ABSTRACT Purpose: Oxidative stress and apoptosis contribute to the pathological basis of doxorubicin (DOX)-induced cardiotoxicity. Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Herein, we intended to explore the potential role and molecular basis of CBN in DOX-induced cardiotoxicity. Methods: C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity. CBN (10 mg/kg/day, i.p.) was administered for four week following DOX injection. Results: DOX administered markedly dampened cardiac function, increased cardiac injury, excessive reactive oxygen species (ROS) production, and cardiomyocyte loss. These alterations induced by DOX significantly alleviated by CBN treatment. Mechanistically, our results demonstrated that the CBN exerts cardioprotection role against DOX by up-regulating silent information regulator 1 (Sirt1) and decreasing acetylation of forkhead box O1 (FOXO1). Moreover, Sirt1 inhibition with Ex-527 significantly blunt the beneficial effect of CBN on DOX-induced cardiotoxicity, including cardiac dysfunction, ROS, and apoptosis. Conclusion: Collectively, CBN attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity through maintaining Sirt1/FOXO1 signaling pathway. Our results demonstrated that CBN might be used to treat DOX-related cardiotoxicity.

Abstract Poor storability is the largest problem thwarting the marketization of fresh goji berries (Lycium barbarum L.). In this study, the storability of fresh fruits from 31 varieties of goji berry was evaluated by their decay index and rate of decay to choose 13 varieties of fresh fruit with excellent, medium and poor storability. Correlation and partial least squares regression analyses were adopted to explore the correlations between storability and 16 physical and chemical indicators from summer and autumn fruits. The storability calculated by the decay rate is significantly positively correlated with the content of flavonoids in the summer fruits, while the storability calculated by the decay index is significantly negatively correlated with the color difference b* and total acids in the summer fruits (P < 0.05). Similarly, the storability calculated by the decay rate is significantly positively correlated with the content of flavonoids, chewiness and elasticity of the autumn fruits (P < 0.05). The storability calculated by the decay index is significantly positively correlated with the content of flavonoids and the chewiness of autumn fruits (P < 0.05).The content of flavonoids in the fresh goji berry revealed a significantly positive correlation with the storability.

Abstract Character strengths could effectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10–12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths ( r = −0.14 to −0.3, p < 0.05 Bonferroni corrected). Character strengths explained a significant proportion of additional variance (14–22%) in five types of behavior problems after controlling the effect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specific character strengths showed an independent contribution ( β = −0.34 to −0.14 for self-regulation, perseverance, zest, humility, and leadership; β = 0.21 to 0.34, for hope; all p < 0.05) to behavior problems. Our study revealed that character strengths were protective factors against behavior problems in early adolescents.

Abstract Purpose of this study the mechanism of curcumin inhibiting pyroptosis in infectious acute lung injury through NLRP3 inflammatory pathway. In this study, SPF SD male rats were randomly divided into blank control group, curcumin group, lipopolysaccharide (LPS) group, LPS + curcumin group, LPS + Nigerin treatment group, LPS + Nigerin + curcumin treatment group. Three in each group. Animal models were established according to the experimental design. Blood samples were collected after anesthesia, and the lung wet/dry weight ratio was calculated. TUNEL was used to detect pyroptosis of alveolar macrophages in left lower lobe, and Elisa was used to detect the expression levels of inflammatory factors IL-1β and IL-18 in left lung tissue. Western Blot was used to detect the expression of pyroptosis-related proteins such as NLRP3, Caspase1 and GSDMD in right lung alveolar lavage fluid. Compared with the blank control group, the lung wet weight and lung dry weight of the curcumin group were significantly increased (P < 0.01, P < 0.05). Compared with the LPS group, the lung wet weight and lung dry weight of the curcumin group There was a statistical difference in weight increase (P < 0.01). Compared with the blank control group, the apoptosis rate of lung tissue in the curcumin group, LPS group and LPS+ nigericin group was significantly increased (P < 0.01). Compared with the LPS + nigericin group, the lung tissue apoptosis rate in the LPS + curcumin + nigericin group was decreased, but there was no statistical difference (P > 0.05). LPS and LPS combined with Nigerian bacteriocin can cause pyroptosis in lung tissue. Curcumin can inhibit pyroptosis of lung tissue macrophages caused by LPS and LPS combined with Nigerian bacteriocin, and reduce inflammatory response.

Abstract The bacterial diversity on the surface of the Chinese Wolfberry (Lycium barbarum) affects the storage tolerance of the fruit. We analyzed the bacterial diversity on the surfaces of eight varieties of Chinese wolfberries using high-throughput sequencing before and after storage. A total of 737 OTUs, including 584 species, 423 genera, 243 families, 153 orders, and 62 classes, were identified by bioinformatic analysis of the OTUs at the 97% similarity level. There were no significant differences among fruit varieties just after picking (O period). The dominant genera during the O period were Massilia and Pseudomonas. However, after a 144-hour storage period (S period), there were significant changes in both the decay rate and surface bacterial compositions. The Z1 variety showed the highest rate of decay, and its surface microbiota was dominated by Pantoea (84.34%), while the variety with the lowest decay rate was O, dominated by both Pantoea (69.06%) and Rosenbergiella (16.99%).

Abstract Blumea balsamifera (L.) DC., a medicinal plant with high economic value in the Asteraceae family, is widely distributed in China and Southeast Asia. However, studies on the population structure or phylogenetic relationships with other related species are rare owing to the lack of genome information. In this study, through high-throughput sequencing, we found that the chloroplast genome of B. balsamifera was 151,170 bp in length, with a pair of inverted repeat regions (IRa and IRb) comprising 24,982 bp, a large single-copy (LSC) region comprising 82,740 bp, and a small single-copy (SSC) region comprising 18,466 bp. A total of 130 genes were identified in the chloroplast genome of B. balsamifera, including 85 protein-coding, 37 transfer RNA, and 8 ribosomal RNA genes; furthermore, sequence analysis identified 53 simple sequence repeats. Whole chloroplast genome comparison indicated that the inverted regions (IR) were more conserved than large single-copy and SSC regions. Phylogenetic analysis showed that B. balsamifera is closely related to Pluchea indica. Conclusively, the chloroplast genome of B. balsamifera was helpful for species identification and analysis of the genetic diversity and evolution in the genus Blumea and family Asteraceae.

Abstract Objective: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). Methods: The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson’s staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors. Alterations in the fibrous actin (F-actin) content and organization and the expression of β-catenin were detected by flow cytometry, immunofluorescence, and Western blotting. Additionally, the association of DACT1 with gap junctions connexin 43 (Cx43) was detected by immunohistochemistry, immunofluorescence, and Western blotting. Results: Decreased cytoplasmic DACT1 expression in the myocardium was associated with AF (P=0.037) and a high degree of fibrosis (weak vs. strong, P=0.028; weak vs. very strong, P=0.029). A positive association was observed between DACT1 and β-catenin expression in clinical samples (P=0.028, Spearman’s rho=0.408). Furthermore, overexpression of DACT1 in HL-1 and H9C2 cells induced an increase in β-catenin and subsequent partial colocalization of DACT1 and β-catenin. In addition, F-actin content and organization were enhanced. Interestingly, DACT1 was positively correlated with the Cx43 expression in clinical samples (P=0.048, Spearman’s rho=0.370) and changed the Cx43 distribution in cardiac cell lines. Conclusion: DACT1 proved to be a novel AF-related gene by regulating Cx43 via cytoskeletal organization induced by β-catenin accumulation in cardiomyocytes. DACT1 could thus serve as a potential therapeutic marker for AF.

RESUMO OBJETIVO O diabetes é um fator de risco para a lesão renal aguda (LRA). No entanto, seu mecanismo de patogênese não foi elucidado. O objetivo do estudo foi investigar o papel da inflamação e do receptor Toll-like 7 (TLR7) na LRA isquêmica no diabetes. MÉTODOS Um modelo de hipóxia-reoxigenação de células epiteliais tubulares renais humanas (HK-2) na presença de concentrações altas de glicose foi utilizado para gerar LRA induzida por isquemia-reperfusão em diabetes. A atividade das células foi medida pelo ensaio Cell Counting Kit-8 (CCK-8) e pela atividade da lactato desidrogenase (LDH). As citocinas inflamatórias foram avaliadas por ensaio imunoenzimático (Elisa). A expressão de TLR7, do fator de diferenciação mieloide 88 (MyD88) e do fator de transcrição nuclear-κB (NF-κB) foi examinada por Western blotting. A apoptose foi avaliada por citometria de fluxo. RESULTADOS Os grupos glicose alta e glicose baixa foram submetidos à hipóxia-reoxigenação. O grupo de baixa glicose desenvolveu apenas danos celulares ligeiros, apoptose e uma resposta inflamatória. Em contraste, no grupo de alta glicose, uma lesão equivalente de hipóxia-reoxigenação provocou danos celulares graves, apoptose e uma resposta inflamatória. A expressão de TLR7 e suas proteínas relacionadas foi medida no grupo de alta glicose antes e após a hipóxia-reoxigenação. O grupo de alta glicose exibiu maiores aumentos na expressão de TLR7 após hipóxia-reoxigenação do que o grupo de baixa glicose. Além disso, a expressão de TLR7 e suas proteínas relacionadas após a hipóxia-reoxigenação foi maior no grupo com alto nível de glicose do que no grupo com baixo nível de glicose. A inibição do TLR7 fornece proteção significativa contra a lesão isquêmica no diabetes. CONCLUSÃO Nossos resultados sugerem que o diabetes aumenta a vulnerabilidade à lesão renal induzida por isquemia. Essa vulnerabilidade acrescida tem por origem uma resposta inflamatória aumentada envolvendo a via de transdução de sinal do TLR7.

SUMMARY OBJECTIVE Diabetes is a risk factor for acute kidney injury (AKI). However, its mechanism of pathogenesis has not been elucidated. The aim of the study was to investigate the role of inflammation and the toll-like receptor 7 (TLR7) in ischemic AKI for diabetes. METHODS A high glucose hypoxia-reoxygenation model of human renal tubular epithelial (HK-2) cells was used to generate AKI induced by ischemia-reperfusion in diabetes. The activity of cells was measured by CCK-8 assay and LDH activity. Inflammatory cytokines were assessed by ELISA. TLR7, MyD88, and NF-κB expressions were examined by western blotting. Apoptosis was evaluated by flow cytometry. RESULTS The high glucose group and low glucose group were subjected to hypoxia-reoxygenation. The low glucose group developed only mild cell damage, apoptosis, and inflammatory response. In contrast, an equivalent hypoxia-reoxygenation injury provoked severe cell damage, apoptosis, and inflammatory response in the high glucose group. Expression of TLR7 and its related proteins were measured in the high glucose group before and after hypoxia-reoxygenation. The high glucose group exhibited more significant increases in TLR7 expression following hypoxia-reoxygenation than the low glucose group. In addition, the expression of TLR7 and its related proteins after hypoxia-reoxygenation were higher in the high glucose group than in the low glucose group. Inhibition of TLR7 provides significant protection against ischemic injury in diabetes. CONCLUSION Our results suggest that diabetes increases the vulnerability to ischemia-induced renal injury. This increased vulnerability originates from a heightened inflammatory response involving the TLR7 signal transduction pathway.

Abstract The aim of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the osteogenic differentiation of dental follicle cells (DFCs) in vitro and on the regenerative effects of DFC-OsteoBoneTM complexes in vivo. DFCs were isolated and characterized. In the in vitro study, DFCs were cultured in an osteogenic medium in the presence or absence of LIPUS. The expression levels of ALP, Runx2, OSX, and COL-I mRNA were analyzed using real-time polymerase chain reaction (RT-PCR) on day 7. Alizarin red staining was performed on day 21. The state of the growth of the DFCs that were seeded on the scaffold at 3, 5, 7, and 9 days was detected by using a scanning electron microscope. In our in vivo study, 9 healthy nude mice randomly underwent subcutaneous transplantation surgery in one of three groups: group A, empty scaffold; group B, DFCs + scaffold; and group C, DFCs + scaffold + LIPUS. After 8 weeks of implantation, a histological analysis was performed by HE and Mason staining. Our results indicate that LIPUS promotes the osteogenic differentiation of DFCs by increasing the expression of the ALP, Runx2, OSX, and COL-I genes and the formation of mineralized nodules. The cells can adhere and grow on the scaffolds and grow best at 9 days. The HE and Mason staining results showed that more cells, fibrous tissue and blood vessels could be observed in the DFCs + scaffold + LIPUS group than in the other groups. LIPUS could promote the osteogenic differentiation of DFCs in vitro and promote tissue regeneration in a DFCs-scaffold complex in vivo. Further studies should be conducted to explore the underlying mechanisms of LIPUS.

Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.

RESUMO OBJETIVO: Este estudo revisou retrospectivamente 46 casos de tumores gástricos estromáticos gastrointestinais tratados por microcirurgia endoluminal endoscópica de ressecção completa (EFR) em nosso centro de endoscopia gastrointestinal. Pretendemos avaliar a EFR para o tratamento de tumores gastrointestinais estromáticos originários da muscularis própria. MÉTODOS: Um total de 46 pacientes com tumores gástricos estromáticos gastrointestinais originários da camada muscular própria, de janeiro de 2012 a junho de 2015, foi tratado com EFR. Os pacientes foram acompanhados com gastroscópio e tomografia computadorizada (TC) para avaliação de efeitos terapêuticos e segurança. RESULTADOS: A EFR foi realizada com sucesso para remover todos os tumores em 46 pacientes. O tempo médio de procedimento foi de 82,5±39,8 min (56-188 min). Exceto em três leiomiomas, exame patológico confirmou tumor estromal gastrointestinal (Gist) em 43 casos. Em nenhum paciente ocorreu sangramento, peritonite e outras complicações após EFR. Posteriormente, todos os pacientes foram acompanhados com gastroscópio após um, seis e 12 meses. CONCLUSÕES: A EFR é eficaz e segura para pacientes com tumores gastrointestinais originários da camada muscular própria e tem a vantagem de ser um tratamento menos invasivo e com maior taxa de ressecção tumoral. Deve ser considerada para posterior aplicação.

SUMMARY OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56-188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastro-scope after 1, 6,12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.

Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.

Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.

RESUMEN El agua al interior de las minas es una amenaza para la minería de carbón. La cantidad del agua en las minas se detecta al perforar en las vías del socavón, con la desventaja de la carga de trabajo y la baja eficacia que significan. Por esto, el presente trabajo propone el Método Electromagnético Transitorio (TEM, del inglés Transient Electromagnetic Method) y utiliza la información generada para detectar las propiedades de producción de agua en una capa específica de una mina de carbón. A través de un sistema de observación tridimensional TEM orientado a minas se puede obtener la señal del voltaje inducido. La capacidad de la información del sistema TEM tridimensional se puede calcular al obtener la resistividad y la conversión tiempo-profundidad. Tan pronto se establece el valor apropiado de la resistividad aparente se puede determinar el rango de distribución de un acuífero. Luego, con el coeficiente de saturación del acuífero se puede calcular la cantidad de agua. Los resultados de la detección de las propiedades de producción de agua en la mina abandonada número cuatro de frente de trabajo número 80101 de la mina Jude, en Shanxi, China, demostró que la resistividad aparente de esta excavación es de 3 Q.m, y el área de proyección de la zona anómala de baja resistividad es 22.383 m2. Al usar la fórmula Q=KMS, se estimó que el volumen de agua es de 33,574 m3. Tres pozos se han construido para el próximo proyecto de dragado y drenaje, cuyos resultados de producción de agua es de 33,089 m3. El porcentaje de error de la predicción de la cantidad de agua es menor al 1.5 %. Se concluye, por ende, que es factible producir el contenido de agua de un acuífero con la información del TEM.

ABSTRACT Mine water is a menace to coal mining. Mine water quantity is detected by drilling in the coal mine roadway, and the disadvantage is the high workload and low efficiency. Therefore, transient electromagnetic method (TEM) was proposed, and TEM data was processed to detect the water yield property of a targeted layer in the coal mine. Through a mine-oriented 3D Transient Electromagnetic Method observing system, the signal of induced voltage is obtainable. Transient Electromagnetic Method 3D data volume can be calculated through the calculation of all-time resistivity and time-depth conversion. After an appropriate apparent resistivity value is set, the spatial distribution range of an aquifer can be determined. Then, with the water-filling coefficient of the aquifer, its water quantity can be estimated. The water yield property detection results in the No.4 coal seam goaf of the No.80101 workface in Jude Mine of Shanxi, China, demonstrates that the apparent resistivity of this goaf is less than 3 Ω.m, and the projection area of low resistivity anomaly zone is 22,383 m2. By using the formula Q=KMS, we can estimate that the water volume is 33,574 m3. Three boreholes have been constructed for the next dredging and drainage project, which results in a total water yield of 33,089 m3. The error percentage of the predicted water quantity is less than 1.5%. It can thus be concluded that it is feasible to predict aquifer water content with TEM data.

ABSTRACT To establish a transfusion-associated graft-versus-host disease (TA-GVHD) mouse model with busulfan and fludarabine for effective treatment evaluation. BALB/c (H-2d) mice were injected with busulfan (15 mg/kg) and fludarabine (30 mg/kg) twice a day for 4 days. The mice were transfused with 106 T cell-depleted bone marrow (TCD-BM )and cells in different groups 3 days after chemotherapy: syngeneic BALB/c, MHC minor mismatch DBA/2 (H-2d), or MHC major mismatch C57BL/6(H2-b). Recipient BALB/c mice were injected with either blood only or blood+splenocyte. TA-GVHD was monitored in terms of body weight loss, clinical scores, and survival. Dexamethasone (50 mg/kg), cyclophosphamide (50 mg/kg), cyclosporine A (30 mg/kg), and anti-CD3 (1 mg/kg) were injected to each group to examine the treatments. Blood transfusion alone is insufficient to induce TA-GVHD in a chemotherapy-based mouse model. A MHC-mismatched TA-GVHD model can be induced by splenocyte and blood transfusion. This MHC-mismatched TA-GVHD model was resistant to dexamethasone treatment. Treatment based on anti-CD3 monoclonal antibody slightly ameliorated TA-GVHD. Treatment effectiveness was associated with T-cell depletion following activation by anti-CD3. Busulfan and fludarabine chemotherapy regimen can be used to establish a TA-GVHD mouse model. Anti-CD3 monoclonal antibody is a potential alternative to treat TA-GVHD.