Abstract
Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role ...and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.
Abstract
The separation of xylene isomers (
para
-,
meta
-,
orth
-) remains a great challenge in the petrochemical industry due to their similar molecular structure and physical properties. Porous ...materials with sensitive nanospace and selective binding sites for discriminating the subtle structural difference of isomers are urgently needed. Here, we demonstrate the adaptively molecular discrimination of xylene isomers by employing a NbOF
5
2−
-pillared metal–organic framework (NbOFFIVE-bpy-Ni, also referred to as ZU-61) with rotational anionic sites. Single crystal X-ray diffraction studies indicate that ZU-61 with guest-responsive nanospace/sites can adapt the shape of specific isomers through geometric deformation and/or the rotation of fluorine atoms in anionic sites, thereby enabling ZU-61 to effectively differentiate xylene isomers through multiple C–H···F interactions. ZU-61 exhibited both high
meta
-xylene uptake capacity (3.4 mmol g
−1
) and
meta
-xylene/
para
-xylene separation selectivity (2.9, obtained from breakthrough curves), as well as a favorable separation sequence as confirmed by breakthrough experiments:
para
-xylene elute first with high-purity (≥99.9%), then
meta
-xylene, and
orth
-xylene. Such a remarkable performance of ZU-61 can be attributed to the type anionic binding sites together with its guest-response properties.
The role of ferroptosis in tumor development and therapy has been previously proved. Nonetheless, its potential role in tumor microenvironment (TME) and immunotherapy for bladder carcinoma remains ...unclear. Based on 38 ferroptosis-related genes, the characteristic of ferroptosis patterns and interactions with immune cell-infiltrating features in 2043 bladder cancer samples were systematically investigated. We further proposed the FerrScore to quantify the ferroptosis patterns for each patient. As results, three diverse ferroptosis patterns with distinct tumor-infiltrating immune cell features were established. By determination of ferroptosis patterns of each patient, we found that high FerrScore was related to lower proportion of luminal-papillary molecular subtype, more frequent TP53 mutations, activation of immunity and stroma, and lower 5-year survival. High FerrScore also seemed to be associated with decreased neoantigen load, tumor mutational burden and poorer response to anti-PD-L1/1 therapy. External verification in two immunotherapy cohorts showed FerrScore was an independent and effective prognostic factor for therapeutic effect and survival outcome. Overall, the present study indicated the ferroptosis strongly is closely correlated with TME diversity. Evaluation of the ferroptosis patterns may strengthen the cognition of TME immune cell infiltrations and guide more individualized immunotherapeutic strategies in bladder carcinoma.
Stem cell therapy may replace lost photoreceptors and preserve residual photoreceptors during retinal degeneration (RD). Unfortunately, the degenerative microenvironment compromises the fate of ...grafted cells, demanding supplementary strategies for microenvironment regulation. Donor cells with both proper regeneration capability and intrinsic ability to improve microenvironment are highly desired. Here, we use cell surface markers (C-Kit
/SSEA4
) to effectively eliminate tumorigenic embryonic cells and enrich retinal progenitor cells (RPCs) from human embryonic stem cell (hESC)-derived retinal organoids, which, following subretinal transplantation into RD models of rats and mice, significantly improve vision and preserve the retinal structure. We characterize the pattern of integration and materials transfer following transplantation, which likely contribute to the rescued photoreceptors. Moreover, C-Kit
/SSEA4
cells suppress microglial activation, gliosis and the production of inflammatory mediators, thereby providing a healthier host microenvironment for the grafted cells and delaying RD. Therefore, C-Kit
/SSEA4
cells from hESC-derived retinal organoids are a promising therapeutic cell source.
Unmanned aerial vehicle (UAV)-based remote sensing provides a flexible, low-cost, and efficient approach to monitor crop growth status at fine spatial and temporal resolutions, and has a high ...potential to accelerate breeding process and improve precision field management.
In this study, we discussed the use of lightweight UAV with dual image-frame snapshot cameras to estimate aboveground biomass (AGB) and panicle biomass (PB) of rice at different growth stages with different nitrogen (N) treatments. The spatial-temporal variations in the typical vegetation indices (VIs) and AGB were first investigated, and the accuracy of crop surface model (CSM) extracted from the Red Green Blue (RGB) images at two different stages were also evaluated. Random forest (RF) model for AGB estimation as well as the PB was then developed. Furthermore, variable importance and sensitivity analysis of UAV variables were performed to study the potential of improving model robustness and prediction accuracies.
It was found that the canopy height extracted from the CSM (Hcsm) exhibited a high correlation with the ground-measured canopy height, while it was unsuitable to be independently used for biomass assessment of rice during the entire growth stages. We also observed that several VIs were highly correlated with AGB, and the modified normalized difference spectral index extracted from the multispectral image achieved the highest correlation. RF model with fusing RGB and multispectral image data substantially improved the prediction results of AGB and PB with the prediction of root mean square error (RMSEP) reduced by 8.33-16.00%. The best prediction results for AGB and PB were achieved with the coefficient of determination (r
), the RMSEP and relative RMSE (RRMSE) of 0.90, 0.21 kg/m
and 14.05%, and 0.68, 0.10 kg/m
and 12.11%, respectively. In addition, the result confirmed that the sensitivity analysis could simplify the prediction model without reducing the prediction accuracy.
These findings demonstrate the feasibility of applying lightweight UAV with dual image-frame snapshot cameras for rice biomass estimation, and its potential for high throughput analysis of plant growth-related traits in precision agriculture as well as the advanced breeding program.
The production and application of nanomaterials have grown tremendously during last few decades. The widespread exposure of nanoparticles to the public is provoking great concerns regarding their ...toxicity to the human body. However, in comparison with the extensive studies carried out to examine nanoparticle toxicity to the human body/organs, one especially vulnerable organ, the eye, is always neglected. Although it is a small part of the body, 90% of outside information is obtained via the ocular system. In addition, eyes usually directly interact with the surrounding environment, which may get severer damage from toxic nanoparticles compared to inner organs. Therefore, the study of assessing the potential nanoparticle toxicity to the eyes is of great importance. Here, the recent advance of some representative manufactured nanomaterials on ocular toxicity is summarized. First, a brief introduction of ocular anatomy and disorders related to particulate matter exposure is presented. Following, the factors that may influence toxicity of nanoparticles to the eye are emphasized. Next, the studies of representative manufactured nanoparticles on eye toxicity are summarized and classified. Finally, the limitations that are associated with current nanoparticle‐eye toxicity research are proposed.
This work covers the recent advances of toxicity of nanomaterials to eyes. It starts with an introduction of eye anatomy and disorders related to particulate matter exposure. Next, the factors that may influence toxicity of nanoparticles to the eyes and studies of representative manufactured nanomaterials on eye toxicity are summarized. Finally, the limitations that are associated with this field are proposed.
Previous surgical strategy of transperitoneal laparoscopic partial nephrectomy (TLPN) and retroperitoneal laparoscopic partial nephrectomy (RLPN) for treatment of renal cell carcinoma (RCC) mainly ...depend on surgeons' preference. The aim of this study was to evaluate whether performing TLPN for anterior tumors and RLPN for posterior tumors is a more beneficial strategy.
214 patients underwent TLPN or RLPN at our center were retrospectively collected and 1:1 matched for surgical approach, tumor complexity as well as operator. Baseline characteristics and perioperative outcomes were evaluated and compared, respectively.
Regardless of tumor location, RLPN was associated with a faster operative time, a quicker time to first oral intake and hospital discharge compared to TLPN approach while other baseline and perioperative outcomes were comparable between groups. After taking tumor location into consideration, TLPN has an advantage in operating time (109.8
115.3 mins, p = 0.03) and ischemic time (20.3
24.1 mins, p = 0.001) for anterior tumor, while RLPN has an advantage in operating time (103.5
116.3 mins, p<0.001), ischemic time (21.8
24.8 mins, p = 7 0.001) and estimated blood loss (65.5
85.4 ml, p = 0.01) for posterior tumor.
The selection of approach should be also dependent of the tumor location, instead of only dependent of surgeons' experience or preference.
Remote estimation of flower number in oilseed rape under different nitrogen (N) treatments is imperative in precision agriculture and field remote sensing, which can help to predict the yield of ...oilseed rape. In this study, an unmanned aerial vehicle (UAV) equipped with Red Green Blue (RGB) and multispectral cameras was used to acquire a series of field images at the flowering stage, and the flower number was manually counted as a reference. Images of the rape field were first classified using K-means method based on Commission Internationale de l’Éclairage (CIE) L*a*b* space, and the result showed that classified flower coverage area (FCA) possessed a high correlation with the flower number (r2 = 0.89). The relationships between ten commonly used vegetation indices (VIs) extracted from UAV-based RGB and multispectral images and the flower number were investigated, and the VIs of Normalized Green Red Difference Index (NGRDI), Red Green Ratio Index (RGRI) and Modified Green Red Vegetation Index (MGRVI) exhibited the highest correlation to the flower number with the absolute correlation coefficient (r) of 0.91. Random forest (RF) model was developed to predict the flower number, and a good performance was achieved with all UAV variables (r2 = 0.93 and RMSEP = 16.18), while the optimal subset regression (OSR) model was further proposed to simplify the RF model, and a better result with r2 = 0.95 and RMSEP = 14.13 was obtained with the variable combination of RGRI, normalized difference spectral index (NDSI (944, 758)) and FCA. Our findings suggest that combining VIs and image classification from UAV-based RGB and multispectral images possesses the potential of estimating flower number in oilseed rape.
Circular RNAs (circRNAs) are involved in the pathogenesis of certain renal diseases, however, the function and mechanism of them in renal fibrosis remains largely unknown. In the present study, RNA ...expression data in unilateral ureteral obstruction (UUO) kidneys was obtained from our previous circRNA Microarray and public Gene Expression Omnibus datasets to construct a ceRNA network. The effects of target circRNA as long as the homologous human circRNA on renal fibrosis was examined in vitro and in vivo. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was further performed among genes regulated by the human circRNA. We found that circRNA_37492, showing well connection degree in the ceRNA network, was abundant expression and high sequence conservation. We observed that the expression of circRNA_37492 was induced by the TGF-β1 or UUO in BUMPT cells and C57BL/6 mice, respectively. In vitro, cytoplasmic circRNA_37492 inhibited type I, III collagen and fibronectin deposition by sponging miR-7682-3p and then upregulated its downstream target Fgb. In vivo, overexpression of circRNA_37492 attenuated fibrotic lesions in the kidneys of UUO mice via targeting miR-7682-3p/Fgb axis. Furthermore, hsa_circ_0012138, homologous with circRNA_37492, may potentially target miR-651-5p/FGB axis in human renal fibrosis. Not only that, GO and KEGG enrichment revealed that hsa_circ_0012138-regulated genes were previously demonstrated to related to the fibrosis. In conclusion, we for the first time demonstrated that circRNA_37492 attenuated renal fibrosis via targeting miR-7682-3p/Fgb axis, and the homologous hsa_circRNA_0012138 was speculated as a possible ceRNA to regulate multiple gene expressions and involve in human renal fibrosis, suggesting that circRNA_37492/hsa_circ_0012138 may serve as potent therapy target for obstructive renal fibrosis disease.
Abstract As transcatheter aortic valve replacement (TAVR) has become an alternative treatment for patients at high risk for surgical aortic valve replacement (SAVR), bicuspid aortic valve (BAV) draw ...our attention again. The reported frequency of BAV was between 0.5% to 2% in western population. However, there was no such epidemiologic study in Chinese population. Our study sought to investigate the prevalence and complications of BAV in China by echocardiographic database. A total of 668 cases who were confirmed with bicuspid aortic valve, identified from 195,708 echocardiographic records of 157,039 patients in the echocardiographic database of West China Hospital (between June 2008 and June 2012), were analyzed retrospectively. The incidence of BAV was 0.43% in the cohort, and 579 (86.68%) patients were complicated by various degree of aortic valve stenosis or aortic valve regurgitation. The incidence of infective endocarditis and aortic dissection was 0.68% episodes per patient-years with mean age of 42.96 ± 11.25 years old and 0.18% episodes per patient-years with mean age of 43.00 ± 5.14 years old, respectively. In conclusion, our study demonstrated that the prevalence of bicuspid aortic valve and complications in Chinese were similar to that in the western population.
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