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IntroductionAPOL1 G1 and G2 nephropathy-risk variants cause mitochondrial dysfunction and contribute to kidney disease. Analyses were performed to determine the genetic regulation of APOL1 and elucidate potential mechanisms in APOL1-nephropathy.MethodsA global gene expression analysis was performed in human primary renal tubule cell lines derived from 50 African American individuals. Follow-up gene knock out, cell-based rescue, and microscopy experiments were performed.ResultsAPOL1 genotypes did not alter APOL1 expression levels in the global gene expression analysis. Expression quantitative trait locus (eQTL) analysis in polyinosinic-polycytidylic acid (poly IC)-stimulated renal tubule cells revealed that single nucleotide polymorphism (SNP) rs513349 adjacent to BAK1 was a trans eQTL for APOL1 and a cis eQTL for BAK1; APOL1 and BAK1 were co-expressed in cells. BAK1 knockout in a human podocyte cell line resulted in diminished APOL1 protein, supporting a pivotal effect for BAK1 on APOL1 expression. Because BAK1 is involved in mitochondrial dynamics, mitochondrial morphology was examined in primary renal tubule cells and HEK293 Tet-on cells of various APOL1 genotypes. Mitochondria in APOL1 wild-type (G0G0) tubule cells maintained elongated morphology when stimulated by low-dose poly IC, whereas those with G1G1, G2G2, and G1G2 genotypes appeared to fragment. HEK293 Tet-on cells overexpressing APOL1 G0, G1, and G2 were created; G0 cells appeared to promote mitochondrial fusion, whereas G1 and G2 induced mitochondrial fission. The mitochondrial dynamic regulator Mdivi-1 significantly preserved cell viability and mitochondrial cristae structure and reversed mitochondrial fission induced by overexpression of G1 and G2.ConclusionResults suggest the mitochondrial fusion/fission pathway may be a therapeutic target in APOL1-nephropathy.

Stem cell-mediated bio-root regeneration is an alternative tooth replacement strategy; however, physiologically functional bio-root regeneration with distinctive dentin structure remains challenging. In this study, the distinct arrangements of collagen fibril bundles were identified that account for hierarchical structural differences between dentin, cementum, and alveolar bone. Thus, an "engineered pre-dentin" was fabricated, which was a dentin hierarchical structure mimicking collagen (MC) scaffold, with well-aligned hierarchical mineralized collagen fibril bundles. The results revealed that it has a stronger effect on promoting biological root regeneration in nude mice and miniature pigs with dental pulp stem cell (DPSC) and periodontal ligament stem cell (PDLSC) sheets compared to hydroxyapatite tricalcium phosphate (HA/TCP). The success rate in the MC group was also higher than that in the HA/TCP group (67% and 33%, respectively). In conclusion, the hierarchical dentin-mimicking scaffold can enhance the regeneration of bio-roots, which provides a promising strategy for tooth regeneration. [ABSTRACT FROM AUTHOR]

In order to evaluate the safety of tebuconazole as a fungicide in bananas, after a simple and rapid pre-treatment, the residues of tebuconazole in different parts of banana were detected by high-performance liquid chromatography (HPLC) within 35 days. The mean recoveries and relative standard deviations in banana samples were 87.17 ~ 96.68% and 2.85 ~ 8.49%, respectively. The half-lives of tebuconazole in whole banana, banana pulp, and banana peel were 7.31 ~ 8.68 days, 11.12 ~ 13.39 days, and 4.06 ~ 5.74 days, respectively. It can be seen that tebuconazole dissipated fastest in the peel and slowest in the pulp. And the contents of tebuconazole in banana pulp and banana peel were 3 ~ 35% and 65 ~ 97%, respectively, which can be seen that tebuconazole was mainly distributed in the peel, and only a small part was transmitted to the pulp. Results also showed that the residual amounts of tebuconazole in banana pulp were increased at the first three days and then gradually dissipated, and were below the maximum residue limit (MRL) in China. The results of dietary intake risk assessment showed that the HQ (hazard quotient) were 0.45 ~ 2.69%, which were within the acceptable range. Overall, our research results show that tebuconazole in the field control of banana freckle disease has high security and low risk with the application dose of 133 g/L and diluted 1000 times in water, and can provide an important reference for the rational use of tebuconazole as a systemic fungicide in the field. [ABSTRACT FROM AUTHOR]

Adopting retrospective verbal report, or RVR as the instrument, this study reports an analysis of the perceptions of native-English-speaking (NES) and non-native-English-speaking (NNES) students, who apologised to their instructors in coursework-related situations. Sixty NESs from different levels and disciplinary areas and 63 NNESs (Arabic and Chinese L1s) from an Intensive English programme were sampled to represent the student population in a US university. Each participant was asked to complete a discourse completion task (DCT) in response to three apology situations, and this resulted in a total of 369 apology messages. A RVR was conducted immediately following the completion of the DCT. Students' perceptions gathered through the RVR were categorised according to four factors, including apology strategy use, professionalism, contextual variables, and language use. Results showed that NES and NNES students had different considerations in producing institutional apologies. For example, multiple NES students addressed the severity of the apology situations, which was not mentioned at all by NNES students. Both groups reported having minimal or no instruction on how apologies should be made in academic communication, an area that warrants pedagogical interventions.

The safety and risk of fosthiazate as nematicide in cucumber field were evaluated in this study. An analytical method for determining the residues of fosthiazate in cucumber was developed. Mean recoveries and relative standard deviations in all samples ranged 85.3 ~ 95.0% and 5.7 ~ 13.3%. The half-lives of fosthiazate in cucumber root, leaf and fruit were 4.71 ~ 5.50 days, 3.52 ~ 4.78 days and 3.32 ~ 3.96 days. The residues in cucumber fruits were below the maximum residue limit (MRL) in China, based on the application dose of 900 g a.i./ha and the pre-harvest interval of 14 days. The transfer rates of fosthiazate from cucumber root to leaf were 17.48 ~ 46.03%, which were significantly higher than those of root to fruit (8.81 ~ 26.52%). These results indicated that fosthiazate was mainly distributed in cucumber root, and it was difficult to be absorbed by the fruit compared to the leaf. The long-term dietary intake risk assessment results showed that the risk quotient (RQ) ranged 20.04 ~ 36.25% and were less than 100%, which indicated that fosthiazate has a low risk for long-term dietary intake of cucumbers. Overall, our results would be considered as important references for safe and reasonable use of fosthiazate, monitoring and assessing the food safety, and protecting consumer health. [ABSTRACT FROM AUTHOR]