Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment. SNHL (SNHL health however disease Recently therapies (MSCs products namely immunogenicity concerns accessibility Nevertheless MSCderived MSC unclear neomycininduced neomycin induced vitro addition effect Mechanistically formation survival ototoxicity summary exosomemediated exosome mediated endocytosisdependent endocytosis dependent manner treatment

Resumen La cardiomiopatía diabética es una complicación grave de la diabetes causada por estrés oxidativo, inflamación, resistencia a la insulina, fibrosis miocárdica y lipotoxicidad. Se trata de un padecimiento insidioso, complejo y difícil de tratar. El inflamasoma NLRP3 desencadena la maduración y liberación de citoquinas proinflamatorias, participa en procesos fisiopatológicos como la resistencia a la insulina y la fibrosis miocárdica, además de estar estrechamente relacionado con la aparición y progresión de la cardiomiopatía diabética. El desarrollo de inhibidores dirigidos a aspectos específicos de la inflamación sugiere que el inflamasoma NLRP3 puede utilizarse para tratar la cardiomiopatía diabética. Este artículo pretende resumir el mecanismo y las dianas terapéuticas del inflamasoma NLRP3 en la cardiomiopatía diabética, así como aportar nuevas sugerencias para el tratamiento de esta enfermedad.

Abstract Diabetic cardiomyopathy (DCM) is a serious complication of diabetes caused by oxidative stress, inflammation, insulin resistance, myocardial fibrosis, and lipotoxicity; its nature is insidious, complex and difficult to treat. NLRP3 inflammasome triggers the maturation and release of pro-inflammatory cytokines, participates in pathophysiological processes such as insulin resistance and myocardial fibrosis, in addition to being closely related to the development and progression of diabetic cardiomyopathy. The development of inhibitors targeting specific aspects of inflammation suggests that NLRP3 inflammasome can be used to treat diabetic cardiomyopathy. This paper aims to summarize NLRP3 inflammasome mechanism and therapeutic targets in diabetic cardiomyopathy, and to provide new suggestions for the treatment of this disease.

Abstract A chitosan-based edible coating was prepared by incorporating γ-polyglutamic acid and curcumin. The physical, mechanical and antimicrobial properties of the chitosan/γ-polyglutamic acid/curcumin edible coating were characterized. Furthermore, the effect of chitosan/γ-polyglutamic acid/curcumin edible coating on the shelf-life of fresh beef was investigated. The γ-polyglutamic acid and curcumin incorporation greatly improved the performance of chitosan coating, including coating formation and antimicrobial activity. After the application of coating, the chitosan/γ-polyglutamic acid/curcumin edible coating had a good protection effect on the color of beef and was conducive to prolonging the shelf life of beef with good quality compared to pure curcumin edible coating. These results revealed that application of chitosan/γ-polyglutamic acid/ curcumin edible coating will be a good way to preserve freshness of fresh beef.

Abstract Objective Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. Methods The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. Results Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. Conclusions The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase.

Abstract Heart Failure (HF) has been one of the leading causes of death worldwide. Though its latent mechanism and therapeutic manipulation are updated and developed ceaselessly, there remain great gaps in the cognition of heart failure. High morbidity and readmission rates among HF patients are waiting to be addressed. Recent studies have found that myocardial energy metabolism was closely related to heart failure, in which substrate utilization, as well as intermediate metabolism disorders, insulin resistance, oxidative stress, and mitochondrial dysfunction, might underlie systolic dysfunction and progression of HF. This article centers on the changes and counteraction of cardiac energy metabolism in the failing heart. Therefore, targeting impaired energy provision is of great potential in the treatment of HF. And shifting the objective from traditional neurohormones to improving the cellular environment is expected to further optimize the management of HF. (HF worldwide ceaselessly failure addressed utilization disorders resistance stress Therefore

Abstract Objective: This study aimed to investigate the demographic and clinicopathological characteristics, and survival outcomes of subglottic Squamous Cell Carcinoma (SCC) based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Demographic and clinicopathological information, including age, sex, race, tumor size, histologic grade, clinical/TNM stage, tumor invasion extent, Lymph Node Metastasis (LNM) extent, size of metastatic lymph nodes, LNM ratio and treatment data, of 842 subglottic SCC patients diagnosed between 1996 and 2016 were acquired. Kaplan-Meier survival analyses were performed to assess the effects of clinicopathological characteristics, treatment modalities, surgical procedures, and adjuvant therapies on overall survival and cancer-specific survival. Results: Subglottic SCC was more frequent among males aged 60-70 years, with low-grade but locally advanced lesions without local or distant metastases. Age and several primary tumor/LNM related variables were independent risk factors for overall survival and cancer specific survival. Advanced-stage and high-grade disease led to unfavorable prognosis. The most common treatment modality and surgical procedure were surgery plus radiotherapy and total laryngectomy, respectively. Surgery plus radiotherapy provided favorable 5-year survival outcomes, while total laryngectomy had the worst. Surgery plus adjuvant therapy showed better survival outcomes than surgery alone. Conclusion: This study confirmed the rarity of subglottic SCC. Patients with subglottic SCCs suffered poor prognosis especially for those with advanced-stage or high-grade lesions. The prognosis of subglottic SCC remained poor over the years, despite recent progress in cancer therapies. Surgery plus adjuvant therapy improved the survival outcome. Although larynx preservation surgery was beneficial for early-stage disease, total laryngectomy was favored for patients with advanced tumors. Level of evidence: Level 4.

Abstract Background: UVB irradiation can cause acute damage such as sunburn, or photoaging and melanoma, all of which are major health threats. Objective: This study was designed to investigate the mechanism of skin photoaging induced by UVB radiation in mice through the analysis of the differential expression of miRNAs. Methods: A UVB irradiation photoaging model was constructed. HE and Masson special stains were used to examine the modifications in the epidermis and dermis of mice. The miRNA expression profiles of the mouse skin model exposed to UVB radiation and the normal skin of mice were analyzed using miRNA-sequence analysis. GO and Pathway analysis were employed for the prediction of miRNA targets. Results: A total of 23 miRNAs were evaluated for significantly different expressions in comparison to normal skin. Among them, 7 miRNAs were up-regulated and 16 were down-regulated in the skin with photoaging of mice exposed to UVB irradiation. The differential expression of miRNA is related to a variety of signal transduction pathways, among which mmu-miR-195a-5p and mitogen-activated protein kinase (MAPK) signal pathways are crucial. There was a significant differential expression of miRNA in the skin of normal mice in comparison with the skin with photoaging induced by UVB irradiation. Study limitations: Due to time and energy constraints, the specific protein level verification, MAPK pathway exploration, and miR-195a-5p downstream molecular mechanism need to be further studied in the future. Conclusions: UVB-induced skin photoaging can be diagnosed and treated using miRNA.

RESUMO: As respostas de duas cultivares de milho (Zea mays L.), ‘LY336’ (tolerante à sombra) e ‘LC803’ (sensível à sombra), ao estresse de sombra em um experimento em vaso conduzido nas safras de 2015 e 2016 foram investigadas. O impacto do tratamento de estresse de sombra de 50% na biomassa da parte aérea, parâmetros fotossintéticos, fluorescência da clorofila e teor de malondialdeído (MDA) foi avaliado. A biomassa da parte aérea dos dois híbridos de milho foi reduzida significativamente pelo tratamento de estresse de sombra, para estresse de sombra 7 d, o LC803 e LY336 foram reduzidos em 56,7% e 44,4% em comparação com a luz natural. Os parâmetros de fluorescência da clorofila de LY336 não foram significativamente afetados pelo estresse de sombra, enquanto aqueles de LC803 foram significativamente afetados, o Fo aumentou sob estresse de sombra, porém Fm, FV / FM e ΦPSII diminuíram sob estresse de sombra. Entre os parâmetros fotossintéticos medidos, a taxa fotossintética líquida (Pn), a condutância estomática (Gs) e a taxa de transpiração diminuíram significativamente em comparação com a luz natural, redução de LY336 e LC803 em 28,0%, 22,2%, 57,7% e 35,5%, 18,9%, 62,4 %, porém a concentração intercelular de CO2 (Ci) aumentou significativamente para as duas cultivares. Sob estresse de sombra para diferentes durações (1, 3, 5, 7 d), os teores de Pn, Gs, Ci e MDA diferiram significativamente entre as duas cultivares. Os resultados indicam que diferentes genótipos de milho apresentam diferentes respostas ao sombreamento. Os genótipos tolerantes à sombra são apenas fracamente afetados pelo estresse de sombra.

ABSTRACT: The responses of two maize (Zea mays L.) cultivars, ‘LY336’ (shade tolerant) and ‘LC803’ (shade sensitive), to shade stress in a pot experiment conducted in the 2015 and 2016 growing seasons were investigated. The impact of 50% shade stress treatment on shoot biomass, photosynthetic parameters, chlorophyll fluorescence, and malondialdehyde (MDA) content was evaluated. The shoot biomass of the two maize hybrids was decreased significantly by shade stress treatment, for shade stress 7 d, the LC803 and LY336 were reduced by 56.7% and 44.4% compared with natural light. Chlorophyll fluorescence parameters of LY336 were not significantly affected by shade stress, whereas those of LC803 were significantly affected, the Fo increased under shade stress; however Fm, FV/FM and ΦPSII were decreased under shade stress. Among photosynthetic parameters measured, net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate were significantly decreased compared with natural light, LY336 and LC803 reduction by 28.0%, 22.2%, 57.7% and 35.5%, 18.9%, 62.4%; however, intercellular CO2 concentration (Ci) was significantly increased, for the two cultivars. Under shade stress for different durations (1, 3, 5, 7 d), Pn, Gs, Ci, and MDA content differed significantly between the two cultivars. Results indicated that different maize genotypes showed different responses to shading. Shade-tolerant genotypes are only weakly affected by shade stress.

Abstract The aim of this study was to investigate the effect of TiO2/N-succinyl-chitosan composite (TiO2/ NSCS) photodynamic therapy (PDT), while considering the effects of various light sources on the activation of photosensitizer. The methyl thiazolyl tetrazolium assay was used to examine the cell survival rate of the cells. The results showed that glioma cell strain (U251) was the most sensitive cancer cell strain to TiO2/NSCS. When the concentration of TiO2/NSCS was between 0 and 800 μg·mL-1, there was no obvious cytotoxicity to normal liver cells (HL-7702) and U251 cells. During the PDT process, the photokilling effect of TiO2/NSCS on U251 cells under ultraviolet-A (UVA) light irradiation was stronger than that of pure TiO2, and its killing effects were positively correlated with concentration and irradiation time. In addition, both UVA and visible light could excite TiO2/ NSCS, which had significant killing effect on U251 cells. The results of acridine orange/ethidium bromide fluorescent double staining and Annexin V/propidium iodide double staining indicated that TiO2/NSCS under UVA and visible light irradiation could kill U251 cells by inducing apoptosis, and the apoptosis rate of TiO2/NSCS treatment groups was higher than that of TiO2 treatment groups. Therefore, TiO2/NSCS might be used as a potential photosensitizer in PDT.

Abstract In this paper, a model of the composite foundation reinforced with geosynthetic encased stone columns was established using the discrete element method, and the characteristics of its action under cyclic loading were studied. The influence of the length and radius of the pile on the settlement of the composite foundation is analyzed. The deformation characteristics of the pile and the stress ratio of pile-soil are studied under different pile lengths and radius. Then, based on this, the analysis of the lateral deformation characteristics of the piles under cyclic loading, the calculation model of the geosynthetic encased pile composite foundation is established. The settlement calculation formula of the composite foundation is solved according to the deformation coordination relationship between the pile and soil, the equilibrium condition, and the boundary condition. The results show that the theoretical value is in good agreement with the simulation value, which verifies the rationality of the theoretical calculation formula.

Abstract Sodium lactate contribution on color stability of chilled beef was evaluated by proteomics analysis combined with the relative Mb content and NADH/ NAD+ ratio. The sodium lactate exhibited a remarkable efficacy against discoloration of chilled beef and showed a desirable color appearance for 6 days, while the control showed an undesirable color appearance on the 3rd day. Based on the significance analysis of protein interaction network, 12 proteins responsible for color stability of chilled beef treated by sodium lactate have been identified, which participated mainly in redox systems, metabolic enzymes, oxidoreductase, structural proteins and heat shock proteins. The proteins were correlated with NADH regeneration. Thus, we suggest that the color stability promotion may attribute to the role of in the regeneration of NADH by sodium lactate treatment.

Abstract Objective Tongue squamous cell carcinoma (TSCC) is an oral cancer, with high malignancy and frequent early migration and invasion. Only a few drugs can treat tongue cancer. Ginsenoside Rd is a ginseng extract with anti-cancer effects. Many noncoding RNAs are abnormally expressed in tongue cancer, thus influencing its occurrence and development. H19 and miR-675-5p can promote cancer cell growth. This study aimed to analyze the regulation effect of ginsenoside Rd on H19 and miR-675-5p in tongue cancer. Methodology We used CCK8 and flow cytometry to study the growth and apoptosis. Transwell assay was used to assess invasion; wound-healing assay to assess migration; and colony formation assays to test the ability of cells to form colonies. H19, miR-675-5p, and CDH1 expressions were analyzed by qPCR. E-cadherin expression was detected using western blot. CRISPR/cas9 system was used for CDH1 knockout. Results Ginsenoside Rd inhibited the growth and increased the apoptosis of SCC9 cells. Ginsenoside Rd also inhibited the migration and invasion of SCC9 cells. H19 and miR-675-5p were highly expressed, while CDH1 and E-cadherin expressions were low. H19 and miR-675-5p promoted SCC9 metastasis. In contrast, CDH1 and E-cadherin inhibited the metastasis of SCC9 cells. Bioinformatics analysis showed that miR-675-5p was associated with CDH1. H19 and miR-675-5p expressions decreased after ginsenoside Rd treatment, while CDH1 and E-cadherin expressions increased. Conclusions Ginsenoside Rd inhibits tongue cancer cell migration and invasion via the H19/miR-675-5p/CDH1 axis.

Abstract Objective: This study aimed to examine changes in miRNAs expression profile of COPD patients. Methods: Thirty-six COPD patients as well as thirty-three healthy volunteers were recruited. Total RNAs were collected from the plasma of each participant. The differentially expressed miRNAs in COPD were screened from the GEO database. RT-qPCR was carried out to detect miRNA expression. Results: In total, 9 out of 55 miRNAs were expressed differentially in COPD patients. Confirmed by RT-qPCR validation, 6 miRNAs increased while 3 miRNAs decreased. Further analysis of miR-423-5p, which has not been reported in COPD, showed that AUC for the diagnosis of COPD was 0.9651, and miR-423-5p levels was inversely correlated with the duration of smoking. Conclusion: The present study demonstrates that miR-423-5p is a potential marker for identifying COPD patients.

ABSTRACT Film mulching is an effective water-saving and yield-increasing measure for potato production in Northwest China. However, the response mechanism of microbial communities to mulching films in the soil is still unclear. In this study, polyethylene film mulching (PM), biodegradable film mulching (BM), liquid film mulching (LM), and non-mulching (NM) were applied on the drip-irrigated soil to investigate the effects of mulching films on soil bacterial and fungal communities through DNA sequencing, Pearson correlation analysis, and redundancy analysis. The results showed that LM treatment significantly increased the contents of soil mineral N (SMN), dissolved organic carbon (DOC), and dissolved organic nitrogen (DON) (p<0.05) in comparison with NM. The soil treated with LM presented high bacterial OTUs (operational taxonomic units), Chao1, ACE, and Shannon indices; however, the same indexes of fungi were low in LM and BM treatments. At the phylum level, Proteobacteria, Actinobacteria, and Chloroflexi were dominant bacterial communities. The LM treatment increased the OTUs of Proteobacteria ; PM treatment increased the OTUs of Actinobacteria and Chloroflexi. Ascomycota was the dominant fungal community, which were decreased in soil under mulching films. In terms of soil properties, DON was closely correlated (p<0.05) with the microbial OTUs, Chao1, and ACE indices. The DOC and SWC (soil water content) contributed 51.2 % to the change of bacterial structure; however, the fungal structure was less sensitive to the variation of soil properties. Our results indicate that liquid film mulching favors increasing the diversity and abundance of dominant bacterial species, which were associated with the variation of soil properties.

ABSTRACT Purpose Various surgical options are available for large proximal ureteral stones, such as extracorporeal shock wave lithotripsy (ESWL), ureteroscopic lithotripsy (URSL), percutaneous nephrolithotomy (PCNL) and laparoscopic ureterolithotomy (LU). However, the best option remains controversial. Therefore, we conducted a network meta-analysis comparing various surgical treatments for proximal ureteral stones ≥10mm to address current research deficiencies. Materials and methods We searched PubMed, Ovid, Scopus (up to June 2019), as well as citation lists to identify eligible comparative studies. All clinical studies including patients comparing surgical treatments for proximal ureteral stones ≥10mm were included. A standard network meta-analysis was performed with Stata SE 14 (Stata Corp, College Station, TX, USA) software to generate comparative statistics. The quality was assessed with level of evidence according to the Oxford Centre for Evidence-based Medicine and risk of bias with the Cochrane Collaboration’s Review Manager (RevMan) 5.3 software. Results A total of 25 studies including 2.888 patients were included in this network meta-analysis. Network meta-analyses indicated that LU and PCNL had better stone-free rates and auxiliary procedures. PCNL could result in major complications and severe bleeding. In initial stone-free rate, final stone-free rate, and auxiliary procedures results, SUCRA ranking was: LU> PCNL> URSL> ESWL. In Clavien Dindo score ≥3 complications, SUCRA ranking was: LU> ESWL> URSL> PCNL. In fever, SUCRA ranking was: ESWL> LU> URSL> PCNL. In transfusion, SUCRA ranking was: LU> URSL> ESWL> PCNL. In Cluster analysis, LU had the highest advantages and acceptable side effects. Considering the traumatic nature of PCNL, it should not be an option over URSL. ESWL had the lowest advantages. Conclusions LU have the potential to be considered as the first treatment choice of proximal ureteral stone ≥10mm.