Abstract Objectives: This study aimed to investigate the effects of an adhesive bone conduction device (aBCD) in children with congenital single-sided deafness (SSD). Specifically, we examined whether the aBCD elicits improvement in the speech perception ability of children with congenital SSD and whether using this device would adversely affect the horizontal localisation abilities of these children. Methods: Thirteen school-aged children with SSD and seven children with Normal Hearing (NH) were included in this study. Speech perception in noise was measured using the Mandarin Speech Test Materials and sound localisation performance was evaluated using broadband noise stimuli (0.5–20 kHz), randomly played from seven loudspeakers at different stimulus levels (65-, 70-, and 75-dB SPL). Results: All children with SSD showed inferior speech perception and sound localisation performance compared with children with NH. The aBCD use remarkably improved the speech perception abilities of these children under quiet and noise conditions; however, their sound localisation abilities neither improved nor deteriorated. Conclusion: This study reveals the effectiveness and safety of a non-surgical aBCD in paediatric patients with SSD. Our results provide a theoretical basis for early hearing intervention with an aBCD in children with congenital SSD who are temporarily unable to undergo ear surgery. Level of evidence: Level 3. Objectives (aBCD singlesided single sided . (SSD) Specifically Methods schoolaged school aged NH (NH 0.5–20 0520 0 5 20 (0.5–2 kHz, kHz , kHz) 65, 65 (65- 70, 70 70- 75dB dB 75 SPL. SPL SPL) Results conditions however deteriorated Conclusion nonsurgical non surgical surgery evidence 3 (SSD 0.5–2 052 2 (0.5– 6 (65 7 0.5– 05 (0.5 (6 0.5 (0. ( 0. (0

Renal fibrosis is a common manifestation in the progression of chronic kidney disease (CKD) to kidney failure. Currently, there is no available therapy to prevent the progression of renal fibrosis. Poricoic acid A (PAA) isolated from Poria cocos shows notable antifibrotic effects. However, its potential mechanism is still unclear. This study aimed to evaluate the effects and the potential mechanisms of PAA against renal fibrosis. A mouse model of renal fibrosis was established using unilateral ureteral obstruction (UUO). We showed that PAA administration significantly alleviated renal lesions and collagen deposition in UUO mice. Mice with UUO resulted in epithelial-to-mesenchymal transition (EMT) and the activation of endoplasmic reticulum stress (ERS) in the renal tissues, while PAA treatment significantly inhibited EMT and ERS activation. Additionally, PAA markedly alleviated ERS-mediated apoptosis in UUO mice. Molecular docking results indicated that PAA stably combined to GRP78 and ATF4. In conclusion, these results demonstrated that PAA possesses a significant bioactivity against renal fibrosis and its treatment mechanism might be the inhibition of ERS-mediated apoptosis. CKD (CKD failure Currently (PAA However unclear UUO. . (UUO) mice epithelialtomesenchymal epithelial mesenchymal (EMT (ERS tissues Additionally ERSmediated mediated GRP GRP7 ATF4 ATF conclusion (UUO

The low-temperature electrochemical corrosion behavior of aircraft 2024 aluminum alloy was investigated in different concentrations of potassium-acetate-type fluid, and the results showed that the corrosion medium initially impacted some corrosiveness on the 2024 aluminum alloy. However, the corrosion rate of the alloy decreased with prolonged immersion in the corrosion medium, and this was attributed to the protective effect of the corrosion products layer, which impeded the attack by the aggressive solution. Time-domain analysis of electrochemical noise measurements at -5 °C revealed the occurrence of uniform corrosion on the alloy at the initial stages of immersion, general corrosion at the middle stages of immersion, and a pitting-dominated corrosion type from the middle to late stages of immersion. lowtemperature low temperature 202 potassiumacetatetype potassium acetate fluid However layer solution Timedomain Time domain 5 - C pittingdominated pitting dominated 20 2

Abstract Dendrobium nobile is a traditional Chinese medicine and functional food in China, with anti-aging, immunity-enhancing, glucose-lowering and lipid-lowering health functions. In recent years, the research value of D. nobile has attracted the attention of more and more experts and scholars. Today, phytochemical investigation of the stems of Dendrobium nobile Lindl., led to the isolation of five sesquiterpene glycosides, including dendromoniliside D (1), dendronobiloside A (2), dendronobiloside C (3), dendronobiloside D (4), dendroside G (5) and their α-amylase and α-glycosidase inhibitory activities were also investigated. Among them, dendromoniliside D (1), dendroside G (5) were first isolated from D. nobile. And dendronobiloside A (2) and dendronobiloside C (3) exhibited better inhibitory activity against α-glycosidases, respectively. In the case of α-amylase inhibition, dendroside G (5) has a relatively good effect. These results suggest that sesquiterpene glycosides of D. nobile have potential hypoglycemic activity and deserve further research and development.

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. Kaempferol healthbeneficial health beneficial medicine food industries biosystem 3hydroxylase hydroxylase 3 AtF3H AtFH AtF H (AtF3H AtFLS1 AtFLS (AtFLS1 length AtF3HGGGGS2AtFLS1 AtFHGGGGSAtFLS GGGGS 2 AtF3H-(GGGGS)2-AtFLS 0129 0 129 0.12 0016 016 0.01 mM parameters 10054 100 54 100.5 054 0.5 mgL mg L mg/L 6826 68 26 68.26 005 05 0.05% addition molecules (AtFLS HGGGGS AtF3HGGGGS2AtFLS 012 12 0.1 001 01 0.0 1005 10 5 100. 0. 682 6 68.2 00 0.05 1 68.

Abstract Dendrobium nobile is a traditional Chinese medicine and nourishing food in China. Alkaloids and sesquiterpene glycosides are the two main active ingredients in D. nobile. The previous reports showed that alkaloids and sesquiterpene glycosides have the same upstream biosynthetic pathway, starting from sesquiterpene components, part of which is converted to sesquiterpene glycosides by the action of UDP-glycosyltransferase, and part of which is further synthesized to alkaloids. Therefore, sesquiterpene UDP-glycosyltransferases play an important role in the biosynthesis of alkaloids and sesquiterpene glycosides in D. nobile. In this study, the key glycosyltransferase genes in sesquiterpene glycosylation in D. nobile were explored, predicted and validated by transcriptome technology. China D pathway components UDPglycosyltransferase, UDPglycosyltransferase UDP glycosyltransferase, UDP-glycosyltransferase Therefore UDPglycosyltransferases glycosyltransferases study explored technology

ABSTRACT Purpose: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. Methods: PCCL was orally administered at a dose of 20 mg·kg–1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg–1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1β levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. Results: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. Conclusions: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.

Abstract Enteromorpha prolifera polysaccharide (EP) is a water-soluble sulfated polysaccharide with many types of biological activities. In this study, the crude polysaccharide was extracted from Enteromorpha prolifera and degraded by different physical, chemical, and biological methods. The results showed that the enzymatic degradation products displayed the best tyrosinase inhibitory activity. The optimal enzymatic degradation conditions were as follows: 30 °C, pH 5.5, 750 U/mL enzyme dosage for 2 h. The enzymatic hydrolysates were then divided into six EP fractions (EPFs) by an ultrafiltration membrane. The in vitro tyrosinase inhibitory activity of these fractions showed that the smaller the molecular weight of EPF, the better the inhibitory effect on tyrosinase. The antioxidant and tyrosinase inhibitory effect of the most effective EPF, a molecular weight below 5 kDa, (EPF5), was further confirmed on B16 cells. A kinetic study of tyrosinase inhibitory activity revealed that EPF5 is a competitive-uncompetitive mixed-type inhibitor of tyrosinase. These findings suggested that EPF5 has significant potential as a skin-whitening agent in cosmetics as well as an antibrowning agent in the food and agriculture industries.

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.

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III–IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III–IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

Malt is the mature fruit of Hordeum vulgare L. after germination and drying and has been applied for treatment female abnormal galactorrhea. Previous studies have showed total alkaloids in malt have anti-HPRL effect. However, total alkaloids of malt change with the growth cycle, and the specified levels of total alkaloids in different bud length of malt have not been decided. To determine the definitive level of total alkaloids in different buds of malt and the most suitable bud length for clinical application by comparing effects on hyperprolactinemia rat. During the budding of malt, the content of total alkaloids first increased and then decreased, and it peaked at a bud length of 0.75 cm. Treated the HPRL model rats with different buds of malt, the PRL level was decreased, the number of PRLpositive cells and the mRNA expression level in the pituitary were significantly declined, and the number of dopamine D1 and D2 receptors in the hypothalamus was increased. The above changes were most significant in 0.75 cm bud. These results suggest that in terms of the content of effective substance and the effects on HPRL model rats, a malt bud length of 0.75 cm is optimal for clinical application.

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.

The objective of this study was to compare the safety and efficacy of 0.2% hyaluronic acid (HA) topical gel and dexamethasone topical ointment in the treatment of recurrent aphthous ulcers (RAU) in children. This retrospective observational study included 104 patients who had more than two episodes of oral aphthous ulcers per year and were treated with HA (n=52) or dexamethasone (n=52) from August 15, 2014 to September 3, 2018. Therapy efficacy was evaluated based on the ulcer size and pain score before versus 7 days after either therapy. The paired t-test, chi-squared test, and independent t-test were utilized for statistical analyses. There was no significant difference in ulcer size or pain score between the HA and dexamethasone groups, on day 1 or day 7. Both treatments were tolerated well and no side effects were reported. No significant differences in body temperature, respiration rate, pulse, or systolic/diastolic blood pressure were observed between the start (day 1) and end of treatment (day 7), for either treatment. HA and dexamethasone showed similar efficacy in reducing ulcer size and pain scores, and were tolerated equally well in children with RAU. Future high-quality studies with larger numbers of patients are needed to confirm our findings.

Abstract Objective To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment.

Abstract Background: Reports regarding the causative drugs of drug-induced cutaneous adverse reactions in China are indistinct, such that different regions have reported the spectrum of drugs differs substantially in different clinical conditions. Objective: To explore the causative drugs that led to cutaneous reactions. Methods: Adverse drug reaction reports from central China were collected and divided into cutaneous adverse reactions and severe cutaneous adverse reactions groups. Cases were reviewed retrospectively for causative drugs. Results: The male:female ratio was equal in both cutaneous adverse reactions and severe cutaneous adverse reactions. In cutaneous adverse reactions (n = 482), the highest incidence happened between 51 and 60 years of age and the top three causative drugs were antibiotics (48%), Chinese medicine (16%), and allopurinol (9%). In severe cutaneous adverse reactions (n = 126), the highest incidence happened between 41 and 50 years of age and the top three causative drugs were sedative-hypnotics and antiepileptics (39%), antibiotics (22%), and allopurinol (15%). Carbamazepine was the most frequently used single-drug (16/18) in sedative-hypnotics and antiepileptics. β-lactams were the most frequently used antibiotics that induced both cutaneous adverse reactions and severe cutaneous adverse reactions. Study limitations: The small sample size, retrospective design, collection of cutaneous adverse reactions and severe cutaneous adverse reactions at different time frames and locations, and exclusion of patients taking more than five medications are limitations of the study. Conclusions: Gender does not affect cutaneous adverse reactions and severe cutaneous adverse reactions. The top three drugs to induce cutaneous adverse reactions are antibiotics, Chinese medicine, and allopurinol, while those that triggered severe cutaneous adverse reactions are sedative-hypnotics and antiepileptics, antibiotics, and allopurinol. Carbamazepine is the most frequent single drug that induces severe cutaneous adverse reactions. β-lactams are the most frequently used antibiotics that induce both cutaneous adverse reactions and severe cutaneous adverse reactions.