Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Abstract Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion We found that PAX9 variants commonly lead to loss of the second molars.

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 Under the influence of the COVID-19, people's awareness of physical health and immunity has increased significantly. Chitooligosaccharide is an oligomer of β-(1, 4)-linked D -glucosamine, furthermore, is one of the most widely studied immunomodulators. Chitooligosaccharide can be prepared from the chitin or chitosan polymers through enzymatically, chemically or physically processes. Chitooligosaccharide and its derivatives have been proven to have a wide range of biological activities including intestinal flora regulation, immunostimulant, anti-tumor, anti-obesity and anti-oxidation effects. This review summarizes the latest research of the preparation methods, biological activities in immunity and safety profiles of Chitooligosaccharide and its derivatives. We recapped the effect mechanisms of Chitooligosaccharide basing on overall immunity. Comparing the effects of Chitooligosaccharide with different molecular weights and degree of aggregation, a reference range for usage has been provided. This may provide a support for the application of Chitooligosaccharide in immune supplements and food. In addition, future research directions are also discussed.

ABSTRACT Due to its high nutritional value, broccoli (Brassica oleracea var. italica Plenck) is one of the most popular vegetables worldwide. This study assessed 36 phenotypic characteristics of 111 broccoli varieties to understand the phenotypic diversity of new broccoli varieties and improve their breeding speed with advantages and characteristics in China, including 108 new varieties and three varieties of common knowledge. The genetic diversity, the principal component, and the cluster of phenotypic characteristics of broccoli varieties were further investigated. The results showed that the coefficients of variation of 36 characteristics ranged between 11.18 % and 94.99 %, with their diversity index between 0.26 and 1.82. The 111 broccoli varieties were further classified into eight groups, primarily attributed to the differences in phenotypic characteristics, including curd weight, main stem thickness, plant development degree, plant height, and anthocyanin coloration. The cumulative contribution rate of the first five principal components reached 81.186 %, corresponding to 12 representative phenotypic traits. The analysis indicated that the phenotypic characteristics of broccoli were rich in diversity, especially for several characteristics appreciated by the market, such as weight, curd firmness, and anthocyanin coloration. This study revealed the basic information on the genetic diversity of new broccoli varieties in China from 2017 to 2019 and provided potential breeding strategies for broccoli to meet diverse market demands.

Abstract Objective To generalise the features of PANP in case of potential clinical and pathological pitfall of diagnosis. Methods Thirteen patients diagnosed as PANP were retrospectively analyzed in the Pathology Department of Capital Medical University from August 2014 to December 2019. Immunohistochemical staining with CD34, CK, Vim, Calponin, Ki67, Bcl-2, and STAT-6 was performed with envision-two steps method. Results PANP is a benign tumor presenting with gross variegated tan to gray soft fleshy tissue with foci of obvious hemorrhage and necrosis. The imaging shows internal heterogeneous hyperintensity with a peripheral hypointense rim while postcontrast images display a strong nodular and patchy enhancement. Vimentin (Vim) stain was consistently positive, while negative for CD34, STAT-6 and Bcl-2 (focal positive in two cases). Calponin and CK stain was positive in nine cases, respectively. Conclusion PANP is a clinically rare tumor which may simulate malignancy lesion. Recognizing of characteristic features in these thirteen patients would be beneficial to avoid misdiagnosis and unnecessary aggressive treatment. Level of evidence: This work was Level 2 of evidence according to the Guide for Authors.

SUMMARY OBJECTIVE: This study aimed to investigate the sex-specific association between hyperuricemia and the risk of hypertension and whether obesity mediates this association. METHODS: This study included 31,395 (47.0% women) adults without hypertension, cardiovascular disease, or cancer at baseline who completed at least one follow-up annual examination between 2009 and 2016. Cox regression models were performed to calculate hazard ratios and 95% confidence intervals. Mediation analysis was conducted to estimate the effect of body mass index on the association between hyperuricemia and hypertension. RESULTS: During a median 2.9-year follow-up, hyperuricemia was significantly associated with a higher risk of hypertension (HR 1.15, 95%CI 1.07-1.24 for all participants; HR 1.12, 95%CI 1.03-1.22 for men; and HR 1.23, 95%CI 1.02-1.48 for women) after adjustment for potential confounders. Additional adjustment for body mass index attenuated this association (HR 1.09, 95%CI 1.08-1.10 for all participants; HR 1.07; 95%CI 0.98-1.16 for men; HR 1.18; 95%CI 0.96-1.44 for women). Mediation analysis showed that BMI partially mediated the relationship between hyperuricemia and incident hypertension (indirect effect HR 1.09, 95%CI 1.08-1.10; direct effect: HR 1.08, 95%CI 1.02-1.15). The percentage of the mediation effect was 53.2% (95%CI 37.9-84.5). CONCLUSION: Hyperuricemia is associated with a risk of hypertension in both sexes, and BMI partially mediates hyperuricemia-related incident hypertension.

Abstract Citric acid is an important and multi-functional organic acid, which is widely used in food, medicine, chemical industry and other fields. It is the largest edible organic acid in the world. Aspergillus niger is an important strain for biosynthesis of citric acid, which is mainly produced by simultaneous saccharification and fermentation with starch raw materials. The reuse of citric acid wastewater is the development direction of comprehensive utilization of citric acid wastewater. In the future, with the combination of novel technology strategies such as gene editing technology and synthetic biology technology, the establishment of fermentation strategies with high yield, high yield, high production intensity and clean production is the development direction to realize efficient green manufacturing in citric acid industry. multifunctional multi functional food medicine fields world materials future yield

RESUMO Introdução: A Quinta Conferência Internacional de Bioquímica Esportiva, define a fadiga esportiva como o processo fisiológico de disfunção em um determinado nível ou incapacidade de manter uma intensidade de exercício predeterminada. Quando não tratada, pode causar efeitos adversos ao sistema musculoesquelético. Há alternativas naturais para o controle da fadiga esportiva na cultura chinesa, mas pesquisas científicas são necessárias afim de descobrir a real efetividade desses tratamentos. Objetivo: Verificar o efeito do banho medicinal tradicional da medicina chinesa na fadiga muscular de atletas. Métodos: 100 atletas com fadiga muscular induzida por exercícios foram aleatoriamente divididos em dois grupos. O grupo controle recebeu injeção de gangliosideo combinada com protocolos de exercícios terapêuticos enquanto o grupo experimental recebeu o banho medicinal baseado na medicina tradicional chinesa. Foi avaliado o tônus de adutores, isquiotibiais, gastrocnêmios além da função motora dos membros inferiores. Resultados: A taxa efetiva total (90,8%) do grupo de observação foi superior à do grupo controle (72,3%) e a diferença foi estatisticamente significante (P<0,05). Após o tratamento, a tensão muscular adutores, jarrete e gastrocnêmio no grupo de observação foi menor que o grupo controle (P<0,05). O escore bruto de avaliação da função motora (GMFM-88), escore de escala de balanço de Berg (BBS), velocidade de caminhada de 10m em uma passarela de 20cm de largura (MWS) no grupo de observação foram maiores do que os do grupo controle (P<0,05). Conclusão: A loção de lavanda de ervas chinesas combinada com o exercício de suspensão pode melhorar efetivamente a força muscular do corpo após os exercícios, acelerar a recuperação da força muscular e reduzir significativamente a fadiga muscular induzida pelo exercício. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

ABSTRACT Introduction: The Fifth International Conference on Sports Biochemistry defines sports fatigue as the physiological process of dysfunction at a certain level or inability to maintain predetermined exercise intensity. When left untreated, it can cause adverse effects to the musculoskeletal system. Natural alternatives for controlling sports fatigue exist in Chinese culture, but scientific research is needed to determine the effectiveness of these treatments. Objective: This study aimed to verify the effect of traditional Chinese medicinal baths on athletes’ muscle fatigue. Methods: 100 athletes with exercise-induced muscle fatigue were randomly divided into two groups. The control group received ganglioside injection combined with therapeutic exercise protocols, while the experimental group received the medicinal bath based on traditional Chinese medicine. Tonus of adductors, ischiotibials, gastrocnemius, in addition to lower limb motor function, was evaluated. Results: The total effective rate (90.8%) of the observation group was higher than that of the control group (72.3%), and the difference was statistically significant (P<0.05). After treatment, adductor, hamstring, and gastrocnemius muscle tension in the observation group were lower than the control group (P<0.05). Gross motor function assessment score (GMFM-88), Berg Balance Scale (BBS), 10m walking speed on a 20cm wide walkway (MWS) in the observation group were higher than those in the control group (P<0.05). Conclusion: Chinese herbal lavender lotion combined with suspension exercise can effectively improve the body's muscle strength after exercises, accelerate the recovery of muscle strength, and significantly reduce exercise-induced muscle fatigue. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMEN Introducción: La Quinta Conferencia Internacional de Bioquímica del Deporte, define la fatiga deportiva como el proceso fisiológico de disfunción a un determinado nivel o incapacidad para mantener una intensidad de ejercicio predeterminada. Si no se trata, puede causar efectos adversos en el sistema musculoesquelético. Existen alternativas naturales para el control de la fatiga deportiva en la cultura china, pero se necesita una investigación científica para descubrir la eficacia real de estos tratamientos. Objetivo: Verificar el efecto del baño medicinal tradicional de la medicina china sobre la fatiga muscular de los atletas. Métodos: 100 atletas con fatiga muscular inducida por el ejercicio fueron divididos aleatoriamente en dos grupos. El grupo de control recibió una inyección de gangliósidos combinada con protocolos de ejercicio terapéutico, mientras que el grupo experimental recibió el baño medicinal basado en la medicina tradicional china. Se evaluó el tono de los aductores, los isquiotibiales y los gastrocnemios, además de la función motora de los miembros inferiores. Resultados: La tasa efectiva total (90,8%) del grupo de observación fue superior a la del grupo de control (72,3%) y la diferencia fue estadísticamente significativa (P<0,05). Tras el tratamiento, la tensión de los músculos aductores, jarretes y gastrocnemios en el grupo de observación fue inferior a la del grupo de control (P<0,05). La puntuación de la evaluación de la función motora gruesa (GMFM-88), la puntuación de la Escala de Equilibrio de Berg (BBS) y la velocidad de marcha de 10 m en una pasarela de 20 cm de ancho (MWS) en el grupo de observación fueron mayores que las del grupo de control (P<0,05). Conclusión: La loción de hierbas chinas de lavanda combinada con el ejercicio de suspensión puede mejorar eficazmente la fuerza muscular del cuerpo después de los ejercicios, acelerar la recuperación de la fuerza muscular y reducir significativamente la fatiga muscular inducida por el ejercicio. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Abstract Two kinds of bacteria, named TDJ-7 and TDJ-9, were isolated from the soil, which could degrade terbutylazine effectively. TDJ-7 and TDJ-9 were identified as Bacillus pumilus and Bacillus subtilis. The degradation efficiency of 10mg/L of terbutylazine by TDJ-7 could reach 95% within 6 days, and the strain TDJ-9 could reach 98% under the same conditions. Both strain TDJ-7 and strain TDJ-7 could also effectively degrade simazine, metribuzin, atrazine and ametryn. In addition, strain TDJ-7 and TDJ-9 had been successfully developed into a live bacterial agent that could be used to degrade terbutylazine residue. These results suggest that strain TDJ-7 and TDJ-9 can be used for the bioremediation of terbutylazine or other s-triazine herbicides contamination.

Abstract In order to realize the rapid nondestructive detection of mildew peanut in the process of peanuts storage, hyperspectral imaging technology was proposed to detect mildew peanut. A total of 200 peanuts were selected from 5 kinds of peanuts purchased in the market for moldy treatment, and the remaining 400 peanuts were kept sterile. After completion, samples were collected with a hyperspectral instrument to obtain spectral data of the samples. According to the characteristics of the data, 10 pre-processing algorithms were used to de-noise the data, and Median Filtering (MF) had the best effect, with the recognition accuracy reaching 97.7%. GBDT, LightGBM, CatBoost and XGBoost algorithms were used to extract important feature bands in the spectral data pre-processed by MF. GBDT, LightGBM, CatBoost and XGBoost algorithms were used to model the extracted feature bands. The results showed that LightGBM is the best algorithm with a detection rate of 99.10%. Optuna algorithm was used to tune its parameters. Compared with the previous model, the running time of the optimized model was improved by about 0.25 s. The results showed that hyperspectral imaging provides an efficient and nondestructive method for detecting mildew in peanut storage.

Abstract This study looked at the inhibitory effects of Apocynum venetum tea flavonoids extract (AVTFE) on mouse glioma G422 cells. Through the use of high performance liquid chromatography, the flavonoids in AVTFE were examined (HPLC). Meanwhile, mice were injected with glioma G422 cells to create a mouse model of a transplanted tumor. AVTFE might significantly (P < 0.05) lower serum sIL-2R content and raise serum IFN-γ content in tumor-bearing mice, according to an analysis of mouse serum. In addition to reducing the rise in spleen weight and spleen index in mice brought on by transplanted tumors, AVTFE can limit the development of transplanted tumors in G422 cell mice. AVTFE can also boost immunity by encouraging T and B lymphocyte proliferation in tumor-bearing animals. AVTFE was therefore verified to have immunomodulatory properties and to limit the proliferation of glioma G422 cells.

Abstract Objective: To investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. Methods: The clinical data of infants (n = 540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n = 253) and control group (n = 287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. Results: Out of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p = 0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p < 0.05). Binary logistic regression showed a childhood history of allergy (OR = 2.14, p = 0.004), no rhIFNα1b use (OR = 1.70, p = 0.028), and living in a crowded house (OR = 1.92, p = 0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR = 0.44, p = 0.008) and hospitalization age of 1-year-old (OR = 0.58, p = 0.024) were protective factors. Conclusions: Early use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.

Abstract To evaluate the effect of medical nutritional therapy (MNT) combined with low glycaemic index (LGI) formula at breakfast for 4 weeks on the glycaemic control of patients with type 2 diabetes mellitus (T2DM). Ninety-six participants were recruited and randomly equally divided into two groups. The intervention group was offered with 40g LGI formula at breakfast adjusted according to MNT, and the control group with regular MNT. After 4 weeks, fasting blood glucose, glycated albumin (GA), insulin, C-peptide levels and metabolic index were compared between the two groups. Compared to the intervention group, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and the change of FBG (–0.64 ± 1.4 vs. 0.3 ± 2.2; p < 0.05) and 2h-PBG (–1.8 ± 3.6 vs.0.8 ± 3.2; p < 0.01) in the control group were significantly decreased. The LGI formulations, having a significant effect on controlling glucose and lipid metabolism, could be used as a non-pharmacological intervention for T2DM self-management.