Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation.

Objectives: The implanted electrodes deliver electric signals to spiral ganglion neurons, conferring restored hearing of cochlear implantation (CI) recipients. Postimplantation intracochlear fibrosis, which is observed in most CI recipients, disturbs the electrical signals and impairs the long-term outcome of CI. The macrophages and fibroblasts activation is critical for the development of intracochlear fibrosis. However, the effect of electric stimulation of cochlear implant (ESCI) on the activity of macrophages and fibroblasts was unclear. In the present study, a human cochlear implant was modified to stimulate cultured macrophages and fibroblasts. Methods: By measuring cellular marker and the expression level of cytokine production, the polarization and activity of macrophages and fibroblasts were examined with or without ESCI. Results: Our data showed that ESCI had little effects on the morphology, density, and distribution of culturing macrophages and fibroblasts. Furthermore, ESCI alone did not affect the polarization of macrophages or the function of fibroblasts without the treatment of inflammatory factors. However, in the presence of LPS or IL-4, ESCI further promoted the polarization of macrophages, and increased the expression of pro-inflammatory or anti-inflammatory factors, respectively. For fibroblasts, ESCI further increased the collagen I synthesis induced by TGF-ß1 treatment. Nifedipine inhibited ESCI induced calcium influx, and hereby abolished the promoted polarization and activation of macrophages and fibroblasts. Conclusion: Our results suggest that acute inflammation should be well inhibited before the activation of cochlear implants to control the postoperative intracochlear fibrosis. The voltage-gated calcium channels could be considered as the targets for reducing postimplantation inflammation and fibrosis. Level of Evidence: NA.

Evaluation of climate factors affecting the quality of red huajiao (Zanthoxylum bungeanum maxim.) based on UPLC-MS/MS and MaxEnt model.

Through field investigation, UPLC-MS/MS technology and MaxEnt model were performed to predict the suitable distribution area for red huajiao (Zanthoxylum bungeanum maxim.) in China from 2021 s to 2060 s, and evaluate the effects of climate factors on the quality of red huajiao. The results demonstrated that mean temperature of the coldest quarter and min temperature of the coldest month were the most important environmental variables influencing red huajiao distribution. Suitable habitats for red huajiao were located mainly in dry and hot valley zone in the Qinba Mountains and the semi-humid and semi-arid areas of the Loess Plateau. The amides contents were higher in high suitability areas, while it was decreased in medium and low suitability areas, and temperature, wind speed and precipitation played a key role in their accumulation. This investigation was of great significance for the planting area optimization, quality control, benefit improvement and industrial development of red huajiao.

Evaluating the Impacts of Climate Factors and Flavonoids Content on Chinese Prickly Ash Peel Color Based on HPLC-MS and Structural Equation Model.

Climate affects Chinese prickly ash peel color directly through temperature and illumination and indirectly influences it through its effect on flavonoid compounds. In this study, a comprehensive evaluation strategy based on high performance liquid chromatography-mass spectrometry (HPLC-MS) technology and a structural equation model was applied to evaluate the effects of climate factors and flavonoids on Chinese prickly ash peel color. There were obvious geographical variations of peel color and flavonoid compounds with an obvious east-west distribution trend which were divided into high-altitude type and low-altitude type. Through path analysis, the wind speed, temperature and annual sunshine duration were found to be the key environmental factors affecting the flavonoids content and peel color, and their direct effects were higher than their indirect effect. Based on HPLC-MS technology and a structural equation model, correlation models of climatic factors and flavonoids with peel color were established, and the factors that had greater weight on pericarp color were obtained. Our results provide experimental evidence that climate factors affect the peel color by affecting flavonoid biosynthesis and accumulation, reveal the geographical variation of peel color and flavonoid component contents in Chinese prickly ash peel, establish a quantization color method for rapid evaluation of peel quality, expand on the influence of climatic factors on flavonoids content and peel coloration and promote agricultural practice in areas with similar climatic conditions.

Populations of Puccinia striiformis f. sp. tritici in Winter Spore Production Regions Spread from Southwestern Oversummering Areas in China.

Stripe rust, caused by Puccinia striifomis f. sp. tritici (Pst), is one of the most destructive wheat diseases in China. Understanding the interregional dispersal of Pst inoculum is important for controlling the disease. In the present study, wheat stripe rust samples collected from the winter spore production and oversummering regions in November 2018 to March 2019 were studied through virulence testing and molecular characterization. From 296 isolates, 96 races were identified using a set of 19 Chinese wheat cultivars and 111 races were identified using 18 Yr single-gene lines as differentials. The isolates from Hubei province in the winter spore production area had the highest similarity in virulence with those from eastern Yunnan in the oversummering area. Molecular characterization using 13 simple-sequence repeat and 43 Kompetitive allele specific PCR-single nucleotide polymorphism markers supported the conclusion that the Pst populations in the winter spore production regions were from Guizhou and eastern Yunnan, key oversummering areas in the southwest. Furthermore, an analysis of wind movement at the 700-hPa high altitude also supported the conclusion of spore dispersal from the southwestern oversummering region to the south-central winter spore production region. The results of this study provide an epidemiological basis for deploying various effective resistance genes in different regions to control stripe rust.

Quality Evaluation of Wild Germplasm of Chinese Prickly Ash (Zanthoxylum bungeanum Maxim) from Qinling Mountains at Different Elevations Based on HPLC-Fingerprint.

Wild Chinese prickly ash resources provide a valuable genetic resource for Zanthoxylum bungeanum Maxim improvement and breeding. The Qinling Mountains was an abundant source for wild Chinese prickly ash. In this study, the phenolic and flavonoid compounds of wild germplasm resources from different altitudes and six cultivated varieties were analyzed by high performance liquid chromatography (HPLC). The chromatograms of them were essentially consistent, although their chemical composition contents were greatly different. The thirty samples were divided into three categories through the hierarchical clustering analysis. Catechin, hyperoside and quercitrin were considered to be key compounds for the quality evaluation, and by contrast, the wild samples with an altitude of 2300±50 m (Group IV) had the highest content of key compounds, and presented stronger antioxidant activity and antibacterial ability, indicating that these wild samples could be identified as the excellent breeding resources. This is the first time to evaluate the quality of wild Chinese prickly ash at different altitudes in Qinling Mountains. These excellent wild germplasm resources provided substantial potential accessions for use directly in Chinese prickly ash breeding programs.

Chemotaxonomic variation in volatile component contents and their correlation between climate factors in Chinese prickly ash peels (Zanthoxylum bungeanum Maxim.).

In this study, we analyzed the characteristics of volatile compounds of Chinese prickly ash peels with different climate conditions and their correlation. The data revealed that the contents of limonene and linalool in peels from southwest and northwest regions were higher, and the aroma was stronger, while the contents of ß-myrcene and (E)-ocimene in them from north, east and central China were higher, and the spicy flavor was heavier. Hierarchical cluster analysis demonstrated that the classification had geographical continuity. Through the correlation analysis and path analysis, it was found that the contents of volatile compounds were closely related to the climatic factors. The influence of wind speed and annual average temperature on volatile substances was greater than that of annual average precipitation and annual sunshine duration. This enriched the effect of climatic factors on the accumulation of volatile substances, and promoted the agriculture practices in area having similar climate conditions.

CRIP1 cooperates with BRCA2 to drive the nuclear enrichment of RAD51 and to facilitate homologous repair upon DNA damage induced by chemotherapy.

Homologous recombination (HR) repair is an important determinant of chemosensitivity. However, the mechanisms underlying HR regulation remain largely unknown. Cysteine-rich intestinal protein 1 (CRIP1) is a member of the LIM/double-zinc finger protein family and is overexpressed and associated with prognosis in several tumor types. However, to date, the functional role of CRIP1 in cancer biology is poorly understood. Here we found that CRIP1 downregulation causes HR repair deficiency with concomitant increase in cell sensitivity to cisplatin, epirubicin, and the poly ADP-ribose polymerase (PARP) inhibitor olaparib in gastric cancer cells. Mechanistically, upon DNA damage, CRIP1 is deubiquitinated and upregulated by activated AKT signaling. CRIP1, in turn, promotes nuclear enrichment of RAD51, which is a prerequisite step for HR commencement, by stabilizing BRCA2 to counteract FBXO5-targeted RAD51 degradation and by binding to the core domain of RAD51 (RAD51184-257) in coordination with BRCA2, to facilitate nuclear export signal masking interactions between BRCA2 and RAD51. Moreover, through mass spectrometry screening, we found that KPNA4 is at least one of the carriers controlling the nucleo-cytoplasmic distribution of the CRIP1-BRCA2-RAD51 complex in response to chemotherapy. Consistent with these findings, RAD51 inhibitors block the CRIP1-mediated HR process, thereby restoring chemotherapy sensitivity of gastric cancer cells with high CRIP1 expression. Analysis of patient specimens revealed an abnormally high level of CRIP1 expression in GC tissues compared to that in the adjacent normal mucosa and a significant negative association between CRIP1 expression and survival time in patient cohorts with different types of solid tumors undergoing genotoxic treatments. In conclusion, our study suggests an essential function of CRIP1 in promoting HR repair and facilitating gastric cancer cell adaptation to genotoxic therapy.

Dynamics of vegetation autumn phenology and its response to multiple environmental factors from 1982 to 2012 on Qinghai-Tibetan Plateau in China.

Autumn phenological shifts induced by environmental change have resulted in substantial impacts on ecosystem processes. However, autumn phenology and its multiple related controlling factors have not been well studied. In this study, the spatiotemporal patterns of the end date of the vegetation growing season (EGS) and their multiple controls (climate change, summer vegetation growth and human activities) over the Qinghai-Tibetan Plateau (QTP) were investigated using the satellite-derived normalized difference vegetation index (NDVI) based on GIMMS3g datasets during 1982-2012. The results showed that there was no significant temporal trend in the EGS during the period of 1982-2012. Spatially, there was a notable advancing trend in the southwest region and a delayed trend in the other regions of the QTP during 1982-2000, and this spatial trend was reversed during 2001-2012. We found average temperature, precipitation and sunshine duration of autumn exerted positive effects on EGS on the QTP, while average temperature and sunshine duration of summer exerted negative effects. Our results indicated that vegetation growth in summer tends to induce an earlier EGS in alpine vegetation, whereas summer vegetation degradation could delay the EGS on the QTP. In contrast, moderate grazing delays vegetation browning in autumn, while overgrazing leads to advancement of grass senescence. This study improves our understanding of how multiple environmental variables jointly affect autumn phenology and highlights the importance of biotic controls for autumn phenology on the QTP.