposed models of these genes documented in other lepidopteran insects. T. sejilaensis AT-rich region exhibits three repetitive sequences of 118bp. Other regions contain 22-bp overlapping nucleotides and 72-bp intergenic nucleotides. The phylogenetic relationships were constructed by two datasets, the amino acid sequence derived from protein-coding genes and the nucleotide sequence of 13 PCGs and 2 rRNAs. Using Maximum Likelihood (ML), we reconstructed a phylogenetic tree which supported a more primitive taxa of Hepialoidea within Lepidoptera. Moreover, according to comparisons based on the CytB sequences and morphological characteristic, Hepialus species reported in China should be revised. Our taxonomic recommendations include assigning these species to the following genera: Thitarodes, Ahamus, Hepialus and Parahepialus.

Objectives: To determine how muscle spindles are involved in the pathophysiology of chronic myofascial trigger spots (MTrSs, similar to myofascial trigger points) in a rat injury model according to the characteristics of the Hoffmann reflex (H-reflex) and the anatomical relationship between muscle spindles and MTrSs. Methods: 16 male Sprague-Dawley rats (7 weeks old) were randomly divided into experimental and control groups. A blunt strike injury and eccentric exercise were applied to the gastrocnemius muscle of rats in the experimental group once a week for 8 weeks as a MTrS modelling intervention. Subsequently, the rats were reared normally and rested for 4 weeks. At the end of the 12th week, the rats were examined for the presence of MTrSs defined by the detection of a palpable taut band exhibiting both a local twitch response and spontaneous electrical activity. After modelling, evocation of the H-reflex and morphological examination of muscle spindles and MTrSs were conducted. Results: The threshold (0.35±0.04 mA) of the H-reflex and latency (1.24±0.18 ms) of the M wave recorded at MTrSs were not significantly different to those at non-MTrSs (P>0.05). Compared with non-MTrSs, a lower Mmax (4.28±1.27 mV), higher Hmax (median (IQR) 0.95 (0.80–1.08) mV) and Hmax/Mmax (median (IQR) 0.21 (0.16–0.40)), and shorter H wave latency (4.60±0.89 ms) were recorded at MTrSs (PDiscussion: Compared with normal muscles, the H-reflex myoelectrical activity was enhanced and some muscle spindles might have been influenced by active MTrSs. Thus, muscle spindles may play an important role in the pathological mechanism underlying myofascial trigger points.

Additional file 1: Figure S1. Chemical structure of ZDHXB-101. Figure S2. Effects of ZDHXB-101 on cell proliferation and activity in 16HBE cells, inhibits TGFβ1-induced increase in soluble epoxide hydrolase (sEH) expression and decrease in 14, 15-EETs levels. (A and D) cell proliferation; (C) cell activity; (D and E) sEH protein expression; (F) 14, 15-EETs level. 16HBE cell was treated with the indicated concentrations (5, 10, 20 μM) of ZDHXB-101or AUDA for 24–72 h. The viability levels of 16HBE cells at the logarithmic phase were determined using the MTT assay (n = 6 per group). The lactate dehydrogenase (LDH) levels were determined using ELISA assay (n = 6 per group). (D and E) The sEH expression of 16HBE cells were induced with the indicated concentrations (1.25–10 μM) of TGFβ1 for 24 h. The protein levels of sEH were assessed by western blot. The 14, 15-EETs levels were determined using ELISA assay (n = 6 per group). The data represent mean ± S.E.M. from 4 independent experiments, *p < 0.05, **p < 0.01 and ***p

Additional file 1: Figure S1. Chemical structure of ZDHXB-101. Figure S2. Effects of ZDHXB-101 on cell proliferation and activity in 16HBE cells, inhibits TGFβ1-induced increase in soluble epoxide hydrolase (sEH) expression and decrease in 14, 15-EETs levels. (A and D) cell proliferation; (C) cell activity; (D and E) sEH protein expression; (F) 14, 15-EETs level. 16HBE cell was treated with the indicated concentrations (5, 10, 20 μM) of ZDHXB-101or AUDA for 24–72 h. The viability levels of 16HBE cells at the logarithmic phase were determined using the MTT assay (n = 6 per group). The lactate dehydrogenase (LDH) levels were determined using ELISA assay (n = 6 per group). (D and E) The sEH expression of 16HBE cells were induced with the indicated concentrations (1.25–10 μM) of TGFβ1 for 24 h. The protein levels of sEH were assessed by western blot. The 14, 15-EETs levels were determined using ELISA assay (n = 6 per group). The data represent mean ± S.E.M. from 4 independent experiments, *p < 0.05, **p < 0.01 and ***p

Background: Diabetic nephropathy constitutes a large proportion of end-stage kidney failure in diabetic patients. However, the underlying molecular mechanisms remain unclear. Methods: Db/db diabetic mouse models and high glucose (HG)-induced human renal mesangial cells (HRMCs) were used as research models in vivo and in vitro. The expression of cancer susceptibility candidate 2 (CASC2) was quantified by qRT-PCR. The regulatory role of CASC2 in cell apoptosis, inflammatory factor release, and fibrosis was verified by flow cytometry, qRT-PCR, and Western blot assay, respectively. The bioinformatics prediction software DIANA and starBase v2.0 were used to predict the putative binding sites. The interactions among CASC2, miR-144, and SOCS2 were explored by the luciferase assay and Western bolt assay. Results: The expression of CASC2 in diabetic mouse models and HG-induced HRMCs was lower than that in the control (p < 0.05). Overexpression of CASC2 resulted in a decrease in the apoptosis rate, inflammatory factor release (TNF-α, IL-6, and IL-1β), expression of cleaved caspase-3, and fibrotic proteins (fibronectin, Col-IV, and TGF-β1) and an increase in Bcl-2 expression. Inhibition of CASC2 caused increased expression of miR-144. Furthermore, mechanistic investigations confirmed that activation of the miR-144/SOCS2 regulatory loop by overexpression of miR‐144 reversed the in vitro effects of CASC2 on inhibiting cell apoptosis, inflammatory factor release, and fibrosis. In addition, simultaneous overexpression of miR-144 and SOCS2 further increased the inhibition of cell apoptosis, inflammatory factor release, and fibrosis by CASC2. Conclusion: CASC2 could alleviate the degree and process of apoptosis, inflammation, and fibrosis in diabetic nephropathic models by regulating the miR-144/SOCS2 axis.

Airway remodeling in asthma is difficult to treat because of its complex pathophysiology that involves proinflammatory cytokines, as well as the arachidonic acid cytochrome P-450 (CYP) pathway; however, it has received little attention. In this study, we assessed the efficacy of a soluble epoxide hydrolase (sEH) on airway remodeling in a mouse model of chronic asthma. The expression of sEH and CYP2J2 and the level of 14,15-epoxyeicosatrienoic acid (14,15-EET), airway remodeling and hyperresponsiveness (AHR) were analyzed to determine the level of sEH inhibition. AUDA, a sEH inhibitor, was given daily for 9 weeks orally, which significantly increased the level of 14,15-EET by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. The inhibition of sEH reduced the expression of remodeling-related molecular markers, such as interleukin (IL)-13, IL-17, matrix metalloproteinase 9, N-cadherin, α-smooth muscle actin (α-SMA), S100A4, Twist, epithelial goblet cell metaplasia, and collagen deposition in bronchoalveolar lavage fluid (BAL fluid) and lung tissues. Moreover, remodeling-related eosinophil accumulation in the BAL fluid and infiltration into the lung tissue were improved by AUDA. Finally, AUDA alleviated AHR, which is a functional indicator of airway remodeling. The effect of AUDA on airway remodeling was related to the downregulation of extracellular-regulated protein kinases (Erk1/2), c-Jun N-terminal kinases (JNK) and signal transducer and activator of transcription 3 (STAT3). To our knowledge, this is the first report to demonstrate that inhibition of sEH exerts significant protective effects on airway remodeling in asthma.

Effects of five photoperiods (Light:Dark = 4:20, 8:16; 12:12, 16:8, 20:4) on the development, survival and reproduction of Neoseiulus barkeri Hughes fed on storage mite Tyrophagus putrescentiae (Schrank) were examined under laboratory conditions at 85 % relative humidity and 24 °C. Development time of almost all immature stages in N. barkeri was the shortest (5.43 ± 0.12 days) under 12 h of daylight. Total duration of immature stages was as high as 8.55 ± 0.16 days during the longest photoperiod. Photoperiod had no effect on hatching rate, but did affect survival of larvae, protonymphs and deutonymphs. Total survivorship ranged from 20 (4:20) to 60 % (12:12). Under 12 h daylight, female adults had the shortest pre- and post-oviposition period, longest oviposition period and longevity, largest total number of eggs (15.95) and and highest daily egg production (1.43) per female. Under 12 h light, N. barkeri experienced its highest net reproductive rate (R 0 = 11.791), intrinsic rate of increase (r m = 0.180), and finite rate of increase (λ = 1.197), and lowest mean generation time (t = 13.71 days) and population doubling time (DT = 3.86 days). All demographic parameters displayed a parabolic relationship with photoperiod. The results of the present study indicated that the photoperiod of 12:12 is optimal for the development and reproduction of N. barkeri fed on T. putrescentiae, and that N. barkeri may serve most efficiently as a biological control agent under this regime.

of the preheating temperature on the microstructure and the optical properties of the films were in particular investigated. The mechanisms for the preheating in the formation of the films and for the reactions involved in the sol solution prepared by the two-step method were also proposed in terms of the experimental results. The preheating not only enhances the volatilization of the solvent 2-methoxyethanol and the decomposition of the residual organic species, but also results into the formation of small number of ZnO particles. The preheating temperature of 300 C is most favorable for the highly-oriented ZnO thin film. Increasing the preheating temperature results into the blue shift of the absorption edges of the films. This can be explained by using the quantum-size eect. The photoluminescence spectra of the films show an UV emission at the near-band edge and a broad green-yellow emission at 470‐620 nm. The former is closely related to the excitons, while the latter is to the intrinsic defect species in the film.

Ambroxol, a metabolite of bromhexine, is shown to exert several pharmacological activities, including secretolytic, anti-inflammatory and antioxidant actions. Oral and intravenous administration of ambroxol is useful for the airway inflammatory diseases. However, little is known about its potential in inhalation therapy for lipopolysaccharide (LPS)-induced mucous hypersecretion and inflammatory response. In the present study, we compared the pharmacological effects of ambroxol by inhalation with intravenous administration and preliminarily explored its mechanism of action. Our results demonstrated that ambroxol administered by inhalation inhibited MUC5AC expression, reduced glycosaminoglycan levels, enhanced the function of mucociliary clearance and promoted sputum excretion, suggesting that ambroxol increases expectoration of sputum by reducing its viscosity. Moreover, ambroxol significantly alleviated LPS-induced the influx of inflammatory cells and the extracellular signal-regulated kinase 1/2 (Erk 1/2) expression in lung tissues, and inhibited increases in the mRNA expression of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, CCL-2 (monocyte chemotactic protein-1), KC (keratinocyte cell protein) and interleukin (IL)-1β in lung tissues. The secretolytic and anti-inflammatory effects of inhaled ambroxol at a dose of 7.5 mg/ml was comparable to that of ambroxol at 20 mg/ml i.v. and dexamethasone at 0.5 mg/kg i.p. In addition, we found that ambroxol dose-dependently inhibited LPS-induced increases in the mRNA expression of MUC5AC, TNF-α, and IL-1β in human bronchial epithelial cell (NCI-H292) by inhibiting the Erk signaling pathway. These results demonstrate the beneficial effects of ambroxol in inhalation therapy for the airway inflammatory diseases.

Highlights • Neutralizing antibodies could be isolated from convalescent patients or libraries. • Different epitopes such as RBD and NTD were identified by structural studies. • Heavy chain germline genes IGHV3-30, IGHV3-53 and IGHV3-66 are enriched most., SARS-CoV-2 causing the worldwide pandemic has changed people’s life in multiple aspects dramatically since it’s first identified in Wuhan, China at the end of 2019. While the numbers of infected patients and death toll keep vigorous increasing, curbing the progression of the pandemic is an urgent goal. Efforts have been made to search for prophylactic and therapeutic approaches including neutralizing antibodies development. By reviewing dozens of studies on anti-spike antibodies identification, we concluded that (1) promising therapeutic antibodies are being fished out by various approaches, such as screening of single B cells of convalescent patients, recombinant antibody library and B cells of immunized animals; (2) the epitopes are mainly RBD, but also some non-RBD domains, without the requisite of overlapping with ACE2 binding sites; (3) Neutralizing antibodies are convergent to a few germline genes, including IGHV3-30, IGHV3-53, IGHV3-66, with varying levels of somatic mutations. This review summarizes the progress in neutralizing antibodies development and the germline enrichment of effective antibodies, which will shed light on COVID-19 treatment and vaccine design.

Various studies have shown that flavones have several pharmacological activities including anti-allergy activities. However, the bioavailability of oral flavones is very low, and whether inhaled administration can improve efficacy in respiratory disease models is unclear. In the present study, the anti-allergic activities of inhaling 5,7-dimethoxy-3,4'-dihydroxyflavone (MHF), a synthetic flavonoid, was investigated by comparison with disodium cromoglycate (DSCG) and nedocromil sodium (NS) in rat allergic models. In an anti-DNP-IgE-induced asthmatic model, inhaled MHF dose-dependently inhibited the increase in airway resistance after antigen challenge. In an ovalbumin (OVA)-induced asthmatic model, inhaled MHF showed significant suppression of airway hyperresponsiveness; a decrease in eosinophil and neutrophil counts, IL-4, IL-5 and leukotriene D4 in bronchoalveolar lavage fluid; a reduction in total IgE and OVA-specific IgE levels in serum; and suppression of eosinophil infiltration in lung tissue after antigen challenge. The efficacy of inhaled MHF was comparable to that of NS and DSCG. In conclusion, based on these findings, the report for the first time that that inhaled MHF may be a potential drug for the treatment of allergic asthma.

A novel photocatalytic protocol is herein described for the preparation of functionalized phenols via radical alkylation of para-quinone methides under transition-metal-free conditions. The reaction is external oxidant free and performed at ambient temperature upon visible light irradiation, allowing the access to various desired products in satisfactory yields. The readily available 4-alkyl-1,4-dihydropyridines serve as the effective alkyl radical precursors.

Post-stroke spasticity is associated with restriction in the range of motion of the shoulder. Reducing muscular dystrophy may help relieve muscular dysfunction in patients with post-stroke shoulder spasticity. Dry needle therapy is a method of needling the trigger points using a syringe needle without the use of a drug. Dry needle therapy is commonly used for pain at the shoulder, neck, waist, and back. In this case study, a 62-year-old male patient affected with cerebral hemorrhage of the right frontal lobe had received rehabilitative treatment for 12 years. However, he still experienced shoulder spasticity. The patient received daily dry needling at the trigger points of infraspinatus, teres minor, posterior deltoid, and pectoralis major on 9 days. After the first and ninth treatment, the Modified Ashworth Scale and the passive range of motion of the shoulder was used to assess the effect of the treatment. The spasticity and range of motion of the shoulder showed obvious improvement. These results indicate that dry needling at the myofascial trigger points can effectively treat chronic post-stroke shoulder spasticity.

Field plot experiments were conducted to study the effect of two-year consecutive As stress [As(V): 0, 20, 80, 140, 200 and 260 mg·kg通过田间小区试验,研究不同As浓度(0、20、80、140、200和260 mg·kg

The present study aimed to investigate the potent inhibitory effects and possible biochemical basis of the novel phosphodiesterase 4 (PDE4) inhibitor ciclamilast, which is a derivative of piclamilast (RP 73401), on PDE4 and allergic inflammation. Ciclamilast was orally administered to allergic rats, their lungs and bronchoalveolar lavage fluid (BALF) were harvested, and their levels of inflammation and goblet cell hyperplasia, particularly cAMP‑PDE activity, and expression and distribution of PDE4 subtypes were determined. The results suggested that oral administration of ciclamilast significantly reduced the total leukocyte number and eosinophil number in BALF and suppressed lung histology changes, including the infiltration of inflammatory cells into the perivascular and peribronchial spaces, structural changes and goblet cell hyperplasia. For eosinophil infiltration, ciclamilast exhibited improved selectivity compared with piclamilast. Furthermore, ciclamilast significantly inhibited the upregulated activity of cAMP‑PDE and showed improved selective inhibition of the protein expression of PDE4B than piclamilast in a dose‑dependent manner. The mRNA expression of PDE4D was significantly increased in allergic rats, but PDE4B was not. PDE4B was mainly distributed in the cytoplasm, whereas PDE4D was mainly distributed in the cell membrane. The improved anti‑inflammatory activity of ciclamilast compared with piclamilast may be due to its higher level of inhibition of the activity, mRNA and protein expression of PDE4, particularly its effect on PDE4B.

To attempt to establish an objective quantitative indicator to characterize the trigger point activity, so as to evaluate the effect of dry needling on myofascial trigger point activity.Twenty-four male Sprague-Dawley rats were randomly divided into blank control group, dry needling (needling) group, stretching exercise (stretching) group and needling plus stretching group (After the modeling cycle, the mean sample entropies of EMG signals was significantly decreased in the model groups (needling group [0.034±0.010], stretching group [0.045±0.023], needling plus stretching group [0.047±0.034]) relevant to the blank control group (0.985±0.196,Dry needling is able to relieve myofascial trigger point activity in rats, which is better than that of simple passive stretching therapy.

As contamination is one of important factors to Panax notoginseng quality and safety. Saponin is one of important compounds with the medicinal values of P. notoginseng. The impact of soil As on production of saponin of P. notoginseng knew very little. This study was performed to determine content and heterogeneity of saponins from P. notoginseng and its mechanisms upon treatments with different concentration levels of As in soil. Plants of P. notoginseng were treated with arsenic [As (V)] at 0, 20, 80, 140, 20 and 260 mg/kg concentration levels which were supplied as sodium arsenate (Na3AsO4). These experimental plants were grown in shade condition in a greenhouse. Plants were harvested at vigorous vegetative growth and fruit ripening stages, separately. Effects of As treatments on saponin content, and heterogeneity of monomers in the mixtures of notoginesenosides and ginsenosides, enzymatic activity and gene expression level of squalene synthetase were determined for rhizome and main root tissues. Results show that：(1) Of all the As treatments from the lowest to the highest concentration levels, the As content in both rhizome and main roots from As-treated plants was within the standard level for superior products derived from P. notoginseng. The content of notoginsenosides from all tissues except the main roots at fruit ripening stage, was 5% higher than the standard level specified in the Chinese Pharmacopoeia; (2) The treatment of As at 20 mg/kg led to an 3.5% - 183.9% increases in total notoginesenosides content in rhizome and main roots, respectively. Treatments with the highest As concentration at 260 mg/kg resulted in a significant decline in total notoginsenosides content, and lower enzymatic activity and gene expression levels of squalene synthetase; (3) Under As treatment conditions, the ratio of Rb1/Rg1 decreased but the ratio of (Rb1 + Rg1)/R1 increased in both rhizomes and main roots. Conclusively, this study demonstrated that low As concentration (20 - 80 mg/kg) treatments resulted in higher notoginsenoside content in P. notoginseng. However, treatments with high As concentrations had an adverse effect. The repression in the synthesis of notoginsenoside and interruption of the conversion process from propanaxadiol into propanaxatriol are responsible for more heterogeneous monomer mixtures and low notoginsenoside content. For plants treated with the highest As concentration of 260 mg/kg, both gene expression and enzymatic activities of squalene synthetase were greatly repressed thus leading to a significantly low saponin content in rhizome and main root tissues.

For ecologists, understanding the reaction of animals to environmental changes is critical. Using networked sensor technology to measure wildlife and environmental parameters can provide accurate, real-time and comprehensive data for monitoring, research and conservation of wildlife. This paper reviews: (i) conventional detection technology; (ii) concepts and applications of the Internet of Things (IoT) in animal ecology; and (iii) the advantages and disadvantages of IoT. The current theoretical limits of IoT in animal ecology are also discussed. Although IoT offers a new direction in animal ecological research, it still needs to be further explored and developed as a theoretical system and applied to the appropriate scientific frameworks for understanding animal ecology.

Inhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists (LABA) is the most important treatment for allergic asthma, although the mechanism still remains unclear. However, mast cells play a central role in the pathogenesis of asthma. In this study, we explored the sole or synergetic effects of des-ciclesonide (ICS) and formoterol (LABA) on the cytokines IL-4 and IL-13 and on histamine release from mast cells (RBL-2H3 cells). We found that des-ciclesonide (0.1, 1 and 10 nM) and formoterol (0.1, 1 and 10 μM) alone attenuated DNP–BSA-induced IL-4 and IL-13 production, respectively, in a concentration-dependent manner in DNP-IgE-sensitized mast cells. Des-ciclesonide (0.2 nM) and formoterol (1 μM) alone also reduced histamine production. However, the combination of des-ciclesonide (0.2 nM) and formoterol (1 μM) had a synergistic inhibition effect on IL-4 mRNA expression and protein production but not IL-13 and histamine release. The JNK inhibitor SP600125 (10 μM) inhibited antigen-induced mRNA expression and protein production of IL-4. Des-ciclesonide and formoterol alone inhibited the activation of JNK in a concentration-dependent manner, and the combination of des-ciclesonide (0.2 nM) and formoterol (1 μM) exhibited greater inhibition effect compared with des-ciclesonide (0.2 nM) or formoterol (1 μM) alone. Taken together, these synergistic effects on mast cells might provide the rationale for the development of the most recent ICS/LABA combination approved for asthma therapy.