Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using “Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence”.

Abstract Background Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1β in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1β and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. Methods Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1β, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1β and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. Results The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1β in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1β, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. Conclusions Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

Abstract Kaempferol, an important flavonol, has numerous health-beneficial bioactivities and possesses a great potential for application in medicine, food, and cosmetics industries. To improve the production of kaempferol in an in vitro synthetic biosystem, we designed and constructed a panel of bifunctional enzymes by fusing the flavanone 3-hydroxylase (AtF3H) and the flavonol synthase (AtFLS1) of Arabidopsis thaliana with different orientation and different peptide linker type and length. By comparing the output of kaempferol, we obtained a highly active bifunctional enzyme AtF3H-(GGGGS)2-AtFLS1 with a Km value of 0.129 ± 0.016 mM. After optimization of a series of reaction parameters, kaempferol was produced at 100.54 ± 0.54 mg/L, the currently highest kaempferol output in an in vitro synthetic biosystem, and the substrate conversion rate was 68.26% ± 0.05%. In addition, we observed substrate inhibition for the AtFLS1, which eventually limited the production of kaempferol. This study provides a highly active biocatalyst for production of kaempferol and an insight into biosynthesis of other valuable molecules.

Abstract Jiangshui is a traditional fermented food in Northwest China with high nutritional value and special pharmacological effects. To study the microbial community structure and differences in the main metabolic pathways and metabolites in naturally fermented Jiangshui, the microbial diversity and nontargeted metabolomics analyses were performed on 18 samples of Jiangshui from three different production areas, namely, Tianshui, Gansu, Guyuan, Ningxia, and Ankang, Shaanxi. First, the microbial diversity was analyzed using 16S rRNA high-throughput sequencing. Lactobacillus was the dominant bacterial genus in the three regions, and the relative abundance of the samples in each region ranged from 72.69% to 99.95%. The dominant fungal genus was Dipodascus, with a relative abundance > 40%. Second, untargeted metabolomics was used to analyze the differences among metabolites in Jiangshui samples. Significant differences were found in 761 different metabolites detected in Jiangshui from the three different regions. Based on ESI+, 78 significantly different metabolites were screened using variable importance projection (VIP) value > 1, fold change (FC) < 1, and P-value < 0.05. Finally, based on joint analysis, the microbiome and metabolite groups of Jiangshui samples from the three different regions were evenly and closely clustered, and the microorganisms and metabolites were highly correlated. The results provide theoretical basis and reference for Jiangshui in other regions.

ABSTRACT Various problems are encountered during the screw feeding process of chopped cornstalk. Therefore, it is important to deeply analyze and understand the relationship between conditions and productivity of screw conveyors. This study reveals the influence of air velocity, pitch, rotational speed, and feeding rate on productivity, power consumption, specific power consumption and pressure of material for a coupled screw-pneumatic conveyor. Through a theoretical analysis, a mathematical model is established that simultaneously considers the compression characteristics of the material, material pressure from the change in pitch and centrifugal force of the screw axis, productivity of the coupled screw-pneumatic conveyor, power consumption and specific power consumption. Then, experiments are conducted to investigate the influence of the structural and working parameters of the conveyor on its performance. Finally, the correctness of the theoretical calculation is verified through a comparison with experimental results. The results of the theoretical analysis are in good agreement with the experimental results, and the relative deviations fall within 10%, 13%, 14% and 11% for the productivity, energy consumption, specific consumption and material pressure of the conveyor, respectively. With increasing airflow speed, pitch, rotational speed and feeding volume, the power consumption increases, and the other parameters have their own trends.

ABSTRACT Introduction: The standardization of body movements is essential for aerobics gymnastic practitioners and motor coordination for the execution of consecutive movements of large amplitudes is strongly related to balance ability. Therefore, it is believed that balance training can positively impact motor coordination in aerobics students Objective: Explore the influences of balance training on motor coordination in aerobics students. Methods: 100 volunteers were selected as aerobics students, divided into an experimental and a control group for a 6-week experiment. The experimental group was given a balance training protocol, while the control group maintained the traditional teaching protocol. Data on functional exercises and fitness indices were collected before and after the experiment for comparison and analysis. Results: The difference in the exercise in the unipodal orthostatic position with eyes closed was 6.45, the difference in the balance test in the swallow position was 4.04, the difference in the later-forward Y balance exercise was 1.88, the later-posterior was 2.09, and posterior Y balance was 2.53. The difference between all items in the control group was small, especially the three items of frontal, lateral, posterior, and mid-posterior Y balance. Conclusion: Balance training positively affected the motor coordination of aerobics students, resulting in a statistically significant increase in all analyzed postural balance indexes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMEN Introducción: La estandarización de los movimientos corporales es esencial para los practicantes de gimnastica aeróbic y la coordinación motora para la ejecución de movimientos consecutivos de gran amplitud está fuertemente relacionada con la capacidad de equilibrio. Por lo tanto, se cree que el entrenamiento del equilibrio puede influir positivamente en la coordinación motora de los estudiantes de aeróbic Objetivo: Explorar las influencias del entrenamiento del equilibrio en la coordinación motora de los estudiantes de aeróbic. Métodos: Se seleccionaron 100 voluntarios estudiantes de aeróbic, divididos en un grupo experimental y un grupo de control para un experimento de 6 semanas. Al grupo experimental se le incrementó un protocolo de entrenamiento del equilibrio, mientras que el grupo de control mantuvo el protocolo de enseñanza tradicional. Se recogieron datos relativos a ejercicios funcionales e índices de aptitud física antes y después del experimento para su comparación y análisis. Resultados: La diferencia en el ejercicio en posición ortostática unipodal con ojos cerrados fue de 6,45, la diferencia en la prueba de equilibrio en posición de deglución fue de 4,04, la diferencia en el ejercicio de equilibrio latero-direccional en Y fue de 1,88, latero-posterior fue de 2,09, y posterior en Y fue de 2,53. La diferencia de todos los ítems en el grupo de control fue pequeña, especialmente los tres ítems de equilibrio frontal, lateral, posterior y medio-posterior en Y. Conclusión: El entrenamiento en equilibrio afectó positivamente a la coordinación motora de los estudiantes de aeróbic, resultando en un incremento estadísticamente expresivo en todos los índices de equilibrio postural analizados. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

RESUMO Introdução: A padronização dos movimentos corporais é essencial para os praticantes de ginástica aeróbica e a coordenação motora para a execução de movimentos consecutivos de grandes amplitudes está fortemente relacionada à capacidade de equilíbrio. Acredita-se, por isso, que o treino de equilíbrio possa impactar positivamente a coordenação motora dos estudantes de aeróbica Objetivo: Explorar as influências do treinamento de equilíbrio na coordenação motora dos estudantes de aeróbica. Métodos: Foram selecionados 100 voluntários estudantes de aeróbica, divididos em grupo experimental e controle para um experimento de 6 semanas. Ao grupo experimental foi incrementado um protocolo de treinamento de equilíbrio, enquanto o grupo de controle manteve o protocolo de ensino tradicional. Os dados pertinentes aos exercícios funcionais e índices de aptidão física foram coletados antes e após o experimento para comparação e análise. Resultados: A diferença do exercício em posição ortostática unipodal de olhos fechados foi 6,45, a diferença no teste de equilíbrio em posição de andorinha foi 4,04, a diferença do exercício de equilíbrio latero-dianteiro em Y foi 1,88, latero-posterior foi 2,09, e posterior em Y foi 2,53. A diferença de todos os itens do grupo de controle foi pequena, especialmente os três itens de equilíbrio frontal, lateral, posterior e médio-posterior em Y. Conclusão: O treinamento de equilíbrio afetou positivamente a coordenação motora dos estudantes de aeróbica, resultando num incremento estatisticamente expressivo em todos os índices de balanço postural analisados. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction: The quality of flexibility greatly impacts the performance of aerobics athletes. It is believed that stretching by proprioceptive neuromuscular facilitation (PNF) can contribute to this aspect by maximizing active joint range motion. Objective: Explore the influences of PNF stretching on the physical fitness of aerobics athletes. Methods: 24 professional aerobics athletes were selected, and randomly distributed into two groups with no statistical discrepancies in physical indices. PNF stretching exercise was performed on aerobics athletes in the experimental group, while no training intervention was performed in the control group. Physical fitness was assessed before and after the nine weeks of the intervention. Results: After PNF stretching training, the lower limb vertical score in the experimental group was from 6.58±0.19 to 8.20±0.47, and the transverse pronation score changed from 5.95±0.35 to 7.09±0.61. The vertical score in the control group was from 6.44±59.89 to 6.83±0.37 after the experiment; the transverse pronation penetration score was from 5.78±0.37 to 6.58±0.33. Conclusion: PNF stretching can effectively improve athletes’ physical fitness, both statically and dynamically, generating gains in range of motion and providing favorable conditioning for overall competitive performance. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMEN Introducción: La calidad de la flexibilidad tiene un gran impacto en el rendimiento de los atletas de aeróbic, y se cree que el estiramiento por facilitación neuromuscular propioceptiva (PNF) puede contribuir en esta cuestión con la maximización de la amplitud articular activa de movimiento. Objetivo: Explorar las influencias del estiramiento PNF en la condición física de atletas de aeróbic. Métodos: Fueron seleccionados 24 atletas profesionales de aeróbic, distribuidos aleatoriamente en dos grupos sin discrepancias estadísticas en los índices físicos. Se realizaron ejercicios de estiramiento PNF en los atletas de aeróbic del grupo experimental, mientras que en el grupo de control no se realizó ninguna intervención de entrenamiento. Se evaluó la aptitud física antes y después de las nueve semanas de intervención. Resultados: Tras el entrenamiento de estiramiento PNF, la puntuación vertical de las extremidades inferiores en el grupo experimental fue de 6,58±0,19 a 8,20±0,47, y la puntuación de pronación transversal cambió de 5,95±0,35 a 7,09±0,61. La puntuación vertical en el grupo de control fue de 6,44±59,89 a 6,83±0,37 después del experimento; la puntuación de penetración de pronación transversal fue de 5,78±0,37 a 6,58±0,33. Conclusión: El estiramiento PNF puede mejorar eficazmente la condición física de los atletas, tanto estática como dinámica, generando ganancias en el rango de movimiento y proporcionando un acondicionamiento favorable para el rendimiento competitivo general. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

RESUMO Introdução: A qualidade da flexibilidade tem um grande impacto sobre o desempenho dos atletas de aeróbica, e acredita-se que o alongamento por facilitação neuromuscular proprioceptiva (PNF) possa contribuir neste quesito com a maximização da amplitude de movimento articular ativa. Objetivo: Explorar as influências do alongamento PNF sobre a aptidão física dos atletas de aeróbica. Métodos: Foram selecionadas 24 atletas profissionais de aeróbica, aleatoriamente distribuídas em dois grupos sem discrepâncias estatísticas nos índices físicos. Foi realizado o exercício de alongamento PNF em atletas de aeróbica no grupo experimental, enquanto nenhuma intervenção de treinamento foi realizada no grupo de controle. A aptidão física foi avaliada antes e após as nove semanas da intervenção. Resultados: Após o treinamento de alongamento PNF, a pontuação de membros inferiores vertical no grupo experimental foi de 6,58±0,19 para 8,20±0,47, e a pontuação da pronação transversal mudou de 5,95±0,35 para 7,09±0,61. A pontuação vertical no grupo de controle foi de 6,44±59,89 para 6,83±0,37 depois do experimento; a pontuação da penetração transversal de pronação foi de 5,78±0,37 para 6,58±0,33. Conclusão: O alongamento PNF pode efetivamente melhorar a aptidão física das atletas, tanto estática quanto dinâmica, gerando ganhos à amplitude de movimento proporcionando um condicionamento favorável ao desempenho competitivo geral. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Objective: To determine the absolute number of serum T lymphocytes and cytokine levels and the characteristics of patients with active pulmonary tuberculosis and to assess their effect on the immune status of these patients and their diagnostic and predictive value for tuberculosis. Methods: We included 1,069 patients with active tuberculosis, 51 patients with latent tuberculosis infection, and 600 health individuals. Absolute serum T-lymphocyte counts and cytokine levels were quantified. Results: T lymphocytes were significantly reduced in patients with active tuberculosis when compared with healthy individuals. The immune function of patients gradually decreased with age and was stronger in female patients than in males. Th1 cells expressed higher levels of cytokines than did Th2 cells. Logistic regression analysis showed that reduced CD3+ T, CD8+ T, and NK cell counts, as well as reduced IL-4 and IFN-g expression, were independent influencing factors for active tuberculosis. ROC analysis showed that the sensitivity and specificity of absolute CD3+ T and CD8+ T lymphocyte counts and combined factors were significantly higher than were those of IL-4 and IFN-g for diagnosing active tuberculosis. Conclusions: Serum T-lymphocyte counts and cytokine levels can assess the immune status of tuberculosis patients; they are also useful biomarkers for predicting and diagnosing tuberculosis.

RESUMO Objetivo: Determinar o número absoluto de linfócitos T séricos e os níveis de citocinas séricas, bem como as características, de pacientes com tuberculose pulmonar ativa e avaliar o efeito desses no estado imunológico desses pacientes e seu valor diagnóstico e preditivo para tuberculose. Métodos: Foram incluídos 1.069 pacientes com tuberculose ativa, 51 pacientes com tuberculose latente e 600 indivíduos saudáveis. Foram realizadas a contagem absoluta de linfócitos T séricos e a quantificação de citocinas séricas. Resultados: Os linfócitos T estavam significativamente reduzidos nos pacientes com tuberculose ativa em comparação com os indivíduos saudáveis. A função imunológica dos pacientes diminuiu gradativamente com a idade e mostrou-se mais forte nas mulheres do que nos homens. As células Th1 expressaram maiores níveis de citocinas do que as células Th2. A análise de regressão logística mostrou que contagens reduzidas de células T CD3+, T CD8+ e NK e expressão reduzida de IL-4 e IFN-g foram fatores de influência independentes para tuberculose ativa. A análise ROC mostrou que a sensibilidade e especificidade dos valores absolutos de linfócitos T CD3+ e T CD8+ e de fatores combinados foram significativamente maiores do que as da IL-4 e do IFN-g para o diagnóstico da tuberculose ativa. Conclusões: A contagem de linfócitos T séricos e os níveis de citocinas séricas podem avaliar o estado imunológico de pacientes com tuberculose; também são biomarcadores úteis na predição e diagnóstico da tuberculose.

Abstract Objectives The deposition of monosodium urate (MSU) crystals within synovial joints and tissues is the initiating factor for gout arthritis. Thus, MSU crystals are a vital tool for studying gout's molecular mechanism in animal and cellular models. This study mainly compared the excellence and worseness of MSU crystals prepared by different processes and the degree of inflammation induced by MSU crystals. Methods MSU crystals were prepared using neutralization, alkali titration, and acid titration methods. The crystals' shape, length, quality, and uniformity were observed by polarized light microscopy and calculated by the software Image J. The foot pad and air pouch models were used to assess the different degrees of inflammation induced by the MSU crystals prepared by the three different methods at different time points. Paw swelling was evaluated by caliper. In air pouch lavage fluid, inflammatory cell recruitment was measured by hemocytometer, and the level of IL-1β TNF- α, and IL-18 by ELISA. Inflammatory cell infiltration was assayed by immunohistochemistry of air pouch synovial slices. Results For the preparation of MSU crystals with the same uric acid, the quantity acquired by the alkalization method was highest, followed by neutralization, with the acid titration method being the lowest. The crystals prepared by neutralization were the longest. The swelling index of the foot pad induced by MSU crystals prepared by acid titration was significantly lower than that of the other methods at 24 h. The inflammatory cell recruitment and level of 1-1β, TNF-α, and IL-18 in air pouch lavage fluid were lowest in animals with crystals prepared by acid titration. IL-1β secretion induced by MSU crystals prepared by acid titration was significantly lower than that of the other two groups, but there was no significant difference in IL-18 secretion between the three groups in THP-1 macrophages and BMDMs. Conclusions All three methods can successfully prepare MSU crystals, but the levels of inflammation induced by the crystals prepared by the three methods were not identical. The degree of inflammation induced by MSU crystals prepared by neutralization and alkalization is greater than by acid titration, but the quantity of MSU crystals obtained by the alkalization method is higher and less time-consuming. Apparently, the window of inflammation triggered by acid titration preparation is shorter compared to other forms of crystal preparation. Overall, MSU crystals prepared by the alkaline method should be recommended for studying the molecular mechanisms of gout in animal and cellular models.

Abstract Objective Second-generation catheters used in mechanical thrombectomy have different advantages and disadvantages. The objective of this study was to evaluate the effectiveness and safety of the combination of contact aspiration and stent retriever technique on the rate of reperfusion after mechanical thrombectomy for large vessel occlusion. Methods Patients who underwent contact aspiration alone (CAA cohort, n = 150), stent retriever alone (SRA cohort, n = 129), or combined contact aspiration and stent retriever (CSR cohort, n = 122) techniques following mechanical thrombectomy were included in the analysis. A balloon guide catheter was used for all thrombectomies. Digital subtraction angiography was used to identify thrombolysis in cerebral infarction. Results The number of patients with thrombolysis in cerebral infarction score of ≥ 2c (near complete or complete antegrade reperfusion) was significantly higher in the CSR cohort than those in the CAA cohort (101 [83%] vs. 90 [60%], p < 0.0001) and those of SRA cohort (101 [83%] vs. 77 [59%], p = 0.0001). Arterial perforation was higher in patients in the CSR cohort than in those in the CAA (p < 0.0001) and SRA (p = 0.015) cohorts. Intracerebral hemorrhage was lower in patients in the CSR cohort than in those in the CAA (p = 0.0001) and SRA (p = 0.0353) cohorts. All-cause mortality at 1 year was fewer in the CSR cohort than in the CAA cohort (p = 0.018). Conclusions The combination of thrombo aspiration by large bore aspiration catheter and stent retriever is the most effective technique but has some related risks. Level of evidence IV. Technical efficacy stage 1.

Abstract Terpenoids are one of the secondary metabolites of plants and are the most widely distributed in nature with a diverse skeleton and significant biological activity, among which sesquiterpenoids are the most abundant. Sesquiterpenoids and triterpenoids are mainly synthesized by the mevalonate pathway, and the processes involve a variety of key enzymes and are regulated by transcription factors. They play important roles in plant growth and development, environmental adaptation, and resistance to pests and diseases. It is important to understand the gene functions of key enzymes to increase the production of sesquiterpenoids and triterpenoids to meet the market demand and to study the mevalonate biosynthesis pathway in depth. In this paper, the progress of gene cloning and transcription factor regulation of sesquiterpenes, triterpenoids and key enzymes of mevalonate synthesis pathway will be briefly reviewed. activity abundant factors development adaptation diseases depth paper sesquiterpenes reviewed

Abstract In herbal markets, an overwhelming majority the Dendrobium nobile are sold in dried strips form, and this product type would lead to the incomplete release of the active ingredient. To increase the bioaccessibility of Dendrobium nobile, we obtained powders of different particle sizes by shear-breaking and superfine-grinding to further compare its sensory properties, physical properties, the leaching rate of active ingredients and antioxidant activity in vitro. The results showed that the superfine-grinding changed the sensory properties and physical properties of Dendrobium nobile, with an increase in bulk density, a decrease in swelling capacity and water-holding capacity and an increase in water solubility index. The method also contributed to the release of total polysaccharides, dendrobine, total polyphenols and total flavonoids components, thereby increasing ABTS, DPPH and nitrite ion scavenging activity. In addition, scanning electron microscopy and infrared spectroscopy analyses showed that superfine-grinding had no effect on the primary structure of the fractions as with decreasing particle size. This study suggested that superfine-grinding could be a promising method for producing Dendrobium nobile powders with higher contents of bioactive compounds and bioactivity. markets form ingredient shearbreaking shear breaking superfinegrinding superfine grinding vitro density waterholding holding index polysaccharides dendrobine components ABTS addition size bioactivity

Abstract Introduction: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. Objective: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. Methods: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. Results: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1β, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. Conclusion: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.