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Hypertensive nephropathy is second only to diabetes for the causation of chronic kidney disease worldwide. As the mortality and morbidity of hypertensive nephropathy keep increasing, it is important to elucidate its pathogenesis and develop new treatment strategies. In this study, an angiotensin II (Ang II)-induced renal cell system was established, and the expression of ubiquitin specific peptidase 1 (USP1) in human kidney (HK-2) cells was found to be regulated by Ang II treatment through quantitative RT-PCR and Western blot assay. The detection of glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and lipid reactive oxygen species (ROS) levels revealed that interference with USP1 reversed Ang II-induced oxidative stress and ferroptosis, which was enhanced by overexpression of USP1. Subsequently, USP1 inhibitor SJB3-019A loaded in MIL-100 and PEGTK was modified to fabricate SJB3-019A@MIL-PEGTK nanoparticles, which was confirmed to exhibit excellent alleviation of hypertension-induced oxidative stress and ferroptosis in renal cells both in vitro and in vivo. Our study identified an important pathogenesis of hypertensive nephropathy and SJB3-019A@MIL-PEGTK nanoparticle was used to develop an effective clinical treatment for hypertensive nephropathy.

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Diabetic nephropathy (DN) is the main cause of end-stage renal disease (ESRD). Bioinformatics technology was adopted to screen and analyze the core genes of early DN to explore its pathogenesis. GSE30528, GSE96804, and GSE30122 chip data were obtained from Gene Expression Omnibus (GEO) database to screen DN and healthy controls for differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional annotation and signaling pathway enrichment; String and Cytoscape were used for protein-protein interaction (PPI) network construction and core gene screening, NCBI-Genes to search the expression profile of core genes. 17 common genes were screened, with 6 genes up-regulated and 11 genes down-regulated. The major functional annotations of differential genes were the generation of precursor metabolites and energy, Immune response, and Phosphorylation. They were concentrated on Focal adhesion, PI3K/Akt signaling pathway, and Human papillomavirus infection pathway. The expressions of VEGFA and THBS1 were down-regulated, while the expressions of ITGB1, MMP7, and SOX9 were up-regulated. The core genes VEGFA and THBS1 were highly expressed in Thyroid and Appendix, but lowly expressed in Testis. MMP7 was highly expressed in the Gall bladder and low in the Adrenal. SOX9 was highly expressed in Thyroid and lowly expressed in the bone marrow. ITGB1 was highly expressed in Fat and low in Pancreas. Bioinformatics technology can mine chip data and present new targets for diagnosing and treating DN, but further verification is needed.

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Bulk nuclear structure properties, such as radii and deformations, leave distinct signatures in the final state of relativistic heavy-ion collisions. Isobaric collisions offer an easy route to establish explicit connections between the colliding nuclei's structure and the observable outcomes. Here, we investigate the effects of nuclear skin thickness and nuclear deformations on the elliptic flow (v_{2}) and its fluctuations in high-energy ^{96}Ru+^{96}Ru and ^{96}Zr+^{96}Zr collisions. Our findings reveal that the difference in skin thickness between these isobars only influences the inherent ellipticity of the collision systems, v_{2}^{rp}. In contrast, differences in nuclear deformations solely impact the fluctuations of v_{2} around v_{2}^{rp}. Hence, we have identified a data-driven method to disentangle the effects of nuclear skin and nuclear deformations, marking a significant step toward assessing the consistency of nuclear phenomena across energy scales.

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Superficial scald is a physiological disorder of fruit, which is easy to occur during long-term cold storage after harvest. Different preharvest bagging treatments (no bagging, polyethylene bagging and non-woven fabric bagging) were used to explore the occurrence mechanism of superficial scald. UHPLC-MS analysis, GC-MS analysis and RNA-seq revealed the influence of the wax of 'Chili' on the occurrence of superficial scald. The wax content and wax components (Lupeol, lup-20(29)-en-3-one, heptacosane, 9-octadecenoic acid, eicosanoic acid, cis-11-eicosenoic acid) were significantly higher in the fruit bagged with non-woven fabric (NWF, with low incidence of superficial scald) than that in fruit bagged with polyethylene (PE, high incidence of superficial scald). Transcriptomics and qRT-PCR data identified a wax synthesis gene, PbKCS10, which exhibited high expression levels in fruit with low of superficial scald. The results of gene function showed that PbKCS10 reduced the occurrence of superficial scald by increasing the wax formation.

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In the hydrodynamic model description of heavy-ion collisions, the elliptic flow v_{2} and triangular flow v_{3} are sensitive to the quadrupole deformation ß_{2} and octupole deformation ß_{3} of the colliding nuclei. The relations between v_{n} and ß_{n} have recently been clarified and were found to follow a simple parametric form. The STAR Collaboration has just published precision v_{n} data from isobaric ^{96}Ru+^{96}Ru and ^{96}Zr+^{96}Zr collisions, where they observe large differences in central collisions v_{2,Ru}>v_{2,Zr} and v_{3,Ru}

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In the hydrodynamic framework of heavy-ion collisions, elliptic flow v_{2} is sensitive to the quadrupole deformation ß of the colliding ions. This enables one to test whether the established knowledge on the low-energy structure of nuclei is consistent with collider data from high-energy experiments. We derive a formula based on generic scaling laws of hydrodynamics to relate the difference in v_{2} measured between collision systems that are close in size to the value of ß of the respective species. We validate our formula in simulations of ^{238}U+^{238}U and ^{197}Au+^{197}Au collisions at top Relativistic Heavy Ion Collider (RHIC) energy, and subsequently apply it to experimental data. Using the deformation of ^{238}U from low-energy experiments, we find that RHIC v_{2} data implies 0.16≲|ß|≲0.20 for ^{197}Au nuclei, i.e., significantly more deformed than reported in the literature, posing an interesting issue in nuclear phenomenology.

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Podocytes are epithelial cells adhering glomerular capillaries, which regulate the integrity of glomerular filtration barrier. Irreversible podocyte injury induces glomerular inflammation and causes chronic renal diseases. Kcnq1ot1, a long noncoding RNA, participates in the pathogenesis of diabetic retinopathy and cardiomyopathy. However, its function in podocyte injury is elusive. Pyroptosis of murine podocyte MPC5 was triggered by sublytic complement C5b-9 (sC5b-9) for subsequent in vitro functional and mechanistic investigation. Gain/loss-of-function analysis was conducted to examine the functional role of Kcnq1ot1 in podocyte pyroptosis. Meanwhile, the molecular mechanism of Kcnq1ot1's effect on podocyte injury was explored by identifying downstream molecules and their intermediate interactions. Kcnq1ot1 was upregulated in sC5b-9-induced podocytes, and silencing Kcnq1ot1 could inhibit sC5b-9's effect on podocyte pyroptosis. We also identified the interaction between Kcnq1ot1 and miR-486a-3p, through which Kcnq1ot1 mediated miR-486a-3p inhibition by sC5b-9. Furthermore, miR-486a-3p reduced the transcriptional activity of NLRP3, while the overexpression of NLRP3 enhanced sC5b-9's effect on podocyte pyroptosis through activating NLRP3 inflammasome. sC5b-9 induces pyroptosis in podocytes through modulating the Kcnq1ot1/miR-486a-3p/NLRP3 regulatory axis, and these uncovered key molecules might facilitate podocyte-targeted treatment for renal inflammatory diseases.

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Protosappanin-A (PrA) and oleanolic acid (OA), which are important effective ingredients isolated from Caesalpinia sappan L., exhibit therapeutic potential in multiple diseases. This study focused on exploring the mechanisms of PrA and OA function in podocyte injury. An in vitro model of podocyte injury was induced by the sC5b-9 complex and assays such as cell viability, apoptosis, immunofluorescence, quantitative real-time polymerase chain reaction, and western blot were performed to further investigate the effects and mechanisms of PrA and OA in podocyte injury. The models of podocyte injury were verified to be successful as seen through significantly decreased levels of nephrin, podocin, and CD2AP and increased level of desmin. The sC5b-9-induced podocyte apoptosis was inhibited in injured podocytes treated with PrA and OA, accompanied by increased protein levels of nephrin, podocin, CD2AP, and Bcl2 and decreased levels of desmin and Bax. The p-AKT/p-mTOR levels were also reduced by treatment of PrA and OA while AKT/mTOR was unaltered. Further, the effects of PrA and OA on injured podocytes were similar to that of LY294002 (a PI3K-AKT inhibitor). PrA and OA were also seen to inhibit podocyte apoptosis and p-AKT/p-mTOR levels induced by IGF-1 (a PI3K-AKT activator). Our data demonstrate that PrA and OA can protect podocytes from injury or apoptosis, which may occur through inhibition of the abnormal activation of AKT-mTOR signaling.

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OBJECTIVE: To compare the clinical effects of two methods of internal fixation in treating unstable femoral intertrochanteric fractures in elderly patients. METHODS: From August 2009 to August 2014, 68 elderly patients with unstable femoral intertrochanteric fracture treated with locking proximal femur plate and auxiliary short reconstructed plate (reconstructing calcar group) and proximal femoral nail antirotation (PFNA group) with clinical course from 1 to 3 days were retrospectively analyzed. In reconstructing calcar group, there were 30 patients including 8 males and 22 females, aged from 63 to 85 years old with an average of (73.41±5.12) years old, the fractures were classified to type AO 31-A2.2 in 12 cases, A2.3 in 11 cases, A3.3 in 7 cases according to AO/ASIF classification. In PFNA group, there were 38 patients including 10 males and 28 females, aged from 65 to 90 years old with an average of (74.26±4.53) years old, the fractures were classified to type AO 31-A2.2 in 15 cases, A2.3 in 13 cases, A3.3 in 10 cases. All fracture were caused by injury, leading pain and swelling. Femoral intertrochanteric fracture was confirmed by X ray films. The data of each group were collected for statistical analysis on the following aspects: the incision length, operation time, blood loss volume, postoperative partial weight bearing standing time, clinical healing time of fracture, postoperative complications, and hip functional score of Harris. RESULTS: All incisions were healed at stage I. In the aspect of postoperative complications, there were 1 case of screw blade cutting and 1 case of deep venous thrombosis in PFNA group; there was 1 case of deep venous thrombosis in the reconstructing calcar group (χ²=0.000, P=1.000). Patients were followed up from 20 to 24 months with an average of 22.5 months. There were no significant in postoperative partial weight bearing standing time, postoperative complications, hip functional score of Harris between two group. There were significant in the incision length, operation time, blood loss volume, clinical healing time of fracture. In the incision length, operation time, blood loss volume, clinical healing time of fracture, the PFNA group was significantly differently less than that of the reconstructing calcar group (P<0.001). In the clinical healing time of fracture, the PFNA group was significantly differently less than that of the reconstructing calcar group (P<0.05). CONCLUSIONS: For the treatment of unstable femoral intertrochanteric fractures in elderly patients, reconstructing calcar and PFNA are both effective, and proximal femoral intramedullary nails may be the best choice, which can be simpler operation, smaller incision and less healing time.

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